Orion Biotechnology Canada Ltd.

Researchers created a germ-free mouse model to evaluate the role of the microbiome in the infection, replication, and pathogenesis of HIV and the Epstein-Barr virus, the virus that can cause mononucleosis and other serious diseases. Over the past decade, the gut microbiome has gained significant interest by scientists and non-scientists alike. Recent research has shown that the bacteria and other microbes in our gut play a supporting role in immunity, metabolism, digestion, and the fight against "bad bacteria" that try to invade our bodies. However, new research published in Nature Biotechnology by Angela Wahl, PhD, Balfour Sartor, MD, J. Victor Garcia, PhD, and UNC School of Medicine colleagues others has revealed that the microbiome may not as always be protective against human pathogens. Using a first-of-its-kind precision animal model with no microbiome (germ-free), researchers have shown that the microbiome has a significant impact on the acquisition of Epstein-Barr virus (EBV) and human immunodeficiency virus-1 (HIV) infection and plays a role in the course of disease. "These findings offer the first direct evidence that resident microbiota can have a significant impact on the establishment and pathology of infection by two different human-specific pathogens," said Wahl, assistant professor in the Division of Infectious Diseases in the UNC Department of Medicine. This research was conducted through a collaboration with scientists at the UNC International Center for the Advancement of Translational Science and the Division of Gastroenterology and Hepatology at the UNC School of Medicine. For the discovery to be made, Wahl and Garcia needed to create a "humanized" mouse model that mimicked a human's immune system to conduct their study. Once exposed to a virus, the humanized models can replicate the virus like a human and could be used for study. But researchers needed to take it one step further. Wahl and Garcia needed to compare a conventional humanized mouse model to one without a microbiome (germ-free). This meant that they needed to create a first-of-its-kind mouse model that was humanized and free of bacteria. Wahl, who is an expert in developing in-vivo models for human pathogens, and former UNC graduate student Morgan Chateau, PhD needed to figure out a way to humanize the animals while keeping them from encountering any germs, including those that live on our food, skin, in the air, or anywhere else in the external environment. To do so, they used a custom surgical isolation chamber, which is essentially a "big sterile bubble," with specialized glove compartments and a microscope. "This had never been done before," said Wahl, who is also assistant director of the UNC International Center for the Advancement for Translational Science. "We humanized the mice and did our viral exposure experiments under strict germ-free conditions. Technically, it was very challenging." HIV is a retrovirus that primarily infects human CD4+ T cells and is mainly acquired through the GI tract. Rectal exposure, for example, in men who have sex with men accounts for more than half of new HIV infections. Breastfeeding is an example of an oral exposure that can also transmit HIV to infants. Dr. Wenbo Yao, PhD, co-first author, found that rectal HIV acquisition was 200% higher in animals colonized with resident microbiome compared to germ-free animals. Similarly, oral HIV acquisition was 300% higher in animals colonized with resident microbiota compared to germ-free animals. Researchers also noticed that animals colonized with resident microbiota had HIV-RNA levels that were up to 34 times higher in plasma and more than 1,000 times higher in tissues than germ-free mice. Co-author R. Balfour Sartor, MD, the Margaret and Lorimer W. Midget Distinguished Professor of Medicine in the Division of Gastroenterology and Hepatology and Department of Microbiology and Immunology, says that their innovative HIV findings may ultimately serve as a foundation from which other doctors and researchers can develop new clinical approaches and therapies. "These findings open up a whole new door," said Sartor, who also directs the National Gnotobiotic Rodent Resource Center that derived the germ- free mice. "Would it be possible to alter the gut microbiota, by decreasing the bacteria, fungi, and viruses that might increase expansion of the HIV infection? Or conversely, we could help patients build up microbes that would prevent that expansion and can work synergistically with antivirals to clear the HIV." Researchers then performed comparisons between colonized and germ-free animals, which revealed that the presence of resident microbiota increased the frequency of CCR5+CD4+ T cells, which are the main target of HIV infection throughout the gut. The findings suggest that enhanced HIV acquisition and replication is due to, at least in part, an increased density of target cells for local infection following oral or rectal HIV exposure. "This is a finding of great significance," said Wahl. "Everyone has a unique composition of microbes that colonize their gut. In the future, it will be important to evaluate how this diversity among people affects their risk for HIV acquisition and the subsequent course of disease." The findings on EBV were also important. EBV is a DNA herpesvirus that infects B cells and can cause mononucleosis. Almost 95% of the adult population harbors latent infection of EBV, but for some people with compromised immune systems, EBV infection can influence the development of certain types of cancers such as Hodgkin's lymphoma, Non-Hodgkin lymphoma, Burkitt's lymphoma and Nasopharyngeal carcinoma. Wahl and Garcia found that mice with a normal microbiome that were exposed to EBV developed large macroscopic tumors in a variety of organs, including the spleen, liver, kidney, and stomach. These tumors were virtually absent in the germ-free mice infected with EBV. Future studies will be needed to evaluate the possible mechanism(s) for enhanced EBV infection and tumorigenesis in the presence of resident microbiota. "We had two human pathogens that are different in every possible way," said Garcia, who is director of the UNC International Center for the Advancement of Translational Science, Oliver Smithies Investigator and professor in the Departments of Medicine and Microbiology and Immunology. "The type of cell that they are infecting, the type of disease that they cause, the type of viruses that they are is completely different. Yet, the microbiome exacerbates the disease that each of those viruses causes." The researchers will now try to pinpoint the factors that determine whether the microbiome plays a role in the persistence of HIV and EBV infections throughout the body and figure out if the microbiome also affects other human-specific pathogens. More specifically, Wahl, Garcia, and Sartor want to understand how the microbiome is contributing to HIV and EBV infections. They also want to identify which specific microbial strains are aiding in the viruses' capacity to replicate and cause disease and of particular importance which ones are protecting the host from the viruses. Sartor, in particular, is interested in learning if there are any additional latent viruses affected by the presence of the microbiome. "Will the gut microbiome also influence reactivation of herpes simplex virus, shingles, and other latent viruses that cause tumors? We don't know, but there's a pretty good track record that microbes can influence certain bacterial and fungal pathogens. That may be something to explore as well." Wahl and Garcia hope that their findings will open a new area of exploration for researchers who are interested in the role of the microbiome on diseases caused by human specific pathogens. "At the heart of all this is that we have created a new series of models that will allow investigators to ask questions they could never ask before," said Garcia. "We have been able to do something that others thought could not be done." Other investigators include Joseph Pagano, MD, Craig Fletcher, DVM ,PhD, M. Andrea Azcarate-Peril, PhD, Michael Hudgens, PhD, Allison Rogala, DVM, and Joseph Tucker, MD, PhD from UNC, Christopher Whitehurst, PhD from New York Medical College, and Ian McGowan, MD, PhD from the University of Pittsburgh and Orion Biotechnology.

Ottawa, Canada, July 18, 2023 (GLOBE NEWSWIRE) -- Orion Biotechnology Canada Ltd. (Orion), a drug discovery and development company unlocking the therapeutic potential of previously undruggable G Protein-Coupled Receptors (GPCRs), today announced that it has successfully completed a discovery campaign against CXCR6, an undrugged small protein GPCR with the potential to provide a new and innovative form of immunotherapy treatment for solid tumor cancers. Completed in only four months, the rapid identification of this first-in-class (FIC) molecule further validates Orion’s PROcisionXTM discovery platform’s industry-leading efficiency. CXCR6 is expressed in several subsets of T cells, natural killer T cells, and bone marrow stromal cells, and the main physiological role of the CXCR6-CXCL16 axis is to activate numerous signaling pathways essential to regulating immunity. Boosting signaling through the CXCR6-CXCL16 axis in the tumor microenvironment has the potential to provide a new route to block solid tumor growth by helping to maintain anti-tumor cytotoxic T cells in an aggressive, non-exhausted state. “We are very excited about the significant progress we continue to make across our portfolio” said Dr. Ian McGowan, the company’s Chief Medical Officer. “Orion’s discovery success will allow for a new and highly differentiated strategy to drug CXCR6 for the treatment of cancer and other inflammatory diseases.” Dr. Oliver Hartley (VP Discovery) commented: “Small protein GPCRs have proven challenging to unlock using established small molecule and antibody-based approaches. This rapid success provides further evidence that Orion’s novel scientific approach can unlock previously undrugged small protein GPCRs and provides a clear illustration of the efficiency of our PROcisionXTM discovery platform.” Orion’s CEO Mark Groper remarked: “Unlocking previously intractable GPCRs represents a tremendous opportunity to develop new treatments across a broad range of therapeutic areas. Our rapid success with a new small protein GPCR marks another key milestone in our mission to deliver medicines that improve the lives of patients. The combination of our highly talented team and our PROcisionXTM platform is allowing our company to rapidly and efficiently build out a multi-product pipeline of high-value GPCR-targeted therapeutics.” About Orion Biotechnology Orion’s mission is to unlock the therapeutic potential of previously undruggable GPCRs. Orion has world-renowned expertise in GPCR pharmacology and protein engineering, and its proprietary drug discovery platform (PROcisionXTM) has been used to rapidly and efficiently advance a diversified portfolio of GPCR-targeted drug candidates for the treatment of cancer and other serious diseases. For more information, follow Orion Biotechnology on LinkedIn or visit . Ross MacLeod Orion Biotechnology Canada Ltd. +1 343.291.1032 ross@orionbiotechnology.com

QUEBEC CITY--( BUSINESS WIRE )--Devonian Health Group Inc. (“ Devonian ” or the “ Corporation ”) ( TSXv: GSD; OTCQB : DVHGF ), a clinical late stage botanical pharmaceutical corporation, focused on developing a unique portfolio of botanical pharmaceutical and cosmeceutical products, announces today that Mr David Baker, Edouard Dahl and Jean Forcione were appointed as a new independent directors to the Company’s Board of Directors. The Corporation also announced the grant of options to directors and consultants. Pierre J. Montanaro, Devonian president and Chief Executive Officer stated, “We are very pleased to welcome these new board members and are looking forward to their active participation in the growth of our company. I take this opportunity to thank M. Terry Fretz who has voluntary left the board of Devonian but will however continue his involvement as a member of the Board of Directors of Altius Healthcare, the division of Devonian Health Group’’ added Mr Montanaro. About David Baker David is a biotech executive and industry veteran, with over 30 years of experience, in large, mid-size, small, and start-up biopharmaceutical companies. Foundational experience in marketing including the commercialization of five different billion-dollar prescription drug brands in three different therapeutical categories. Broad experience in leadership roles and global general management with specific experience in strategy development/execution, fund raising, investor relations, commercialization, business development/licensing, clinical development, regulatory, manufacturing, and general business operations. Proven track record building, leading, and developing teams. Extensive experience serving on public and private company and non-profit boards. Mr. Baker most recently served at President & CEO of Vallon Pharmaceuticals (NASDAQ: VLON), a company he co-founded in 2018 and took public in 2021, before leading the company through a successful reverse merger in 2023. During his time at Vallon, he built the management team, raised over $30 million, advanced a lead asset from the pre-clinical stage to the late stages of clinical development, and secured a European partnership. Previously, he was the Chief Commercial Officer and interim CEO of Alcobra Ltd., a CNS specialty pharmaceutical company where he led the merger with Arcturus Therapeutics (NASDAQ: ARCT). Prior to Alcobra, he worked at Shire Plc for 10 years as Vice President of Commercial Strategy and New Business in the Neuroscience Business Unit, Global General Manager for Vyvanse® and Vice President, ADHD Marketing. He led the commercialization of Adderall XR® and Vyvanse, the two most successful ADHD brands based on annual revenue. Prior to Shire, he worked at Merck & Co. for over a decade in marketing, sales, market research, and business development. Mr. Baker's therapeutic expertise includes ADHD, autism, Fragile X Syndrome, osteoporosis, migraine, and hyperlipidemia. About Edouard Dahl Ed Dahl is a retired pharmaceutical executive with over 30 years of highly diversified business experience in three different industries: industrial lighting (GTE Sylvania) consumer packaged goods (Gillette), and pharmaceuticals (Nordic, Marion Merrell Dow, Hoechst Marion Roussel, Aventis, Sanofi and Dermik Labs). His experience at Dermik Labs, a Dermatology company will be especially valuable to Devonian. As GM of the company, he helped grow the Canadian business, quadrupling sales in just 5 years. As Director of Mergers and Acquisitions at Sanofi Canada he completed a $50 million skin care transaction. When retired, he consulted various institutional and private clients in business evaluations. Ed holds a Bachelor of Commerce from Concordia University in Montreal with a major in economics (1979). In addition, Ed was previously a Chartered Professional Accountant (CPA) and held a Certification in Production and Inventory Control (CPIM). About Jean Forcione Jean Forcione 35-year career has been devoted to the healthcare industry, spanning prescription pharmaceuticals, consumer healthcare, diagnostics, and medical devices. Jean has held senior executive and board positions at both privately held and publicly traded organizations, including Aventis, Pharmacia, Pfizer, Johnson &Johnson, Phadia, Thermo Fisher Scientific, BBI Group and Orion Biotechnology. Jean’s focus and expertise revolves around general management, commercialization and M&A. Geographically, he has worked and been responsible for businesses around the globe. In the past 14 years, he has been focused on Private Equity backed businesses, first as an investor/executive and in the last 8 years as an investor, non-executive director, and chairman. During this period, Jean has been closely involved with exits totalling 2.9B € in EV. Mr. Forcione has a proven track record of building high performance teams and delivering outstanding value creation for shareholders. Grant of options The Company announces that the Board of Directors has approved the granting of 775,000 stock options (the “ Options ”) to directors and consultants. Of these options, 250,000 were granted to directors. These options are exercisable (‘‘ vested ’’) at a price of $0.20 from their grant date, for a period of 10 years following the grant date. About Devonian Devonian Health Group Inc. (Devonian)is a late-stage botanical pharmaceutical corporation with novel therapeutic approaches to targeting unmet medical needs. Devonian’s core strategy is to develop prescription botanical drugs from plant materials and algae for the treatment of inflammatory-autoimmune diseases including but not limited to ulcerative colitis and atopic dermatitis. Based on a foundation of over 15 years of research, Devonian’s focus is further supported by a US-FDA set of regulatory guidelines favouring a more efficient drug development pathway for prescription botanical drug products over those of traditional prescription medicines. Devonian is also involved in the development of high-value cosmeceutical products leveraging the same proprietary approach employed with their pharmaceutical offerings. Devonian is listed on the TSX Venture Exchange ( TSXV: GSD ) as well as the OTCQB Venture Exchange ( OTCQB: DVHGF ). For more information, visit www.groupedevonian.com Forward Looking Statements This press release contains forward-looking statements about Devonian’s objectives, strategies and businesses that involve risks and uncertainties. These statements are “forward-looking” because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, Devonian’s ability to develop, manufacture, and successfully commercialize value-added pharmaceutical and dermo-cosmeceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Devonian to take advantage of business opportunities in the pharmaceutical and dermo-cosmeceutical industries, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Devonian’s prospectus dated April 21 st , 2017 under the heading “Risk Factors” related to Devonian’s business. As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.