Stem Cell Clinic

Can progenitor cells go further than gene therapy in retinal disorders? A biotech’s answer shines in PhIIb – Endpoints News

By the time the FDA approved Luxturna the pioneering gene therapy for an inherited retinal disease Henry Klassen had been researching and treating the group of diseases known as retinitis pigmentosa for more than 20 years.

Spark Therapeutics success there had not just inspired a $4.3 billion takeover by Roche, it had also emboldened other biotechs pursuing a therapy that would deliver one of the genes tied to different variations of the disorder. Nightstar Therapeutics subsequently scored its own buyout with Biogen, and MeiraGTx recently posted early but exciting data on its J&J-partnered program.

But Klassen went a different way.

Catching on the stem cell craze right at the turn of the millennium, he took inspiration from scientists who transplanted neural progenitor cells into the retina and developed a method to grow retinal progenitor cells instead as a therapy. Starting out as the director of stem cell research at the Childrens Hospital of Orange County, he continued the work at the University of California, Irvine, eventually spinning out a biotech dubbed jCyte in 2012.

Over the weekend jCyte reported positive Phase IIb results from what they call one of the largest studies ever conducted in RP, suggesting that patients on the treatment saw improved functional vision compared to the placebo group.

The credit to the gene therapies is that theyre actively trying to fix the gene underlying the problem. Thats very commendable, and were not doing that, Klassen told Endpoints News. But our treatment as it stands should have impact across a variety of different genotypes.

The study enrolled a total of 84 patients, of whom 74 were included for the final analysis. For each patient on the primary endpoint of best corrected visual acuity (measured with glasses on), the mean change from baseline to month 12 for the sham, low dose and high dose arms were +2.81, +2.96, and +7.43 letters, respectively.

In a post hoc analysis for a target subgroup, the difference was even more prominent: +1.85, -0.15, and +16.27 letters, respectively.

There was one serious adverse event in the low dose arm, but jCyte said the grade 3 ocular hypertension resolved with treatment and other side effects were generally minor.

CEO Paul Bresge noted that the target subgroup analysis was intended to hammer out the criteria they might use to recruit patients into Phase III which would likely have a similar design and use the same primary endpoint of BCVA, the gold standard in the context of FDA. The late-stage trial is slated for 2021.

We did enroll a very wide patient population into our Phase IIb, including patients that had vision anywhere from 20/80 to 20/800, just to learn which patients would potentially be the best responders, he said.

The target subgroup is characterized by having reliable fixation on the study eye, and a study eye that does not have significantly worse BCVA (15 letters) than the fellow eye.

He added that investigators also observed encouraging results with the secondary endpoints such as low light mobility, contrast sensitivity kinetic visual fields and a vision function questionnaire, although the data werent disclosed.

Typically people think about the disease as a narrowing of this peripheral vision in a very nice granular way, but thats actually not what happens, he said about the visual fields finding. What happens in the disease is that patients lose like islands of vision. So what were doing in our tests is actually measuring [] islands that the patients have at baseline, and then what were seeing after treatment is that the islands are expanding. Its similar to the way that one would track, lets say a tumor, in oncology of course were looking for the opposite effect. Were looking for the islands of vision to expand.

The therapy works primarily by preserving photoreceptors, Klassen posits, not by generating new ones. But what he thinks is happening is that photoreceptors are regenerating the outer segment if photoreceptors are radios, these would be the antenna thereby regaining some function.

That could position it as a treatment for a different stage of the disease than Sparks or Nightstars. Klassen, whos also researching retinal reconstruction using stem cells, is happy to not view it through the competitive lens.

If you look into the future, one could imagine that gene therapies will be most effective very early in the course of a disease before photoreceptors are lost, he said. Then as photoreceptors begin to be lost anyway, if that happens, then a therapy like ours would become extremely valuable. And if ours starts to lose power late in the course of a disease, maybe cell transplantation under the retina could have a role.

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Can progenitor cells go further than gene therapy in retinal disorders? A biotech's answer shines in PhIIb - Endpoints News

BrainStorm Cell Therapeutics to Announce Second Quarter Financial Results and Provide a Corporate and R&D Update – Stockhouse

NEW YORK, July 27, 2020 /PRNewswire/ -- BrainStorm-Cell Therapeutics Inc. (NASDAQ: BCLI), a leader in developing innovative autologous cellular therapies for highly debilitating neurodegenerative diseases, announced today that the Company will hold a conference call to update shareholders on financial results for the second quarter ended June 30, 2020, and provide a corporate update, at 8:00 a.m., Eastern Daylight Time (EDT), on Wednesday, August 5 2020.

On the call, BrainStorm CEO Chaim Lebovits will present a corporate update, including details on the timeline for the data readout of the Company's Phase 3 pivotal trial studying the safety and efficacy of NurOwn® (MSC-NTF cell) in people with ALS. In addition, Dr. Revital Aricha. Brainstorm's Vice President of Research and Development, will provide an R&D update including recently announced data from the Company's groundbreaking preclinical study evaluating NurOwn-derived exosomes for the treatment of COVID-19 ARDS.

Thereafter, senior management officers will join the call for a Q&A session. Participants are encouraged to submit their questions prior to the call by sending them to: q@brainstorm-cell.com. Questions should be submitted by 5:00 p.m. EDT, Monday, August 3, 2020.

Teleconference Details BRAINSTORM CELL THERAPEUTICS 2Q 2020

The investment community may participate in the conference call by dialing the following numbers:

Participant Numbers:

Toll Free: 877-407-9205 International: 201-689-8054

Those interested in listening to the conference call live via the internet may do so by visiting the "Investors & Media" page of BrainStorm's website at http://www.ir.brainstorm-cell.com and clicking on the conference call link.

Those that wish to listen to the replay of the conference call can do so by dialing the numbers below. The replay will be available for 14 days.

Replay Number:

Toll Free: 877-481-4010 International: 919-882-2331 Replay Passcode: 36017

Teleconference Replay Expiration:

Wednesday, August 19, 2020

About NurOwn®

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and initiated enrollment in March 2019.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) started enrollment in March 2019. For more information, visit the company's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTS

Investor Relations: Preetam Shah, MBA, PhD Chief Financial Officer BrainStorm Cell Therapeutics Inc. Phone: +1-862-397-1860 pshah@brainstorm-cell.com

Media: Paul Tyahla SmithSolve Phone: +1-973-713-3768 Paul.tyahla@smithsolve.com

View original content:http://www.prnewswire.com/news-releases/brainstorm-cell-therapeutics-to-announce-second-quarter-financial-results-and-provide-a-corporate-and-rd-update-301100141.html

SOURCE Brainstorm Cell Therapeutics Inc

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BrainStorm Cell Therapeutics to Announce Second Quarter Financial Results and Provide a Corporate and R&D Update - Stockhouse

HKUMed reveals pathogenic gene of carpal tunnel syndrome providing new directions for prevention and treatment – Mirage News

The LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with China-Japan Union Hospital of Jilin University, Mainland China, Harvard University and National Institutes of Health (NIH), U.S., have discovered that genetic mutation is one of the key risk factors of carpal tunnel syndrome (CTS). The study revealed a previously unrecognized mechanism in CTS pathogenesis and provided new insight into the development of new preventive and therapeutic strategies. The findings are now published in the leading multidisciplinary science journal Nature Communications [link to the publication].

Background

CTS, sometimes also known as mouse hand, is a fairly common condition in people, who have repeated and forceful movements of the hand and the wrist in their work and daily life, such as I.T. professionals, construction workers, cleaners and housewives. CTS is characterized by pain, numbness, tingling and weakness in the hand and the wrist due to excessive pressure on the median nerve within the carpal tunnel, which is often caused by swelling and thickening of soft connective tissues surrounding the median nerve.

CTS is a progressive disorder that can worsen without appropriate treatment, leading to nerve damage, permanent muscle atrophy, or loss of hand function. It is estimated to affect 1-5% of the general population[1] and is a leading cause of work disability. It is more common in people older than 40, and women are more likely to develop the condition than men; and more than one-half of cases will experience bilateral symptoms. According to the 0.1-0.3% incidence of CTS in U.S., the number of new cases in Hong Kong is estimated to be at least 7,000 per year[2].

In the past, most people believed that environmental factors, such as repetitive use of hands and wrists, were the main causes of CTS. However, familial occurrence of CTS in 1739% of cases[3] [4], a number of CTS families reported over the world and a large twin study that found an approximate 46% genetic contribution[5], suggest that genetic factors significantly influence CTS susceptibility. Nevertheless, so far, no causal genes were identified.

Research findings

It is challenging to study the pathogenesis of complex human diseases due to their multifactorial and polygenic nature, but Mendelian forms of common diseases have proven invaluable in identifying disease genes and elucidating pathogenic mechanisms. In this study, the research team analyzed two large pedigrees of CTS (nearly 100 cases) by using clinical, genetic, histological and biochemical methods. They discovered that mutations in a gene called COMP caused CTS in these two families.

COMP is highly expressed in the soft connective tissues surrounding the median nerve. The mutant COMP induced cellular stress response, leading to an accumulation of fibrotic and adipogenic cells. Eventually, fibrotic connective tissues in the human carpal tunnel become thickened and swollen, thus compressing the median nerve in causing CTS. Scientists further generated a CTS animal model, which recapitulated the progressive phenotype of human patients, and found that injury could significantly accelerate CTS onset.

Our findings provide solid evidence that genetic mutations can cause CTS, and COMP is the first identified causative gene. We also revealed cellular stress response as a novel mechanism underlying the pathogenesis of CTS, which lays the foundation for the future development of new treatments by inhibiting such response, said Dr Gao Bo, Assistant Professor of the School of Biomedical Sciences, HKUMed, who led the research.

The onset time and symptoms of familial patients are usually earlier and stronger than sporadic patients because the major risk factor is intrinsic (e.g. genetic) rather than extrinsic (e.g. life style, occupation). But sporadic CTS more likely result from combined effects of genetic susceptibility and environmental factors. When consulting a doctor, the patient should inform whether there are other affected members in his/her family, which will assist in diagnosis. I would also suggest, when introducing CTS to the public, the Hospital Authority should include genetic predisposition as one of the important risk factors of CTS, Dr Gao said.

About the Research Team

In collaboration with multiple institutions, the research was led by Dr Gao Bo, Assistant Professor of the School of Biomedical Sciences, HKUMed. Dr Li Chun-yu, China-Japan Union Hospital of Jilin University, Mainland China and Dr Wang Ni, Research Associate, School of Biomedical Sciences, HKUMed are co-first authors. Key international collaborators include Professor Yang Ying-zi, Harvard University, U.S.; Professor Cui Shu-sen, China-Japan Union Hospital of Jilin University, Mainland China and Dr Alejandro Schaffer, National Institutes of Health, U.S.. Other HKU scientists contributing to the research include Professor Danny Chan, S Y and H Y Cheng Professorship in Stem Cell Biology and Regenerative Medicine, Interim Director of School of Biomedical Sciences, HKUMed and Assistant Dean (Research postgraduate studies), HKUMed; Dr Wang Jin, Post-doctoral Fellow, School of Biomedical Sciences, HKUMed; Dr Wang Cheng, former Post-doctoral Fellow, School of Biomedical Sciences, HKUMed; and Ms Vanessa Choi Nga-ting, Technician, School of Biomedical Sciences, HKUMed.

The work was supported in part by Health and Medical Research Fund (Project #05160946) in Hong Kong.

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HKUMed reveals pathogenic gene of carpal tunnel syndrome providing new directions for prevention and treatment - Mirage News