Gangliosidoses

Unique international partnership marks significant momentum for new gene therapy entity PHILADELPHIA, Oct. 8, 2024 /PRNewswire/ -- Today, GEMMA Biotherapeutics ("GEMMABio") – a new therapeutics company founded by gene therapy pioneer Dr. Jim Wilson – announced a major agreement with the Oswaldo Cruz Foundation ("Fiocruz"), a public health research institution that is part of the Ministry of Health of Brazil and has extensive experience in biomanufacturing. GEMMABio partnered with Fiocruz – which is the main supplier of immunobiologics, biopharmaceuticals and diagnostics to the Brazilian Ministry of Health – to sponsor research that will bring gene therapy treatments to the people of Brazil under the Sistema Único de Saúde (SUS), Brazil's publicly funded health care system. Fiocruz will fund up to $100 million, which will be used to conduct clinical research and manufacturing – ultimately securing approval for programs that will allow the country to increase distribution of rare disease treatments and at a more affordable cost. "By combining our resources and knowledge, this collaboration represents a major advancement in making gene therapies accessible to more patients quickly and at a fraction of the typical cost," said Dr. Wilson, who will serve as President and CEO of GEMMABio. "We are optimistic that this deal will serve as a global example for expanding access to advanced medical therapies as well as pursuing non-traditional ways to capitalize biotech companies." A key component of the partnership will involve tech transfer, replicating GEMMABio's manufacturing technologies and process so that the companies can collaborate on programs and production in Brazil and for Fiocruz to utilize with other sponsors and programs. The agreement will also fund clinical development activities in Brazil for six core programs, including GM1 gangliosidosis (GM1), Krabbe Disease, Metachromatic leukodystrophy (MLD), and three unnamed programs. In return for their financial support, Fiocruz will be able to license related treatments to supply the Brazilian public health system. "Brazil has the largest public health system in the world, offering health services and products to more than 200 million people. We are very proud to bring this innovation to the Brazilian system, a technology that was previously restricted to those with higher incomes, will now be accessible to the entire Brazilian population" said Marco Krieger, Vice President of Production and Innovation in Health, Fiocruz. About GEMMABio GEMMABio is a therapeutics company focused on speeding the research of and global access to life-changing advanced therapies for those living with rare diseases. The company will provide research and product development functions to bring gene therapy discoveries from the bench to the bedside faster and affordably. GEMMABio is led by gene therapy industry pioneer Jim Wilson and his team of experts, who previously conducted their work in academia. Wilson is also the Chairperson of Franklin Biolabs, a Contract Research Organization. The collective goal of the two affiliated companies is to translate innovative scientific work into clinical trials, to then commercialize and distribute the new therapies around the world to patients who need them most. For more information, please visit gemmabiotx.com. About Fiocruz The Oswaldo Cruz Foundation (Fiocruz) is the largest biomedical research institution in Latin America, which also produces vaccines, medicines and in vitro diagnostics (IVD) to supply the Unified Health System (SUS, acronym in Portuguese for the Brazilian public health system). Linked to the Brazilian Ministry of Health, the Foundation was created on May 25, 1900 to initially manufacture serums and vaccines against bubonic plague. Since then, the institution has experienced an intense trajectory, which is intertwined with the development of public health in Brazil. Currently, Fiocruz is installed in 10 states, in addition to the Federal District, and has an office in Maputo, capital of Mozambique, Africa. In addition to the institutes based in Rio de Janeiro, the Foundation maintains units in the Northeast, North, Southeast and South regions of Brazil, and offices in Ceará, Mato Grosso do Sul, Piauí and Rondônia. In total, there are 16 technical-scientific units, focused on teaching, research, innovation, assistance, technological development and extension in the field of health. For more information, visit . Contact: Scott Hoeflich [email protected] SOURCE GEMMA Biotherapeutics and Franklin Biolabs WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

A gene therapy pioneer thinks he has a solution to the field’s struggle to commercialize breakthrough cures: Go global. Jim Wilson’s Philadelphia-based company GemmaBio on Tuesday announced up to $100 million in funding to manufacture and test six gene therapies in Brazil. The company’s plan, funded by Brazil’s Ministry of Health, looks to produce the potential medicines at a fraction of the millions of dollars that they often cost. Drugmakers big and small have found that the price tag for gene therapies made them a tough sell, or impractical to develop. In an interview, Wilson told Endpoints News that he’ll soon board flights to Korea, Saudi Arabia and other countries in hopes of making similar partnerships with organizations there. “What I’d like to be remembered for, and this is the chapter that we’re working on now that we have not yet achieved, is to be an advocate for global access of genetic medicines,” Wilson said. Wilson, initially known for a tragedy that halted the gene therapy field 25 years ago, managed a comeback by leading an influential group at the University of Pennsylvania. His academic unit developed methods for delivering genes to cells, a major step in breakthrough therapies, like Novartis’ therapy Zolgensma for spinal muscular atrophy. That progress, however, couldn’t overcome another trend: Companies began to abandon rare disease medicines that were deemed commercially unviable. Endpoints reported last year that dozens of companies had shelved dozens of treatments for rare conditions, often citing the cost of development and commercial uncertainty. Those failures led Wilson to conclude that the existing model for those rare diseases and their tiny groups of patients had reached its limit. “We had sort of run our course of what we can do in an academic setting,” Wilson said. In late July, the University of Pennsylvania board of trustees approved a spinout of Wilson’s research group that became GemmaBio. The company is initially working on eight therapies, three of them licensed from Passage Bio, a company Wilson co-founded in 2018. Under a licensing deal reached in August, GemmaBio paid Passage Bio $10 million upfront, and the agreement calls for additional milestone payments. Many drugmakers have turned away from gene therapies aimed at rare conditions because of the limited size of the markets. Wilson believes that GemmaBio’s global approach will maximize the number of patients treated. To reach them, the company is zeroing in on countries that look to benefit the most from its potential medicines. One of the diseases it’s targeting — a fatal disorder called GM1 gangliosidosis that destroys neurons in the brain and spinal cord — is 10 times as common in Brazil compared to the rest of the world. “You have to go to where the prevalence is higher to conduct the clinical trials,” Wilson said. For GemmaBio, Brazil made sense in additional ways. The company is partnering with Fiocruz, a division of Brazil’s Ministry of Health, that has built up the country’s biomanufacturing sector to lessen costs and be closer to patients. During the pandemic, Fiocruz partnered with AstraZeneca to locally produce the company’s Covid-19 vaccine. Fiocruz has also worked with a nonprofit to domestically manufactur e CAR-T therapies. Fiocruz’s up to $100 million in funding to GemmaBio will go toward clinical trials and manufacturing, with an eye toward securing approval for the six therapies in the region and potentially other countries. “Brazil could be a foothold to gain broader access throughout Latin America,” Wilson said. In exchange for Fiocruz’s financial support, the organization has the option to license related treatments to supply the Brazilian public health system. Often, drugmakers first worry about FDA clearance, which quickens approvals in other countries. But Wilson said he’s encouraged by an FDA pilot program that looks to develop uniform standards across countries. “While we’re focusing this announcement on Brazil, we’re thinking globally,” Wilson said. GemmaBio’s mission aligns with calls to make gene therapies accessible. “Researchers, drug developers and drug manufacturers are squandering the chance to make gene therapies viable even in wealthier countries, let alone transformative for the world,” co-authors Evelyn Mwesigwa Harlow and Jennifer Adair wrote earlier this year in Nature . “To seize the opportunity, they must take into account the populations most in need, as well as the global market for treatments — both when developing and when valuing the drugs.” It was once unthinkable that Wilson could be at the forefront of bringing gene therapies to the world. In 1999, he led a first-of-its-kind experiment in which 18-year-old Jesse Gelsinger died because of a gene therapy that triggered an immune system reaction. The death was a major setback for the field and for Wilson, whose gene therapy center was disbanded, and he was barred from working on clinical trials for five years. In a comeback over the intervening years, Wilson’s lab discovered a family of viruses that could be engineered to shuttle gene therapies to cells, leading to a resurgence of the field. GemmaBio’s mission is being cheered on by rare disease advocates, who have watched drugmakers leave the space en masse . “You don’t do that unless you really care,” Christine Waggoner, the co-founder of the Cure GM1 Foundation, which jumpstarted one of the therapies that was paused by Passage Bio and licensed by GemmaBio. GemmaBio still faces a major challenge. Companies like Taysha Gene Therapies have tried to standardize gene therapy development only for their plans to crumble. A cash crunch at Taysha led the company to scrap most of its work, and it has been slow to offload paused programs that were initially funded by families. Wilson said GemmaBio distinguishes itself through both a global strategy and a focus on diseases with a smoother path for regulatory approval. “Many of the diseases that they selected were complicated,” Wilson said of other efforts. “Clinical development wasn’t clear. Endpoints weren’t clear. Natural history wasn’t clear. Potential for accelerated approval wasn’t clear.” Beyond just disease selection, GemmaBio could benefit from the FDA’s increasing openness to accelerated approval for gene therapies. And the agency is developing a so-called platform policy that could allow drug developers to simultaneously target multiple diseases without redoing critical work. Alongside GemmaBio, Wilson founded Franklin Biolabs, a contract research organization that specializes in viral vectors for gene therapies. It has received an undisclosed amount in funding from Savanne Life Sciences, the investment arm of Bioculture Group, a breeder of non-human primates for research. Plans call for soon disclosing how much GemmaBio received in seed funding, and from whom, according to Wilson. Besides venture capital, he’s hoping for a long-term extension of a federal voucher program that’s designed to incentivize the development of rare disease drugs. And the $100 million from Fiocruz is the first, he hopes, of more government partnerships. “It sends a message there is a different way for all of us to succeed in our business,” Wilson said.

GT-02287 Demonstrates Disease Modifying Capacity in Both GBA1 and Idiopathic Parkinson’s Disease Models GT-02287 Improves Mitochondrial Function and Provides Neuroprotective Effect in GBA1-Parkinson’s Disease Models GT-02287 Prevents Tau Accumulation in a Cellular Model BETHESDA, Md., Oct. 07, 2024 (GLOBE NEWSWIRE) -- Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a clinical-stage biotechnology company leading the discovery and development of the next generation of allosteric small molecule therapies, today announced the presentation of new evidence supporting the disease-modifying activity of GT-02287 in preclinical animal models of both GBA-1 and idiopathic Parkinson’s disease during a late-breaker poster session yesterday at the Society for Neuroscience (SfN) 2024 conference that is being held October 5-9 in Chicago, IL. In animal models of GBA-1 and idiopathic Parkinson’s disease, rescue of motor and cognitive function associated with administration of GT-02287 was observed to be persistent upon wash out of GT-02287 without significant effect in performance for more than a week following discontinuation when compared to the animals in which treatment was continued. Another presentation for GT-02287 yesterday described its association with improved mitochondrial function and neuroprotection in GBA1-Parkinson’s disease models. Finally, a second late-breaker was presented describing the reduction in Tau accumulation associated with GT-02287 in both GBA-1 mutation and wild type cell lines, suggesting GT-02287 may have broader potential as a treatment for tauopathies such as Alzheimer’s disease. “The robust preclinical development dossier for GT-02287 presented further strengthen our belief that GT-02287 has the potential to be a disease-modifying therapy for people suffering from Parkinson’s disease. The data demonstrate rescue of motor deficit and prevention of development of deficits in cognition which persisted even once the compound was removed. Moreover, GT-02287 demonstrated a positive effect on mitochondrial health as well as on lysosomal health which further demonstrates that the molecule acts throughout the disease cascade resulting from dysfunction of the lysosomal enzyme glucocerebrosidase (GCase), which GT-02287 was designed to target. Additionally, GT-02287 prevented Tau accumulation in human cellular models which demonstrates its potential to be a treatment for Alzheimer’s disease and other tauopathies,” commented Joanne Taylor, Ph.D., Senior Vice President of Research at Gain “The preservation of motor and cognitive improvement in animal models of Parkinson’s disease associated with GT-02287 after its discontinuation coupled with the neuroprotective effects after delayed administration support the potential of GT-02287 to slow or stop the progression of Parkinson’s disease,” said Gene Mack, Interim CEO and CFO of Gain Therapeutics. “The potential of GCase as a therapeutic target beyond Parkinson’s Disease is an encouraging finding that we can incorporate into our future development plans for GT-02287.” The late-breaking poster titled, “GT-02287, a clinical stage GCase regulator, demonstrates disease modifying capacity in both GBA1 and idiopathic Parkinson’s disease models,” was presented on-site October 6 at 3pm CT. In animal models of both GBA1 and idiopathic Parkinson’s disease, GT-02287 was administered after a clinical phenotype was established and then withdrawn from half the animals for more than one week prior to conclusion of the study. Neuromuscular function, motor coordination, and activities of daily living/cognition were measured in wire hang, beam walk, and nest building tests, respectively, throughout the study. GT-02287 was shown to rescue deficits in neuromuscular function and motor coordination in both models as well as to prevent the development of deficits in cognition and activities of daily living. Notably, withdrawal of GT-02287 for more than one week did not significantly affect performance in any of the tests, suggesting a disease modifying effect. The poster titled, “GT-02287, a clinical stage GCase regulator, improves mitochondrial function and provides a neuroprotective effect in GBA1-Parkinson's disease models,” was presented on-site October 6 at 10am CT. In an in vitro model - in which cultured rat mesencephalic dopaminergic neurons were treated with conduritol beta epoxide (CBE) to cause partial knockdown of GCase activity comparable to that seen in PD patients carrying heterozygous GBA1 mutations (GBA1 is the gene encoding GCase)- treatment with GT-02287 reduced the level of mitochondrial reactive oxygen species (ROS) as well as ameliorating lysosomal pathology, reducing α-synuclein aggregation, and providing a neuroprotective effect. In an in vivo model in which mice were subjected to toxic insult by CBE and injection of α-synuclein preformed fibrils (PFFs) into the striatum – delayed administration of GT-02287 reduced levels of mitochondrial protein Miro1, an important maker for mitophagy; aggregated α-synuclein and plasma neurofilament light chain (NfL), a marker of neurodegeneration; as well as completely restoring motor function to control levels. The late-breaking poster titled, “GT-02287, a GCase modulator and Gain Therapeutics’ PD drug candidate prevents Tau accumulation in a cellular model,” was presented on-site October 6 at 1pm CT. Lysosomal Tau accumulation was quantified in human fibroblasts, carrying either the L444P mutant or wild-type (WT) GBA engineered to express labelled Tau protein, at basal conditions as well in the presence of Alzheimer’s brain-derived Tau seeds. Basal and seed-induced Tau accumulation was significantly higher in Tau-GBA L444P cells, which express defective GCase, compared to Tau WT GBA cells. Treatment with GT-02287 reduced Tau accumulation in both cells carrying the L444P GBA mutation and those carrying wild-type GBA, demonstrating GT-02287’s potential as a disease-modifying treatment for Alzheimer’s disease and other tauopathies. This work was carried out in collaboration with scientists in the group of Professor Paolo Paganetti at the Laboratories for Translational Research of the Ente Ospedaliero Cantonale (LRT-EOC) in Bellinzona, Switzerland. This study was conducted under the support of an Innosuisse-Swiss Innovation Agency grant with the LRT-EOC and the Università della Svizzera italiana-affiliated Institute for Research in Biomedicine in Bellinzona, Switzerland. PDFs of the posters presented at Neuroscience 2024 are available on the Science and Technology section of the Company’s website at https://gaintherapeutics.com/science-and-technology/posters. About GT-02287Gain Therapeutics’ lead drug candidate, GT-02287, is in clinical development for the treatment of Parkinson’s disease with or without a GBA1 mutation. The orally administered, brain-penetrant small molecule is an allosteric protein modulator that restores the function of the lysosomal protein enzyme glucocerebrosidase (GCase) which becomes misfolded and impaired due to mutations in the GBA1 gene, the most common genetic abnormality associated with PD, or other age-related stress factors. In preclinical models of PD, GT-02287 restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels and improved motor function and cognitive performance. Additionally, GT-02287 significantly reduced plasma neurofilament light chain (NfL) levels, an emerging biomarker for neurodegeneration. Compelling preclinical data in mouse models of GBA1-PD, including that presented at FENS Forum 2024 in June describing improvement in cognitive performance in addition to motor performance after administration of GT-02287, suggests that GT-02287 may have the potential to slow the progression of Parkinson’s disease. Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse – Swiss Innovation Agency. About Gain Therapeutics, Inc.Gain Therapeutics, Inc. is a clinical-stage biotechnology company leading the discovery and development of next generation allosteric therapies. Gain’s lead drug candidate, GT-02287 is currently being evaluated for the treatment of Parkinson’s disease with or without a GBA1 mutation. Results from a Phase 1 study of GT-02287 in healthy volunteers demonstrated favorable safety and tolerability, plasma exposure in the projected therapeutic range, CNS exposure, and target engagement and modulation of GCase enzyme. Gain’s unique approach enables the discovery of novel, allosteric small molecule modulators that can restore or disrupt protein function. Deploying its highly advanced Magellan™ platform, Gain is accelerating drug discovery and unlocking novel disease-modifying treatments for untreatable or difficult-to-treat disorders including neurodegenerative diseases, rare genetic disorders and oncology. Forward-Looking StatementsThis release contains “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as “believes,” “expects,” “anticipates,” “intends,” “will,” “may,” “should,” or similar expressions. These forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct or that those goals will be achieved, and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, risks associated with market conditions and the satisfaction of customary closing conditions related to the offering and uncertainties related to the offerings and the use of proceeds from the offerings. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the Company’s business in general, please refer to the Company’s prospectus supplement to be filed with the SEC, and the documents incorporated by reference therein, including the Company’s Form 10-K for the year ended December 31, 2023 and Form 10-Q for the quarter ended June 30, 2024. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contacts:Apaar Jammu and Chuck Padalaajammu@gaintherapeutics.comchuck@lifesciadvisors.com Media Contacts:Russo PartnersNic Johnson and Elio Ambrosionic.johnson@russopartnersllc.comelio.ambrosio@russopartnersllc.com(760) 846-9256