Fulcrum repurposes failed GSK drug for rare disease

pharmaphorum | April 24, 2019

GSK’s failed cardiovascular drug losmapimod looks like it might get a new lease of life after being picked up by biotech Fulcrum Therapeutics, who want to repurpose the drug to treat the rare genetic disease facioscapulohumeral muscular dystrophy (FSHD). Fulcrum had identified inhibitors of p38/ mitogen activated protein kinase (MAPK) as powerful inhibitors of DUX4 expression. DUX4 is the gene that is the root cause of FSHD, a progressive muscle wasting disorder. This insight into the DUX4 regulatory pathway led the team to review existing p38/ MAPK inhibitors and identify losmapimod as a compound with the potential to address the root cause of FSHD by decreasing DUX4 expression. GSK initially trialled losmapimod as a cardiovascular disease treatment, before shelving the drug after late-stage failures. The drug was never tested in muscular dystrophies, but Fulcrum notes that the 24 trials it went through proved the drug to have a robust safety profile. Meanwhile, the company has conducted preclinical testing of losmapimod in patient-derived cell models and observed “precise and potent” downregulation of DUX4 expression and restoration of a healthy muscle phenotype without an effect on myogenesis.

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PCI Pharma Services has invested in state-of-the-art containment equipment and created a ‘Potent Passport’ philosophy to identify the specific handling requirements for any Highly Potent Active Pharmaceutical Ingredients (HPAPI) project. Backed by 30 years’ experience of managing potent molecules, PCI Pharma Services is the logical choice when selecting an outsourcing partner. The pharmaceutical landscape continues to evolve, with much R&D focusing on more specialized medicines. As the biological activity and specificity of the API increases, dosage strengths decrease – resulting in increased potency of the APIs in terms of occupational handling for drug product manufacture. At PCI, we are seeing continued investment in R&D with a visible shift towards speciality/potent medicines, with oncology being a particularly intense area of focus for the global pharmaceutical market. Latest data suggests approximately 25 per cent of New Chemical Entities (NCEs) in development are deemed potent.


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Athira Pharma Announces Topline Results from ACT-AD Phase 2 Proof of Concept Study of Fosgonimeton in Mild-to-Moderate Alzheimer’s Disease

Athira Pharma, Inc. | June 27, 2022

Athira Pharma, Inc. a late clinical-stage biopharmaceutical company focused on developing small molecules to restore neuronal health and slow neurodegeneration, today announced topline results from its exploratory ACT-AD Phase 2 study of fosgonimeton in patients with mild-to-moderate Alzheimer’s disease. Fosgonimeton is a small molecule designed to enhance the activity of Hepatocyte Growth Factor and its receptor, MET, which are expressed in the central nervous system to promote brain health and function. “Following compelling ERP P300 latency biomarker data from a small Phase 1b trial over eight days in Alzheimer’s patients on fosgonimeton monotherapy, this Phase 2 trial provides valuable insights into the nature of this novel intervention over 26 weeks. ACT-AD was designed as a learning study to further investigate the ERP P300 biomarker signal over 6 months, assess safety in a patient population more representative of the real world, by allowing the use of add-on standard-of-care acetylcholinesterase inhibitors (AChEIs, e.g., donepezil), and explore fosgonimeton’s effect on psychometric outcomes, including ADAS-Cog11, to inform the ongoing Phase 3 LIFT-AD study. To that end, this study achieved its goal,” said Hans Moebius, M.D., Ph.D., Chief Medical Officer of Athira. “The study was intended to show differences on the biomarker ERP P300 latency. This primary endpoint was not met by protocoled analysis, however a pre-specified subgroup analysis indicated a potential diminished effect of fosgonimeton when given in combination with AChEIs. A subsequent post hoc analysis of the data from patients on fosgonimeton monotherapy showed a meaningful improvement in both ERP P300 latency and cognitive performance compared to placebo at 26 weeks. “These data points are very encouraging as they indicate the expected pharmacological activity of fosgonimeton by parallel improvement on ERP P300 latency and ADAS-Cog11 and show a favorable safety profile over six months. This is the first time monotherapy fosgonimeton has shown an effect on ADAS-Cog11, suggesting a potential cognitive benefit. We will use these insights for a rational optimization of the ongoing LIFT-AD trial. We plan to seek advice from our scientific advisors, investigators, and ultimately regulators on how to expeditiously analyze and potentially adapt the LIFT-AD study,” Dr. Moebius “The data from the fosgonimeton monotherapy analysis are encouraging and show biologic activity that may support the potential role of the HGF/MET pathway in neurodegenerative diseases,” said Marwan Sabbagh, M.D., FAAN, professor of neurology at Barrow Neurological Institute, Phoenix, AZ. “ACT-AD adds to the body of literature suggesting ERP P300 latency as an important biomarker for cognitive status.”

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invoX Pharma to Acquire F-star Therapeutics, Inc. a Pioneering Next Generation Bispecific Discovery Platform and Clinical Programs

F-star Therapeutics, Inc. | June 24, 2022

invoX Pharma a wholly owned subsidiary of Sino Biopharmaceutical Limited focused on research and development and business development activities outside of China, and F-star Therapeutics, Inc. a clinical-stage biopharmaceutical company pioneering bispecifics in immunotherapy so more people with cancer can live longer and improved lives, today announced that the companies have entered into a definitive agreement whereby invoX will acquire all of the issued and outstanding shares of F-star common stock for $7.12 per share. The proposed acquisition values F-star at approximately $161 million. The transaction has been unanimously approved by the invoX and F-star Boards of Directors and is expected to close in the second half of 2022. F-star’s proprietary platform technology pioneers the use of tetravalent (2+2) bispecific antibodies that enable the simultaneous targeting of two different antigens and a unique set of pharmacology to deliver focused, potent and safe immune activation in the tumor microenvironment. Four programs are progressing in clinic, three based on F-star’s tetravalent platform and one next generation STING agonist, with multiple further undisclosed programs in development. These programs represent potentially first- and best-in-class drug candidates for many areas of unmet medical need, including patients with cancer and other serious diseases who have few other options available. Leveraging its modular antibody technology, F-star has forged collaborations with major international biopharma companies across a wide range of therapeutic areas including oncology, immunology and neurology. invoX, established in 2021 in the United Kingdom, is Sino Biopharm’s international expansion platform, focusing on R&D and business development activities outside of China, with a core focus on oncology and respiratory therapeutics. F-star will form a key element of invoX’s strategy to accelerate Sino Biopharm’s development of innovative medicines to transform the lives of patients worldwide, complementing its existing R&D platforms and pipeline. “Today’s proposed acquisition is aligned with invoX’s strategy to become a fully integrated biopharmaceutical company with an advancing pipeline of innovative products addressing unmet healthcare needs, worldwide. We are excited to welcome F-star employees and look forward to working with them as we invest in the company to progress and grow its clinical pipeline to realize the full potential of the platform.” Ben Toogood, Chief Executive Officer of invoX Eliot Forster, Chief Executive Officer of F-star said: “We believe our tetravalent bispecifics offer the best approach to tackle hard-to-treat cancers and other serious diseases, with the ambition to deliver longer and improved lives for patients. Today’s announcement is good news for F-star, for our shareholders and, of course, for patients. This transaction enables greater and longer-term opportunities to develop the F-star platform and accelerate delivery of our novel medicines as we work together towards a future free from cancer and other serious diseases. I’d like to thank the fantastic team at F-star as well as our partners for all their hard work, support and dedication and I’m delighted to share this exciting development.” About invoX Pharma invoX Pharma was incorporated in March 2021 and is a wholly owned subsidiary of Sino Biopharm, a global top 40 pharmaceutical company with more than 24,000 employees. United Kingdom-based invoX is Sino Biopharm’s international expansion platform, focusing on R&D and business development activities outside of China, with a core focus on oncology and respiratory therapeutics. At its core, the Company aspires to improve patients’ lives by creating access to innovative medicine. About Sino Biopharm Sino Biopharm, together with its subsidiaries, is a leading, innovative research and development driven pharmaceutical conglomerate in China, with a business scope that is vertically integrated including research and development, manufacturing and sales and marketing infrastructure. The Company’s product offerings include a variety of biologics and small molecule drugs, and in therapy areas that include hepatology, oncology, cardiovascular and cerebrovascular diseases, orthopaedics, digestive and immune and respiratory diseases. About F-star Therapeutics, Inc. F-star Therapeutics, Inc. is a clinical-stage biopharmaceutical company pioneering bispecifics in immunotherapy so more people with cancer can live longer and improved lives. F-star is committed to working towards a future free from cancer and other serious diseases, through the use of tetravalent (2+2) bispecific antibodies to create a paradigm shift in treatments. The Company has four second-generation immuno-oncology therapeutics in the clinic, each directed against some of the most promising IO targets in drug development, including LAG-3 and CD137. F-star’s proprietary antibody discovery platform is protected by an extensive intellectual property estate. F-star has over 500 granted patents and pending patent applications relating to its platform technology and product pipeline. The Company has attracted multiple partnerships with biopharma targeting significant unmet needs across several disease areas, including oncology, immunology, and CNS.

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Can-Fite Granted Key NASH Patent in Israel

Can-Fite BioPharma Ltd. | May 17, 2022

Can-Fite BioPharma Ltd. a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, announced that its patent titled "An A3 Adenosine Receptor Ligand For Use In Treating Ectopic Fat Accumulation" has been granted by the Israel Patent Office. This patent has been issued in approximately 40 countries and territories including Japan, South Korea, Hong Kong, Mexico, and in the European Union. It addresses the use of the A3 Adenosine Receptor ligand, the target receptor for Can-Fite's drug platform technology, for the treatment of ectopic fat accumulation particularly in fatty liver as manifested in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. The treatment of NASH is a market estimated to reach $35 billion by 2025. Can-Fite is currently enrolling and treating patients in a Phase IIb NASH study of its liver drug candidate Namodenoson. The multi-center, randomized, double blind, and placebo controlled study of biopsy-confirmed NASH patients will measure efficacy periodically through biomarkers, with a primary efficacy endpoint determined by liver biopsy at the end of the treatment period. In a prior Phase IIa study, Namodenoson met endpoints including reduced liver fat content, anti-inflammatory effects, and decreased body weight with excellent safety. “The treatment of NASH is an enormous unmet need that Can-Fite seeks to meet through our advanced stage clinical trial and our expanding patent estate for the use of our target A3AR in the treatment of fatty liver disease,” Can-Fite CEO Dr. Pnina Fishman About Namodenoson Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor. Namodenoson is being evaluated in a pivotal Phase III trial as a second line treatment for hepatocellular carcinoma, and in a Phase IIb trial as a treatment for non-alcoholic steatohepatitis. A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. About Can-Fite BioPharma Ltd. Can-Fite BioPharma Ltd. is an advanced clinical stage drug development Company with a platform technology that is designed to address multi-billion dollar markets in the treatment of cancer, liver, and inflammatory disease. The Company's lead drug candidate, Piclidenoson has completed enrollment in a Phase III trial for psoriasis. Can-Fite's liver drug, Namodenoson, is being evaluated in a Phase IIb trial for the treatment of non-alcoholic steatohepatitis (NASH), and enrollment is expected to commence in a Phase III trial for hepatocellular carcinoma (HCC), the most common form of liver cancer. Namodenoson has been granted Orphan Drug Designation in the U.S. and Europe and Fast Track Designation as a second line treatment for HCC by the U.S. Food and Drug Administration. Namodenoson has also shown proof of concept to potentially treat other cancers including colon, prostate, and melanoma. CF602, the Company's third drug candidate, has shown efficacy in the treatment of erectile dysfunction. These drugs have an excellent safety profile with experience in over 1,500 patients in clinical studies to date.

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PHARMACY MARKET

Medison Pharma Announces Extension of Multi-territorial Agreement with Immunocore and Expansion into Australia and New Zealand

Medison Pharma | May 30, 2022

Medison Pharma a global pharma company focused on providing access to highly innovative therapies to patients in international markets, announced the addition of new markets to its multi-territorial agreement with Immunocore Holdings plc a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infection and autoimmune disease. The multi-territorial agreement to help seek regulatory authorization and commercialize Immunocore's KIMMTRAK® for the treatment of unresectable or metastatic uveal melanoma, a rare and aggressive form of melanoma that affects the eye, which covers Canada, twenty markets across Central Eastern Europe and Israel, will now extend to Australia and New Zealand. KIMMTRAK has been approved by both by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), where it is the first and only treatment approved in the E.U. to treat patients with unresectable or metastatic uveal melanoma. "We are delighted to deepen our partnership with Immunocore and proud to further grow the reach of their breakthrough treatment, as part of our mission that knows no borders. We believe that every patient, wherever they are in the world, deserves a fair chance to receive lifesaving, highly innovative therapies. By adding new countries and continents, we are continuing in our efforts to turn our mission into a reality." Meir Jakobsohn, Founder and CEO of Medison "It can be challenging for biotechs to commercialise in a large number of countries, often resulting in delayed access to highly innovative therapies in many areas of the world. Medison's global platform is designed to address this challenge," said Gil Gurfinkel, VP Corporate Development at Medison. "Immunocore's novel therapy for unresectable or metastatic uveal melanoma and our ability to treat patients suffering from this rare and aggressive form of cancer in additional countries is a win-win outcome of our partnership." Medison's expansion of its commercial presence to Australia and New Zealand is the latest addition to its geographic growth, enabling Medison to capitalize on growing market opportunities for its commercial partners. Medison is further enlarging its footprint in Europe with a new office location for its international headquarters in Zug, Switzerland, and operations in Greece and Cyprus, which enlarge its European offering of Central Eastern Europe, the Baltic states, and Balkans. In Canada, the team is also growing and recently moved into larger office space in downtown Toronto. With this latest growth, Medison increases its commercial presence across 25 locations around the world. Medison is hiring across all locations and in key functions. About Medison Pharma Medison is a global pharma company focused on providing access to highly innovative therapies to patients in international markets. Medison is the first to create an international commercialization platform for highly innovative therapies, helping to save and improve lives by making the best available novel treatments accessible to patients in international markets. Medison has a track record of multi-territorial partnerships with leading pharmaceutical and biotech companies seeking to expand their global reach. Medison is also an active investor in disruptive healthcare technologies and provides its partners with exposure to innovation in biotech and digital health. About KIMMTRAK® KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore's ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. KIMMTRAK has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States, Accelerated Assessment by the EMA, and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. KIMMTRAK is currently approved in 31 countries, including the United States and European Union.

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PCI Pharma Services has invested in state-of-the-art containment equipment and created a ‘Potent Passport’ philosophy to identify the specific handling requirements for any Highly Potent Active Pharmaceutical Ingredients (HPAPI) project. Backed by 30 years’ experience of managing potent molecules, PCI Pharma Services is the logical choice when selecting an outsourcing partner. The pharmaceutical landscape continues to evolve, with much R&D focusing on more specialized medicines. As the biological activity and specificity of the API increases, dosage strengths decrease – resulting in increased potency of the APIs in terms of occupational handling for drug product manufacture. At PCI, we are seeing continued investment in R&D with a visible shift towards speciality/potent medicines, with oncology being a particularly intense area of focus for the global pharmaceutical market. Latest data suggests approximately 25 per cent of New Chemical Entities (NCEs) in development are deemed potent.

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