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SPY001 is a novel, half-life extended α4β7 antibody in development for the treatment of Inflammatory Bowel Disease (IBD) SPY001 pharmacokinetic (PK) data up to eight months continues to support a potential best-in-class profile, including a half-life more than three times that of vedolizumab SPY001 pharmacodynamic (PD) data up to eight months showed that a single dose of SPY001 resulted in rapid and sustained saturation of α4β7 receptors at expected Phase 2 trough concentrations Spyre remains on track to initiate its planned platform Phase 2 trial in mid-2025 that includes SPY001, followed by SPY002 (TL1A), SPY003 (IL-23), and combinations thereof, with initial monotherapy data expected in 2026 WALTHAM, Mass., May 5, 2025 /PRNewswire/ -- Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the "Company" or "Spyre"), a clinical-stage biotechnology company advancing best-in-class antibody engineering, dose optimization, and rational therapeutic combinations for the treatment of Inflammatory Bowel Disease ("IBD") and other immune-mediated diseases, today announced two poster presentations at Digestive Disease Week (DDW) 2025, being held May 3-6, 2025, in San Diego, California. Spyre presented results out to eight months of follow up from its SPY001 Phase 1 program. Updated results from our ongoing Phase 1 trial of SPY001, our novel half-life extended α4β7 antibody for the treatment of IBD, continues to show that SPY001 is well tolerated, has a half-life of more than three-fold compared to vedolizumab based on population PK modeling, and sustains target engagement at expected Phase 2 trough concentrations. This longer follow-up data strengthens the potential for SPY001 to demonstrate improved induction responses with greater exposures as well as durable responses with quarterly or biannual maintenance dosing. Spyre presented expanded preclinical data on combined inhibition of α4β7 integrin and TL1A cytokine in murine colitis models. Data presented demonstrate that combined inhibition of α4β7 integrin and TL1A cytokine is superior to either monotherapy in mouse models of colitis. "Extended follow-up data continue to show that SPY001 is well tolerated and has a PK and PD profile that supports potential best-in-class quarterly or biannual dosing for patients with IBD," said Deanna Nguyen, MD, SVP of Clinical Development at Spyre. "We look forward to testing SPY001 as a monotherapy and as a backbone for combinations in our Phase 2 platform trial in ulcerative colitis patients, which remains on-track to begin mid-year." The poster will be available for viewing during the DDW exhibition, and details are as follows: Title: Interim PK Data for SPY001, a Novel Half-Life Extended Monoclonal Antibody Targeting α4β7, Suggest a Potential for Q3M or Q6M Maintenance Dosing for Inflammatory Bowel Disease Authors: D Nguyen, L Yan, K Hew, P Patel, R McLean, R Himes, T Das, M Huyghe, B Connolly, J Friedman Title: Combined inhibition of TL1A and integrin β7 is superior to either monotherapy in mouse models of colitis and coadministration of SPY001 and SPY002 demonstrates no drug-drug effects on exposure in non-human primates Authors: M Siegel, J Friedman, D Nguyen, J McNally, M Kennedy, O Ballew, M Rose, A Spencer Full session details can be accessed via the DDW Program. About SPY001 SPY001 is an investigational novel, extended half-life monoclonal antibody targeting α4β7 for the 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. SPY001 targets the same epitope as vedolizumab and demonstrates equivalent potency and selectivity as vedolizumab in head-to-head preclinical studies. Interim data from a Phase 1 trial demonstrated that SPY001 was well tolerated and exhibited a human half-life of ~80 days, approximately three-fold greater than vedolizumab. This half-life supports potential quarterly or biannual SC maintenance dosing in a single autoinjector compared to vedolizumab's Q2W SC profile. Based on initial Phase 1 clinical data, the company plans to initiate a Phase 2 platform trial in ulcerative colitis in mid-2025. About Spyre Therapeutics Spyre Therapeutics is a biotechnology company that aims to create next-generation inflammatory bowel disease (IBD) and other immune-mediated disease products by combining best-in-class antibody engineering, dose optimization, and rational therapeutic combinations. 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 including, without limitation, Spyre's ability to achieve the expected benefits or opportunities with respect to its pipeline of product candidates such as potential best-in-class dosing regimen and safety profile of SPY001 in humans; expectations regarding the drug delivery of SPY001, including in the form of a single autoinjector; Spyre's future clinical development activities, including the expected design and timing of the planned platform Phase 2 trial of SPY001, SPY002, SPY003 and combinations thereof and timing of each cohort and data readouts; the potential therapeutic benefits of Spyre's product candidates as monotherapies or in combinations and their extended half-life, including the expected duration of half-life in comparison to competitor products and the potential efficacy, durability and exposure of induction responses for SPY001; and the timing and results of clinical trials. 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 From 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. SOURCE Spyre Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

— XENITH-UC, a Phase 2b study of XmAb942 in participants with ulcerative colitis, to begin in the second half of 2025 — — Single and multiple doses of XmAb942 are well tolerated and safety profile is consistent with the anti-TL1A drug class — — XmAb942 half-life supports a 12-week maintenance dosing interval in XENITH-UC — — Lead selection for XmAb TL1A x IL23p19 program on track for first-in-human study start in 2026 — — Management hosting webcast and conference call at 5:00 p.m. ET / 2:00 p.m. PT today — PASADENA, CA, USA I April 29, 2025 I Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and autoimmune diseases, today announced positive interim results from its first-in-human study of XmAb942, a high-potency, extended half-life, investigational anti-TL1A antibody in clinical development for patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). Interim results from the healthy volunteer dose-escalation study indicate that XmAb942 is well tolerated at single and multiple doses. Pharmacokinetic analysis of the single dose cohorts estimates a human half-life of greater than 71 days for XmAb942, which supports a 12-week dosing interval during maintenance treatment. Based on these positive interim results, Xencor is initiating the XENITH clinical program, advancing XmAb942 into a Phase 2b study in patients with moderate-to-severely active UC (XENITH-UC), with the expected study start in the second half of 2025. Lead selection for Xencor’s XmAb TL1A x IL23p19 bispecific antibody continues to advance. New in vitro studies show that several lead candidates match the target inhibition potency of commercial monospecific antibodies, but in a simple bispecific immunoglobulin G (IgG) format. Currently, these candidates are in final lead selection studies and manufacturing, in parallel, to prepare for the first-in-human study planned for 2026. “Our Phase 1 data for XmAb942 validate our design goals for a best-in-class anti-TL1A therapy, combining high potency with less frequent dosing to potentially improve clinical outcomes and convenience for patients living with inflammatory bowel disease,” said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. “We are excited to start our Phase 2b XENITH-UC trial later this year to efficiently support dose selection for pivotal studies, and we are poised to select our TL1A x IL23p19 bispecific lead candidate for an anticipated Phase 1 start in 2026. These and other milestones across our clinical portfolio are supported by our strong cash position.” Key Highlights From Phase 1 Study Interim Results The Phase 1 study of XmAb942 in healthy volunteers is a randomized, double-blind, placebo-controlled, dose-escalation trial, exploring intravenous (IV) and subcutaneous (SC) dose administration, at three escalating dose levels. The interim results reflect analyses with subjects in single dose cohorts (IV, n=24; SC, n=24) and in multiple dose cohorts (IV, n=16). XENITH-UC: Phase 2b Study in Ulcerative Colitis (UC) The Phase 2b study of XmAb942 in UC (XENITH-UC) will be a randomized, double-blind, placebo-controlled trial in patients with moderate-to-severely active UC, whose disease has progressed after at least one conventional or advanced therapy. XmAb942 will be administered intravenously during the 12-week induction period and subcutaneously every 12 weeks during the maintenance period. The primary endpoint of the study will be clinical remission based on the modified Mayo score at week 12. The study is designed to enroll approximately 220 patients across three induction dose levels and powered to enable Phase 3 dose selection. XENITH-UC is expected to start in the second half of 2025. Conference Call and Webcast Xencor will host a conference call and webcast today at 5:00 p.m. ET (2:00 p.m. PT) to review the interim results outlined in this news release. The live webcast of the conference call may be accessed through this link and through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com . A recording will be available for at least 30 days. About XmAb942 XmAb942 is a high-potency, extended half-life, investigational anti-TL1A antibody in clinical development for patients with inflammatory bowel disease (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The first generation of anti-TL1A antibodies, designed to block the interaction between the DR3 receptor and its ligand TL1A, have reduced disease activity in patients with UC and CD in multiple clinical studies. Interim results from a Phase 1 dose-escalation study in healthy volunteers indicate that XmAb942 is well tolerated at single and multiple doses. Pharmacokinetic analysis of the single dose cohorts estimates a human half-life of greater than 71 days for XmAb942, which supports a 12-week dosing interval during maintenance treatment. About Xencor Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and autoimmune diseases. More than 20 candidates engineered with Xencor’s XmAb® technology are in clinical development, and multiple XmAb medicines are marketed by partners. Xencor’s XmAb engineering technology enables small changes to a protein’s structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com . SOURCE: Xencor

MIDDLETOWN, DE, USA I April 17, 2025 I Earendil Labs, a global leader in AI-driven research and development of next-generation biologics therapeutics, and Sanofi today announced that they have entered into a license agreement for two potential first-in-class bispecific antibodies in the field of autoimmune and inflammatory bowel diseases. Under the agreement, Sanofi will obtain exclusive worldwide rights to two bispecific antibodies, HXN-1002 and HXN-1003, both utilizing Earendil Labs’ proprietary AI and high-throughput discovery & research platform. This transaction is subject to customary closing conditions. As part of the agreement: “We are thrilled to collaborate with Sanofi, a global leader in immunology, to advance the development of two bispecifics, HXN-1002 and HXN-1003, for autoimmune and inflammatory bowel diseases,” said Jian Peng, PhD, CEO of Earendil Labs, “Our platform leverages state-of-the-art predictive protein modeling and high-throughput biology, revolutionizing the discovery and development of bispecific antibodies. This collaboration underscores Earendil Labs’ capability to generate potential first-in-class or best-in-class product candidates, with the aim of transforming patient care.” Zhenping Zhu, MD, PhD, President & co-CEO of Earendil Labs, added: “Autoimmune diseases, which affect multi-millions of patients, are characterized by chronic disease process and high relapse rates. These diseases often require life-long treatment, severely impacting patients’ quality of life and significantly increasing the societal burden. Though multiple agents have been approved for clinical treatment, their efficacy often remains limited, highlighting significant unmet medical needs. We firmly believe that Sanofi’s extensive expertise in the autoimmune disease field will significantly accelerate the development of HXN-1002 and HXN-1003, ultimately bringing these potentially life-changing treatments to patients worldwide as soon as possible.” About Earendil Labs ： Earendil Labs is a US-based biotech company redefining biopharmaceutical innovation with its cutting-edge AI-powered platform. By combining advanced machine learning, generative protein engineering, and high-throughput experimental techniques, Earendil Labs and its affiliate Helixon Therapeutics streamline drug discovery & research process with aim of significantly accelerating drug development. Earendil Labs’ proprietary integrated framework enables precise optimization of functionality, manufacturability, and developability of protein-based biologics with first-in-class or best-in-class potential. About HXN-1002: HXN-1002 is a bispecific antibody targeting both α4β7 and TL1A. By simultaneously inhibiting two clinically validated targets, HXN-1002 holds great potential to significantly improve clinical efficacy, particularly for the refractory patients. It is designed to provide a treatment option for patients with moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD). About HXN-1003: HXN-1003 targets TL1A and IL23, two central drivers of inflammation in various human autoimmune diseases. By simultaneously blocking both pathways, the bispecific antibody has shown synergistic efficacy in preclinical models of colitis and skin inflammation, with great potential to address unmet needs in patients refractory to currently existing therapies. SOURCE: Earendil Labs