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- Oral and poster presentations show novel, differentiated properties optimized to progress company’s nomination of lead development candidate for the treatment of autoimmune diseases - - FOCIS recognizes Exo with 2024 Annual Meeting Award for exceptional research and posters of merit - CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Exo Therapeutics, Inc., a company developing a pipeline of drug candidates that target exosites, unique small-molecule binding pockets that are distal to traditional active and allosteric sites, thereby reprogramming enzyme activity for precise and robust therapeutic effect, today presented a poster and oral presentation on its preclinical program targeting TBK1/STING interaction of the cGAS-STING pathway at the 24th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2024) in San Francisco. Data presented in both the poster and oral presentation show that the company has identified potent, selective exosite-targeted TBK1/STING inhibitors, demonstrated efficacy across preclinical models and optimized properties towards development candidate nomination. FOCIS also recognized Exo with the 2024 Annual Meeting Award for exceptional research and posters of merit for the Company’s poster and oral presentation. “Exo’s data look very promising, particularly the targeting of both interferon-beta and NF-kB pathways by your molecule,” said Mary K. Crow, M.D., Physician-in-Chief Emeritus at Hospital for Special Surgery and Professor of Medicine at Weill Cornell Medical College. “There is a great need to define the role of the TBK1/STING pathway in Systemic Lupus Erythematosus (SLE) and other autoimmune diseases. I hope Exo’s development program can soon move forward into patients with their interesting drug!” Exo’s goal is to expand the druggable universe with exosite-specific molecules that enable a new, tailored way to target and reprogram enzymes. Historically, active-site inhibitors have failed because of inadequate selectivity of their inhibitory activity, leading to off-target effects and poor therapeutic indices. Moreover, molecules focused on active or allosteric sites typically inhibit the full functionality of proteins, which can direct both beneficial and harmful effects. In contrast, TBK1/STING exosite inhibitors have the promise of mitigating the unwanted effects while providing therapeutic benefit. The presentations detailed Exo’s novel TBK1 exosite inhibitors that disrupt recruitment by STING for downstream activation of type-1 interferon and NF-κB responses. More specifically, TBK1 exosite inhibitors selectively inhibit the TBK1-STING axis while sparing non-disease relevant housekeeping functions of the kinase, which will be more likely to offer superior efficacy and an improved therapeutic window versus traditional approaches. The company also shared findings from rational and structure-based drug discovery efforts that demonstrated identification of a series of selective TBK1 exosite inhibitors with potent binding affinities that translate into nanomolar inhibition of IFNβ in THP1 cells and primary human cell types. Additionally, orally bioavailable TBK1 exosite inhibitors were evaluated in both in vivo and ex vivo models to inhibit proximal and distal pharmacodynamic markers upon stimulation with a STING agonist. Treatment with TBK1 exosite inhibitors caused a dramatic reduction of pro-inflammatory cytokines including IFNβ, CXCL-10, CXCL-9 and IFIT1 in a pathway-driven model, the TREX-1 null mouse. Additionally, Exo’s TBK1 exosite inhibitors have shown robust effects in SLE and Scleroderma patient samples. Most notably, when assessed for activity in SLE patient-derived human whole blood and PBMC, TBK1 exosite inhibitors robustly suppressed pathway activation. Similarly, upon activation of cGAS-STING-TBK1 pathway, TBK1 exosite inhibitors inhibited cytokine production in disease-relevant skin inflammatory models, fibroblasts and keratinocytes. Poster Details Title: A Novel Inhibitor of cGAS-STING-TBK1 Pathway with Broad Application in Autoimmune Diseases Date: Wednesday, June 19, 2024, 7:30 AM - 7:30 PM Poster Number: W102 Location: San Francisco Marriott Marquis – Salon 9, Lower B2 Level Oral Presentation Details Title: A Novel Inhibitor of cGAS-STING-TBK1 Pathway with Broad Application in Autoimmune Diseases Date: Wednesday, June 19, 2024, 4:15 PM - 4:30 PM Presenter: Bhavatarini Vangamudi, Ph.D. About Exo Therapeutics Exo Therapeutics is a small molecule drug discovery and development company co-founded by Professors David R. Liu, Alan Saghatelian, and Juan Pablo Maianti with a pioneering technology to address intractable pharmaceutical targets. By leveraging the company’s ExoSight™ platform, Exo is developing a deep pipeline of potent drug candidates that bind exosites, distal and unique binding pockets that have the potential to reprogram enzyme activity for precise and robust therapeutic effect. Through this specific and selective approach to challenging targets, the company's team of world-class researchers is unlocking breakthrough therapeutics in inflammation, oncology and a broad range of other diseases. For more information, visit .

Reports new positive interim data from the ongoing Phase 1 study of BHV-1300, Biohaven's lead investigational drug from its Molecular Degrader of Extracellular Proteins (MoDE™) platform BHV-1300 demonstrates dose-dependent and rapid IgG reductions within hours of administration No SAEs, no severe AEs, most AEs were mild, deemed unrelated to study drug and resolved spontaneously No clinically significant changes in LFTs across any dose cohorts to date Highlights advances from novel ion channel program targeting Kv7 activation and TRPM3 antagonism across multiple neurological, pain and neuropsychiatric disease indications Recently initiated a total of 5 pivotal clinical trials with selective Kv7 activator, BHV-7000, targeting focal epilepsy, idiopathic generalized epilepsy, bipolar disorder and major depressive disorder Released positive Phase 1 data with TRPM3 antagonist BHV-2100 showing drug concentrations above EC90 target and well-tolerated profile across all doses in SAD/MAD study; advancing Phase 2 study in migraine Anticipates Myostatin program topline data for Phase 3 Spinal Muscular Atrophy (SMA) study in 2H2024 Reports new preclinical data highlighting potential for taldefgrobep alfa as monotherapy and in combination with GLP-1 agonists for weight loss: Taldefgrobep alfa in combination with GLP-1 in the diet-induced obesity preclinical model showed greater reductions in body weight and fat mass, and a larger increase in lean muscle mass, compared to GLP-1 alone Taldefgrobep alfa demonstrated direct effects on fat reduction as measured by changes in adipocytes independent of increasing muscle mass Releases positive Phase 1 data with BHV-8000, a brain-penetrant TYK2/JAK1 inhibitor, showing preliminary safety and achievement of target concentrations with reductions in inflammatory biomarkers in SAD/MAD study Key updates for BHV-8000 include favorable regulatory feedback enabling initiation of registrational programs for the prevention of ARIA associated with amyloid lowering drugs and Parkinson's disease As announced in an earlier press release today, first patient dosed with Biohaven's novel Trop-2 antibody drug conjugate (ADC), BHV-1510, in Phase 1/2 trial, as monotherapy and initiating combination with Regeneron's anti-PDL1 Libtayo®(cemiplimab-rwlc), in advanced or metastatic epithelial tumors NEW HAVEN, Conn., May 29, 2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies, provides an overview of its development and regulatory advances across multiple therapeutic areas, and highlights the progress of its innovative degrader pipeline at the Company's 2024 Investor R&D Day today, held concurrently with the Yale Innovation Summit in New Haven, Connecticut. Members of Biohaven's senior management team and key opinion leaders will share updates with investors and research analysts. The presentation slides will be available on the Events and Presentations page of the Biohaven website. An audio webcast will be available within 24 hours of the presentation. Continue Reading Figure 1: Biohaven presented the first human dosing experience with a MoDE degrader of IgG at its annual R&D Day. Preliminary data shows rapid, dose-dependent, maximal mean reductions (% change from baseline) in IgG for each cohort observed within 96hrs after administration of BHV-1300 in its ongoing Phase 1 Study. (NOTE: the Box plot shows the placebo adjusted mean as a diamond and the red stars represent model predicted values. The top and bottom of the box represent the 75th and 25th percentiles of the data. The whiskers (“T” shapes) are drawn from the top and bottom of the box to the most distant observation within 1.5 times the interquartile range (1.5x IQR). Observations more than 1.5x IQR from the top or bottom of the box are shown as dots; preliminary data presented from Study 1300-101 is from an ongoing study and subject to change as database not yet cleaned or locked; IgG1-4 analyzed at Mayo Clinic Laboratories, Rochester MN). Figure 2: Biohaven’s novel TRPM3 antagonist has successfully completed Phase 1 study. Target plasma concentrations exceeded the EC90 by 20 minutes and were sustained above EC90 for several hours at all dose levels, confirming a potentially attractive PK profile for acute treatment of migraine and pain relief. Figure 3: New preclinical data presented at Biohaven’s R&D Day showing taldefgrobep alfa directly lowered lipid storage in adipocytes. This direct effect on adipocytes is in addition to the muscle enhancing effects of taldefgrobep alfa. Figure 4: Pharmacodynamic data from BHV-8000, brain penetrant TYK2/JAK1 inhibitor, from Biohaven’s Phase 1 study showing biomarker reduction of inflammatory pathways including hs-CRP and IFN-beta which are thought to drive the pathology of a numerous neurodegenerative disorders. Figure 5: Preclinical profile of BHV-1510 Trop-2 ADC positioned for potential differentiation as monotherapy as well as robust combination with anti-PD1. The combination of BHV-1510 + Anti-PD1 shows compelling synergy in syngeneic preclinical models. Figure 6: BHV-1510 toxicokinetic data demonstrates a highly stable ADC with minimal free payload in circulation.

CAMBRIDGE, Mass., Feb. 26, 2024 /PRNewswire/ -- Nona Biosciences, a wholly-owned subsidiary of HBM Holdings Limited committed to cutting-edge technology innovations and providing a total solution from "Idea to IND" ("I to ITM"), announced today that it has entered into a collaboration agreement with Boostimmune, a biotech company dedicated to developing next-generation anti-cancer therapies via modulating immune systems. The collaboration aims to leverage Nona's proprietary Harbour Mice® H2L2 (two light and two heavy chain) platform to accelerate the development of Antibody-Drug Conjugates (ADCs) against novel targets. Jingsong Wang, MD, PhD, Chairman of Nona Biosciences, expressed, "By leveraging our accumulated knowledge of ADC discovery and utilizing our advanced therapeutic antibody platforms validated by partners worldwide, this collaboration will expedite the development of first-in-class ADCs targeting cancer. Working alongside Boostimmune, we anticipate delivering transformative treatments, ultimately improving outcomes for all patients affected by cancer." Gwanghee Lee, Founder and CEO of Boostimmune, stated, "We are excited to collaborate with Nona Biosciences. Our strategic alignment of resources and knowledge will accelerate the development of ADC therapies against novel targets. Through this collaboration, we are confident in making significant strides in addressing the unmet needs of cancer patients." About Nona Biosciences Nona Biosciences (a wholly-owned subsidiary of HBM Holdings, HKEX: 02142) is a global biotechnology company committed to cutting-edge technology innovations and providing a total solution from "Idea to IND" ("I to ITM"), ranging from target validation and antibody discovery through preclinical research. The integrated antibody and antibody-related discovery services with multiple modalities range from antigen preparation, animal immunization, single B cell screening, to antibody lead generation and engineering, developability assessment and pharmacological evaluation, leveraging advantages of Harbour Mice® platforms and the experienced therapeutic antibody discovery team. Harbour Mice® generates fully human monoclonal antibodies in classical two light and two heavy chain (H2L2) format, and heavy chain only (HCAb) format. Integrating Harbour Mice® and a single B cell cloning platform, Nona Biosciences is focused on driving global inventions of transformative next-generation drugs. For more information, please visit: About Boostimmune Boostimmune is a biotech company developing innovative, first-in-class antibody-based therapies to address unmet needs in oncology. Its pipeline projects consist of naked monoclonal antibodies to modulate the tumor immune microenvironment, ADCs to novel targets with potential patient selection biomarkers and an ISAC (Immune Stimulator Antibody Conjugate) directly targeting immunosuppressive myeloid cells. Boostimmune was co-founded in 2021 by a world-class pioneering immunologist, Professor Tadatsugu Taniguchi at the University of Tokyo, who originally identified interferon beta, interleukin-2, and interferon regulatory factors (IRFs). SOURCE Nona Biosciences