A rare disease is defined as any disease that affects a small percentage of the population. In the United States, a disease is classified as rare when fewer than 200,000 individuals are affected by it. According to the National Institutes of Health, there are approximately 6,500 to 7,000 known rare diseases affecting an estimated 25 million Americans.

One of these is Loeys-Dietz Syndrome (LDS), a disorder of connective tissue that can affect blood vessels, including the aorta, as well as bones, joints, cognitive ability and internal organs.

Here, Michigan Medicine cardiologist Marion Hofmann, M.D., who typically treats 10 to 15 Loeys-Dietz patients each year, sheds some light on this complex rare disease.

LDS is caused by a mutation in the TGFBR1, TGFBR2, SMAD3, TGFB2 or TGFB3 genes, as we know today. More could be identified in the future.

Loeys-Dietz Syndrome is a genetic condition, but not always inherited. In patients with the condition, we usually recommend genetic testing of the parents and siblings to see if it is inherited or if it is a new mutation. If the parent or siblings of a patient diagnosed with LDS do not test positive for the genetic variant, we assume the variant is present for the first time in one family member. This occurs in approximately 75% of LDS cases. There is a 50% chance the gene will be passed on regardless of whether LDS was inherited or a first time mutation.

Because relatively common symptoms can camouflage LDS, the condition may go undiagnosed until a serious complication occurs. Patients might be diagnosed with Loeys-Dietz after an aortic aneurysm (a weakened or bulging area on the wall of the aorta) is found on a CT scan or echocardiogram, or after experiencing a life-threatening aortic dissection (a tear in the inner layer of the aorta) or a dissection in other arteries. If a patient experiences either of these vascular conditions, we would likely suggest genetic testing to determine if Loeys-Dietz Syndrome was the cause.

In approximately 20% of patients experiencing an unexplained aortic dissection, we find gene abnormalities, including LDS, that predispose to aortic disease.

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Some patients, but not all, are diagnosed because of certain skeletal characteristics that point to Loeys-Dietz. These include a chest wall deformity in which the chest wall pushes outward or appears sunken, scoliosis, long and slender fingers, flexible joints, flat feet, translucent skin, abnormal scarring of the skin and a bulging or widening of the spinal sac surrounding the spinal cord. However, the spectrum of the disease is very broad and were finding that not all LDS patients exhibit these characteristics.

Genetic testing confirms a suspected LDS diagnosis. Other similar disorders such as Marfan Syndrome and Ehlers-Danlos Syndrome can present similar characteristics, so genetic testing is important to differentiate these disorders. In recent years weve realized just how complex LDS is. As clinical genetic testing is more commonly used, diagnostic accuracy for LDS has improved and were learning more about how LDS presents. For example, were finding that family members carrying the same mutation are affected differently. Cardiac and genetic evaluation of all family members is important for patients with LDS to identify other relatives at risk for the condition.

Patients with Loeys-Dietz need regular checkups and vascular imaging to identify high-risk situations that could lead to aortic dissection. We recommend medication to avoid high blood pressure, which puts stress on weakened areas of the aortic wall, lifestyle modifications and preventive surgery to treat aortic aneurysms deemed to be at high risk for dissection. Patients with LDS are typically prescribed beta blockers or angiotensin receptor blockers.

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Anyone experiencing an aortic dissection or an aneurysm requires lifelong care as they are more likely to have a future event. Patients with LDS require special counseling for family planning and during pregnancy.

Additional information comes from nationwide patient support groups and their symposiums. The U-M Frankel Cardiovascular Center, in collaboration with the Marfan Foundation, is hosting the Detroit regional symposium for Marfan Syndrome and related disorders on April 25, 2020.

Weve been able to gain important knowledge about LDS and other aortic-related conditions through worldwide collaboration of researchers interested in LDS and aortic dissection in general. The International Registry on Aortic Dissection was launched in 1996 and the Montalcino Aortic Consortium was formed in 2013 to collect and share information about the genetic causes of aortic dissection. The next GenTAC Aortic Summit, which is committed to advancing research, education and treatment of heritable aortic diseases, will be held October 10 and 11, 2020, in Ann Arbor, Michigan, and will be hosted by Michigan Medicine cardiologist Kim Eagle, M.D. Through these resources, were learning more about the condition and gaining insight into diagnosis and treatment advancements.

Importantly, 10-20% of patients with a history of what was thought to be sporadic or unexplained aortic dissections actually have an identifiable genetic cause, including LDS. Being able to pinpoint the genetic causes of disease is very powerful. It allows health care providers to use a gene-based medical management strategy, which is the goal of personalized medicine. Genetic counseling and potentially genetic testing is very important for family members of patients with unexplained aortic dissections as well as with Loeys-Dietz Syndrome.

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Loeys-Dietz Syndrome A Rare and Complex Heart Disease - University of Michigan Health System News

Recommendation and review posted by Bethany Smith

I love working with people, says Allison Werner-Lin of the School of Social Policy & Practice (SP2). Werner-Lins office overlooking Locust Walk is homey and lamp-lit, with student gifts sharing space with scholarly tomes. This is just one of her workspaces, however. Recently returned from sabbatical, Werner-Lin has been working with the National Cancer Institute (NCI), as well as out of her home in upstate New York, which doubles as a private practice for families seeking bereavement therapy. The divide between academia and clinical practice suits her. I feel like I have one foot in each world and in a very positive way, Werner-Lin says.

Werner-Lin has extensive clinical and research experience and uses both to inform her work, which centers on heritable cancers. She began her academic work studying young adults with mutations in genes associated with breast and ovarian cancer, BRCA1 and BRCA2. Recently, her work with the NCI has branched out to the study of Li-Fraumeni syndrome (LFS). Patients with LFS have a mutation in a tumor-suppression gene, resulting in a high incidence of cancer starting in childhood, and 50% of LFS patients develop cancer by age 40. Both patient populations make life-altering decisions based upon their family histories and medical diagnoses.

Dr. Werner-Lins groundbreaking research merges science with social work at the intersection of qualitative health research, the structure and evolution of genes, hereditary cancer, and how it impacts individuals and families at various stages of life, says SP2 Dean Sara Sally Bachman. Each day, Allison is pushing the frontiers of genomic study and oncological social work while also mentoring other social change agents who will undoubtedly make a difference locally, nationally, and internationally.

For more than a decade, Werner-Lin has worked in the Clinical Genetics Branch of the Division of Cancer Epidemiology and Genetics of the NCI organizing the human side of research. Patients come annually to the NCI to receive full-body MRI cancer screenings and participate in data collection that covers everything from cancer history to family communication to risk management. Werner-Lin mentors an interdisciplinary team of predoctoral and postdoctoral fellows to explore how these families understand and cope with genetic information. Her work is used to train providers in delivering holistic medical and psychological care.

We talk with families about their experiences communicating cancer-risk information with loved ones, making reproductive decisions, and managing the endless cycle of screening, Werner-Lin says. She has seen patterns in how families share cancer-risk information and seek support, noting that information travels based on relationship patterns and emotional closeness, not necessarily degree of risk.

People with LFS have limited options for cancer prevention, and expectations for a cancer diagnosis and early death are common. Were seeing a lot of physical loss, where amputations and other changes in physical function are common consequences of treatment.

Many of the people Werner-Lin speaks with are looking at different pathways to parenthood or are choosing not to have children at all, she says. Grief becomes a chronic part of their lives, and those kinds of sustained of losses can connect individuals in and across families.

Former SP2 graduate student Catherine Wilsnack is a Cancer Research Training Award Fellow at the NCI, doing qualitative research as part of Werner-Lins team. Wilsnack first met Werner-Lin while in her second year at SP2 and calls the encounter transformative. Werner-Lin is a phenomenal mentor in every way, says Wilsnack, who earned her masters in social work (MSW) in 2019. She always goes above and beyond for her students. I would not be where I am today if it were not for her and her guidance, so I just feel extremely lucky.

Now in midcareer, Werner-Lin is taking the time to mentor younger generations. There are so many opportunities to focus on other peoples career development without such a bounded focus on my own professional needs, she says, crediting her own mentors with the ability to achieve professional success.

At Penn, Werner-Lin is involved in the Cancer Moonshot initiative led by Katherine Nathanson and Steve Joffe, an effort designed to accelerate cancer research aimed at prevention, detection, and treatment. Werner-Lins aspect of the project, based at the Abramson Cancer Center at Penn Medicine, involves issues surrounding genetic testing in people aged 18 through 40. Susan Domchek, executive director of the Basser Center for BRCA, says, Allisons work in terms of the psychosocial implications of having a BRCA mutationhow an individual can come to terms with that and how that information gets disseminated between familieshas been extremely helpful. She has a deep expertise on helping families navigate these situations.

Approximately 1 in 400 people carry mutated breast cancer genes, though mutations are more common in certain groups of people. The gene mutations are passed in an autosomal dominant pattern, meaning each parent with a mutation has a 50% chance of passing it on. Children of a BRCA-positive parent can pursue genetic testing to learn if they carry the mutation, adding pressure to family planning.

Werner-Lin was one of these children. Her mother has a BRCA1 mutation. She recovered from colon cancer when Werner-Lin was in college and is currently in remission from a rare ovarian cancer. When I was 23 and was thinking about having kids, I couldnt figure out how to do it, Werner-Lin says. I started talking to people, talking to other women, and that became my dissertation.

This curiosity and compassion led Werner-Lin to operate a private therapy practice out of her home, where she exclusively sees children and young adults with a deceased parent. People often dont see how therapy is connected to the genetics part of my work, but for me they are inseparable, Werner-Lin says. In my cancer work, parents often die young, leaving small children. Frequently, the children of cancer patients conflate their parents lives with their own, not seeing options, degrees of freedom, or technological innovation.

Working together with an MSW student, Werner-Lin does whole family-therapy, from diagnosis to end-of-life, through the grieving process. She helps to facilitate goodbyes, talks about legacy building, and makes the concept of death more concrete for young people.

The language adults use to talk about death is often confusing and shrouded in existential concepts, Werner-Lin says, citing references to angels or going to a better place. Young kids dont necessarily understand time or geography, she says. If were in New York, and Mommy went to the other side, is that a better place?

Instead, she says, we talk about the brain being a light switch, and once you turn it off you cant turn it on again. We talk about how the heart stops beating and the eyes stop seeing. These practical realities are important, Werner-Lin says. Kids need to understand the way the world is predictable, especially when people they love and need can fall off the earth at any moment.

Now back on campus, Werner-Lin is focusing on teaching and engaging with her graduate students. Acting in service to her patients, her students, and her colleagues is a core part of Werner-Lins brand of academia. If you tell her that you want to do something, Wilsnack says, she will go out of her way to help.

See original here:
Working on 'the human side' of heritable cancers - Penn: Office of University Communications

Recommendation and review posted by Bethany Smith

LOS ANGELES, California Fit Foodie Chef and Grow Green Industries, Inc. (GGI) CEO Mareya Ibrahim is set to emcee the 27th annual International Restaurant and Foodservice Show of New York March 8-10, 2020 at the Javits Center in New York City. Side-by-side with both the Healthy Food Expo New York and Coffee Fest, this years event will feature one badge that grants attendees access to all three trade shows.

This is the fourth Healthy Expo event featuring Chef Mareya as the Center Stage Emcee, including the 2018 Los Angeles and Orlando shows. The GGI founder and CEO and author of Eat Like you Give a Fork: The Real Dish on Eating to Thrive will preparing signature dishes.

Mareya is simply magnetic with endless energy and pizazz. She is incredibly knowledgeable of the industry and possesses the talent to amp up attendees and build hunger for our demonstrations, shares Patricia Copela from Clarion UX. We are delighted to have her as a Center Stage emcee and look forward to another wonderful and exciting event!

Its truly an honor to be hosting for the fourth time and sharing the stage with such an incredible lineup of talent, explains Mareya, Attendees are in for such a treat! Theyll gain incredible knowledge from leaders in the industry, try tasty bites and watch how-tos from some of the worlds best chefs.

The Expos main stage is the place to be, so I suggest you grab your seat early and stick around, because you wont want to miss a minute.

Attendees are invited to meet Chef Mareya and her team at center stage. Visit http://www.InternationalRestaurantNY.com for more information and to register for the three-day event. To schedule an interview with Chef Mareya, please contact Leigh-Anne Anderson on leighanne@anderson-pr.com or visit http://www.mareyaibrahim.com, and to learn more about GGI, Inc.s lab-proven line of food safety and shelf life extension products, please visit http://www.growgreenindustries.com.

About Grow Green Industries, INC./ eatCleaner:

Winner of the Worlds Best Technologies Gold Prize, Grow Green Industries, Inc. dba eatCleaner is a Southern California based, Certified Woman-Owned Business leading the way in eco solutions for produce food safety and shelf life extension to inhibit food waste. Co-founded in 2010 by Dr. Shawki Ibrahim, Ph.D. and nationally recognized food safety and clean eating expert, award-winning entrepreneur, chef, author and inventor, Mareya Ibrahim, aka The Fit Foodie, the company is dedicated to providing safe, effective wholesale and consumer products that enhance lives and improve health. Featured on HSN, QVC and reputable retail locations, their award-winning, patented solutions include the best-selling eatCleaner Triple Action Fruit + Veggie Wash and Wipes, eatFresh-FC anti-browning powder, and avoFresh for cut avocados, and are used in schools, homes, retail locations, food-service businesses and produce processing facilities Visit http://www.growgreenindustries.com to learn more.

Read the rest here:
Fit Foodie Chef Mareya Ibrahim to Emcee at the International Restaurant and Foodservice Show Live in New York City - PerishableNews

Recommendation and review posted by Bethany Smith

SAN DIEGO, Feb. 26, 2020 (GLOBE NEWSWIRE) -- Pfenex Inc. (NYSE American: PFNX) announced today that it will report its financial results for the fourth quarter and year ended December 31, 2019, after the market close on Wednesday, March 11, 2020. Pfenex will host a conference call and webcast to discuss its financial results and provide a company update that day at 1:30 PM Pacific Time (4:30 PM Eastern Time).

About Pfenex Inc.

Pfenex is a development and licensing biotechnology company focused on leveraging its Pfenex Expression Technology to develop and improve protein therapies for unmet patient needs. Using the patented Pfenex Expression Technology platform, Pfenex has created an advanced pipeline of potential therapeutic equivalents, and vaccines. Pfenexs lead product candidate is PF708, a therapeutic equivalent candidate to Forteo (teriparatide injection). PF708 has been approved in the U.S. for the treatment of osteoporosis in certain patients at high risk for fracture, and marketing authorization applications are pending in other jurisdictions. In addition, Pfenex is developing hematology/oncology products in collaboration with Jazz Pharmaceuticals, including PF743, a recombinant crisantaspase, and PF745, a recombinant crisantaspase with half-life extension technology. Pfenex also uses its Pfenex Expression Technology platform to produce CRM197, a diphtheria toxoid carrier protein used in prophylactic and therapeutic vaccines.

Pfenex investors and others should note that Pfenex announces material information to the public about Pfenex through a variety of means, including its website (http://www.pfenex.com/), its investor relations website (http://pfenex.investorroom.com/), press releases, SEC filings, public conference calls, corporate Twitter account (https://twitter.com/pfenex), Facebook page (https://www.facebook.com/Pfenex-Inc-105908276167776/timeline/), and LinkedIn page (https://www.linkedin.com/company/pfenex-inc) in order to achieve broad, non-exclusionary distribution of information to the public and to comply with its disclosure obligations under Regulation FD. Pfenex encourages its investors and others to monitor and review the information Pfenex makes public in these locations as such information could be deemed to be material information. Please note that this list may be updated from time to time.

Company Contact:investorrelations@pfenex.com

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Pfenex to Announce Fourth Quarter and Year-End 2019 Financial Results on March 11 - Yahoo Finance

Recommendation and review posted by Bethany Smith

Key Point:Retrofitted with more fuel-efficientCFM-56turbojets and benefiting from expanded fuel tanks, theE-6Acould remain in the air up to fifteen hours, or seventy-two with inflight refueling.

In a military that operates Raptor stealth fighters, A-10 tank busters, B-52 bombers and Harrier jump jets, the U.S. Navys placid-looking E-6 Mercury, based on the 707 airliner, seems particularly inoffensive. But dont be deceived by appearances. Though the Mercury doesnt carry any weapons of its own, it may be in a sense the deadliest aircraft operated by the Pentagon, as its job is to command the launch of land-based and sea-based nuclear ballistic missiles.

Of course, the U.S. military has a ground-based strategic Global Operations Center in Nebraska, and land-based transmitters for communicating with the nuclear triad. However, the E-6s sinister purpose is to maintain the communication link between the national command authority (starting with the president and secretary of defense) and U.S. nuclear forces, even if ground-based command centers are destroyed by an enemy first strike. In other words, you can chop off the head of the U.S. nuclear forces, but the body will keep on coming at you, thanks to these doomsday planes.

The E-6s basic mission is known as Take Charge and Move Out (TACAMO). Prior to the development of the E-6, theTACAMOmission was undertaken by land-based transmitter and laterEC-130Gand Q Hercules aircraft, which had Very Low Frequency radios for communication with navy submarines. Interestingly, France also operated its ownTACAMOaircraft until 2001, four modifiedTransallC-160HAstarttransports, which maintainedVLFcommunications with French ballistic-missile submarines.

The first of sixteenE-6sentered service between 1989 and 1992. These were the last built in averylong line of military variants of the venerable Boeing 707 airliner, in particular the707-320BAdvanced, also used in theE-3 Sentry. Bristling with thirty-one communication antennas, theE-6Aswere originally tasked solely with communicating with submerged Navy submarines. Retrofitted with more fuel-efficientCFM-56turbojets and benefiting from expanded fuel tanks, theE-6Acould remain in the air up to fifteen hours, or seventy-two with inflight refueling.

To use its Very Low Frequency radios, an E-6 has to fly in a continuous orbit at a high altitude, with its fuselage- and tail-mounted VLF radios trailing one- and five-mile-long wire antennas at a near-vertical attitude! The VLF signals can be received byOhio-class nuclear ballistic-missile submarineshiding deep underwater, thousands of miles away. However, the VLF transmitters limited bandwidth means they can only send raw data at around thirty-five alphanumeric characters per secondmaking them alotslower than even the old 14k internet modems of the 1990s. Still, its enough to transmit Emergency Action Messages, instructing the ballistic-missile subs to execute one of a diverse menu of preplanned nuclear attacks, ranging from limited to full-scale nuclear strikes. The E-6s systems are also hardened to survive the electromagnetic pulse from nuclear weapons detonating below.

Between 1997 and 2006, the Pentagon upgraded the entire E-6A fleet to the dual-role E-6B, which expanded the Mercurys capabilities by allowing it to serve as an Airborne Nuclear Command Post with its own battle staff area for the job. In this role it serves as a backup for four huge E-4 command post aircraft based on the 747 Jumbo jet. The E-6B has ultra-high-frequency radios in its Airborne Launch Control system that enable it to remotely launch land-based ballistic missiles from their underground silos, a task formerly assigned to U.S. Air Force EC-135 Looking Glass aircraftyet another 707 variant. The E-6s crew was expanded from fourteen to twenty-two for the command post mission, usually including an onboard admiral or general. Additional UHF radios give the E-6B access to the survivable MILSTAR satellite communications network, while the cockpit is upgraded up with new avionics and instruments from the 737NG airliner. The E-6B can be distinguished in photos by its additional wing-mounted pods.

The Mercurys abundant communications gear allows it to perform nonnuclear Command, Control and Communications (C3) operations as well. For this reason, E-6s have at times been deployed to Europe and the Middle East to serve as flying C3 hubs. For example, VQ-4 was deployed in Qatar for three years from 2006 to 2009, where it relayed information such as IED blast reports and medical evacuation requests from U.S. troops in Iraq who were out of contact with their headquarters.

Two Navy Fleet Air Reconnaissance Squadrons currently operate the E-6: VQ-3 Ironmen and VQ-4 Shadows, both under the Navy Strategic Communications Wing 1. These have their home at Tinker Air Force Base in Oklahoma, but also routinely forward deploy out of Travis AFB in California and Patuxent River Naval Air Station in Maryland. At least one E-6 is kept airborne at all times. E-6s on the submarine-communication mission often fly in circles over the ocean at the lowest possible speedfor as long as ten hours at a time. Those performing the nuclear command post mission typically remain on alert near Offutt Air Force Base in Nebraska. The E-6s nuclear mission has also made its operations occasional fodder for conspiracy theorists and foreign propaganda outlets.

The E-6 platform should remain in service until 2040 thanks to a service-life extension program and continual tweaks to its systems and radios. While the Mercury has demonstrated its usefulness as an airborne communication hub for supporting troops in the field, the airborne command post will be considered a success if it never has to execute its primary mission. The heart of nuclear deterrence, after all, is convincing potential adversaries that no first strike will be adequate to prevent a devastating riposte. The E-6s are vital component in making that threat a credible one.

Sbastien Roblin holds a masters degree in conflict resolution from Georgetown University and served as a university instructor for the Peace Corps in China. He has also worked in education, editing and refugee resettlement in France and the United States. He currently writes on security and military history forWar Is Boring.

This first appeared in December 2017. It is being republished due to reader interest.

Image:566th Aircraft Maintenance Squadron personnel assigned to the Oklahoma City Air Logistics Center at Tinker Air Force Base, Okla., are scheduled to begin work on the service life extension program for the Navy's fleet of E-6B Mercury aircraft flown by Strategic Communications Wing One here. (U.S. Air Force photo/Margo Wright)

More:
Study This Plane: It Could Fight a Nuclear War and Kill Billions - The National Interest Online

Recommendation and review posted by Bethany Smith

The report titled, Global Shelf Life Extension Ingredients Market Report, History and Forecast 2018-2026 has been recently published by TMRR. The authors of the report have done extensive study of the global Shelf Life Extension Ingredients market keeping in mind the key aspects such as growth determinants, opportunities, challenges, restraints, and market developments. This analysis will enrich the ability of the companies involved in the global Shelf Life Extension Ingredients market to make precise decisions. The report also emphasizes on the current and future trends in the global Shelf Life Extension Ingredients market, which may bode well for the global Shelf Life Extension Ingredients market in the coming years. Impact of the driving factors on the global Shelf Life Extension Ingredients market growth has been mapped by the report. Besides, factors that are likely to challenge the global Shelf Life Extension Ingredients market growth in the years to come are discussed by the industry experts in the report.

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Shelf Life Extension Ingredients MARKET 2019 REVENUE, INDUSTRY GROWING DEMAND, SIZE, SHARE, BUSINESS OPPORTUNITIES, TOP COMPANIES, REGIONAL OUTLOOK...

Recommendation and review posted by Bethany Smith

Cleveland Bridge UK has continued to grow its activity in the bridge inspection and refurbishment market by securing a landmark project in Nottingham.

Its Bridge Rehabilitation Team will deliver a high-profile seven-month maintenance programme on the citys iconic Trent Bridge, which includes the application of 120m2 of gold leafing to the bridge fascia.

Cleveland Bridge UK will also paint all steel and cast-iron elements of the bridge, covering more than 11,000m2, along with replacing a small number of damaged cast iron parapet components and completing some stonework repairs to the piers and abutments.

In addition to enhancing its cosmetics, the painting of the bridge, which is adjacent to the international cricket ground of the same name and Nottingham Forests City Ground, more importantly provides ongoing resistance to corrosion and degradation of the structure, securing the long-term load-carrying capacity of the bridge.

Part of a 1.1m investment, equally funded between Nottingham City Council and Nottinghamshire County Council, the project draws upon the depth of skills and proven expertise developed by Cleveland Bridge UKs Rehabilitation Team.

With wide experience of project management, inspection and bridge rehabilitation worldwide, the team supports life extension programmes across the UKs bridge network and internationally.

Jim Mawson, Head of Operational Delivery at Cleveland Bridge UK, said: We are very proud to be awarded this prestigious refurbishment project for one of the UKs most iconic city centre bridges.

Working in close collaboration with the city and county councils, our rehabilitation team will apply its extensive experience to extend the lifespan of Trent Bridge, including having the honour of applying the highly-recognisable gold leaf that greets commuters and visitors to the city as they cross the river.

Nottingham City Councils Portfolio Holder for Transport, Cllr Adele Williams, said: With its nearby cricket ground namesake known worldwide, Trent Bridge is an iconic gateway to the city which together with the County Council we are committed to maintaining and keeping looking its best. This re-painting will help to protect and preserve the bridge while freshening it up for many years to come.

Excerpt from:
Bridge Rehabilitation Team secures Trent Bridge maintenance project - Business Up North

Recommendation and review posted by Bethany Smith

A kind gesture towards the victims in china

If anyone is familiar with the 2009 thriller Orphan, they know that it was just a story. But people are rushing to correlate dwarfism depicted in the movie with several other cases of dwarfism in real life.

The movie Orphan follows a 33-year-old woman with hypopituitarism who disguises herself as a young child so that she is adopted by a family. The adoption is followed by several events that point out that she is a woman and the family was in trouble. The current case of a young boy with dwarfism is trending on Twitter with people rushing to prove that he is, in fact, an 18-year-old posing as a 9-year-old.

The internet can be a beautiful place where people are supportive and understanding, but sometimes the support goes to the wrong person and everyone feels scammed. This has made people question everything that is being posted on the internet. Unfortunately, this has also led to people having mixed thoughts about the Quaden Bayles, the young boy from Australia who is allegedly going through bullying in his school because of dwarfism.

A heartbreaking video showed Quaden crying and saying that he wants to kill himself because of the bullying. So the internet did its job and made it go viral, and now the internet sea has split.

Quaden recently received a GoFundMe page donation to go to Disney land after several Hollywood and other stars came forward supporting the young boy and asking him not to worry. Brad Williams, the comedian set up a GoFundMe page for the young boy to bring him to the US for a vacation.

But several believe that this is a scam set up by the Bayles to make money. People went into Quaden's Instagram handle. According to the Twitterati, it showed Quade celebrating his 18th birthday and had pictures of him wearing expensive clothes.

People are continuously arguing on various platforms that Bayles is lying about his age. According to the investigative work done by several people on the internet, they believe that the videos posted by Quaden on his Instagram handle looked like those of an adult. The Instagram account @quadosss that had the videos has since disappeared from the internet.

Quade Bayles is said to have been born with achondroplasia dwarfism. He was diagnosed with it just days after he was born. Quade's mother Yarraka is his supporting pillar. Under her son's name, the mother has worked towards creating awareness about dwarfism.

There have been three videos where the boy was in front of the camera before this incident. One was associated with his first case of bullying and unwanted attention. Yarraka posted a video in 2015 when a group of girls started pointing towards the boy and following them around while they were out shopping. The video was trending in Australia which led to Yarraka and Quade coming in front of the screen during a Studio 10 interview.

There is another video from 2015 which sets the records straight. It is a feature where Yarraka explains what Quade's condition is when he was around 4-years old in an SBS program called Living Black.

Apart from this, there is another evidence that says that he is actually 9-years-old. According to the family, the child was posing with a friend who turned 18 on his Instagram picture. Two years ago his mother posted a picture that showed them celebrating Quaden's 8th birthday.

Several of the pictures and videos have since been removed because of the extreme levels of negative attention that the family is receiving.

Similar to Quaden there is someone else who has gone through extreme trauma and that is Natalia Grace. The young girl was abandoned by her family who adopted her at a very young age. She was the Ukranian orphan who was called rude names by the internet including comparing her with Esther from the Orphan.

Natalia is said to be a teenager and her adoptive family said that she is actually in her 30s. Her adoptive parents Kristine Barnett, 46, and her ex-husband Michael Barnett, 43, were charged with neglect of a dependent, to which they pleaded not guilty.

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Is dwarf boy Quaden Bayles 18-year-old or just 9? Internet is divided and debate continues - International Business Times, Singapore Edition

Recommendation and review posted by Bethany Smith

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Some Antibiotics Prescribed During Pregnancy Linked to Birth Defects

Researchers at the University College London found that children of mothers prescribed macrolide antibiotics in the first trimester of pregnancy were at increased risk of major birth defects. The research was published in The BMJ. The birth defects include major malformations such as heart and genital defects, and four neurodevelopment disorders, cerebral palsy, epilepsy, ADHD, and autism spectrum disorder.

Macrolide antibiotics are used to treat a wide variety of bacterial infections and are among the most frequently prescribed antibiotics during pregnancy in Western countries, said Heng Fan, PhD candidate at UCL Great Ormond Street Institute of Child Health, and lead author of the study. This work builds on previous evidence of rare but serious adverse outcomes of macrolide use, especially for unborn babies. These adverse outcomes were assumed to be associated with the arrhythmic effect of macrolides, and policy advice about their use in pregnancy varies.

The investigators analyzed data from 104,605 children born in the UK from 1990 to 2016 from the Clinical Practice Research Datalink (CPRD), with a median follow-up of 5.8 years after birth. An additional 82,314 children whose mothers were given macrolides or penicillins before pregnancy and 53,735 who were siblings of children in the study acted as control cohorts. Major malformations were seen in 186 children of 8,632 whose mothers received macrolides at any point during pregnancy and 1,666 of 95,973 children whose mothers were dosed with penicillins during pregnancy. The researchers concluded that macrolides during the first three months of pregnancy were associated with an increased risk of any major malformation compared to penicillin.

The Mediterranean Diets Key Ingredient for Extending Lifespan

The Mediterranean diet has been noted for being heart-healthy and potentially improving lifespanheavy on fish, fruits, vegetables, grains, olive oil and red wine. Much research suggested the resveratrol found in red wine was the major contributor, but new research suggests it is actually the fat found in olive oil that activated a pathway known to increase lifespan and prevent aging-related diseases. It appears that the fat gets stored in lipid droplets and when the fat is broken down during exercise or fasting, the signaling and health benefits occur.

What Facebook and Genomes Have in Common

Computational biologists at Carnegie Mellon University took an algorithm used to study social networks like Facebook and adapted it to identify how DNA and Proteins behave in communities inside the cell nucleus. Proximity is a factor, because genes controlled by the same regulatory proteins benefit from being close to each other, but others can be relatively far apart but drawn together via shared interests. The MOCHI algorithm analyzes the spatial arrangement of all the genes and transcription factor proteins in a nucleus based on genome-wide chromosome interactions and global gene regulatory networks.

A 3D Atomic Scale Map of the 2019 Coronavirus

Investigators at the University of Texas at Austin and the NIH created the first 3D atomic scale map of the 2019 novel coronavirus. They used AMETEK Gatans K3 camera to map part of the virus called the spike protein, which is how the virus penetrates the host cells. The breakthrough should allow for more rapid vaccine and therapy development.

How Lung Cancer Cells Suck Up Energy

Researchers working with human lung cancer cells discovered how they modulate their energy consumption based on their surroundings. In addition, they discovered how cancer cells override those factors to maximize their energy use. They identified a protein called TRIM21 that appears able to prevent the degradation of metabolic enzymes, resulting in cancer cells keeping their metabolism high. Being able to interrupt this pathway could lead to new approaches to cancer therapies.

New Hope for Muscular Dystrophy

Although there are now a couple therapies on the market for Duchenne muscular dystrophy (DND), it is still incurable. Researchers at the University of Pennsylvania School of Medicine recently identified a group of small molecules that might lead to new treatments. The compounds eased repression of a specific gene, utrophin, in mouse muscle cells. This allows the body to produce more utrophin protein, which can be substituted for dystrophin, the protein whose absence causes DMD.

Were trying to find therapies that will restore a patients muscle function without resorting to gene therapy, said Tejvir S. Khurana, the studys senior author and professor of Physiology. Increasing utrophin is a major focus of muscular dystrophy research. While, ideally, we would replace the missing dystrophin in patients, there are a number of technical and immunological problems associated with this approach.

One is simply that the dystrophin gene is the largest in the body, and cant be fit into the viruses used for gene therapy. Most approaches along those lines use truncated dystrophin genes or other means to introduce a partial dystrophin gene or gene product. The other problem is that because the human body of DMD patients doesnt have regular amounts or types of dystrophin, introducing dystrophin to the body often stimulates an immune response as the immune system reacts to it as an invader.

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Research Roundup: Antibiotics Linked to Birth Defects and More - BioSpace

Recommendation and review posted by Bethany Smith

A large biotech is partnering with a firm developing cell and gene therapies on treatments for neurological diseases like Alzheimers and Parkinsons.

Cambridge, Massachusetts-based Biogen said Thursday afternoon after markets closed that it had partnered with Brisbane, California-based Sangamo Therapeutics in a deal that could be worth up to $2.7 billion. The partnership will initially focus on two preclinical Sangamo gene therapy candidates ST-501 for tauopathies such as Alzheimers and ST-502 for synucleinopathies like Parkinsons disease, plus an undisclosed neuromuscular target. It also includes exclusive rights for up to nine other undisclosed neurological targets.

Biogen will pay Sangamo $350 million upfront, which includes a license fee and equity investment, while Sangamo will be eligible for up to $2.37 billion in milestone payments, plus royalties.

Shares of Sangamo were up more than 28% on the Nasdaq after markets opened Friday. The company had also announced its fourth quarter and full year 2019 financial results. Biogens shares were down 2.6%.

Sangamo had reached out to multiple companies in a competitive process. While declining to say how many companies the biotech had spoken to, Sangamo head of corporate strategy Stephane Boissel said in a phone interview that it had put together multiple term sheets.

Its a combination of economics, but also the expertise of that partner in that particular field, Boissel said, referring to why the company had chosen Biogen. Biogen, in the pharma world, is probably the best franchise when it comes to neurology.

Adrian Woolfson, Sangamos executive vice president for research and development, said in the same call that it was also because of an appreciation for Biogens enthusiasm and energy.

I think its fair to say we had a very good chemistry with them at a personal level when we went to meet with them in Boston, and we seemed to get along very well, Woolfson said.

Sangamo has existing partnerships with a number of other firms, including Pfizer and Gilead Sciences.

Biogens moves into Alzheimers disease have not been without controversy. The company plans to file for Food and Drug Administration approval of aducanumab, a monoclonal antibody targeting the amyloid beta protein that has long dominated Alzheimers research. The company initially halted the Phase III development program for the drug when it was predicted to fail, but revived it when a post-hoc analysis indicated potential efficacy. Investors have remained skeptical.

Still, that did not come up in the minds of Sangamos executives, Boissel said. While emphasizing that he could not compare the two companies approaches, Woolfson added that gene therapies are potentially better ways to address neurological diseases like Alzheimers because they can switch off genes completely rather than being limited to taking out specific proteins, as monoclonal antibodies are.

ST-501 targets tau, another protein that has been researched as a potential therapeutic target in Alzheimers. ST-501 and ST-502 use adeno-associated viral vectors to deliver zinc finger protein transcription factors (ZFP-TFs), a form of gene therapy that Sangamo said in its quarterly earnings presentation is ideally suited to neurological disorders due to its ability to up- or down-regulate gene expression.

Boissel did not disclose specific timelines for ST-501 and ST-502, but noted that the next steps in their development will be preclinical studies to enable them to enter the clinic.

Photo: John Tlumacki, The Boston Globe, via Getty Images

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Biogen teams up with Sangamo in gene therapy deal worth up to $2.7B - MedCity News

Recommendation and review posted by Bethany Smith

Newswise CLEVELANDResearchers at Case Western Reserve University have used a unique method to safely deliver gene therapy to fight a rare, but irreversible, genetic eye disorder known as Stargardt disease.

By using chemically modified lipidsinstead of the viruses most commonly used as carriersStargardt disease did not return in animal models for up to eight months after treatment, said lead researcher Zheng-Rong Lu, the M. Frank Rudy and MargaretDomiter Rudy Professor ofBiomedical Engineering at the Case School of Engineering, with a dual appointment at the School of Medicine.

Lus research, recently published in the journal Molecular Therapy, was funded in part through a Gund-Harrington Scholar grant, a partnership between Harrington Discovery Institute at University Hospitals and the Foundation Fighting Blindness.

This grant provides innovative scientists like Dr. Lu both funding and drug development expertise to advance research that will defeat diseases that limit millions of people from experiencing the gift of sight, said Jonathan S. Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation at University Hospitals and Case Western Reserve University School of Medicine. It is very encouraging to see Dr. Lus work move closer to human trials.

A so-far incurable disorder

The research may give some hope to people with Stargardt disease, an inherited disorder of the retina also known as macular dystrophy or juvenile macular degeneration because it often surfaces during childhood or adolescence.

Although individuals with Stargardt disease rarely go completely blind, they progressively lose vision in both eyes, become very sensitive to light and, in some cases, develop color blindness.

Were really excited because there is a potential to help people with Stargardt, Lu said. But we believe this success could also apply to other disorders as a platform therapy for delivering other genes through the use of the lipids.

Lipids are simple organic compounds, or fatty acids, that are insoluble in water, including various natural oils, waxes and steroids.

Because they are basically unsaturated oil, the likelihood of damage to the eye is low, which isnt always true with the viral gene therapy, Lu said.

Gene therapy offers best hope

There are a lot of researchers trying to figure out how to treat this disease right now with little success, Lu said. The best hope is gene therapy.

Gene therapy is the technology in which genetic material is introduced into cells by an engineered carrier to compensate for abnormal genes or to make a beneficial protein.

The most successful gene therapy carriers so far have been certain viruses (the AAV, or adeno-associated virus, especially) because they can deliver the new gene by infecting the target cell.

But the Stargardt-associated gene, known as the ABCA4 gene, turns out to be too large to fit within that popular virus, Lu said.

Lu said other researchers have attempted to remedy that problem by splitting ABCA4 into pieces and then trying to reassemble it inside the eyewith limited success.

Other researchers have modified a larger virus to carry ABCA4 into the eyes, a technology tested in human trials as far back as 2011, but which still hasnt been fully commercialized.

He said he and his collaborators have also already met with investors to expedite the commercialization of the platform used for Stargardt.

Further, this gene therapy product could be classified as an orphan drug by the U.S. Food and Drug Administration (FDA) because Stargardt is a rare disease, increasing the likelihood of faster FDA approval after clinical trials, Lu said.

The non-viral gene therapy is also much more cost-effective for production than the virus-based therapy and has a potential to significantly reduce the high price of gene therapy in the eye, he said.

We think that within two to three years we could really be helping people after further demonstration of its safety and efficacy, Lu said.

MEDIA CONTACTS:

Michael Scott, Case Western Reserve University

216.368.1004, mike.scott@case.edu

Carly Belsterling, University Hospitals

412.889.8866, carly.belsterling@uhhospitals.org

###

Case Western Reserve University

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,100 undergraduate and 6,200 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.

Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, OHpart of The Harrington Project for Discovery & Developmentaims to advance medicine and society by enabling our nations most inventive scientists to turn their discoveries into medicines that improve human health.The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a Better World.

The Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines. For more information, visit:HarringtonDiscovery.org.

Visit link:
Scientists successfully test new way to deliver gene therapy - Newswise

Recommendation and review posted by Bethany Smith

Rare Disease Day is celebrated across the globe to raise awareness amongst the general public and policymakers about rare diseases and how they impact patients lives. The first Rare Disease Day was celebrated in 2008 on February 29 because of its rare date and since then, occurs on the last day in February each year, a month with a rare number of days.

Although rare suggests not many people are affected with a condition, collectively, 300 million people around the world live with a rare disease and they face similar challenges. The barrier to an accurate diagnosis means patients may doctor hop and spend years getting a host of tests done because no one is familiar with the condition and can diagnose it. Theres often frustration due to this lack of understanding from health care professionals, and living in the unknown.

Even with a diagnosis, more than 90% of rare diseases are still without an FDA approved treatment, according to the National Organization for Rare Disorders.

Some rare diseases may cause a multitude of different health problems that keep children from going to school or being able to socialize with others in the same way their peers can. Similarly, rare diseases may affect physical appearance and make children self-conscious or have low self-esteem.

LISTEN UP: Add the newMichigan Medicine News Breakto your Alexa-enabled device, orsubscribe to our daily updates oniTunes,Google PlayandStitcher.

Michigan Medicine researchers are constantly working to better understand the mechanisms behind rare diseases. Education helps health care professionals make accurate diagnoses, create treatment methods and improve the quality of life for those that live with these conditions.

Heres a sampling of their research from the last year.

Systemic Scleroderma Treatments: Where Are We Now?A new and novel outcome measure is being used to determine effectiveness of new scleroderma treatments.

Gene Therapy Treatment Targets Rare Mutation Tied to BlindnessAdvances in gene therapy are yielding new options for treating inherited retinal degenerations, giving specialists new tools and new hope for patients and families.

A Mission to Improve Cystic Fibrosis Treatment Across the GlobeTo reach patients in need, one doctor has developed atraining program to improve testingand care available for those with thegenetic disease, starting intheMiddle East.

Accelerating Childrens Access to New Treatments for High Risk Brain TumorsMichigan Medicine joins an exclusive, global network that helps speed up the process of linking children with incurable brain cancer to promising clinical trials.

A New Clue in the Mystery of ALS, Frontotemporal DementiaMichigan Medicine researchers identify a potential therapeutic target for neurodegenerative conditions using animal models.

Drug Trial Seeking First Ever Treatment for Dangerous Side Effect of Prader-Willi SyndromeA worldwide research effort is underway for finding a treatment option for hyperphagia, the most common genetic cause of life threatening childhood obesity.

Arthritis Treatment Could Provide Relief for Lichen Planus Skin RashIts often difficult to manage patients with this skin inflammation, but new research identifies a target that existing medications may be able to address.

Approach Could Help in Treating Glioblastoma, Other Rare CancersMichigan led research presents a new way of uncovering predictive biomarkers when data from large randomized trials arent available.

Sickle Cell Disease Could Be Treated by Turning Back the ClockReactivating genes normally active before birth could prevent the harmful effects of this blood disorder with few treatment options.

Registry Helps Move Aortic Dissection Care Forward Diagnosis, treatments and outcomes for acute aortic dissection have evolved, with an international registry revealing trends and the power of using data.

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To learn more about Rare Disease Day, visit the National Organization for Rare Disorders website.

Read more here:
10 Studies That Highlight the Importance of Rare Disease Research - Michigan Medicine

Recommendation and review posted by Bethany Smith

We made tremendous progress last year as we build a diversified portfolio in retinal diseases that includes both therapeutics and gene therapy, setting the stage for IVERIC bio to be a leader in developing transformative therapies to treat retinal diseases, stated Glenn P. Sblendorio, Chief Executive Officer and President of IVERIC bio. We achieved a major milestone with our positive Zimura pivotal clinical trial results in geographic atrophy secondary to dry AMD. Our goal is to continue to build on this momentum. Following the positive data, our team quickly started working on our second Zimura pivotal clinical trial in GA with plans to enroll the first patient next month. Our lead gene therapy programs in rhodopsin mediated adRP and BEST1 related retinal diseases continue to advance towards Phase 1/2 clinical trials and we expect to identify our lead minigene construct for LCA10 later in the year.

Therapeutics Programs

Zimura (avacincaptad pegol): Complement C5 Inhibitor

HtrA1 Inhibitor

Gene Therapy Programs in Orphan Inherited Retinal Diseases

Corporate Update

In December 2019, the Company completed an underwritten public offering in which it sold 7,750,000 shares of its common stock at a price of $4.00 per share, and it also sold to certain investors pre-funded warrants to purchase 3,750,000 shares of its common stock at a price of $3.999 per share underlying each warrant. The Company raised approximately $42.6 million in net proceeds from this offering.

During the fourth quarter of 2019, IVERIC bio appointed Guangping Gao, PhD as Chief Strategist, Gene Therapy, and Abraham Scaria, PhD as Chief Scientific Officer.

Fourth Quarter and Year End 2019 Financial Results and 2020 Cash Guidance

As of December 31, 2019, the Company had $125.7 million in cash and cash equivalents. The Company estimates that its year-end 2020 cash and cash equivalents will range between $60 million and $70 million. The Company also estimates that its cash and cash equivalents will be sufficient to fund its operations and capital expenditure requirements as currently planned into the beginning of 2022. These estimates are based on the Companys current business plan, including initiation of the Zimura ISEE2008 trial and the continuation of the Companys other on-going research and development programs. These estimates do not reflect any additional expenditures, including associated development costs, in the event the Company in-licenses or acquires any new product candidates or commences any new sponsored research programs.

2019 Financial Highlights

Conference Call/Web Cast Information

IVERIC bio will host a conference call/webcast to discuss the Companys financial and operating results and provide a business update. The call is scheduled for February 27, 2020 at 8:00 a.m. Eastern Time. To participate in this conference call, dial 800-458-4121 (USA) or 323-794-2598 (International), passcode 6010573. A live, listen-only audio webcast of the conference call can be accessed on the Investors section of the IVERIC bio website at http://www.ivericbio.com. A replay will be available approximately two hours following the live call for two weeks. The replay number is 888-203-1112 (USA Toll Free), passcode 6010573.

About IVERIC bio

IVERIC bio is a biopharmaceutical company focused on the discovery and development of novel treatment options for retinal diseases with significant unmet medical needs. Vision is Our Mission. For more information on the Company please visit http://www.ivericbio.com.

Forward-looking Statements

Any statements in this press release about the Companys future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include any statements about the Companys strategy, future operations and future expectations and plans and prospects for the Company, and any other statements containing the words anticipate, believe, estimate, expect, intend, goal, may, might, plan, predict, project, seek, target, potential, will, would, could, should, continue, and similar expressions. In this press release, the Companys forward looking statements include statements about its expectations to use its previously announced clinical trial of Zimura for the treatment of geographic atrophy as a pivotal trial, its development strategy for Zimura, including its plans and expectations regarding a second, pivotal clinical trial evaluating Zimura for the treatment of geographic atrophy, the implementation of its business plan, the projected use of cash and cash balances, the timing, progress and results of clinical trials and other research and development activities, the potential utility of its product candidates, and the potential for its business development strategy. Such forward-looking statements involve substantial risks and uncertainties that could cause the Companys development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, those related to the initiation and the progress of research and development programs and clinical trials, availability of data from these programs, reliance on university collaborators and other third parties, establishment of manufacturing capabilities, expectations for regulatory matters, need for additional financing and negotiation and consummation of business development transactions and other factors discussed in the Risk Factors section contained in the quarterly and annual reports that the Company files with the Securities and Exchange Commission. Any forward-looking statements represent the Companys views only as of the date of this press release. The Company anticipates that subsequent events and developments will cause its views to change. While the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so except as required by law.

ISEE-G

2019

2018

2019

2018

$

11,567

$

16,128

$

39,644

$

41,737

6,275

5,667

21,628

23,612

17,842

21,795

61,272

65,349

(17,842

)

(21,795

)

(61,272

)

(65,349

)

369

677

2,151

2,389

-

125,000

-

Go here to see the original:
IVERIC bio Reports Fourth Quarter and Year End 2019 Operational Highlights and Financial Results - BioSpace

Recommendation and review posted by Bethany Smith

BOSTON and LONDON, Feb. 27, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global leader in gene therapy, today reported business highlights and financial results for the year ended December 31, 2019, as well as 2020 strategic priorities and upcoming milestones.

We are inspired by the possibilities ahead for Orchard in 2020 and beyond to bring the benefits of our gene therapy approach to patients worldwide, said Mark Rothera, president and chief executive officer of Orchard. As we prepare for the anticipated EU approval of OTL-200 for MLD, we are strengthening the foundation of our global commercial infrastructure that could one day support multiple potentially transformative products. We are also continuing to propel the business forward by advancing our next wave of proof-of-concept trials evaluating the potential for gene-corrected stem cells in a broader range of neurometabolic disorders.With strong execution in 2019 and a solid balance sheet heading into 2020, we are well-positioned to deliver value to our shareholders.

Recent 2020 Achievements

2020 / 2021 Corporate Priorities and Expected Key Milestones

1Patient was treated by the Royal Manchester Childrens Hospital (RMCH) under a Specials license, granted by the UK government for the use of an unlicensed pharmaceutical product in situations of high unmet need when there is no other treatment option available. Orchard holds the license to the MPS-IIIA investigational gene therapy product (OTL-201) and is funding the proof-of-concept clinical trial being conducted at RMCH, which utilizes the same technology and procedures that were used to treat this first MPS-IIIA patient.

Fourth Quarter 2019 Financial Results

Cash, cash equivalents and investments as of December 31, 2019, were $325.0 million compared to $335.8 million as of December 31, 2018. The decrease was primarily driven by the net cash used to fund operations in 2019, partially offset by proceeds from the companys public equity offering in June 2019 and the proceeds from the first drawdown under a credit facility entered in May 2019. During the three months ended December 31, 2019, the companys cash used to fund operations and capital expenditures totaled approximately $43.8 million. The quarterly burn rate is expected to increase in 2020 due to the growth in operating expenses to support the potential launch of OTL-200 in the second half of 2020 and the companys planned capital investment on its in-house manufacturing facility.

During the three months ended December 31, 2019, the company recognized $0.6 million in revenue related to European sales of Strimvelis, the first gene therapy approved by the EMA for ADA-SCID.

Research and development expenses were $30.9 million for the three months ended December 31, 2019, compared to $17.4 million in the same period in 2018. R&D expenses include the costs of clinical trials and preclinical work on the companys portfolio of investigational gene therapies, as well as costs related to regulatory, manufacturing, license fees and milestone payments under the companys agreements with third parties, and personnel costs to support these activities. The company expects R&D expenses to continue to increase as its programs advance through development.

Selling, general and administrative expenses were $18.5 million for the three months ended December 31, 2019, compared to $12.0 million in the same period in 2018. The increase was primarily due to increased investment to prepare for the potential commercialization of multiple late-stage programs, as well as higher costs to support public company operations and stock-based compensation.

Net loss attributable to ordinary shareholders was $45.4 million for the three months ended December 31, 2019, compared to $25.1 million in the same period in 2018. The increase in net loss as compared to the prior year was primarily due to higher costs related to pre-launch activities on the companys later-stage programs in development and expenses associated with being a public company. The company had 96.9 million ordinary shares outstanding as of December 31, 2019.

The company expects that its existing cash, cash equivalents and investments will enable funding of its anticipated operating and capital expenditure requirements into the second half of 2021.

Conference Call & Webcast Information

Orchard will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss its 2019 financial results and other business updates. To participate in the conference call, please dial 866-930-5155 (U.S. domestic) or +1-409-937-8974 (international) and refer to conference ID 8096875. A live webcast of the presentation will be available under "News & Events" in the Investors & Media section of the company's website at orchard-tx.com and a replay will be archived on the Orchard website following the presentation.

About OrchardOrchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically-modified blood stem cells and seeks to permanently correct the underlying cause of disease in a single administration. The company has one of the deepest gene therapy pipelines in the industry and is advancing seven clinical-stage programs across multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist, including inherited neurometabolic disorders, primary immune deficiencies and blood disorders.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About OrchardInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (twitter.com/orchard_tx and http://www.linkedin.com/company/orchard-therapeutics), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements may be identified by words such as anticipates, believes, expects, plans, intends, projects, and future or similar expressions that are intended to identify forward-looking statements. Forward-looking statements include express or implied statements relating to, among other things, the companys business strategy and goals, the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release, Orchards expectations regarding the timing of regulatory submissions for approval of its product candidates, including the product candidate or candidates referred to in this release, the timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates, the timing of announcement of clinical data for its product candidates and the likelihood that such data will be positive and support further clinical development and regulatory approval of these product candidates, the likelihood of approval of such product candidates by the applicable regulatory authorities, the likelihood the company will initiate construction of an in-house manufacturing facility in 2020, and the companys financial condition and cash runway into the second half of 2021. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be approved, successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates,the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 20-F for the year ended December 31, 2018, as filed with the U.S. Securities and Exchange Commission (SEC) on March 22, 2019, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Consolidated Statements of Operations Data(in thousands, except share and per share data)(Unaudited)

Consolidated Balance Sheet Data(in thousands)(Unaudited)

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaMolly CameronManager, Corporate Communications+1 978-339-3378media@orchard-tx.com

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Orchard Therapeutics Reports 2019 Financial Results and Reviews Key Strategic Priorities for 2020 - BioSpace

Recommendation and review posted by Bethany Smith

Gene therapy products approved between the years 2003 and 2017 include Gendicine, Oncorine, Rexin-G, Neovasculgen, Glybera, Imlygic, Strimvelis, Zalmoxis, Kymriah, Yescarta and Luxturna. Gendicine was approved for head and neck squamous cell carcinoma and has been in the Chinese market since 2003. Rexin-G was approved in the Philippines back in 2007 for the treatment of primary and metastatic cancer. Oncorine was approved in China in 2005 for nasopharyngeal carcinoma. The Russian market has Neovasculgen from 2011 for the treatment of peripheral arterial disease (PAD) and critical limb ischemia. The first gene therapy approved in E.U. was Glybera in 2012 for the treatment of familial lipoprotein lipase deficiency (LPL), however in October 2017 it was pulled from the market due to lack of patient demand. In 2015, Imlygic was approved in E.U. and also in the U.S. to treat melanoma, and Phase II results released in 2017 indicated its efficacy in combination with the checkpoint-inhibitor, Yervoy. In the E.U., Strimvelis was approved in 2016 for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2016, Zalmoxis was approved in E.U. for the treatment of leukemia. 2017 was a bumper year for gene therapy with Kymriah, Yescarta and Luxturna all gaining FDA approval.

Browse Complete Global Gene Therapy Market Analysis and Forecasts Report at https://www.reportsnreports.com/reports/1370259-global-gene-therapy-market-analysis-forecast-to-2022.html

Since the FDA approved Kymriah (tisagenlecleucel), Yescarta (Axicabtagene ciloleucel) and Luxturna (voretigene neparvovec-rzyl) in 2017, the US gene therapy space has expanded significantly, underlined by the fact that over 55% of completed and ongoing trials are located in this geographic. Growth in the gene therapy industry has resulted in new commercial initiatives and the emergence of new startups and spin-off biotechs. Furthermore, gene therapy specifically has raised well over $600 million of venture capital in the last five years. Early stage companies have raised seed, Series A and Series B investment steadily since the market took off, including Spark Therapeutics, Avalanche Biotech, uniQure, Voyager Therapeutics, Editas Medicine and GenSight.

In 2017, theGene Therapy Marketfor technologies, services and products was estimated to be worth $x million, with a potential to reach $363 million by 2022. The main market space is cancer which currently holds x% market share. This indication generated $x million in 2017 and will generate $x million in 2022. This is followed by rare diseases, cardiovascular, neurological and ocular indications. Looking at the market by technology, at present, gene product therapeutics generate the majority of revenue with over $x million in 2017, growing to $x million by 2022. Viral vectors are set to generate $x million in 2017, and will rise to $x million in 2022, and by then gene therapy services such as vector development and transfection will hit $x million. At present, the Americas have penetrated the market significantly with 65% geographic share, followed by Europe (x%) and the RoW (x%).

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Global gene therapy market is forecast to hit $363 million by 2022 from $x million in 2017. Strengthened by recent approvals of Kymriah, Yescarta and Luxturna in the US, and a committed European, Japanese and Chinese environment, gene therapy is set to become a significant player in the bio-pharmaceutical industry. The space covers many therapeutic areas specifically, oncology, rare diseases, Parkinsons, HIV, severe combined immuno-deficiencies (SCID) and hemophilia. Recently, in November 2017, the FDA indicated that gene therapies will now qualify for a fast approval process, which will bring more therapies to market faster. However, the space also has significant challenges, such as manufacturing logistics, reimbursement and its high cost. This 310 page market analysis cutting-edge report tackles this growing but challenging industry, it highlights its strengths, weaknesses and opportunities and provides a comprehensive account of major companies, clinical trials and technological advancement.

Renewed interest has encouraged start-up companies to affiliate with academic centers for tech know-how. As clinical trials advance towards licensure, more meticulous product characterization using improved analytical methods and progressively higher regulatory compliance will be required. Some of the ongoing clinical trials are closing on to produce promising results, including one for hemophilia B caused by the deficiency of Factor IX using a recombinant adeno-associated virus (AAV) as a vector. The product candidate if succeeds will be a relatively cheaper alternative to the expensive and lifelong factor replacement therapy.

A second example of a successful outcome in gene therapy are studies conducted by independent laboratories focusing on sub-retinal delivery of recombinant AAV expressing retinal pigment epithelial RPE65 for Leber Congenital Amaurosis Type 2. A third example is the clinical trial involving nine children with X-linked severe combined immunodeficiency (SCID-X1) treated with autologous bone marrow CD34+ cells transduced with a self-inactivating (SIN) -retroviral vector expressing the IL-2 receptor -chain. This novel strategy involves ex vivo gene transfer using recombinant retroviral or lentiviral vectors of chimeric antigen receptors consisting of antibody-binding domains fused to T-cell-signaling domains into patient T lymphocytes.

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As gene therapies are generally meant for one time or short duration treatments, they are customized to individuals confined to small patient populations. Therefore, manufacturing firms are expected to seek premium prices for these therapies. Because of this, these therapies will have to face valuation and reimbursement challenges. Stakeholders will show reservations about the hefty price tags and they will require significant data to be convinced. With the removal of Gylbera from the EU market in 2017, due to the fact that only one patient was treated with the drug, all eyes are focused on the number of end patients that will be treated, and their ability to pay. To that end, launching of new drugs may have to be delayed in order to collect more data for payers. Furthermore, annuity based reimbursement agreements and pay-for-performance scenarios will have to be tackled.

This report provides the reader with:Current Global Market Worth and Forecast with CAGR Through 2022Sub-Market Worth by Therapeutic Area (Cancer, Rare Diseases, Cardiovascular, Neurological, Ocular) and Forecast with CAGR Through 2022Sub-Market Worth by Geography (Americas, Europe, RoW) and Forecast with CAGR Through 2022Sub-Market Worth by Technology (Gene Product, Service, Viral Vectors) and Forecast with CAGR Through 2022Insight into gene therapy technologies, challenges associated with developing therapeutic genes and disadvantages of gene therapy.Full outline of the gene therapy industry from the formative years through to products discovered during 1990 and 2017.Detailed descriptions of commercialized products approved between 2003 and 2017 that include: Gendicine, Rexin-G, Oncorine, Neovasculgen, Glybera, Imlygic, Strimvelis, Zalmoxis, Kymriah, Yescarta and Luxturna.Description of seven of the Phase III product candidates that include: Generx, Collategene, LentiGlobin, Lenti-D, VM-202, Invosa and GS-010.Description of 21 Phase II product candidates that are set to have significant market share.Commercialization status of gene therapies in by geographic regionEvaluation of gene therapy pricingDescription of the firstever warranty offer by GSK for Strimvelis.A detailed analysis of various types of viruses used as vectors.Description of clinical applications of gene therapy and the various genetic and infectious diseases addressed by gene therapy.Description of 77 companies that are directly and indirectly associated with gene therapy industry.

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Key Questions Answered in this Report:

What is the size of gene therapy market?What is the CAGR and market size over the next five years?What are the different sub-markets and their worth/CAGR over the next five years?What is gene augmentation therapy?What is suicide gene therapy?How is ex vivo gene delivery different from in vivo gene delivery?What are the types of gene therapies classified on the basis of targeted cell types?What is the role of CRISPR technology in gene therapy?What are the approved gene therapy products?How many gene therapy product candidates have reached the Phase III stage?How many Phase II gene therapy product candidates are there?What is the commercialization status of gene therapies in E.U. member countries?What are the prices of gene therapy products?What are the reasons for this extortionate pricing of gene therapies?Which company is offering warranty for its gene- therapy product?What is the current strength of gene therapy industry?Is it true that the real strength of gene therapy industry is based on the number of clinical trials?What is the total number of ongoing clinical trials as of 2017?What is the distribution of clinical trials by geography?Which countries are associated with gene therapy clinical trials?What are the major indications addressed by the clinical trials?Which genes are transferred in these clinical trials?How many Big Pharma are associated with the gene therapy industry?What are non-viral and viral vectors?What are the various features of viral vectors?Which viral vectors are predominantly used in gene therapy clinical trials?What are the major diseases addressed by therapeutic genes?Where is the gene therapy market heading, and what opportunities and challenges will it face?

This content has been distributed via WiredRelease press release distribution service. For press release service enquiry, please reach us at contact@wiredrelease.com.

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Gene Therapy Market CAGR and Market Size over the next five years - PharmiWeb.com

Recommendation and review posted by Bethany Smith

Early proponents of genome sequencing made misleading predictions about its potential in medicine.

An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention, and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of bipolar disorder, schizophrenia, and alcoholism, among other conditions and behaviors. These articles drew massive attention in the popular media, but were soon retracted or failed attempts at replication. These reevaluations completely undermined the initial conclusions, which often had relied on misguided statistical tests. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

A silver bullet genetic fix is still elusive for most diseases.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.

Written by Ari Berkowitz, Presidential Professor of Biology; Director, Cellular & Behavioral Neurobiology Graduate Program, at the University of Oklahoma.

Originally published on The Conversation.

Read the original:
Sequencing the Human Genome Was Supposed to Revolutionize Treatment of Disease Heres Why It Failed - SciTechDaily

Recommendation and review posted by Bethany Smith

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Orchard Therapeutics(NASDAQ:ORTX)Q42019 Earnings CallFeb 27, 2020, 8:00 a.m. ET

Operator

Ladies and gentlemen thank you for standing by and welcome to the Orchard Therapeutics Fourth Quarter 2019 Earnings Conference Call.

[Operator Instructions] I would now like to hand the conference over to your host for today Ms. Renee Leck.

Renee Leck -- Director of Investor Relations

Thanks operator. Good morning everyone and welcome to Orchard's Fourth Quarter 2019 Investor Update. You can access slides for today's call by going to the Investors section of our website orchard-tx.com. Before we get started I would like to remind everyone that statements we make on this call will include forward-looking statements. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risk factors and uncertainties including those set forth in the most recent Form 20-F filed with the SEC and any other filings that we make. In addition any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

And with that I'll turn the call over to our President and CEO Mark Rothera.

Mark Rothera -- President and Chief Executive Officer

Good morning. Thank you for joining us and happy Rare Disease Week. One of the themes of this year's campaign is to reframe what it means to have a rare disease. This fits really well with our view that the term patient should be considered a temporary label given the potentially transformative and even curative effect that our one-time investigational gene therapies can provide. At Orchard we are harnessing the power of genetically modified blood stem cells as we seek to correct the underlying cause of severe rare diseases. We have now treated over 170 patients across seven different diseases and demonstrated durable outcomes going out to 18 years or more. If you break this down into cumulative patient years of exposure that's about 750 patient years of data supporting the clinical profile of our gene therapies. This is all to say that our clinical data is really on another level in terms of durability of response and safety. Our business strategy is to create value by commercializing multiple valuable gene therapy programs for rare diseases via highly efficient global commercial platform and benefiting from increasing manufacturing and regulatory efficiencies over time. The key steps to executing on our strategy can be broken down into a number of components.

Firstly we have built a fully integrated company with industry-leading capabilities in research in medical corporate strategy manufacturing regulatory affairs and commercial across an organization that is approximately 300 people strong. Secondly we've established an extensive pipeline of seven clinical stage hematopoietic stem cell gene therapy programs. Thirdly we're establishing an efficient global manufacturing and supply chain leveraging our existing CMO relationships but also our emerging in-house capabilities. Fourthly we're establishing a global commercial footprint on a phased basis. And finally we are keeping in mind the potential to use business development as a tool to create additional value. Now turning to our three lead programs in MLD ADA-SCID and WAS. There are a number of exciting near-term milestones as these programs progress toward potential regulatory filings approvals and launch. For MLD our key priority is to obtain approval for and launch OTL-200 in Europe in the second half of 2020. A BLA filing for OTL-200 in the United States is planned for late 2020 or early 2021. Regulatory filings for OTL-101 for ADA-SCID and OTL-103 for WAS are not that far behind. We plan to initiate a rolling BLA filing in the United States for OTL-101 in the first half of the year with completion of the file anticipated within 12 months. BLA and MAA regulatory filings for OTL-103 in the U.S. and Europe are planned for 2021.

The clinical work supporting efficacy and safety for ADA-SCID and WAS is complete. For ADA-SCID as per FDA guidance work on process validation runs and release criteria is ongoing using the commercial drug manufacturing process with patient cells. For WAS we've enrolled six patients in the ongoing cryopreserve study and expect to report preliminary data sometime this year. It's our plan that the focused commercial infrastructure we are establishing for MLD will serve as the backbone for the future planned launches of ADA-SCID and WAS with only modest additions needed to accommodate the additional launches. All together we believe there is at least a $1.5 billion incidence-based annual opportunity for our lead three programs in the geographies that we intend to cover that reimburse orphan drugs. Now let's focus on the MLD commercialization strategy. We're focused on four strategic imperatives that are key to the commercial launch preparations: patient identification a phased global infrastructure build supply readiness and market access. Starting with patient identification this is an area of high importance as the earlier patients are treated the better their long-term clinical outcomes. So far we've studied MLD patients with the infantile and juvenile forms of the disease and so we'll be targeting a pediatric label at launch. In MLD we estimate that approximately 500 to 800 patients are born each year in the approximately 50 countries that typically reimburse rare disease therapies. Of these we estimate 80% of the incident population will be eligible for OTL-200 at launch.

In terms of prevalence we believe that up to 30% of MLD patients living with a slower progressing juvenile form of the disease could be eligible at launch assuming we secure our target pediatric MLD label. This figure could grow to approximately 80% if we take into account adult MLD patients and assuming we can successfully expand our label. In order to identify these patients we have near and longer term initiatives ongoing. Disease awareness is the first key area. Now that a first-ever treatment for MLD is approaching a potential regulatory approval there is a strong incentive to improve patient diagnosis. Together with patient advocacy groups we are using targeted tools and resources to educate pediatricians and other specialists on the early symptoms of MLD so physicians suspect and test for an MLD diagnosis sooner. Improving access to the appropriate diagnostic tests is another important area. We have a sponsor diagnostic testing program to help identify patients prior to newborn screening coming online. Our goal is that within 14 days of early suspicion a confirmatory test can be done. Our ultimate goal is universal newborn screening using blood spots. An assay has been developed and we're now initiating with collaborators pilot studies in both Europe and the United States starting with New York State and Italy to validate these assays find patients and ultimately support the adoption of national screening programs. When launching a product for a rare disease it's important to have a focused and dedicated commercial team that enables you to bring these medicines to patients around the world as soon as possible. Building a global commercial footprint is our second imperative. We're doing this on a phased approach through a combination of direct Orchard team presence but also coverage via highly experienced partners in some geographies for example in the Middle East and Turkey where we expect a higher incidence of patients also.

Phase one is the EMEA regional buildout which is mostly complete and includes a team of 25 commercial FTEs. We are working on qualifying approximately six treatment centers in the EMEA region at launch with specialized expertise in transplant and neurometabolic disease area knowledge. Phase two is our U.S. buildout which is under way and will grow over the next 18 months in anticipation of the OTL-200 filing at the end of this year or early next and a potential subsequent approval. Phase three will extend Orchard coverage to the countries in other parts of the world that typically reimburse orphan drugs particularly key countries in Latin America and Asia. This will start in 2021. Our third imperative covers the commercial launch supply. We have a great partner in MolMed based in Milan Italy. They have been working on the MLD program for eight years now and also have commercial manufacturing experience supporting Strimvelis. Our goal is to have vector inventory at launch in line with anticipated demand and a robust supply chain between MolMed and the qualified treatment centers. I'll touch on the fourth strategic imperative around pricing and market access at the close of the call. We believe there is a tremendous potential to treat a broad range of diseases with high unmet need using hematopoietic stem cell gene therapy approach including other neurometabolic and neurodegenerative disorders.

Let me now hand it over to Bobby to develop this topic along with providing updates from the MPS-I and MPS-IIIA programs. Bobby?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Thanks Mark. Data in both MPS-I and MPS-IIIA were featured at WORLD and I'll start by briefly highlighting those presentations. I'll also be providing an overview of our proof-of-concept study in MPS-IIIA which was recently initiated. Our approach for both diseases use the same ex vivo HSC gene therapy approach that has delivered such promising results in MLD that is the overexpression of enzyme in HSCs that have the ability to migrate across the blood-brain barrier and deliver enzyme to the CNS. Let's start with MPS-I. And I want to spend some time discussing the proof-of-concept cohort as a whole now that median follow-up is out to six months in seven evaluable patients. As a reminder MPS-I is a lysosomal storage disease characterized by neurodevelopmental deterioration severe skeletal manifestations and cardiopulmonary complications leading to death in early childhood. Allogeneic hematopoietic stem cell transplant remains the standard of care; however significant residual manifestations of the disease remain after treatment. As of the later stage cut all patients undergoing HSC gene therapy have engrafted and all evaluable patients showed sustained supranormal IDUA activity in the bloodstream and the cerebrospinal fluid or CSF. This was accompanied by a concurrent drop in heparan and dermatan sulfate both in the urine and CSF that normalize rapidly within three to six months post-treatments.

The most important aspect of this data is that murine studies and analysis of patients undergoing allogeneic HSCT suggest that clinical outcomes correlate strongly with the level of IDUA enzyme expression. For example in a murine model of MPS-I a transplant with wild type cells did not fully correct the CNS and skeletal defects whereas overexpression of IDUA through lentiviral vector-mediated HSC gene therapy was able to do so. Similarly in a large published study of allo HSCT patients the level of IDUA expression achieved in the periphery was a highly significant predictor of long-term clinical outcomes. At 12 months post-gene therapy the patient with the longest follow-up is showing signs of resumed growth and bone remodeling improved motor skills and a stable cognitive score in line with evidence of metabolic correction. The trial has currently treated eight patients and we expect additional interim data to be presented this year before full proof-of-concept results are available in 2021. Let's now turn our attention to MPS-IIIA. This is one of the most frequent forms of mucopolysaccharidosis and has no approved treatments. At WORLD we were encouraged to see the University of Manchester present data on the first MPS-IIIA patient treated with ex vivo HSC gene therapy on a compassionate use basis who is doing very well. Engraftment of gene-corrected cells appears stable and enzyme levels well above the upper limits of normal at nine months post-treatment.

The vector and cell transduction protocols used to treat those compassionate use patients are the same as those used in our recently initiated proof-of-concept study. I'll briefly review the study's outcome measures and target patient population in order to provide a sense of scope and objectives. Patients between the ages of three months and two years with normal cognitive function are eligible for the trial. We're enrolling young patients in this initial study because as we've seen in MLD patients treated at a very early stage of the disease or who are asymptomatic have the best response presumably because the extent of irreversible CNS damage is limited. As a first-in-human study the primary objective is to evaluate the safety and tolerability of OTL-201 in addition to engraftment and biological efficacy measured by SGSH expression in leukocytes at 12 months post-treatment. Key secondary endpoints include cognitive and behavioral measures as well as quality of life and activities daily living at three years post-gene therapy which is typically when we begin to see decline in these functions in untreated individuals. The first patient in this trial has been enrolled and we expect to report preliminary data later this year. As patients are enrolled and the study progresses interim data cuts will be presented.

I want to look ahead now to some exciting new initiatives. Using the natural ability of HSCs to deliver therapeutic genes to the CNS and other tissues we believe there is a tremendous potential to treat more neurodegenerative diseases and new therapeutic areas. We will do this by external collaborations and also through in-house discovery and preclinical efforts in our established research laboratories in London. In January we were excited to announce in a new agreement with Dr. Alessandra Biffi a leading expert in gene therapy to help support the expansion of our portfolio into additional areas of critical need for patients including new programs for rare and non-rare neurodegenerative diseases. As the expert that first established our MLD and MPS-I programs her experience and partnership will be invaluable.

It's an exciting time at Orchard and we look forward to keeping you updated on these programs as the data matures. On that I'll turn the call over to Frank.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Thanks Bobby. I'm going to start by reviewing our fourth quarter results which are summarized in this morning's press release. Then I'll touch a bit on our outlook for the rest of the year and the upcoming launches for our lead programs. Starting with the financial results we ended the fourth quarter with $325 million in cash and investments compared to $336 million at the end of 2018. Consistent with our previous guidance we expect that our existing cash and investments will fund our anticipated operating and capital expenditures into the second half of 2021. During the fourth quarter we recognized $0.6 million in revenue related to Strimvelis. Research and development expenses were approximately $31 million in the fourth quarter of 2019 compared to $17 million in 2018. The increase was primarily driven by higher cost to advance our programs through later stages of development including the addition of our clinical stage MPS-I program in 2019. SG&A expenses were $19 million for the fourth quarter of 2019 compared to $12.0 million in 2018. The increase was primarily due to investments to prepare for the potential commercialization of our late-stage programs as well as G&A costs to support public company operations in 2019.

We used about $44 million of cash to fund operations in the fourth quarter of 2019. We expect the quarterly burn rate to increase in 2020 due to the capital investment for the manufacturing facility as well as sequential quarterly growth in operating expenses to support the potential launch of OTL-200 in the second half of 2020. I wanted to also use today's call to touch on our outlook for our lead programs. We are building a global commercial infrastructure and a manufacturing platform that we can leverage with each subsequent product launch. Notably each rare disease in our portfolio has its own set of unique factors that will influence the uptake curves as we enter the launch phase. A few of these factors include first is there a pool of prevalent patients and how easy will it be to identify and treat these patients? Second does the disease currently have a high level of awareness and diagnostic tools in place to aid patient identification? And third where will we launch first? To illustrate this with an example for a disease like ADA-SCID newborn screening is already established in all 50 states in the U.S. and some countries in Europe. So this gives us confidence that we should be able to quickly identify the incident population eligible for gene therapy driving faster uptake. Another example for a disease like WAS patients typically live longer due to the slower progressing nature of the disease and many have already been diagnosed. This will likely make the treatment of prevalent patients a key driver in early uptake. We are also planning to launch these two therapies first in this U.S. where adoption can often happen quicker.

Turning to MLD OTL-200 is an investigational treatment for a condition that is characterized by rapid progression. This means that our work to raise the awareness for physicians and implement diagnostic initiatives will be crucial in driving adoption before newborn screening is in place. Also we are planning to launch MLD first in Europe assuming approval and there will be country-by-country negotiations with payers which will mean a phased rollout across the continent. With the potential second half European MLD approval we expect meaningful revenues starting in 2021. We anticipate all three lead programs to be generating U.S. revenue by 2022. So in conclusion we believe that we're taking the necessary steps to position these programs for long-term success and demonstrating the scalability of our platform approach. As I said earlier in my remarks the investments we made in 2019 and the continued buildout of commercial and manufacturing in 2020 will take us a long way toward achieving our vision of building a fully integrated company with industry-leading capabilities.

And now Mark back to you.

Mark Rothera -- President and Chief Executive Officer

Thank you Frank. In closing as we get closer to our anticipated OTL-200 launch I'd like to address the four strategic imperatives for OTL-200 namely market access. We are seeking to bring a new type of medicine to the world. A one-off administration with the potential to deliver lifelong transformative benefit including the potential to cure. As a company we have committed to four key principles that will guide our approach to value and pricing which we've been proactively discussing and sharing with stakeholders. Firstly we are committed to share value. I think our investigational gene therapies are intrinsically very valuable medicines to the patient but also to the family whom according to recent research spends an average of 17 hours a day on caregiving responsibilities for an MLD child. We also expect the healthcare system and society more broadly to benefit from the potential value of these medicines. And certainly we want to reinvest some of this value in future innovation for other rare disease patients who are in need. Secondly we're committed to risk sharing. We recognize that gene therapies are still new to the system and questions exist about the durability of response over the long term. Having treated more than 170 patients and seeing follow-up now in our own portfolio spanning upwards of 18 years we are confident in the durability of response and are willing to engage in payment models that share risk if that is so required.

Thirdly we are committed to informed pricing applying well-developed robust and recognized tools to the best available evidence we have to measure value and in turn determine pricing. For instance we recently conducted an MLD caregiver research exercise in close partnership and consultation with leading KOLs and advocacy groups using standard well-accepted instruments like PedsQL. Early findings from this project presented two weeks ago at WORLD indicate that children with MLD experience roughly 20 outpatient visits and three inpatient visits in the last year. On average six days are spent in hospital per inpatient visit. That's an incredible amount of time for these parents to be away from work away from the rest of their family and community and knowing that the care for their child is only palliative. Unsurprisingly then our findings suggest 83% of parents were forced to miss work caring for their child with 68% of this being unpaid leave. Finally we will engage with stakeholders across the continuum to help evolve the way our healthcare system thinks about delivers and pays for gene therapy medicines. For years it's mostly been about managing chronic conditions and treating symptoms of disease. It's in everyone's interest that there is a successful path forward for one-off potentially curative medicines to be made available to patients.

Thank you for your time and attention. Operator you may now open the line for questions.

Operator

[Operator Instructions] Our first question or comment comes from the line of Anupam Rama from JP Morgan. Your line is open.

Anupam Rama -- JP Morgan -- Analyst

Hey, guys, thanks so much for taking the question. And how are you thinking about the initial size and scope of the sales infrastructure buildout in the EU for OTL-200 particularly as we think about layering on indications over the next several years? And maybe you can touch on the U.S. market as well. And then a quick second one on OTL-101. The rolling BLA's supposed to be starting here in the first half but what are the gating factors to completing it given the known preclinical data and clinical data? Is it really CMC related? I guess the guidance is that the OTL-101 filing would complete within 12 months but I guess why wouldn't it be quicker given everything that we know so far? Thanks so much.

Mark Rothera -- President and Chief Executive Officer

And the first one was about the size and scope of the team in Europe and then the overlay for the additional launches. And so as we mentioned for rare disease programs you really need a highly focused team. It doesn't have to be a large team but focused and dedicated as we have. We've guided to the fact that we have 25 FTEs out in markets in Europe with the major focus on the biggest markets such as Germany France UK and Italy. But I think one of the advantages of having our team in those countries is they are also sort of regional hubs for clusters of countries. So with the teams that we're building we expect patients to be referred not only from within those countries but from adjoining countries into those referential qualified centers for treatment. You asked a bit about how do we scale up. Well the good thing is that once you've established sort of a core group with some of the key capabilities like for example a general manager for Germany medical marketing and sales you really are looking at sort of adding just incrementally. You don't need another general manager you don't need another medic you don't need another head of marketing but what you might need is some additional people on the ground to meet additional customers to support patients getting to those treatment centers. So it is kind of incremental.

And the same is true in the U.S. where we'll begin well we are already preparing the buildout this year and into next with the MLD timeline in mind. And the other thing that I think is very efficient is for the most part you're talking about the same treatment centers the same qualified centers that can treat MLD patients or ADA-SCID patients or WAS patients. And again you might add a few incrementally to what you start with over time but again it's not a copy/paste. So the second question you asked was about the ADA-SCID program. So you're quite right that essentially we've done the clinical work on efficacy and safety. We've last year we talked about the cryo data that showed that cryo is performing like fresh. And really our key focus as per FDA guidance is the process validation work where we're using the commercial vector with a commercial drug manufacturing process using patient material which is something that they've specifically asked for. So we're guiding to initiating the rolling BLA in the first half of this year. That work that I just alluded to is ongoing and I think we'll feature in the final module that we will then present to close the filing. And as you mentioned we have up to 12 months to do that. And that for the moment is the guidance we're giving.

Anupam Rama -- JP Morgan -- Analyst

Great. Thanks for taking our questions.

Mark Rothera -- President and Chief Executive Officer

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Whitney Ijem from Guggenheim. Your line is open.

Whitney Ijem -- Guggenheim -- Analyst

Hey, good morning. Thanks for taking the question. This one is to follow up on some of the comments around market access. Kind of sounds like you're doing a lot of work on sort of the establishing value side. But from a logistical perspective on the reimbursement side I guess what work is ongoing around coding or kind of any other like logistical reimbursement type considerations that we should be thinking about?

Mark Rothera -- President and Chief Executive Officer

I think the first focus from a market access point of view is the potential launch of OTL-200 in Europe in the second half of this year. So for that there are many aspects that have been ongoing. Engagement with payers and making sure that the payers appreciate the background to the product the data and the benefit that we're able to convey to patients and the durability of that response. So a lot of this is an educational exercise. One thing we're very delighted with is a clear signal of willingness to pay given the fact that this is a product for a very high unmet need very severe condition that affects children and for which there are no treatments today and where the dataset that you've seen is very compelling. As you know in Europe there are I think this was alluded to in Frank's comment it's a sort of phased launch and so we also are engaging in the variety of different processes in different countries in order to be able to be well prepared on approval to move those forward as quickly as possible. And to remind you the lead country in Europe is typically Germany where you can launch relatively fast after an approval and have about a one-year time frame to complete the negotiations. So I hope that answers your question. If there's anything else you need to know please let me know.

Whitney Ijem -- Guggenheim -- Analyst

Maybe just one quick follow-up. Sort of in that same vein as we think about uptake or kind of penetration into the European markets versus the U.S. markets again with sort of reimbursement and the difference in the reimbursement frameworks in those geographies any color you can give or kind of how you guys thinking about that at this point?

Mark Rothera -- President and Chief Executive Officer

So it is a cascade of launches in Europe. So it's a very large market collectively as you know with 450 million inhabitants 28 countries. And it is a cascade of different launches with each country having a specific process for approval. I would say that one of the things that we have I think in the favor of launching a product like MLD in terms of the impetus to get this to market quickly is that really there's no treatment for these children and it is very severe. And so and the data is compelling. And so I think that there is a willingness to work with us now prospectively but also rapidly through these processes because time really matters for these children.

Operator

Thank you. Our next question or comment comes from the line of Esther Rajavelu from Oppenheimer. [Operator Instructions] Okay we'll move on. Our next question or comment comes from Gena Wang from Barclays. Your line is open.

Gena Wang -- Barclays -- Analyst

Thank you for taking my questions. I have two. One is regarding the MLD launch and the other is regarding the pipeline. So for the MLD launch just wondering Mark you mentioned that MolMed had a will have sufficient inventory being produced to meet expected launch demand. Just wondering those inventory are you referring to vectors and the plasmid? And what is the expected launch demand in terms of the number of patients? And also the capacity of the MolMed how many patient product can they process at the same time?

Mark Rothera -- President and Chief Executive Officer

Yes we're obviously delighted to have a partner like MolMed who have been working on the MLD program now for eight years and they have commercial manufacturing experience doing that already for the Strimvelis program. So it's a great partner to have on this program. So we work with MolMed actually on a whole range of programs. And we have capacity that is if you like fungible flexible depending on the various programs and their different stages of importance in demand. So we have the ability with MolMed to titrate very rapidly according to demand which is helpful. But the key thing that I was alluding to was the vector inventory as being one of the things that we wanted to make sure we had in place to allow us to meet the demand. Drug product manufacturing suites are also available at MolMed. And again there is certain flexibility there because we can manage across our portfolio of programs with them. At this time we're not guiding to patient numbers specifically. If that changes in the future we'll let you know. But our intention is to make sure we're matching supply with anticipated demand.

Gena Wang -- Barclays -- Analyst

And then my next question is regarding the pipeline. For MPS-IIIA and the MPS-I just wondering what based on your discussion with FDA and the other drug approval in the past what could be the latest thoughts for approvable endpoints and will you start to share the data of those the endpoints with us in the future?

Mark Rothera -- President and Chief Executive Officer

I'm going to turn that over to Bobby.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

So as far as let me start with MPS-I first of all. So this is a proof-of-concept study where the primary endpoints currently are as far as efficacy endpoints are concerned are around biological parameters; the enzyme activity reduction in substrate levels. The clinical endpoints are exploratory at the moment in this proof-of-concept study. And so we will move from this to a registrational study and the data from the proof-of-concept study will inform the endpoints for the registrational study. And so obviously we are having thoughts about what those endpoints would be in the registrational study and they need to be clinically meaningful endpoints. And we'll I'd say we can't give you details about that at the moment but obviously the major issues in MPS-I are around cognitive defects skeletal defects etc. And so we'll look at how we can capture those in the registrational study. And once we've got to more detail and agreement around that we'll share that data with you. As far as MPS-IIIA is concerned again we're in a proof-of-concept study at the moment at the University of Manchester. And again within that there are cognitive endpoints that are and behavioral endpoints that are being measured. And so that study has just started with the first patient having been enrolled.

Gena Wang -- Barclays -- Analyst

Bobby just follow-up question regarding MPS-I. So that has been a while ago. IDUA then got approval based on the SVC and the 6-minutes walk test. Do you think this will still be the case or you think that going forward the endpoint that could change also diverge from this?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

I mean I think at the moment I'd say we are looking at a number of exploratory endpoints within the proof-of-concept study and that includes we're looking at IQ we're looking at skeletal abnormalities growth etc. So we're looking at a number of things. And so I'd say we'll need to take that on board first before we decide what the endpoints will be for the registrational study. And I know you've talked about ERT being approved on the basis of 6-minute walk test etc. but things have moved on since that time. And also remember ERT doesn't have the ability to correct the CNS which is one of the major abnormalities one of the severe problems associated with MPS-I. So we would want to capture that within our endpoints for the registrational study.

Gena Wang -- Barclays -- Analyst

Okay great. Thank you very much.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Okay. Thank you.

Operator

Thank you. Our next question or comment comes from the line of Graig Suvannavejh from Goldman Sachs. Your line is open.

Graig Suvannavejh -- Goldman Sachs -- Analyst

Hi, good morning, or good afternoon, folks. Thanks for taking my questions. I've actually got a few but I'll try to keep them to maybe two or 3. First just on your opening comments around seeing the commercial revenue opportunity for your three lead programs at $1.5 billion is there any other color you can provide in terms of perhaps sizing magnitude if they're all equally say $500 million apiece or how should we be thinking about that? My second question just has to is focused more around OTL-200 and given that you're launching into Europe first how should we think about subsequent U.S. pricing? Should we be expecting that the price will be similar between the two geographies or we commonly think about pricing in Europe being less than what we see in the U.S. And then my final question is for Frank and the model. Thanks for the color around quarterly cash burn and how it will increase versus your exit rate in fourth quarter. But first half or second half should we just continue to steadily assume quarterly increase in cash burn as we evolve from the beginning of the year toward the second half of the year? Thanks.

Mark Rothera -- President and Chief Executive Officer

So I'll start with the first two and then hand over to Frank. You ask about any more color on the $1.5 billion annual incidence opportunity-driven revenue opportunity for the lead three programs. So reminding ourselves it's MLD ADA-SCID and WAS. And when we look at the global incidence in those key markets around the world when you you asked about more color the largest indication is MLD and then WAS and then ADA-SCID on an incidence basis. And we're expecting approximately 80% of the incident patients in those three indications to be eligible for our gene therapies at a minimum. It could actually be higher for a number of reasons I could go into as well. And when you look at that collectively using current gene therapy pricing analogs as a guide you can see it's at least a $1.5 billion annual opportunity. But I think very important color here is that that does not account for a really important upside which is prevalence. And we've also given an indication about the prevalent pool in each of the indications. I think Frank alluded to that in the prepared remarks. So Wiskott-Aldrich syndrome for example which is a slower progressing disease has a very significant prevalent pool. We estimate 3000 to 5000 patients worldwide living with that condition living with a sort of that need treatment. And we expect that about 55% of those could be eligible for gene therapy. So I think as Frank alluded to we see that as an especially prevalent play as far as the revenue build is concerned in that incident.

With regard to MLD we see it roughly as a balanced approach with both incidence but a 30% prevalent pool in the juvenile population that would be eligible for treatment we think at launch. But ultimately this would be an incident-based treatment. So on the second point you talked about which is OTL-200 pricing I think there are many reasons to consider the fact that MLD pricing could be actually with a relatively tight corridor between U.S. and Europe because this is a very high unmet need very severe disease. There are no treatment options. And I think given the data that we've generated as well as the durability of response I think we have a compelling case to make to payers both sides of the Atlantic. But that said I think we are of course launching in Europe first and the pricing will be set for Europe to start with. And then there's another year or so before we get to the U.S. launch. So in that time we will be watching carefully listening learning and we'll take a view on the U.S. price ultimately closer to the U.S. launch. So the third question was over to you Frank if I can hand it over to you.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Yes sure. No problem. So Graig on the modeling question I think for 2020 think about the growth in opex to be sort of incremental sequential growth on top of Q4. And I wouldn't say I mean if there's an inflection within there it would likely come in the second half of the year as we start to ramp up some of the commercial spend on the U.S. in preparation for a potential launch in the U.S. for MLD. But I would say generally just incremental growth quarter on quarter. In terms of the other piece which is the capex because we'll start construction on the manufacturing facility in 2020 I think we've previously earmarked about $70 million to $80 million total capex which will be spread over 2020 and 2021. So the construction activities will ramp up I would say second half of 2020 and first half 2021 largely. So that's how I would model the capex and the burn associated with the manufacturing facility.

Graig Suvannavejh -- Goldman Sachs -- Analyst

Great. Thank you very much for my questions.

Frank Thomas -- Chief Operating Officer and Chief Financial Officer

Thank you.

Operator

Thank you. Our next question or comment comes from the line of Yaron Werber from Cowen. Your line is open.

Yaron Werber -- Cowen -- Analyst

Ron, thanks very much for taking the question. Actually two if I might actually. So just really briefly I wanted to touch first on Strimvelis how we should kind of think about the slight up and down quarter-over-quarter sales. And more importantly I think how you're thinking about the drug moving forward particularly as the other ADA-SCID therapy approaches commercialization. And then just a question on the X-CGD and thalassemia programs mostly just kind of regarding on excuse me regarding timelines there when you think we might have next data and whether you're also considering a staggered filing and launch between Europe and the U.S. for X-CGD as well. Thanks.

Mark Rothera -- President and Chief Executive Officer

So Strimvelis has been a tremendously helpful learning tool for us about ex vivo gene therapy. It is a great product. It's available only in one center in the world in Milan Italy. And so we've learned a lot about helping patients move to treatment center in fact in many cases from one country to another what it takes to help those patients be well-managed and go through the treatment process. And yes it is a little bit bumpy and that to some extent depends on the identification of patients. And then the various stages of patient going through the decision making process between staying locally let's say for bone marrow transplant what the risks of that entails or going over to a center in Milan Italy for treatment. And I think one of the important distinctions to make going forward is that with our programs as you know we've gone from cryopreserved gene modified stem cells so where Strimvelis is only available as a fresh formulation which means patients have to do the traveling. As we look forward with our cryopreserved gene modified stem cells it's really those cells that are going to do the travel for the most part which is going to make it a lot easier for patients along this journey. So again I think the overall message is we've used this as a learning tool to prepare ourselves for launch for our OTL-200 and beyond. So for Bobby maybe you could answer the next question?

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Yes. So Yaron as far as X-CGD and beta-thal is concerned there are some similarities as far as the work we're doing in those two programs. So for X-CGD as you know the proof of concept is complete. And our initial thoughts on the pivotal study was that it would focus on late adolescence and adults where the best results were seen. But really in order to treat as many patients as possible we want to be able to treat pediatric patients as well. And so we need to see this year outcomes in pediatric patients. So that's part of the work for this year. But the other thing is this is a large prevalent population that we've talked about and so we need to get a manufacturing process that is appropriate to treat that number of patients. So we are spending again time this year on ensuring a manufacturing process that is fit for the commercial opportunity and that involves the use of transduction enhances for example to optimize the use of vectors. So that CMC work is ongoing as well. And third that latter part is really again what is what we're doing as far as beta-thalassemia is concerned. Proof of concept again established in that condition large patient population and opportunity and trying to get the manufacturing process correct in order to be able to serve that opportunity. And as I say that's predominantly looking at both the drug product process use of transduction enhances and also looking at vector as well. So I hope that addresses your question.

Yaron Werber -- Cowen -- Analyst

Sure. Thanks very much guys.

Bobby Gaspar, M.D., Ph.D. -- President of Research and Chief Scientific Officer

Thanks.

Operator

Thank you. Our next question or comment comes from the line of David Nierengarten from Wedbush Securities. Your line is open.

David Nierengarten -- Wedbush Securities -- Analyst

Hey, thanks for taking the question. I had one on the MLD patient numbers and incidence versus prevalence. And I know there's a little bit of a probably a blurry line but the incidence numbers that you provided are strictly births or new diagnoses? And I'm asking about new diagnoses because of course those might be a delayed diagnosis and so might actually be counted by some as a prevalent patient. So I was just wondering if you could provide a little bit more detail on those patient estimates for MLD. Thanks.

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Orchard Therapeutics (ORTX) Q4 2019 Earnings Call Transcript - Motley Fool

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Experts at Infiniti Research Explain How Channeling Data Effectively Into Pharma R&D Can Help Transform the Process of Drug Development - Yahoo...

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The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them or one of the couple of Americans who arrived later got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

We dont have too much time, Andre Kalil, the trials lead investigator, told Endpoints News. Everythings moving really fast.

Unlock this story instantly and join 73,300+ biopharma pros reading Endpoints daily and it's free.

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Read the original post:
UPDATED: A name emerges out of the Gilead M&A rumor mill, and it's a cancer biotech - Endpoints News

Recommendation and review posted by Bethany Smith

Alongside resolutions, the new year tends to come with biopharma acquisitions. The first two months of 2018 brought four deals worth $1 billion or more. The same was true in 2019, which barely got off the ground before a mammoth bid for Celgene was announced.

The early days of 2020, by contrast, have notched just one billion-dollar deal.

Analysts and consultants are mostly waving off this period of lighter activity. "We don't think a lack of deals over a couple of months is really anything notable," said Phil Nadeau of Cowen & Co. "It's probably just a bit of a dry period for no reason at all."

And yet, the slow start could seem oddly timed. It doesn't fit with the early and splashy dealmaking seen in recent years, nor does it align with some investment bank expectations that drug companies might try to ink deals sooner in the year to avoid possible disruptions from the U.S. presidential election.

But perhaps most glaring: the downswing comes as many large biotech and pharmaceutical companies are seemingly in need of M&A.

Two of the biggest biotechs, Gilead and Biogen, are under pressure to acquire because they haven't convinced investors that their experimental drugs can make up for problems on the commercial side of the business.

Among the pharmas, Sanofi, Eli Lilly and GlaxoSmithKline are trying to play catch up in the industry's hottest research area, oncology, and have shown a willingness to speed up that process through buyouts. Swiss drug giants Roche and Novartis, meanwhile, paid hefty premiums for footholds in the rapidly evolving gene therapy field.

Even Vertex and Merck & Co., which are considered to be in strong financial and competitive positions, turned to M&A several times last year to seed themselves for future growth.

"It's clear that, given the growth rates among the large companies in the industry, they have to keep filling their pipeline through acquisition, partnership or in-licensing," Nadeau said.

*Transaction value classified by acquiring company type. 2019 data through Nov. 30 of last year

Image Source: Jacob Bell / BioPharma Dive, data from EY

With buyers still on the lookout, industry followers predict 2020 will deliver a healthy level of M&A in spite of the early drought.

What they don't foresee, however, is this year being defined by a mega-deal like the last two were. Instead, bolt-on deals in the $5 billion to $10 billion range will be a "sweet spot" for large pharma acquirers, according to PwC.

Companies hold ample resources to support such deals too, as EY estimates the life sciences industry has more than $1 trillion at its disposal for deals. Notably, that's after a record-setting 2019 in which the industry spent north of $350 billion on M&A.

"There was so much moving and shaking that happened last year. And for me, I just feel like the underlying activity is still there. It just hasn't reached the surface yet," said Glenn Hunzinger, U.S. Pharmaceutical and Life Sciences Deals Leader at PwC.

If and when the activity surfaces, it's likely to target rare disease treatments, cell and gene therapy, and cancer drugs, with the latter proving particularly attractive. A recent Jefferies analysis found two-thirds of small- to mid-sized biotechs that got a cancer drug approved since 2010 were later acquired.

Many potential buyers, though, are in more comfortable financial positions now than they were even a couple years ago, and may not be as open to a less-than-perfect fit when considering a deal.

"Growth has returned to the large cap space, partially through acquisitions, and free cash flow across a number of large-cap companies has never been higher," said Kennen MacKay, an analyst at RBC Capital Markets. These companies now "have the luxury of time on their side, and they can be a little bit more selective."

That's especially true with regard to pricing, according to MacKay, who said the current lull in M&A may have something to do with a rebound in biotech stocks. The XBI, an exchange traded fund of about 130 biotechs, is up about 20% since hitting a relative low point in October. The rise also comes after multiple years in which cancer and gene therapy-focused biotechs have sold for high double-digit and sometimes triple-digit premiums.

"I think there's real reluctance to buy when small-, mid-cap stock prices are really running up," MacKay said.

Nadeau from Cowen, conversely, sees valuation as less of a barrier.

"Occasionally you do hear business development executives or former management teams talk about how valuation has gotten rich and they don't see attractive targets at a right price," he said. "But on the other hand, when you get these business development folks in private, offline, they'll admit that valuations are very flexible too. And if there's a strategic deal that a company wants to do, they can make any valuation work."

On his end, Nadeau isn't reading too much into 2020's slow M&A start. He guesses it's either due to happenstance, or because some of the deals that might have been inked this quarter were tied up early. Between October and December there were at least nine biopharma acquisitions, including five valued at more than $2 billion.

Peter Behner, global transactions leader for EY's Health Science & Wellness business, also doesn't envision the quiet period will last much longer. Whether in pharmaceuticals or other industries, companies don't just go dormant after a productive year of dealmaking, he said.

"I don't have a great explanation," Behner added. "At the same time, I don't have much doubt that the year should be a solid year."

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Pharmacquired: Where are all the deals? - BioPharma Dive

Recommendation and review posted by Bethany Smith

The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them or one of the couple of Americans who arrived later got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

We dont have too much time, Andre Kalil, the trials lead investigator, told Endpoints News. Everythings moving really fast.

Unlock this story instantly and join 73,300+ biopharma pros reading Endpoints daily and it's free.

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Biogen touts new evidence from the gene therapy company it wagered $800M on - Endpoints News

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Princeton Feb 28, 2020 (Thomson StreetEvents) -- Edited Transcript of IVERIC bio Inc earnings conference call or presentation Thursday, February 27, 2020 at 1:00:00pm GMT

* David F. Carroll

IVERIC bio, Inc. - Senior VP, CFO & Treasurer

* Glenn P. Sblendorio

IVERIC bio, Inc. - CEO, President & Director

IVERIC bio, Inc. - VP of IR & Corporate Communications

* Kourous A. Rezaei

IVERIC bio, Inc. - Senior VP & Chief Medical Officer

Good day, and welcome to IVERIC bio Fourth Quarter and Year-End 2019 Results Conference Call. Today's conference is being recorded.

At this time, I would like to turn the conference over to Kathy Galante. Please go ahead.

Kathy Galante, IVERIC bio, Inc. - VP of IR & Corporate Communications [2]

Good morning, and welcome to IVERIC bio's conference call. Representing IVERIC bio today are Mr. Glenn Sblendorio, Chief Executive Officer and President; Dr. David Guyer, Executive Chairman; Dr. Kourous Rezaei, Chief Medical Officer; Mr. Dave Carroll, Chief Financial Officer; and Mr. Keith Westby, Chief Operating Officer.

I would like to remind you that today we will be making statements relating to IVERIC bio's future expectations regarding operational, financial and research and development matters, including statements regarding our expectations to use our previously announced clinical trial of Zimura for the treatment of geographic atrophy as a pivotal trial; our development strategy for Zimura, including our plans and expectations for our second pivotal clinical trial evaluating Zimura for the treatment of geographic atrophy; our hypothesis regarding complement inhibition as a mechanism of action for the treatment of geographic atrophy; our projected use of cash and cash balances; the timing, the progress and results of clinical trials and other research and development activities; the potential utility and development potential for our product candidates; the size of the potential market indications our product candidates are intended to treat; and the potential for our business development strategy.

These statements constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. These statements cover many events and matters that are subject to various risks that could cause actual results to differ materially from those expressed in any forward-looking statement including risks related to initiation and the progress of research and development programs and the clinical trials; availability of data from these programs; reliance on university collaborators and other third parties; establishment of manufacturing capabilities; expectations for regulatory matters; need for additional financing and negotiation and consummation of business development transactions and other risks. I refer you to our SEC filings and in particular to the Risk Factors section in our quarterly report on Form 10-Q filed on November 12, 2019, for a detailed description of the risk factors affecting our business.

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we disclaim any obligation to do so as required by law.

I would now like to turn the call over to Glenn.

--------------------------------------------------------------------------------

Glenn P. Sblendorio, IVERIC bio, Inc. - CEO, President & Director [3]

--------------------------------------------------------------------------------

Thanks, Kathy, and good morning, everyone. As always, we appreciate you joining our call this morning. We made tremendous progress last year, as we continue to build a diversified portfolio in retinal diseases that include both therapeutics and gene therapy, setting the stage for IVERIC bio to be a leader in developing transformative therapies to treat retinal diseases.

At the end of October last year, we achieved a major milestone with positive Zimura clinical trial date in geographic atrophy or GA, secondary to age-related macular degeneration or AMD. These positive results position IVERIC bio as a late-stage clinical company, with Zimura as a potential treatment option for geographic atrophy, secondary to dry AMD, a potential multibillion dollar market, for which there are currently no FDA- or EMA-approved treatments available. I'd like to review some of the characteristics and results of this trial with you.

As reported in October 2019, individual administration of both Zimura 2-milligram and 4-milligram dose met the prespecified primary efficacy endpoint reached statistical significance in our international, multicenter, randomized, double-masked, sham-controlled clinical trial for GA secondary to dry, showing a 27% reduction in GA growth over a 12-month period in both the 2-milligram and 4-milligram treatment groups.

Based on our recent FDA guidance, we believe that this reduction in growth is not only statistically significant, but also clinically meaningful.

Zimura was well tolerated in this trial. And based on the potentially superior safety profile of Zimura observed to date, we believe that Zimura may potentially differentiate itself in the field of complement inhibitors for the treatment of GA secondary to dry AMD in elderly patients that we are seeking to treat.

Based on the prespecified screening trial design, robust masking, detailed statistical analysis with a prespecified statistical analysis plan and an independent and masked imaging analysis performed by one of the leading imaging centers in the world for retinal imaging, we believe that this clinical trial may serve as 1 of 2 pivotal trials typically required for marketing approval.

We are leveraging our deep expertise and efficient execution in retinal drug development, with the goal of bringing Zimura to patients with GA secondary to dry as soon as possible. We are in the process of initiating the second Zimura pivotal trial called ISEE2008 and are planning to enroll the first patient next month. As we initiate ISEE2008, we will seek to leverage our global network of top clinical trial sites for retinal diseases to assist with our plan to enroll approximately 400 patients. Kourous will review the design of ISEE2008 in more detail in a moment.

The results from OPH2003 Zimura pivotal trial have already been presented or planned to be presented at several prestigious retinal meetings around the world, including the Macula Society in San Diego; Angiogenesis, Exudation, and Degeneration Meeting in Miami; the Association for Research in Vision and Ophthalmology, the ARVO meeting in Baltimore; the American Society of Retinal Specialists, ASRS, that's going to be held in Seattle; the International Symposium on Ocular Pharmacology and Therapeutics in Spain; the Retina 2020: New Trends conference in Italy; and the Asia-Pacific Vitreo-retina Society meeting in China.

The safety and efficacy of Zimura is being assessed in an ongoing Phase IIb randomized, double-masked, sham-controlled screening trial in patients with autosomal recessive Stargardt disease. This is an orphan inherited retinal degeneration disease. Although autosomal recessive Stargardt disease is a monogenic retinal disease caused by genetic mutations to the ABCA4G, complement activation may play a role in this rare disease. In 2019, we completed the enrollment of 95 patients in this trial, and the trial is on track with initial top line data expected during the second half of 2020.

Although bringing Zimura to patients is our top priority, we continue to advance our gene therapy portfolio in orphan inherited retinal diseases.

Natural history studies and IND-enabling activities for IC-100, which is intended to treat with rhodopsin-Mediated adRP; and IC-200, which is intended to treat BEST1-related retinal diseases are both on track, and we expect to identify the lead minigene construct for LCA10 by midyear.

Over the past several months, we hosted 3 research and development symposium with panelists that include top retinal specialists from the U.S. and around the world, gene therapy scientists and KOLs, providing their insight, ensuring their expertise and feedback in regard to our Zimura and gene therapy programs.

We hope that these R&D symposium provided a deep understanding of our programs and want to thank all the investors and analysts who attended these meetings or listened to the corresponding webcast. These symposiums are currently posted on our website, and we'd like to invite you to participate. For those that did not participate live can listen to them online.

In November, we had the privilege of announcing Dr. Guangping Gao as our Chief Strategist, Gene Therapy at IVERIC bio. Guangping has deep gene therapy expertise with over 30 years of scientific research experience in AAV vectors and gene-based treatments.

As one of the world's leading gene therapy experts, Guangping's highly distinguished career includes his major contributions to the development of the adeno-associated virus gene delivery technology. Guangping is currently President of the American Society of Gene and Cell Therapy. He's also a Director of the Horae Gene Therapy Center, Co-Director of the Research Institute for Rare Diseases, and Professor of Microbiology and Physiological Systems at the University of Massachusetts Medical School.

Our goal is to combine Guangping's deep expertise in gene therapy and advisory capacity together with our expertise in drug development for retinal diseases to shape IVERIC bio's gene therapy strategy in the coming years.

We're also happy to welcome Dr. Abraham Scaria to the position of Chief Scientific Officer. He joined us in October. Abraham leads the company's research and preclinical gene therapy activities. His extensive experience includes positions at Genzyme, Sanofi, and most recently, Casebia Therapeutics, leading multiple ocular gene therapy programs. Extremely happy and pleased to be working with both Guangping and Abraham.

On the financial front, we continue to build our financial position and completed a successful follow-on public offering of our common stock and prefunded warrants, resulting in net proceeds for the company of approximately $42.6 million in December 2019. This transaction resulted in the company finishing 2019 with approximately $126 million in cash and cash equivalents. With the addition of this capital, we expect that we will have sufficient cash and cash equivalents to fund our operations and capital expenditures as currently planned into the beginning of 2022.

We are currently -- we are continuing to explore all options for future development and potential commercialization of Zimura, including plans for potential partnering.

We are pleased about the excitement generated by Zimura data and the progress in our gene therapy programs. We are excited about Zimura's potential to positively impact and transform the lives of the many patients with GA, who currently do not have any treatment options available to them and are potentially confronted with irreversible bilateral vision loss as well as the potential to bring our gene therapy to patients with orphan inherited retinal disease, who also do not have any treatment options available to them.

I'll now turn the call over to Kourous.

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Kourous A. Rezaei, IVERIC bio, Inc. - Senior VP & Chief Medical Officer [4]

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Thank you, Glenn, and good morning, everyone. Age-related macular degeneration is characteristically a disease of the elderly and is the leading cause of visual loss in individuals of 50 years of age or older in developed countries.

In the United States, it is estimated that approximately 11 million individuals are affected with AMD, with a reported global prevalence of approximately 170 million individuals. Because of increasing life expectancies in developed and developing countries, the elderly sector of the general population is expected to continue to increase in the coming decades. While 1 in 8 Americans was considered to be elderly in 1994, it is expected that the 1 in 5 will fall into this category by 2030.

As AMD progresses with age, it generally progresses to either the nanovascular or the atrophic dry form of AMD or the neurovascular form of the disease or wet AMD. In the dry atrophic form, the loss of photoreceptors, these are the cells that perceive light; RPE cells, these are the cells that support the photoreceptors; and associated choriocapillaries, which is the blood supply, leads to the formation of the geographic atrophy.

Currently, approximately 1.5 million individuals are reported to have geographic atrophy in the United States, with an incidence of approximately 159,000 patients per year, which is even slightly higher than what is reported for annual incidents for wet AMD.

Furthermore, development or progression of geographic atrophy over time is the common cause of vision loss in patients diagnosed with the wet form of AMD. For generally treated with anti-VEGF therapy, indicating that in many patients, regardless of whether they have the dry or wet form of AMD, the final anatomic outcome leading to loss of vision is geographic atrophy. Currently, there are no FDA- or EMA-approved treatment for GA, which leads to bilateral irreversible loss of vision in this large group of patients.

As Glenn pointed out, we are excited about the results of our first pivotal trial for Zimura in geographic atrophy, secondary to AMD, indicating that Zimura was well tolerated over 12 months and was able to slow down the growth of GA over the 12-month period in a statistically significant degree. Following these results, we immediately started a process to initiate our second pivotal trial in GA, ISEE2008, with the goal of enrolling our first patient next month. And we believe that we are on track.

ISEE2008 is an international, randomized, double-masked, sham-controlled, multicenter pivotal clinical trial evaluating the safety and efficacy of Zimura 2-milligram in patients with geographic atrophies secondary to dry AMD. As you may recall, in the first pivotal clinical trial, both Zimura 2-milligram and Zimura 4-milligram cohorts demonstrated a statistically significant reduction in the mean rate of GA growth over 12 months when compared to the corresponding sham-controlled cohorts with a similar 27% reduction. And since Zimura 2-milligram is administered as a single intravitreal injection, whereas the Zimura 4-milligram requires 2 intravitreal injections, we selected the Zimura 2-milligram dose for evaluation in the ISEE2008 clinical trial.

Our understanding from the FDA is that regarding the Zimura 2-milligram dose, for marketing approval purposes, from a safety perspective, at least 300 patients need to be treated with monthly Zimura 2-milligram or at a higher dose for a duration of at least 12 months, with a portion of these patients treated for 24 months. Therefore, we are planning to enroll approximately 400 patients in the ISEE2008 trial. These patients will be randomized 1:1 into 2 cohorts, the first cohort receiving monthly administration of Zimura 2-milligram for 12 months and a second cohort receiving monthly administration of sham.

The prespecified primary efficacy endpoint will be the same as our first pivotal trial and is the mean rate of change in geographic atrophy growth over 12 months measured by fundus autofluorescence at 3 time points: baseline, month 6 and month 12.

If we receive positive 12-month data from ISEE2008, we plan to file for marketing approval for Zimura for the treatment of GA with the FDA and EMA. At month 12, we plan to re-randomize patients in the Zimura 2-milligram arm to receive either monthly or every other month administration of Zimura 2-milligram. All patients will initially receive monthly administrations of sham, will continue to receive monthly administrations of sham. We intend to treat and follow our patients for 24 months.

The inclusion and exclusion criteria for ISEE2008 are similar to our first Zimura pivotal trial. However, in the first trial, when patients were reported to have developed choroidal neovascularization or CNV in the study eye during the trial, they got excluded from further participation in the study, because we were concerned that fundus autofluorescence images could not be reliably evaluated in the presence of CNV in the study eye. After discussions with our independent reading center who have reviewed the images from our ongoing Zimura GA trial, we believe that many of these images could potentially be reliably assessed by fundus autofluorescence.

Therefore, in the upcoming ISEE2008 trial, we are planning to keep patients who develop CNV in the study eye in the trial. And the measurement of these patient GA size will be included in the primary efficacy analysis as well as their fundus autofluorescence images can be reliably assessed by the masked reading center.

As Glenn mentioned earlier, Zimura met its prespecified primary endpoint in the first pivotal trial by reducing the rate of GA growth in patients with dry AMD in an international, multicenter, randomized, double-masked, sham-controlled clinical trial. The reduction in the mean rate of GA growth over 12 months was 27.38%, with a P-value of 0.0072 for the Zimura 2-milligram group as compared to the corresponding sham-controlled group and 27.81% with a P-value of 0.0051 for the Zimura 4-milligram group as compared to the corresponding sham-controlled group.

These data for both those groups were statistically significant. And based on the recent FDA guidance, we consider them to be clinically meaningful. Most importantly, based on our preliminary review of the safety data today, Zimura was generally well tolerated over 12 months of administration. Over this 12-month period, there were no investigator-related -- investigator-reported Zimura-related adverse events, no cases of Zimura-related interocular inflammation, no ocular serious adverse events, no cases of Zimura-related increase in intraocular pressure, no cases of end of endophthalmitis and no discontinuations attributed by investigator to Zimura.

Further, the investigator-reported rate of choroidal neovascular membrane incidents appears to be lower than what has been reported in literature for complement inhibition in GA. Based on recent literature, this may potentially be to Zimura blocking the complement cascade downstream at the level of C5 and not blocking the cleavage of C3. We believe that potentially superior safety profile of Zimura today could potentially differentiate Zimura in the field of complement inhibitors for the treatment of GA in these elderly patients.

The design of our first pivotal clinical trial for Zimura in patients with GA, secondary to dry AMD, possessed a few important characteristics that differentiated from other Phase IIb trials done in the field and we believe supported to qualify as a pivotal trial. I would like to go over some of these important differentiating factors.

This trial was designed as a Phase IIb screening trial, which means that it's designed and conducted as a Phase III trial with all necessary Phase III requirements, but with a smaller number of patients. The prespecified design of a screening trial provided if the study drug is efficacious enough to reach statistical significance with a smaller sample size, then trial could qualify as a pivotal clinical trial. As reported earlier, the reduction of GA growth reached statistical significance for both the Zimura 2-milligram dose and the 4-milligram doses, with compared to the corresponding sham-controlled arms at month 12, fulfilling this important criteria.

To minimize bias in this trial, patients, evaluating physicians, IVERIC bio as a sponsor and the independent reading center were all masked to the treatment that the individual patients were receiving throughout the trial.

A prespecified statistical analysis plan or SAP was used for statistical analysis. Based on the prespecified criteria in this SAP, a dose of Zimura would be statistically significantly more effective than the sham-control is the strength of evidence met the standard requirement of a 0.0125 one-sided false-positive error rate, incorporating an adjustment for multiplicity arising from comparing each dose with a sham control. Further, robust prespecified density analysis was planned and performed, which indicated the analysis results were robust to missing data.

For the assessment of the primary endpoint, the images were evaluated by a leading independent masked reading center. The reviewers were completely masked, and its visit -- and each visit was evaluated independently.

As indicated earlier, our first Zimura pivotal trial is still ongoing and patients continue to be treated and followed until they reach the month 18 time point. Patients, evaluating physicians, the independent reading center and we, as a sponsor, continues to be masked regarding the 2 main groups, in which each individual patient was randomized and expect to remain masked until the patients reach month 18. It is important to point out that this trial was not designed to assess statistical significance between individual cohorts at month 18 and any month 18 results will be descriptive only. We expect to report month 18 data by the end of second quarter.

To conclude, GA is a significant cause of bilateral, irreversible and severe loss of functional vision with a major impact on the quality of life and independence of our elderly patients. Although anti-VEGF therapy is available for treatment of wet AMD, no FDA- or EMA-approved treatments are currently available for geographic atrophy.

Further, development or progression of geographic atrophy over time is a common cause of vision loss in patient diagnosed with wet AMD or being treated with anti-VEGF therapy, indicating that regardless of whether patients have the dry or the wet form of AMD, the final anatomic outcome leading to loss of vision in many patients is geographic atrophy.

The absence of treatment options for geographic atrophy represents an area of urgent unmet medical need and a major public health concern for the expanding elderly population. We look forward to keeping you updated regarding the progress of our Zimura program and to potentially help these patients.

I would now like to turn the call over to Dave. Dave?

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David F. Carroll, IVERIC bio, Inc. - Senior VP, CFO & Treasurer [5]

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Thank you, Kourous, and good morning, everyone. I'd like to highlight a few items from our press release of this morning and provide some guidance on our expected year-end 2020 cash balance and cash runway.

For the quarter, our net loss totaled $17.5 million or $0.39 per share compared to a net income of $104.1 million or $2.62 per share for Q4 2018, as Q4 2018 reflects $125 million gain on extinguishment of a royalty purchase liability payable to Novo Holdings.

Our net loss for 2019 totaled $58.9 million or $1.39 per share compared to a net income of $63.1 million or $1.70 per share for 2018, as 2018 reflects the impact of the aforementioned gain on extinguishment of a royalty purchase liability.

Turning to our expected year-end cash balance and cash runway. As we previously announced, our cash balance at December 31 was approximately $126 million. We now estimate our year-end 2020 cash balance will range between $60 million and $70 million. We also estimate that our available cash will be sufficient to fund our operations and capital expenditures as currently planned into the beginning of 2022.

These estimates are based on our current business plan, which includes the initiation of our ISEE2008 trial and the continuation of our other R&D programs. Of course, these estimates don't reflect any additional expenses resulting from the potential in-licensing or acquisition of additional product candidates or technologies or any associated development the company may pursue.

I'll now turn the call back over to Glenn. Thank you for your time.

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Glenn P. Sblendorio, IVERIC bio, Inc. - CEO, President & Director [6]

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Well, thank you, everybody, for listening this morning. And we're focused on execution over the next few months. The first, obviously, is to get patients into our second pivotal trial next month. And obviously, we're looking forward to the 18-month data that will come in the second quarter. So it's a focus on execution, working with our collaborators to move these programs forward.

So thanks again. Thanks for your continued support. And operator, would you please open the line for some questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) We'll now take our first question, it comes from Ken Cacciatore of Cowen and Company.

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Kenneth Charles Cacciatore, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [2]

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Just congratulations on all the progress you've been making. Just a few questions here. First, just wondering if you've actually been thinking about or entered into any ex U.S. partnering discussions and trying to think of nondilutive ways you may be looking to bolster your cash position? And then secondly, I know it's difficult to do, and you're just going to get going here on enrollment. But can you give us some thoughts or ways of putting perspective around the timing to complete enrollment for the Phase III program? And then lastly, Apellis is clearly running a program as well, and we understand they're doing 2 studies versus your 1, given you already have a pivotal completed. But can you talk about any subtleties and differences between the 2 programs that you'd like to share?

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Glenn P. Sblendorio, IVERIC bio, Inc. - CEO, President & Director [3]

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Yes. Thank you, Ken, for those 3 questions. I'll take the first 2. On the partnering, we had a very good JPMorgan, and we had an opportunity to talk with a number of potential partners. We're going to continue to speak to those partners. What I was encouraged by was sort of the strength of the data, obviously, attracts some people that have interest. So as you know, these are -- and we've been saying that we're committed to exploring partnering. And we'll keep you updated over the coming months if those discussions progress. Obviously, I don't want to put any time lines or commitments on that. But your thought about ways to further strengthen the company, not only in terms of collaboration, but also nondilutive financing is something we're thinking about as well.

On the topic of enrollment, let us get started first. Obviously, those are always very competitive questions as to enrollment. I'll just focus -- in my summary, I talked about our focus on execution. I think you'll see the same intensity once we get the trial up and going. And as we move forward, if possible, we'll update the community. But right now, that's something we want to hold a little close. You know that we can do this based on our past track record, so stay tuned on that too. And I'm sorry for not being more specific. Kourous, do you want to take the third question about differences in the trial?

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Kourous A. Rezaei, IVERIC bio, Inc. - Senior VP & Chief Medical Officer [4]

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Originally posted here:
Edited Transcript of OPHT earnings conference call or presentation 27-Feb-20 1:00pm GMT - Yahoo Finance

Recommendation and review posted by Bethany Smith

Wall Street has been sharply attuned to coronavirus news. In fact, the extreme volatility in the market brought 24 trading halts on Thursday.

Several biotech or pharmaceutical-related stocks were halted and reopened several times for volatility in the regular trading session. Here is a look at those stocks and each company's connection to the coronavirus.

In partnership with Italys Takis Biotech, Applied DNA Sciences Inc (NASDAQ: APDN) is pursuing a linear DNA vaccine for COVID-19.

Allied Healthcare Products Inc (NASDAQ: AHPI) manufactures respiratory devices, emergency medical supplies and mass casualty ventilation products designed for pandemics.

With schools closed for quarantines, China Online Education Group - ADR (NYSE: COE) is taking over Chinas English tutoring services.

Oncology pharmaceutical Cleveland BioLabs, Inc. (NASDAQ: CBLI) develops immune-receptor activators for vaccines targeting various types of infection. Its vaccine adjuvant is currently in Phase 1 trials.

Utah medtech company Co-Diagnostics Inc (NASDAQ: CODX) is developing a test for the new coronavirus strain. Chinese officials and fearful travel companies demonstrate high demand for accurate diagnostics, as fever has proven an unreliable indicator of disease.

Global consulting firm CRA International, Inc. (NASDAQ: CRAI) is likely reacting less to coronavirus fears than to a quarterly earnings miss.

Tech developer Digimarc Corp (NASDAQ: DMRC) is similarly responding to an earnings miss.

EQT Corporation (NYSE: EQT), a natural gas producer, beat fourth-quarter earnings estimates and announced a deal with Equitrans.

Equitrans Midstream Corp (NYSE: ETRN) announced a deal with EQT, a stock buyback and a restructuring into a C-Corp.

Genetic Technologies Limited (NASDAQ: GENE), which develops and commercializes genetic risk assessment technology, commonly partners with medical companies and research organizations on R&D.

Biotech company Genprex Inc (NASDAQ: GNPX) touts a proprietary gene technology platform but has made no public entrance into coronavirus therapies.

Greenland Technologies Holding Corp (NASDAQ: GTEC) manufactures machine transmission products in China.

Biotech Ibio Inc (NYSE: IBIO) has partnered with CC-Pharming to develop a coronavirus vaccine using tobacco-related plants.

Jiayin Group Inc - ADR (NASDAQ: JFIN) is an online finance marketplace that facilitates consumer lending in China. Its remote offering may see increased uptake amid local quarantines.

LHC Group, Inc. (NASDAQ: LHCG) beat bottom-line estimates but missed the top line in its fourth-quarter earnings report.

Liberty Tripadvisor Holdings Inc (NASDAQ: LTRPB) holds an online travel site whose forum has seen some activity by fearful travelers.

IT services company Mastech Digital Inc (NYSE: MHH) offers clients data management, engineering and science.

Moderna Inc (NASDAQ: MRNA) received new funding from vaccine alliance CEPI to accelerate its work on a coronavirus vaccine, and it has joined forces with the Coalition for Epidemic Preparedness Innovations on a vaccine approach.

Diabetic therapy manufacturer Oramed Pharmaceuticals, Inc. (NASDAQ: ORMP) announced a public offering to raise funds for its oral insulin trial.

Qurate Retail Inc (NASDAQ: QRTEA), which curates product collections on Zulily, Frontgate and other online marketplaces, missed fourth-quarter earnings estimates and attributed the miss partly to Chinese exposure.

Smart home manufacturer Resideo Technologies Inc (NYSE: REZI) beat fourth-quarter earnings forecasts.

SigmaTron International (NASDAQ: SGMA) provides electronics manufacturing services through facilities in four countries, including China.

Vaxart Inc (NASDAQ: VXRT) has initiated a coronavirus vaccine program using its proprietary oral-delivery platform.

The portfolio of Vir Biotechnology Inc (NASDAQ: VIR) includes an antibody for another coronavirus strain, but management is testing to determine efficacy on the Wuhan strain.

"We have a library of multiple fully-human mAbs that bind and neutralize coronaviruses such as SARS and MERS,"Chief Scientific Officer Herbert 'Skip'Virgin said in a press release. "...Some of these mAbs are able to neutralize zoonotic coronaviruses, and we believe may have the potential to treat and prevent Wuhan coronavirus. We are also exploring the isolation of new mAbs specific for this virus."

2020 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

See original here:
Diagnosis: Volatility Every Coronavirus-Related Stock That Was Halted For Trading Today - Benzinga

Recommendation and review posted by Bethany Smith

SELBYVILLE, Del., Feb. 27, 2020 /PRNewswire/ -- Global Market Insights, Inc. has recently added a new report on genetic testing market which estimates the global market valuationfor genetic testing will cross US$ 28.5 billion by 2026. A growing demand for DTC genetic testing will drivemarket expansion over the forecast period. Genetic testing can project the risk of diseases, identify carriers and establish diagnoses. DTC genetic testing can help individuals identify ancestral origins and predisposition to certain illnesses. This can enable individuals to prepare or prevent the onset of certain diseases. Increasing awareness among people regarding their health will drive industry growth.

Growing adoption of genetic testing in oncology and genetic diseases in North America will propel the market expansion. Genetic testing to determine the probability of cancer and rare diseases helps in planning the treatment. Genetic testing helps in the formulation of the most effective treatment for cancer and other diseases. Hence, the growing application of genetic testing in cancer and genomic disorders will fuel the genetic testing market growth.

Requesta sample of this research report @https://www.gminsights.com/request-sample/detail/2490

Nutrigenomic testing was valued at USD 408.9 million in 2019 and will witness significant growth over the forecast period. Nutrigenomic testing determines how genetic variations change the individual reaction to nutrients. Nutrigenomic can assist with optimum nutritional planning. Rising incidence of obesity due to increased consumption of junk food and sedentary lifestyle will fuel the segment growth over the forecast period. Furthermore, growing awareness regarding customized diets will fuel market growth.

The cancer testing market held nearly 52% market share in 2019 and will exhibit robust growth in the forecast period. The growth can be attributed to the advancements in genetic testing that can confirm the diagnosis. Furthermore, genetic testing can help with the formulation of the most effective drugs for the treatment of cancer, improving patient outcomes. These factors will boost the growth of the cancer testing segment.

The European genetic testing market held a substantial value in 2019 and is poised to exhibit nearly 13% CAGR over the forecast period. The growing geriatric population will boostdemand for genetic testing in the region. Furthermore, presence of key market players in the region will positively impact the technology adoption. Additionally, favorable government initiatives to harmonize genetic testing and ensure accurate and reliable results will boost market growth.

Browse key industry insights spread across 146 pages with 138 market data tables & 8 figures & charts from the report, "Genetic Testing Market Share & Forecast, 2020 2026" in detail along with the table of contents:

https://www.gminsights.com/industry-analysis/genetic-testing-market

Some major findings of the genetic testing market report include:

Few notable players in the genetic testing market share are 23andME, Abbott Molecular, Bayer Diagnostics, Cepheid, Counsyl, PacBio, Illumina Inc., Qiagen, Roche Diagnostics, BioCartis, and Siemens. The market players are adopting strategies such as innovative product launches and acquisitions to expand their customer base and market share.

Make an inquiry for purchasing this report @https://www.gminsights.com/inquiry-before-buying/2490

Partial chapters of report table of contents (TOC):

Chapter 2. Executive Summary

2.1. Genetic testing industry 360synopsis, 2015 - 2026

2.1.1. Business trends

2.1.2. Test-type trends

2.1.3. Application trends

2.1.4. Regional trends

Chapter 3. Genetic Testing Industry Insights

3.1. Industry segmentation

3.2. Industry landscape, 2015 - 2026

3.3. Industry impact forces

3.3.1. Growth drivers

3.3.1.1. Physician adoption of genetic tests into clinical care

3.3.1.2. Technological advancements and availability of new tests

3.3.1.3. Growing application of genetic testing in oncology and genetic diseases in North America

3.3.1.4. Consumer interest in personalized medicines in Europe

3.3.1.5. Growing demand for direct-to-consumer genetic testing

3.3.2. Industry pitfalls & challenges

3.3.2.1. High costs of genetic testing

3.3.2.2. Dearth of experienced professionals and advanced infrastructure in developing and underdeveloped economies

3.4. Growth potential analysis

3.4.1. By test type

3.4.2. By application

3.5. Regulatory landscape

3.5.1. U.S.

3.5.2. Europe

3.6. Market share analysis, 2018

3.6.1. Market share analysis, by North America, 2018

3.6.2. Market share analysis, by Europe, 2018

3.6.3. Market share analysis, by Asia Pacific, 2018

3.6.4. Market share analysis, by Latin America, 2018

3.6.5. Market share analysis, by Middle East & Africa, 2018

3.7. Porter's analysis

3.8. Competitive landscape, 2018

3.8.1. Strategy dashboard

3.9. PESTEL analysis

About Global Market Insights

Global Market Insights, Inc., headquartered inDelaware, U.S., is a global market research and consulting service provider, offering syndicated and custom research reports along with growth consulting services. Our business intelligence and industry research reports offer clients with penetrative insights and actionable market data specially designed and presented to aid strategic decision making. These exhaustive reports are designed via a proprietary research methodology and are available for key industries such as chemicals, advanced materials, technology, renewable energy and biotechnology.

GMIPulse,our business analytics platformoffers an online, interactive option of exploring our proprietary industry research data in an easy-to-use and dynamic manner. Clients get to explore market intelligence across 11 top-level categories and hundreds of industry segments within them, covering regional, company level and cross-sectional statistics that make our offering a stand-out for decision-makers.

Contact Us:

Arun HegdeCorporate Sales, USAGlobal Market Insights, Inc.Phone:1-302-846-7766Toll Free:1-888-689-0688Email:sales@gminsights.com

Related Images

genetic-testing-market-size-will.jpg Genetic Testing Market size will exceed $28.5 Bn by 2026 Genetic Testing Market size slated to surpass USD 28.5 billion by 2026, according to a new research report by Global Market Insights, Inc.

Related Links

Direct-to-Consumer Genetic Testing Market

Prenatal and New-born Genetic Testing Market

SOURCE Global Market Insights, Inc.

Read more:
Genetic Testing Market demand to hit USD 28.5 Bn by 2026: Global Market Insights, Inc. - PRNewswire

Recommendation and review posted by Bethany Smith

Its hard enough for any cancer patient to get into clinical trials. Its even harder for a patient with a rare cancer like Todd Mercer.

Mercer, a 52-year-old defense industry professional, lives in Michigan with his wife and their two teenagers. At age 50, Mercer got a colonoscopy, as is recommended for people his age, and received a clean bill of health. Six weeks later, his appendix burst.

The diagnosis, which came in December 2017, was cancer of the appendix. It was the tumor that had ruptured his appendix just beyond the reach of the endoscopic exam meaning his cancer was effectively stage 4 at diagnosis. Mercers cancer has since spread to his liver and lungs.

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Mercer first started looking for clinical trials in November 2018, after his cancer recurred for the first time. Since then, hes been turned down from five studies, and is now trying to get into a sixth.

Mercer recently called in to STATs podcast The Readout LOUD to talk about his experience hunting for a trial that will be willing to take him. Its an experience thats frustratingly familiar in a system in which only about one-seventh of adult cancer patients who are eligible to enroll in clinical trials actually sign up.

What kinds of trials are you looking at?

Originally, I looked at clinical trials that were new and exciting and seemed to have some science behind them that might be promising. Lately, though, Ive done some genetic testing thats revealed some genetic information that is leading me towards trials that are designed for the particular blockades or the phenotypes that my genetic testing has introduced. So, now, Im actually being more strategic about my trial hunt.

Ill be lucky to see five years, and I almost wont see 10 years. There are only a few things that I can do directly to affect the outcome.

Why is it important to you to enroll in a clinical trial?

For me, its hope. And its a little bit of hope for others as well.

If I look online, if I look at the data, I can see the trajectory of where my disease is headed with standard of care. Ill be lucky to see five years, and I almost wont see 10 years. There are only a few things that I can do directly to affect the outcome thats understanding my diagnosis, understanding my cancer, becoming an advocate for myself, for my treatments, for my care.

I can also look out at whats on the horizon: What other new drugs and new treatments are out there that are helping people? And some of those are in trials, or at least thats my hope. New drugs are being created all the time. There has been promise in other cancers, and so Im looking for that promise in my cancer.

Youve tried to get into five clinical trials and were turned away. Tell us some of the reasons why you were unable to participate in those studies.

For me, the tumor origination in my appendix was my number one obstacle. A lot of trials are designed to enroll only people whose cancer originated in a particular organ. Thats because drug makers are often seeking FDA approval only for cancer with that particular site of origin. And so trials are very careful about which patients they let into the trial because it wont do them any good to collect data on someone with an orphan disease like mine. Not all trials are prohibitive of appendiceal cancer, but many of them are.

Number two for me and so this probably affects more people is something called measurable disease. When you have measurable disease, that means your cancer has formed in such a way that doctors can do a particular measurement. For example, a radiologist can do a measurement to say how large your cancer is to begin with and then how much the treatment affects it in terms of percentage. Is it growing by 10%? Is it shrinking by 20% or 30%? If you dont have measurable disease, many trials wont take you because then they cant get those data.

But theres another factor called evaluable disease, which means the cancer may not be technically measurable but it can still be evaluated. Some clinical trials will use that characteristic. And so I have to find an evaluable trial because, so far, my cancer hasnt been measurable. Now, it could develop that way, but for now, I have to look at other things.

And then Id say the third biggest obstacle for me is exposure. If youve already been exposed to a drug thats in the trial, many trials will exclude you from being in that study. They want virgin candidates who have never been exposed to those particular drugs before, so they know that its the way the drug is administered in the study thats affecting the outcome.

Which kinds of drugs have you been exposed to so far?

Because of my particular situation with an orphan disease, my oncologist has been open to trying some drugs off-label, meaning well do a trial of one for just me. Hell request the drugs, and then we will design a trial that mimics a trial that might be out there at an institution. So he has a pretty good idea of its safety profile and that the drugs arent going to interact inappropriately.

I tried an immunotherapy drug in that situation. And then once I did that, it didnt work. That now prevents me from most trials that have that particular drug in it. I wanted to try it because I wanted to try immunotherapy. Thats a big hope out there for a lot of cancer patients, that can not only bring you into remission, but possibly a cure. So I wanted to expose myself to that, but the tradeoff is that I cant apply to some other trials.

This is not a unique situation in terms of patients getting access to clinical trials. What are you hearing from fellow patients about why theyre getting rejected and how they feel about it?

I havent run into this, butsome people get turned down as they get sicker and sicker ,and their blood work comes back with higher enzymes or is deemed out of tolerance. So, theyre not allowed into the trials as theyre too sick. So we try to advocate to people with cancer: Dont wait until the very end to try trials. Try them while youre still healthy enough to test the medicine, when theyll take you.

People can also be shut out of trials even they meet a trials inclusion criteria. Cost is a big obstacle. The trial will usually pay for the drugs, but a lot of the time it wont pay for the travel to get there, or the doctor exams and the radiology exams, and things like that. So if you dont have good insurance, those costs would become out-of-pocket costs.

Location is another obstacle. Im lucky Im healthy enough to travel right now, so I can get to a trial anywhere. But a lot of people arent either financially or health-wise able to travel to some of these trial locations.

There can, of course, be sound medical and scientific reasons why certain patients arent allowed to enroll in a trial; the goal of scientific research, after all, is to evaluate an experimental treatment as rigorously as possible. But at the same time, theres a growing line of thought that certain exclusion criteria are overly restrictive, especially when so many clinical trials go unfilled. From your vantage point as a patient, how do you think these concerns should be balanced?

Things are restrictive. I mean, cost, location, the exclusion criteria. I try to look at it a little bit differently.

There are a lot of trials out there and a lot of patients. But the trials dont necessarily always publish what their target is. What is the science behind the trial? Are they attacking a particular mutation, a typical blockade, a phenotype? What science directed them to try that combination of drugs or develop that new drug? What are they trying to determine? That needs to be a required piece of information about trials.

And then correspondingly, the patients and the doctors need to be educated on the value of genetic testing.

No patient should ever be diagnosed with cancer without getting genetic testing. That way, you learn what the particular characteristics of your cancer, of your tumor are, what mutations you have, what your blockades are? And if you have that information about your cancer, and the trial is making that information available about what theyre targeting, then youre going to be more desirous of getting into that trial.

So itll incentivize the patients and the doctors to seek out those trials. And then if those trials know that there is a population of patients out there with those particular characteristics that theyre looking for, then theyre incentivized to reach out to those doctors and those patients to find them, to make those matches. Youve got to match the two.

And really, there just needs to be a platform that matches the patients to the trials, and the trials to the patients. Right now, there are for-profit companies out there working on this. Its a large endeavor to gather patient information. Theres all kinds of privacy ramifications. But the problem is theyre selling that information to institutions. So the institution has to buy the information to understand the patient population, the trial population. It becomes problematic very quickly for that information to get into the hands of the doctor, into the hands of the patients, or the hands of the trials where those patients are. Its not being done right now.

Youre now trying to get into a sixth trial. Tell us where things stand there.

So far, its encouraging. It has been delayed, though.

My genetic mapping indicates that there are two drugs that are my highest blockades. And this particular trial has those two drugs in it.

Dont wait until the very end to try trials.

The problem is its a first-in-humans Phase 1 trial. Theyre doing a dose escalation meaning they start by enrolling three people and start them out at a minimal dose. And then when those three people dont have any adverse reactions, then they incorporate three more people and they increase the dose. And then if they dont have any adverse reactions, then three more and then three more until they find out what the maximal tolerating dose is.

The way they they recruit for it, they dont really open slots until theyre ready for the next three people. So Ive located the trial. It happens to be 30 minutes from where I live. So its very fortuitous.

I attended the ASCO-GI conference in San Francisco last month. I just so happened to be flying back from San Francisco to Michigan, and I sat down next to the trial director for the trial that I wanted to get into. So I was able to strike up a conversation and find out where it was with his particular institution, if there were openings or not. And the problem is: no slots have been opened because theyre still waiting for the dose escalation process to work its way out.

I was progressing on my previous treatment, so I was getting sicker and couldnt wait for the slot to open. Im now recycling the previous treatment that I was on last year to see if it will have some effectiveness, just to get me through until potentially a slot opens up. And then I will go through a 28-day detox period where they want no chemo or medicines in your system so that when you do get to the trial, they can better gauge the results. The idea is to show its not residue medicine in my system, its the actual trial drugs, that are making an effect.

Please keep us updated when you get word on that trial. Were rooting for you.

I absolutely will.

This is a lightly edited transcript from a recent episode of STATs biotech podcast, The Readout LOUD. Like it? Consider subscribing to hear every episode.

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Rejected from five clinical trials, a cancer patient waits for one to say yes - STAT

Recommendation and review posted by Bethany Smith