Lets talk about a painful subject. I am of the opinion and Im far from alone that the most reliable way to determine if a possible therapy has any usefulness is a randomized, double-blinded controlled clinical trial. I can be a bit more specific than that, even: lets make that a trial that is run with sufficient statistical power to have a good chance of providing a meaningful readout.

The worldwide coronavirus pandemic has featured some well-run trials that have truly advanced our knowledge of the disease and how to treat it. But it has featured far, far more garbage. That word was chosen deliberately. There have been too many observational trials, too many uncontrolled (or poorly controlled) ones, too many open-label ones, and above all, there have been way too many trials whose number of patients would be insufficient to tell us much of anything even if everything else had been run properly.

I am not revealing any hidden tricks of the trade here. Clinical trial design is a subject with a very large literature, and there are any number of people and organizations who can provide useful guidance on both its theoretical and practical aspects. Among these aspects are the calculations that should be made for how many patients a trial is likely to need to be well-powered enough for a clean read on its clinical endpoints. You can start to learn the basic outlines of the subject online. Now, thats not to say that its an easy subject to get ahold of. Youre going to have to estimate some of your key parameters as well as you can, among them what you think the effect size of your treatment might be, what the patient-to-patient variability might be like, the time course of treatment that might be needed, and more. Just picking the proper clinical endpoints is a subject all in itself (and its one that can have a huge effect on a trials design and on its chances for success). And at the other end of things, your inclusion criteria and patient enrollment process is a place for serious thought, too. Who should be evaluated (or definitely not evaluated) in your trial, and how long will it take you to round those people up? Where are you thinking about doing all this, anyway?

There are a wide variety of trial designs out there as well, and you can find yourself sorting through some that are clearly inappropriate to the problem at hand, some that would be great if you had about ten times as much money and time as you do, and several that at first glance look like they could all work out, but which have real-world differences that its crucial that you be aware of. You would be well advised to consult with experience practitioners before you start, to make sure youre on the right track.

Unfortunately, underpowered, badly-run, and badly designed trials have been with us for a long time. Here are some well-justified concerns from 2002, for starters, and various fields of clinical research undergo periodic bouts of soul-searching over the years about these issues. But the pandemic year has really made some of our problems more obvious. Not only do we have trouble with badly run trials, but mixing in with that is a bandwagon effect. Clinicians all over the world just piled onto some of the coronavirus ideas, and kept piling on for months and months and months.Think, for example, about the hydroxychloroquine situation. Now, I still get messages condemning me as an implacable, irrational foe of the One True Coronavirus Therapy. But its worth remembering that I started out as a Huh, I dont know how that would work, but lets look into it person, which I really think should be the default setting. And in that spirit, I was all for running trials and getting more hard data.

But what did we get? A search through clinicaltrials.gov for hydroxychloroquine|coronavirus gives you 113 trials. Whats more, thirty-six of those are still listed as recruiting patients. This is ridiculous, but its not amusing. There are some large, well-controlled data sets available that indicate that HCQ is very likely not a useful therapy, but as you can see, there are also dozens of other smaller ones that say Yes! No! Maybe! Sorta! Kinda! Kinda Not! Depends! Could Be! Who Knows? And that adds up not just to a lack of knowledge, it turns into an actual hindrance to knowledge as you try to sort through the data. The heap of fuzzy indeterminate results also fuels the extrascientific political and cultural arguments about the drug, since everyone can find some sort of support for whatever opinion they might have.

You have to think that there were other therapies that deserved a look in the clinic as compared to the forty-third, sixty-seventh, or ninety-eighth hydroxychloroquine study. Youll recall that for a while, HCQ ended up mixed into other clinical trials just because everyone wanted it or imagined that it was some sort of standard of care, and that did no one much good, either. Now, HCQ isnt the only offender, but its a big one, and I think it illustrates what we should try not to do next time.

How, then, should we try not to do that? (Update: some thoughts here on this problem from a distinguished team of authors with exactly the same concerns). Its not like the US (to pick a big example) has a National Clinical Trial Authority that passes judgment on these things. To be honest, the downsides of having such an agency might worry me even more. But letting everyone go into Headless Poultry Mode and pile up overlapping crap in the clinic isnt such a good way to go, either. You would hope for a little more coordination among major medical research centers, and youd also hope for some local university/research hospital review boards to be aware that greenlighting the East Porkford Covid-19 Treatment Study with 47 patients isnt really going to advance medical science very much. Especially when its covering the same ground as the trials kicking off in Mashed Potato Falls, Rancho Malario, and Kidneystone Pass. But Im being unfair to East Porkford some of these lackluster trials were conducted at larger institutions that should have known better. The way were set up, its down to the review boards and the sources of funding to police things better, and to keep their heads while all about them are losing theirs.

And its also down to the NIH and the CDC to lead the way more than they did during 2020. The RECOVERY trial in the UK has been an example of what can be accomplished in that line. The NIH has helped run some good trials, but weve had nothing that comprehensive in the US as compared to the UK effort, and I really wish we had. I fear that some day, eventually, were going to have a chance to do better, and I hope that we take it.

More:
The Problem with COVID-19 Clinical Trials | In the Pipeline - Science Magazine

Recommendation and review posted by Bethany Smith

Most genetic tests focus on your odds of developing certain diseases or health conditions. But some known as pharmacogenomic (or pharmacogenetic) tests can reveal how your body may respond and react to different medications. To date, researchers have identified more than 400 genetic variations known to affect the metabolism of numerous drugs, including some that help lower cholesterol or prevent blood clots (see "Pharmacogenomics of common heart drugs").

In theory, knowing how people metabolize specific drugs could help doctors choose the safest, most effective treatment for their patients. But in practice, it's not that straightforward, says Dr. Jason Vassy, assistant professor of medicine at Harvard Medical School and a primary care physician at the VA Boston Healthcare System.

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Genetic testing to tailor heart drug prescriptions? - Harvard Health - Harvard Health

Recommendation and review posted by Bethany Smith

This article was originally published here

J Surg Oncol. 2021 Mar 18. doi: 10.1002/jso.26372. Online ahead of print.

ABSTRACT

BACKGROUND: Genetic testing for hereditary breast cancer has implications for breast cancer decision-making. We examined genetic testing rates, factors associated with testing, and the relationship between genetic testing and contralateral prophylactic mastectomy (CPM).

METHODS: Patients with breast cancer (2000-2015) from The Health of Women Study were identified and categorized as low, moderate, or high-likelihood of the genetic mutation using a previously published scale based on period-relevant national guidelines incorporating age and family history. Genetic testing and CPM rates were compared using univariate and multivariate logistic regression.

RESULTS: Among 4170 patients (median age 56-years), 38% were categorized as high-likelihood of having a genetic mutation. Among high-likelihood women, 67% underwent genetic testing, the odds of which were increased among women of higher-education and White-race (p < .001). Among 2028 patients reporting surgical treatment, 385 (19%) chose CPM. CPM rate was highest among mutation-positive women (41%), but 26% of women with negative tests still underwent CPM. Independent of test result, genetic testing increased the odds of CPM on multivariate analysis (adjusted-OR: 1.69; 95% CI: 1.29-2.22).

CONCLUSIONS: Genetic testing rates were higher among women at high-likelihood of mutation carriage, but one-third of these women were not tested. Racial disparities persisted, highlighting the need to improve testing in non-White populations. CPM rates were associated with mutation-carriage and genetic testing, but many women chose CPM despite negative testing, suggesting that well-educated women consider factors other than cancer mortality in selecting CPM.

PMID:33735483 | DOI:10.1002/jso.26372

Read more here:
Genetic testing and surgical treatment after breast cancer diagnosis: Results from a national online cohort - DocWire News

Recommendation and review posted by Bethany Smith

This article was originally published here

J Genet Couns. 2021 Mar 21. doi: 10.1002/jgc4.1413. Online ahead of print.

ABSTRACT

Clinical guidelines recommend that women at high risk of breast cancer should consider various risk-management options, which remain widely underutilized. We conducted semi-structured, qualitative interviews with 50 high-risk women to understand how financial constraints affect use of genetic counseling, genetic testing, and further risk-management decisions. Inductive analyses revealed three categories of health-related financial constraint: (a) lack of insurance, (b) underinsurance, and (c) other financial constraints (e.g., medical debt, raising children, managing comorbidities). Various breast cancer risk-management actions were limited by these financial constraints, including genetic counseling, genetic testing, enhanced screening, and prophylactic surgeries. Womens narratives also identified complex relationships between financial constraint and perceptions of healthcare providers and insurance companies, particularly as related to bias, price transparency, and potential genetic discrimination. Results from this study have implications for further research and expansion of genetic counseling services delivery to more economically and racially diverse women.

PMID:33749063 | DOI:10.1002/jgc4.1413

Excerpt from:
Financial constraints on genetic counseling and further risk-management decisions among U.S. women at elevated breast cancer risk - DocWire News

Recommendation and review posted by Bethany Smith

Decisive Markets Insights publishes detailed report on Global Genetic Testing Market. Experts predict the market to grow exponentially from its earlier record of US$XX billion in 2020 to an estimated value of US$XX billion by 2027 with an annual compound growth rate of 5.6% over the next seven years. Nevertheless, the global COVID-19 pandemic, business has registered steady growth and there are huge prospects of investment opportunities.

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Report Summary

The Genetic Testing report is a one-stop station for providing industry research reports. The experts have used their intelligence and experiences in building the report. This report will be helpful for clients who are looking for solutions related to the industry. The report consists of a special section for consultation and recommendations regarding the industry. It is specially dedicated to the clients so they can feel more delighted after getting the solutions, that they are looking for. The report has made a special focus on the analysis of the global trend. A detailed study of product type, application, geography, and market segmentation is done as well. During the forecast period, a high amount of growth is expected regarding the industry. Significant statistics on the market status of the leading market players of the industry are provided in the report. In this way, the customers can be well aware of the threats and opportunities of the industry.

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Key Companies Operating in this MarketAbbott LaboratoriesBio-Rad Laboratories, Inc. (RainDance Technologies, Inc.)Myriad Genetics, Inc. (Myriad RBM, Inc.)Danaher Corporation (Cepheid)F. Hoffmann-La Roche Ltd.Eurofins ScientificIllumina, Inc.Qiagen N.V.Thermo Fisher Scientific, Inc.CSL Ltd

Market By TypePredictive & Presymptomatic TestingCarrier TestingPrenatal & Newborn TestingDiagnostic TestingPharmacogenomic TestingOthers

Market By TechnologyCytogenetic TestingBiochemical TestingMolecular Testing

Market By ApplicationCancer diagnosisGenetic Disease DiagnosisCardiovascular Disease DiagnosisOthers

A competitive analysis is done in the report. This competitive analysis provides an insightful data on the market leaders in the industry. The intension is to help the clients to know about the existing market players as well as potential market entrants of the industry. The report is made in a way such that the clients can not only make proper decisions regarding the industry but also can make stable growth in the industry in the long run. The aim is to direct the clients towards the steady progress of their growth in the industry. There are many contents in the report like networking and distribution strategies, revenue shares in the market,companies with their profiles and comprehensive profiles of their offerings and many more.

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The primary motive is to track the evolution of the growth path of the market from the year 2021 to the year 2027. The Genetic Testing report also offers an extensive assessment of manufacturing scenario and demand supply structures based on the segmental performance of the industry and its key dynamics. Through this report, the buyers of this industry are contributed with a full picture of the players that are highly influential regarding the industry. Besides this, there are different attributes based on the parameters like gross margin, profit, performance of the companies and their strategic movements. All these are well explained through various resources like graphs, tables and charts.

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Reasons to Buy a Full Report

An insight into the market size and growth 2020-2027 CAGR: 2020 to 2027, calculating 2019 as the base year Detail information about the dominant players in this segment Demand and supply chain mapped to clearly evaluate the market Apart from primary and secondary research methodology, data triangulation method is used for a clear understanding of the report Analysis by Industry expert

Kindly contact us and our expert will get back to you within 30 minutes:Decisive Markets InsightsSunil KumarSales HeadEmail [emailprotected]US +18317045538UK +441256636046

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Genetic Testing Market to Observe Positive Growth | Players Illumina, Inc., Qiagen NV, Thermo Fisher Scientific, Inc., CSL Ltd KSU | The Sentinel...

Recommendation and review posted by Bethany Smith

ROCKVILLE, Md., March 24, 2021 /PRNewswire/ --To support quality improvement (QI) projects in colorectal cancer, the Association of Community Cancer Centers (ACCC) has joined with Pfizer Global Medical Grants to issue a Request for Proposals (RFP) with the intent of funding QI initiatives that focus on the integration of biomarker testing into the treatment planning for patients with metastatic colorectal cancer (mCRC). The RFP seeks individual grant requests up to a maximum of $150,000. In total, Pfizer will provide $1.5 million in funding for these quality improvement grants.

"Efficient processes for the timely integration of molecular biomarker and genetic testing is increasingly recognized as a component of metastatic colorectal cancer care," said Advisory Committee Member Al B. Benson III, MD, FACP, FASCO, Professor of Medicine; Associate Director for Cooperative Groups Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL. "Through this grant program, ACCC member programs and practices are offered a significant opportunity to submit proposals to expand understanding and explore approaches for patient care in colorectal cancer."

In a survey of practitioners conducted by ACCC to assess the status of biomarker testing in patients with unresectable or mCRC, over 70% of respondents reported that more than half of their patients undergo biomarker testing. Fifty-two percent of respondents (52%), however, indicated that their cancer program has no standard biomarker testing protocol for patients with unresectable or mCRC. Over 40% of respondents reported that patients with mCRC who have had biomarker testing are treated with systemic medical therapy "frequently" or "almost always" before all biomarker test results are available.

Survey respondents reported that challenges to the optimal use of biomarker testing in this population include patient factors such as patients' general health and physical fitness, patient preference, insurance coverage, clinical trial eligibility, and age. There are also practice-level factors including insufficient tissue for testing, poor tissue quality, long turn-around time, patient refusal, quality of in-house testing, difficulty getting reimbursed, lack of availability of in-house testing, no access to molecular tumor board(s), and inadequate staffing.

Access the survey summary on the ACCC website at http://accc-cancer.org/colorectal-survey-summary.

The opportunity to submit a proposal in response to the RFP is only available to ACCC-member cancer programs and practices. Grant requests should describe concepts and ideas for design and implementation of systems or programs that will close clinical practice gaps related to biomarker testing in patients with mCRC through establishment of education and support mechanisms for community providers.

The RFP process has two stages. Stage one is submission of a three-page letter of intent (LOI). If the LOI is selected, the applicant will be invited to submit a full proposal. Deadline for LOI submission is May 12, 2021.

For more information and to view the RFP, visit https://www.accc-cancer.org/projects/colorectal-cancer/overview.

About the Association of Community Cancer Centers

The Association of Community Cancer Centers (ACCC) is the leading education and advocacy organization for the cancer care community. Founded in 1974, ACCC is a powerful network of 28,000 multidisciplinary practitioners from 2,100 hospitals and practices nationwide. As advances in cancer screening and diagnosis, treatment options, and care delivery models continue to evolve - so has ACCC - adapting its resources to meet the changing needs of the entire oncology care team. For more information, visit accc-cancer.org or call 301.984.9496. Follow us on Facebook, Twitter, and LinkedIn; read our blog, ACCCBuzz; and tune in to our podcast, CANCER BUZZ.

SOURCE ACCC

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Association of Community Cancer Centers and Pfizer Offer Grant Opportunities Focused on Improving Quality of Metastatic Colorectal Cancer Care Through...

Recommendation and review posted by Bethany Smith

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Breast & Ovarian Cancer, Cardiovascular Screening, Diabetic Screening & Monitoring, Colon Cancer, Parkinsonism/Alzheimers Disease, Urologic Screening/Prostate Cancer Screening, Orthopedic & Musculoskeletal, Other Cancer Screening, Other diseases

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Predictive Testing, Consumer Genomics, Wellness Genomics

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Read more:
Global Predictive Genetic Testing & Consumer/Wellness Genomics Market Comprehensive Analysis on types and application 2020-2026 - The Courier

Recommendation and review posted by Bethany Smith

Army Veteran Keisha Bellamy begins each day with a cup of coffee, opens her laptop and logs in to Zoom.

She facilitates a six-week course on healthy living for Veterans, and on one particular morning, one woman in the group was struggling. The Veteran lives with post-traumatic stress disorder, and was feeling defensive, disrupting the group conversation.

Bellamy has seen these actions before in others. As a registered nurse with a background in mental health nursing, she redirects the conversation with skill and compassion.

You see, at VA we offer a safe haven to Veterans like this woman who others might dismiss or find difficult to work with in a group setting, Bellamy says. Thats because many employees at VA are Veterans. We see ourselves in our patients and they see themselves in us.

After six weeks, the Veterans graduate with new skills and goals for managing chronic illness. They also finish the course as comrades in healthier living, offering each other friendship and support as they manage their illness together.

For Bellamy, this is the best part of her job.

Bellamy has 15 years of service at VA with the last two years at the San Francisco VA Healthcare System. There, she oversees programs in health promotion and disease prevention.

To encourage Veterans to sign-up, its important to be a good role model, Bellamy says. You have to build relationships and practice what you preach.

So, every week before the pandemic, Bellamy would unroll her yoga mat and go into downward-facing dog with fellow Veterans at a community yoga studio. Afterward, she would chat with classmates and tell them about other health and wellness programs at San Francisco VA.

And when VAs Million Veteran Program launched in 2011, Bellamy was one of the first to enroll.

The program collects a blood sample from participating Veterans for genetic testing along with information on their health, lifestyle and military exposures to better understand disease in Veteran populations.

With this data, the program supports groundbreaking research in precision medicine that will one day offer Veterans the personalized care they deserve.

Being part of MVP allows me to explain what its like to enroll and be part of the program, says Bellamy, who is now joined by 830,000 fellow Veterans in what has become one of the largest genetics research programs in the world.

Bellamy has a connection with Veterans that other colleagues do not. As a Black female health care provider, Black Veterans in the Bay Area feel heard and understood by her.

Its rare for patients of color to see someone on the clinical side who looks like them, especially on the West Coast, Bellamy says. And theres still some concern as it relates to research, she adds.

While MVP has the largest Black cohort of any genetic research study approximately 19% of Veterans in the program are African American the program aims to increase diversity so it can support groundbreaking discoveries for Veterans of all genders and races.

She hopes her participation in MVP will show Veterans of color, especially women Veterans like herself, that this research is safe and valuable.

Its important that women and people of color are represented if we also want tomorrows medicine, Bellamy says. Our community and the future of their health care depends on our participation.

To learn more about VAs Million Veteran Program, visit mvp.va.gov or call 866-441-6075.

Sandra Glover is the chief communications officer forVISN 9.

Excerpt from:
Army Veteran a champion for health and research - VAntage Point - VAntage Point Blog

Recommendation and review posted by Bethany Smith

But new scientific evidence suggests that's not what happened.

Genomic testing shows at least two of the Australian's babies likely died from a previously undiscovered genetic mutation that led to heart complications -- meaning she may have been wrongfully imprisoned for almost two decades.

The ramifications don't end there.

Early years

In the late 1980s, she married Craig Folbigg, who she had met at a disco in the Australian city of Newcastle. They had their first child when she was 21, a boy named Caleb.

Folbigg soon fell pregnant again, and in 1990 she had another son, Patrick. Tests showed he was normal and healthy. But at four months, he had an unexplained ALTE, an apparent life-threatening event, that left him with brain damage and seizures. Four months later, he died as a consequence of seizures.

Her third child, Sarah, died age 10 months -- her cause of death was listed as SIDS. When her fourth daughter, Laura, died age 18 months on March 1, 1999, police started investigating.

The couple's marriage broke down. After Folbigg left, her husband found her diary and read an entry that he said made him want to vomit. He took the diary to police on May 19, 1999, according to the inquiry.

On April 19, 2001, Folbigg was arrested and charged with four counts of murder.

Her childhood best friend Tracy Chapman describes Folbigg as a caring animal lover who was a "really good mom." But at trial in 2003, the prosecution argued Folbigg had smothered her children. There was no conclusive forensic proof -- instead, the prosecution relied on a maxim credited to British pediatrician Roy Meadow: "One sudden infant death is a tragedy, two is suspicious and three is murder, until proven otherwise."

The prosecutor compared the chance of the children dying of natural causes to pigs flying.

"I can't disprove that one day some piglets might be born with wings and that they might fly. Is that some reasonable doubt? No," the prosecutor told the jury during the 2003 trial. "There has never ever been before in the history of medicine that our experts have been able to find any case like this. It is preposterous. It is not a reasonable doubt. It is a fantasy and, of course, the Crown does not have to disprove a fanciful idea."

The prosecution pointed to Folbigg's journals, which they said contained virtual admissions of guilt.

"I feel like the worst mother on this Earth, scared that (Laura) will leave me now, like Sarah did. I knew I was short tempered and cruel sometimes to her and she left, with a bit of help," Folbigg wrote in one. "It can't happen again. I'm ashamed of myself. I can't tell (my husband) about it because he'll worry about leaving her with me."

Folbigg didn't confess, there was no obvious motive, and no one claimed to have seen her murder her children. But the jury found her guilty of the murder of three children and the manslaughter of one.

Folbigg was eventually sentenced on appeal to 30 years in prison with a non-parole period of 25 years. By the time she is eligible for parole, Folbigg will be 60 years old.

The fight to get her out

In 2015, with her appeals exhausted, Folbigg's lawyers submitted a petition to the governor of New South Wales, asking him to direct that an inquiry be held into her convictions. The lawyers argued new evidence had come to light since her unsuccessful appeals -- including a growing understanding of SIDS -- that lead to a "feeling of disquiet" over her convictions. If the former NSW District Court chief judge Reginald Blanch, who headed the inquiry, agreed, he could refer the case back to the Court of Criminal Appeal.

As part of that inquiry, Folbigg's legal team approached Prof. Carola Vinuesa, co-director of the Centre for Personalised Immunology at Australian National University, to ask her to sequence the children's genomes to see if there was a genetic mutation that could have caused SIDS.

"There was a chance -- even though it might be a long shot -- that (Folbigg) was carrying something that might be passed on to the children," Vinuesa said. "To my knowledge, this is the first case in which a court (anywhere in the world) has used whole genome sequencing to find evidence of a cause of death."

When they sequenced the genomes of all four children, they found both daughters carried the same CALM2 mutation as their mother.

After the inquiry had closed, more evidence came to light, prompting Vinuesa and her team to write to the judge telling him it was likely the daughters died as a result of the variant. Despite the new finding, Judge Blanch opted not to reopen the inquiry. After taking all the evidence -- including the diaries -- into account, Blanch said he remained of the view Folbigg had smothered Sarah and Laura.

New developments

Last November, scientists published even more compelling evidence.

Led by Danish professor Michael Toft Overgaard, a team of experts across six countries found the CALM2 variant in Folbigg and her two girls could cause disease -- just like other CALM2 variants.

They concluded the variant altered the girls' heart rhythm, making them susceptible to heart conditions -- particularly given the medication they were given. Sarah was on antibiotics for a cough, while Laura was being treated with paracetamol and pseudoephedrine for a respiratory infection shortly before she died. Laura had inflammation of the heart when she died to the extent that three professors said they would have listed it as her cause of death.

"To my knowledge, this is the first case in which a court (anywhere in the world) has used whole genome sequencing to find evidence of a cause of death."Professor Carola Vineusa

In both of the boys, scientists found other variations in their BSN, also known as Bassoon, genes -- one variant had been inherited from their mother, and the other likely from their father, although he refused to provide a sample to the researchers. When both copies of the BSN gene are defective in mice it can cause them to die young during epileptic fits. Scientists are still investigating whether this variant could have caused the two boys' deaths. Patrick experienced seizures before he died.

Only 75 people in the world are known to carry mutations in their CALM1, CALM2 or CALM3 genes that have been shown to be lethal in children. But while genetic mutations that cause SIDS may be rare in the general population, once a parent has a genetic mutation there is a high chance of them passing it on, Vinuesa says.

"In the end it's not about these variations being very rare in the world, it's about the chances of Kathleen meeting someone like Craig and having this combination of mutations between both of them. Once genetics come into play, statistics go out the window," Vinuesa added.

Vinuesa said the case shows that contrary to what was suggested at trial, there doesn't need to be one explanation for all four of the deaths.

"The pathology already told us there were different causes," Vinuesa said.

The research hasn't yet freed Folbigg, but it has already had an impact. Folbigg's lawyers launched a case in the New South Wales Court of Appeal, arguing that the commissioner of the 2019 inquiry incorrectly applied the law to his decisions. The genome findings also prompted a petition with more than 90 signatures to the New South Wales governor earlier this month.

"It is deeply concerning that medical and scientific evidence has been ignored in preference of circumstantial evidence. We now have an alternative explanation for the death of the Folbigg children," Prof. Fiona Stanley, who has been recognized for her work on child health, said in a statement at the time of the petition.

"The reality is, Kath's lost four children. And she hasn't been allowed to grieve as a mother should."Tracy Chapman

A spokesperson for Gov. Margaret Beazley said the state's attorney general is considering the petition and will advise her. According to New South Wales' Department of Communities and Justice, few people have ever received a pardon by the state.

Even if Folbigg is freed, her legal fight may not be over. She will need to go to the Court of Criminal Appeal to get her conviction overturned if she wants to clear her name -- and it will be another legal matter again if she wants to get compensation for the years she's spent in prison.

For Folbigg, the research offers some hope -- but it was also emotional for her to hear, says Chapman, who talks to Folbigg every day.

"You're being told potentially the thing that you carried has been passed onto the children. So that's emotionally quite heart-wrenching," Chapman said. "The reality is, Kath's lost four children. And she hasn't been allowed to grieve as a mother should."

Science in the court room

Folbigg's case is part of a bigger picture -- a growing understanding of SIDS, a changing view about what multiple deaths in a family means, and a wider criticism of how science is presented in the courtroom.

Much of Folbigg's conviction was based on a maxim credited to Meadows that three infant deaths are murder, unless proven otherwise -- a maxim that had already started to draw skepticism.

"In our community, and in any civilized community, that is abhorrent."

In a similar case to Folbigg's, Australian woman Carol Matthey was accused of murdering her four children between 1998 and 2003, but the case against her was dropped due to a lack of evidence -- even though the same experts that testified against Folbigg were set to do so against Matthey.

Gary Edmond, a law professor at the University of New South Wales who is an expert in trial evidence and forensic science, said it was unfortunate Folbigg went to trial when she did. If she was tried a few years later, when the doubt over Meadow's maxim was better established, the courts might have been more cautious about admitting the expert evidence used to convict her, he said.

But even now, the way Australian courts handle evidence is outdated -- and lagging behind United States, Canada, New Zealand and the United Kingdom, Edmond said. While other jurisdictions assess whether science is reliable before it comes to court, Australia's system leaves it up to the juries to decide what's valid. That's a problem because juries don't have enough knowledge to make complex scientific judgments, Edmond said.

Folbigg's lawyer Rhanee Rego -- who has been working on her case for almost five years unpaid -- agrees courts need to be careful about which experts are allowed to give evidence. "I think that one of the biggest lessons we can take from this case is that we need to listen more carefully in the legal system to peer-reviewed and evidence-based science and medicine," she said.

Genetic answers

The advances in genetic testing -- including the findings in Folbigg's case -- could also help give answers for others dealing with the unexplained deaths of their children.

Vinuesa says it's likely that in the next few years, other families who have experienced SIDS will find a genetic mutation is to blame.

"We need to listen more carefully in the legal system to peer reviewed and evidence-based science and medicine."Rhanee Rego

"In most families where there have been SIDS deaths, nobody has yet gone back and sequenced the genomes of the children," she said. As molecular autopsies become more common, she thinks there will be more genetic explanations for otherwise unexplained deaths.

That could help families looking for answers -- and also help those worried about being targeted by the law.

"Many families live in fear, because they've had two or more children dying and they're worried that one day someone will be knocking at their door with some type of police investigation," she said. "We know now that when you have a genetic condition ... it's not rare."

Chapman says her childhood friend hopes her case helps other parents explain otherwise unexplainable deaths.

"It's not just about having Kath free," Chapman says. "The most important thing after Kath is freed is that this never happens to anybody else ever again."

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Genetics may free a woman convicted of killing her 4 babies and help other parents explain the unexplainable - CNN

Recommendation and review posted by Bethany Smith

The results showed that in half of patients with cancers of unknown origin, next-generation sequencing located the primary site of origin and, in those who were matched to a therapy, half achieved a clinical benefit.

New study results support the use of next-generation sequencing (NGS) as standard-of-care (SoC) in patients with advanced solid tumors, particularly for certain groups.

Appearing in JAMA Oncology,1 results showed that in half of patients with cancers of unknown origin, NGS located the primary site of origin and in those who were matched to a therapy, half achieved a clinical benefit.

Based on the data presented by Cobain et al and others, it is evident that such precision medicine strategies are especially fruitful in cancer types without clear standard-of-care options, such as carcinoma of unknown primary and other rare tumors, said researchers in an accompanying editorial.2 Such efforts will allow us to deliver personalized therapies with potential therapeutic benefit to patients and to further refine the development of precision medicine efforts in oncology.

In total, there were 1000 patients included in the study, which analyzed approximately 7 years worth of data.

The findings also have important implications for inheritable cancer risk, as results showed that potentially inheritable cancer risk was detected in 16% of patients. The researchers of the study said this suggests directed germline testing for inherited cancer predisposition in all patients with advanced cancer is warranted.

Any family members who have also inherited those same mutations may be at increased risk for cancer, explained study author Erin Cobain, MD, an oncologist at Michigan Medicine in a press release. So, a lot of this testing prompted downstream genetic testing and counseling across families. Thats how sequencing can have even more far-reaching impact than just looking for therapies to directly help a current patient.

Overall, potentially actionable genomic alterations were identified in approximately 80% of patients. There were 132 patients who underwent sequencing-directed therapy, 20% of whom had exceptional responses and around 40% of whom exhibited any clinical benefit.

However, study authors acknowledged challenges associated with determining the clinical utility of NGS testing in the cancer space, including:

References:

1. Cobain EF, Wu Y, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. Published online February 25, 2021. doi:10.1001/jamaoncol.2020.7987

2. Yap TA, Johnson A, and Meric-Bernstam F. Precision medicine in oncologytoward the integrated targeting of somatic and germline genomic aberrations. JAMA Oncol. Published online February 25, 2021. doi:10.1001/jamaoncol.2020.7988

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Study Makes the Case for NGS Testing as SoC in Certain Patients With Advanced Cancer - AJMC.com Managed Markets Network

Recommendation and review posted by Bethany Smith

The global cell and gene therapy drug delivery devices market was valued at $55.75 thousand in 2019, and is expected to reach $375.13 thousand by 2030, registering a CAGR of 16.61% during the forecast.

The global cell and gene therapy drug delivery devices marketis projected to reach $375.13 thousand by 2030, reveals the premium market intelligence study by BIS Research. The study also highlights that the market is set to witness a CAGR of 16.61% during the period between 2020 and 2030.

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To emphasize the dominance of the intravenous catheter segment of cell and gene therapy drug delivery devices market by product segment over other segments under the product category of cell and gene therapy drug delivery devices market in 2020 and 2030, Raviteja Palakurthy, Senior Research Analyst BIS Research, states, "The reason for market growth and the dominance of intravenous catheter segment can be attributed to the increasing global usage of intravenous catheters to deliver drugs that are dosed frequently for fairly long periods of time and for specific disease conditions. For most of currently approved cell and gene therapies such as Kymriah, Yescarta, Zolgensma, Provenge, Strimvelis, Zynteglo, and Tecartus intravenous catheter are used as its drug delivery device

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Key insights are drawn from in-depth interviews with the key opinion leaders of more than 20 leading companies, market participants, and vendors. The key players profiled in the report include Amgen, Inc., Bausch & Lomb Incorporated, Becton, Dickinson and Company, Bluebird bio, Inc., Castle Creek Biosciences, Inc (Fibrocell Technologies, Inc.), Dendreon Pharmaceuticals LLC., Helixmith Co., Ltd (ViroMed Co., Ltd), Human Stem Cell Institute, Kite Pharma, Inc., Kolon Tissue Gene, inc., Novartis AG, Orchard Therapeutics plc., Pfizer, Inc., Renova Therapeutics, Spark Therapeutics, Inc., uniQure N.V., and Vericel Corporation.

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BIS Research Study Highlights the Global Cell and Gene Therapy Drug Delivery Devices Market to Reach $10.82 Billion by 2030 investigated in the latest...

Recommendation and review posted by Bethany Smith

BioCentriq, the New Jersey Innovation Institutes cell and gene therapy development and manufacturing center, on March 23 announced it partnered with Kytopen, a Cambridge-based startup spun out of the Massachusetts Institute of Technology (MIT).

Our mission at BioCentriq is to work with innovative industry partners like Kytopen to advance the production and manufacturing of cell and gene therapies, making them accessible and affordable for the patients who so desperately need them, said Haro Hartounian, and SVP, general manager, BioCentriq. This partnership aligns perfectly with that mission.

Kytopen leadership team KYTOPEN

Kytopens proprietary Flowfect technology is a flexible, complete technology solution for non-viral cell engineering that integrates the discovery, development, and manufacturing of cell and gene therapeutics. The platform speeds therapies from the clinic to commercial use by enabling cell engineering without compromising functionality or viability. Kytopens technology reduces risk and provides maximum control and flexibility to drive higher yields, faster approvals, and better outcomes for curative cellular disease treatment.

The Flowfect platform is a transformative solution that eliminates the complexity of gene delivery for cell engineering and links discovery, development and manufacturing in one flexible scalable solution, stated Paulo Garcia, CEO and co-founder of Kytopen. Our goal is to enable simple and efficient non-viral manufacturing of cell therapies in days versus weeks to help patients; our partnership with BioCentriq accelerates that goal.

Our Flowfect technology utilizes a novel combination of electrical energy and continuous fluid flow to engineer cells, said Bethany Grant, head of research and development at Kytopen. Our ability to engineer billions of cells in minutes with minimal disruption unlocks new opportunities to enable curative therapies in autologous or allogeneic therapeutic applications.

In the initial phase of the collaboration, the Kytopen and BioCentriq teams will demonstrate the impact to both autologous and allogeneic cell therapies by integrating this novel transfection technology with other steps in the manufacturing process.

BioCentriq has a manufacturing facility in Newark and a pilot plant in South Brunswick.

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BioCentriq partners with Kytopen to advance production and manufacturing of cell and gene therapies - NJBIZ

Recommendation and review posted by Bethany Smith

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Maze Therapeutics, a company translating genetic insights into new precision medicines, today revealed its first three lead therapeutic candidates in the companys wholly owned pipeline. The candidates include:

Each of the three lead candidates was enabled by Mazes COMPASS platform, which uncovered important new findings for the genetic target, discerning which specific signals may be critical for the treatment of patients, and which are likely non-actionable. The Maze pipeline will have the potential to serve as precision medicines for rare diseases and mechanistically defined subsets of common diseases based on certain genetic drivers.

In addition, Maze is concurrently leveraging COMPASS to advance additional discovery-stage research programs across three main therapeutic areas of focus: metabolic, cardio/renal and neurological diseases. These programs will constitute a broad, diverse pipeline for Maze and will be a combination of wholly owned and partnership-led collaborations.

Maze was built by co-founders, including Charles Homcy and other preeminent thinkers in the field of genetics, on a bold vision to leverage growing knowledge of genetic drivers of disease in order to create precision medicines for the treatment of both rare and more common diseases, said Jason Coloma, Ph.D., president and chief executive officer of Maze. Since our founding, we have been leveraging insights from leading geneticists, combined with the growing availability of paired human genetic and clinical data, the evolution of functional genomic technologies and advances in computational power, to build our COMPASS platform in order to bring unique insights into efficient, genetics-based drug development. We are excited by the significant progress we have made with our platform and pipeline, bringing us an important step closer to our goal of delivering the right drug to the right patient at the right time.

Mazes therapeutic candidates are designed to: 1) target genes whose activity affects the phenotype associated with another, often distant, gene, referred to as genetic modifiers; 2) mimic the activity of protective genetic variants; 3) correct the effects of toxic genetic variants; or 4) leverage new genetic insights to address otherwise challenging drug targets.

COMPASS is a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. In addition, Maze is exploring applications of COMPASS in diseases of haploinsufficiency by identifying genetic mechanisms that increase levels of a deficient protein and translating them into therapeutics.

New findings using COMPASS helped fill in fundamental data gaps, turning known but challenging targets into exciting, differentiated approaches to the genetic drivers of disease for our first three programs, said Sarah Noonberg, M.D., Ph.D., chief medical officer of Maze. While it has been shown that targets with human genetic evidence are more likely to yield efficacious treatments, very few groups have had the capabilities to then turn genetic insights into viable drug programs. We believe our COMPASS platform, integrated with our extensive drug discovery capabilities, will allow us to accelerate the pace of therapeutic development, as well as increase the likelihood of producing therapies that provide meaningful clinical benefit for patients. We are excited to advance these initial programs and look forward to continued progress toward the clinic as efficiently as possible.

About Mazes Wholly Owned Programs

GYS1 Program for Pompe DiseasePompe disease is a rare, inherited autosomal recessive disorder with an incidence of approximately 1 in 40,000 live births in the U.S., and is estimated to affect 5,000 to 10,000 patients worldwide. It is caused by mutations in the GAA gene, which codes for an enzyme responsible for breaking down lysosomal glycogen into glucose. As a result of this mutation, glycogen accumulates in various tissues, particularly skeletal and cardiac muscle tissues, causing progressive weakness and respiratory insufficiency.

Maze is developing a novel, oral approach to treating Pompe disease by inhibiting the protein muscle glycogen synthase, which is encoded by the gene GYS1. Targeting this protein leads to reduction in the synthesis of glycogen, which is expected to restore glycogen balance through a mechanism called substrate reduction. While GYS1 has been a therapeutic target of interest, its attractiveness as a therapeutic target has been limited due to its structural complexity and uncertainties related to the tolerability of a long-term reduction in muscle glycogen levels. Critical insights derived from COMPASS have enabled Maze to overcome these challenges. Maze has interrogated the structurally complex protein to develop an oral inhibitor of muscle glycogen synthase, a target not previously addressable by small molecule therapies. Maze is rapidly progressing its GYS1 program toward an Investigational New Drug application and expects to initiate clinical trials in the first half of 2022.

APOL1 Program for Chronic Kidney DiseaseCKD affects approximately 37 million people in the U.S., including more than 700,000 patients who suffer from end-stage renal disease (ESRD), many of whom require chronic dialysis. Individuals of African ancestry are at an approximately 3.5-fold greater risk of developing ESRD than individuals of European ancestry. Previous studies have shown that two coding variants of the apolipoprotein L1 (APOL1) encoded by the gene APOL1 cause toxic gain-of-function variants and are important genetic drivers of kidney disease that are responsible for much of the increased risk for CKD and ESRD in individuals of African ancestry. There are currently no approved therapies that address the underlying causes of APOL1-associated CKD, and efficacious treatment options for individuals with APOL1 risk variants and CKD represent a significant unmet medical need.

Maze employed COMPASS to functionalize human genetic variants to uncover the underlying biology of the target and has designed a small molecule that corrects the effects of toxic gain-of-function variants to potentially enable a therapeutic solution. Maze plans to name the development candidate in early 2022.

ATXN2 Program for Amyotrophic Lateral SclerosisALS is a progressive and fatal neurodegenerative disease with a prevalence of approximately 16,000 patients in the U.S. Current available treatments for ALS primarily focus on providing symptomatic relief and have limited impact on disease progression. A high variability in disease phenotype and life expectancy is observed and believed to be related to the presence of genetic modifiers.

One of Mazes founders, Aaron Gitler, identified a potent genetic modifier, ATXN2, whose inhibition has been shown to limit the toxicity of a certain protein, TDP-43, which is involved in pathologic aggregates seen in up to 97% of all ALS cases. Maze is translating these important insights by developing a novel microRNA gene therapy that targets ATXN2 and has used the proprietary application of its functional genomics tools to optimize its properties. Maze plans to name the development candidate in early 2022.

About Maze TherapeuticsMaze Therapeutics is focused on translating genetic insights into new precision medicines for rare diseases and mechanistically defined subsets of common diseases. Maze has developed the COMPASS platform, a proprietary, purpose-built platform that combines human genetic data, functional genomic tools and data science technology to map novel connections between known genes and their influence on susceptibility, timing of onset and rate of disease progression. Using COMPASS, Maze is building a broad portfolio, including wholly owned programs targeting Pompe disease, chronic kidney disease and amyotrophic lateral sclerosis, as well as partnered programs in cardiovascular and ophthalmic diseases. Maze is based in South San Francisco. For more information, please visit mazetx.com, or follow us on LinkedIn.

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Maze Therapeutics Reveals Its Initial Three Lead Programs Targeting Underlying Genetic Drivers of Life-Threatening Diseases - Business Wire

Recommendation and review posted by Bethany Smith

- Initial data from Cohort 1 of the PEARL-1 study shows safety and tolerability of repeat KB301 injections

- Dr. Bhushan Hardas M.D., MBA appointed President, Jeune, Inc.

PITTSBURGH, March 24, 2021 (GLOBE NEWSWIRE) -- Krystal Biotech Inc., (Krystal) (NASDAQ: KRYS), the leader in redosable gene therapies for rare diseases, today announced the launch of Jeune, Inc., a wholly owned subsidiary of Krystal Biotech, and initial safety data from the ongoing Phase 1 trial of Jeunes lead product candidate, KB301 for treatment of aesthetic skin conditions.

Jeune was formed to advance innovative aesthetic medicines and has an exclusive license to a portfolio of candidates derived from Krystals proprietary technology platform. Jeunes products are designed to directly address biological changes in the skin associated with intrinsic and extrinsic aging. The lead product candidate, KB301, delivers the human COL3A1 gene to increase production of normal type III collagen at the site of administration.

My initial clinical experience with KB301 injections has been highly encouraging, said Dr. Mark Nestor, director of the Center for Clinical and Cosmetic Research and the Center for Cosmetic Enhancement. Not only were the injections well-tolerated, but we see clear signs of new collagen generation which underscores the potential of this treatment to directly address the declining levels of collagen that lead to wrinkles and other skin changes.

Initial data from Cohort 1 in the PEARL-1 studyThe Phase 1, open-label, dose-ranging study is being conducted in adult subjects aged 18-75 (NCT04540900). The primary outcome measure in this first-in-human study was to assess the safety profile of KB301. Secondary outcome measures include COL3A1 transgene expression. In Cohort 1, three different dose levels of KB301 were evaluated in seven (7) healthy subjects who received two intradermal injections into healthy buttock tissue spaced 30 days apart (day 0, day 30). KB301 injected areas were compared to uninjected or saline injected control tissue within the same subject. Treatment and control sites were biopsied at day 2 or day 32. Initial results are as follows:

More detailed data from Cohort 1 will be presented as an e-Poster talk at the Society for Investigative Dermatology (SID) Annual Meeting, held virtually May 3-8.

The presentation will be available on-demand for those registered for the SID conference from May 3, 2021 May 31, 2021. The poster will also be available on the companys website at http://www.jeuneinc.com

The company plans to begin enrollment in the efficacy cohorts of the Phase 1 study in the second half of 2021.

Jeune, Inc. LeadershipJeune has assembled a veteran team of leaders and advisors, comprised of pharmaceutical and biotechnology executives who together have decades of experience developing products in the aesthetic medicine space. Dr. Bhushan Hardas M.D., MBA will join the company on March 29th, 2021 as President of Jeune. Before joining Jeune, Dr. Hardas served as Chief Scientific Officer, Executive Vice President, Global Head of Licensing at Almirall and previously served as Chief Medical Officer of Allergan's Dermatology and Medical Aesthetics business.

I am thrilled to be joining Jeune at such an exciting time. With the ability to deliver genes directly to skin cells, this platform has tremendous potential to address underlying biological changes in aging or photo-damaged skin, noted Dr. Hardas. We are starting with KB301 and type III collagen which I look forward to advancing through the clinic, and the team is already working on pipeline programs that will address additional proteins of interest.

Prior to joining Allergan, Dr. Hardas served as Senior Vice President, Global Head of Dermatology and Aesthetics R&D and Chief Scientific Officer of the North American Business at Merz Pharmaceuticals. Dr. Hardas received advanced training in clinical immunology and molecular biology at King's College at the University of London, in London, England. He also completed a research fellowship in the Department of Dermatology at the University of Michigan, and received his Master of Business Administration degree in healthcare management from the University of California - Irvine.

We are thrilled to welcome Bhushan to Jeune, said Krish S. Krishnan, chairman and chief executive officer of Krystal Biotech. His expertise and development experience in aesthetics is an important asset presently and will help guide next steps for both the pipeline and Jeune overall.

Jeune, Inc. Board Krish Krishnan, Chairman and CEO at Krystal Biotech will serve as the Chairman of the Jeune Board. Joining Mr. Krishnan on the Board are Marc Forth, President and CEO of Aeon BioPharma and Suma Krishnan, Founder and COO of Krystal Biotech.

AboutJeune Inc. Jeune Inc., a subsidiary of Krystal Biotech, is a biotechnology company leveraging a clinically validated gene-delivery platform to fundamentally address and reverse the biology of aging and/or damaged skin. For more information, please visithttp://www.jeuneinc.com

AboutKrystal BiotechKrystal Biotech, Inc.(NASDAQ:KRYS) is a pivotal-stage gene therapy company leveraging its novel, redosable gene therapy platform and in-house manufacturing capabilities to develop therapies to treat serious rare diseases. For more information, please visit http://www.krystalbio.com.

Forward-Looking StatementsAny statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc., or its subsidiary Jeune, Inc., including but not limited to statements about the development of Krystals and Jeunes product candidates, such as plans for the design, conduct and timelines of ongoing clinical trials of KB301 the clinical utility of KB301, the ability of these candidates to fundamentally address and potentially reverse the biology of aging or damaged skin, plans to pursue research and development of other product candidates; and other statements containing the words anticipate, believe, estimate, expect, intend, may, plan, predict, project, target, potential, likely, will, would, could, should, continue, and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from clinical trials, whether results of early clinical trials or trials will be indicative of the results of ongoing or future trials, uncertainties associated with regulatory review of clinical trials and applications for marketing approvals, the availability or commercial potential of product candidates including KB301 and such other important factors as are set forth under the caption Risk Factors in Krystals annual and quarterly reports on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Krystals views as of the date of this release. Krystal anticipates that subsequent events and developments will cause its views to change. However, while Krystal may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Krystals views as of any date subsequent to the date of this release.

CONTACTS:

Investors:Whitney Ijemwijem@krystalbio.com

Media:Mary CoyleTellMed Strategiesmary.coyle@tmstrat.com

Source: Krystal Biotech, Inc.; Jeune, Inc.

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Krystal Biotech Announces Launch of Jeune, a Gene-Based Aesthetics Company, and Initial Phase 1 Safety Data for KB301 in Aesthetic Indications -...

Recommendation and review posted by Bethany Smith

Company to use its novel gene editing technology to explore a potential in vivo gene therapy treatment for cystic fibrosis

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- Life Edit Therapeutics Inc, a next generation gene-editing company, today announced that it has received an award from the Cystic Fibrosis Foundationto identify potential gene editing approaches to treat certain patients with cystic fibrosis (CF). The award will enable Life Edit to screen its library of proprietary base editors for a potential treatment targeting people with CF that are not able to be treated by existing small molecule treatments due to what are known as nonsense genetic mutations (also known as stop mutations). This award is part of the Cystic Fibrosis Foundations Path to a Cure initiative that was launched in October 2019 to address and treat the underlying cause of CF.

Due in large part to the efforts of the CF Foundations support for the development of new medicines, there are now effective therapies available to most people living with the disease, but there remain as many as 7% of patients with CF for whom recent medical advances are not effective, said Mitchell Finer, Ph.D., Chief Executive Officer, Life Edit Therapeutics. Were looking forward to working with the CF Foundation to leverage the unique benefits that our platform offers to develop a highly targeted gene editing approach for these individuals. We believe our science and this approach can be applied across a range of diseases, which will be our focus as we work to build a pipeline of life-changing therapies for severe genetic diseases like CF.

Dr. Allie Crawley, Principal Investigator for the project and member of the Life Edit team, continued by saying, We are thankful to be a part of the Path to a Cure initiative from the CF Foundation which is focused on curing cystic fibrosis by addressing the underlying cause of the disease. We believe our base editor technology has potential to make a great impact in the lives of cystic fibrosis patients with nonsense mutations and are excited about the opportunity to begin early research in this development.

Despite tremendous progress in advancing therapeutics to help people with CF live longer and healthier lives, there remain unmet needs to help all those living with this disease. Approximately 13% of people living with CF have nonsense mutations. These mutations cause the cells to stop the production of the cystic fibrosis transmembrane conductance regulator (CFTR) protein midway through the process, resulting in shortened, non-functional protein.

As part of the $400,000 award from the Foundation, Life Edit will explore its large collection of adenine base editors, or A-base editors, that can potentially be used to correct the six most common, Class I, cystic fibrosis nonsense mutations to restore CFTR function in vivo. A unique feature of the base editors under development by Life Edit is their small size which will allow in vivo delivery with Adeno-associated viruses (AAV) vectors to specific tissue types in the lungs. As part of the agreement, Life Edit will benefit from materials, resources, and expertise from the Cystic Fibrosis Foundation.

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare genetic disease found in more than 30,000 people in the U.S. CF is a hereditary disease that affects the lungs and digestive system that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that affect the production of the CFTR protein. When the CFTR protein is not made correctly, it affects the balance of salt and fluids inside and outside of the cell. This imbalance leads to thick, sticky mucus in the lungs, pancreas, and other organs. In the lungs, the mucus clogs the airways and traps germs, like bacteria, leading to infections, inflammation, respiratory failure, and other complications. CF is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time.

About Genome Editing and Life Edit Therapeutics Platform

Genome editing technologies have revolutionized the way cell and gene therapies and regenerative medicines are discovered and developed by allowing genetic material to be removed, added, or altered at specific locations in the genome. While these technologies are in widespread use experimentally, enzymes that offer broader coverage and greater specificity are needed for creating novel cell and gene therapies.

To meet the need for better genome editing approaches, Life Edit Therapeutics has built one of the worlds largest and most diverse arrays of novel RNA-guided nucleases (RGNs) and base editors that are active in mammalian cells. These RGNs were developed using AgBiomes proprietary collection of more than 90,000 microbes and their complete genomes. Life Edit Therapeutics is investigating these proprietary RGNs, which are sourced exclusively from non-pathogenic organisms, to develop new gene editing tools with higher fidelity, novel functionality, reduced immune response risk, and easier delivery. Life Edit Therapeutics nuclease collection also has a broad range of Protospacer Adjacent Motifs (PAMs) short sequences that must follow the targeted DNA sequence in order for the enzyme to make cuts that offer unprecedented access to genomic loci of interest. The Life Edit Therapeutics RGNs offer flexible editing options which encompass knock-out and knock-in capabilities, transcriptional regulation, and base editing when coupled with its proprietary deaminases.

Life Edit Therapeutics next generation editing systems will propel the development of novel human therapeutics by enabling ex vivo engineering for cell therapies and regenerative medicines and in vivo delivery of gene therapies. In addition to developing its own pipeline of gene therapies, Life Edit Therapeutics will continue to build its platform of novel nucleases, provide gene editing expertise to strategic partners and ElevateBios portfolio companies, and form other third-party partnerships to discover and develop new therapies.

About Life Edit Therapeutics Inc.

Life Edit Therapeutics is a next-generation gene editing company that has built a highly innovative genome editing platform with one of the worlds largest and most diverse collections of novel RNA-guided nucleases (RGNs) and base editors. Life Edit Therapeutics next generation editing systems will propel the development of novel human therapeutics by enabling ex vivo engineering for cell therapies and regenerative medicines and in vivo delivery of gene therapies. The company is continuing to strengthen the platform, developing a pipeline of in vivo gene therapies to address severe genetic disease, and sharing its expertise through strategic partnership. Life Edit is an ElevateBio portfolio company. For more information visit lifeeditinc.com.

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Life Edit Therapeutics Announces Award from Cystic Fibrosis Foundation - BioSpace

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-- Protein expression in muscle was sustained for two years following treatment in the low dose cohort, with mean beta-sarcoglycan expression of 54% at 24 months, compared to 36% at Day 60, as measured by western blot ---- Mean NSAD score improvement of 5.7 points from baseline was sustained through 24 months in low-dose cohort, and mean NSAD score improvement of 4.0 points from baseline at one year in high-dose cohort ---- Results in both cohorts continue to reinforce the safety and tolerability profile of SRP-9003 --

CAMBRIDGE, Mass., March 18, 2021 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc.(NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today shared new results from the ongoing study of SRP-9003 (rAAVrh74.MHCK7.hSGCB), the Companys investigational gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). In the first look at expression data from biopsies taken two years after a single administration of SRP-9003, results found sustained protein expression in muscle tissue. In functional outcomes assessments taken two years following treatment in Cohort 1 (low-dose cohort) and one year after treatment in Cohort 2 (high-dose cohort), patients continued to demonstrate stability in their NSAD (North Star Assessment for Dysferlinopathies) total score and improvements on timed function tests. Results are being presented today at the 2021 Muscular Dystrophy Association (MDA) Annual Clinical and Scientific Conference.

SRP-9003 is in development for the treatment of LGMD2E (also known as beta-sarcoglycanopathy and LGMDR4), a devastating monogenic neuromuscular disease caused by a lack of beta-sarcoglycan (beta-SG) proteins. SRP-9003 is a gene therapy construct that transduces skeletal and cardiac muscle, delivering a gene that codes for the full-length beta-SG protein, the absence of which is the sole cause of the progressive degeneration and a shortened lifespan characterized by the disease.

This data is the first look at longer-term expression data with any gene therapy for muscular dystrophy. The meaningful and sustained levels of beta-sarcoglycan protein expression at two years and continued strength of the functional outcomes measured are tremendously positive and support continued advancement of this investigational treatment for patients, said Louise Rodino-Klapac, Ph.D., executive vice president and chief scientific officer, Sarepta Therapeutics. In Cohort 2, we also saw strong expression of delta-sarcoglycan and gamma-sarcoglycan proteins in addition to beta-sarcoglycan, which suggests that SRP-9003 is working to restore the dystrophin associated protein complex, or DAPC, which provides biological support for the sustained functional benefits observed in both cohorts. LGMD2E is one of the most severe forms of LGMD and causes significant disability in children while frequently leading to early mortality and the data continue to suggest this treatment could bring much needed hope to these patients.

Efficient transduction in skeletal muscle and robust beta-sarcoglycan protein expression were seen in both dose cohorts following infusion with SRP-9003, and significant creatine kinase (CK) reductions were observed.

Cohort 1 (Dosed at 1.851013 vg/kg), 24 months following treatment:

Cohort 2 (Dosed at 7.411013 vg/kg), 12 months following treatment:

In an exploratory evaluation of all SRP-9003 treated patients compared to a natural history cohort; patients treated with SRP-9003 demonstrated significant improvements in functional outcomes after 24 months. The mean decline in total NSAD score for patients in the natural history cohort was 4.6 points while SRP-9003 treated patients demonstrated a mean improvement of 4.6 points for a clinically meaningful difference of 9.2 points.

Since the last update from this study in October 2020, there have been no new drug-related safety signals observed, and no decreases in platelet counts outside of the normal range and no evidence of clinical complement activation observed in either dose cohort.

About SRP-9003 and the StudySRP-9003 uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. AAVrh74 has lower immunogenicity rates than reported with other human AAV vectors. The MHCK7 promoter has been chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications.

This open label, first-in-human study is evaluating a single intravenous infusion of SRP-9003 among children with LGMD2E between the ages of 4 and 15 years with significant symptoms of disease. The SRP-9003 study has two cohorts, each studying a different dose-per-kilogram based on the weight of the patient. Three participants in the low-dose cohort (Cohort 1) were treated with a one-time infusion of SRP-9003 dosed at 1.851013 vg/kg and an additional three participants in the high-dose cohort (Cohort 2) received a one-time infusion dosed at 7.411013 vg/kg based on linear standard qPCR titer method. The six participants were between the ages of 4 and 13. Post-treatment biopsies were taken at 60 days.

Sarepta has exclusive rights to the LGMD2E gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Childrens Hospital.

About Limb-girdle Muscular DystrophyLimb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begin in muscles around the hips and shoulders before progressing to muscles in the arms and legs.

Patients with limb-girdle muscular dystrophy Type 2E (LGMD2E) begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E.

Sarepta has five LGMD gene therapy programs in development, including subtypes for LGMD2E, LGMD2D, LGMD2C, LGMD2B and LGMD2L, and holds an option for a sixth program for LGMD2A.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.comor follow us onTwitter,LinkedIn,InstagramandFacebook.

Forward-Looking StatementsThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding, SRP-9003 being the ideal candidate to treat peripheral neuromuscular diseases; the potential benefits of SRP-9003, including its potential to restore the dystrophin associated protein complex (DAPC); the potential benefits of MHCK7 and the AAVrh74 vector, including its potential to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle; and potential market opportunities.

These forward-looking statements involve risks and uncertainties, many of which are beyond our control. Known risk factors include, among others: success in preclinical trials and clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful; the data presented in this release may not be consistent with the final data set and analysis thereof or result in a safe or effective treatment benefit; different methodologies, assumptions and applications we utilize to assess particular safety or efficacy parameters may yield different statistical results, and even if we believe the data collected from clinical trials of our product candidates are positive, these data may not be sufficient to support approval by the FDA or foreign regulatory authorities; if the actual number of patients suffering from LGMD is smaller than estimated, our revenue and ability to achieve profitability may be adversely affected; we may not be able to execute on our business plans and goals, including meeting our expected or planned regulatory milestones and timelines, clinical development plans, and bringing our product candidates to market, due to a variety of reasons, some of which may be outside of our control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover our product candidates and the COVID-19 pandemic; and even if Sareptas programs result in new commercialized products, Sarepta may not achieve the expected revenues from the sale of such products; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Companys business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

InternetPosting of InformationWe routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com.Weencourageinvestorsandpotentialinvestorsto consult our website regularly for important information about us.

Source:Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics' Investigational Gene Therapy SRP-9003 for the Treatment of Limb-Girdle Muscular Dystrophy Type 2E Shows Sustained Expression and...

Recommendation and review posted by Bethany Smith

MONTPELLIER, France--(BUSINESS WIRE)--Regulatory News:

Sensorion (FR0012596468 ALSEN) a pioneering clinical-stage biotechnology company which specializes in the development of novel therapies to restore, treat and prevent within the field of hearing loss disorders, announces today its full-year 2020 financial results and provides an update on its business activities and outlook for 2021.

We are pleased with the progress made in 2020. We raised 36 million in equity financing to help advance our otoprotective small molecule SENS-401 and our pipeline of promising preclinical gene therapies from our strategic partnership with Institut Pasteur. We expanded our unique technology platform in gene therapy by further building our internal preclinical, process development and analytical capabilities. In Q4 2021, we expect the topline data readout from the Phase 2 trial of SENS-401 to treat sudden sensorineural hearing loss (SSNHL). In H2 2021, we also expect to initiate a clinical trial of SENS-401 to treat cisplatin-induced ototoxicity, a large indication with a significant unmet medical need said Nawal Ouzren, CEO of Sensorion.

Key developments in 2020: science and operational

Gene therapy collaboration with Institut Pasteur on hearing loss

On June 9, 2020, Sensorion announced positive preliminary preclinical data in non-human primates for its gene therapy program targeting Otoferlin deficiency (OTOF-GT), showing that it could deliver an intracellular marker to the inner hair cells at levels that reflect the future clinical requirements. The company plans to discuss its OTOF-GT program with regulatory authorities in H1 2021.

Additionally, Sensorion announced an agreement with Novasep on October 27, 2020, for the process development and manufacturing of adeno-associated viruses (AAV) gene therapy products for the Companys OTOF-GT program.

Technology platform expanded

Sensorion has built a unique R&D technology platform over the years to deepen the understanding of the pathophysiology and etiology of inner ear related diseases. The platform is being actively deployed to select targets, identify biomarkers and to optimize small molecules and gene therapy candidates.

The strengthened platform includes in-vitro assays encompassing the key cochlear cell types, systems to investigate explant tissue and advanced electrophysiological methods for assessing neuronal activity.

On the in-vivo side, Sensorion is developing a suite of validated preclinical models reflecting specific pathologies and inner ear lesions, as well as advancing the use of techniques such as auditory brainstem response (ABR) and distortion product oto-acoustic emission (DPOAE) audiometry for measuring and analysing hearing parameters in those models.

The last pillar of the Companys technology platform focuses on developing biomarkers to improve diagnosis and guide treatment in the key areas of unmet medical need in hearing loss.

Drug candidate SENS-401

Our clinical program with small molecule SENS-401 continued to progress in 2020.

Sensorion is conducting a Phase 2 clinical trial of SENS-401 in the treatment of SSNHL in adults. This Phase 2, randomized, double-blinded, placebo-controlled study is being conducted in multiple countries in Europe and Canada.

On February 17, 2020, Sensorion received Ethics Committee approval to include new military sites in this study, allowing clinical investigators to recruit volunteer military personnel who have suffered from acute hearing loss.

On March 13, 2020, Sensorion provided an update on the recruitment schedule for the ongoing SENS-401 Phase 2 study for the treatment of SSNHL. Due in part to the impact of COVID-19 on patient enrolment, the availability of topline data were expected to be delayed to Q4 2021 (see below in 2021 announcements).

On June 5, 2020, the independent Data Safety Monitoring Board (DSMB) confirmed the absence of safety concerns and recommended continuation of the Phase 2 trial as scheduled.

Having demonstrated otoprotective activity in several preclinical models, SENS-401 is being studied as a potential option to preserve residual hearing in people with cochlear implants under a collaboration with Cochlear, the world leader in implantable hearing solutions. Positive preclinical data were announced on January 5, 2021 (see below in 2021 announcements). Next steps are being discussed with Cochlear.

On December 15, 2020, Sensorion and Sonova Holding AG, a leading provider of hearing solutions, announced that Sonova had acquired a 3.7% equity stake in Sensorion via an investment of 5 million. At the same time, the two companies signed a letter of intent to exclusively explore potential plans for a strategic collaboration in the field of innovative diagnostic and therapeutic solutions for certain types of hearing loss. Discussions between Sensorion and Sonova are ongoing.

Strengthened scientific and medical leadership

As part of Sensorions strategic move into gene therapy for hearing restoration, on February 19, 2020 the Company announced the appointment of Dr. Graldine Honnet as Chief Medical Officer. Dr. Honnet has extensive expertise both in gene therapy and small molecule clinical development across numerous disease areas.

During 2020, Sensorion also increased its R&D headcount by 30% strengthening its team with experienced scientists and researchers in gene therapy, the inner ear and neurosciences. In addition to Dr Honnet, Sensorion also appointed a preclinical head in gene therapy and a new CMC gene therapy lead with more than 20 years of experience in the field.

On July 29, 2020, Sensorion announced the appointment of five distinguished experts to its Scientific Advisory Board (SAB); Prof. Alain Fischer, Dr. Robert Dow, Prof. Paul Avan, Dr. Diane Lazard and Dr. Hernn Lpez-Schier. The SAB is chaired by Prof. Christine Petit, Founding Director of the French Hearing Institute and a world-renowned geneticist and neurobiologist in hearing and hearing disorders.

Scientific communications

Sensorion presented at various scientific congresses and hosted two Key Opinion Leaders (KOLs) calls in 2020, including:

Governance: appointment of a new Chairman of the Board of Directors

On July 6, 2020, Sensorions Board of Directors was strengthened by the appointment of Edwin Moses as Chairman of the Board of Directors. Dr. Moses has more than 25 years of executive experience as both CEO and Chairman of numerous life science companies, including Ablynx, where he led its rapid growth from a small research-focused organization to one of Europes leading biotechnology companies, prior to its $4.8 billion acquisition by Sanofi in 2018.

2021 announcements

Since the end of the fiscal year, the key business updates are as follows:

On January 5, 2021, Sensorion provided an update on plans and progress made in the development of SENS-401 for the prevention of hearing loss. After encouraging efficacy data in preclinical models, the Company expects to begin a proof-of-concept clinical trial with SENS-401 to treat patients suffering from cisplatin-induced ototoxicity (CIO) in the second half of 2021. A natural history study of CIO in adult cancer patients is expected to start in the first half of 2021. Successful clinical findings would significantly expand Sensorions target market for SENS-401: approximately 500,000 cancer patients are treated annually with cisplatin in the USA and EU5, a significant proportion of whom will experience severe hearing loss.

At that time, Sensorion also announced a delay in the availability of the topline results from the Phase 2 study of SENS-401 in SSNHL to Q4 2021, due to the impact of COVID-19. Additionally, Sensorion indicated that it planned to review the study design and consider opportunities to aid its successful on-time completion. Following this review, an amendment to the statistical analysis plan (SAP), which would significantly reduce the sample size without compromising on the quality and potential outcome of the trial, has been submitted to the regulatory authorities. The responses from regulators so far have been encouraging and this increases the Companys confidence in being able to generate topline data this year.

On January 19, 2021, Sensorion announced positive preclinical data demonstrating the potential of SENS-401 to preserve residual hearing after cochlear implantation, in a collaboration with Cochlear, the global leader in implantable hearing solutions. Cochlear implants are very effective in treating severe to profound hearing loss, but preserving acoustic hearing in patients with residual hearing who receive cochlear implants could provide substantial benefit. Sensorion and Cochlear are making progress in the discussion around potential clinical study designs. Next steps are being discussed with Cochlear.

On February 15, 2021, Sensorion announced a third gene therapy collaboration with Institut Pasteur around the GJB2 gene targeting important pediatric and adult deafness markets. GJB2 mutations had already been widely recognized as the most prevalent cause of congenital deafness and now, new findings from Institut Pasteur have now demonstrated that GBJ2 mutations also underlie a wide range of other instances of severe hearing loss in the adult population. Sensorion will pursue three initial GBJ2-related indications: congenital deafness, progressive childhood hearing loss and early onset of severe presbycusis in adults.

2021 strategy and prospects

As of 31st December 2020, the Company had 62 million in cash, boosted by a successful 31 million Reserved Offering conducted in September and the December investment of 5 million by Sonova. Sensorion intends to use the new funds to develop its current gene therapy programs (OTOF-GT, GJB2-GT and USHER-GT), to support its pharmacology and clinical studies of SENS-401 and for general corporate purposes.

Nawal Ouzren, CEO of Sensorion commented: We are working hard to secure further approvals of the protocol amendment to reduce the sample size for the SENS-401 Phase 2 SSNHL trial which will help ensure that we could complete this study on time. Sensorion will also engage with regulatory authorities in Europe and the US to discuss our potential Otorferlin gene therapy clinical trial design. We recently added a promising third program to the Sensorion gene therapy pipeline centered around the GJB2 gene, the most prevalent cause of congenital deafness. This program will focus on major new markets with an estimated patient population of 300,000 children and adults in Europe and the United States. We remain very focused on delivering on our ambitious goals this year and we will stay true to our vision to serve patients with hearing loss.

Expected future milestones and estimated timelines:

2020 financial results

The annual accounts at 31 December 2020, drawn up according to IFRS standards and approved by the Board of Directors on 17 March 2021, have been duly reviewed by statutory auditors.

The simplified income statement as of 31 December 2020 is as follows:

In Euros IFRS standards

31.12.2020

31.12.2019

Operating income

2,421,267

2,522,717

Research & Development expenses

-7,679,365

-10,208,520

General & Administrative expenses

-3,631,123

-3,128,236

Total operating expenses

-11,310,488

-13,336,756

Operating profit/loss

-8,889,220

-10,814,039

Financial charges

-88,869

-1,282,141

Net profit/loss

-8,978,089

-12,096,181

For the year ended 31st December 2020, Sensorion reported operating income of 2.4 million, which included 1.8 million in research tax credit and 0.6 million in grants from Audinnove (RHU) and Patriot (PSPC) collaborations. The decrease of -0.1 million compared to 2019 is explained by a decrease of -0.7 million in research tax credit partly offset by an increase of +0.6 million in grants.

Operating expenses declined by 15% from 13.3 million in 2019 to 11.3 million for fiscal year 2020.

R&D expenses decreased by 2.5 million mainly due to the completion of the SENS-111 clinical trial in 2019 and a slowdown of SENS-401 activities linked to the global Covid-19 pandemic situation, and partly offset by an increase in headcounts to strengthen the R&D team with Gene Therapy expertise.

G&A expenses increased by 0.5 million, mainly driven by an increase in headcount.

Operating loss at 31 December 2020 was -8.9 million compared with -10.8 million at 31 December 2019.

The net financial charges decreased by 1.3 million compared to 2019 which was mainly due to the costs related to the convertible bond operations.

Net loss was -9.0 million at 31 December 2020 compared with -12.1 million at 31 December 2019.

As of 31 December 2020, the company employed 28 persons.

Financial structure

The simplified balance sheet at 31 December 2020 is as follows:

In Euros IFRS standards

31.12.2020

31.12.2019

Non-current Assets

1,474,117

1,724,348

Other Current Assets

4,254,909

5,946,864

Cash & cash equivalent

62,174,948

30,428,319

Total Assets

67,903,976

38,099,532

Equity

58,379,653

13,218,525

Non-current Liabilities

5,246,408

2,036,933

Current Liabilities

4,277,915

22,844,074

Total Liabilities

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Sensorion Reports Full-Year 2020 Financial Results and Provides Business Highlights - Business Wire

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BOONE, Iowa, March 19, 2021 /PRNewswire/ -- Gene therapy company ENDSULIN has expanded to a second study site at Boone Veterinary Hospital, where it is looking for diabetic dogs to participate in a study to evaluate the effectiveness of a treatment that could reduce or even eliminate insulin injections.

The study could be a critical step in advancing a one-time gene therapy treatment for diabetes in both dogs and humans. The treatment, which has proven efficacy in hundreds of small animals, is based on more than 25 years of research at the University of WisconsinHospitals and Clinics in Madison, where the company is based.

"We hope to free families who are caring for their diabetic pets around the clock," said Hans Sollinger, ENDSULIN founder. "Giving dogs and their families their independence back is a step in our mission to do the same for millions of people suffering with diabetes."

ENDSULIN covers the cost of the procedure, which takes about 30 minutes total and is administered by a certified veterinarian. After treatment, the ENDSULIN team will periodically monitor dogs' health to observe the long-term effects.

While this particular gene therapy is novel, dogs treated with gene therapies in Barcelona, Spain have been followed for up to 8 years, with no evidence of adverse events.

Ideal dogs are small, and have been recently diagnosed with diabetes. Families must be able to bring their pet to either the Boone or Waunakee, WI, clinics for the one-time treatment and five follow-up visits, and also provide follow-up information to the ENDSULIN research team.

People with diabetic dogs can learn more about the study or ask about enrollment at endsulin.com/pilot-study, or contact ENDSULIN directly at [emailprotected].

ABOUT ENDSULINENDSULIN is reshaping the way we approach a cure for diabetes. They are working to free patients from daily injections and 24/7 management using the most cutting-edge gene therapy technology, developed from decades of research by noted diabetes leader Hans Sollinger, MD, PhD, Dr hc, at the University of Wisconsin Hospitals and Clinics. Their sole focus is to get a durable, one-time treatment to the millions of people who need it.

SOURCE ENDSULIN

https://www.endsulin.com

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Diabetic Dogs Needed for Study that Could Reduce or Eliminate Insulin Injections - PRNewswire

Recommendation and review posted by Bethany Smith

NEW YORK, March 24, 2021 /PRNewswire/ --Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") today announced that its collaborator, Memorial Sloan Kettering Cancer Center ("MSK"), has commenced patient enrollment in the Phase 1 study evaluating Iomab-ACT for targeted conditioning prior to treatment with MSK's CD19 targeted CAR T-cell 19-28z. Iomab-ACT is a low dose version of Actinium's Phase 3 drug candidate Iomab-B, a CD45 targeting antibody radiation conjugate ("ARC"). Actinium and MSK were jointly awarded National Institutes of Health Small Business Technology Transfer grant funding for this first ever trial to evaluate ARC-based targeted conditioning prior to CAR-T therapy. The scientific rationale for this trial builds on preclinical data published in 2020 and is further supported by clinical observations from the SIERRA trial to justify combining MSK's 19-28z CAR T-cell therapy with Iomab-ACT. Manufacturing of patient CAR T-cells has commenced and patient conditioning with Iomab-ACT followed by 19-28z CAR T-cell infusion is expected early in the second quarter of 2021, with proof-of-concept data expected in the second half of 2021.

Results of a Phase 2 trial in 53 patients with relapsed and refractory B-cell acute lymphoblastic leukemia with MSK's 19-28z CAR-T published in the New England Journal of Medicine reported complete remissions in 83% (44/53) of patients, median event-free survival (EFS) of 6.1 months and median overall survival (OS) was 12.9 months at a median follow up period of 29 months (range 1 65 months). There was a 26% (14/53) rate of Grade 3 of greater cytokine release syndrome (CRS), with 1 patient death as a result, and 42% of patients experienced Grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS).

Dr. Dale Ludwig, Actinium's Chief Scientific and Technology Officer, said "MSK's 19-28z CAR T-cell therapy has produced high response rates in patients with relapsed or refractory B-ALL who have previously undergone several lines of standard therapy. However, toxicities such as cytokine release syndrome and neurologic toxicity, as well as durability of response, remain a significant challenge. The ARC technology Iomab-ACT employs enables the delivery of targeted radiation that selective and specifically targets immune cells including those implicated in the CAR-T-associated toxicities of neurotoxicity and cytokine release syndrome. We are eager to begin treating patients in this first of its kind pilot study to explore the potential of Iomab-ACT targeted lymphodepletion to modulate the immune system and improve the safety profile of CAR T-cell therapy. We are hopeful this technology may ultimately enhance our ability to deliver CAR T-cell therapies more safely. Positive results from pilot study could have a meaningful impact on the way we condition patients for CAR-T and other adoptive cell therapies, which have transformed the treatment of patients with blood cancers."

Sandesh Seth, Actinium's Chairman and CEO, said "This is a major milestone for Actinium and one we are very excited by. Adoptive cell therapies like CAR-T and gene therapies have emerged as some of the most promising areas in medicine and hold tremendous promise for patients, many of whom have limited or no treatment options remaining. This promise has led to a large and growing field of therapies where we intend to establish Iomab-ACT as the universal solution for targeted, non-chemotherapy conditioning, that harnesses the power of radiation. With Iomab-B nearing complete enrollment in the Phase 3 SIERRA trial for bone marrow transplant conditioning, starting to treat patients in this Iomab-ACT trial for CAR-T conditioning could not come at a better time. We look forward to continuing to build out our strategic business unit in targeted conditioning to best serve patients seeking potentially curative bone marrow transplant, adoptive cell therapy and gene therapy to improve patient access and outcomes."

About Iomab-ACT

Iomab-ACT targets cells that express CD45, an antigen found on immune cells such as lymphocytes and macrophages as well as leukemia and lymphoma cancer cells and delivers the radioisotope warhead iodine-131 to achieve cell depletion. Iomab-ACT is intended to deplete CD45+ immune cells such as macrophages that are implicated in CAR-T related toxicities and may also have an anti-tumor effect on chemo-refractory cancers. Iomab-ACT is a low dose extension of Actinium's lead program, Iomab-B, which is being studied in a pivotal Phase 3 trial for targeted conditioning prior to a bone marrow transplant. Preclinical data supporting Iomab-ACT's application in targeted lymphodepletion prior to ACT such as CAR-T was recently published in the journalOncotarget(https://www.oncotarget.com/archive/v11/i39/).

In addition, clinical data with trace doses of Iomab-B has shown transient, reversible lymphodepletion in patients and drug clearance pharmacokinetics that fit within the vein-to-vein time of CAR-T manufacturing and administration.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over seventy-five percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. Iomab-ACT (low dose I-131 apamistamab) is also be studied as a targeted conditioning agent in a Phase 1 study with a CD19 CAR T-cell Therapy with Memorial Sloan Kettering Cancer Center and is intended to be studied for conditioning prior to gene therapy. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 140 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website:https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Hans Vitzthum LifeSci Advisors, LLC[emailprotected](617) 430-7578

SOURCE Actinium Pharmaceuticals, Inc.

http://www.actiniumpharma.com/

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Actinium Announces Initiation of Patient Enrollment in Iomab-ACT Trial for Targeted Conditioning Prior to CD19 CAR T-Cell Therapy - PRNewswire

Recommendation and review posted by Bethany Smith

CAMBRIDGE, Mass.--(BUSINESS WIRE)--ElevateBio, a cell and gene therapy technology company focused on powering transformative cell and gene therapies, today announced that the companys Chief Scientific Officer of Regenerative Medicine, Dr. Melissa Carpenter, has been appointed to the International Society for Stem Cell Research (ISSCR) Board of Directors. In this role, Dr. Carpenter will work with the ISSCR officers and board to advance the organizations mission of bringing together researchers, clinicians, academics, and industry to promote excellence in stem cell science and applications to human health.

I am honored to have been elected to, and serve on the Board of, the ISSCR and foster the continued progress in advancing stem cell science alongside this impressive leadership and fellow board members, said Melissa Carpenter, PhD, Chief Scientific Officer of Regenerative Medicine at ElevateBio. Collaboration across the stem cell professional community is critical to our ability to translate promising stem cell research and regenerative medicine science into treatments that can have dramatic benefit for global human health globally.

Dr. Carpenter served on the ISSCR Task Force to revise the Guidelines for Stem Cell Research and Clinical Translation that will be released in May and advocated in support of the value of stem cell research as part of the Societys 2019 Advocacy Day, meeting with members of the U.S. Congress. She has also served on the Clinical Translation Committee.

We are delighted to welcome Melissa Carpenter to the ISSCR Board of Directors, said Christine Mummery, ISSCR President. Melissas dedication to supporting the translation of stem cell discoveries into therapeutics and her leadership has been crucial for advancing the clinical development of multiple therapies. Her experience will be an asset to the Board as the field of stem cell science continues to rapidly evolve.

The International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to stem cell research and its translation to the clinic. With nearly 4,000 members from more than 60 countries, the ISSCR mission is to promote excellence in stem cell science and applications to human health.

About ElevateBio:

ElevateBio is a cell and gene therapy technology company built to power the development of transformative cell and gene therapies today and for many decades to come. The company has assembled industry-leading talent, built world-class facilities, and integrated diverse technology platforms necessary for rapid innovation and commercialization of cell, gene, and regenerative therapies. The company has built an initial technology stack, including gene editing, induced pluripotent stem cells, and protein, viral, and cellular engineering. At the center of the business model is ElevateBio BaseCamp, a centralized R&D and manufacturing company that offers research and development (R&D), process development (PD), and Current Good Manufacturing Practice (CGMP) manufacturing capabilities. The company is focused on increasing long-term collaborations with industry partners while also continuing to develop its own highly innovative cell and gene therapies. ElevateBio's team of scientists, drug developers, and company builders are redefining what it means to be a technology company in the world of drug development, blurring the line between technology and healthcare.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, visit us at http://www.elevate.bio, or follow Elevate on LinkedIn, Twitter, or Instagram.

*As of the date of this press release, SoftBank Group Corp. has made capital contributions to allow investments by SoftBank Vision Fund 2 ("SVF 2") in certain portfolio companies. The information included herein is made for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy limited partnership interests in any fund, including SVF 2. SVF 2 has yet to have an external close, and any potential third-party investors shall receive additional information related to any SVF 2 investments prior to closing.

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ElevateBio Announces Chief Scientific Officer of Regenerative Medicine, Melissa Carpenter, PhD, Elected to the International Society for Stem Cell...

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Dive Brief:

Sarepta has three marketed products treating Duchenne, plus a beefy pipeline of 39 experimental RNA-based programs and genetic medicines for rare diseases. One towers above them all, however: SRP-9001. Its clinical trial setback in January cut the company's valuation in half as a rival treatment from Pfizer appeared to be taking a lead.

With the path to market looking longer for SRP-9001, other pipeline projects may figure more prominently in Sarepta's outlook, and the data from the follow-up project, known as SRP-9003, may be reassuring to investors.

SRP-9003 treats a type of muscular dystrophy called Limb-girdle that particularly affects the arms and legs. To do so, it helps replenish the deficiency of a protein called beta-sarcoglycan, the lack of which is thought to trigger the disease.

The first three patients in Sarepta's early-stage trial were infused with a low dose of the gene therapy, and after 18 months of treatment had improved their score by 5.7 points on a 20-item test that measures their ability to do such tasks as stand up from a chair or stand briefly on one foot. That improvement was sustained at two years, Sarepta reported Thursday.

In a research note, SVB Leerink's Schwartz wrote that untreated patients would have been expected to decline by 4.6 points over the same time period. Biological measures, such as expression of the beta-sarcoglycan protein, also showed positive signs, although they were short of expression seen in the healthy population.

Three higher-dose patients also showed improvements at one year. Their four-point increase on the functional test was short of the six points seen in the lower-dose group at 12 months, although Schwartz noted that biomarkers indicated the high-dose group may have been less disabled when they received the gene therapy.

The company hasn't seen any new safety signals. One adverse event was reported in an earlier data release, a patient who was dehydrated from vomiting.

Schwartz wrote that the data could set the stage for a study that could be submitted to regulators to support approval. There are no treatments for limb-girdle muscular dystrophy, so a regulatory pathway will need to be discussed with the Food and Drug Administration, as well as a quality assessment of the batch of gene therapy to be used in that trial. That could make the path forward for limb-girdle gene therapy different than the one Sarepta's traversing in Duchenne, where there are at least some marketed drugs for the condition.

The next study should begin this year, Schwartz wrote.

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With new results, Sarepta's 2nd gene therapy holds steady - BioPharma Dive

Recommendation and review posted by Bethany Smith

GERMANTOWN, Md., March 18, 2021 (GLOBE NEWSWIRE) -- Orgenesis Inc. (NASDAQ: ORGS) (Orgenesis or the Company), a global biotech company working to unlock the full potential of celland gene therapies, announces that it has entered a collaboration with MIDA Biotech B.V. (MIDA). Together, the companies will work to establish point-of-care centers at hospitals and other medical institutions across western Europe.

Orgenesis and MIDA plan to deploy Orgenesis Mobile Processing Units and Labs (OMPULs) at leading hospitals for the onsite development of promising cell and gene therapies and immunotherapies from MIDA. The OMPULs are multi-purpose, mobile, autonomous good manufacturing practice (GMP) facilities used to develop, optimize, and manufacture cell and gene therapies at the point of care. Via the collaboration, the teams will align with various hospitals with projects focused on scaling the therapies through to commercialization with regulatory compliance and governmental approval standards as guiding principles.

In connection with the Agreement, Orgenesis and MIDA entered into agreements to establish point-of-care centers and deploy OMPULs within leading hospitals in Italy, Germany, Spain and Benelux, as well as other activities including joint research, development and validation activities related to the development of cell and gene therapies.

These agreements mark a major milestone towards the commercial launch of our OMPULs across Europe, and we believe provide further validation of our platform, as each of the respective hospitals conducted extensive due diligence and verification around our technology and capabilities prior to signing the agreements, stated Vered Caplan, CEO of Orgenesis. We see MIDA as an ideal partner based on their established relationships with the leading medical centers across western Europe and their promising science. Our teams are aligned in the desire to help lower costs and eliminate the logistical nightmares of building a centralized production facility or cleanrooms in the hospitals, which can stand in the way of getting a therapy to market effectively.

The additional sites will significantly expand the Orgenesis POCare Network capacity, which already includes active development centers in the United States, Belgium, Israel, and South Korea, as well as a growing number of joint venture agreements with regional partners and ongoing therapeutic development programs.

About OrgenesisOrgenesis is a global biotech company working to unlock the full potential of celland gene therapies (CGTs) in an affordable and accessible format at the point of care. The Orgenesis POCarePlatform is comprised of three enabling components: a pipeline of licensedPOCare Therapeuticsthat are processed and produced in closed, automatedPOCare Technologysystems across a collaborativePOCare Network. Orgenesisidentifies promising new therapies and leverages its POCare Platform to provide a rapid, globally harmonized pathway for these therapies to reach and treat large numbers of patients at lowered costs through efficient, scalable, and decentralized production. The POCare Network brings together patients, doctors, industry partners, research institutes and hospitals worldwide to achieve harmonized, regulated clinical development and production of the therapies. Learn more about the work Orgenesis is doing atwww.orgenesis.com.

Notice Regarding Forward-Looking StatementsThis press release contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities and Exchange Act of 1934, as amended. These forward-looking statements involve substantial uncertainties and risks and are based upon our current expectations, estimates and projections and reflect our beliefs and assumptions based upon information available to us at the date of this release. We caution readers that forward-looking statements are predictions based on our current expectations about future events. These forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions that are difficult to predict. Our actual results, performance or achievements could differ materially from those expressed or implied by the forward-looking statements as a result of a number of factors, including, but not limited to, our reliance on, and our ability to grow, our point-of-care cell therapy platform, our ability to achieve and maintain overall profitability, our ability to manage our research and development programs that are based on novel technologies, our ability to control key elements relating to the development and commercialization of therapeutic product candidates with third parties, the timing of completion of clinical trials and studies, the availability of additional data, outcomes of clinical trials of our product candidates, the potential uses and benefits of our product candidates, our ability to manage potential disruptions as a result of the coronavirus outbreak, the sufficiency of working capital to realize our business plans, the development of our POCare strategy, our trans differentiation technology as therapeutic treatment for diabetes, the technology behind our in-licensed ATMPs not functioning as expected, our ability to further our CGT development projects, either directly or through our JV partner agreements, and to fulfill our obligations under such agreements, our license agreements with other institutions, our ability to retain key employees, our competitors developing better or cheaper alternatives to our products and the risks and uncertainties discussed under the heading "RISK FACTORS" in Item 1A of our Annual Report on Form 10-K for the fiscal year ended December 31, 2020, and in our other filings with the Securities and Exchange Commission. We undertake no obligation to revise or update any forward-looking statement for any reason.

Contact for Orgenesis:Crescendo Communications, LLCTel: 212-671-1021Orgs@crescendo-ir.com

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Orgenesis Enters into Collaboration Agreement with MIDA to Deploy OMPULs for Point-of-Care Research and Development of Promising Cell and Gene...

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SparingVision Announces Upcoming Presentations at the Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting

Paris, March 19, 2021 SparingVision (the Company), a genomic medicine company developing vision saving treatments for ocular diseases, announces today that three abstracts highlighting the companys recent research into ocular diseases and its lead gene therapy treatment SPVN06 have been accepted for the Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting, to be held virtually from 1-7 May. The three abstracts will be given as poster presentations for which the details can be found below.

Title: SPVN06, a Novel Mutation-Independent AAV-based Gene Therapy, Protects Cone Degeneration in a Pig Model of Retinitis PigmentosaDate and Time: May 3, 2021 from 11:15 AM to 1:00 PM EDT

Presenter: Dr. Jennifer Noel, University of LouisvilleSession Title: Drug delivery and Gene Therapy

Title: Correlations between progression markers in rod-cone dystrophy due to mutations in RHO, PDE6A, or PDE6BDate and Time: May 3, 2021 from 4:30 PM to 6:15 PM EDT

Presenter: Dr. Daniel Chung, Chief Medical Officer, SparingVisionSession Title: Visual Impairment - Assessment and Measurement

Title: A 1-Month Toxicology and Biodistribution NHP Pilot Study Evaluating a Single Subretinal Bilateral Administration of SPVN06 - A Novel AAV-Based Gene Therapy for the Treatment of Rod-Cone Dystrophies Agnostic of the Causative Mutation Date and Time: May 5, 2021 from 2:45 PM to 4:30 PM EDT

Presenter: Dr. Melanie Marie, SparingVisionSession Title: AMD and retinal physiology

**ENDS**

Contacts:

NOTES TO EDITORS:

About SparingVision:SparingVision is a genomic medicines company, translating pioneering science into vision saving treatments. Founded to advance over 20 years of world-leading ophthalmic research from its scientific founders, SparingVision is leading a step shift in how ocular diseases are treated, moving beyond single gene correction therapies. At the heart of this is SPVN06, a gene independent treatment for retinitis pigmentosa (RP), the most common inherited retinal disease affecting two million people worldwide. SPVN06 could form the basis of a suite of new sight saving treatments as it could be applicable to many other retinal diseases, regardless of genetic cause.

The Company is supported by a strong, internationally renowned team who aim to harness the potential of genomic medicine to deliver new treatments to all ocular disease patients as quickly as possible. SparingVision has raised 60 million to date and its investors include 4BIO Capital, Bpifrance, Foundation Fighting Blindness (US), Fondation Voir & Entendre, UPMC Enterprises, Jeito Capital and Ysios Capital. For more information, please visit http://www.sparingvision.com.

About SPVN06:SPVN06 is a proprietary, mutation-agnostic, AAV gene therapy approach comprised of one neurotrophic factor and one enzyme reducing oxidative stress which, acting synergistically, aim at slowing or stopping the degeneration of cone photoreceptors, which inevitably leads to blindness in patients with rod-cone dystrophies (RCD). SparingVisions primary disease target is Retinitis Pigmentosa (RP), one of the most common inherited retinal diseases that affects two million patients worldwide. There is currently no treatment approved to treat RP patients independently of their genetic background. This approach is potentially applicable to many more diseases where the loss of rods is known to be an early signal of the disease. First-in-man trials, with SPVN06 in patients with RP, will be commencing in H2 2021.

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SparingVision Announces Upcoming Presentations at the Association for Research in Vision and Ophthalmology (ARVO) 2021 Annual Meeting - GlobeNewswire

Recommendation and review posted by Bethany Smith

24 Mar 2021

FPIs raison detre is to get effective, international clinical trials on the road (see Part 6of this series). At ICFTD, FPIs co-leader, Adam Boxer of the University of California, San Francisco, summarized what trials exist already, and offered a glimpse of the future.

Currently, the field lacks biomarkers for the underlying neuropathology of FTD, so there is no concrete way to know whether tau fibrils or TDP-43 inclusions lurk within the brain of a patient who has no known autosomal-dominant mutation. Hence, present-day FTD trials are limited to carriers of pathogenic C9ORF72, GRN, or MAPT mutations, and to people whose clinical syndromes are known to be tauopathies, such as progressive supranuclear palsy.

Trials for carriers of GRN mutations are the farthest along. At centers that are part of FPI, Alector is conducting Phase 2 and Phase 3 trials evaluating AL001, an anti-sortilin antibody meant to slow progranulins degradation. Early trials of AL001 indicated that it restores CSF progranulin levels in mutation carriers. The Phase 3 trial is the first in the field to include presymptomatic mutation carriers. They can enroll if their plasma NfL is elevated, suggesting they are nearing symptom onset. The trial aims for 180 participants total, and also includes symptomatic carriers. It uses the CDR-NACC-FTLD as a clinical primary endpoint, and is slated to run through 2023.

Two companiesPrevail Therapeutics (recently acquired by Eli Lilly & Company) and Passage Bioare pursuing a gene-therapy approach. Both are hoping to replenish progranulin levels by injecting an adeno-associated virus bearing the progranulin gene directly into the cisterna magna of GRN mutation carriers with FTD. Prevails trial of PR006started in July 2020, while Passage Bios trial of PBFT02 is slated to start this month.

Julio Rojas of the University of California, San Francisco, said the combination of sensitive disease biomarkers (CSF progranulin, plasma NfL, and others) and progranulin-targeted treatment in trials bodes well for this form of familial FTD. Its likely well see a treatment for GRN mutation carriers with FTD before we see one for AD, Rojas said.

Carriers of hexanucleotide expansions in the C9ORF72 gene are also being included within the progranulin umbrella. Owing to the lysosomal dysfunction wrought in both familial forms of the disease, C9ORF72 carriers are included in Alectors Phase 2 study of AL001.

Other trials are targeting the C9ORF72 mutation specifically. They enroll people with ALS and/or FTD. The furthest along is Ionis/Biogens antisense oligonucleotide BIIB078, in Phase 1. The multiple-ascending-dose trial includes 114 people with ALS; results are expected later this year. Participants in the randomized portion of the trial are being enrolled in a two-year, open-label extension. WaveLife Sciences, Cambridge, Massachusetts, is planning to start a Phase 1 trial of its C9-ASO, called WVE-004, in people with ALS and FTD due to C9ORF72 expansion this year (see press release).

Yet another C9-ASO, called afinersen, was designed in Robert Browns group at the University of Massachusetts in Worcester. At ICFTD, Boxer showed data from a man with ALS who was treated with afinersen for over a year. During this time, his CSF levels of poly-GP, a dipeptide translated from transcripts of the hexanucleotide expansion, plummeted, and his disease stayed stable during treatment.

The diabetes drug metformin is being tested at the University of Florida, Gainesville, in a Phase 1 clinical trial for C9ORF72 hexanucleotide expansion carriers with ALS or FTD. Besides its better-known effects on glucose levels and insulin sensitivity, metformin has been reported to squelch repeat-associated non-AUG (RAN) translation, the mechanism responsible for translating toxic dipeptides from the C9 repeats (Zu et al., 2020). This open-label study includes 18 participants, and is expected to finish in August 2022.

What about trials for FTLD-tau? So far, most trials have focused on people with clinical syndromes, such as progressive supranuclear palsy, which is known to have underlying tau pathology, but not necessarily a pathogenic tau mutation. Two different anti-tau monoclonal antibodies failed in trials for PSP last year (Jul 2019 news; Dec 2019 news). This prompted cancellation of a basket trial that had also included people with non-fluent primary progressive aphasia, corticobasal syndrome, and MAPT mutation carriers with FTD.

Why did these trials fail? A definitive answer is not in, but Boxer noted that CSF studies from the trials indicated that both antibodies, which target taus N-terminus, did not rid the brain of all forms of tau pathology. Boxer said the field eagerly awaits results of Biogens trial of BIIB080, a tau-targeting ASO in people with mild AD, which could provide proof-of-concept data for primary tauopathies. That Phase 2 trial will finish in May of 2022.

One hurdle to treating primary tauopathies is the lack of fluid biomarkers or PET imaging tracers for many non-AD forms of tau. While some tracers have been found to bind to the 4R-tauopathies PSP and CBD, so far none reliably tag tau in people with bvFTD or PPA, who could have underlying tau or TDP-43 pathology (Jul 2020 news). Once the field develops a marker for either one, people with sporadic FTD will be able to join clinical trials targeting their specific pathology.

MAPT mutations are the rarest cause of familial FTD, i.e., patients with these mutations are scarce. To ensure that trials in this far-flung group of patients are run with the most power possible, the FPI is working to coordinate international platform trials for them, which will test multiple therapies simultaneously against a shared placebo group, Boxer said.Jessica Shugart

No Available Further Reading

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FTD Trials: The Now and the Future | ALZFORUM - Alzforum

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Guest editorial: Technology to meet the challenge of efficiency in the regulated AAV vector space

In this guest editorial, based on a blog post by Gyros Protein Technologies, learn how scientists at AstraZeneca developed a reliable method for adeno-associated virus (AAV) capsid titer quantification.

Vectors based on AAV are used widely in gene therapy for in vivo gene delivery. The success of AAV-based therapeutic production depends on the availability of laboratory tools that can efficiently deliver reliable data, including the determination of virus particle titer (physical titer). To achieve this, a team at AstraZeneca searched for an immunoassay platform that could improve on ELISA in terms of dynamic range, sample volume, and productivity. Its evaluation showed that Gyrolab systemmet its needs for AAV process development, with a more reliable measurement of AAV capsid titer for in-process and purified samples.

Gene therapy has seen a massive explosion in activity since the first clinical trial in 1989, and, by the latter half of 2020, had engaged 536 advanced therapy developers, with 373 clinical trials ongoing1. There are currently three gene therapy products approved by the US Food and Drug Administration (FDA), and the field continues to expand with more than 900 investigational new drug (IND) applications for ongoing gene therapy clinical studies2.

Recombinant vectors based on the non-pathogenic AAV are currently one of the most widely used vehicles for delivery in gene therapy. Different serotypes of AAV can be used to specifically target certain tissues and organs and are the subject of intensive research to improve their properties. AAV has also been used in a vaccine against COVID-19.

Regulatory authorities are increasing their support for initiatives in cell and gene therapy, resulting in new guiding documents on gene therapy manufacturing and clinical development of products3, but there are issues with inconsistent directives that are confounding manufacturing efforts4.

Some of the biggest challenges in manufacturing AAV therapeutics concern chemistry, manufacturing, and control (CMC). Gene therapy drugs often target rare diseases with trials involving only 1020 participants, and yet organizations must conduct all the CMC operations normally required for product commercialization in much larger manufacturing batches.

Advances in AAV-based therapeutics range from vector engineering to increasing transduction efficiency, to fine-tuning tissue tropism, and the avoidance of host immune response activation, as well as optimization of the small- and large-scale vector production. Support of bioprocess development relies on the availability of fit-for-purpose analytical tools to assess potential critical quality attributes (pCQAs) that are relevant to characterization and lot release testing. In the case of AAV-based therapeutics, this includes the ability to determine the concentrations of viral genomes (genome titer) and viral particles (capsid titer). Genome titer can be determined by PCR, but determining the capsid titer is more of a challenge.

In a recent webinar on capsid titer quantification for AAV-based therapeutics, AstraZeneca scientist Dr. Tomasz Witkos talks about how miniaturized immunoassays can be used to measure purified AAV vector as well as in-process samples and how the immunoassay experimental setup can be modified to measure several AAV serotypes.

He describes the need for a method to measure titer that could meet several criteria:

The drive to engineer recombinant AAVs to improve their properties can make capsid titer determination a challenge. The few commercial kits available for measuring capsid titer did not meet AstraZenecas needs in terms of dynamic range and accuracy. The team also needed a kit that could handle small sample volumes, preferably on an automated platform to save time.

In the webinar, Witkos presents an immunoassay developed on Gyrolab platform with AAV serotype-specific antibodies that can reliably measure AAV capsid titer in purified and in-process samples, delivering accurate and precise data suitable for AAV process development. The assay is versatile, with an antibody pair comprising a capture antibody that recognizes a broad range of AAV serotypes and another that is serotype-specific.

This assay setup can be readily adapted to titer measurements of various AAV serotypes and has a broader quantification range (3 3.5 logs) compared to a commercially available capsid ELISA kit (1 1.5 logs). The Gyrolab assay could be used to test neat samples and at low dilutions, which increases reproducibility compared to ELISA, which requires greater than 1,000x dilutions. Throughput was estimated at 50 samples in four dilution series in a 5-CD run, with reproducibility in the range of 1015 % CV. The team also appreciates Gyrolab Viewer as a very valuable tool to spot any issues with AAV particle aggregation.

Find out more about how Gyrolab system is improving the productivity of gene therapy efforts at AstraZeneca, by watching the Gyros Protein Technologies webinar, Capsid titer quantification for AAV-based therapeutics.

Discover the new Gyrolab AAVX Titer Kit when used in combination with Gyrolab system, this kit is designed to quickly deliver high-quality titer data for AAV serotypes 18 and AAVrh10 using smaller sample volumes compared to ELISA.

References

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Capsid titer quantification for AAV-based therapeutics - SelectScience

Recommendation and review posted by Bethany Smith