Diabetes Mellitus, Type 1

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

Topas Therapeutics, a small German biotech company attempting to quell overactive immune systems, has revealed the first data from a study of its “tolerance induction” therapy for celiac disease. The results, to be presented at the Digestive Disease Week conference on Monday, come more than six months after Topas first declared success in the study via a press release , without divulging any data. The company discussed the therapy and shared the data with Endpoints News in an exclusive interview ahead of the conference, though many questions remain about the results. The 38-person trial focused on the safety of the company’s experimental nanoparticle treatment over seven weeks, its ability to steer immune cells toward a less inflammatory state, and patient-reported changes in gastrointestinal symptoms. Topas executives told Endpoints that the therapy was successful against those goals, even though granular data on safety and patient outcomes was missing from the presentation. They conceded that bigger and longer studies are still needed, but added that any relief from celiac disease would be a breakthrough. “There is both very much a medical need and big commercial opportunity in celiac,” Topas CEO Hugo Fry told Endpoints. Celiac disease is caused by an unwanted immune reaction to gluten, which is abundant in food. There’s no treatment or cure for the condition that, by some estimates, may affect as many as 1 in 100 people. Despite that, there are relatively few drug developers working on treatments. Topas is one of three companies, along with Anokion and Takeda, developing a potential immune tolerizing therapy in a Phase 2 study. Rather than merely tamping down on inflammation, the efforts aim to retrain the immune system to ignore triggers like gluten. “Tolerization is at that disease-modifying, almost curative end of the spectrum,” Fry said. It aims to do so by presenting nanoparticles decorated with tidbits of peptides that resemble the problematic parts of proteins that set off the immune system, known as antigens. For the celiac therapy, dubbed TPM502, the company uses three nanoparticles, each with a different antigenic peptide from the gluten protein. In many ways, the goal is opposite to that of a vaccine, which presents antigens to build the body’s reaction and create an immune response. Instead, Topas’ infused nanoparticles target specific cells in the liver that serve as a calming zone for T cells, where they learn to live peacefully alongside antigens that don’t warrant being attacked. “That’s the body’s natural hub of induced tolerization,” Fry said. “And it pushes them through that natural route.” Celiac was a good place to start looking for signals that the tolerization approach was working because doctors can easily provoke the immune system to flare up by having participants consume gluten, said Topas chief medical officer Cristina de Min. The company tested four doses of its nanoparticle therapy, ranging from 0.72 micromolar to 7.2 micromolar, in 26 patients. The other 12 patients got a placebo. Participants got the drug or placebo on day 1 and day 15 of the study and then consumed gluten a week later. De Min said that “the drug was remarkably safe,” largely resulting in side effects that resemble gluten consumption in celiac disease, including headache, pain, nausea and vomiting in 27 patients. But the company didn’t break this safety data down by side effect, or between participants who got the drug versus placebo. The company also said that there were three “grade 3” adverse events, the second highest severity, but didn’t say what they were. To get an idea of whether the treatment was working, Topas measured the release of the inflammatory immune protein IL-2 in response to being “challenged” with gluten. Only the highest dose of the therapy resulted in a significant decrease in IL-2 release. But when studying the gene expression of T cells before and after the therapy, the company found that all dose levels helped turn on genes that tamped down on inflammation and reduced genes that promoted inflammation. Topas also asked patients to rate their gastrointestinal symptoms before and after the treatment. The company said that people who got higher doses of the therapy had reduced symptoms, but the presentation was light on specific details. Topas emphasized that the study was not designed to test for efficacy. Another major caveat was the study’s strict inclusion criteria. Topas screened 391 people and recruited only one-tenth of them. Many prospective participants were excluded because they didn’t produce high enough levels of IL-2 in response to gluten consumption. “We wanted to make sure that only patients with measurable response would be involved,” de Min said. Even more patients were excluded because they didn’t have the certain immune system genotype that Topas focused on in this study. Topas is planning a Phase 2b study that will include a broader range of immune genotypes, accounting for 85% to 90% of people with celiac disease. Topas also wants to develop a tolerization therapy for type 1 diabetes, Fry said. But doing so will require more funding, and Fry is setting out to raise a €70 million Series D round. The company is currently funded through 2026 and isn’t planning to start a new study before then, he said.

- T1D Fund Joins Financing Syndicate - - Proceeds to Fund Remainder of Phase 2a 'ZONE' Trial and Nonclinical Development of a Once-Weekly Version of ZT-01 - TORONTO, May 1, 2025 /PRNewswire/ - Zucara Therapeutics Inc., ("Zucara" or the "Company") a diabetes life sciences company developing ZT-01, the first once-daily therapeutic to prevent hypoglycemia (low blood glucose levels) in people with diabetes, today announced that it has completed the second and final closing of its US$25 million Series B Financing (the "Financing"). The T1D Fund: A Breakthrough T1D Venture and other new investors invested a combined US$5 million to complete the Financing. As previously announced, strategic investor, Sanofi, and existing investor, The Perceptive Xontogeny Venture Fund ("PXV Fund I"), invested a combined US$20 million as part of the Financing's first closing. "We are thrilled to close our Series B financing, which will enable us to complete our Phase 2a clinical trial and the nonclinical activities to support a once-weekly version of ZT-01," said Michael Midmer, CEO of Zucara. "As one of the largest disease-focused impact investing funds in the world, the T1D Fund focuses on funding therapies that have significant potential for clinical impact in Type 1 diabetes, so we are delighted to have their support." T1D Fund Managing Director, Sylvia Tobé, commented, "Our investment builds on funding that our parent organization, Breakthrough T1D, previously granted to Zucara to support the discovery and clinical development of ZT-01. Having followed Zucara for some time, we are excited to support the further advancement of this promising candidate that has the potential to address a common and potentially life-threatening complication of Type 1 diabetes." In connection to the Financing, Dr. Tobé will join Zucara as a Board Observer. Dr. Tobé is an experienced biotech industry professional with over a decade of experience in the sector. Prior to joining the T1D Fund, she was a Principal on the investment team at Omega Funds, where she focused on early-stage investments and company creation in various therapeutic areas. She also previously served at publicly traded Ra Pharmaceuticals, a peptide drug discovery company, where she provided scientific leadership for multiple discovery programs within its internal pipeline and in collaboration with Merck. Dr. Tobé is a Board Director at DiogenX and a Board Observer at various biotech companies across the auto-immune and regenerative spaces. Proceeds from the Financing are expected to fund the remainder of Zucara's ongoing Phase 2a trial of the effect of ZT-01 On Nocturnal hypoglycemia Events in Type 1 diabetes ("T1D") mellitus ("ZONE"), and the nonclinical development of a once-weekly version of ZT-01. About The T1D Fund The T1D Fund is an impact investment fund focused on accelerating life-changing solutions to treat, prevent, and ultimately cure type 1 diabetes (T1D). Launched in December 2016, the T1D Fund is a unique, evergreen construct that is the first scaled, mission-driven venture fund established to catalyze the development of T1D cure-oriented therapies through equity investments. By partnering with additional sources of capital, including venture capital, corporations, and foundations, the T1D Fund is able to attract and effectively deploy capital towards disease-modifying therapies and potential cures for T1D. Managed by a dedicated team of investment professionals and supported by its foundational partners - including Breakthrough T1D (formerly JDRF) and the Helmsley Charitable Trust, the leading global organizations funding T1D research - the T1D Fund continues to pursue innovative approaches that have the curative potential to make a significant impact for people living with T1D. For more information, visit t1dfund.org or follow the T1D Fund on LinkedIn. About ZT-01 ZT-01 is designed to prevent potentially dangerous low blood glucose by restoring the body's ability to counterregulate hypoglycemia. In people without diabetes, α-cells secrete glucagon that signals the body to release its own glucose stores to prevent or reverse hypoglycemia. However, in people with insulin-dependent diabetes – including those with T1D and insulin-dependent Type 2 diabetes – evidence suggests that elevated secretion of pancreatic somatostatin suppresses glucagon release from α-cells. Zucara has demonstrated that, in people with T1D, the glucagon response can be increased with ZT-01, a first-in-class SST receptor 2 antagonist. About Zucara Therapeutics Inc. Zucara Therapeutics is developing ZT-01, a first-in-class, once-daily therapeutic to prevent hypoglycemia in people with T1D and insulin-dependent Type 2 diabetes. ZT-01 is designed to inhibit somatostatin, a pancreatic hormone that impairs the glucagon response to hypoglycemia in people with these conditions. ZT-01 is designed to restore glucagon secretion to prevent hypoglycemia, which could dramatically change diabetes disease management and improve both patient health and quality of life. For more information, visit . SOURCE Zucara Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED