ASC2

Initiated by the licensing of a Duke-NUS invention to Paratus, the two parties also signed an agreement to enable the potential development of other therapeutics from future collaborative research into bat immunology. SINGAPORE, 15 August 2023 – Duke-NUS and Paratus Sciences Corporation, a start-up headquartered in New York, today announced that they have signed two agreements to advance innovations in human health arising from research in bat immunology. The joint effort aims to translate insights about the biology of bats' unique resistance to disease into the development of human therapeutics, including therapeutics targeting infections and inflammation. In the first instance, Paratus will develop a new class of anti-inflammatory drugs under a license to commercialise a Duke-NUS invention based on findings summarised in a paper recently published in the journal Cell by Professor Wang Linfa and his team from Duke-NUS’ Emerging Infectious Diseases Programme. In this paper, Prof Wang and his team revealed that a bat protein called ASC2 is a powerful inhibitor of the bat’s inflammatory mechanism. The findings explain bats’ ability to avoid significant illness even when they are infected with viruses that can cause symptoms in humans. The license from Duke-NUS allows Paratus to develop drug candidates that could mimic the anti-inflammatory effect of ASC2. “The extreme stress that flying exerts on bats’ cells has forced them to evolve a unique inflammation-dampening resilience. This resilience is so effective that bats can carry dangerous viruses, including coronaviruses and viruses like Ebola, without falling sick,” said Prof Wang, one of the world’s leading experts in zoonotic diseases, bat immunology and pathogen discovery. “Our deep understanding of bat immunology provides a scientific foundation from which we can develop novel therapeutics. We are learning from bats to fight human diseases.” Paratus has established a subsidiary in Singapore (Paratus Sciences Singapore), headquartered at ClavystBio’s Node 1, a collaborative innovation space at Singapore Science Park. Paratus Sciences Singapore will collaborate with Duke-NUS, beyond the initial technology license, on a broader investigation of bat immunology for new insights with therapeutic potential. The collaboration will bring together the biological, genomics, bioinformatics expertise of both organizations and will leverage their resources and infrastructure to find new therapeutic opportunities right here in Singapore. Associate Professor Christopher Laing, Vice-Dean for Innovation and Entrepreneurship at Duke-NUS, said, “Close partnerships with industry partners, starting at the earliest stages of innovation and continuing as long-term collaborations, are essential for successful transition from the lab to the clinic. With Paratus, we will not only bring one of Prof Wang’s inventions closer to the market—and to patients—but will find new directions for innovative solutions based on his lab’s ground-breaking research.” “We are thrilled to be strengthening our relationship with Duke-NUS and its phenomenal scientists,” said Dr Phil Ferro, President of Paratus. “We believe the insights gleaned from the in-depth study of bat biology, as Professor Wang’s team has demonstrated, will unlock the ability to develop many novel therapeutics for unmet needs in human health.” Reference: Ahn, M., Chen, V.C.W., Rozario, P., Ng, W.L., et al. 2023. Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases. Cell. 2023; 186: 2144-2159.e22. DOI: 10.1016/j.cell.2023.03.036

SINGAPORE, 12 May 2023 – By studying the unusual ability of bats to host viruses without significant illness, scientists at Duke-NUS Medical School have discovered a protein that could unlock new strategies for fighting inflammatory diseases in humans. “Bats have attracted great attention as a likely reservoir of the SARS-CoV-2 virus responsible for the COVID-19 pandemic,” said Professor Wang Lin-Fa, from Duke-NUS’ Emerging Infectious Diseases (EID) Programme, the senior author of the study published in the journal Cell. “But this unique ability to host yet survive viral infections could also have a very positive impact on human health if we can understand and exploit how they achieve this.” The research is focused on multi-protein complexes called inflammasomes that are responsible for the overactive inflammation that causes serious symptoms in many diseases. Inflammasomes are also implicated in functional decline in ageing. The Duke-NUS team discovered that a bat protein called ASC2 has a powerful ability to inhibit inflammasomes, thereby limiting inflammation. “This suggests that the high-level activity of ASC2 is a key mechanism by which bats keep inflammation under control, with implications for their long lifespan and unique status as a reservoir for viruses,” explained Dr Matae Ahn, first author and co-corresponding author of the study, who is an Adjunct Research Fellow with the EID Programme and the SingHealth Duke-NUS Medicine Academic Clinical Programme. Dr Ahn is also a full-time clinician in SingHealth’s Postgraduate Year One (PGY1) Residency Programme after graduating from Duke-NUS in 2022. Ms Vivian Chen, co-first author of the study and an MD-PhD candidate in Duke-NUS, highlighted that the team was able to demonstrate the potential for exploiting the powers of the bat protein in humans by showing it could also be effective in mice*. She elaborated, “Expression of the bat protein in genetically-modified mice dampened inflammation and reduced the severity of the diseases driven by various triggers, including viruses.” Examination of the ASC2 protein in detail identified four amino acids in the molecule that were key to making the bat protein more effective at dampening inflammation than its corresponding human protein. This provides valuable insight for the development of drugs that can mimic the anti-inflammatory effect of the bat protein. The next step for the team is to investigate the potential of their findings for treating humans. Prof Wang said: “We have filed patents based on this work and are exploring commercial partnerships for drug discovery. We are hoping to develop a new class of anti-inflammatory drugs for inflammasome-driven human diseases.” Prof Wang strongly believes that it is time to focus on the more promising aspects of what makes bats special “to help fight the human diseases of the future.” Duke-NUS’ Senior Vice-Dean for Research, Professor Patrick Casey, commented on the study, “Even as COVID-19 begins to recede from the public’s attention, Professor Wang and his team continue to break new ground with their basic research into bat biology, yielding unique insights that can potentially strengthen global pandemic preparedness. This is a prime example of the immense value basic scientific research brings to solving major public health challenges.” (Concept art representing the study and its findings developed by the study team) Flying in the starry night are our nocturnal and echo-locating bats, the only mammals capable of powered flight. The fire symbolises the inflammation driven by the activation of inflammasomes—multi-protein complexes that assemble inside cells in response to danger or microbial signals. Adaption to flight (a metabolically costly process) may have driven key changes in the bat's immune system that enable it to survive viral and other diseases that would kill other mammals. Among these key changes are differences in the highly expressed protein ASC2, a potent negative regulator of inflammasomes in bats and humans. In bats, however, the ASC2 protein has naturally evolved to dampen inflammation. This insight could lead to the development of novel therapeutics against inflammatory diseases. Credit: Qi Su * All work with laboratory animals in this study fully complied with policies and guidelines for the humane care and use of laboratory animals set forth by the Institutional Animal Care and Use Committee (IACUC). Reference: Ahn, M., Chen, V.C.W., Rozario, P., Ng, W.L., et al. 2023. Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases. Cell. 2023; 186: 2144-2159.e22. DOI: 10.1016/j.cell.2023.03.036

Aug. 16, 2022 12:30 UTC NEW YORK--(BUSINESS WIRE)-- Olatec Therapeutics LLC, a leader in the developing class of selective NLRP3 inhibitors, today announced that Craig T. Basson, MD, PhD has been elected to their Board of Directors. This press release features multimedia. View the full release here: Craig T. Basson, MD, PhD Joins the Board of Directors of Olatec Therapeutics, a leader in the developing class of selective NLRP3 inhibitors (Photo: Business Wire) Excited to join Olatec’s Board of Directors, Dr. Basson explained: “I am thrilled to contribute to Olatec’s development of lead compound, dapansutrile – starting in gouty arthritis and to realize [dapansutrile’s] potential to translate the science of the NLRP3 inflammasome in multiple disease areas. I am confident in Olatec’s ultimate ability to deliver this important medicine globally to the many patients suffering from inflammatory diseases.” A veteran of both large pharmaceutical and biotechnology companies, Dr. Basson served as Chief Medical Officer, Global Head of Research and Development and/or interim Chief Executive Officer of Boston Pharmaceuticals, Inc., between February 2020 and August 2022 when he became an advisor to the Board of Directors. At Boston Pharmaceuticals, Dr. Basson led the acquisition and development of a broad pipeline of innovative drug candidates into the clinic. In the preceding decade, Dr. Basson served as the Global Head of Translational Medicine for the Cardiovascular and Metabolic Therapeutic Areas at the Novartis Institutes for Biomedical Research (NIBR) in Cambridge, MA. Leading a team of physicians with expertise in translational medicine, Dr. Basson oversaw more than 10 successful clinical studies and supported the development of Entresto™, licogliflozin, iscalimab and abelacimab, among other novel medicines, for patients suffering from cardiovascular disease, diabetes and metabolic disorders. Dr. Basson’s experience in drug development synergizes with Olatec’s focus in inflammation, since his work at Novartis advanced clinical programs for the anti-IL-1β biologic, canakinumab (Ilaris™), into multiple disease areas and supported translational studies in the landmark CANTOS trial. Prior to joining Novartis, Dr. Basson was the Gladys and Roland Harriman Professor of Cardiology and Internal Medicine at Weill Cornell Medical College, whose faculty he joined in 1997. He completed his BA and MA at Washington University in St. Louis, MO and received an MSc in Physiological Sciences from the University of Oxford as a Marshall Scholar. Dr. Basson holds an MD and PhD from Yale University. He completed his residency in Internal Medicine at Johns Hopkins Hospital and his clinical Cardiology fellowship and postdoctoral Cardiovascular Genetics fellowship at Harvard University and the Brigham and Women’s Hospital. Dr. Basson is an elected member of the American Society for Clinical Investigation and a Fellow of the American Heart Association and of the American College of Cardiology. Currently, Dr. Basson is a Senior Lecturer at Harvard Medical School and an attending physician at Brigham and Women’s Hospital, while also serving on scientific advisory boards. Reflecting on Dr. Basson’s election, Olatec’s CEO & Chairman, Damaris B. Skouras, said: “We are very pleased to have Craig join our Board. Craig brings to Olatec deep, proven expertise in translational medicine and an impressive track record in drug development directly relevant to our field of inflammation therapeutics. Craig will undoubtedly make valuable contributions to the development journey of dapansutrile and our OLT Analogues.” About Dapansutrile Dapansutrile (lab code: OLT1177®) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL‑1β and IL‑18. NLRP3 is one of the most well characterized inflammasome sensors due to its involvement in a wide range of disorders, including sterile inflammation, infections and rare genetic autoimmune syndromes. Dapansutrile is in Phase 2 clinical development and has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology) and heart failure (see Journal of Cardiovascular Pharmacology). Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction, diabetes, contact dermatitis, melanoma, pancreatic and breast cancers, spinal cord injury and Alzheimer’s disease. About Olatec Therapeutics LLC Olatec is a privately held, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1. In addition to the lead compound, dapansutrile, Olatec’s platform of proprietary compounds includes approximately 60 analogues (OLT Analogues) being screened as viable drug candidates. An IP portfolio protecting Olatec’s compounds consists of over 130 patents granted, covering dapansutrile and OLT Analogues. Olatec’s drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology and has been involved in the discovery and development of first-line inflammation treatments in the market today. For more information, please visit . Disclaimer & Forward-looking Statement The information contained herein is being provided for information purposes only. The Company makes no express or implied representation or warranty as to the completeness of this information. Any forward-looking statements contained in this release are based on assumptions made by Olatec at the time this Press Release was prepared. Any forward-looking statement contained in this Press Release is subject to known and unknown risks, uncertainties and other factors that may be materially different from those contemplated in such forward-looking statements. All information with respect to industry data has been obtained from sources believed to be reliable and current, but the accuracy thereof cannot be guaranteed by the Company. Olatec does not undertake any obligation to update or revise the forward-looking statements contained in this Press Release to reflect events or circumstances occurring after the date this Press Release was prepared, or to reflect the occurrence of unanticipated events.