MAdCAM-1

Portfolio of Oral Selective α4β7 Inhibitors Acquired from EA Pharma, Eisai’s GI Subsidiary Phase 2 Clinical Program in Ulcerative Colitis to Start in First Half of 2025 with Lead Asset Seasoned Executive Team with History of Execution in Inflammatory Bowel Disease Drug Development toJoin Ensho on July 1 Founded by Neena Bitritto-Garg, Veteran Biotech Equity Research Analyst and Former Eisai Staffer MORRIS PLAINS, N.J., June 27, 2024 (GLOBE NEWSWIRE) -- Ensho Therapeutics, Inc., a privately held, clinical-stage biopharmaceutical company focused on developing breakthrough oral therapies for patients with inflammatory diseases, launched today with the announcement that it has acquired a portfolio of oral α4β7 integrin inhibitors through a worldwide exclusive license agreement with EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd. Under the terms of the agreement, Ensho has the right to develop, manufacture, and commercialize these assets globally, excluding certain Asian jurisdictions. The two companies jointly announced the exclusive license agreement in a separate press release today. Based on results of an extensive Phase 1 clinical program, Ensho has selected NSHO-101, (also known as EA1080), as its lead drug candidate from the portfolio. The Phase 1 program evaluated single and multiple ascending doses of NSHO-101 in over 180 healthy subjects. Results demonstrated favorable pharmacokinetics (PK) and pharmacodynamics (PD), including target engagement. NSHO-101 was generally safe and well-tolerated in healthy subjects. Results of the Phase 1 program support Ensho’s plans to initiate Phase 2 clinical development in the first half of 2025, starting with ulcerative colitis (UC). Neena Bitritto-Garg, CFA, founder, president and chief executive officer of Ensho, stated, “We are thrilled to acquire this portfolio of oral selective α4β7 integrin inhibitors derived from AJM300, an oral α4 inhibitor that has been approved in Japan for induction therapy in UC. This, along with my history with Eisai and EA Pharma’s impeccable standards for continuous improvement in drug development, led me to found Ensho around this portfolio. We believe NSHO-101 could be a transformational alternative therapy for patients who continue to suffer from IBD despite multiple lines of therapy.” Ensho has recruited a world-class team of executives with decades of experience in inflammatory and gastrointestinal (GI) disease drug development. The team will join Ms. Bitritto-Garg to develop and potentially commercialize these important oral agents for the inflammatory bowel disease (IBD) market. Ms. Bitritto-Garg continued, “I am very pleased to welcome to Ensho our seasoned team of executives, including Bittoo Kanwar, M.D., former chief medical officer of Telavant, which was acquired by Roche last year. The team’s decades of experience in IBD drug development will enable us to not only move quickly, but also smartly, into Phase 2 clinical development with NSHO-101.” Bittoo Kanwar, M.D., stated, “Joining Neena to advance Ensho and its portfolio of promising IBD assets was a tremendously attractive opportunity, given the significant unmet medical needs in IBD, the high potential and validated mechanism of α4β7, and the potential of our novel, oral clinical development candidates to offer differentiated attributes to patients and physicians looking for therapeutic alternatives. In collaboration with our newly formed Ensho team, many of whom have a long history of working together, we look forward to expeditiously advancing our lead asset, NSHO-101, into Phase 2 development early next year.” Ensho Therapeutics was borne out of Ms. Bitritto-Garg’s experience working at Eisai, the parent company of EA Pharma, on business development and in management of the company’s key alliance with Biogen Inc. on Leqembi (lecanemab), which is currently being launched in multiple countries for the treatment of early Alzheimer’s disease. She brings to Ensho nearly a decade’s worth of experience as an equity research analyst covering the biotechnology sector, including the neuroscience and immunology therapeutic areas. Immediately prior to founding Ensho, she led biotech and biopharma equity research strategy at multiple global banks, including at Citigroup Inc., where she was the head of U.S. biotechnology equity research. Ms. Bitritto-Garg is a graduate of the Roy and Diana Vagelos Program in Life Sciences and Management (LSM) at the University of Pennsylvania and holds dual degrees in Biochemistry (B.A.) from the College of Arts and Sciences and Economics (B.S.) with a concentration in finance from Wharton. Seasoned Executives to Join Ensho July 1, 2024Effective July 1, 2024, a seasoned team of executives with decades of experience in the discovery, development, and management of biotechnology companies in the inflammatory disease and IBD space will join Ensho. This team will be led by Bittoo Kanwar, M.D., who will join Ensho as chief executive officer. Andy Whitney, Ph.D. will be named chief scientific officer, Suzanne Vyvoda will act as chief operating officer, and Emily Weng, Sc.D. will join the company as chief data science officer. Neena Bitritto-Garg will continue to oversee the team as founder, president and executive chair of Ensho. Bittoo Kanwar, M.D. Dr. Kanwar will join Ensho as chief executive officer. His strategic development and execution of inflammatory disease programs spans more than two decades and includes roles as chief medical officer of Telavant Holdings, Inc., a Roivant company acquired by Roche in 2023, where he oversaw the clinical development of RVT-3101, an anti-TL1A antibody, in UC; chief medical officer of Applied Molecular Transport, Inc., where he led the company’s IBD-focused clinical development programs; vice president, head of clinical development at Protagonist Therapeutics, Inc., where he also led clinical programs in IBD; and clinical domain lead for IBD at Gilead Sciences, Inc., where he also supported programs in liver fibrosis/NASH, and Hepatitis B and C. Dr. Kanwar was an associate professor at the University of California, San Francisco (UCSF), focused on researching the role of the gut adaptive immune response in both HIV infection and IBD. He holds a B.S. from the University of Minnesota and an M.D. from the University of Iowa. He completed his residency at Rush University Hospitals in Chicago and a fellowship in pediatric gastroenterology at UCSF. Andy Whitney, Ph.D.Dr. Whitney will join Ensho as chief scientific officer. He brings to Ensho over 25 years of experience in drug discovery and development in autoimmune/inflammatory, oncology, and rare diseases. He has led multiple drug discovery projects as senior vice president, head of preclinical development and translational science at Applied Molecular Transport; vice president, biology at BridgeBio Pharma, Inc.; director in Gilead’s inflammation and oncology research group; and was one of the earliest scientists at CGI Pharmaceuticals where he led biology, bioinformatics, and project teams until its acquisition by Gilead. Andy was an NSF postdoctoral fellow at the University of Geneva, Switzerland. He holds an A.B. from Harvard College and a Ph.D. in cell biology from Yale. Suzanne VyvodaMs. Vyvoda will join Ensho as chief operating officer. She brings to Ensho over 20 years of execution and management of drug development and clinical operations programs, including as vice president and head of development operations at Telavant, a Roivant company acquired by Roche in 2023; vice president of development operations and head of clinical operations at Applied Molecular Transport; director of clinical operations at AbbVie Inc.; senior clinical program manager at Gilead and senior manager of clinical operations at BioMarin Pharmaceutical Inc. Suzanne holds a B.S. in sociology and economics from the University of Utah. Emily Weng, Sc.D. Ms. Weng will join Ensho as chief data science officer. She brings to Ensho two decades of expertise in applying statistical and design methods throughout the diverse aspects of research and development programs across broad therapeutics pipelines in biopharmaceutical industry, including immunology and inflammatory diseases. She served as vice president, head of biometrics and data science at Telavant, a Roivant company acquired by Roche in 2023; vice president, head of biometrics at Applied Molecular Transport; senior director, biometrics, and statistical head of respiratory TA at Theravance Biopharma, Inc., and director, biostatistics at Allergan Plc, acquired by AbbVie in 2020. Ms. Weng holds an Sc.D. in cancer biology with a minor in biostatistics and an M.S. in epidemiology from Harvard T.H. Chan School of Public Health. She holds an Executive M.B.A. from the UCLA Anderson School of Management. About Selective a4b7 Integrin Inhibitionα4β7 is a cell surface receptor that helps regulate the migration of immune cells to the intestine and plays a key role in controlling inflammatory responses. It binds to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on intestinal venules and is upregulated in response to inflammation. This interaction helps facilitate the transport of leukocytes and recruitment of effector lymphocytes to the gut mucosa in IBD. Because α4β7 is found primarily in the gut, this localized action provides immune cell inhibition where it is most relevant, potentially minimizing side effects and preserving overall immune cell function. Decades of research validate α4β7 inhibition as an anti-inflammatory mechanism in IBD, which has been further substantiated by the approval of a commercially available antibody, vedolizumab. Yet, there are no approved orally administered α4β7 inhibitors agents for the treatment of IBD. About NSHO-101 (also known as EA1080)NSHO-101 is a novel, oral, selective α4β7 integrin inhibitor designed for the potential treatment of patients with IBD. The Phase 1 clinical program for NSHO-101 evaluated 184 healthy subjects to assess safety, tolerability, food effects, PK and PD of single and multiple ascending doses of NSHO-101. NSHO-101 demonstrated target engagement in this Phase 1 program. There were no appreciable increases in peripheral lymphocytes, suggesting its activity is gut-restricted. NSHO-101 was generally safe and well tolerated. Ensho plans to initiate Phase 2 clinical development of NSHO-101 as a potential treatment for UC in the first half of 2025. About Ensho Therapeutics, Inc.Ensho Therapeutics, Inc. is a privately held, clinical-stage biopharmaceutical company focused on developing breakthrough oral therapies for patients with inflammatory diseases. The company’s initial focus is on a pipeline of oral, selective small molecule inhibitors of lymphocyte homing integrin α4β7 for IBD, a mechanism already validated by a commercially available antibody. Ensho’s assets were acquired from EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd., that is focused on gastrointestinal disease. Ensho is preparing to initiate a Phase 2 clinical program in UC with NSHO-101, the lead asset in the company’s pipeline. For additional information on Ensho Therapeutics, Inc., please visit www.enshorx.com. Contacts:Media:Aljanae ReynoldsAreynolds@wheelhouselsa.com Investors: info@enshorx.com

Ensho Acquired Rights to Develop and Commercialize EA1080 and Portfolio of Other Oral Selective α4β7 Integrin Antagonists in All Territories Excluding Japan, China, Hong Kong, Macau, South Korea, Taiwan and ASEANCHUO-KU, TOKYO and MORRIS PLAINS, N.J., June 27, 2024 (GLOBE NEWSWIRE) -- EA Pharma Co., Ltd. (President, Hidenori Yabune; “EA Pharma”) and Ensho Therapeutics, Inc. (Founder, President and Chief Executive Officer; Neena Bitritto-Garg; “Ensho”) announced today that the two companies have signed a worldwide exclusive license agreement for the rights to develop, manufacture and commercialize novel oral inflammatory bowel disease treatments EA1080 and a portfolio of other oral selective α4β7 integrin antagonists for the global market excluding Japan, China, Hong Kong, Macau, South Korea, Taiwan and ASEAN. Under the terms of the license agreement, in exchange for full commercialization rights in its territory, Ensho will conduct global clinical studies for EA1080, in collaboration with EA Pharma. EA Pharma will receive from Ensho payments on achievement of certain development, regulatory, and commercial milestones, and tiered royalties up to a low double digit percentage of net sales for EA1080. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease, and is characterized by inflammation in the gut mucosa which results in abdominal pain, diarrhea, and bloody stools. In many cases, patients may experience remission, but ultimately relapse, which results in an overall decline in quality of life. The mechanism of onset of IBD remains unknown. In Japan, IBD is considered a “designated intractable disease” by the Ministry of Health, Labour and Welfare. In 2019, the number of patients registered in Japan with UC and Crohn’s disease were nearly 220,000 and 70,000, respectively, with prevalence increasing in recent years.1 In IBD, lymphocytes and other inflammatory cells excessively surround and invade the gut mucosa, mediated by binding of integrins expressed on the surface of inflammatory cells to adhesion molecules, such as MAdCAM-1, that are excessively expressed on endothelial cells in the gut mucosa. EA1080 is an orally-available small molecule antagonist of α4β7 integrin. EA1080 can selectively inhibit α4β7 integrin cell adhesion mediated by binding to MAdCAM-1, suppressing invasion of lymphocytes into the gut mucosa and quelling inflammation. “EA1080 is a novel orally-available small molecular α4β7 integrin antagonist created based on our original and unique drug discovery platform. We expect that the collaboration with Ensho, which is based in the United States and has strengths in the immunology and inflammatory disease area, will synergize the knowledge of both companies to accelerate the global development of EA1080 to provide a new treatment option for patients with IBD,” said Hidenori Yabune, President of EA Pharma. “Ensho is thrilled to acquire this portfolio of oral, highly selective α4β7 integrin antagonists, led by EA1080, that have been refined through years of impeccable research by the EA Pharma team,” stated Neena Bitritto-Garg, CFA, Founder, President, and Chief Executive Officer of Ensho. “We believe these compounds could be transformational for patients suffering with IBD, as selective α4β7 antagonists have been proven to be safe and effective, but the need for oral agents remains. Our clinical development strategy is already set, and we plan to advance EA1080 into Phase 2 clinical development in the first half of 2025 so that we may deliver new solutions to patients expeditiously.” More Information About EA Pharma EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd. for gastrointestinal disease area, was established in April 2016 by integration of the gastrointestinal business unit with more than 60 years' history of the Eisai Group and the gastrointestinal business unit of the Ajinomoto Group having amino acid as its business core. EA Pharma Co., Ltd., is a gastrointestinal specialty pharmaceutical company with a full value chain covering R&D, production & logistics and sales & marketing. For further information on EA Pharma Co., Ltd., please visit https://www.eapharma.co.jp/ About Ensho Therapeutics, IncEnsho Therapeutics, Inc. is a privately held, clinical-stage biopharmaceutical company focused on developing breakthrough oral therapies for patients with inflammatory diseases. The company’s initial focus is on a pipeline of oral, selective small molecule inhibitors of lymphocyte homing integrin α4β7 for inflammatory bowel disease (IBD), a mechanism already validated by a commercially available antibody. Ensho’s assets were acquired from EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd. focused on gastrointestinal disease. Ensho is preparing to enter Phase 2 clinical trials in IBD with EA1080, the lead asset in the company’s pipeline. For additional information on Ensho Therapeutics, Inc., please visit www.enshorx.com. Forward-looking statementsThis Website contains forward-looking statements that involve risks, uncertainties, and assumptions. If risks or uncertainties ever materialize or the assumptions prove incorrect, our actual results may differ from those expressed or implied by such forward-looking statements. All statements other than statements of historical facts could be deemed forward-looking, including, but not limited to, any statement of the plans, strategies, and objectives of management for future operations, including but not limited to our clinical development and commercialization plans; any projections of financial information; any statements about historical results that may suggest trends for our business; any statements of expectation or belief regarding future events, potential markets or market size, technology developments, our product pipeline, clinical data, results or practices or the implications thereof, enforceability of our intellectual property rights, competitive strengths or our position within the industry; and any statements of assumptions underlying any of the items mentioned. Media InquiriesEA Pharma Co., Ltd.Corporate Communication Dept.TEL： +81(0)80-4176-5206Ensho Therapeutics, Inc.Investor and Media Relations Email：info@enshorx.com 1 “Basic treatment guidance for patients with ulcerative colitis” (revised March 2020), Research group for intractable inflammatory bowel diseases, Research project on rare and intractable diseases, Health and Labour Sciences Research Grants

Preclinical data for SPY001 demonstrate the potential for improved dosing over standard of care, including the potential for dosing every eight or twelve weeks compared to dosing every two weeks for subcutaneous vedolizumab Interim subcutaneous pharmacokinetic and safety data from healthy volunteers anticipated by year-end 2024 SPY002, an extended half-life anti-TL1A antibody designed for enhanced potency to both TL1A monomers and trimers, remains on track to begin first-in-human studies in the second half of 2024 All three next-generation antibodies targeting α4β7, TL1A, and IL-23 are on track to be in the clinic within 12 months, each serving as backbones for potential best-in-class combinations WALTHAM, Mass., June 18, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the "Company" or "Spyre"), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches to target improved efficacy and convenience in the treatment of Inflammatory Bowel Disease ("IBD"), today announced that it has initiated dosing of healthy volunteers in its first clinical trial of SPY001, an investigational novel half-life extended anti-α4β7 monoclonal antibody. "The Spyre team has executed efficiently to achieve this milestone within a year of our public launch. SPY001 is the first of our programs across three of the most impactful mechanisms in IBD, namely α4β7, TL1A, and IL-23, all of which are expected to enter the clinic within the next twelve months," said Cameron Turtle, D.Phil., Chief Executive Officer of Spyre. "We look forward to highlighting interim data for SPY001 by the end of this year, which we expect will confirm that SPY001 is well tolerated with a half-life that enables a convenient Q8-12W subcutaneous dosing schedule, with interim data for our T1LA program to follow." The SPY001 Phase 1 trial is a double blind, placebo-controlled study in healthy volunteers and consists of a single-ascending dose (SAD) component and a multi-ascending dose (MAD) component. The study is expected to enroll approximately 48 healthy adult participants into four SAD cohorts and two MAD cohorts. The primary endpoint is safety, with pharmacokinetics (PK) serving as a secondary endpoint. We expect interim safety and PK data from this trial by year-end 2024. Pending data from the Phase 1 trial, the company anticipates progressing into Phase 2 development with SPY001 in 2025. "α4β7 inhibition is a preferred first-line treatment option among gastroenterologists given its favorable safety pro a gut-selective mechanism of action and demonstrated efficacy superiority over TNF inhibition in the VARSITY study," said Deanna Nguyen, M.D., SVP of Clinical Development at Spyre. "We believe this unique safety and efficacy profile, combined with a more convenient dosing frequency, could make SPY001 an ideal backbone for combination therapy for IBD with the inhibition of other highly active mechanisms including T1LA and IL-23." About SPY001 SPY001 is an investigational novel, subcutaneous extended half-life monoclonal antibody targeting α4β7 for the potential treatment of IBD. IBD is a chronic condition characterized by inflammation in the gastrointestinal tract and encompasses two main disorders: ulcerative colitis and Crohn's disease. In the United States, it is estimated that approximately 2.4 million individuals currently have IBD. In head-to-head preclinical studies, SPY001 demonstrated equivalent potency to vedolizumab in blocking MadCAM-1 adhesion and exhibited significantly longer half-life with the potential to deliver dosing as infrequently as once every two or three months. A Phase 1 trial of SPY001 in healthy volunteers is ongoing, and the Company expects interim safety and pharmacokinetic data by year-end 2024. Pending data from the Phase 1 trial, the company anticipates progressing into Phase 2 development with SPY001 in 2025. About Spyre Therapeutics Spyre Therapeutics is a biotechnology company that aims to create next-generation inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, visit Spyre's website at . Forward Looking Statements Certain statements in this press release, other than purely historical information, may constitute "forward-looking statements" within the meaning of the federal securities laws, including for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995, concerning Spyre and other matters. These forward-looking statements include, but are not limited to, express or implied statements relating to Spyre's management team's expectations, hopes, beliefs, intentions or strategies regarding the future of its pipeline and business including, without limitation, Spyre's ability to achieve the expected benefits or opportunities with respect to SPY001 including obtaining interim data supporting target safety pro dosing schedule by end of year, the timing of commencing clinical studies for Spyre's two other programs and obtaining interim data for SPY002, patient enrollment results for the SPY001 Phase 1 trial and the potential of SPY001, SPY002 and SPY003 to become backbones for potential best-in-class combinations for IBD. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words "opportunity," "potential," "milestones," "pipeline," "can," "goal," "aim," "strategy," "target," "seek," "anticipate," "achieve," "believe," "contemplate," "continue," "could," "estimate," "expect," "intends," "may," "might," "plan," "possible," "predict," "project," "should," "will," "would" and similar expressions (including the negatives of these terms or variations of them) may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements are based on current expectations and beliefs concerning future developments and their potential effects. There can be no assurance that future developments affecting Spyre will be those that have been anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Spyre's control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited those uncertainties and factors described under the heading "Risk Factors" and "Note about Forward-Looking Statements" in Spyre's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors included in other filings by Spyre from time to time. Should one or more of these risks or uncertainties materialize, or should any of Spyre's assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Spyre. Follow Spyre Therapeutics on social media: @spyretx and LinkedIn Company Codes: NASDAQ-NMS:SYRE