MDA5

Odyssey Therapeutics and Sionna Therapeutics have the sorts of attributes that have enabled biotechs to successfully navigate choppy IPO waters in the recent past.\n Odyssey Therapeutics and Sionna Therapeutics have filed IPO paperwork, swelling the pack of startups that will provide an early look at how receptive public investors could be to biotech listings in 2025.Maze Therapeutics and Metsera filed to list their stocks earlier in January. Like those two companies, Odyssey and Sionna have clinical-phase programs, sizable bank balances and investor syndicates stocked with well-known VCs—the sorts of attributes that have enabled biotechs to successfully navigate choppy IPO waters in the recent past.Sionna is building on the efforts of Sanofi and AbbVie in cystic fibrosis. Greg Hurlbut, Ph.D., and Mark Munson, Ph.D., set up the biotech after working together at Sanofi, and it wasn\'t long before Sionna had licensed compounds designed to stabilize NBD1 from the French pharma for $1.5 million upfront.Multiple companies have studied NBD1, reflecting its key role in CFTR function, but are yet to develop a drug against the target. Pfizer called its results “discouraging,” adding that the binding domain “may not contain the features needed to build high‐affinity interactions.” However, Sionna believes it can hit the target, positioning it to advance treatments for the 90% of cystic fibrosis patients with F508del mutations. Vertex already sells its triple combination therapies Trikafta and Alyftrek for use in patients with F508del mutations. Sionna wants to test its lead NBD1 stabilizer candidate in combination with Trikafta, but it also plans to study the molecule with its own CFTR modulators. The biotech added to its portfolio of CFTR modulators last year by picking up three candidates from AbbVie.Sionna plans to advance a combination of an NBD1 stabilizer and complementary modulator through phase 1 and phase 2a and into phase 2b using the IPO funds. The biotech is yet to pick which molecules to include in the combination. AbbVie could benefit from the choice, with Sionna agreeing to give the Big Pharma up to $360 million in milestones and rights of first negotiation.The IPO filing acknowledges some of the challenges Sionna may face if it runs trials that require people to stop taking standard of care. Sionna said AbbVie terminated part of a phase 2 trial that planned to test a CFTR potentiator and corrector after deeming it “not enrollable due to, among other reasons, the increasing availability of Trikafta.” The biotech licensed the CFTR potentiator and corrector from AbbVie.Meanwhile, Odyssey is seeking funding for autoimmune and inflammatory disease programs, according to its filing. The pipeline is led by a RIPK2 inhibitor that is set to start a phase 2a monotherapy trial for ulcerative colitis this quarter. Odyssey said the IPO funding will enable it to complete the monotherapy trial and generate induction-stage data from a phase 2a trial that will test the candidate in combination with Takeda’s Entyvio. The biotech has struck deals to add to its assets and capabilities, buying Rahko for its machine learning prowess and acquiring IFM Discovery for MDA5 and NLRP1 discovery programs. IFM was a subsidiary of IFM Therapeutics, a biotech founded by Odyssey CEO Gary Glick, Ph.D. Glick previously set up and ran Scorpion Therapeutics, which Eli Lilly is now buying for up to $2.5 billion.Johnson & Johnson and Pfizer have partnerships with Odyssey. J&J paid $6.5 million to jointly discover and optimize small molecules using Odyssey’s artificial intelligence and machine learning capabilities. Pfizer paid $1 million as part of a collaboration intended to identify novel hits using Odyssey’s natural product platform.

BOSTON--(BUSINESS WIRE)-- #Biotech -- Odyssey Therapeutics, Inc. , a biotechnology company pioneering next-generation precision immunomodulators for inflammatory diseases, today announced the formation of its Scientific Advisory Board (SAB), which includes renowned experts in the fields of immunology and therapeutic development. The SAB will be chaired by Stephen Blacklow, M.D., Ph.D., who holds positions at Harvard Medical School and the Dana- Farber Cancer Institute and is a recognized drug discovery innovator. “The lens by which we evaluate therapeutic opportunities is supported by the profound knowledge of immune biology among our team and trusted advisors,” said Gary Glick, Ph.D., founder and CEO of Odyssey Therapeutics. “We are fortunate to work with a group of preeminent scientific minds and recognized drug hunters with extensive track records in developing molecules that have successfully translated from scientific hypothesis to clinical validation and regulatory success. We look forward to benefiting from their collective experience as we move our lead programs into the clinic and advance our earlier-stage pipeline.” Dr. Blacklow commented, “I am excited to work alongside Gary, my esteemed SAB members and the Odyssey team. Odyssey’s differentiated approach and dedication to advancing medicines for inflammatory disease is inspiring, and I look forward to contributing my expertise to help drive these groundbreaking programs forward.” Odyssey’s SAB is comprised of the following members: Dr. Blacklow, M.D., Ph.D., Gustavus Adolphus Pfeiffer Professor and Department Chair of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, member of the Department of Cancer Biology at the Dana-Farber Cancer Institute: Dr. Blacklow is a globally recognized expert in signal transduction at the structural and molecular level. His research on the Notch pathway, a complex signaling pathway integral to immune cell function, has led to the development of multiple investigational therapies for hematologic malignancies, such as T cell acute lymphocytic leukemia. Of his many awards and affiliations, Dr. Blacklow received the National Cancer Institute’s prestigious Outstanding Investigator Award in 2017, and was elected to the Association of American Physicians in 2018 and the American Academy of Arts and Sciences in 2024. He received his M.D. and Ph.D. degrees from Harvard University. Robert Abraham, Ph.D., former Executive Vice President of Cancer Biology at Odyssey: Dr. Abraham previously served as Chief Scientific Officer at Vividion Therapeutics, which was acquired in August 2021 by Bayer for $2 billion. He has extensive experience in both the pharmaceutical industry and academia, including 10 years at Pfizer where he served as Senior Vice President and group head in Oncology Research and Development, with oversight of cancer drug discovery and early clinical development. He previously held roles at Duke University Medical Center, including an Endowed Chair in the Department of Cancer Biology. Throughout his career, he has made significant contributions to multiple research areas, including cell signaling, T lymphocyte biology, rapamycin pharmacology and mTOR functions, cancer metabolism and DNA damage responses. He received a B.S. in biology from Bucknell University and a Ph.D. in pharmacology from the University of Pittsburgh. Richard Flavell, Ph.D., F.R.S., Sterling Professor of Immunobiology, Yale School of Medicine, and Investigator, Howard Hughes Medical Institute: Dr. Flavell is a co-discoverer of introns in cellular genes, and his research focuses on the molecular and cellular mechanisms that govern immune responses, from the characterization of signal transduction pathways to the regulation of immune cell differentiation and activation. His work has been instrumental in identifying key components of the innate immune system, such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs), and activation of the innate immune system and inflammatory disease. He received his B.Sc. and Ph.D. in biochemistry from the University of Hull, England. Alexander (Sasha) Rudensky, Ph.D., Director, Ludwig Center for Cancer Immunotherapy, Tri-Institutional Professor at Memorial Sloan Kettering Cancer Center, The Rockefeller University and Cornell University, and Investigator, Howard Hughes Medical Institute: Dr. Rudensky’s research has defined regulatory T cells and the roles they play in autoimmunity, tolerance, allergic disease, infections and cancer. His current work addresses the molecular mechanisms underlying regulatory T cell activity, and the role these cells play in autoimmunity, tumor immunity and immunity to infections. He received his candidate of sciences degree from the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, and completed his postdoctoral work at the Yale School of Medicine. Ruslan Medzhitov, Ph.D., Sterling Professor, Yale University School of Medicine and Investigator, Howard Hughes Medical Institute: Dr. Medzhitov’s work has identified innate immune sensing pathways and established the principle of innate control of adaptive immunity. His current research is focused on inflammation biology, allergic diseases and evolutionary medicine. Dr. Medzhitov has been a recipient of numerous awards and honors, including the 2019 Dickson Prize in Medicine. He earned his Ph.D. from Moscow State University. Sun Hur, Ph.D., Professor at Harvard Medical School and Boston Children’s Hospital and Investigator, Howard Hughes Medical Institute: Dr. Hur’s work on the molecular mechanisms of how the immune system distinguishes between self and non-self-entities led to the discovery of MDA5 and its role in innate immunity, autoimmunity and autoinflammatory diseases. She is a past recipient of the Vilcek Prize for Creative Promise in Biomedical Science for her research on inflammatory and autoimmune diseases and experimental enzymology. She earned her B.Sc. from Ewha Womans University and her Ph.D. in physical chemistry from the University of California, Santa Barbara. Seth Masters, Ph.D., Centre Head, Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research: Dr. Masters’ research on understanding the innate immune pathways that drive diseases led to the identification of the mechanisms by which NLRP1 mediates autoinflammatory disease. His current research explores how innate immune pathways contribute to inflammatory bowel disease, asthma, metabolic diseases and neurodegeneration. Dr. Masters obtained his B.Sc. in biochemistry from The University of Melbourne, Australia, and his Ph.D. in medical biology from the Walter and Eliza Hall Institute. Michael B. Yaffe, M.D., Ph.D., Professor of Biology and Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology: Dr. Yaffe’s research focuses on uncovering signaling pathways in cells that respond to stress, DNA damage and inflammatory cytokines and how the outputs of these pathways are integrated at the molecular and systems level to control the cell outcomes. Dr. Yaffe received his B.S. in materials science and engineering from Cornell University, M.D., Ph.D. degrees from Case Western Reserve University and advanced postdoctoral training with Prof. Lew Cantley at Harvard Medical School. About Odyssey Therapeutics Odyssey Therapeutics is a clinical-stage biotechnology company focused on discovering, developing and commercializing the next generation of inflammatory precision medicines. Since its founding in 2021, Odyssey has rapidly advanced a pipeline of clinical- and research-stage programs, leveraging the scientific expertise of its team of drug hunters and a comprehensive suite of tools to tackle drug targets with the greatest potential to benefit patients. Odyssey’s mission is to create extraordinary leaps in patient outcomes and change the standard of care for those living with serious inflammatory diseases. For more information, please visit odysseytx.com and follow Odyssey Therapeutics on X (formerly Twitter) and LinkedIn . Contacts Josh George jgeorge@spectrumscience.com 713-828-1913

A rare condition surged among previously unaffected groups of people during the COVID-19 pandemic and led to the deaths of nine patients, researchers say. The condition is a type of autoimmune response linked to the body immune system mistakenly attacking itself. Intriguingly, the system being attacked normally works as a sentinel or guard, whose job it is to detect invading viruses. It is mainly seen in East Asian women and girls and was very uncommon in the UK. But researchers who were examining data on MDA5 autoimmunity in Yorkshire during the pandemic noted an unprecedented 60 cases among mainly white men and women. Researchers investigating the increase in cases believe that exposure to the COVID-19 virus may trigger the condition, which causes distinctive skin rashes, pneumonia and interstitial lung disease, a rapidly progressing lung inflammation with damage which is often fatal. A rare condition surged among previously unaffected groups of people during the COVID-19 pandemic and led to the deaths of nine patients, researchers say. The condition is a type of autoimmune response linked to the body immune system mistakenly attacking itself. Intriguingly, the system being attacked normally works as a sentinel or guard, whose job it is to detect invading viruses. It is mainly seen in East Asian women and girls and was very uncommon in the UK. But researchers at the University of Leeds and Leeds Teaching Hospitals NHS trust, who were examining data on MDA5 autoimmunity in Yorkshire during the pandemic, noted an unprecedented 60 cases among mainly white men and women. Researchers investigating the increase in cases believe that exposure to the COVID-19 virus may trigger the condition, which causes distinctive skin rashes, pneumonia and interstitial lung disease, a rapidly progressing lung inflammation with damage which is often fatal. Principal Investigator Dennis McGonagle, Professor of Investigative Rheumatology in the University of Leeds' School of Medicine and Leeds Teaching Hospitals NHS Trust, said: "Whilst we very occasionally see this disease in the UK, this surge in cases was completely new and very different. "It is important that physicians understand the symptoms so that patients can be quickly referred for treatment and have the best chance of a rapid and full recovery. Lives could undoubtedly be saved but there is a great need for research to try and slow or stop the rapid lung progression that occurs in some patients." The research paper is published in The Lancet eBioMedicine. Viruses and autoimmune response The immune system contains a protein called MDA5, which helps detect RNA viruses like COVID-19. Normally, this protein helps trigger an immune response in the body, where more of the protein is produced to help fight off the virus. However, sometimes the immune system releases antibodies which mistakenly attack this protein, leading to MDA5 autoimmune diseases such as the rare disease described in this study. The exact cause is not well understood, but scientists believe the virus itself could trigger the response. Autoimmune diseases seen after viral infections have similar features, such as fatigue, joint pain and swelling, skin rashes and digestive issues. During the COVID-19 pandemic, physicians saw a rare condition in children called multisystem inflammatory syndrome in children (MIS-C) where there was no evidence of active viral infection of the lungs. This MIS-C syndrome affected multiple systems in the body, including the heart, kidneys, brain, skin, eyes, and digestive organs, but usually spared the lungs. The disease seen in Yorkshire was dubbed MIP-C (pronounced "mipsy") because of its similarities to MIS-C in that it occurred around the time of the pandemic but where active infection was usually absent. The 60 patients in the study presented at their GPs or to A&E with a range of symptoms including shortness of breath, muscle pain, rashes, and reduced blood flow to the fingers, known as Raynaud's disease. These symptoms are associated with autoimmune disease. The patients were referred to rheumatology specialists for further testing and all were diagnosed with the condition. Of the 60 patients, 35 had received COVID-19 vaccinations, and 15 had previously tested positive for COVID-19. However, patients were not systematically tested for COVID-19, and some may have been infected, but were asymptomatic at the time. Such cases could have developed MDA5 disease due to an overreaction of their immune system to minimal exposure to the virus. Twenty-five out of the 60 patients (41.7%) developed interstitial lung disease, and despite treatment with immunosuppressant medication, eight of those patients died. A ninth patient, who did not have interstitial lung disease, died from sepsis. To understand the increase in cases of this rare condition, researchers collected data on the number of these tests between January 2018 and December 2022, alongside data on COVID-19 infections and vaccination, and information about each patient's symptoms. Analysis showed that just six cases of the rare condition had been diagnosed between 2018 and 2019. However, in the 3 years after 60 new cases appeared, eight cases were diagnosed in 2020; 35 cases were diagnosed in 2021 and 17 cases were diagnosed in 2022. Very few cases have occurred since then. Patient demographics Patients were aged between 43 and 71 years, with 36 of them being female. Ethnicity: Researchers noted that there was a strong overlap in 2021 between vaccination rates in Yorkshire and the surge in MDA5 disease cases. This peak, though, also occurred shortly after a community wave of coronavirus infection occurred in late 2021. A smaller overlap was seen between confirmed COVID-19 infection and MDA5. However, it was interesting to note that almost half (42%) of patients were not documented to have been vaccinated against COVID-19 before they tested positive for MDA5. Four children who tested positive for MDA5 were unvaccinated, pointing to the idea of an overreacting immune response after exposure to a virus. Professor McGonagle said: "We know that vaccines can trigger an immune overreaction, but given that not all of these patients were vaccinated against COVID-19, and the increase in cases occurred when the COVID-19 virus was circulating in significant numbers, the evidence strongly suggests that the increase in cases of this rare disease is linked to exposure to the virus." The data was generated by Dr Paula David and Dr Gabriele DeMarco from the University of Leeds' School of Medicine and the Leeds Teaching Hospitals NHS Trust, with their Trust colleague Dr Khizer Iqbal. This work was done in collaboration with Dr Pradipta Ghosh and her team at the University of California, San Diego, who showed that the MDA5 protein was found in higher amounts in patients with COVID-19 and in patients with other diseases involving MDA5. They discovered that this increase was linked to an abnormal immune response that slows the virus's ability to multiply and spread. Additionally, they found that higher levels of the MDA5 protein were associated with increased levels of Interleukin-15, a protein that activates T-cells, or immune cells. This interaction could be contributing to the autoimmune response. The investigators say that doctors should be aware of their findings so that patients can be more quickly diagnosed and referred for treatment, which could help lessen lung damage and save lives. This is especially so in subjects with suspected pneumonia not getting better on therapy and where the rashes, muscle involvement and other disease features are absent. Dr Paula David, the first author of the paper, said: "We think that this large, unprecedented outbreak of MDA5 disease in Yorkshire will help advance the field to better appreciate the role between viruses and autoimmunity." Dr Saptarshi Sinha, the co-first author of the paper and the interim director of PreCSN, added: "Here at PreCSN, we enjoy the ability to help researchers such as the McGonagle group dive into big data and find patterns rapidly with precision that allows us to connect the dots. In this case, we are glad we could find a connection between a clinical presentation of autoimmune disease in the backdrop of COVID-19 at a molecular level."