Category Archives: Transhuman News

News Release

Wednesday, December 8, 2021

Researchers have linked a rare genetic mutation found mostly in Black Americans and other people of African descent to an earlier onset of heart failure and a higher risk of hospitalization. The findings suggest that earlier screening for the mutation could lead to faster treatment and improved outcomes for heart failure in this vulnerable group, the researchers said. The results of the study, which was largely supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear in the Journal of the American College of Cardiology: Heart Failure.

This is the most comprehensive evaluation of the association between this mutation and measures of cardiac structure, heart function, and heart failure risk in an exclusively Black population, said lead study author Ambarish Pandey, M.D., assistant professor of internal medicine in the Division of Cardiology at University of Texas Southwestern Medical Center in Dallas. The results also highlight the importance of early genetic screening in patients at higher risk for carrying the mutation.

Heart failure is a chronic, debilitating condition that develops when the heart cant pump enough blood to meet the bodys needs. Despite the name, it does not mean that the heart has stopped beating. Common symptoms include shortness of breath during daily activities or trouble breathing when lying down. The condition affects about 6.5 million people in the United States alone. Black Americans are at higher risk for the condition than any other racial/ethnic group in the U.S., and they experience worse outcomes.

The genetic variant studied in the current research had long ago been linked to a higher risk of heart failure in people of African ancestry. Known as TTR V142I, the gene can cause a condition called transthyretin amyloid cardiomyopathy, which is potentially fatal because protein builds up inside the heart. However, little was known about the impact of the mutation on important clinical-related factors such as heart structure, heart function, hospitalization rates, and blood biomarkers.

To learn more, the researchers studied TTR V142I in a group of middle-aged participants from the 20-year-long Jackson Heart Study, the largest and longest investigation of cardiovascular disease in Black Americans. Of the 2,960 participants selected from the study, about 119 (4%) had the genetic mutation, but none had heart failure at the start. The researchers followed the participants for about 12 years between 2005 and 2016.

During the study period, the researchers observed 258 heart failure events. They found that patients who carried the genetic mutation were at significantly higher risk of developing heart failure, compared to those without the mutation. These patients also developed heart failure nearly four years earlier and had a higher number of heart failure hospitalizations. Researchers said they found no significant difference in death rates between the two groups during this study period.

During follow-up studies, however, they observed significant increases in blood levels of troponin, a protein complex that is an important marker of heart damage, among carriers of the genetic mutation. They did not see any significant associations between the genetic mutation and changes in heart structure and function as evaluated by echocardiographic and cardiac MRI assessments.

What that means is that the gene is causing heart damage slowly over time, said Amanda C. Coniglio, M.D., the lead author of the study and a physician with Duke University School of Medicine in Durham, North Carolina. The changes are subtle but significant.

The researchers noted that more studies will be needed to continue assessing participants heart structure and function and to see, long-term, if increased hospitalization risk translates into higher risk of death.

Identification of genetic susceptibility to amyloid cardiomyopathy is an important advance related to heart failure, especially given its disproportionate effect on older and multiethnic populations, said Patrice Desvigne-Nickens, M.D., a medical officer in the Heart Failure and Arrhythmia Branch in NHLBIs Division of Cardiovascular Sciences.

Adolfo Correa, M.D., Ph.D., study co-author and former director of the Jackson Heart Study, agreed. About half of Black American men and women living in the United States today have some form of cardiovascular disease, but the root causes are poorly understood, he said. This study brings us a step closer to better understanding this particular form of gene-related heart failure, as well as the life-saving importance of early screening.The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001) and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities. Additional NIH funding support includes the National Institute of Diabetes and Digestive and Kidney Diseases grant 1K08DK099415- 01A1; National Institute of General Medical Sciences grants P20GM104357 and 5U54GM115428.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults. JACC-Heart Failure.DOI: 10.1016/j.jchf.2021.09.006

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Rare gene mutation in some Black Americans may allow earlier screening of heart failure - National Institutes of Health

NEW YORK & BRISBANE, Calif.--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) and Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A. The Alta study data, in patients with severe hemophilia A, are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA. The oral presentation slides, which include follow-up data up to 195 weeks for the longest-treated patient, are available on Sangamos website in the Investors and Media section under Events and Presentations.

At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate (ABR) was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up as of the October 1, 2021 cutoff date. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort have resumed prophylaxis.

These latest results further suggest the potential of this investigational therapy to bring transformational benefit to eligible patients living with severe hemophilia A, if confirmed in ongoing clinical trials, said Seng H. Cheng, Senior Vice President and Chief Scientific Officer, Pfizer Rare Disease.

We continue to be encouraged by findings from the Phase 1/2 Alta study in patients with severe hemophilia A, said Rob Schott, M.D., M.P.H, F.A.C.C, Head of Development at Sangamo. We believe these two-year results demonstrate the potential of this gene therapy candidate to minimize significant symptoms associated with hemophilia A and become an alternative to the current burden of disease management.

Giroctocogene fitelparvovec was generally well-tolerated in this Phase 1/2 study. Among the five patients in the highest dose cohort, four received corticosteroids for liver enzyme (ALT/AST) elevations. All elevations fully resolved with oral corticosteroids. As previously reported, one patient in the highest dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec and resolved approximately 12 hours post-infusion. Across all four cohorts, 26 treatment-related adverse events occurred in six patients as of the October 1, 2021 cutoff date. No other treatment-related serious adverse events were reported as of the cutoff date. Additionally, no confirmed FVIII inhibitor development occurred, and no thrombotic events were reported.

The Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec in patients with hemophilia A has started and is over 50% enrolled. Following the observation of FVIII levels greater than 150% in some treated patients, Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment to provide clinical management guidance for elevated FVIII levels. Subsequently, on November 3, 2021, the U.S. Food and Drug Administration (FDA) informed Pfizer that this trial has been placed on clinical hold while the protocol amendment and associated documents are reviewed.

About the Alta Study

The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The mean age of the 11 male patients assessed across four dose cohorts (9e11 vg/kg - 2 patients, 2e12 vg/kg - 2 patients, 1 e13 vg/kg - 2 patients and 3e13 vg/kg - 5 patients) is 30 years (range 18-47 years). Patients in this study will be assessed every six months until they enroll in a long-term follow-up study.

About the AFFINE study

The Phase 3 AFFINE (NCT04370054) study is an open-label, multicenter, single arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. Eligible study participants will have completed at least six months of routine FVIII prophylaxis therapy during the lead-in Phase 3 study (NCT03587116) in order to collect pretreatment data for efficacy and selected safety parameters.

The primary endpoint is impact on annualized bleeding rate (ABR) through 12 months following treatment with giroctocogene fitelparvovec. This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 12 months following infusion of giroctocogene fitelparvovec.

About giroctocogene fitelparvovec

The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency. Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer. Giroctocogene fitelparvovec is currently being studied in the Phase 3 AFFINE study.

About Hemophilia A

Hemophilia is a genetic hematological rare disease that results in a deficiency of a protein that is required for normal blood clotting clotting factor VIII in hemophilia A. The severity of hemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems.

Hemophilia A occurs in approximately one in every 5,000-10,000 male births worldwide. For people who live with hemophilia A, there is an increased risk of spontaneous bleeding as well as bleeding following injuries or surgery. It is a lifelong disease that requires constant monitoring and therapy.

About Pfizer Rare Disease

Rare diseases include some of the most serious of all illnesses and impact millions of patients worldwide, representing an opportunity to apply our knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare disease builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within a number of disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. We innovate every day leveraging our global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about our Rare Disease portfolio and how we empower patients, engage communities in our clinical development programs, and support programs that heighten disease awareness.

About Pfizer: Breakthroughs That Change Patients Lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at http://www.Pfizer.com. In addition, to learn more, please visit us on http://www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

About Sangamo Therapeutics

Sangamo Therapeutics is a clinical-stage biopharmaceutical company with a robust genomic medicines pipeline. Using ground-breaking science, including our proprietary zinc finger genome engineering technology and manufacturing expertise, Sangamo aims to create new genomic medicines for patients suffering from diseases for which existing treatment options are inadequate or currently dont exist. For more information about Sangamo, visit http://www.sangamo.com.

PFIZER DISCLOSURE NOTICE:

The information contained in this release is as of December 12, 2021. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about an investigational hemophilia A therapy, giroctocogene fitelparvovec (SB-525 or PF-07055480), including its potential benefits and the phase 1/2 and phase 3 clinical trials, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether and when the clinical hold of the Phase 3 AFFINE clinical trial will be lifted; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications for any potential indications for giroctocogene fitelparvovec may be filed in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether giroctocogene fitelparvovec will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of giroctocogene fitelparvovec; uncertainties regarding the impact of COVID-19 on Pfizers business, operations and financial results; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at http://www.sec.gov and http://www.pfizer.com.

SANGAMO DISCLOSURE NOTICE:

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the therapeutic potential of giroctocogene fitelparvovec (SB-525), including its potential clinical benefit to patients with hemophilia A and its potential as an alternative to the standard of care for patients with hemophilia A, the anticipated implementation of a protocol amendment for, and the response to the clinical hold of, the Phase 3 AFFINE study of giroctocogene fitelparvovec and the expected timing thereof, and other statements that are not historical fact. These statements are not guarantees of future performance and are subject to risks and uncertainties that are difficult to predict. Sangamos actual results may differ materially and adversely from those expressed in these forward looking statements. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties related to: the evolving COVID-19 pandemic and its impact on the global business environment, healthcare systems and the business and operations of Sangamo and Pfizer, including the initiation and operation of clinical trials; the research and development process; the uncertain timing and unpredictable nature of clinical trial results, including the risk that any protocol amendment for the Phase 3 AFFINE trial of giroctocogene fitelparvovec may not be accepted by the relevant review bodies in a timely manner, or at all, each of which could further delay or preclude further patient dosing in the trial, as well as the risk that therapeutic effects observed in the preliminary results of the Phase 1/2 Alta study will not be durable in patients and that final clinical trial data will not validate the safety and efficacy of giroctocogene fitelparvovec; reliance on results of early clinical trials, such as the Phase 1/2 Alta study, which results are not necessarily predictive of future clinical trial results, including the results in the Phase 3 AFFINE study; the unpredictable regulatory approval process for product candidates across multiple regulatory authorities; the manufacturing of products and product candidates; the commercialization of approved products; the potential for technological developments that obviate technologies used by Sangamo and Pfizer in giroctocogene fitelparvovec; the potential for Pfizer to terminate the giroctocogene fitelparvovec program or to breach or terminate its collaboration agreement with Sangamo; and the potential for Sangamo to fail to realize its expected benefits of its collaboration with Pfizer, including the risk that Sangamo may not earn any additional milestone or royalty payments under its collaboration with Pfizer. These risks and uncertainties are described more fully in Sangamo's filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2020 and the most recent Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. The information contained in this release is as of December 12, 2021, and Sangamo undertakes no duty to update forward-looking statements contained in this release except as required by applicable laws.

See the rest here:
Pfizer and Sangamo Announce Updated Phase 1/2 Results Showing Sustained Bleeding Control in Highest Dose Cohort Through Two Years Following Hemophilia...

For a long time, the thinking was the same. To make a career in medical research, it was critical to pick a promising area of study. That often meant steering clear of ALS.

Short for amyotrophic lateral sclerosis, ALS is a progressive and fatal illness that causes nerves to break down. The disease was first discovered more than a century ago, but became widely known only after famed baseball player Lou Gehrig was diagnosed with it in the late 1930s.

Today, estimates hold that about 30,000 people in the U.S. have ALS, with 5,000 new cases annually. These patients desperately need new treatments; yet, the complicated biology of their disease has thwarted most attempts at developing effective medicines. The Food and Drug Administration has approved only three so far, and each has limitations. ALS patients still live about four years on average once they're diagnosed.

Experts say there are reasons for hope, though. Scientific and technological breakthroughs have given drug hunters better tools to understand and potentially combat ALS. Patients may soon have another treatment, a pill shown to modestly slow people's decline and help them live longer, and could see more options arrive in the next several years if more advanced approaches pan out.

"The science is really exciting, and I think that's driving a lot of companies to have programs," said Merit Cudkowicz, director of the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital.

"I remember people telling me it was a dead-end career to go into ALS research," she added. Now, "it's a hot time to be an ALS scientist. They all want you."

But as with many diseases of the brain, much about ALS remains unclear. The vast majority of cases are "sporadic," for example, meaning their cause isn't fully understood.

For drugmakers hoping to crack the disease, these uncertainties create major roadblocks. In the last year alone, experimental treatments from Brainstorm Therapeutics, Alexion Pharmaceuticals and Biogen the world's largest biotech focused on neuroscience have all faltered in late-stage clinical trials, tempering enthusiasm among doctors, patients and investors.

And for patient advocates, these continued setbacks have only intensified calls for companies to accelerate research and for drug regulators to work more flexibly.

"The drug development process takes a long time. And when you're looking at one year, two years, three years of life left, you just don't have time," said Larry Falivena, who serves on the board of trustees of The ALS Association, a patient advocacy group, and who was diagnosed with a slower progressing form of the disease in 2017.

In the U.S., patients with ALS have few treatment options. There's one called riluzole, which was approved in 1995 and has been shown to extend survival by a few months. There's also Nuedexta, which was cleared in 2011 to treat a symptom of the disease. And then there's Radicava, which was greenlit in 2017 as a way to slow the physical decline associated with ALS.

About four in five U.S. patients take riluzole, according to Cudkowicz, as it appears to consistently extend people's lives without harsh side effects.

Far fewer are on Radicava, largely because of the way it's administered. The drug is given as an hourlong infusion each day for about a third of every month. That inconvenience, coupled with its often small effect, has led many patients to not consider it worthwhile.

"In any one patient, you don't really notice the difference whether they're on the drug or not. It's that type of benefit you only really see in trials," said Stephen Scelsa, a neurologist at Mount Sinai Hospital in New York City.

Another option could be on the horizon, though.

In 2019, Amylyx Pharmaceuticals, a small Cambridge, Massachusetts-based company, announced that a drug it has been developing appeared to slow ALS in a placebo-controlled clinical trial. Results later published in The New England Journal of Medicine showed those who took the drug, known as AMX0035, scored a couple points better on average on a scale used to evaluate how well ALS patients speak, walk, breathe and perform other essential functions.

Further analysis found early signs the drug kept people alive longer, too. Looking at 135 study participants, those treated with AMX0035 lived a median of just over two years about six and a half months longer than those who received a placebo.

Amylyx's co-founders Justin Klee and Josh Cohen at a manufacturing site for AMX0035

Courtesy of Amylyx Pharmaceuticals

Experts note that, while positive, the effect of Amylyx's drug is still modest. Patients who took it continued to decline, and the chances of them living up to two years after enrolling in the study were about 50%. The study also found AMX0035 didn't do significantly better than the placebo on secondary tests that looked at health measures like breathing, hospitalization rates and overall muscle strength.

Amylyx's founders acknowledge their drug's limitations. But they, along with others, argue it's a step in the right direction.

"I do think it's incremental, but it's an important increment," said Cudkowicz, who helped lead the investigation of AMX0035. "It is really the first drug to slow loss of function but also prolong survival. That is a big step."

Amylyx has asked regulators in Canada and the U.S. to approve its drug, and plans to do the same in Europe before the end of the year. The FDA has yet to decide whether it will review AMX0035, but if it does, an approval verdict would come sometime in 2022.

"We're really proud of the data we generated," said Justin Klee, one of Amylyx's co-founders. "But there's also so much else to do, and so many other opportunities."

Companies are already at work exploring some of these opportunities. Swiss pharmaceutical giant Novartis is investigating a drug designed to block a protein involved with inflammation in the nervous system. Another drug, from the neuroscience company Alector, targets a protein that performs critical duties for cells both in and outside the brain. That drug is being tested across multiple neurodegenerative disorders, including ALS.

Biogen and its longstanding partner Ionis Pharmaceuticals have attracted attention as well, with one of the few experimental medicines to have moved to the final stage of human testing.

Called tofersen, the medicine was created with a technology that, while not new, has been increasingly validated thanks to a string of recent FDA approvals in other diseases. Tofersen is also the byproduct of a flood of research aimed at the role genes play in ALS.

A recent setback, however, has raised doubts about its chances at ever becoming available outside of clinical trials.

The human genome has been an invaluable source of information in the fight against disease. DNA was first sequenced in the mid-1970s. Less than a decade later, Huntington's disease which is also characterized by the progressive breakdown of nerve cells became the first illness traced back to changes in a specific chromosome.

The first gene associated with ALS, named SOD1, was identified in 1993. Scientists have since uncovered at least several dozen more that look to have some effect on the disease.

These discoveries have encouraged ALS researchers and doctors, especially as technological advances in drugmaking have made it easier to target genes. Tofersen, for example, is a type of precision medicine known as an antisense therapy, meaning it blocks the body's cells from acting on the genetic instructions used to make certain proteins. Specifically, it's designed to inhibit the activity of the SOD1 gene.

"I do think the genetic forms, since we know the targets, will have some of the first big breakthroughs, where we find treatments that really modify the disease," Mount Sinai's Scelsa said.

But, nearly three decades after SOD1 was identified, researchers are still hunting for those breakthroughs. In many cases, drug developers aren't yet sure how best to target these genes, or how to regulate them in a way that positively impacts function or survival. Just two months ago, Biogen and Ionis disclosed results from a late-stage study of tofersen, and while the drug did substantially lower levels of SOD1 protein along with another chemical marker associated with ALS, it wasn't any better than a placebo at slowing down the disease.

Biogen said it will discuss the data with regulators and the broader ALS community to determine tofersen's future.

"Technology has advanced so much it's easy to identify a target," said Kuldip Dave, vice president of research at The ALS Association. "But then, can we really manipulate the target? I think that's the first challenge, the first transition: from target identification to target validation."

Moreover, the mutations tied to ALS have only been observed in a tiny fraction of patients. That fraction could grow with additional genetic research; but in the meantime, it's estimated that at least 90% of cases don't have a known cause.

For those patients, new treatments may be harder to come by.

"In the case of sporadic ALS, we really don't know," said Raymond Roos, director of the University of Chicago's ALS and Motor Neuron Disease Clinic. "We don't know whether there are multiple genes plus environment, or which genes and which environment. We're struggling."

An ALS researcher prepares a petri dish.

Courtesy of The ALS Association

Researchers aren't giving up, though. A search of a federal clinical trial database shows at least five dozen that are evaluating potential ALS drug treatments and currently recruiting participants. Many of these studies are enrolling people with sporadic disease.

Similar to how the treatment of cancer and certain genetic diseases like cystic fibrosis evolved over the past decade, the hope is that therapies like those or like Amylyx's, which was tested against both sporadic and genetic ALS, will improve patients' daily lives and help keep them alive until more specialized drugs are developed.

Technology that's been used in a more targeted fashion may also prove valuable to broader populations. Biogen, for one, is sponsoring a small study of a different antisense therapy aimed at preventing the buildup of a toxic protein observed in many ALS patients.

"The whole field finds that exciting," Cudkowicz said, "because it's basically learning from the tools and technologies for the familial form of the illness [to then have] something that could also be for sporadic disease."

As with other neurodegenerative diseases, researchers seem to agree that the best treatments for ALS will involve a mix of drugs. Yet, identifying and testing these combination therapies can be difficult, as Amylyx found with AMX0035, which itself is a pairing of two drugs.

"As we proceeded, we realized just how many things developing a combination drug makes more challenging," said Josh Cohen, Amylyx's other co-founder.

"With a single drug you have to worry about dose. For a combination drug you have to worry about dose squared," he said. "You have to worry about the levels of A and the levels of B, and the interaction between [them]. And that pervades everything" from toxicology studies to manufacturing.

Another obstacle is that, while many researchers believe treating patients earlier could lead to better outcomes, ALS is hard to diagnose even after symptoms start to show.

Falivena of The ALS Association knows this obstacle well. While training for a marathon, the now 53-year-old said he noticed weakness in his left arm that later spread to his leg. Despite numerous tests and doctor's visits, it took a few years before Falivena was officially diagnosed.

"It's not like you can just take a blood test," he said, "it's more a process of: 'we have to eliminate everything else.' I'm sure no doctor wants to tell a patient they have a terminal disease with no cure, so it makes sense they want to eliminate everything else. But it can be frustrating."

As scientists attempt to work through these problems, one source of hope among patients has been clinical trials.

At the Healey Center, for example, a first-of-its kind "platform" trial testing five experimental therapies at once has enrolled volunteers two- to three-times faster than is typical for an ALS study, according to Cudkowicz.

"It used to be that it was hard to find people to be in trials," she said. "We now have [situations] where the sites can't keep up with the waitlist. And it's not only because we're doing this platform trial; there's so much patient advocacy that's getting the word out."

Patients like Falivena, who participated in the tofersen study and has since enrolled in a subsequent "open-label" investigation of the drug, have found these trials valuable even when they don't succeed.

"There's so much about this disease that makes you feel like you have no control," he said. "This is a level of control; it's a level of hope, positivity, which in itself can help people live better."

And yet, there is also some resentment toward drug developers, which are often reluctant to broaden enrollment in their clinical trials beyond narrowly defined groups they see as most likely to benefit. Biogen, for one, was heavily pressured to expand access to tofersen and eventually did so after initially resisting.

Patient advocates have criticized the FDA as well for not moving fast enough to make promising yet unproven ALS treatments available to patients. The ALS Association even called out the agency earlier this year, after it looked as though Amylyx would have to conduct another clinical trial before asking for approval of AMX0035.

The FDA has since reversed course, allowing Amylyx to submit its drug before completing the additional trial. Falivena said he's optimistic the agency's change of heart means it was listening to patients.

Drugs used in ALS research

Courtesy of The ALS Association

Patients could have more trials to choose from, too, if recent moves by drug companies are any indication. In just the past year and a half, big-name companies like Merck & Co., Bristol Myers Squibb, GlaxoSmithKline and CRISPR Therapeutics have teamed up with smaller biotechs or research institutions in an effort to discover new treatments for ALS.

And on a broader scale, investors have demonstrated a renewed interest in battling brain diseases. Venture capitalists last year poured more than $2 billion into young biotechs focused on neuroscience, a 10-year high, according to data compiled by the trade group BIO. A bill passed last week by the U.S. House of Representatives, meanwhile, would provide $500 million in funding for ALS research via federal grants.

"The number of companies that are calling and having advisory boards is overwhelming," Cudkowicz noted.

While these investments are welcome, time will tell if they actually lead to treatments that improve the lives of ALS patients.

"Sometimes things take longer than one wants," said Roos from the University of Chicago.

"I've been surprised in my scientific career in the sense I thought, 'We're going to have a cure in Huntington's, it's around the block, we know what the mutation is,'" Roos added. "That was a while ago, and we're still working on it. Things are difficult."

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On the hunt for new ALS drugs, researchers see progress, and a long road ahead - BioPharma Dive

CHICAGO, Dec. 9, 2021 /PRNewswire/ -- In-depth analysis and data-driven insights on the impact of COVID-19 included in this Europe cell and gene therapy market report.

The Europe cell and gene therapy market is expected to grow at a CAGR of over 23% during the period 20202026.

Key Insights:

Key Offerings:

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Europe Cell and Gene Therapy Market Segmentation

Europe Cell and Gene Therapy Market by Product

Europe Cell and Gene Therapy Market by End-user

Europe Cell and Gene Therapy Market by Application

Europe Cell and Gene Therapy Market by Geography

The following factors are likely to contribute to the growth of the Europe cell and gene therapy market during the forecast period:

Europe Cell and Gene Therapy Market Vendor Landscape

Many regional vendors are also investing in the new therapy products in Europe. Many regional and local companies are posing a threat to global players due to their innovative and cost-effective products and technologies. This indicates that the market offers tremendous growth opportunities both for existing and future/emerging players. This is due to the presence of a large pool of target patient population with chronic diseases such as cancer, wound management, DFUs, CVDs, and other genetic diseases. The major players are focusing on strategic acquisitions, licensing, and collaboration agreements with emerging players to enter the cell and gene therapy market and to gain access to commercially launched products. They are also focusing on market expansion in existing and new markets to cater to the needs of a growing customer base, widen their product portfolios, and boost their production capabilities to gain traction from end-users.

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Europe Cell and Gene Therapy Market Size to Reach Revenues of USD 2.9 Billion by 2026 - Arizton - PRNewswire

In a new mouse study, scientists at the Icahn School of Medicine at Mount Sinai demonstrate how the activity of one gene, turned on in a newly discovered group of bone-bordering cells, may play an important role in shaping the skull.

The findings are published in the journalNature Communications in a paper titled, Single-cell analysis identifies a key role for Hhip in murine coronal suture development, and led by Greg Holmes, PhD, assistant professor of genetics and genomic sciences at Icahn Mount Sinai.

Craniofacial development depends on formation and maintenance of sutures between bones of the skull, the researchers wrote. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure.

Researchers focused on the cells of the coronal suture, a fibrous joint that connects the front and middle bone plates.

The Holmes lab worked with researchers in the labs of Bin Zhang, PhD, Harm van Bakel, PhD, and Ethylin Wang Jabs, MD, of Icahn Mount Sinai. Together they studied how the genetic activity in the cells of the coronal suture changes during early development.

Their findings suggested that a gene encoding a molecule called hedgehog interacting protein (HHIP) plays a unique role in coronal suture development. The researchers observed the gene was more active in a novel group of mesenchyme cells than it was in osteoblasts.

Using single-cell with bulk RNA-seq analysis we have better defined the distinctive composition of the coronal suture at the transcriptional and cell population levels, the researchers wrote.

Looking toward the future, the researchers hope that advanced single-cell genetic studies like this one will pave the way for a more thorough understanding of how a skull is shaped under healthy and disease conditions.

Our transcriptomic approach greatly expands opportunities for hypothesis-driven research in coronal and other suture development, concluded the researchers.

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Researchers Dig Up Genes and Cells Related to Skull Formation in Mice - Genetic Engineering & Biotechnology News

In the summer of 2015, a 7-year-old named Hassan was admitted to the burn unit of the Ruhr University Childrens Hospital in Bochum, Germany, with red, oozing wounds from head to toe.

It wasnt a fire that took his skin. It was a bacterial infection, resulting from an incurable genetic disorder. Called junctional epidermolysis bullosa, the condition deprives the skin of a protein needed to hold its layers together and leads to large, painful lesions. For kids, its often fatal. And indeed, Hassans doctors told his parents, Syrian refugees who had fled to Germany, the young boy was dying.

The doctors tried one last thing to save him. They cut out a tiny, unblistered patch of skin from the childs groin and sent it to the laboratory of Michele de Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia. De Lucas team used a viral vector to ferry into Hassans skin cells a functional version of the gene LAMB3, which codes for laminin, the protein that anchors the surface of the skin to the layers below.

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Then the scientists grew the modified cells into sheets big enough for Ruhr University plastic surgeons Tobias Hirsch and Maximilian Kueckelhaus to graft onto Hassans raw, bedridden body, which they did over the course of that October, November, and the following January.

It worked better than the boys doctors could have imagined. In 2017, de Luca, Hirsch, Kueckelhaus, and their colleagues reported that Hassan was doing well, living like a normal boy in his lab-grown skin. At the time though, there was still a big question on all their minds: How long would it last? Would the transgenic stem cells keep replenishing the skin or would they sputter out? Or worse could they trigger a cascade of cancer-causing reactions?

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Today, the same team is out with an update. Five years and five months after the initial intervention, Hassan is still, for the most part, thriving in fully functional skin that has grown with the now-teenager. He is attending school, and playing sports with his friends and siblings, though he avoids swimming due to blistering in the areas that werent replaced by the lab-grown skin. One of his favorite activities is a pedal-powered go kart. There are no signs his modified stem cells have lost their steam, and no traces of tumors to be found.

The encouraging follow-up data has been instrumental in moving forward a larger clinical trial of the approach, offering hope to the 500,000 epidermolysis bullosa patients worldwide currently living without treatment options.

We were astonished by the speedy recovery, Kueckelhaus, now at University Hospital Muenster, told STAT via email. But experience from skin transplantation in other settings made him and his colleagues wary of the grafts failing as the months and years wore on. Thankfully, wrote Kueckelhaus, those fears never materialized. We are very happy to be able to prove that none of these complications appeared and the genetically modified skin remains 100% stable. The chances are good that he will be able to live a relatively normal life.

Over the last five years, Hassans team of doctors and researchers has put his new skin through a battery of tests checking it for sensitivity to hot and cold, water retention, pigmentation and hemoglobin levels, and if it had developed all the structures youd expect healthy skin to have, including sweat glands and hair follicles. Across the board, the engineered skin appeared normal, without the need for moisturizers or medical ointments. The only flaw they found was that Hassans skin wasnt as sensitive to fine touch, especially in his lower right leg. This mild neuropathy they attributed not to the graft itself, but to how that limb was prepared doctors used a more aggressive technique that might have damaged the nerves there.

The team also used molecular techniques to trace the cells theyd grown in the lab as they divided and expanded over Hassans body. They found that all the different kinds of cells composing the boys new skin were being generated by a small pool of self-renewing stem cells called holoclone-forming cells, carrying the Italian teams genetic correction.

This was quite an insight into the biology of the epidermis, said de Luca. Its an insight he expects will have huge consequences for any efforts to advance similar gene therapies for treating other diseases affecting the skin. You have to have the holoclone-forming cells in your culture if you want to have long-lasting epidermis, he said.

The approach pioneered by de Lucas team will soon be headed for its biggest clinical test yet, after nearly a decade of fits and starts. They expect to begin recruiting for a multi-center Phase 2/3 trial sometime next year.

De Luca first successfully treated a junctional EB patient in 2005. But then a change to European Union laws governing cell and gene therapies forced his team to stop work while they found ways to comply with the new rules. It took years of paperwork, building a manufacturing facility, and spinning out a small biotech company called Holostem to be ready to begin clinical research again. Hassan came along right as they were gearing up for a Phase 1 trial, but data from the boys case, which was granted approval under a compassionate use provision, convinced regulators that the cell grafts could move to larger, more pivotal trials, according to de Luca.

We didnt cure the disease, he told STAT. But the skin has been restored, basically permanently. We did not observe a single blister in five years. The wound healing is normal, the skin is robust. From this point of view, the quality of life is not even comparable to what it was before.

Continued here:
Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT

Gideon Meyerowitz-Katz is an epidemiologist and writer based in Sydney, Australia. His work covers chronic disease, the pandemic response, and more recently, error detection in science. In this op-ed, he discusses issues with research that have become increasingly apparent during the pandemic.

There are no two ways about it: Science is flawed. Were not talking about the philosophical leanings of science or the origins of white coats and linoleum-floored laboratories, but about the nuts and bolts of the process by which we determine whether things are true or false.

In the decades before the pandemic, scientists spent endless hours wrestling with the painful fact that much of the knowledge base of science and medicine is reliant on research that is flawed, broken, or potentially never occurred at all.

Science has a gap between its mechanics and outputs. The mechanics of science are fine. The machines always get bigger and more efficient. New tools are always developed. Techniques become more sophisticated over time, and more knowledge is acquired.

The outputs of science are not. The culture of academia demands publication and warrants little retrospection about potential errors this means that mistakes are rarely corrected, and even outright fraud is often left undetected in academic literature.

And then along came a pandemic, and the gaps in science widened to an inescapable chasm. While biomedical research has had obvious and immediate success in COVID-19 mitigation, it has been accompanied by an enormous tidal wave of garbage, which instantly overwhelmed our garbage mitigation mechanisms.

From fraud to wasteful research to papers so error-filled that it is amazing that theyve been published, the pandemic has produced a tidal wave of woeful scientific output that has, nevertheless, had staggering consequences for peoples lives.

Take ivermectin. It is an amazingly successful antiparasitic medication that has treated literally billions of people in the time since it was invented, and it has almost eliminated some parasitic diseases from the world.

It has also been globally promoted as a cure for COVID-19 by a group of passionate fans. It is likely that more ivermectin has been taken to prevent or treat COVID-19 than any other single medication, except perhaps dexamethasone.

And yet, we do not know if ivermectin is actually useful in the treatment of COVID-19 at all.

A recent review from the Cochrane collaboration long considered the gold standard in medical research concluded that ivermectin should not be used for the treatment or prevention of COVID-19 outside of well-conducted clinical trials, which is a stark contrast to the hundreds of millions of doses still being taken for those exact reasons.

In early 2020, people were desperate for any kind of treatment for COVID-19. A melange of partial evidence emerged.

This included: a laboratory study showing that the drug acted as a strong antiviral in a petri dish, a study in a French nursing home where the residents took ivermectin to treat a scabies outbreak and seemed to subsequently enjoy higher survival rates, and preprint reporting that ivermectin reduced the mortality from COVID-19 by 90%.

All three were weak evidence in different ways. Single in vitro studies are very poorly predictive of eventual clinical outcomes, and the nursing home paper was an accidental and uncontrolled observational study what if the residents had never been exposed to SARS-CoV-2 in the first place?

The clinical study was entirely fabricated and later withdrawn from the preprint server, subsequent to great scandal.

The ivermectin story somehow got even worse from there. In late 2020, studies started popping up showing what can only be described as simply incredible results for the medication a 90% mortality benefit or a 100% reduction in cases when used as a prophylactic.

After nearly a year, myself and other data sleuths demonstrated that many of these studies probably never happened, but the damage was well and truly done long before the first fake paper was retracted.

A meta-analysis of ivermectin, which is usually considered the gold standard of research practices, found a huge benefit for the drug. However, the paper has not been corrected, even though the studies underlying its results were found to be likely fraudulent.

In any other discipline media, government, private enterprise such an analysis would be taken down with apologies immediately. Instead, the paper is allowed to stand as a testament to the general disinterest of the scientific world in correcting errors.

This story couldve been told very differently. Imagine a world where the initial laboratory paper came with a disclaimer, where the fraudulent preprint was looked on with skepticism immediately, and where the positive trials were assessed for fraud before they were even published.

Instead, at every stage, the process of highlighting concerns with data is ignored, with peer-review being the only flimsy barrier to publication for terrible research.

When we most needed effective fact-checking, our grand institutions of scientific research instead reviewed studies in a matter of days, if not hours, and posted fraudulent studies online to be shared across the world.

Its tempting to say that research into ivermectin is uniquely flawed, but thats clearly not true realistically, it would be remarkable if a broken system produced only one failure.

Trials of favapiravir, another repurposed COVID-19 medication, have recently been retracted due to data concerns.

There are now nearly a dozen studies looking at whether vitamin D has a benefit in COVID-19 that have been corrected or withdrawn entirely over the last 18 months.

The website Retraction Watch keeps a running tally of the pandemic-related studies that have been retracted. As of publication, the figure is 199 and growing every week.

Even worse, those are just the papers that people have looked into. Errors in science are rarely noticed because there is simply no reward for pointing out other peoples mistakes.

If we were to start looking at all of the useless, wasteful, terribly done research, we might expand that number to thousands, or even tens of thousands of papers.

There are published ecological studies of ivermectin where researchers compare entire countries drug use and COVID-19 mortality. These studies use mass drug administration protocols as their measure of the number of people who received ivermectin during the pandemic. This is despite those protocols mostly being disrupted or canceled early in 2020.

One study of vitamin D was retracted from the SSRN preprint server after it became clear that the authors had incorrectly labeled it as a randomized trial, though they had not randomized the participants at all. It has since been republished largely unchanged, with no mention of the previous retraction at all in the final paper.

None of this is to say that there is no good science. The vaccine trials alone are perhaps the most impressive scientific work that has ever been done, with efficacious immunizations developed, tested, and trialed in under 1 year.

The RECOVERY and SOLIDARITY clinical trials, which looked at repurposed drugs to treat COVID-19, have almost certainly saved millions of lives during the pandemic.

The problem is that large, well-conducted clinical trials are far from the norm. In a recent systematic review of hydroxychloroquine for COVID-19, the median number of people enrolled per arm in clinical trials was 59 one study looked at just two patients.

Without even carefully assessing these studies, we can say that most of them were probably a waste of time.

Indeed, if you look at the meta-analytic model from this review, virtually our entire knowledge of hydroxychloroquine for COVID-19 comes from just two studies, which recruited about 70% of all the people whom this drug had ever been tested on.

This is despite nearly 300 trials of the drug registered on clinicaltrials.gov, and the highest research spend of any single medication in the early pandemic.

If all of those tiny trials had been linked together, they may have achieved something useful, but instead, were left with two good studies and a smattering of largely pointless research.

All of this is, perhaps, the predictable outcome of a system that pushes publication above all else and punishes error-checking with disdain, scorn, and lawsuits. Publishing a terrible study can earn you praise and promotions; at worst, it might end up a line on your CV somewhere.

Checking studies for errors publicly earns you a steady payment of hate mail and death threats, and it nets you none of the citations, publications, and awards that academia regards as important.

Science has some enormous issues. Unless we can find a way to reward error-checking with actual money, we will continue to accept that a worrying proportion of our research output the studies that we use to make life-and-death decisions is either fake or incredibly problematic.

While it is tempting to think of this as a tedious problem among eggheads, that couldnt be further from the truth.

It is not unlikely that you or your family have personally been impacted by bad research during COVID-19 maybe you were given hydroxychloroquine during a hospital stay or took some metformin just in case. Perhaps you live in a place that reopened schools based on a study with mathematical errors or were told that masks constituted child abuse due to a paper that was later withdrawn.

Overall, there is a real impact of bad science in our everyday lives that the pandemic has thrown into stark relief.

Worse still, we know another pandemic is coming eventually. If we dont fix these issues now, the next time a new disease spreads through our world, we will be doomed to repeat the mistakes of COVID-19. And that is perhaps the most worrying thought of all.

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The perils of flawed research and the ivermectin debacle - Medical News Today

Basel, 13 December 2021 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the launch of the AVENIO Edge System, a core component of Roches strategy to advance sequencing technologies. Built on best-in-class foundational capabilities to deliver a fully-automated, integrated sequencing solution.

The AVENIO Edge System is a pre-analytical platform for sequencing library preparation, target enrichment and quantification steps that deliver integrated, end-to-end control with reliable, consistent high-quality results.

Roche is committed to developing diagnostic solutions with the goal of providing the healthcare community with faster and more accurate medical information to predict risk and detect disease, said Thomas Schinecker, CEO Roche Diagnostics. We are pleased to offer next-generation sequencing laboratories and translational researchers the new automated AVENIO Edge System that aims to drastically reduce human error and help ensure fast, reliable and accurate results.

Next-generation sequencing samples are precious. Every step of sample preparation has the potential to impact results. The AVENIO Edge Systems high reproducibility and low error rate can support the goal of reducing the number of rejected samples which otherwise might have to be re-collected.

The new AVENIO Edge System offers ready-to-use components in addition to customisable workflow parameters, making it a scalable, cost-efficient solution for sequencing laboratories seeking high performance and agility. With a setup to initiation of 20 minutes, this walkaway system demonstrated more than a 96 percent lower error opportunity and an 84 percent reduction in hands-on time.

The AVENIO Edge System will be available at select locations worldwide with timelines that vary country by country.

About the AVENIO Edge SystemThe AVENIO Edge System is Class I, In Vitro Diagnostics (IVD), 510(k) exempt, in the US. It is Class A in the EU in accordance with EU Regulation 2017/746 (IVDR) of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices. At launch, the AVENIO Edge Instrument can be used for Research Use Only (RUO) workflows. Consumables are General Laboratory Use (GLU). Compatible reagents and workflows are Research Use Only (RUO). Not for use in diagnostic procedures.

The AVENIO Edge System simplifies next-generation sequencing (NGS) and elevates automated sample preparation with integrated workflows, reagents, barcoded consumables and connectivity to enable reliable, high-quality results and the freedom to do more.

The AVENIO Edge System delivered high sequencing performance and demonstrated high uniformity, specificity and reproducibility in our in-house technical validation and early customer studies. At an early evaluation study site, the AVENIO Edge System replaced 384 manual steps while preparing 24 DNA libraries in one run versus manually preparing 24 DNA libraries.

The AVENIO Edge System is a fully automated liquid handling technology consisting of all-in-one hardware and traceable solutions that guides the operators through the process, provides real-time tracking of samples and delivery of the results to the laboratory information system (LIS). It is intended for routine laboratory tasks and designed to support multiple library prep, target enrichment and quantification workflow steps with customizable parameters. The AVENIO Edge System offers a wide set of modular, barcoded and ready-to-run reagents in addition to customizable workflow parameters, making it a scalable, cost-efficient solution for sequencing laboratories seeking high performance and agility.

About Roche Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics, as well as growing capabilities in the area of data-driven medical insights help Roche deliver truly personalised healthcare. Roche is working with partners across the healthcare sector to provide the best care for each person.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. In recent years, the company has invested in genomic profiling and real-world data partnerships and has become an industry-leading partner for medical insights.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the thirteenth consecutive year, Roche has been recognised as one of the most sustainable companies in the pharmaceutical industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2020 employed more than 100,000 people worldwide. In 2020, Roche invested CHF 12.2 billion in R&D and posted sales of CHF 58.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

All trademarks used or mentioned in this release are protected by law.

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com

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Roche launches the AVENIO Edge System to simplify and automate next-generation sequencing sample preparation, reduce human error and advance precision...

Dr. Koichi Kobayashi, adjunct professor at the College of Medicine and lead author of the paper.

Texas A&M College of Medicine

The immune system is a complex network of cells and proteins that is designed to fight off infection and disease, especially those likethe coronavirus, or SARS-CoV-2, that can cause numerous issues in the human body. But many individuals are still at risk of being infected with the coronavirus, letting it replicate in the body and further transmitting to other individuals.

The underlying mechanism of how SARS-CoV-2 escapes from the immune system has been poorly understood. However, researchers from theTexas A&M University College of Medicine and Hokkaido University have recently discovered a major mechanism that explains how SARS-CoV-2 can escape from the immune system and replicate in the human body.Their findings were recently publishedin the journalNature Communications.

We found that the SARS-CoV-2 virus carries a suppressive gene that acts to inhibit human gene in the immune system that is essential for destroying infected cells, said Dr. Koichi Kobayashi, adjunct professor at the College of Medicine and lead author of the paper.

Naturally, the cells in a humans immune system are able to control virus infection by destroying infected cells so that the virus cannot be replicated. The gene that is essential in executing this process, called NLRC5, regulates major histocompatibility complex (MHC) class I genes, which are genes that create a pathway that is vital in providing antiviral immunity.Kobayashi and his colleagues discovered this in 2012.

During infection, the amount and activity of NLRC5 gene become augmented in order to boost our ability of eradication of viruses, Kobayashi said. We discovered that the reason why SARS-CoV-2 can replicate so easily is because the virus carries a suppressive gene, called ORF6, that acts to inhibit the function of NLRC5, thus inhibiting the MHC class I pathway as well.

Kobayashi, who holds a joint appointment as a professor at Hokkaido University in Japan, collaborated withPaul de Figueiredo, associate professor in the Department of Microbial Pathogenesisand Immunology at the College of Medicine, on this paper.

Kobayashi and his teams discovery shed light on the mechanism to how SARS-CoV-2 can replicate in the human body and can potentially lead to the development of new therapeutics to prevent the coronavirus from escaping the immune system and replicating in the body.

Although the introduction of COVID-19 vaccines, such as the Pfizer and Moderna vaccines, can lower an individuals chance of contracting the virus, there is currently no permanent therapy that can entirely prevent a human from contracting SARS-CoV-2.

We hope that this new discovery will allow us to develop a new drug that can block this gene so our immune system will be able to fight off the coronavirus for good, de Figueiredo said.

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Why Does The COVID-19 Virus 'Escape' From Our Immune Systems? - Texas A&M University Today

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Graphite Bio, Inc. (Nasdaq: GRPH), a clinical-stage, next-generation gene editing company focused on therapies that harness targeted gene integration to treat or cure serious diseases, today presented a trial-in-progress poster for the companys Phase 1/2 CEDAR trial for GPH101, an investigational therapy designed to directly correct the genetic mutation responsible for sickle cell disease (SCD). The poster is being presented at the 63rd American Association of Hematology (ASH) Annual Meeting and Exposition taking place virtually and at the Georgia World Congress Center in Atlanta from December 11-14. GPH101 was recently granted orphan drug designation from the U.S. Food and Drug Administration (FDA).

Sickle cell disease is a devastating illness for which a cure is desperately needed. By directly correcting the mutation that causes sickle cell disease, we believe that GPH101 has the potential to be a one-time cure that restores normal physiology and alleviates the life-threatening morbidities associated with the disease, said Josh Lehrer, M.Phil., M.D., chief executive officer at Graphite Bio. We are excited to share details about our CEDAR clinical trial for GPH101, in which we recently enrolled our first patient, and we look forward to continuing to advance GPH101s development in anticipation of sharing initial proof-of-concept data by the end of next year.

The trial-in-progress poster is being presented by Julie Kanter, M.D., associate professor of medicine and co-director of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham and an investigator in the CEDAR trial.

While allogeneic transplant is the only available cure for sickle cell disease, the procedure has several limitations, mainly lack of available donors and risk of graft-versus-host disease. Other available therapies are considered palliative as they do not specifically reverse end-organ damage. This type of gene therapy reducing sickle hemoglobin production at the same time as restoring adult hemoglobin expression through direct gene correction would be an ideal curative option in sickle cell disease, said Dr. Kanter. As an investigator in the CEDAR trial, I look forward to assessing GPH101s potential to be a curative option for patients.

The CEDAR trial is an open-label, single-dose, multi-site clinical trial evaluating GPH101 in approximately 15 participants with severe SCD. GPH101 is an autologous hematopoietic stem cell therapy developed using Graphite Bios next-generation targeted gene integration platform, which uses high-fidelity Cas9 and a non-integrating DNA template to precisely find the genetic mutation in the beta-globin gene and directly correct the mutation through the cells natural homology directed repair (HDR) cellular pathway. GPH101 has demonstrated in preclinical studies the potential to permanently reduce sickle hemoglobin (HbS) production and restore adult hemoglobin (HbA) expression. The trial-in-progress poster provides an overview of the GPH101 treatment process, which includes local stem cell selection and cryopreservation before shipment to a central manufacturing facility.

The primary objective of the CEDAR trial is to evaluate the safety of GPH101. Secondary objectives include pharmacodynamic and efficacy read-outs such as levels of HbA, HbS and total hemoglobin and effect on clinical manifestations such as vaso-occlusive crisis and acute chest syndrome. Additionally, characterization of gene correction rates, changes in the function of organs like the brain, heart, kidney and liver, and assessment of red blood cell health and function will be explored.

The poster is now available on the ASH website and on the Graphite Bio website here. Details are as follows:

Poster Session: 801. Gene Therapies: Poster IPoster #1864: CEDAR Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe SCDPresenting Author: Julie Kanter, M.D., University of Alabama at BirminghamDate/Time: Saturday, December 11, 2021, 5:30-7:30 p.m. ETLocation: Hall B5 (Georgia World Congress Center)

About Sickle Cell Disease (SCD)

SCD is a serious, life-threatening inherited blood disorder that affects approximately 100,000 people in the United States and millions of people around the world, making it the most prevalent monogenic disease worldwide. SCD is caused by a single mutation in the beta-globin gene that leads red blood cells to become misshapen, resulting in anemia, blood flow blockages, intense pain, increased risk of stroke and organ damage, and reduced life expectancy of approximately 20-30 years. Despite advancements in treatment and care, progressive organ damage continues to cause early mortality and severe morbidity, highlighting the need for curative therapies.

About GPH101

GPH101 is an investigational next-generation gene-edited autologous hematopoietic stem cell (HSC) therapy designed to directly correct the genetic mutation that causes sickle cell disease (SCD). GPH101 is the first investigational therapy to use a highly differentiated gene correction approach that seeks to efficiently and precisely correct the mutation in the beta-globin gene to decrease sickle hemoglobin (HbS) production and restore normal adult hemoglobin (HbA) expression, thereby potentially curing SCD.

Graphite Bio is evaluating GPH101 in the CEDAR trial, an open-label, multi-center Phase 1/2 clinical trial designed to assess the safety, engraftment success, gene correction rates, total hemoglobin, as well as other clinical and exploratory endpoints and pharmacodynamics in patients with severe SCD.

About Graphite Bio

Graphite Bio is a clinical-stage, next-generation gene editing company harnessing high efficiency targeted gene integration to develop a new class of therapies to potentially cure a wide range of serious and life-threatening diseases. Graphite Bio is pioneering a precision gene editing approach that could enable a variety of applications to transform human health through its potential to achieve one of medicines most elusive goals: to precisely find & replace any gene in the genome. Graphite Bios platform allows it to precisely correct mutations, replace entire disease-causing genes with normal genes or insert new genes into predetermined, safe locations. The company was co-founded by academic pioneers in the fields of gene editing and gene therapy, including Maria Grazia Roncarolo, M.D., and Matthew Porteus, M.D., Ph.D.

Learn more about Graphite Bio by visiting http://www.graphitebio.com and following the company on LinkedIn.

Forward-Looking Statements

Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act). These statements may be identified by words such as aims, anticipates, believes, could, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our gene editing platform and our product candidates, and the timing for treating the first patient in the Phase 1/2 CEDAR trial of GPH101 and the availability of initial proof-of-concept data, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions.

Any forward-looking statements in this press release are based on Graphite Bios current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in patient enrollment and in the initiation, conduct and completion of our planned clinical trials. These risks concerning Graphite Bios programs and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report. Graphite Bio is providing the information in this press release as of this date and explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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Graphite Bio Presents Overview of Phase 1/2 CEDAR Trial Evaluating Investigational Gene Editing Therapy GPH101 in Sickle Cell Disease at 63rd ASH...