Archive for the ‘Gene Therapy Doctor’ Category

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, Inc., a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Phesgo, a fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab) with hyaluronidase, administered by subcutaneous (SC, under the skin) injection in combination with intravenous (IV) chemotherapy, for the treatment of early and metastatic HER2-positive breast cancer. This is the first time that Genentech has combined two monoclonal antibodies that can be administered by a single SC injection.

The FDA approval of Phesgo reflects our commitment to improving outcomes for the many people living with HER2-positive breast cancer, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. Phesgo offers a treatment administration that supports the needs and preferences of individual patients, and helps to meet the increasing demand across the healthcare system for faster and more flexible treatment options.

Phesgo is available in one single-dose vial. Administration can take approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines. Phesgo can be administered by a healthcare professional in a treatment center or at a patients home.

The approval is based on results from the pivotal Phase III FeDeriCa study, which met its primary endpoint with Phesgo showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The safety profile of Phesgo with chemotherapy was comparable to IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.

The Phase II PHranceSCa study showed that 85% (136/160) of people receiving treatment for HER2-positive breast cancer preferred treatment under the skin to IV administration due to less time in the clinic and more comfortable treatment administration.

For those who qualify, Genentech will offer patient assistance programs for people prescribed Phesgo by their doctor through Genentech Access Solutions. Please contact Genentech Access Solutions at (866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About the FeDeriCa study

FeDeriCa is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the pharmacokinetics, efficacy, and safety of SC injection of Phesgo in combination with chemotherapy, compared with standard IV infusion of Perjeta and Herceptin in combination with chemotherapy, in 500 people with HER2-positive EBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pathological complete response, meaning there is no tumor tissue detectable in the tissue removed at the time of surgery. The safety profile of Phesgo was comparable with that of Perjeta and Herceptin administered intravenously.

Data from the FeDeriCa study were presented at the San Antonio Breast Cancer Symposium in December 2019. The FeDeriCa study met its primary endpoint of non-inferior levels of Perjeta in the blood. The geometric mean ratio (GMR; a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI: 1.14 to 1.31), with the lower limit of the 90% CI of the GMR=1.140.80 (the pre-specified non-inferiority margin). A secondary endpoint of non-inferior levels of Herceptin was also met, with blood concentrations for people receiving the fixed-dose combination non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI: 1.24 to 1.43]; lower limit of 90% CI of GMR=1.240.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals.

About the PHranceSCa study

PHranceSCa is a randomized, multi-center, multinational, open-label, cross-over Phase II study evaluating patient preference for and satisfaction with subcutaneous (SC) administration of Phesgo. All patients completed neoadjuvant treatment with Perjeta, Herceptin and chemotherapy and had surgery before randomization. The primary endpoint of the study is the percentage of participants who indicate that they prefer treatment with Phesgo compared to the standard intravenous (IV) formulations of Perjeta and Herceptin. Secondary endpoints include participant-reported satisfaction and health-related quality of life outcomes; healthcare professionals' perceptions of time and resource use and convenience compared with IV formulations; as well as the safety and efficacy of each study regimen.

About HER2-positive breast cancer

Breast cancer is one of the most common cancers among women worldwide. According to the American Cancer Society, close to 280,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2020. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20% of breast cancers are HER2-positive based on the result of a diagnostic test.

About Phesgo

Phesgo (subcutaneous Perjeta and Herceptin) is a new fixed-dose formulation of Perjeta and Herceptin with Halozyme Therapeutics Enhanze drug delivery technology.

Trastuzumab in Phesgo is the same monoclonal antibody as in IV Herceptin and pertuzumab in Phesgo is the same monoclonal antibody as in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

Halozymes Enhanze drug delivery technology may enable and optimize SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.

Phesgo Indications and Important Safety Information

Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) is a prescription medicine approved for use in combination with chemotherapy for:

Phesgo is also approved for use in combination with docetaxel in adults who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Important Safety Information

What should patients know about side effects with Phesgo?

Most serious side effects with Phesgo

Phesgo may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

Receiving Phesgo during pregnancy can result in the death of an unborn baby and birth defects.

Phesgo may cause serious lung problems.

Who should not receive Phesgo?

Other possible serious side effects

Most common side effects

The most common side effects of Phesgo when given with chemotherapy as part of an early breast cancer regimen are:

The most common side effects of Phesgo when given with docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Patients should talk to a healthcare professional for more information about the benefits and risks of Phesgo.

Please see full Prescribing Information for additional Important Safety Information, including most serious side effects.

If a patient cannot afford their medication, visit http://www.genentech-access.com/patient for financial assistance information.

About Expanded Access Treatment Protocol for Continuity of Care During COVID-19

Genentech launched an expanded access treatment protocol in the United States, where the FDC of Perjeta and Herceptin is administered at home by a home health nursing provider. The study will continue beyond approval, aiming to help continuity of care during the COVID-19 pandemic for certain patients with HER2-positive breast cancer who have completed chemotherapy concurrent with Perjeta and Herceptin intravenously and are currently receiving or will be receiving Perjeta and Herceptin alone. To learn more, please visit here.

About Genentech Access Solutions

Access Solutions is part of Genentechs commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About Genentech in breast cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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FDA Approves Genentech's Phesgo (Fixed-dose Combination of Perjeta and Herceptin for Subcutaneous Injection) for HER2-positive Breast Cancer -...

In an interview with CURE, Dr. Mazyar Shadman discussed the enormous variety of treatment preferences among patients with CLL and said that emphasis should be placed on treating each person according to their wishes.

BY Ryan McDonald and Dr. Mazyar Shadman

A common mistake that tends to occur when patients are treated for chronic lymphocytic leukemia is the notion that only a patients cells are being treated, according to Dr. Mazyar Shadman.

In an interview with CURE, Shadman, of Seattle Cancer Care Alliance and Fred Hutchinson Cancer Center, discussed the enormous variety in treatment preference among patients with CLL and said that emphasis should be placed on treating each person according to their wishes.

Transcription:

The main bulk of my discussion is really what they want. You will be surprised at how different patients are in terms of what's important for them. One side of the spectrum, I have patients who really don't want a treatment that's forever, and that makes sense, right? No matter how safe the drug is, no matter how disease-free you are, just for some patients, just the thought of being on medication forever that's for cancer is important. And they just don't want it; they want to be disease-free, but also treatment-free as long as possible. And so that's important for some patients, and in the appropriate setting, if I feel that, yes, you know, we can go with either chemotherapy-based therapy in this patient or now venetoclax-based therapy (which) is a non-chemotherapy and a time-limited option potentially. For those patients based on that decision, of course, that's what I will provide to them.

I also have patients who really don't (care, and will say) I'm taking four medications for years, four different products, and (if) you give me something, I don't want to deal with the whole rampup and checking MRD, (but) as long as I'm fine,, I'll take it, so that you see both sides, and you do see patients who still come for chemotherapy. So, yes, patient preference is important. Patients need to understand and need to be educated on what to expect. It's always easy to start treatment. We get patients who come back six months, seven months later, and (say) You know what, I'm taking this for seven months it works, but can I stop? I mean, what do you mean (this) is going to go forever? The doctor who started didn't talk to me about (that).

So, I think those conversations are actually very important. And I add one more thing, they're important because we don't have a head-to-head trial that tells me that acalabrutinib or venetoclax which one is better. If I have that, then I probably won't give that option, or if I do, I make sure they understand that they're going for a treatment that's not superior, but we don't have that. So really, you have to sit and present both treatments and pros and cons and have them decide based on what's the best fit for them. And that's why it's important to have really a comprehensive approach to the patient I mean, it's really treating a patient, not the molecular kind of finding in the CLL cell, and that's a common mistake: Oh, I have somebody with a mutated (gene, and) that (means) I give chemo. No: You have a patient who has CLL whose CLL has this (mutation). So, then you kind of look at the patient and not the other factors.

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Conversations Between Patient and Oncologist Are Important in Avoiding 'Common Mistake' When Treating CLL - Curetoday.com

Image: Neuroblastoma rosettes. Credit:Dr. Maria Tsokos, National Cancer Institute(Public domain).

A type of drug known as a PARP inhibitor, already used to treat breast and ovarian cancer, may be useful in treating children with high-risk neuroblastoma a common childhood tumourwith a low survival rate.

Neuroblastoma is a cancer in childrenwhich arises from nerve cells in either the chest or the abdomen. In some neuroblastoma cases there is an abnormal gene called MYCN that makes it particularly difficult to treat.

Currently, children receive intense chemotherapy, radiotherapy and surgery but despite this only about half of children with high-risk neuroblastoma will survive.

Researchers at Sheffield Universitycollaborated with The Institute of Cancer Research, London, to conduct research to find a new, more effective and less toxic way to target high-risk neuroblastoma tumours with increased levels of MYCN.

MYCN affects how tumour cells grow and makes them more dependent on a protein called PARP for survival. This means that the tumour cells are specifically killed by a drug that stops PARP working. An advantage to this type of therapy is that normal non-tumour cells are not harmed so the damaging side-effects often seen with chemotherapy are reduced.

The study, funded by childhood cancer research charity Children with Cancer UK, was led by Dr Helen Bryant and Dr David King in Sheffield, in collaboration with Professor Louis Chesler at The Institute of Cancer Research (ICR).

They found that the use of PARP inhibitors alone, and alongside chemotherapy, was effective in killing neuroblastoma cells, leaving behind healthy cells. This is one of the first studies to show this in neuroblastoma cells and in tumour models.

Dr David King, childrens doctor at Sheffield Children's NHS Foundation Trust and Children with Cancer UK researcher, said:

Children with neuroblastoma and MYCN currently receive some of the most intense treatment used for any type of cancer. The harsh treatment causes numerous side effects and children often have long hospital stays. And despite the treatment, only about half of children with high-risk neuroblastoma will survive. PARP inhibitors are known to have very few side effects in adults and we have shown they may be an effective treatment for neuroblastoma. Their use in neuroblastoma could mean more children survive the disease and need less toxic treatment.

We have shown that PARP inhibitors kill neuroblastoma cells with MYCN in the laboratory. The next step is to see whether they are beneficial in children with neuroblastoma, probably in combination with chemotherapy or radiotherapy. This would be done in a clinical trial.

The ICR is an internationally leading research centre in the study of childhood cancers and cancers in children, teenagers and young adults.

Find out more

Dr Helen Bryant, research group lead and senior lecturer at Sheffield University, said:

Our study has examined the way DNA is damaged and repaired one of the features common in all cancers is that there are changes in that process. We were interested in how that process changes in neuroblastoma and whether we can exploit those changes to specifically kill cancer cells and leave the normal cells around the tumour unharmed. In this way we hope to develop kinder and less toxic therapies for children.

PARP inhibitors are being used successfully in women with breast and ovarian cancer so we are optimistic that this can be translated fairly quickly into children with neuroblastoma.

Mark Brider, Chief Executive Officer, Children with Cancer UK, said:

Neuroblastoma is one of the most common childhood tumours with around 100 children, mostly under five years old, diagnosed every year in the UK. Yet it also has one of the lowest survival rates in its high-risk form the survival rate is sadly around just 50%. It remains one of the most difficult childhood cancers to cure.

It is crucial that we find more effective and personalised treatments for children with neuroblastoma. The findings of Dr Bryant, Dr King and the teams in Sheffield and London represent an important step towards the development of new and kinder treatments that reduce the burden of toxicity for young cancer patients and improve survival rates in this aggressive and hard-to-treat cancer.

We are building a new state-of-the-art drug discovery centre to create more and better drugs for cancer patients. The centre is a 75m project and we now have less than 2m to raise. Help us finish and equip the building to get our research off to the best possible start.

Find out more

Alice Latham, 3, from Derbyshire, was diagnosed with high-risk neuroblastoma, with the MYCN gene, a week before her second birthday in January 2019. Her parents, Jamie and Helena, explain the harmful side-effects of Alices treatment.

Alices neuroblastoma treatment has been very aggressive and harsh on her body, she has experienced many side effects, including hair and weight loss. The treatment may also have an impact on her later in life she may not grow to her full height and there is a chance she may not be able to carry children. If treatments could be developed that are less harmful to childrens growing bodies that would be incredible, said Helena.

Jamie added:

As a parent you know nothing about neuroblastoma you understand when you get the diagnosis that the prognosis for the high-risk form is 40-50% survival after all of the treatment. The research for this type of cancer has really lagged behind and the treatment is very hard hitting. It is vital for charities like Children with Cancer UK step in and continue to fund this lifesaving research.

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Drug used in breast and ovarian cancer could lead to safer, more effective treatment for neuroblastoma - The Institute of Cancer Research

The family of a Santa Clarita teen with Batten disease, a fatal degenerative genetic disorder, is pleading with the community for help after suddenly learning that scheduled life-saving research had been halted, and is now being faced with an urgent need for additional fundraising support.

Affectionately known as Sebi, Sebastian Velona was born in 2003, and was a perfectly happy, healthy young boy with a big heart for the first several years of his life, according to his mother, Teri Hughes Fox.

He would also have the biggest heart and just want to hug everyone, Teri said. He just felt like, if you had a boo-boo, if you had a scrape, if you were crying, if youre hurt, if youre sad He felt he could hug people and heal them with his hugs.

Then, in October of 2007, four-year-old Sebi and his family were on vacation in Hawaii when tragedy struck.

He collapsed in the hallway going back to the room after having a fun day swimming in the pool, Teri said. He collapsed and had his first seizure. We thought he was dying. We didnt know what was wrong. He was turning blue. He was shaking. It was just horrible.

When the family returned home, a series of tests were unable to find any cause for Sebastians seizure, and a neurologist deemed it a one-off fever seizure.

Six months later, he had a second seizure. At that point, Sebi was diagnosed with epilepsy.

That was just the worst word at that time Id ever heard, Teri said. Our world changed.

After that came years of trial and error with medications, some of which came with side effects that further endangered Sebis health. Some medications resulted in mood swings and outbursts of anger, where others caused him to suffer more than 10 seizures in a day.

Eventually, Sebis doctors discovered a cocktail of three medications that managed to control his seizures, but the problems were just beginning.

When he was six, Sebi began to lose his vision, eventually being diagnosed with retinitis pigmentosa, a degenerative eye disease that will eventually cause him to lose his sight entirely.

He was at school learning to read and all of a sudden, overnight, it seemed like he couldnt see what was on the page, Teri said. It was fuzzy, he couldnt read it. There was something wrong.

It was at this time that Sebis family began to notice other issues developing in his behavior. He became clumsier and his speech began to slur. His parents insisted that there was something else at work, and obtained a DNA test to narrow down the cause of Sebis health issues in order to get him treatment.

Im thinking: Its not just retinitis pigmentosa and epilepsy. Theyre not separate issues where my son is just developing all these horrific diseases, Teri said. Theres something else wrong, everything about him is different, everything is changing and unless a doctor sees you every day, they dont see what were talking about.

After months of waiting, Sebi was diagnosed with CLN8 Batten disease in 2012. Batten disease is a disorder that primarily affects the nervous system, leading to neurological impairment, including developmental regression, seizures, blindness, behavior changes and dementia, according to health officials.

Teri described Batten disease as similar to a juvenile form of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs disease. The two conditions share many of the same symptoms.

The condition occurs in an estimated two-to four-in-100,000 live births in the United States, according to the National Institute of Neurological Disorders and Stroke (NINDS).

His parents immediately set to work to advocate on behalf of their child, working hard to raise the $3.5 million that would be needed in order to fund life-saving gene therapy research for Sebi and other children with CLN8. They founded the Sebastian Velona Foundation (SVF) to help raise the necessary funds.

Over the past several years, the family has advocated for gene therapy for their son after discovering successful forms of gene therapy to battle CLN6, another form of the disease.

In 2018, Senator Scott Wilk, R-Santa Clarita, sponsored a bill that designated the first weekend in June as Batten Disease Awareness Week. Wilk was made aware of the deadly disease and the need for more awareness after Chris Velona, Sebis father, traveled to Sacramento and sought out support for his son, as well as the thousands of other children and their families who have been affected by the disease.

Unfortunately, due to Food and Drug Administration (FDA) guidelines and other safety regulations, it has taken more than three years to reach the point where gene therapy research is able to take place. The SVF partnered with Columbus, Ohio-based Nationwide Childrens Hospital, which had placed gene therapy on the map according to Teri.

Nationwides Childrens Hospitals gene therapy program was bought by another company, before eventually being acquired by Amicus Therapeutics approximately 18 months ago.

Unfortunately for us because of the regulations, and the changing of the companies and the acquisitions, were kind of confused as to where were at, Teri said. Its really slowed us down.

The gene therapy is now in the process of being transferred back to Nationwide Childrens Hospital in order to complete the process and bring the result to human trials as quickly as possible.

Although Nationwide Childrens Hospital is more than willing to perform the research, they simply do not have the budget available to fund the project. The funding for the final stretch of research instead falls to the Velona family, with a price of at least $500,000.

We need to raise $500,000 and we need to do it yesterday, Teri said. We need to do this now and get the word out there, that there are so many with Batten disease that we could help with this gene therapy. As the pioneer, its going to get less expensive to bring this treatment to the masses.

According to Teri, the gene therapy treatment can not only halt the progression of the disease, but also save Sebis life as well as the lives of others affected by it. Without treatment, it is highly likely that within a few years at most, his condition will progressively deteriorate until he is unable to speak, see, walk, or even eat, until he would eventually die.

Teri worries that all families can do is wait for funds and treatment, knowing that waiting will only worsen their childs condition and quality of life.

We dont have the time to wait if he gets any worse we dont want to leave him in a state where its not a good quality of life, she said.

According to his mother, as of early June, Sebi is barely able to see, his speech is muddled and often unrecognizable, his cognitive thinking has deteriorated, and his physical and motor skills have so declined that he is unable to write or walk unaided. He is deteriorating on a daily basis, she said.

This is my son, he was fine, it just happened so fast, Teri said. Now were scrambling, kicking down any door, looking for anyone that will hear us, listen to us. We cant just watch our son deteriorate and die. Im not a good mom if I sit there and do nothing.

The news about new funding and the delays in gene therapy comes just as Sebi lost one of his grandfathers to COVID-19 in April, a death that has been devastating for him, according to his mother.

Hes very frustrated and sad. He keeps asking When is the gene therapy? asking me It was going to be soon, where is it? Teri said. Its my job to take care of him and fix him, and I cant fix him. So its hard.

Teri says that her 16-year-old son understands what is happening to him and why he cant go to school or get a drivers license like other teens his age, but he keeps a positive outlook through the difficulties he experiences every day, and even attempts to comfort her whenever the frustration becomes too much to handle.

He has an amazing attitude he wants to help people with his hugs, she said. If he saw me crying right now he would lose it, and be hugging me, and petting me and telling me, Mom its going to be okay, Im going to get gene therapy.

Although his body is failing him, it is Sebis good attitude about the situation that helps motivate his family, according to his mother.

He is so positive in his outlook that he makes me a better mom. Im not allowed to get down, or cry, or get frustrated, or kick and scream, Teri said. Im mad this gene therapy is taking so long. But Im so grateful that we have this opportunity to actually get a treatment

After receiving funding for gene therapy treatment, Teri and the SVF plan to continue helping other children with CLN8 around the world, and to help others with rare diseases.

Everyone deserves a chance, she said. The disease can be stopped by one injection, replacing the good gene with the bad gene. It baffles me.

In a literal race against time, the doctors at National Childrens Hospital and the Velona family remain dedicated to making sure that the gene therapy goes to trial before it is too late to save Sebastian and the other children like him.

Im not going to let my baby go that way, we need to fight, we need to raise money, its worth everything, Teri said. I know there are so many amazing charities out there, but you can actually save some childrens lives right now.

To support gene therapy research for Sebi, or to learn more about the SVF, click here.

KHTS FM 98.1 and AM 1220 is Santa Claritas only local radio station. KHTS mixes in a combination of news, traffic, sports, and features along with your favorite adult contemporary hits. Santa Clarita news and features are delivered throughout the day over our airwaves, on our website and through a variety of social media platforms. Our KHTS national award-winning daily news briefs are now read daily by 34,000+ residents. A vibrant member of the Santa Clarita community, the KHTS broadcast signal reaches all of the Santa Clarita Valley and parts of the high desert communities located in the Antelope Valley. The station streams its talk shows over the web, reaching a potentially worldwide audience. Follow @KHTSRadio on Facebook, Twitter, and Instagram.

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Botond Roska, a Hungarian neurobiologist researching in Switzerland, will receive the Krber Foundations prestigious award, the Krber European Science Prize, which recognizes a single European scientist each year, alternating between life sciences and physical sciences. The Hungarian physician, one of the worlds leading experts in the study of vision and the retina, is to be awarded for his work that revolutionised ophthalmology.

According to the website of the Krber Foundation, the Hungarian neurobiologist Botond Roska has set himself the goal of restoring sight to the blind. Roska and his research group in Switzerland investigate how various cell types in the visual system extract visual information from the environment. Based on molecular mechanisms, they have designed novel gene therapies for restoring vision in genetic forms of blindness. The scientist has carried out pioneering work to identify approximately one hundred different cell types in the retina and their complex interplay in signal processing.

The Krber European Science Prize honors outstanding and excellent scientists working in Europe. The prize is awarded to research projects that show great potential for possible application and international impact. In the last ten years alone, the Krber Prize winners included six scientists who were later awarded the Nobel Prize.

Roska is now working on making these fundamental insights beneficial for patients and using gene therapies to alleviate or cure their diseases. A genuine breakthrough was achieved by reprogramming a cell type in the eye, enabling it to take over the function of defective light receptor cells. He was thus able to make blind retinas light-sensitive again and clinical trials with blind people have already begun.

Hungarian-born Researcher Awarded for Helping People Regain Their Sight

In 2019, Roska was awarded the Louis-Jeantet Prize for Medicine for the discovery of basic principles of visual information processing and the development of therapeutic strategies, such as gene therapy, to restore vision in retinal disorders. He is also the first Hungarian to earn the Bressler Prize for his vision-restoring therapy, and the Alden Spencer Prize for understanding the vision process.

Later last year, President Jnos der decorated the neurobiologist with the Hungarian Saint Stephen Order on August 20th, Hungarys national holiday. der referred to Roska as a doctor who does not treat patients but enables others to heal through his research.

August 20 Saint Stephen Order Goes to Outstanding Neurobiologist Botond Roska

The father of the world-renowned researcher was electrical engineer Tams Roska, founder of the research of neural networks in Hungary. Botond Roska, although first studying cello at the Liszt Ferenc Academy of Music in Budapest, had to give up his music career because of an injury. He later received his medical degree from Semmelweis University, a PhD in neurobiology from the University of California, Berkeley, and studied genetics and virology at Harvard University. Roska currently works in Basel, Switzerland as co-director of the Institute of Ophthalmology Basel (IOB).

The Krber European Science Prize 2020 will be presented to Roska on7 September in the Great Festival Hall of Hamburg City Hall.

featured photo: Nomi Bruzk/MTI

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Hungarian Neurobiologist Botond Roska to Receive This Year's Krber European Science Prize - Hungary Today

The Black Hole

Both David and Jonathan hope that many new and good things can come from this period of lockdown.

BY DAVID KENT | JUN 23 2020

This quarter has been different there is no doubt about that. Both Jonathan and I have spent lockdown with working partners (medical doctor and scientist) and two little ones each (all four kiddies under the age of five) and we were chatting the other day about how odd it is that he and I have only ever met physically in person three times. Sometimes people just get on and have aligned goals and ambitions, and The Black Hole has been a tremendous pleasure to share with Jonathan (and Beth Snow before!). This period of enforced online interaction has led to some serious Zoom fatigue, but we both hope that many new and good things can come from this period of lockdown as youll see from the range of posts below.

This quarters most popular posts were my recent post on career considerations during lockdown and Joanthans post from last summer entitled You are not a failure for wanting to leave academia which we imagine also got some extra readers during lockdown for similar reasons as the career considerations post. We hope that readers enjoy these and others. We also hope to write more on the positive things that might emerge from the introspective journey that many of us have been on over the last months (or the one well go on after life gains some semblance of normality!). Our recent posts are listed below:

This quarter Dave has also written some more science-y stuff with a series of articles exploring recent scientific advances in blood stem cell gene therapy for a wide range of diseases over on the Signals blog:

Were looking forward to getting back to normal (even to whatever the new normal will be) and as always, encourage our readers to contribute their own articles to this column to gain some exposure for issues near and dear to their hearts.

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Quarterly summary: the COVID-19 lockdown and the importance of scientists - University Affairs

CALGARY -- After being diagnosed with ALS, Calgary Flames assistant general manager Chris Snow appreciates every minute he gets to spend with his family.

He never takes it for granted.

He also appreciates recent fundraising efforts similar to the Ice Bucket Challenge that have been taking social media by storm, in his honour.

On Monday Snow was tossing the ball around with his children, eight year old Cohen and five year old Willa.

Just over a year ago, he didnt think he was going to be able to do that.

He says hell never forget that day, when a doctor told him he had ALS.

"He looked at me and said this is the early stage and you just sink," he said.

"You think your life is over because it really is. At least until now, in every case, it's a no hope disease."

About 3,000 Canadians currently live with ALS. Its a rapid and always fatal neurodegenerative disease that typically hits those aged between 55 and 65.

Chris is just 38 years old and ALS runs in his family. His dad, two uncles and a cousin all passed away from it.

The Snows have the most aggressive sub-type of the disease. Chris was given just 12 months to live.

But he and his wife Kelsie werent about to give up. Kelcie did the research and Chris was enrolled in a gene therapy clinical trial.

Kelcie says that gave them hope.

You know when I asked the doctor, 'is it possible this could stop their progression entirely?' and he said, 'we dont know but its not outside the realm of possibility,'" she said.

"We held onto that and we keep holding onto that."

Chris says so far its appears to be working.

My right hand, it doesnt really do anything for me. But it hasnt since I enrolled in the trials. I didnt see that as a form of progression because that was already gone," he said.

My upper arm on that side remains very strong. I can lift and hold my kids with that. Just have to catch them right way.

June is ALS awareness month. And Snow and the Flames came up with a unique idea to help raise money to fight the disease.

Its called Trick Shot for Snowy and has taken twitter by storm. Snow says hes been loving all of the creativity.

Its like the ice bucket challenge but its fun," he said. "You get to show off a little bit. And do things that are either skillful or ridiculous. And social media has the ability to reach so many people at this point in time."

So far, Trick Shot for Snowy has raised more than $150,000. Chris says all the money raised will be put toward the best research they can find in Canada.

Kelcie says she couldnt be more proud of her husband.

You know in some ways its like he was made for something like this," she said. "Hes so positive and he always finds a way to get by and to keep going and smiling."

Just over a year ago Snow thought he was given a death sentence. On Sunday, Fathers Day, he hiked a mountain with his family.

See more here:
Flames assistant GM continues to defy the odds in his battle against ALS - CTV News

For years, I consistently urged investors to focus the bulk of their portfolios on what I term megatrends. While making a quick buck on momentum plays is great, your highest probabilities of success rest on long-term developments in technology and innovation. And few hit all the right buttons like Crispr Therapeutics (NASDAQ:CRSP). Levered to the groundbreaking gene-editing industry, CRSP stock deserves extra attention for anyone interested in phenomenal gains.

Source: Catalin Rusnac/ShutterStock.com

Its amazing to think how far technology has come. What was once the exclusive realm of science fiction, we are now closer than ever to a fully automated society. From driverless vehicles to automated customer service platforms to smart city infrastructures, investing in innovation has never been more relevant.

At the same time, medical innovations have somewhat lagged the profound changes were seeing everywhere else. Try as we might, we havent had many breakthroughs regarding the human condition. Primarily, our practically available medical solutions involve mitigating symptoms, not addressing root causes. Crispr Therapeutics hopes to disrupt this paradigm entirely, thereby imbuing CRSP stock with its potential.

Underlining the biotechnology firms awe-striking platform is CRISPR, which is a specialized stretch of DNA. Associated with CRISPR is a protein called Cas9, which essentially acts as a pair of molecular scissors. This function enables the gene-editing process, which from a broad summary view involves cutting problematic gene sequences and correcting them.

One of the most important components of the CRISPR-Cas9 technology is that scientists adapted it from a naturally occurring genome editing system in bacteria. Thus, were not necessarily talking about playing God. Instead, were utilizing breakthroughs in biotechnology to transfer natural processes to aid humanity.

I couldnt think of a better argument for CRSP stock. But here are three more for your consideration.

In the biotech space, the biggest prize is the cure for cancer. By the end of this year, experts predict that 1.8 million Americans will be diagnosed with the disease. Tragically, over 600,000 will succumb to cancer. Thus, its imperative that we marshal all available resources to fight this scourge.

Unfortunately, the mechanisms by which we treat the disease is rather antiquated. Years from now, I can imagine that people will look back and consider our tactics barbaric. Rather than attacking the cancer cells themselves, we address symptoms, mainly through surgery, chemotherapy and radiation therapy.

In other words, cut em, drug em and fry em. That might work if were in the fake meat processing business. But to treat our loved ones, it seems crude and anachronistic.

And this is why Im very excited about the potential of CRSP stock. To be clear, Im not suggesting that Crispr is on the cusp of a cancer breakthrough. However, with their innovative approach modifying a patients immune cells to efficiently attack cancer cells the possibilities are simply astonishing.

Currently, the major knock against this platform is its extreme cost, which brings up ethical concerns. However, through industry partnerships and synergies, its likely that over time, these costs will come down, making them a more affordable choice for patients.

One of the worst pieces of bad news you can get from the doctor is a diagnosis of a rare disease. Unlike other conditions, such as cancer, support networks may be limited in number. In addition, the treatment options may be few as well. Plus, the available solutions are typically very expensive.

But the most difficult challenge is the helplessness that patients suffer. For instance, with lupus, the body basically attacks itself. Traditional medicines have focused on symptom mitigation. But what can you do when your body stands divided?

Its precisely this type of condition for which Crispr provides meaningful hope. With the companys gene-editing technology, it can potentially alter the lives of millions who suffer silently.

As with cancer, Crisprs current mechanism isnt cheap and therefore, isnt practical for all but the wealthiest patients. Again, though, advancing technologies always drive down costs. And frankly, having the foundation for such groundbreaking solutions is far better ethically than not having it whatsoever.

Therefore, I believe investors can buy into CRSP stock with a clear conscience.

Easily the most powerful yet controversial implication of the CRISPR-Cas9 technology is the development of gene drives. According to Live Science contributor Aparna Vidyasagar, gene drives are:

genetic systems, which increase the chances of a particular trait passing on from parent to offspring. Eventually, over the course of generations, the trait spreads through entire populations, according to theWyss Institute. Gene drives can aid in controlling the spread of diseases such as malaria by enhancing sterility among the disease vector

Where it gets tricky is this technologys potential to enhance or eliminate certain traits of parents to their offspring; Im talking of course about designer babies.

Obviously, this is a discussion that extends well beyond the scope of this article. However, I will say this: the possibility of improving the human condition is likely worth the risk of unintended consequences. Therefore, I remain bullish on CRSP stock despite some nuances associated with the underlying narrative.

Matthew McCall left Wall Street toactually helpinvestors by getting them into the worlds biggest, most revolutionary trends BEFORE anyone else. The power of being first gave Matts readers the chance to bank +2,438% in Stamps.com (STMP), +1,523% inUltaBeauty (ULTA) and +1,044% in Tesla (TSLA), just to name a few.Click here to see what Matt has up his sleeve now. Matt does not directly own theaforementioned securities.

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3 Reasons to Go Long Crispr Therapeutics - InvestorPlace

My life changed forever the day I became the father to a son with extreme special needs. But I could never have imagined just how much being Brysons dad would continue to change my identity. While our familys COVID-19 isolation has been challenging, it has provided me with the opportunity to reflect on the evolving nature of my role as father.

Happy Faw-vers Day.

My two-and-a-half-year-old son Connor stumbles toward me, carrying a gift almost as big as he is. I unwrap a PlayStation 2. Its a surprisingly expensive gift, but my wife Laura reminds me that this is a special Fathers Day. Shes seven months pregnant, and even though we havent met our second child, were already in love with the newest member of our family.

I thank Connor before leaning in close and kissing Lauras belly. Thank you, baby.

If you'd like to make your Father's Day crafty, have your little ones try a fun printable print it here.

Baby Brysons first year has been tough. Hes missed all his milestones and doctors have confirmed that he isnt developing typically. Hes 10 months old but cant sit independently, or crawl, or track objects with his eyes. Hes nowhere near being able to say his first word or take his first steps. But doctors dont know why.

When Connor was born, my identity changed. I was no longer just a guy. I was a father. Becoming a special needs dad has changed me once again. The responsibility feels weightier; theres less room for error. I need to get this right.

A few days before Fathers Day, we go out for dinner at an all-you-can-eat Asian restaurant. The food is tasty but the service is slow. And Bryson is loud. Theres this sound he makes that we call singing but its really more of a happy wail. Were accustomed to it, but the diners around us are not. Someone complains and a manager drops by our table.

"You need to tell your son to be quiet," she says, waving at Bryson. "Other guests are complaining."

"My single greatest fear is whos going to protect him when Laura and I arent around."

We ask her to pack up our food and we head home, full of sadness and fear for Brysons future. Once hes in bed, I sit down and type out what I call my Fathers Day pledge, to be by his side to protect him from the judgments of this world until the day I die.

My single greatest fear is whos going to protect him when Laura and I arent around.

You can listen to Keith McArthur and Bryson's story in his podcast Unlocking Bryson's Brainright now. Listen here.

This ones hard. My own father died of cancer a couple months earlier. Theres this massive hole in my life that cant be filled, and on Fathers Day, it feels particularly unbearable. Ive become so depressed over the past couple of months that I cant seem to handle life anymore. I find myself leaving my desk at work and sneaking off to my car to hide, sometimes for hours.

Fears about Bryson are also weighing heavily. Hes almost eight but he cant walk or talk. His brain seems to be locked at the developmental age of 12 months. He also has violent episodes where he hurts himself and those around him. Hopes that he might just grow out of this are a distant memory. Doctors have performed so many tests dozens of blood draws, MRIs, muscle biopsies but they cant figure out whats causing Brysons condition.

I love Bryson so much, but I cant help wondering if hes even capable of loving back.

It all feels too hard. I promise Laura Ill see a doctor about my depression. Two weeks later Im on anti-depressants. Life isnt easy, but at least its manageable again.

Were celebrating Fathers Day in a hotel room in suburban Pittsburgh. Connor hands me some gifts, including a barbecue cookbook and a broken picture frame, the casualty of an overpacked suitcase and a six-hour road trip.

Our lives have changed dramatically over the past two years. I got off the anti-depressants, then experienced kidney failure, then got a second chance at life when my sister Stephanie donated one of her kidneys to me.

And after nearly a decade of searching, we finally got a diagnosis for Bryson. A genetic sequencing test revealed that Bryson has a mutation in his GRIN1 gene one of several genes that encode receptors in the brain that play a critical role in learning and memory. Pathogenic variants in this cluster of genes are known as GRIN Disorder.The diagnosis is why were here in Pittsburgh, meeting other GRIN Disorder families from across the country. Bryson is no longer alone.

Weve agreed to host this years GRIN family conference in Toronto, so I spend Fathers Day finalizing plans. Families travel in from across North America and we line up a panel of scientists who can help us understand this rare disease. Im shocked when they tell us that a cure for GRIN Disorder might be possible. Bryson is perfect; I dont want to change him. But if new treatments could allow him to communicate and make more of his own decisions, wouldnt he want that?

My paternal identity changes once again. Im no longer just a father or a special needs dad, but a rare disease warrior putting my life on hold to chase down a cure. I make a podcast series about this journey. Unlocking Brysons Brain launches two years later in the midst of a global pandemic.

The world is slowly getting back to normal but not for my family. GRIN Disorder usually isnt fatal, but some GRIN kids have died suddenly from respiratory complications. Im also on post-transplant drugs that lower my immune system. We cant risk allowing COVID-19 into our family, so well be spending this Fathers Day much as we have spent the past three months in isolation.

Brysons medical appointments are all on hold. So is the physio and speech therapy he usually gets through school. And the Grade 8 graduation ceremony Id been looking forward to for years? Its not happening this year. Worse still, all the research Ive been pushing to help find a cure is on hold as labs that arent focused on COVID-19 shut their doors.

On the plus side, pandemic life means more family time. And on a cloudy weekend in May, my son Bryson delights me with two early Fathers Day gifts.

Bryson does well in his walker at school, but hes been struggling at home. He just plops down on the safety seat instead of moving forward. So Laura has an idea. She removes the seat. And suddenly Bryson takes off, walking better than Ive ever seen him move before. Its the best gift I could hope for.

"We cant risk allowing COVID-19 into our family...."

But theres a bigger one yet to come.

Bryson loves it when I kiss him on the left side of the neck, just under his ear. When he wants me to do this he puts his hands on the back of my head and pulls me close. But this time, he pulls me in close and, for the first time, starts kissing my face. The kisses are wet and toothy, and make both of us erupt with laughter.

And they are unmistakable acts of love.

Read more here:
GRIN Disorder, Kidney Failure and Fathers Day How One Family is Surviving it All - CBC.ca

A Cure for Hemophilia? BioMarin Attempts to Stop the Bleeding with a Single Shot

By Matthew Rojas, Biotech Analyst

Most people recall learning about hemophilia from the history books. Specifically, Queen Victoria of England, who ruled from 1837-1901, was a suspected carrier of the hemophilia B trait that causes the infamous, potentially fatal bleeding disorder. Since then, hemophilia has commonly been referred to as a royal disease due to its prevalence in various royal families throughout England, Germany, Russia, and Spain during the 19th and 20th centuries.

In the United States, there are approximately 20,000 people with hemophilia, and an estimated more than 400,000 individuals have the disorder worldwide. In addition to hemophilia B, there is also hemophilia A. The difference between the two conditions lies in which clotting protein is defective or missing for hemophilia B it is factor IX and for hemophilia A, factor VIII. Nevertheless, the symptoms of both variations of hemophilia are the same and range in severity from excessive bleeding only after an injury to frequent, spontaneous bleeding.

Presently, people with hemophilia A or B need infusions of the respective clotting protein two to three times per week. Not to mention, the weekly injections do not stop all bleeding episodes. Going to the doctor this frequently is extremely time-consuming, making it inconvenient for most individuals. Hence, many people with hemophilia fail to receive adequate treatment for their condition, which puts them at great risk. There is a pressing need for a more efficient way to treat individuals with hemophilia this is where BioMarin comes to the rescue.

BioMarin is a California-based biotechnology company that focuses on rare diseases driven by genetic causes. Currently, they have something revolutionary in their clinical pipeline for patients suffering from hemophilia A: valoctocogene roxaparvovec or valrox. Unlike traditional methods for treating hemophilia, valrox does not require repeated injections to temporarily mitigate symptoms; valrox uses gene therapy and only requires a single infusion to cure hemophilia A patients. Yes, you read that right cure. Gene therapy is a complicated process that works by inserting genetic material, via a carrier or vector, into cells so that they can make a protein in this case, factor VIII. For valrox, the vector is AAV5; a concern arose because people with AAV5 antibodies are ineligible to receive valrox. However, BioMarin estimates that 80% of people with hemophilia A do not have AAV5 immunity, so this should not be a problem.

A cure almost seems too good to be true, but the data are clear. In BioMarins Phase III clinical trial, seven out of 16 hemophilia A patients exhibited required levels of factor VIII. The company submitted this data along with three years of Phase I/II data for FDA approval. The application is currently under priority review, and a decision is expected on August 21, 2020. Therefore, now is the perfect time to invest in BioMarin because its current stock price does not reflect the potential revenue from valrox in the near future.

According to Hank Fuchs, president, Global Research and Development at BioMarin, Valoctocogene roxaparvovec has the potential to be the first gene therapy to be approved in any type of hemophilia. In the gene therapy space, it is critical to be a first mover because once patients are treated, they are taken off the market. After all, people only need a single shot.

Some of BioMarins competitors include Pfizer and Sangamo Therapeutics SB-525 and Spark Therapeutics SPK-8011, both gene therapies for hemophilia A. However, SB-525 is still in the process of Phase III clinical trials, and Spark ran into trouble when one patient ended up in the hospital due to an immune reaction related to SPK-8011. On the other hand, valrox is safe, has already completed its clinical trials, and is currently under priority review by the FDA. Thus, BioMarin is on track to be the first mover.

To further ensure its dominance in the hemophilia A gene therapy space, BioMarin increased the number of doses its gene therapy facility could produce from 4,000 to 10,000. To put that increase in perspective, the company can now treat all of the hemophilia A patients in the United States in two years. If established as the first mover, BioMarin has sufficient capacity to quickly dose hemophilia A patients before other gene therapies are approved to go to market.

As stated above, the current treatments for hemophilia A are weekly, expensive injections of prophylactic FVIII. Patients are dependent on these injections for their entire lives, costing an estimated $700,000 to $750,000 per year. Also, many hemophilia patients have greater costs due to frequent hospital visits, procedures, various tests, etc.

One study analyzes the possible cost-effectiveness of valrox compared to traditional prophylactic FVIII injections. The results are astounding the average patient cost of valrox is an estimated $16.7 million, whereas the average patient cost of the prophylactic FVIII injections is an estimated $23.5 million. Therefore, valrox provides a reduction in costs of $6.8 million per patient, on average. Because valrox is cheaper and more effective, it is likely to become the dominant way that hemophilia A patients are treated.

Unlike many biotechnology companies, BioMarins stock (BMRN) has come out on top at the tail-end of the COVID-19 pandemic. Before the crisis, the company was trading at around $97.00, and now the share price has increased by about 10% to $106.00. This increase in share price is promising because if BioMarin can perform well in times of economic-downturn, imagine what they can do in times of economic health. The reason for this continued growth is likely because BioMarin has steady revenue streams from a diversified portfolio of products for rare diseases; in 2019 alone, the company generated nearly $1.7 billion in revenue from its product lines, a 13% increase compared to 2018. With the likely approval of valrox in late August, I expect that the stock price will increase even further.

Furthermore, BioMarin has solid financials across all of its first-quarter 2020 statements. As of its most recent balance sheet, BioMarin has a current ratio slightly above 1, indicating that it can cover its short-term debt obligations. Additionally, the company generated over $100 million in revenues in the first quarter, a 25% increase from the fourth quarter of 2019. Lastly, BioMarin ended the most recent quarter with an increase of about $40 million in cash, which shows that it can generate liquidity even in times of crisis. BioMarins financials are stronger than ever, allowing it to continually achieve success.

Hundreds of thousands of hemophilia patients around the world have an unmet need: a permanent treatment for their disorder. BioMarin meets that need. With the use of revolutionary gene therapy, BioMarin has developed valrox, a single infusion that will cure hemophilia A patients once and for all. Not only is valrox more effective than the leading treatments for hemophilia A, but it is also much cheaper, saving patients and payers millions of dollars. With BioMarin scheduled to be the first-mover in the hemophilia A gene therapy space, now is the critical time to invest before valrox stops the bleeding.

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Gene Therapy: Regal Profits From Curing "The Royal Disease"? - Sick Economics

Cancer isnt waiting for Covid-19 to go away. Neither is Karen Howley.

Diagnosed two years ago with advanced ovarian cancer, Howley started on a new experimental drug in mid-March, just as coronavirus case counts were soaring in Massachusetts. Her treatment, part of a clinical trial at Dana-Farber Cancer Institute in Boston, began with a four-week hospital stay, and since then, shes been returning every Monday for infusions.

While the study drug dripped into her body, she heard the hospital staff apprehensively discussing the coming surge of cases. Howley felt safe on a floor devoted to cancer patients, where there was no shortage of personal protective gear for the medical workers, but she still wiped down her tray each time a a meal was delivered to her bedside.

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Ambulance sirens wailing endlessly outside her window made her anxious. The hospitals no-visitor policy made her lonely. But Howley, who has faced her cancer with both humor and realism, never considered quitting the clinical trial.

I dont think it occurred to me, Howley, 56, said during an infusion appointment last week that she wryly called her spa day.

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Treatment for me is prolonging my life at this point. And if I do get Covid, I do.

Around the world, Covid-19 has disrupted all types of clinical trials, decreasing by 74% the number of new patients enrolling. In cancer, the number of new patients entering Phase 2 and 3 cancer trials in the U.S. plummeted by about 46% to 48% in the last two weeks of March, said Margaret Mooney, associate director of the Cancer Therapy Evaluation Program in the Division of Cancer Treatment and Diagnosis at the National Cancer Institute. By the last week of May and first week of June, the cliff wasnt so steep, moderating to a 25% to 30% decline.

Some medical centers put certain research trials on hold, stretched too thin by the needs of treating Covid-19 patients. Others continued their cancer trials by taking advantage of NCI-modified protocols allowing patient consent by phone or delivery of oral drugs to patients homes. Depending on where an individual site was located, they made local decisions that were best for their patients and their patient population in terms of clinical trials, Mooney said.

At Dana-Farber, Ursula Matulonis, chief of gynecologic oncology and Howleys oncologist, recalled patients feeling frightened and doctors feeling uncertain about exactly how they would carry on in the early days of the pandemic but no one ever doubted that they would.

We said, look, weve got to go in to see our patients because theyve got cancer. They want to continue to be treated in the same way, she said. We have a job to do and we have to continue to do that job.

Doing that job at Dana-Farber means patients are screened for symptoms when they enter the cancer center and at each step along the way. Howley answers the same set of questions Any fever? Any cough? Any contact with anyone who has Covid-19? when she has her vitals checked, gets her blood drawn, sees her doctor, receives her infusion.

Shes used to the waiting-room chairs zip-tied in opposite directions to keep single patients (no more friends or family) from getting too close. She expects to park her own car rather than turn it over to a valet. Because shes enrolled in a research trial, there are more blood samples taken for analysis and for tracking her response to the drug, but the entire visit moves along more quickly now, streamlined to reduce waiting times so no patient is exposed longer than necessary to other people.

Andrew Wagner, an oncologist who is leading Dana-Farbers efforts to keep patients safe and on treatment during Covid-19, said in consultation with study sponsors, some tissue biopsies were canceled, or for some patients chemotherapy was adjusted from every week to every three weeks. Physician visits to discuss imaging scans moved from in-person to video. Dana-Farber had zero telemedicine before March, but virtual visits now account for just under half of patient appointments, holding lessons for the future.

Its been hard in oncology, of course. Such a large part of what we do is the emotional care of patients and their families, Wagner said. Being able to hold someones hand is really hard to do through telemedicine, but certainly the video aspect of it is much better than just the telephone. Youre able to express yourself empathically.

Patient visits to Dana-Farber plunged by 40% in the course of one week in mid-March but chemotherapy appointments slipped by only 10% to 15% over that same week. Now doctors are encouraging patients to come back in. We think that its very safe here. We are certainly safer than in the grocery store, Wagner said. Cancer is not going to wait for Covid to go away.

Other cancer centers made similar adjustments. At the Ohio State University Comprehensive Cancer Center in Columbus, where close to 1,000 clinical trials are typically underway, Ohio Gov. Mike DeWines March 23 stay-at-home policy kept 200 research nurses and other staffers away from their duties. That meant only trials with a critical therapeutic outcome, extremely modest staffing needs, or time-sensitive enrollment targets continued, said Raphael Pollock, director of the cancer center.

Now that Ohios stay-at-home policy has been lifted and the research machinery is gearing up again, he expects trial participation to tick back up, too. Cancer didnt take time off, Pollock said. Well be quite busy by the mid- to late summer.

And at Memorial Sloan Kettering Cancer Center in New York City, the U.S. epicenter of the pandemic, no therapeutic trials were put on hold, but in-clinic volume in March and April did drop by about 75%. Telemedicine helped, said Paul Sabbatini, an oncologist and deputy physician-in-chief for clinical research. We and most centers have developed processes to rationally deal with the Covid risk as best we can so [clinical trials] can proceed now.

Now patients are coming back.

While it was prudent for patients to avoid the medical setting when the pandemic was at peak, enough time has elapsed that many of those patients clearly now have a benefit/risk ratio in favor of care, Sabbatini said. Clinical trials remain the only way we evaluate and ultimately approve new therapies for patients with cancer.

NCIs Mooney believes some good may come from adjustments made to ensure the safety of patients participating in studies and medical staff. But its still a work in progress, as hotspots rise and fall.

I think were learning more as we go along, she said. Some of the adaptations weve made have made all of us realize that perhaps there is better use we can make of technology telemedicine or technologies like that to take care of the patient. Thats a benefit to everyone, and they may be things that we can continue into the future once the public health emergency, as we all hope, has been resolved.

At Dana-Farber, Howley is enrolled in a Phase 1 trial of REGN4018, a bispecific antibody developed by the biotech company Regeneron. It grabs onto cancer cells at two points connected by a bridge. One side targets MUC16, a gene mutated in ovarian cancer and previously known as CA125 (which is still the name for the biomarker measured in diagnostic blood tests). The other side of the antibody binds to a T cell receptor that can then kill the cancer cell, the theory goes.

You realize this [Covid-19] is temporary and one day we will be back. For me, its like, I dont know how long I have.

When patients are hospitalized at the outset of the trial, which at this early phase is designed to test safety and dosing, its not an easy time for them with or without a pandemic. They are waiting for the drug to provoke their immune systems into killing their cancers. Howley felt savage pain across her abdomen and the wrath of a cytokine storm, the massive inflammatory response that also occurs in some Covid-19 patients whose immune systems go into overdrive.

We believe that the best antibodies you can get are the specific antibodies that travel to the sites of tumors. And thats what causes the abdominal pain, Matulonis, her oncologist, said.

From the beginning, Howleys treatment path has not been easy. After initial surgery to remove her tumor, she endured peritoneal delivery of the chemotherapy drug cisplatin directly to her abdomen, which was both painful and ultimately ineffective. She went on a standard drug called Doxil, but her cancer still progressed. Next she started a clinical trial that combined three drugs: one immunotherapy drug, one drug that blocks new blood vessel growth, and one PARP inhibitor that interferes with how cancer cells repair DNA damage. It was an aggressive regimen designed to expose the cancer to three agents it had never seen before, Matulonis said.

But one drug caused a bowel perforation, a known side effect. She continued to take the immunotherapy and the PARP inhibitor, but by November her cancer was progressing, measured by blood tests gauging her CA125 levels and imaging scans that spot metastasis.

The new trial, of the bispecific antibody, started in February.

I think for her, Ive always wanted to go beyond standard chemotherapy, Matulonis said. You can see that the tumor was a harder nut to crack. We really have to think outside the box to treat her.

Matulonis said Howley can stay on the current trial as long as she meets three conditions: She is benefiting from the drug, she is not having any significant toxicities, and she wants to continue. Howleys CA125 has hit four figures in the past. Before last weeks blood test, her last reading was 499. She was both nervous and eager to know the latest, though she tries not to put too much stock in the biomarker. The reading can vary with inflammation and the drug she is on causes inflammation, irritating one hip so much that she wants to ask if a cortisone shot would be allowed under the trials rules.

Except for the cancer, shell tell you shes healthy, and Matulonis agrees. Retired now from a career in client services, she lives with her husband in Sudbury, Mass., about a 40-minute drive to Boston. She walks three miles every morning, and she just got back to playing tennis. She ran the Falmouth Road Race last summer, astonishing a research nurse on her medical team who was volunteering on the sidelines.

For her visit last week, she wore a white, cowl-necked knit top port-friendly for blood draws and drug infusions through an opening high on her chest. Her lively blue eyes were set off by sparkly deep-blue eye shadow, her dark hair accented with blond highlights. Shes been the woman in the waiting room with no hair or eyebrows and knows how it feels when people look at you. Now she jokes about reluctantly giving up her fashion-coordinated cloth face mask for the fresh paper one Dana-Farber offers each patient upon check-in.

Howley has dual motivations for participating in cancer research. One is to help other women with ovarian cancer. Hopefully Im a piece of that puzzle thats going to give them a little insight, she said. They might have something here thats going to be so critical down the road for others.

Her other driving force is her 29-year-old daughter. She doesnt worry about their sharing BRCA1 or BRCA2 mutations her genetic tests were negative for those mutations but she is concerned about being a role model.

So much of my determination is just really providing an example to her, she said. Im not saying Ive got it down at all, but I try very hard to show her how to do it kind of gracefully. It doesnt mean Im going to do it. But I still try.

Cancer has already narrowed how she thinks about the future. Six months is as far out as shell plan these days, and Covid-19 has cramped her dreams of traveling to one of her favorite places, Marco Island in Florida. You realize this [Covid-19] is temporary and one day we will be back, Howley said. For me, its like, I dont know how long I have.

No one can tell her that, but she looks to Matulonis to see if her new CA125 number matches how good shes felt, even if she hit lousy on the tennis court.

The number is still moving in the right direction, Matulonis tells her: 259, down from 499 a month ago. That could mean her cancer burden is diminishing, Matulonis said, but cautioned that imaging scans will have to confirm it.

Howley knows that.

If it goes up 50 points, it doesnt necessarily mean anything. But at the same time, Im just blown away, she said. Today, its almost surreal to me, its going to take me a while to digest.

She is still elated as she climbs into the infusion chair for her next dose of the trial drug.

Maybe I better plan that trip.

See the original post here:
Cancer patients and doctors carry on with clinical trials during Covid-19 - STAT

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the Phase III IMpassion031 study, evaluating Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane [albumin-bound paclitaxel, nab-paclitaxel]; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy (including Abraxane), met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in pathological complete response (pCR) for the treatment of people with early triple-negative breast cancer (TNBC), regardless of PD-L1 expression.

Triple-negative breast cancer remains an aggressive disease with high rates of recurrence, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. Our goal in treating TNBC at its earliest stages is to provide people with the best chance for a future cure. Adding Tecentriq to chemotherapy now has the potential to help women with TNBC at multiple different stages of the disease.

In the study, fewer patients who received the Tecentriq combination as a neoadjuvant (before surgery) treatment had evidence of tumor tissue detectable at the time of surgery (known as pCR), regardless of PD-L1 expression, in comparison to the control arm. Neoadjuvant treatment may allow a doctor to quickly assess whether a medicine is working, and may also reduce a tumor's size so it is easier to surgically remove. pCR is a common measure of neoadjuvant treatment effect in breast cancer and can be assessed more quickly than traditional endpoints in early-stage breast cancer.

Safety for the Tecentriq combination appeared to be consistent with the known safety profiles of the individual medicines and no new safety signals were identified. Results of the IMpassion031 study will be presented at an upcoming medical meeting and will be discussed with global health authorities including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The IMpassion031 study is the second positive Phase III study from Genentech demonstrating the benefit of Tecentriq in TNBC, and the first Tecentriq study to demonstrate benefit in early TNBC. Tecentriq in combination with nab-paclitaxel is currently approved in more than 70 countries worldwide, including the U.S. and across Europe, for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumors express PD-L1 (IC1%).

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMpassion031 study

The IMpassion031 study is a Phase III, multi-center, randomized, double-blind study evaluating the efficacy and safety of Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane, [albumin-bound paclitaxel; nab-paclitaxel]; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy, in people with previously untreated, early TNBC. The primary endpoint is pCR using the American Joint Committee on Cancer (AJCC) staging system in the intention-to-treat (ITT) population and in the PD-L1-positive population. Secondary endpoints include overall survival, event-free survival, disease-free survival and quality of life measures.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

About triple-negative breast cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, close to 280,000 people in the United States will be diagnosed with invasive breast cancer, and more than 42,000 will die from the disease in 2020. Breast cancer is not one, but many diseases based on the biology of each tumor. In triple-negative breast cancer, tumor cells lack hormone receptors and do not have excess HER2 protein. Approximately 15 percent of breast cancers are triple-negative based on the results of diagnostic tests. It is an aggressive form of the disease with few treatment options.

Tecentriq U.S. Indications (pronounced t-SEN-trik)

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma.

Tecentriq may be used in patients with urothelial carcinoma if their bladder cancer has spread or cannot be removed by surgery, and if they have any one of the following conditions:

The approval of Tecentriq in these patients is based on a study that measured the amount of time until patients disease worsened. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as the first treatment in patients with lung cancer if:

Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as the first treatment in patients with lung cancer if:

Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as the first treatment in patients with lung cancer if:

Tecentriq may be used alone in patients with lung cancer if:

If a patients tumor has an abnormal EGFR or ALK gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound in patients with TNBC when their breast cancer:

The approval of Tecentriq in these patients is based on a study that measured the amount of time until patients disease worsened. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

A type of lung cancer called small cell lung cancer (SCLC).

A type of liver cancer called hepatocellular carcinoma (HCC).

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

The most important information about Tecentriq is:

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life-threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

The most common side effects of Tecentriq when used in TNBC with paclitaxel protein-bound include:

The most common side effects of Tecentriq when used in hepatocellular carcinoma with bevacizumab include:

Tecentriq may cause fertility problems in females, which may affect their ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects of Tecentriq.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555.

Please visit http://www.Tecentriq.com for the Full Tecentriq Prescribing Information for additional Important Safety Information.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentechs approved PD-L1 checkpoint inhibitor, the companys broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit http://www.gene.com/cancer-immunotherapy.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200617005876/en/

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Genentech's Tecentriq in Combination With Chemotherapy (including Abraxane) Meets Primary Endpoint of Improved Pathological Complete Response,...

A new study by researchers at Tulane University, located in the city of New Orleans, United States, revealed the discovery of the gene behind the most aggressive form of breast cancer, as well as how to disable it to curb tumor growth and cancer spread.

We also recommend: High-performance cancer vaccine developed in China

The report published in the Scientific Report of the journal Nature, explains that the research focused on triple negative breast cancer (TNBC), the most aggressive form of this type of cancer. It is a difficult disease to treat and where the chances of survival are lower than in other types of this cancer.

The researchers looked at the role two specific genes play in TNBC called Rab27a and TRAF31P2. Subsequently, they suppressed these two genes causing them to stop working and found positive impacts in the fight against breast cancer.

Doctor Reza Izadpanah, team leader, explains:

Our findings show that both genes play a role in the growth and metastasis of breast cancer. Although the Rab27a target slows the progression of tumor growth, it does not affect the spread of small numbers of cancer cells or micrometastases. Conversely, attacking TRAF3IP2 suppresses tumor growth and spread, and interfering with it reduces preformed tumors and prevents further spread. This exciting discovery has revealed that TRAF3IP2 may play a role as a novel therapeutic target in the treatment of breast cancer.

And it is that the scientists of the University of Tulane discovered that when they turned off the TRAF3IP2 gene, the metastasis of the cancer, that is, its spread, did not take place for a full year after treatment. Furthermore, deletion of this gene was also related to stagnant tumor growth and shrinking the tumor to undetectable levels.

So far, these positive effects have been seen in animals, meaning that gene deletion therapy has yet to be tested in humans. However, Izadpanah and his team are quite positive about it and have already turned to the FDA. to speed up the path and be able to carry out clinical trials.

See the original post here:
They discover how to stop tumor growth in breast cancer - Explica

The first symptom I had was a hot flush. To say peri-menopausal was not on my radar is an understatement says Cathy Brooks, development manager with the UCD Foundation.

I had no idea. Id just lost my mum in October and I remember by Christmas being with friends in Collins Barracks, having a coffee walking around and I just started getting these hot flushes and I was thinking what the hell is this? To be honest, I just attributed it to the grief and losing my mum and all of that.

It was only when I googled it and I saw the symptoms that I thought, could I be? Im too young.

She was 39 at the time.

Initial blood tests suggested Cathy was not peri-menopausal but with her symptoms continuing she decided to seek advice from a second GP. On hearing her symptoms, the doctor immediately suspected haemochromatosis and decided to carry out a blood test.

I like to think Ive a very positive outlook on life, Cathy says, explaining how she made the decision that she wasnt going to focus on this. I just got on with living life.

Every year I go for a check-up in the haematology clinic in St Vincents . They do your bloods before and they check your liver, your heart all the organs that can be damaged. Its like going in for an annual MOT really, she continues.

Only in the last six months Ive started to get really achey in my index finger and my middle finger. When I close my fist I can feel my fingers kind of crunching. Thats a symptom of haemochromatosis.

Because Cathys joints are getting really stiff, she has been referred to a rheumatologist.

Cathy describes herself as being very active.

I do a lot of sport. I do it for my mental health as well as my physical health, she adds, discussing her love of rowing and cycling. But this year, like most of the world, Ive just been sitting on the couch eating, she says. Im more stiff now because Im not active.

Cathy has phlebotomies every three months to treat her haemochromatosis but shes keen that her blood doesnt go to waste just because of her condition.

If Ive to give blood for the rest of my life, I dont want my blood to be dumped because theres too much iron in it. I want my blood used. So I go to this clinic where they can use my blood, she says adding that people with haemochromatosis travel from all over the country to the clinic in Stillorgan for this very reason.

The service has been extended and now, many people with haemochromatosis can become regular blood donors at all blood donation clinics nationwide, including local community clinics.

Potential donors must meet specific haemochromatosis management criteria, the Irish Blood Transfusion Service states, which includes having completed iron depletion therapy, and not suffering from any serious complications as a result of haemochromatosis.

They must also satisfy standard blood donation criteria to be able to attend clinics to give blood which can then be used to save patients lives throughout the country

Thankfully, Cathy hasnt experienced any difficulties giving blood in Covid-19 times.

I happened to give blood about two weeks ago. Ive heard loads of people are having trouble giving blood during coronavirus. I havent had any problem. Ive had nothing but a positive experience with all of this and all the professionals.

What is haemochromatosis?

Haemochromatosis is a genetic condition which, in many people who have the condition, gives rise to excess iron absorption and retention within the body, explains Prof Suzanne Norris, professor of hepatology and gastroenterology, Trinity College, Dublin.

Over time, and its a very slow, gradual process, iron accumulation builds up and the iron is absorbed and deposited in various organs. We have the highest rate of haemochromatosis of any European and worldwide country

What are the symptoms of haemochromatosis?

Chronic fatigue is the main symptom, Prof Norris explains. Achey joints would be another. The problem with haemochromatosis is that it doesnt really have a symptom that would make you say aha thats haemochromatosis. Its all subtle signs. Its a disease thats under the radar because it doesnt produce a symptom that would make a doctor think that has to be that condition. Its literally chronic fatigue and unfortunately most chronic conditions will give rise to chronic fatigue.

How is haemochromatosis diagnosed?

To make the diagnosis, you need to have inherited the gene for excessive iron accumulation from both parents. Only about 50 per cent of people who have the two genes actually ever develop iron overload, so theres obviously another trigger, which may be environmental, we dont quite know, Professor Norris says.

What are the potential complications of haemochromatosis?

Typically the organs that end up having too much iron absorbed within them are the liver, the pancreas which may give rise to diabetes, the joints which may give rise to arthritis, Prof Norris explains.

Bronze diabetes, or brown discolouration of the skin is actually quite rare. There are other symptoms which may occur around depression and low mood. Its not clear whether thats just in relation to general inflammation because of the iron burden, or because of not feeling well and low mood associated with chronic ill health in that regard.

What is the treatment for haemochromatosis?

The treatment is very simple. Its blood letting or having blood removed on initially maybe a weekly or monthly basis in the acute stage when the person is coming in with a new diagnosis, ProfNorris explains.

Once the excess iron has been removed its like giving blood to the blood bank, you donate blood once or twice a year, that might be sufficient for most people. Some people may do it four times a year and that keeps the condition totally under control.

When the iron level is back within the normal range and its maintained at that level by either once to four times a year, depending on the persons needs, it keeps it completely under control and there is no risk of developing serious potential complications from late diagnosis once its diagnosed early, Professor Norris emphasises.

Our message is always, at this time of year, for healthcare professionals to really think about chronic fatigue could it be iron overload, rather than anaemia giving rise to chronic fatigue.

For more information, visit the Irish Haemochromatosis Association at haemochromatosis-ir.com (to donate 4, text IRON to 50300).

Follow this link:
The subtle signs that point the way towards haemochromatosis - The Irish Times

Eighteen years ago, former Alabama football coach Gene Stallings made a difference in the life of a grieving woman and her beautiful newborn.It's a story about love and compassion, a story that has not been told until now.This is the story of The Coach and Little Grace:Her heart was heavy on Mother's Day 2002.Laura Davis was depressed and confused as her first child slept at her side.Was she crazy to feel so sad? So hopeless? After all, her daughter Grace was a mere 14 days old. Laura Davis was supposed to be happy.As Grace slept, Laura asked God for answers. How was she supposed to care for a child with Down Syndrome? How was she supposed to see the future as her child had just been diagnosed with two holes in her heart? How was she supposed to have hope when her doctor told her that little Grace would never walk, talk or read?Her husband was doing his residency in Columbus, Ohio, and while Chris was working hard, Laura cried. She was overwhelmed. She missed her hometown of Vestavia Hills. She missed talking about life and Bama football with her friends.And getting out of bed? It just wasn't happening.The phone rang, and Laura took a deep breath, inhaling tears that had fallen from her eyes."Hello," said Laura."Hello, Laura, this is Gene Stallings. I wanted to call to wish you a Happy Mother's Day."Laura's heart jumped.Was it really THE Gene Stallings? The head coach of her beloved Crimson Tide?Why in the world was Gene Stallings calling Laura Davis, who was in Columbus, Ohio?"I also want to congratulate you on your newborn, Grace," the Tide coach said.How in the world did Coach Stallings know about Grace?The two exchanged pleasantries, and then Stallings revealed why he was really calling: To give Laura Davis hope. To get her out of bed.The coach proposed a question to Laura:"What is the one thing that you want for little Grace? You want her to someday go to heaven, right?""Of course," Laura replied.And then came just one of many bits of advice that the coach offered up:"Well, Laura, Grace has a one-way ticket because God loves her and so do you," he said. "You may not know this right now, but you are in for the ride of your life. You will never stop loving little Grace."And another piece of advice from the coach:"If the Lord asked me if I would rather have had John Mark the way he is or had him as a 'normal' child, I would tell Him that I would rather have had Johnny just the way he is."Coach Stallings said "goodbye" and hung up the phone.The tears in Laura's eyes returned. But this time they were happy tears. She had chill bumps.Little Grace remained next to her, asleep.We never know when that moment might come, but on Mother's Day 2002 that moment came for Laura Davis.She closed her eyes and prayed, promising God that she was going to make the most of Grace's life and offer her daughter every ounce of love that she could muster.And suddenly, good things started to happen:The two holes in Grace's heart closed on their own.Grace smiled.Physical therapy began, then speech therapy.Laura and Chris would move back to Vestavia Hills as Grace turned two. Years of hard work followed. Reading, writing, speaking.Vestavia Hills' special education teacher Jennifer Greer came into their lives and Grace blossomed as a cheerleader, a student and a friend.God was good.And now for the cherry on top:Three days ago, Grace Davis, the girl who was doubted, mocked, and given little chance to live a fulfilling life, graduated from Vestavia Hills High School. Grace will enter Auburn's "Eagles" program this fall. Yes, 18 years after doctors doubted her, Grace Davis will be going to college.Chris and Laura Davis are enjoying life in Vestavia Hills. Chris is an ENT doctor, and their sons Jack and Will are growing fast.Laura tells me that she will never forget Mother's Day 2002, the day that she received an unexpected phone call not from a football legend, but rather from the father of a Down Syndrome child.It was a phone call that motivated Laura to get of bed and look to the future one that ended up being more amazing than she could have ever imagined.And now you know the story of The Coach and Little Grace.A story with a happy ending!

Eighteen years ago, former Alabama football coach Gene Stallings made a difference in the life of a grieving woman and her beautiful newborn.

It's a story about love and compassion, a story that has not been told until now.

This is the story of The Coach and Little Grace:

Her heart was heavy on Mother's Day 2002.

Laura Davis was depressed and confused as her first child slept at her side.Was she crazy to feel so sad? So hopeless? After all, her daughter Grace was a mere 14 days old. Laura Davis was supposed to be happy.

As Grace slept, Laura asked God for answers. How was she supposed to care for a child with Down Syndrome? How was she supposed to see the future as her child had just been diagnosed with two holes in her heart? How was she supposed to have hope when her doctor told her that little Grace would never walk, talk or read?

Her husband was doing his residency in Columbus, Ohio, and while Chris was working hard, Laura cried. She was overwhelmed. She missed her hometown of Vestavia Hills. She missed talking about life and Bama football with her friends.

And getting out of bed? It just wasn't happening.

The phone rang, and Laura took a deep breath, inhaling tears that had fallen from her eyes.

"Hello," said Laura.

"Hello, Laura, this is Gene Stallings. I wanted to call to wish you a Happy Mother's Day."

Laura's heart jumped.

Was it really THE Gene Stallings? The head coach of her beloved Crimson Tide?

Why in the world was Gene Stallings calling Laura Davis, who was in Columbus, Ohio?

"I also want to congratulate you on your newborn, Grace," the Tide coach said.

How in the world did Coach Stallings know about Grace?

The two exchanged pleasantries, and then Stallings revealed why he was really calling: To give Laura Davis hope. To get her out of bed.

The coach proposed a question to Laura:

"What is the one thing that you want for little Grace? You want her to someday go to heaven, right?"

"Of course," Laura replied.

And then came just one of many bits of advice that the coach offered up:

"Well, Laura, Grace has a one-way ticket because God loves her and so do you," he said. "You may not know this right now, but you are in for the ride of your life. You will never stop loving little Grace."

And another piece of advice from the coach:

"If the Lord asked me if I would rather have had John Mark the way he is or had him as a 'normal' child, I would tell Him that I would rather have had Johnny just the way he is."

Coach Stallings said "goodbye" and hung up the phone.

The tears in Laura's eyes returned. But this time they were happy tears. She had chill bumps.

Little Grace remained next to her, asleep.

We never know when that moment might come, but on Mother's Day 2002 that moment came for Laura Davis.

She closed her eyes and prayed, promising God that she was going to make the most of Grace's life and offer her daughter every ounce of love that she could muster.

And suddenly, good things started to happen:

The two holes in Grace's heart closed on their own.

Grace smiled.

Physical therapy began, then speech therapy.

Laura and Chris would move back to Vestavia Hills as Grace turned two. Years of hard work followed. Reading, writing, speaking.

Vestavia Hills' special education teacher Jennifer Greer came into their lives and Grace blossomed as a cheerleader, a student and a friend.

God was good.

And now for the cherry on top:

Three days ago, Grace Davis, the girl who was doubted, mocked, and given little chance to live a fulfilling life, graduated from Vestavia Hills High School.

Vestavia Hills City Schools

Grace will enter Auburn's "Eagles" program this fall. Yes, 18 years after doctors doubted her, Grace Davis will be going to college.

Chris and Laura Davis are enjoying life in Vestavia Hills. Chris is an ENT doctor, and their sons Jack and Will are growing fast.

Laura tells me that she will never forget Mother's Day 2002, the day that she received an unexpected phone call not from a football legend, but rather from the father of a Down Syndrome child.

It was a phone call that motivated Laura to get of bed and look to the future one that ended up being more amazing than she could have ever imagined.

And now you know the story of The Coach and Little Grace.

A story with a happy ending!

See more here:
Coach and Little Grace: Mother of child with Down Syndrome gets life-changing phone call - WVTM13

Welcome back to The Rundown, our daily breakdown on comic news stories we missed from the previous day. Have a link to share? Email our team at rundown@multiversitycomics.com.

In case you missed it, we got an exclusive preview of Sera and the Royal Stars #7.

Nathan W. Pyles Strange Planet will be getting a subscription box from Culturefly, The Pop Insider reports. Fans will be able to get exclusive merchandise inspired by the comic as part of this new subscription box. Each box includes a vinyl figure, an exclusive comic on a canvas print, and five to seven additional items featuring the creatures. The subscription box will launch on June 1.

Via Bleeding Cool, Doctor Who fans were treated to a special comic strip written by James Peaty, illustrated by Mike Collins, and narrated by Richard Ashton, in which fans find out more about Danny Pink. Its unclear when the next series of Doctor Who will premiere, although the show will return in the next year with the special Revolution of the Daleks.

Variety reports that Nick Jonas and Lawrence Fishburne are set to star in AGC Studios The Blacksmith, based on the graphic novel from Kickstart Comics by Malik Evans and Richard Sparkman. Pierre Morel (Taken) will direct from a screenplay adapted by Ben Ripley (Flatliners). Jonas will play Wes Loomis, a go-to weapons expert for the intelligence community, who goes on the run after his lab is destroyed and colleagues are murdered. Fishburne will play Mather, a retired blacksmith, and Loomiss mentor. With the aid of a CIA analyst named Noelle Hazlitt, the trio will embark on a journey that keeps this improbable pair one step ahead of their pursuers in a breathless, action-filled thriller. Production on the film will begin later in 2020.

Via Comicbook.com, Cartoon Network announced that We Bare Bears: The Movie will officially release for purchase on digital platforms on June 8, 2020. This is the first movie for the We Bare Bears franchise, which follows three talking bears as they explore life in the woods and city. In addition to the release date, Cartoon Network has also revealed a poster and trailer. The movie will depict the bears as they make their way to Canada after being chased from their home by antagonist, Agent Trout. Eric Edelstein, Demetri Martin, and Bobby Moynihan star in the movie as the bears Grizz, Ice, and Panda. Agent Trout is voiced by Marc Evan Jackson and many of the shows guest stars will also be featured in the movie. We Bare Bears: The Movie is scheduled to release for purchase on digital platforms for $14.99 on June 8, 2020.

Netflix has released the official trailer for The Old Guard, based on the comic by Greg Rucka and Leandro Fernandez. Like the comic, the movie follows a group of immortal soldiers led by Andy, played by Charlize Theron, who must fight to keep their immortality a secret, or otherwise see their gifts exploited. The film will begin streaming on Netflix on July 10, 2020. You can check out the trailer here.

Deadline reports that Sony has hired Marc Guggenheim to write a script for Jackpot, another installment in the larger Spider-Man Cinematic universe following the Venom franchise, and Jared Letos Morbius. In the comics, Jackpot is Sara Ehret, a scientist, who, while pregnant, is doing gene therapy research and is exposed to Lot 777, a virus that rewrites the DNA in her cells. She becomes imbued with superhuman strength and takes on the name Jackpot. Morbius is scheduled to be released on March 19, 2021, while Venom: Let There Be Carnage is set to hit theaters June 25, 2021.

TV Line reports that ABC has renewed 13 shows on their current lineup, including Stumptown. The TV show is based on the comic book series from creators Greg Rucka and Matthew Southworth, and follows Dex, an army vet turned private detective. Season 1 premiered in September. Its unknown when production will begin on season 2 of Stumptown.

Here is the original post:
The Rundown: May 22, 2020 - Multiversity Comics

The evolution of CAR T-cell therapy has been an exciting development for the treatment of all lymphomas, including mantle cell lymphoma, according to Dr. Ian Flinn.

BY Dr. Ian Flinn

The evolution of CAR T-cell therapy has been an exciting development for the treatment of all lymphomas, including mantle cell lymphoma, according to Dr. Ian Flinn.

In an interview with CURE, Flinn, the director of lymphoma research at Sarah Cannon Research Institute, discussed the use of CAR T-cells to treat lymphomas, as well as how the ZUMA-2 trial is shaping up to influence the treatment of patients with mantle cell lymphoma.

Transcription:

CURE: I'm curious about the ZUMA-2 trial. I know that you're an investigator on that trial. So, if you could talk a little bit about the drug, what it targets, how it works in the body and where things are with that study so far.

Flinn: ZUMA-2 is a clinical trial looking at a CAR T-cell product that targets CD19, which is an antigen on a lot of lymphomas, in this case mantle cell lymphoma, in patients who have had multiple prior therapies for their mantle cell lymphoma, and who are really no longer responding.

So, in this trial, we administered CAR T-cells to these patients. And after giving them some what's called lymphodepleting chemotherapy, and then infuse the CAR T-cells into the patients, we saw a really pretty remarkable outcome.

First (let me offer) a little bit about what a CAR T-cell is. Its a white blood cell, a lymphocyte, that is harvested from the blood of a patient. It's then sent to a central manufacturing facility, where a gene is inserted into the lymphocyte to have the lymphocyte activate as well as target the lymphoma. In this case, it's targeting that antigen called CD19, that's present on most B cell lymphomas and most all the mantle cell lymphoma, many other types of lymphoma as well.

So, it's a really exciting development in the treatment of all lymphomas and in certain forms of leukemia. A similar CAR T-cell product had previously been shown to be very effective in patients with an aggressive form of lymphoma, known as large cell lymphoma. And studies in that patient population led to the approval of CAR T-cells for patients with diffuse large B-cell lymphoma, who also similarly were not really responding to any agents anymore. The therapy had really run the course of what conventional treatments (could offer). And in that patient population there was about a 40%, what looks like long term cure rate for that patient population, so really fabulous results in large cell lymphoma.

And so, in this trial, this trial ZUMA-2, we're hoping to see similar activity in patients with, again, very difficult-to-treat mantle cell lymphoma, patients who already had standard of care therapies such as a tyrosine kinase inhibitor, and chemo immunotherapy. And we saw very remarkable results. Two-thirds of patients achieved a complete remission in this study, and the follow up is relatively short, but in a subgroup of patients that have been followed for more than two years on, about 40% of patients remain in remission.

So, this would be the first CAR T-cell product that will be available to patients with mantle cell lymphoma?

Right. This would be the first CAR T-cell product that's available for mantle cell lymphoma patients. We hope to see FDA approval sometime this summer. It's been submitted to the FDA for approval, and they have certain timelines that the FDA has to make. And based on that, we know that we should hear the latest by August on whether this drug will be approved.

Is there anything else that people should know about this particular study?

I think the other thing to know is when anybody is looking at any kind of therapy, is what are the risks and benefits of this? It sounds wonderful, augmenting the immune system and you're harnessing the immune system to fight the cancer, which is really what this is doing. But it does have side effects. And, and those side effects are sometimes scary.

There's something called cytokine release syndrome, where basically as I explain it to patients, it's like someone's getting the worst flu of their life. I mean, sometimes they can have fevers as high as 104 (degrees). But when you think about it, that's kind of what we're wanting. We want the immune system to be turned on. We want it to go after this lymphoma, what it thinks is foreign. (But) then we've learned better ways of decreasing those side effects now by using other medications to decrease the incidence and severity of cytokine release syndrome.

The other toxicity is called neurological toxicity, or neurotoxicity, and this can be very disturbing to patients and their family members. Because it can sometimes range from just being a little bit sleepy to people being in a full coma. Luckily, nobody died in this study from this, and we're getting better at intervening earlier to decrease the severity of neurologic toxicity. And so, for the vast majority of patients, it's reversible, but it's definitely something for patients who are considering this (drug) to talk to their doctor about.

Read more here:
CAR T-Cell Therapy a 'Really Exciting' Development in Treatment of Lymphomas - Curetoday.com

The danger of cancer continues to cast a shadow of fear in the lives of Indian women. According to experts, the women being diagnosed grow younger by day compared to the same in developed countries. UK-born Dr Asima Mukhopadhyay is a clinician-scientist in womens cancer. Having set up the Project Ovarian Transnational Group of Studies in Kolkata in 2015 and the Kolkata Gynecological Oncology Trials and Translational Research Group, the first-ever research group from India to become a member of the Gynecological Cancer Intergroup, she is one of the leading voices in women's cancer research and in the country. This year, she donated her royalty money as a co-developer of the PARP inhibitor Rucaparib (an anti-cancer drug) to build research capacity for cancer in India. We spoke to her about what needs to be done in cancer research in the country and how we can ensure that treatment reaches the people who need it the most. Excerpts:

What is the current status of women's cancer care in India? Could you outline the areas where we need to move ahead?

The keys areas where we need to move ahead are public awareness through media and community-based programmes. School and college health education would be a major step in ensuring that women with symptoms get to see a cancer specialist in regional cancer centres in the first place rather than reaching thereafter a significant financial drain and loss in valuable time or inadequate treatment. Secondly, we need more trained specialists and dedicated organ-specific cancer teams capable of addressing our specific needs. We also need preventive measures like vaccination, screening, genetic testing and risk-reducing surgeries, as well as ensuring access to life-saving cancer drugs and treatment options.

What led you to make the decision to donate your royalty payment?

On a personal front, I decided on a career in cancer care and research after the demise of my father at a relatively young age in 1998 due to cancer. It was not so long after that I had graduated from Medical College Kolkata. As a cancer survivor family and a young budding doctor, I had the first-hand experience of the emotional, social and economic turmoil and helplessness that one has to undergo to fight this disease and the need for better treatment options and research towards this.

After my return to India in 2015 from the UK, I had joineda reputed cancer centre in Kolkata as an onco-surgeon; I noticed that in India, a majority of cancer patients are not aware of the need to participate in studies or clinical trials which automatically improves the quality of care. In countries like the UK, major cancer research organisations are heavily supported through public funding and donations. We need similar support mechanisms in India including media support and goodwill for promoting better patient care.

Could you describe your discovery around epithelial ovarian cancer and the implications it has for treating cancer?

It had been previously shown by the Newcastle University group of researchers in the UK and various other groups that cancers harbouring a genetic defect in the BRCA genes are very sensitive to a new class of anti-cancer drug called PARP inhibitors. I joined this group in 2008 as a clinician-researcher for my PhD. In 2010, I showed that approximately that 50% epithelial ovarian cancer patients harbour a defect called BRCAness or homologous recombination deficiency (HRD), therefore providing the scope for extending the use for PARP inhibitors to a lot more women compared to only 10-20% of women who have inherited detects in the BRCA gene.

In 2011, this was published as the first-ever report showing the importance of functional BRCAness. I developed a functional biomarker assay (used to understand the mechanism of action of a drug) using ascitic fluid from ovarian cancer patients at the Northern Gynaecological Oncology Centre in Gateshead. After 10 years of my original publication, there is a renewed interest in adopting the functional HRD assay as a better biomarker for selecting patients suitable for PARP inhibitor therapy.

Are women in India at a position where they can seek medical help successfully? How do we spread more gynaecological awareness among the general public?

Partially, yes. There are health systems available and women can seek proper medical health at the tertiary centres. However, many primary and secondary health centres are not much developed and we often find patients referred to us with partial or incomplete treatment. The need of the hour is to train the trainer. Healthcare workers should be trained regarding various cancers, their symptoms, risk factors, hereditary factors and their preventive and treatment opportunities, so that they are able to identify the population at risk of cancers and create health education camps for enlightening the population.

School health awareness campaigns can be created so that children of ages 12 years and above are educated regarding breast self-examination, menstrual hygiene, personal hygiene, obesity and hereditary cancer history so that they are aware of their physical and hereditary risks and act accordingly to prevent cancers in future. These children are the future of our society and if we can incorporate the knowledge of health awareness, the cancer risk in women will sufficiently decrease in future. I firmly believe that if we can incorporate such community-based awareness and screening camps integrated within the existing governmental structures, the access of women from low-income households will surely increase.

See more here:
Meet this Newcastle University scientist who donated all her royalty money to improve cancer research in India - EdexLive

Image source: The Motley Fool.

Protagonist Therapeutics, Inc. Common Stock(NASDAQ:PTGX)Q12020 Earnings CallMay 07, 2020, 5:00 p.m. ET

Operator

Good day, and welcome to the Protagonist Therapeutics PTG-300 development update Call. Please note that today's conference is being recorded. At this time, I would like to introduce Don Kalkofen, Protagonist's chief financial officer. Please go ahead.

Don Kalkofen -- Chief Financial Officer

Thank you, operator. Good afternoon, everyone. Please note that a replay of today's call will be available at the Investors section of our website at protagonist-inc.com. Before we begin, I'd like to remind you that today's discussion will include statements about the company's future expectations, plans and prospects that constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our quarterly and annual reports on forms 10-Q and 10-K, which are on file with the SEC. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our view should change. With that, I will now turn the call over to Dinesh Patel, president and CEO, to provide you an update on the company's progress to date.

Dinesh Patel -- President and Chief Executive Officer

Thanks, Don. Good afternoon, everyone, and thank you all for joining us today. On today's call, we'll also hear from Samuel Saks, our chief medical officer; and Dr. Ronald Hoffman, Professor of Medicine in Hematology and Medical Oncology at the Mount Sinai Hospital in New York City.

Dr. Hoffman has been involved in the Phase II clinical study of PTG-300 in polycythemia vera, and he will provide a brief overview of the disease and his perspectives on PTG-300 and its potential benefits as the novel treatment for polycythemia vera or PV. Also present for the call today are David Liu, our chief scientific officer and head of R&D and Suneel Gupta, our chief development officer. We are pleased to have all these individuals available to address questions during the Q&A session of today's call.

So let's start with Slide No. 3. As you are well aware, Protagonist started the year 2020 with three clinical assets, all of which have been discovered through the use of our peptide technology platform in six different clinical proof-of-concept studies. The three assets fall in two broad categories: PTG-300 for various blood disorders, most of which are rare disease; and oral GI-restricted targeted peptide PTG-200 and PN-943 for inflammatory bowel disease, or IBD.

All of these assets have a multibillion-dollar potential in multiple indications. PTG-300 peptide mimetic of the natural hormone hepcidin that serves as a master regulator of iron homeostasis storage and distribution in the body was being pursued in Phase II open-label proof-of-concept studies in beta-thalassemia, or beta-thal; polycythemia vera, or PV; hereditary hemochromatosis, or HH; and an investigator-sponsored study in myelodysplastic syndrome, or MDS. As you may recall, a major objective for 2020 was to pick our first clinical indication for PTG-300 that we can progress toward a pivotal study in 2021. Today, we are pleased to announce initial but yet very robust clinical data from our polycythemia vera program.

And the selection and prioritization of polycythemia vera as the first indication for a pivotal study with 300. This decision is based on three criteria: strength and consistency of the clinical data, favorable regulatory path forward and the commercial opportunity. This is our major announcement today. And while most of our discussion will be around 300 and polycythemia vera, let me also take this opportunity to talk briefly about our oral gut-restricted IBD assets, largely in the context of corporate update and cash runway.

The enrollment rate of Phase II studies of these agents, namely the oral alpha-4-beta-7 integrin antagonist PN-943 for ulcerative colitis and the oral interleukin-23 receptor antagonist PTG-200 for Crohn's disease are understandably going to be influenced by the current COVID-19 situation. Therefore, while these studies are continuing, we believe it is appropriate to remove future guidance on the timelines for top line data from these studies. In addition to the decision to focus our efforts toward rapidly advancing 300 in polycythemia vera indication, we are continuing the ongoing proof-of-concept study of 300 in hereditary hemochromatosis as a potential second indication and are also deciding to now discontinue further development of 300 for beta-thalassemia as well as for myelodysplastic syndrome. On the financial side, we ended the first quarter of this year with about $117 million in cash and investments.

By factoring in the delay in enrollment and the associated clinical development costs, coupled with a reduction in operational needs and expenditures, we are now extending our cash runway by an additional six months through the middle of 2022. Now let's go to Slide No. 4, and let me turn to PTG-300, a major highlight of today's call and to provide rationale for why we are pursuing polycythemia vera as our first indication. First and foremost, it's the robust and consistent clinical responses we have seen in our ongoing Phase II PV trial.

Although small, the data set is very compelling and consistent. On six out of six, dose compliant patients treated for up to 28 weeks with 300 are phlebotomy free as of today. These are very noteworthy results. Keeping in mind that prior to entering our study, these subjects were receiving frequent phlebotomies in the weeks leading up to enrollment.

We are obviously very encouraged by these results, and the enrollment in the study continues with eight patients enrolled to date. And we have also decided to now expand the current study from 30 patients to 50 patients. The second factor is the regulatory path forward for the development of 300 in polycythemia vera indication. As you know, approved drugs for polycythemia vera fall into the orphan drug designation category by virtue of it being a rare disease in the U.S.

and Europe. And orphan status provide certain benefits to the drug developer, including seven years of market exclusivity upon FDA approval, prescription drug use of fee waivers and tax credits for qualified clinical trial. The third factor besides the data and the regulatory path is the very significant commercial opportunity that lies ahead of us based on the significant unmet need that exists today for these patients. And specifically, by virtue of PTG-300 being a novel mechanism-based, first-in-class non-cytoreductive natural hormone mimetic agent.

While PV is a rare disease, there are approximately 100,000 people in the U.S. living with this disease, and this number is unfortunately expected to grow as the population ages. The majority of PV patients are treated with phlebotomies, cytoreductive therapies or a combination of those treatments. Jakafi is the only FDA-approved cytoreductive therapy in PV and despite having a limited indication in patients who have had an inadequate response to current treatment, Jakafi is expected to reach almost $2 billion in sales in 2020, and the largest percentage growth is in the PV population, 19% year-over-year based on their most recently quarterly update.

PTG-300 has the potential to address a significant unmet need in this category where there is a lack of new cytoreductive agents in development. 300 offers the potential of keeping patients phlebotomy-free without causing iron deficiency. So to summarize, we are incredibly encouraged by our preliminary but strong and consistent data and, therefore, are electing to focus our resources on expedited development of 300 for polycythemia vera. To speak more about this, I would now like to introduce our chief medical officer, Dr.

Samuel Saks. Sam?

Sam Saks -- Chief Medical Officer

Thanks, Dinesh. As Dinesh mentioned, we are really encouraged by the results we have seen in the ongoing Phase II study of PTG-300 in patients with polycythemia vera. Dr. Hoffman is going to walk you through the study results in detail, but I wanted to highlight why I believe this data has prompted us to focus on PV as the first indication for 300.

The majority of PV patients today are treated with phlebotomy, or phlebotomy in combination with cytoreductive therapies to control erythrocytosis and keep the hematocrit levels below 45%, as indicated in many treatment guidelines. There is a large body of evidence that shows that managing hematocrit is challenging and regardless of best available therapy, they're a substantial portion of patient segments that have poorly controlled hematocrit and therefore, a higher mortality rate compared to age match controls. The treatment paradigm of PV allows patients to enter what I call the danger zone before they get the next treatment. So even those people who are considered well-controlled have increased hematocrit leading up to their phlebotomy.

Self-administered 300 may reduce doctor visits and the anxiety associated with the uncertainty of phlebotomy at that time. Phlebotomy is those of donated blood know, is associated with acute symptoms and difficulties. But the real problem in these patients is the potential for chronic symptoms related to iron deficiency in phlebotomized patients. PTG-300 offers the possibility of putting the control of the hematocrit in the patient's hands with a weekly self-injected mimetic of an endogenous hormone mimetic.

With a clear decision to focus PTG-300 development in PV, we are expanding the current study to include additional patients, and we'll be also hosting a scientific planning meeting with leaders in the field of myeloproliferative neoplasms. We will also be working with patient advocates to discuss pivotal and future studies in polycythemia vera. I will close by saying that while further follow-up and data from additional patients will be needed to confirm the continuity of the robust clinical responses observed to date, we believe this study provides a compelling rationale to initiate planning for a pivotal program in PV. In the near term, we are expanding the current study to include additional patients as we focus on these encouraging results.

Finally, I want to express how proud I am of the entire clinical development team of Protagonist and all the Protagonist employees that helped us to get where we are today with this program. With that, I would like to turn it over to Dr. Hoffman, who needs no introduction. He's a recognized expert in the field of myeloproliferative disorders and is Director of the Myeloproliferative Disease Program at The Icahn School of Medicine at Mount Sinai and an investigator in the 300 study.

Dr. Hoffman?

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

Yes. Thank you very much, Sam. Thanks for the opportunity to present this really exciting data. So if we can go to Slide 7, I can educate the audience on what polycythemia vera is so they can have a better understanding of the potential for 300 and put this in context.

So as you can see here, this slide is entitled "What is Polycythemia Vera?" Well, polycythemia vera is a member of a group of chronic hematologic malignancies termed myeloproliferative neoplasms. And these neoplasms are unusual in that patients frequently live several decades. And these neoplasms occur at the level of the hematopoietic stem cell. And unlike leukemia, they are characterized by increased production of mature blood cells.

In polycythemia vera, the cell that's most destructive to the patients are really the increased production of red blood cells. And that's the term erythrocytosis that you've heard previously and we'll hear subsequently. Now the interesting thing about this disease is that there are 100,000 cases of polycythemia vera in the United States. This disease occurs across races and age groups.

And the critical diagnostic warning sign is that of an elevated hematocrit, which is the hallmark of the disease. I think the importance of this drug is that although there's 100,000 cases of these patients, these patients, as I mentioned, live for several decades, so the usage of this drug would be quite prolonged over that period of time. The disease occurs primarily in individuals who are 50 to 70 years of age. There is, however, a higher incidence in young females who present with life-threatening thrombotic events.

The thrombotic events that occur in patients with polycythemia vera include strokes, as well as life-threatening thrombosis of arteries or veins within the venus within the abdominal cavity. There's a very high incidence of acute myocardial infarction, cerebral vascular incidents and strokes. The women that we've talked about, the young women, they are particularly prone to develop thrombosis within the abdominal cavity, especially the hepatic vein, and that leads to a life-threatening condition called Budd-Chiari syndrome. In its most severe forms, it requires liver transplantation.

Over the last 15 years, there's been tremendous understanding, new understanding of this group of myeloproliferative neoplasms. And they've been shown to be characterized by mutations in genes that are associated with myeloid blood cell production. So the myeloproliferative neoplasms are associated with three driver mutations: one involving JAK2, the other gene called calreticulin and the other MPL, which is a receptor for the hormone thrombopoietin. Virtually 99% of patients with polycythemia vera have a mutation in JAK2.

Most commonly, it is a mutation that occurs at exon 14, which is the JAK2V617F mutation. A smaller group of patients have a mutation in exon 12, and those are referred to as exon 12 patients, and they have a similar phenotype, again, elevated hematocrits, increased thrombosis and shorter lifespan due to these thrombotic events and severe erythrocytosis. Next slide, please. We're going to talk now about the diagnosis, symptoms and treatment of polycythemia vera, so that you can get an understanding of the role, the potential role of PTG-300.

The diagnosis of polycythemia vera is triggered by finding an elevated hematocrit serendipitously or by a thrombotic event, and that initiates the physician looking for the diagnosis. So for instance, a patient could present within an acute myocardial infarction and be found to have hematocrit. These warning signs, then prompt, the blood tests to be performed that look for the presence of the JAK2V617F mutation or the exon 12 mutation of JAK2V617F is not present. And sometimes, a bone marrow examination is required to perform histopathologic confirmation of the diagnosis.

This disease is not only complicated by thrombotic episodes, but it's also complicated by burdensome systemic symptoms, including fatigue, headache, visual symptoms, night sweats and itchiness. And this itchiness characteristically occurs on exposure to water and has termed aquagenic pruritus. This might seem like a trivial symptom but aquagenic pruritus can be so severe that patients are unable to shower for months or can lead to such stress that occasionally, we've unfortunately had patients who have succumbed to suicide. Thrombotic events is the greatest risk to patients with polycythemia vera.

These thrombotic events, as I mentioned, include heart attacks, strokes, deep vein thrombosis or pulmonary embolism or the Budd-Chiari syndrome. The cardinal feature of treatment and reduction of this thrombotic risk is to reduce the hematocrit below 45%. Again, the hematocrit is just the measure that we use of the number of red blood cells and the degree of erythrocytosis. And that assures that essentially the viscosity of the blood or the stickiness of the book is reduced, thereby reducing the incidence of thrombosis.

So normalization of the hematocrit using therapeutic phlebotomy is very common, and it is really the first treatment in newly diagnosed patients with polycythemia vera. Unfortunately, therapeutic phlebotomy leads to the removal of red blood cells, which contain iron and it leads to more severe iron deficiency contributing to many of the exacerbation, of many of the systemic symptoms that I referred to previously. And those patients that require frequent phlebotomies or at their advanced stage that is over 60 years of age or have thrombosis, a prior thrombosis, it is the recommendation of the standard of care that those patients all be treated with hydroxyurea, interferon or Jakafi. It is in this situation that 300 is especially attractive drug because it can be used to treat patients who are not requiring myelosuppressive agents or it could be a replacement for those myelosuppressive agents.

Again, the site of the reductive agents are hydroxy and interferon, which are used in combination with phlebotomy, with supplemental phlebotomy, or an alternative drug is Jakafi or ruxolitinib, which is the only U.S. FDA-approved product for phlebotomy. Each of these drugs, and I can go into that in detail during the question-and-answer period are associated with significant adverse effects and have a questionable surrounding their tolerability. Significant evidence, as I've mentioned, shows that controlling the hematocrit below 45% is the most important factor in minimizing thrombosis, cardiovascular events and death due to thrombosis.

Please let's go to the next slide. So we're going to talk a little bit about phlebotomy, which many of you have probably experienced when you donate blood. So most patients receive phlebotomy initially. Phlebotomy is basically the removal of a unit of blood to reduce the hematocrit below 45%.

So our target is to keep those patients always below 45% because it's been well demonstrated in the literature that, that reduces significantly the incidence of thrombosis. And the incidence of thrombosis has been shown to be reduced when the degree of time with an adequate of 45% is maximized. In addition, these would patients receive low-dose aspirin to paralyze their platelets and their or further augment this antithrombogenesis in patients with polycythemia vera. Patients who undergo phlebotomies will often report feeling tired or dizzy after the phlebotomy.

And especially in the elderly, this is a major factor. Many of these patients become hypertensive, require long stays in our outpatient facility or require fluid infusions because or going to congestive heart failure because of their poor fluid balance. Furthermore, regular phlebotomy results in iron deficiency that makes the augmentation of iron deficiency that may have debilitating symptoms. As I mentioned, particularly severe fatigue, weakness and cognitive impairments.

This cognitive impairment is a really big deal because many of the patients complain of having a fuzzy brain syndrome, and they cannot concentrate and do their jobs. In addition, some of the patients have craving for unusual substances such as ice or clay, which is termed pica. And then, unfortunately, some of the patients have a restless leg syndrome, which prevents them from going to sleep. Three or more phlebotomies in a year in those patients receiving hydroxyurea is associated with an inferior prognosis and a higher incidence of thrombotic events.

So you can also think that in that situation, even in a patient who is receiving hydroxyurea, their combination therapy with 300 could eliminate those frequent phlebotomies and further improve the treatment regimen for these patients. I think the most important part that you'll see about this drug are the real high-quality aspect of it is that we see these patients, let's say, a three or four-month intervals. At that three or four-month interval, we see that they have an elevated amount of hematocrit and that triggers us to do a phlebotomy. But in reality, we have no way to monitor them during the interval between their visits, and it's likely that for significant periods of time, they have an elevated hematocrit that's only detected at the time of their visit to our clinic.

So as you'll see, the really cool part about PTG-300 is that there's a sustained hematocrit control, which we've really never been able to achieve with any of the other agents or with phlebotomy alone. Let's go now on to Slide No. 10, which is PTG-300 and non-cytoreductive hepcidin hormone mimetic, its mechanism of action. So how does this drug really work? Well, hepcidin hormone, has been established recently in the last couple of decades, is playing a primary role in promoting the sequestration of iron and macrophages and decreasing iron availability for the production of red blood cells.

So macrophages are a type of white blood cell, and they are present not only in the bone marrow, but they're also present in all other body tissues. But the macrophages in the marrow are termed nursing cells because their activity is essentially to feed iron to red blood cells in the marrow and to alter to allow them to produce additional red cells. This process is disregulated by the JAK2 mutation leading to erythrocytosis. So PTG-300 is believed to limit the excess production red cells in polycythemia vera by essentially allowing that iron to remain in the macrophages.

Therefore, preventing its transfer into the erythroid precursors. In addition, it blocks the iron that's present in the macrophages in the tissues outside of the marrow. And therefore, we believe alleviates many of the systemic symptoms that are associated with polycythemia vera. Let's now go on to Slide 11, which is the Phase II study design.

This is a really interesting manner in which this study has been constructed. You can see there are three phases. Part one is the dose-finding period, which is over 28 days. And there are two components to that.

I believe effective dose-finding phase, where we essentially dose-escalate patients to meet the inadequate requirements. Then a 12 to 14-week period where we essentially have efficacy evaluation that is to maintain the patient's hematocrit below 45%. And then there's part two as a blinded withdrawal where the patients are randomized to receive either the fixed active dose or placebo dose for up to 12 weeks. And then I'm sure the patients will be happy about that, those that go on placebo, they will then allow them we will be allowed to put them on to an open-label extension phase up to 52 weeks where they will again be able to receive 300.

If the patient's hematocrits exceed 45%, they get supplemental phlebotomies. Let's go on to Slide No. 12. This is essentially the responses that we've seen in the seven patients that have been described, that have been evaluated.

The red triangles indicate the phlebotomies, and you can see a lot of them to the left of the solid line. And that's the 32 weeks prior to treatment. And you can see that each of these patients, and these were entry criteria, had at least three phlebotomies during that period. And then you can see this dotted line, and that's the time at which the doses the drug was started.

And the first thing that strikes you is that there are a lot of red triangles to the left and only one red triangle to the right, and that's one of our patients who missed one dose due to the unfortunately, due to the pandemic. And the numbers indicate the doses that were administered over that period of time. So for instance, you can see in patient 150201, there was a dose escalation and then de-escalation, which I'll discuss on the subsequent slide. So this slide really summarizes and probably is our most important slide.

And it basically shows that with the administration of this drug and careful titration that phlebotomy is almost virtually eliminated. Next slide. Let's focus on two patients. One is the top patient, which is the blue line.

And you can see that this patient, this is the individual who missed the dose because of the COVID infection. And you can see that he was started at 10 milligrams, then went up to 20 milligrams. And on 20 milligrams, he had a hematocrit 47.5, he was unable to come in at that time because of the COVID infection. So we increased his dose to 40 milligrams, his hematocrit dropped, but it was still above 45.

He came in, we phlebotomized him, and we've kept him now on 40 milligrams, and you would have seen on Wednesday, and he did not require a phlebotomy and his hematocrit was below 45. If you look at the bottom patient who is in bright red, you can see that, that patient started at time 0 on 10, then was increased to 20 and then on week seven got 40 milligrams and then on week 12 got 80 milligrams. And you can see that, that led to a hematocrit dropping to 37.5. We cut our dose to 40 milligrams, and you can see that over that period of time, she has remained phlebotomy-free.

We saw her on Wednesday, and she again remains below hematocrit of 45. So there's a dose adjustment that you can easily do. The drugs are being administered at home by the patients, giving them a lot of freedom and also empowering them to control their own disease. If we go to Slide 14.

This addresses how do we know that PTG-300 is really hitting its target. And what we're measuring here is serum ferritin. And if you can recall, ferritin is a molecule that reflects storage iron. And you can see these numbers in the vertical column, and if you're below 25, that indicates that one is iron-deficient.

And you can see it with the administration of the drug at subsequent doses over time, the ferritin doses, the ferritin levels increased in each of these patients except the bottom line where a patient received an extremely hematocrit control with an extremely low dose of 300. So these data indicate that the drug is acting on target. What about the adverse defense? Because this is a chronic disease, one must anticipate that patients will be treated over decades. This is a small sample set but you can see that we had no serious adverse events and the adverse events that were recorded were essentially just irritations, essentially at the injection site that slowly resolved and one of the patients had a bruise at a 10-milligram dose.

Let's go on now to Page 16, which is our summary. So just to start this off. I think phlebotomy has probably been used for almost 100 years. And for at least, since I've been in this field, which is from the 70s, there's been great debate about what is the optimal myelosuppressive agent.

There's great concern about chemotherapy being used in these patients, perhaps increasing the incidence of evolution to acute myeloid leukemia. We never really anticipated that a hormone therapy might be used for this type of disease. So I think this trial really represents a paradigm shift and it has great importance for patients with polycythemia vera. So I think we can easily conclude that the additional data demonstrates the potential of this drug to almost entirely avoid the need for bottoming the treatment of polycythemia vera.

All dose compliant patients were phlebotomy-free. Persistent control of hematocrit levels, I think that's really one of the most important issues is that the patients have a sustained control of their hematocrit, which we anticipate will lead to sustained alleviation of their systemic symptoms and elimination of thrombotic episodes. And again, as I tried to indicate to you these elevated hematocrit levels are associated with significant cardiovascular events such as heart attack and stroke. This drug also offers the possibility of weekly administration without the up and down excursions inherent in phlebotomy therapy or any of the toxicities associated with phlebotomy therapy that I discussed with you.

Also, this reduction in phlebotomy may allow sufficient iron to be available systemically to avoid symptoms that we know that are related to iron deficiency. So PTG-300 has the potential as the first non-cytoreductive therapy for PV. This drug is well tolerated and has a safety profile similar with results in prior studies. So as you can see from my presentation, I'm extremely enthusiastic about this drug and its future.

Thank you for your time.

Dinesh Patel -- President and Chief Executive Officer

Thank you, Dr. Hoffman. I would like to note that the results we have discussed today address the study data as of May 1, and the study continues to enroll. And our plan will be to submit to present additional data at upcoming medical meetings.

So at Protagonist, we are now working on four clinical programs with our three candidates, all discovered through our technology platform. Our priorities are: one, advancing PTG-300 in polycythemia vera as well as in hereditary hemochromatosis; two, advancing PN-943 to a Phase II study in ulcerative colitis; and three, working closely with our partner, Janssen, to continue Phase II development of PTG-200 in Crohn's disease. As a result of our ability to limit our focus with 300 to PV and HH, we have organized our efforts to extend our cash runway for an additional six months. We have taken steps to manage and lower our operating costs and align our resources around our current studies.

As a consequence, we now have adequate financial resources to fund planned operating and capital expenditures through the middle of 2022. Finally, we are mindful of the impact that the current coronavirus outbreak may have on our local operations and global activities. As we disclosed in our financial results released today, we are suspending guidance for PN-943 Phase II initiation and PTG-200 Phase II data, and we are actively working to minimize impact on timelines and move as quickly as conditions would permit. Our priority is maintaining the health and safety of our employees and those who are participating in our studies.

We will continue to monitor changing conditions carefully and provide updates as appropriate. With that, we would like to now open up the call for questions. Operator?

Operator

[Operator instructions] Our first question comes from the line of Chris from Nomura. Your line is now open.

Chris Marai -- Nomura Instinet -- Analyst

Hi. This is Chris Marai from Nomura Instinet. Maybe the first one is for the physician on the line. Thank you so much for the overview of PV.

I was curious how you look at a therapeutic like PTG-300 in terms of clinical practice on sort of an everyday basis as you see PV patients? And how do you think it may fit, assuming this profile remains consistent in sort of the treatment lines of PV, how you may see its usage, in particular relative to drugs like Jakafi? Thank you.

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

OK. I think that's a really terrific question. I think its use would be quite wide. I think virtually all patients with PV would be candidates for this drug.

As you can see, we have treated young patients and also older patients with this drug. So it's been well tolerated. I think the advantage, again, is that, especially with young patients, those individuals, we do not want to give life-long myelosuppressive therapy or interferon or Jakafi because of unanticipated potential for unanticipated adverse effects. So if they have an increased phlebotomy requirement, this would be an ideal treatment for those folks because basically, it would free them up from returning to the clinic as frequently as they do and requiring repeated phlebotomies.

When we risk-stratify these patients, those patients that go on the three treatments that I've discussed before, frequently, they still require phlebotomies, and it's been shown by European investigators, if you have additional phlebotomies during your administration of these drugs, that you are an increased risk of thrombosis. So in that setting, this drug could be an adjunctive agent that would eliminate the needs for phlebotomy. Alternatively, and I could see this developing quite quickly, patients are frequently unwilling to take any of these agents, especially hydroxyurea and interferon because of the potential of hydroxyurea and the concern about interferon essentially having systemic symptoms, problems with individuals about immune disease and also its effect to exacerbate depression in patients. So in those individuals, I could see and even in those high-risk patients, if we can control their hematocrits with this drug, which I think we can easily do, and we've demonstrated that.

That this drug would be a real competitor for any of those agents. So I think it could be essentially utilized potentially for the broad swath of patients with polycythemia vera. So I think and for long periods of time, that's the issue that I'd like to really emphasize to you. For instance, like young females who have Budd-Chiari syndrome, and we usually put those young females on myelosuppressive therapy and interferon for life-long periods of time, and they can live several decades.

They would far prefer being on a non-chemotherapy, non-biologic agent like interferon, it would really liberate them, especially from the adverse effects.

Chris Marai -- Nomura Instinet -- Analyst

OK. That's very helpful. And then I was wondering if we could touch upon the data for a minute. Dr.

Hoffman, could you elaborate on some of the effects of spleen size that you may have observed in the trial, if any? What you would hope to see there on an endpoint like that in a patient population like this? Thank you.

Ronald Hoffman -- M.D., Director of the Myeloproliferative Diseases Program

Yes. So in this situation, what you have to understand is this is not myelofibrosis. So in reality, most patients with or virtually all patients, I'll say most, the overwhelming majority of patients with patients with polycythemia that don't have symptomatic splenomegaly. So the endpoints that have been used in the past, let's say, for Jakafi for reduction of spleen size are of minimal importance.

So these patients, even though some of them have high-risk disease, really didn't have they had minimal splenomegaly at all, only 40% of patients with polycythemia vera have splenomegaly and only for our advanced disease it's symptomatic. So the sample size is too small. In animal models, when hepcidin mimetics were given, those are polycythemia vera animal models, the administration of a different hepcidin mimetic did lead to reduction in splenomegaly but we really were not able to assess this because none of these patients really had significant splenomegaly. So we await treating patients like that to see if the data in the mice is recapitulated in humans as it relates to spleen size.

Chris Marai -- Nomura Instinet -- Analyst

Very helpful. Thank you.

Operator

Our next question comes from the line of George Farmer of BMO. Your line is now open.

Gobind Singh -- BMO Capital Markets -- Analyst

Hi, everyone. This is Gobind Singh on for George. Congrats on making a decision and moving forward with those two indications. I guess we had two buckets of questions.

The first two, maybe for Dinesh. I know you guys were thinking about once-weekly dosing and possibly twice weekly dosing in beta-thal. I was wondering if maybe going forward, at least with PV, do you think you might be looking at twice weekly dosing at all? And I was wondering since we are moving past beta-thal and MDS, if you'd be willing to comment at all as to what kind of data we're seeing in those indications? And I'll have a follow-up for Dr. Hoffman, if that's OK.

Dinesh Patel -- President and Chief Executive Officer

Yes. Gobind, thanks for the question. And I will have Sam Saks, our CMO, answer the first question.

Sam Saks -- Chief Medical Officer

Sure. So with respect to the use of 300, we think that it's going to be used widely. You were asking me...

Dinesh Patel -- President and Chief Executive Officer

About the once-weekly.

See the rest here:
Protagonist Therapeutics, Inc. Common Stock (PTGX) Q1 2020 Earnings Call Transcript - The Motley Fool

When looking at treatment outcomes for small, hormone-receptor-positive, HER2-positive breast cancers that have not spread to the lymph nodes, a study suggests that women diagnosed with cancers 810 mm (about 0.31 inches to 0.39 inches) in size had better survival when they were treated with chemotherapy after surgery compared to women diagnosed with smaller cancers.

The research was published on April 9, 2020, by the journal JAMA Network Open. Read the abstract of Association of Survival With Chemoendocrine Therapy in Women With Small, Hormone Receptor-Positive, ERBB2-Positive, Node-Negative Breast Cancer.

The HER2 gene is also called the ERBB2 (Erb-B2 receptor tyrosine kinase 2) gene.

Research shows that very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers have a 5-year recurrence risk the risk of the cancer coming back within 5 years that ranges from 5% to 25%, with or without treatments after surgery. Doctors call treatments given after surgery adjuvant treatments.

Because HER2-positive cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with chemotherapy after surgery to reduce recurrence risk. Still, it has been unclear whether the benefits of treating very small, node-negative, hormone-receptor-positive, HER2-positive breast cancers with chemotherapy after surgery outweighed the risks.

It wasnt clear what to do with these patients, who make up a really small population of breast cancer patients, Anurag Singh, M.D., of Roswell Park Comprehensive Cancer Center, one of the researchers who did the study, said in an interview.

We know that if you have an ERBB2 tumor, it's worse, and the idea has been they should get chemotherapy,he continued. You have an otherwise healthy 60-year-old, mammographically screened and detected patient. When you give them the information, they're saying, 'OK, I have all of these good things, but I've got a 2-mm tumor and you want to give me 6 months of chemo. Are you serious? I'm going to lose my hair, I'm going to have this, I'm going to have that. It seems like an awful long way to go.' We didn't really have good evidence for them.

The researchers looked at the records of 10,065 women diagnosed with node-negative, hormone-receptor-positive, HER2-positive breast cancer that was 10 mm or smaller in size between 2010 and 2015.

All of the women were treated with hormonal therapy after surgery:

From 2013 to 2015, anti-HER2 therapy such as Herceptin (chemical name: trastuzumab) was coded differently than chemotherapy in patient records; 15% of the women treated during this time had either chemotherapy or anti-HER2 therapy alone.

Follow-up time ranged from about 2 years to about 5 years.

The researchers compared the outcomes of women treated with hormonal therapy and chemotherapy to women treated with hormonal therapy alone. They also looked to see if the size of the cancer affected any benefits from chemotherapy.

The analysis showed that chemotherapy was associated with better overall survival for women diagnosed with cancers that were 810 mm in size. Women diagnosed with cancers that were smaller did not seem to get any survival benefits from chemotherapy.

To our knowledge, this is the first report to suggest that there is an association between improved survival and adjuvant chemoendocrine therapy specifically for HR-positive, ERBB2-positive tumors 8 mm to 10 mm compared with those smaller than 8 mm, the researchers wrote. It is evident that tumors 10 mm and smaller represent a heterogeneous group whose treatment should be tailored to improve the risk-to-benefit ratio of systemic therapy.

The results of this study offer helpful information about which women may benefit from chemotherapy after surgery for very small, hormone-receptor-positive, HER2-positive breast cancer that hasnt spread to the lymph nodes.

Still, the results are based on extremely small differences in cancer size millimeters and require expert pathology review of the cancer. The researchers also didnt know the exact chemotherapy regimens the women had.

Also, anti-HER2 medicines, such as Herceptin, are often given along with chemotherapy. In this study, for 2 years of the 5-year study, anti-HER2 therapy and chemotherapy were not coded differently. So, a number of women may have been receiving both anti-HER2 therapy and chemotherapy during that time, which may have affected the study results.

If youve been diagnosed with a very small, hormone-receptor-positive, HER2-positive breast cancer that hasnt spread to the lymph nodes and are considering treatments after surgery, it makes sense to talk about this study with your doctor. The results offer more information about outcomes and can help you decide on the best treatments for your unique situation.

For more information on chemotherapy, including types of medicines and side effects, visit the Breastcancer.org Chemotherapy pages.

Written by: Jamie DePolo, senior editor

Published on May 7, 2020 at 12:02 PM

Excerpt from:
Chemotherapy for Certain Small, Hormone-Receptor-Positive, HER2-Positive Breast Cancers Seems to Improve Survival - Breastcancer.org

Updated: May 8, 2020 3:18:58 pm

By Dr Uma Vaidyanathan

Thalassaemia is a disorder of the haemoglobin structure. A tetramer molecule present in the RBCs, haemoglobin is responsible for supplying oxygen in the body and is a rich source of protein in the blood. The human Hb/HbA has two sets of globin chains. These are a-globin chain and -globin chain. Four genes (two inherited from the mother and two from the father) regulate the production of a-globin chain, while only two genes (each inherited from father and mother) control the production of -globin chain.

The thalassaemia syndromes are characterised by a basic defect in the synthesis of one type of globin chains. As a result, there is insufficient Hb content in the resultant red cells, leading to decreased haemoglobin concentration, anaemia and need for multiple blood transfusions in severe cases.

Each year, more than 70,000 babies are born with thalassaemia worldwide and this defect is very often seen in the Indian subcontinent. Haemoglobin electrophoresis is the gold standard in diagnosing this condition. Patients with thalassemia traits do not require long-term monitoring. They usually do not have iron deficiency, so iron supplements are unlikely to improve their anemia.

Read| Pregnant during the COVID-19 crisis? Heres how to take care of mental health

Alpha thalassaemia

In alpha thalassaemia, the hemoglobin does not produce enough alpha protein. To make alpha-globin protein chains we need four genes, two on each chromosome 16. We get two from each parent. If one or more of these genes is missing, it will result in alpha thalassemia. The severity of thalassemia depends on how many genes are faulty, or mutated.

One faulty gene: The patient has no symptoms. A healthy person who has a child with symptoms of thalassemia is a carrier. This type is known as alpha thalassemia minima.

Read| Covid-19 and pregnancy: What expectant mothers need to know

Two faulty genes: The patient has mild anemia. It is known as alpha thalassemia minor.

Three faulty genes: The patient has hemoglobin H disease. This is a type of chronic anemia. In this case, the patient needs regular blood transfusions throughout their life.

Four faulty genes: Alpha thalassaemia major is the most severe form of alpha thalassemia. It is known to cause hydrops fetalis, a serious condition in which fluid accumulates in parts of the fetus body. A fetus with four mutated genes cannot produce normal hemoglobin and is unlikely to survive, even with blood transfusions.

Beta Thalassemia

Two globin genes are required to make beta-globin chains: one gene from each parent. Beta thalassaemia is caused when one or both genes are faulty.

Severity depends on how many genes are mutated.

One faulty gene: This is called beta thalassaemia minor.

Two faulty genes: There may be moderate or severe symptoms. This is known as thalassaemia major (earlier known as Colleys anemia).

Medical management of thalassaemia major depending on severity would be:

Blood transfusions

Chelation therapy removal of excess iron overload in body

Bone marrow transplant

Gene therapy

Management during Pregnancy can be divided as follows:

Periconceptional care

Screening and counseling pre-pregnancy: Screening can identify couples having 25 per cent risk or more of having a pregnancy with signi?cant haemoglobinopathy. If a pregnant woman is found to be a carrier of haemoglobinopathy, the partner needs to be screened as soon as possible. If a risk of the fetus having major haemoglobinopathy is detected, urgent expert counselling is provided to the couple so that they can make an informed choice regarding the prenatal diagnosis and the possible termination of pregnancy.

Folic acid supplementation: Beginning in the preconceptual period, at least three months prior to conception, folic acid in the dosage of 5 mg/day helps in preventing neural tube defects.

Some additional tests also might be needed. Doctor might ask the patient to take blood sugar and thyroid function tests. Patients could be asked for cardiovascular assessment. Ultrasound of liver and the gallbladder (and spleen, if present) should be performed. This helps in detecting gallstones and evidence of liver cirrhosis due to iron overload or transfusion-related viral hepatitis.

Antenatal care

Women with thalassaemia should be reviewed on a monthly basis until 28 weeks of gestation and fortnightly thereafter. Women with thalassaemia are best treated in a multidisciplinary team setting, including an obstetrician with expertise in managing high-risk pregnancies and a hematologist.

Ultrasound scanning

An early scan after 7 to 9 weeks of gestation is needed to determine viability as well as the presence of a multiple pregnancy. A detailed anomaly scan must also be done after 11-12 weeks and 18 to 20 weeks of gestation. Later, ultrasounds may be needed to assess foetal growth restriction.

Care during labour and delivery

Thalassaemia is not an indication for cesarean section. Patients may need blood transfusion in case of excessive blood loss during the delivery.

Postpartum care

Women with thalassemia are at high risk for venous thromboembolism due to the presence of abnormal red blood cells in the circulation.

Breastfeeding is safe and should be encouraged. In addition, there is no contraindication to the use of hormonal methods of contraception, such as the combined oral contraceptive pill, the progestogen-only pill, hormonal implants, and the Mirena intrauterine system in women with thalassaemia.

(The writer is Senior Consultant, Obstetrics and Gynecology Fortis Hospital, Shalimar Bagh.)

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World Thalassaemia Day: What does the condition mean for pregnancy? - The Indian Express

In August 1989, scientists made a blockbuster discovery: They pinpointed the faulty gene that causes cystic fibrosis, a cruel lung disease that killed many of its victims before they reached adulthood.

The human genome was uncharted territory, and the gene hunt had become an all-out international race, with laboratories in three countries searching for the root of the disease.

That fall, biologist James Wilson stood before an audience of researchers, physicians and cystic fibrosis patients and their families and described gene therapy, a way to replace the faulty gene with a good copy. Wilson had intended his talk to be technical and prophetic, but he was overwhelmed by the surging thrill in the room that science was about to save peoples lives.

It was one of the most amazing experiences that Ive ever had, Wilson said, adding, The expectations were through the roof.

The importance of the cystic fibrosis gene discovery went far beyond a single illness. It helped build the case for the $3 billion project to sequence the entire human genome, which would alter understanding of human biology and shed light on rare and common diseases.

But the story of cystic fibrosis has been illustrative in a way that no one could have anticipated back then. In the early days of human genetics, the path seemed straightforward: Find the gene, fix the gene and repeat for other diseases. The cystic fibrosis journey, from an exuberant moment of insight to a major success, would take 30 years of persistent, methodical work: a feat of science, business, fundraising and patience that has become a model for other diseases.

I specifically remember sitting with my doctor in the exam room, having the conversation that the gene was discovered, said Josh Taylor, 48, of Virginia Beach, who has cystic fibrosis. And him telling me the cure is just he literally said, In 5 to 10 years, were going to beat this.

It was not until late 2019 that another breakthrough fulfilled many of the hopes of 1989. Now, Taylor has what he has been waiting for all these decades a new drug, Trikafta, that is effective for 90 percent of patients. Doctors marvel at what they think will be possible if it is given at an early age: a full life span.

Cystic fibrosis developed when a child had the bad luck to inherit two faulty genes, one from each parent. Back then, there was no test to detect whether a parent carried a defective gene because no one even knew what the gene was.

As scientists developed new tools to probe human genetics, cystic fibrosis quickly became one of the top targets. It is the most common inherited disease among Caucasians, afflicting 30,000 Americans, and its motivated patient group spurred the work forward with funding.

All these human disease genes were floating around. We knew they were inherited, but we knew very little. We didnt know what the genes were, or where they were located, said Robert Nussbaum, a medical geneticist who was hunting genes for other diseases.

Francis Collins, now director of the National Institutes of Health and then a scientist at the University of Michigan working on cystic fibrosis, was photographed for the universitys graduates magazine sitting in a haystack holding a needle, to convey the magnitude of the technical challenge.

Almost everybody knew some family where it had happened, and it was heartbreaking to see what these kids go through, Collins said.

Robert Beall, then an executive vice president at the Cystic Fibrosis Foundation, which was funding the work, was also the most impatient human being I ever met to his credit, Collins said.

Collins partnered with biologist Lap-Chee Tsui, in Toronto holding joint lab meetings at a midway point on the long drive, in London, Ontario.

After years of work, Tsuis lab had narrowed the search to ever smaller stretches of DNA, pioneering new techniques in the search for the gene. Collins had invented a method to speed up the process called chromosome jumping, which allowed scientists to leap over sections of DNA something he compares to leaping from one street corner to the next to initiate searches. Jack Riordan, another scientist in Toronto, discovered a bit of DNA that looked like it might be a part of the gene, providing an essential lead.

In May, a scientist in Tsuis lab found a tantalizing clue three missing letters of DNA in a patient with cystic fibrosis. The team would need to confirm that this genetic mutation was the cause of the disease. Collins and Tsui were at a scientific conference at New Haven, Conn., a month later when they got more evidence.

One rainy night after the days program was over, the pair raced to Tsuis room, where he had installed a portable fax machine to receive updates from the lab. Among the papers that had spilled onto the floor was a table showing those three letters of DNA missing in multiple patients with cystic fibrosis, while they were present in healthy people.

Lap-Chee was a little more skeptical, Ive got to see more data, Collins recalled. I bought it, that was it. I wanted to scream and jump up and down.

The news report triggered frantic preparations to present the findings officially, and the work was published in Science magazine that September in three papers.

Collins would testify before Congress that it was necessary to fund the human genome project because the flat-out effort to find the cystic fibrosis gene simply would not be scalable in trying to understand thousands of other diseases.

Gene therapy, the thinking went, would soon cure cystic fibrosis, marking a turning point in the treatment of genetic diseases. The idea was relatively straightforward: Use a virus to ferry a good, functioning copy of the gene into patients lung cells.

But human biology turned out to have all sorts of ways of resisting an easy fix, and it quickly became clear that gene therapy would not be simple in real lungs.

Then the entire gene therapy field screeched halted in 1999 with the death of Jesse Gelsinger, a teenager with a metabolic disorder who died after being treated for the disorder in one of Wilsons gene therapy trials.

As the hope for a high-profile gene therapy success crashed, research continued on the basic, less glamorous work to untangle what went wrong with the cystic fibrosis gene. That understanding made it possible to develop ways to screen chemicals, to see if any showed promise as a drug.

Beall and Preston Campbell of the Cystic Fibrosis Foundation visited Aurora Biosciences, a San Diego biotech company that used robotics to massively speed up such testing.

Bob and I were like kids in a candy shop, Campbell recalled. After a small initial investment, the foundation stunned the nonprofit world in 2000 by awarding the company $40 million, a new kind of venture philanthropy arrangement in which if the company was successful, the nonprofit group would receive a share of the royalties.

A Massachusetts company, Vertex Pharmaceuticals, acquired Aurora in 2001, and although the cystic fibrosis work continued, it was considered a long shot, called the fantasy project internally, recalled Fred Van Goor, a scientist who joined the company around that time and became the biology lead for the cystic fibrosis program.

The scientific problem was huge: The most common gene mutation in cystic fibrosis created a protein that couldnt do its essential job in the cell. The protein didnt fold correctly, which interfered with its ability to reach the surface of the cell. And it didnt function well once there, where it was supposed to work as a gate. That meant theyd need multiple drugs to help patients one to get the protein to the right spot, the other one to open the gate.

Vertexs first drug candidate was focused on just one of the problems getting the gate to work better. Alone, it would help only about 4% of patients, whose disease was caused by a rare mutation. That drug, Kalydeco, was approved in 2012, but it remained unclear whether a drug could be made that would work for a larger group of patients.

Then, Vertexs main product a hepatitis C drug was eclipsed by a better treatment from a competitor, and the future of the company and its cystic fibrosis research was cast in doubt.

It obviously created an incredible crisis here at Vertex, said Jeff Leiden, chief executive of the company.

Vertexs board decided to bet on cystic fibrosis, and in 2015, a two-drug combination called Orkambi, was approved for a larger group of cystic fibrosis patients. Excitement about the drugs began to yield to a societal debate about their high prices; Orkambis launch price was $259,000 a year.

Meanwhile, the company would need to develop a third drug to treat more patients.

Drug trials are blinded so that neither the patients nor the scientists know which people are receiving the drug and which are receiving a placebo. When Trikafta, the triple drug combination that would ultimately be approved, was unblinded from one trial in October 2018, researchers finally saw the slide showing how the drug affected lung function.

There was a stunned silence in the room for a full minute. The drug worked.

Ten percent of cystic fibrosis patients, or about 3,000 people in the United States, are still waiting for a therapy that works for them.

Stacy Carmona, who was born just three years before the gene was discovered, is one of them.

Im so excited for the community. Im so excited for the CF friends I have who so desperately need the drug. There are so many people hanging on by a thread, waiting for this, Carmona said. The flip side of that is you cant help but wonder when is it going to be my turn?

See original here:
A cystic brosis success story -- over 30 years | Health - The Union Leader

WATERTOWN, Mass., April 28, 2020 (GLOBE NEWSWIRE) -- Selecta Biosciences, Inc. (NASDAQ: SELB), a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance platform, ImmTOR, today announced the appointment of Dr. Goran Ando to its Board of Directors, replacing Amir Nashat, effective April 24, 2020. Amir will continue to serve in an advisory capacity to Selecta.

The addition of Dr. Ando to our Board means that Selecta now has another proven leader with a successful track record in product development and commercialization, said Carrie S. Cox, Chairman of the Board, Selecta Biosciences. This addition to our team puts us in a position of strength for the next evolution of ImmTOR initiating the Phase 3 clinical trial of SEL-212, bringing our gene therapy program into the clinic, and applying the platform in other areas of significant unmet need. I would also like to recognize Amir Nashat for his long-term commitment to our organization and the important role he played in advancing Selectas scientific platform. From an early stage, Amir recognized the potential of ImmTOR for patients with serious diseases, and I want to thank him for helping put Selecta in the position it is in today.

The opportunity to work alongside the Selecta team to advance the ImmTOR platform is of undeniable interest to me, said Dr. Ando. The ability to re-dose patients with AAV gene therapy may be pivotal in improving outcomes, while Selectas late-stage asset in chronic refractory gout could provide patients with this debilitating disease a much-needed alternative. I look forward to being part of the effort to increase the applicability of the ImmTOR platform for the benefit of patients.

Dr. Ando brings more than 37 years of experience as a respected global pharmaceutical leader. He currently serves as the Chairman of the Board for Eyepoint Pharma, and holds seats on the Boards of Parexel, Tessa Therapeutics, and EUSA Pharma. He is also the retired Chairman of the Board of Novo Nordisk A/S. Dr. Ando began his pharmaceutical industry career as Medical Director of Pfizer AB, progressing to Director, Clinical Research with Pfizer International in the U.S. He went on to hold various senior positions at leading global healthcare and pharmaceutical businesses, including Bristol-Myers Squibb and GlaxoSmithKline. He was the VP, Medical and Scientific Affairs at Bristol-Myers Squibb before taking the role of President of the Astra Research Centre in Sweden. In 1989, Dr. Ando joined GlaxoSmithKline, where he held various senior appointments, including Research & Development Director for Glaxo Group Research. He later joined Pharmacia AB as Executive Vice President, and ascended to Deputy CEO in 1995, moving to the U.S. in 1997 to lead R&D with additional responsibilities for manufacturing, information technology, business development and M&A. During his eight-year tenure as Head of R&D at Pharmacia/Pharmacia & Upjohn, 17 new drugs were approved by the U.S. Food & Drug Administration prior to Pharmacias acquisition by Pfizer for $60 billion. He then served as the Chief Executive Officer of Cell Tech Group PLC, one of the most successful European biotech companies, until it was acquired by UCB Pharma for $3 billion in 2005. He has been a Senior Adviser to leading specialist healthcare investment group Essex Woodlands since 2007. Dr. Ando received his Bachelor of Arts degree from Uppsala University in Sweden and Doctor of Medicine degree from Linkping University in Sweden.

About Selecta Biosciences, Inc.Selecta Biosciences, Inc. is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance (ImmTOR) platform. Selecta plans to combine ImmTOR with a range of biologic therapies for rare and serious diseases that require new treatment options due to high immunogenicity. The companys current proprietary pipeline includes ImmTOR-powered therapeutic enzyme and gene therapy product candidates. SEL-212, the companys lead product candidate, is being developed to treat chronic refractory gout patients and resolve their debilitating symptoms, including flares and gouty arthritis. Selectas proprietary gene therapy product candidates are in preclinical development for certain rare inborn errors of metabolism and incorporate ImmTOR with the goal of addressing barriers to repeat administration. Selecta is based in Watertown, Massachusetts. For more information, please visit http://selectabio.com.

Forward-Looking StatementsAny statements in this press release about the future expectations, plans and prospects of Selecta Biosciences, Inc. (the company), including without limitation, statements regarding the progress of the clinical development of SEL-212, expectations surrounding the enrollment and design of the Phase 2 head-to-head (COMPARE) clinical trial comparing SEL-212 and Krystexxa, timing of related data readouts and the ability of the COMPARE results to inform the planned Phase 3 clinical trial of SEL-212, the anticipated timing of the planned Phase 3 clinical trial, whether the head-to-head trial with Krystexxa will demonstrate superiority, the unique proprietary technology platform of the company and the unique proprietary platform of its partners, the potential of ImmTOR to enable re-dosing of AAV gene therapy, the potential of SEL-212 to fulfill unmet needs in chronic refractory gout patients including sustained SUA reduction, reduced flares, and once monthly dosing, the companys commercial plans, the ability of the companys ImmTOR platform, including SEL-212, to unlock the full potential of biologic therapies, the potential of SEL-212 to treat chronic refractory gout patients and resolve their debilitating symptoms, the potential treatment applications for product candidates utilizing the ImmTOR platform in areas such as enzyme therapy and gene therapy, the ability of the ImmTOR platform to enhance transgene expression, the ability of the Company and AskBio to develop gene therapy products using ImmTOR and AskBios core technology, the novelty of treatment paradigms that the Company and AskBio are able to develop, the potential of any therapies developed by the Company and AskBio to fulfill unmet medical needs, AskBios ability to make milestone payments, AskBios ability to develop and commercialize a drug product containing ImmTOR for the treatment of Pompe disease, the companys plan to apply its ImmTOR technology platform to a range of biologics for rare and serious diseases, the potential of the companys two gene therapy product candidates to enable repeat administration, the Companys ability to re-dose patients and the potential of ImmTOR to allow for re-dosing, the potential of the ImmTOR technology platform generally and the companys ability to grow its strategic partnerships, the Companys plans to present at the American College of Rheumatology Annual Meeting, the sufficiency of the companys cash, cash equivalents and short-term investments, and other statements containing the words anticipate, believe, continue, could, estimate, expect, hypothesize, intend, may, plan, potential, predict, project, should, target, would, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including their uncertain outcomes, whether or not the COVID-19 outbreak will impact the companys ability to initiate a Phase 3 clinical trial for SEL-212 or to initiate a clinical trial in any of its gene therapy programs, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, the unproven approach of the companys ImmTOR technology, potential delays in enrollment of patients, whether due to the COVID-19 outbreak or for other reasons, other issues surrounding the COVID-19 outbreak which may cause the company to discontinue or pause its ongoing or planned clinical trials, undesirable side effects of the companys product candidates, its reliance on third parties to manufacture its product candidates and to conduct its clinical trials who could be affected by the COVID-19 outbreak or could otherwise materially fail to perform, the companys inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, managements ability to perform as expected, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the companys recurring losses from operations and negative cash flows from operations raise substantial doubt regarding its ability to continue as a going concern, substantial fluctuation in the price of its common stock, the impact of the COVID-19 outbreak on the companys operations, including its supply chain, clinical and financial operations, and other important factors discussed in the Risk Factors section of the companys most recent Annual Report on Form 10-K, and in other filings that the company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the companys views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The company specifically disclaims any intention to update any forward-looking statements included in this press release.

For Media:Joshua R. MansbachSolebury Trout+1-646-378-2964jmansbach@soleburytrout.com

For Investors:Lee M. SternSolebury Trout+1-646-378-2922lstern@soleburytrout.com

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Selecta Biosciences Appoints Dr. Goran Ando to its Board of DirectorsGlobal pharmaceutical and biotech industry veteran brings significant clinical...

I awoke on Monday morning to the sad news that Max Randell had passed away on April 18. He would have been 23 on October 9.

Maxie wasnt expected to live past the age of 8, or even much past toddlerhood, according to some doctors. But gene therapy, and his incredible family, had something to say about that. COVID-19 didnt claim him his body just tired of fighting.

Max Randells legacy is one of hope, to the rare disease community whose family members step up to participate in the clinical trials that lead to treatments. In this time of the pandemic, attention has, understandably, turned somewhat away from the many people who live with medical limitations all the time. Ill explore that story next week.

A Devastating Diagnosis

Max was diagnosed at 4 months of age with Canavan disease, an inherited neuromuscular disease that never touched his mind nor his ability to communicate with his eyes, even though his body increasingly limited what he could do. Fewer than a thousand people in the US have the condition.

Canavan disease is an enzyme deficiency that melts away the myelin that insulates brain neurons. Gene therapy provides working copies of the affected gene, ASPA.

Babies with Canavan disease are limp and listless. Most never speak, walk, or even turn over. Yet their facial expressions and responses indicate an uncanny awareness. A child laughs when his dad makes a fart-like noise; a little girl flutters her fingers as if they are on a keyboard when a friend plays piano. Theyre smart.

Today, with excellent speech, occupational, and physical therapy and earlier diagnosis, people with Canavan disease can live into their teens or twenties. Those with mild mutations live even longer.

Maxs passing is a tragedy, but he taught researchers about gene therapy to the brain. And that may help others.

Gene Therapy for Canavan

Max had his first gene therapy at 11 months of age and a second a few years later, after slight backsliding when clinical trials halted in the wake of the death of Jesse Gelsingerin a gene therapy trial for a different disease.

Ive written about Maxs journey through many editions of my human genetics textbook, in my book ongene therapy, and in several DNA Science posts, listed at the end.

Ive had the honor to attend two of Maxs birthday parties, which celebrate Canavan kids and the organization that his family founded, Canavan Research Illinois. At one party I brought along birthday cards that students whod read my gene therapy book made for him. And his grandma Peggy, who emailed me of his passing this past Monday, showed me how Max communicated with eyeblinks of differing duration and direction.

Heres what his mom Ilyce wrote about one yearly gathering:

This year will be the 20th Annual Canavan Charity Ball. Each year as I plan this event Im faced with the undeniable reality that theres a chance Maxie wont be here by the time the day rolls around. With each passing year this fear grows stronger and it becomes increasingly difficult to put into print that our annual event is in honor of Maxies birthday. Ive been talking to Maxie a lot lately about his life. He feels happy, strong, loved, content, productive, and fulfilled and he is looking forward to his upcoming 21st birthday. Im excited to celebrate this incredible milestone.

Maxs parents and brother Alex have had the unusual experience of time, of being able to watch their loved one as the years unfolded following gene therapy. They were able to see more subtle improvements than can the parents whose children have more recently had gene therapy to treat a brain disease. Parents watch and wait and hope that language will return, or that a child will become more mobile or less hyperactive, depending on the treated condition. The changes may be subtle, or slow, or restricted and thats what Max taught the world.

For him, the viruses that ferried the healing genes into his brain seem to have gathered at his visual system. His parents noticed improvements in the short term, just before his first birthday, as well as long term.

Within two to three weeks, he started tracking with his eyes, and he got glasses. He became more verbal and his motor skills improved. His vision is still so good that his ophthalmologist only sees him once a year, like any other kid with glasses. She calls him Miracle Max, Ilyce told me in 2010.

In 2016 I heard from Ilyce again:

I wanted to give you an update on Maxie. Hes going to be 19 on October 9th. He graduated from high school in June and is beginning a work program on Monday. Its been very exciting to watch him grow into a young man!

Max had an appointment with his ophthalmologist this week and his vision continues to improve. His doctor said that the gene is still active in his brain because his optic nerve shows absolutely no signs of degeneration and looks the same each year. I wish we could have been able to express the gene throughout more of his brain, but I am grateful for the treatments because of the progress hes made.

Even though gene therapy wasnt a cure for Max, the things we are experiencing definitely give me a lot of hope that once the delivery system is perfected, I can see a potential cure for Canavan disease in the future. Just knowing that the gene is still there 15 years later gives me confidence that a one-time gene transfer would actually work!

Maxs gene therapy circa 2002 targeted less than 1% of brain cells, with fewer viral vectors than are used to deliver healing genes in todays clinical trials. But it looks like some of the vectors may have made their way beyond the optic nerves, judging by the interest in math he had in high school and his critical thinking skills.

A Choice of Gene-Based Therapies

When the Randell family decided to pursue gene therapy, it was pretty much the only game in town. Thats changed.

Only two gene therapies have been approvedin the U.S. But a search at clinicaltrials.gov yielded 602 entriesdeploying the technology. The list still rounds up the usual suspects of years past mostly immune deficiencies, eye disorders, or blood conditions, with a few inborn errors of metabolism.

But one clinical trial mentions the gene-editing tool CRISPR, which can replace a mutant gene, not just add working copies as classical gene therapy does. TheCRISPRtrial is an experiment on stem cells removed from patients with Kabuki syndrome, which affects many body systems.

Spinal muscular atrophy now has two FDA-approved treatments, one an antisense therapy (Spinraza) that silences a mutation and the other (Zolgensma) a gene therapy that infuses copies of the functioning gene. Without treatment, the destruction of motor neurons in the spinal cord is usually lethal by age two.

In 2018, FDA approved the first drug based on RNA interference (RNAi), yet another biotechnology. It silences gene expression, which is at the RNA rather than the DNA level of the other approaches. Onpattro treats the tingling, tickling, and burning sensations from the rare condition hereditary transthyretin-mediated amyloidosis.

When I wrote my book on gene therapy in 2012, the technology was pretty much the only choice of research to pursue besides protein-based therapies like enzyme replacement. Now families raising funds for treatments for single-gene diseases can add antisense, RNAi, and CRISPR gene editing to the list of possibilities.

In any battle, a diversity of weapons ups the odds of defeating the enemy.

RIP Max Randell.

DNA Science posts:

Fighting Canavan: Honoring Rare Disease Week

A Brothers Love Fights Genetic Disease

Gene Therapy for Canavan Disease: Maxs Story

Celebrating the Moms of Gene Therapy

To support research:Canavan Research Illinois

Read more from the original source:
A Tribute to Max Randell, Gene Therapy Pioneer - PLoS Blogs

In early April, about four months after a new, highly infectious coronavirus was first identified in China, an international group of scientists reported encouraging results from a study of an experimental drug for treating the viral disease known as COVID-19.

It was a small study, reported in the New England Journal of Medicine, but showed that remdesivir, an unapproved drug that was originally developed to fight Ebola, helped 68% of patients with severe breathing problems due to COVID-19 to improve; 60% of those who relied on a ventilator to breathe and took the drug were able to wean themselves off the machines after 18 days.

Repurposing drugs designed to treat other diseases to now treat COVID-19 is one of the quickest ways to find a new therapy to control the current pandemic. Also in April, researchers at Vanderbilt University enrolled the first patients in a much-anticipated study of hydroxychloroquine. Its already approved to treat malaria and certain autoimmune disorders like rheumatoid arthritis and lupus but hasnt been studied, until now, against coronavirus. Yet the medication has become a sought-after COVID-19 treatment after first Chinese doctors, and then President Trump touted its potential in treating COVID-19. The data from China is promising but not conclusive, and infectious disease experts, including Trumps coronavirus task force scientific advisor Dr. Anthony Fauci, arent convinced its ready for prime time yet in Americas emergency rooms and intensive care units.

But doctors facing an increasing flood of patients say they dont have time to wait for definitive data. In a survey of 5,000 physicians in 30 countries conducted by health care data company Sermo, 44% prescribed hydroxychloroquine for their COVID-19 patients, and 38% believed it was helping. Such off-label use in using a drug approved to treat one disease to treat another is allowed, especially during a pandemic when no other therapies are available. A similar percentage said remdesivir was very or extremely effective in treating COVID-19. (Although remdesivir is not approved for treating any disease, the Food and Drug Administration granted special authorization for doctors to use it to treat the sickest COVID-19 patients.)

That explains the unprecedented speed with which the hydroxychloroquine studyand others like itare popping up around the world. There are no treatments proven to disable SARS-CoV-2, the virus that causes the disease, which means all the options scientists are exploring are still very much in the trial-and-error stage. Still, they are desperate for anything that might provide even a slim chance of helping their patients survive, which is why studies are now putting dozens of different therapies and a handful of vaccines to the test. The normal road to developing new drugs is often a long oneand one that frequently meanders into dead ends and costly mistakes with no guarantees of success. But given the speed at which SARS-CoV-2 is infecting new hosts on every continent across the globe, those trials are being ushered along at a breakneck pace, telescoping the normal development and testing time by as much as half.

The newly launched Vanderbilt study, led by the National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health, will enroll more than 500 people who have been hospitalized with COVID-19 and randomly assign them to receive hydroxychloroquine or placebo. It would be the first definitive trial to test whether hydroxychloroquine should be part of standard therapy for treating COVID-19, and its lead scientist expects results in a few months.

The sense of urgency is pushing other researchers at academic institutes as well as pharmaceutical companies to turn to their libraries of thousands of approved drugs or compounds that are in early testing and screening to see if any can disable SARS-CoV-2. Because these are either already approved and deemed safe for people, if any emerge as possible anti-COVID-19 therapies, companies could begin testing them in people infected with the virus within weeks. Other teams are mining recovered patients blood for precious COVID-19-fighting immune cells, and because the virus seems to attack the respiratory system, scientists are also finding clever ways to stop it from compromising lung tissue.

These are all stop-gap measures, however, since ultimately, a vaccine against COVID-19 is the only way to arm the worlds population against new waves of infection. Established pharmaceutical powers like Johnson & Johnson, Sanofi and Glaxo SmithKline are racing shoulder-to-shoulder to with startups using new technology to develop dozens of potential new vaccines, with the hope of inoculating the first people next yearnone too soon before what public health officials anticipate might be another season of either the same, or potentially new, coronavirus.

We know these viruses reside in animal species, and surely another one will emerge, says Dr. David Ho, director of the Aaron Diamond AIDS Research Center and professor of medicine at Columbia University, who is heading an effort to screen antiviral drug compounds for new COVID-19 treatments. We need to find permanent solutions to treating them, and should not repeat the mistake that once an epidemic wanes, interest and political will and funding also wanes.

Its an old-school approach that dates back to the late 19th century, but the intuitive logic behind using plasma from recovered patientstechnically called convalescent plasmaas a treatment might still apply today. Plasma treatments have been used with some success to treat measles, mumps and influenza. The idea is to use immune cells extracted from the blood of people who have recovered from COVID-19 and infuse them into those who are infected, giving them passive immunity to the disease, which could at least minimize some of its more severe symptoms.

Its part of a broader range of tactics that utilize the bodys own immune response as a molecular North Star for charting the course toward new treatments. And by far, antibodies against the virus are the most abundant and efficient targets, so a number of pharmaceutical and biotechnology companies are concentrating on isolating the ones with the strongest chance of neutralizing SARS-CoV-2.

In late March, New York Blood Center became the first U.S. facility to start collecting blood from recovered COVID-19 patients specifically to treat other people with the disease. Doctors at New Yorks Mount Sinai Health System are now referring recovered (and willing) patients to the Blood Center, which collects and processes the plasma and provides the antibody-rich therapy back to hospitals to treat other COVID-19 patients.. Its not clear yet whether the practice will work to treat COVID-19, but the Food and Drug Administration (FDA) is allowing doctors to try the passive immunity treatment in the sickest patients on a case by case basis, as long as they apply for permission to use or study the plasma an investigational new drug. If we can passively transfuse antibodies into someone who is actively sick, they might temporarily help that person fight infection more effectively, so they can get well a little bit quicker, says Dr. Bruce Sachais, chief medical officer at New York Blood Center Enterprises.

The biggest drawback to this approach, however, is the limited supply of antibodies. Each recovered donor has different levels of antibodies that target SARS-CoV-2, so collecting enough can be a problem, especially if the need continues to surge during an ongoing pandemic. At the Maryland-based pharmaceutical company Emergent BioSolutions, scientists are trying to overcome this challenge by turning to a unique source of plasma donors: horses. Their size makes them ideal donors, says Laura Saward, head of the companys therapeutic business unit. Scientists already use plasma from horses to produce treatments for botulism (a bacterial infection), and have found that the volume of plasma the animals can donate means each unit can treat more than one patient (with human donors, at this point, one unit of plasma from a donor can treat one patient). Horses plasma may also have higher concentrations of antibody, so the thought is that a smaller dose of equine plasma would be effective in people because there would be higher levels of antibody in smaller doses, says Saward. By the end of the summer, the company expects its equine plasma to be ready for testing in people.

Scientists are also looking for other ways to generate the virus-fighting antibodies produced by COVID-19 patients. At Regeneron, a biotechnology firm based in New York, researchers are turning to mice bred with human-like immune systems and infected with SARS-CoV-2. Theyre searching hundreds of antibodies these animals produce for the ones that can most effectively neutralize the virus. By mid-April, the company plans to start manufacturing the most powerful candidates and prepare them (either solo or in combination) for human testingboth in those who are already infected, as well as in healthy people, to protect from getting infected in the first place, like a vaccine.

Its not just people and animals that can produce antibodies. Scientists now have the technology to build what are essentially molecular copying machines that can theoretically churn out large volumes of the antibodies found in recovered patients. At GigaGen, a San Francisco-based biotech startup founded by Stanford University professor Dr. Everett Meyer, scientists are identifying the right antibodies from recovered COVID-19 patients and hoping to use them as a template for synthesizing new ones, in a more consistent and efficient way so a handful of donors could potentially produce enough antibodies to treat millions of patients. What GigaGens technology does is almost Xerox copy a big swath of the human repertoire of antibodies, and then takes those copies and grows it in cells [in the lab] to manufacture more antibodies outside of the human body, says Meyer. So we can essentially keep up with the virus. If all goes well and the FDA gives its green light, the company intends to start testing their antibody concoctions in COVID-19 patients early next year.

Researchers at Rockefeller University are following another clue from the human bodys virus-fighting defenses. They discovered in 2017 that human cells make a protein called LY6E that can block a viruss ability to make copies of itself. Working with scientists at the University of Bern in Switzerland and the University of Texas Southwestern Medical Center, they found that mice genetically engineered to not produce the protein became sicker, and were more likely to die after infection with other coronaviruses, including SARS and MERS, compared to mice that were able to make the protein. If the mice have the protein they pretty much survive, says John Schoggins, associate professor of microbiology at the University of Texas. If they dont have it, they dont survivebecause their immune system cant control the virus. While these studies havent yet been done on SARS-CoV-2, given its similarity to the original SARS virus, theres hope a therapy based on LY6E might be useful.

Ideally, Schoggins is hoping to start testing LY6Es potential in infected human lung cells, which SARS-CoV-2 appears to target for disease. The closest mouse model for coronavirus, created to study the original SARS virus, has been retired since research on that virus dwindled after cases wanted following the 2003 outbreak. There wasnt the need to keep the mouse around, and that tells us a lot about the state of our research, says Schoggins. We dont really work on thing unless everyones hair is on fire.

Its not just immune cells that make good targets for new drugs. Other companies are looking at broader immune-system changes triggered by stressduring cancer, for example, or infection with a new virus like SARS-CoV-2that end up making it easier for a virus to infect cells. Drugs that inhibit these stress-related changes would act like molecular gates slamming shut on the cells that viruses are trying to infect.

Because SARS-CoV-2 preferentially attacks lung tissue and causes cells in the respiratory tract to launch a hyperactive immune response, researchers are exploring ways to tame that aggressive response by dousing those cells with a familiar gas: nitric oxide, often used to relax blood vessels and open up blood flow in hospital patients on ventilators who have trouble breathing. While working on a new, portable system for delivering nitric oxide developed by Bellerophon Therapeutics to treat a breathing disorder in newborns, Dr. Roger Alvarez, an assistant professor of medicine at University of Miami, got the idea that the gas might be helpful for COVID-19 patients as well. One symptom of the viral infection is low oxygen levels in the lungs, and nitric oxide is ideally designed to grab more oxygen molecules from the air with each breath and feed it to the lungs. With this system, patients dont need to be in the ICU [Intensive Care Unit] at all, he says. The patient can be in a regular hospital bed, or even at home. So you save the cost of the ICU and from a resource standpoint, you save on needing nursing care, respiratory therapists and other ICU monitoring.

In theory, if this system could be used for COVID-19 patients with moderate symptoms, it could keep those patients from needing a ventilatora huge benefit in the current context where ventilator shortages are one of the biggest threats to the U.S. health care system. So far, Alvarez has received emergency use authorization from the FDA to test a version of his system on one COVID-19 patient at the University of Miami Health System. That patient improved and is ready to go home. Its great news and gives me the information to say that this appears at least safe to study further, he says, which is what he plans to do with the first small trial of nitric oxide for COVID-19 at his hospital.

When it comes to developing a new antiviral treatment, it doesnt always pay to start from scratch. There are dozens of drugs that have become life-saving therapies for one disease after their developers accidentally discovered that the medications had other, equally useful effects. Viagra, for example, was originally explored as a heart disease drug before its unintended effect in treating erectile dysfunction was discovered, and gabapentin was developed as an epilepsy drug, but is now also prescribed to control nerve pain.

Within weeks of COVID-19 cases spiking to alarming levels in China, researchers at Gilead in Foster City, Cal., saw an opportunity. A drug the company had developed against Ebola, remdesivir, had shown glimmers of hope in controlling that virus in the laband also showed promise as a tool to treat coronaviruses like those that caused SARS and MERS. In fact, says Merdad Parsey, chief medical officer of Gilead, We knew in the test tube that remdesivir had more activity against coronaviruses like SARS and MERS than against Ebola. So it wasnt entirely surprising that when the company began testing it in people during last years Ebola outbreak in the Democratic Republic of Congo, the results were disappointing. The early studies against Ebola werent as encouraging in people as they were in animals. So we were basically on hold with the drug, waiting to see if there would be another [Ebola] outbreak to see if we could test it earlier in the infection, says Parsey.

Then COVID-19 happened. As the infection roared through Wuhan, Chinathe original epicenter of the diseaseresearchers there reached out to Gilead, knowing that the company had released data suggesting that remdeisivir had strong antiviral effects in lab studies against coronaviruses. They launched two studies of the drug in the sickest patients.

In mid-January, a man in Everett, Wash., who had recently visited Wuhan, checked into a clinic after a few days of feeling sick. He quickly went from having a fever and cough to having difficulty breathing because of pneumonia. Concerned that the man was worsening by the day, his doctor contacted the U.S. Centers for Disease Control; suspecting this might be a case of COVID-19and knowing there was no proven treatment for the infectionexperts at the agency suggested he try an experimental therapy, remdesivir.

The CDC team felt relatively confident about the drugs safety, if not its effectiveness, since Gilead had studied it extensively in animal models and, in the early trials in people, it didnt lead to any serious side effects and appeared safe. They were also aware of the companys promising data with human cells against the original SARS.

For the Washington patient, the experimental drug might be a lifesaver. A day after receiving remdesivir intravenously, his fever dropped, and he no longer needed supplemental oxygen to breathe. About two weeks after entering the hospital, he was discharged to self-isolate for several more days at home.

That set off a rush for remdesivir as cases in the U.S. went from a trickle to a flood, and doctors grasped for anything to treat quickly declining patients. Gilead initially offered the drug on a compassionate use basis, a process that allows companies, with the FDAs permission, to provide unapproved drugs currently being studied to patients who need them as a last resort. These programs are designed for one-off uses, and companies usually receive two to three requests a month from doctors . But in this case, Gilead was flooded with requests for remdesivir at the beginning of March. And because each one is evaluated on a case-by-case basis to ensure that each patient is eligible and that the potential risks of trying an untested drug dont outweigh the benefits, a backlog developed and the company couldnt respond to the requests in a timely way, says Parsey. So on March 30, Gilead announced it would no longer provide remdesivir through that program but through an expanded access program instead. Doctors can get access to the drug for their COVID-19 patients via dozens of clinical trials of remdesivir, two of which Gilead initiated. One is focused on patients with mild symptoms and one involves those with severe symptoms. The National Institutes of Health is currently heading another large study of the drug, at multiple centers around the country.

Finding a new purpose for existing drugs is ideal; they are likely already proven safe and their developers have a substantial dossier of information on how the drugs work. Thats what happened with hydroxychloroquine, a malaria drug developed after the parasite that causes the illness became resistant to the chloroquine, a drug discovered during World War II and since used widely to fight the disease. As researchers studied hydroxychloroquine in the lab in recent decades , they learned it can block viruses, including coronaviruses, from infecting cells. In lab studies, when researchers infected human cells with different viruses and then bathed them in hydroxychloroquine, those cells could generally stop viruses like influenza, SARS-CoV-2, and the original SARS virus, another type of coronavirus, from infecting the cells. The problem is that what happens in the lab often doesnt predict what happens in a patient, says Dr. Otto Yang, from the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at the University of California Los Angeles. In fact, in the case of influenza, the drug wasnt as successful in stopping infection in animals or in people. Similarly, when scientists brought hydroxychloroquine out of the lab and tested it in people, the drug failed to block infection with HIV and dengue as well.

Thats why doctors are approaching hydroxychloroquine with healthy skepticism when it comes to COVID-19 and are only using it on the sickest patients with no other options. Doctors at a number of hospitals, including Johns Hopkins, the University of California Los Angeles, and Brigham and Womens, for example, are starting to use hydroxychloroquine to treat patients with severe COVID-19 symptoms when they dont improve on current supportive treatments. Its not ideal, but If someone is sick in the ICU you try everything possible you can for that person, says Dr. David Boulware, a professor of medicine at the University of Minnesota, who is conducting a study of hydroxychloroquine effectiveness both in treating those with severe disease and in protecting health people from infection.

Other researchers are attempting to trace the same path with other repurposed drugs, including a flu treatment from Toyama Chemical, a pharmaceutical division of the Japanese conglomerate Fujifilm, called favipiravir, which Chinese researchers used to treat patients with COVID-19. More rigorous studies of both remdesivir and favipirivir against SARS-CoV-2 are ongoing; all researchers can say at this point is that they are worth studying further, and that they appear to be safe.

Even cancer drugs are showing promise as COVID-19 treatments, not by neutralizing the virus but by healing the damage infection does to the immune system. The Swiss pharmaceutical giant Novartis, for example, has ruxolitinib (sold under the trade name Jakavi), which was approved by the FDA in 2011 to treat a number of different cancers, and is designed to tamp down an exaggerated immune responsewhich can be caused by both tumor cells and a virus. In the case of SARS-CoV-2, a hyperactive immune response can trigger breathing problems, called a cytokine storm, that require extra oxygen therapy or mechanical ventilation. In theory, ruxolitinib could suppress this virus-caused cytokine storm. Novartis is making its drug available on an emergency use basis for doctors willing to try it on their sickest patients.

Eli Lilly is also testing one of its anti-inflammatory drugs, baricitinib, in severe COVID-19 patients. Like ruxolitinib, baricitinib interferes with the revved up signalling among immume cells that can trigger the inflammatory cytokine storm. According to president of Lilly Bio-Medicines Patrik Jonsson, there are even early hints from case studies of doctors treating COVID-19 patients that the drug may target the virus too, which could mean that it helps to lower the viral load in infected patients. The company is working with NIAID to confirm whether this is the case in a more rigorous study of severe COVID-19 patients, and expects to see results by summer.

It wasnt immediately obvious that baricitinib could potentially treat COVID-19; it took an artificial intelligence effort by UK-based BenevolentAI to scour existing medical literature and descriptions of drug structures to identify baricitinib as a possible therapy.

Such machine learning-based techniques are making the search for new therapies far more efficient than ever before. Chloroquine, hydroxychloroquines parent, came out of a massive war-time drug discovery effort in the 1940s, when governments and pharmaceutical companies combed through existing drug libraries for promising new ways to treat malaria. With computing power that is orders of magnitude greater now, its now possible to single out not just existing drugs with antiviral potential, but entirely new ones that may have gone unnoticed.

When Sumit Chanda first heard of the mysterious pneumonia-like illnesses spiking in Wuhan, China, he had an eerie feeling that the world was about to face a formidable viral foe. He had spent his entire career studying all the clever and devilish ways that bacteria, viruses and pathogens find hospitable hosts and then take up residence, oblivious to how much illness, disease and devastation they may cause. And as director of the immunity and pathogenesis program at Sanford Burnham Prebys Medical Discovery Institute in San Diego, Chanda knew that if the mystery illness striking in China was indeed caused by a new virus or bacteria, then doctors would need new ways to treat itand quickly.

So, he and his team started canvassing a 13,000 drug library, which is funded by the Bill and Melinda Gates Foundation and created by Scripps Research. Our strategy is to take existing drugs and see if they might have any efficacy as an antiviral to fight COVID-19, he says. The advantage of this approach is that you can shave years upon years off the development process and the studies on safety. We want to move things quickly into [testing] in people. In a matter of weeks, he has narrowed down the list of potential coronavirus drug candidates, and because these are already existing drugs and approved for treating other diseases, they are relatively safe, and can quickly be tested in people infected with SARS-CoV-2.

Chandas team isnt the only one taking advantage of this approach. Researchers at numerous pharmaceutical companies, biotech outfits and academic centers are screening their libraries of drugsboth approved and in developmentfor any anti-COVID-19 potential.

At Columbia University, Dr. David Ho, who pioneered ways of creating cocktails of drugs to make them more potent against HIV, is scouring a different library of virus-targeting drugs to pluck out ones that could be effective against SARS-CoV-2. Altogether, he has some 4,700 drugs (approved and in development) to look through, and he believes there is a strong chance of finding something that might be effective against not just SARS-CoV-2 but any other coronavirus that might pop up in coming years. The key, says Ho, is to be prepared for the next outbreak so the work on finding antiviral drugs doesnt have to start from scratch. We know these viruses reside in animal species, he says. We predict in the coming decade there will be more [outbreaks]. And we need to find permanent solutions. We should not repeat the mistake we made after SARS and after MERS, that once the epidemic wanes, the interest and the political will and the funding also wanes. If we had followed through with the work that had begun with SARS, we would be so much better off today.

But today, we are in the midst of a pandemic, and scientists are eager to leave no potentially promising technology untried. Banking on the growing body of science looking at how newborn babies are able to avoid life-threatening infections in their first days in the world, researchers at New Jersey-based Celularity are investigating how placental cells, rich with immune cells that protect the baby in utero, might also become a source of immune defense therapy against COVID-19. Its part of a broader strategy of cell-based treatments that scientists are beginning to explore for treating cancer as well as infectious disease.

On April 1, the company received FDA clearance for its placental cell treatment, based on a group of immune cells called natural killer cells that circulate in the placenta, and are designed to protect the developing fetus from infection. They are programmed to recognize red flags typically sent up by cells infected with viruses like SARS-CoV-2, and destroy them. After the 2002-2003 SARS epidemic, researchers in China found that people who had more severe symptoms of that disease also had deficient populations of natural killer cells.

The FDA green light means the company can launch a small human study using placental natural killer cells against COVID-19. Dr. Robert Hariri, Celularitys founder and CEO, wants to test them first in people who are infected, to see if they can stop the infection from getting worse. Our approach is to flatten the immunologic curve, he says. Our hope is to decrease the size of the viral load and keep it below the threshold of serious symptomatic disease until the patients own immune system can be revved up and respond. If those studies are encouraging, then the company will look at how natural killer cells might be used to pre-charge the immune system to prevent infection with SARS-CoV-2 in the first place.

As effective and critical as these therapies might be, they are a safety net for the best weapon against an infectious disease: a vaccine.

The main reason that a new virus like SARS-CoV-2 has such free license to infect hundreds of thousands of people around the world is because its an entirely new enemy for the human immune system making the planets population an open target for infection. But a vaccine that can prime the body to build an army of antibodies and immune cells trained to recognize and destroy the coronavirus would act as an impenetrable molecular fortress blocking invasion and preventing disease.

Unfortunately, vaccines take time to developyears, if not decades. Scientists at Johnson & Johnson are currently working on a vaccine using fragments of the SARS-CoV-2 spike protein, an easy protein target that sprinkles the surface of the virus like a crown (hence the name coronavirus, from the Latin for crown). The company loads the viral gene for the spike protein into a disabled common-cold virus vector that delivers the genetic material to human cells. The immune system then recognizes the viral fragments as foreign and deploys defensive cells to destroy it. In the process, the immune system learns to recognize the genetic material of the virus, so when the body is confronted by the actual virus, its ready to attack.

Given the manufacturing requirements to build the vaccine, and the studies in animals needed to get a hint of whether the vaccine will work, however, J&Js project is unlikely to come to fruition until mid-2021. We plan to have the first data on the vaccine before the end of the year, says Paul Stoffels, chief science officer at J&J. I would hope that in the first half of next year, we should be able to get vaccines ready for people in high risk groups like health care workers on the front lines.

That timeline is already accelerated quite a bit compared to vaccine research in non-pandemic contexts. But new technology that doesnt require a live transport system could shrink the time to human tests even further. Working with the National Institute of Allergy and Infectious Diseases, Moderna Therapeutics, a biotech based in Cambridge, Mass., developed its mRNA vaccine in a record 42 days after the genetic sequence of the new coronavirus was released in mid January. Its system turns the human body into a living lab to churn out the viral proteins that activate the immune system.

Researchers at Moderna hot wired the traditional vaccine-making process by packing their shot with mRNA, the genetic material that comes from DNA and makes proteins. The viral mRNA is encased in a lipid vessel that is injected into the body. Once inside, immune cells in the lymphatic system process the mRNA and use it like a genetic beacon to attract immune cells that can mount toxic responses against the virus. Our vaccine is like the software program for the body, says Dr. Stephen Hoge, president of Moderna. So which then goes and makes the [viral] proteins that can generate an immune response.

Because this method doesnt involve live or dead virusesall it requires is a lab that can synthesize the correct genetic viral sequencesit can be scaled up quickly since researchers dont have to wait for viruses to grow. Almost exactly two months after the genetic sequence of SARS-CoV-2 was first published by Chinese researchers, the first volunteer received an injection of the Moderna vaccine. The companys first study of the vaccine, which will include 45 healthy participants, will monitor its safety. Hoge is already gearing up to produce hundreds and thousands of more doses to prepare for the next stage of testing, which will enroll hundreds of people, most likely those at high risk of getting infected, like health care workers.

If those results arent as promising as health experts hope, there are other innovative options in the works. At the University of Pittsburgh, scientists who had been developing a vaccine against the original SARS virus have switched to making a shot against the new one. Their technology involves hundreds of microneedles in a band-aid like patch that deliver parts of the coronavirus protein directly into the skin. From there, the foreign viral proteins are swept into the blood and into the lymph system, where immune cells recognize them as invaders and develop antibodies against them. After seeing animals inoculated with their vaccine develop strong antibodies against SARS-CoV-2, the team is ready to submit an application to the FDA to begin testing in people.

Whats different about these new coronavirus efforts is the fact that they arent all designed to control SARS-CoV-2 alone. Recognizing that this coronavirus is the third in recent decades to cause pandemic disease, scientists are focusing on building therapies, including vaccines, that can quickly be adapted to target different coronaviruses that might emerge in coming years. We hope these new technologies become the kinds of things we build in our tool kits that as humans will allow us to respond in a much more accelerated way to the next pandemic, says Modernas Hoge. Because we expect continuing threats from viruses in the future.

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Vaccines, Antibodies and Drug Libraries. The Possible COVID-19 Treatments Researchers Are Excited About - TIME