Spyre Therapeutics Inc (SYRE) 2025 Conference June 04, 2025 08:10 AM ET Speaker0 Alrighty. Good morning, everyone. Really appreciate you joining us. My name is Akash Jawari. I am a pharma and biotech analyst here at Jefferies and this is day one of our wonderful New York Healthcare Conference. I've got Cameron from Spire. Cameron, why don't I hand it off to you for some brief introductory remarks and then we'll get started with the Q and A. Speaker1 Sounds good. Thanks for having me as always. So the the br ...

Spyre Therapeutics (SYRE) closed the last trading session at $15.55, gaining 6.1% over the past four weeks, but there could be plenty of upside left in the stock if short-term price targets set by Wall Street analysts are any guide. The mean price target of $53.50 indicates a 244.1% upside potential.The mean estimate comprises 10 short-term price targets with a standard deviation of $16.36. While the lowest estimate of $21 indicates a 35.1% increase from the current price level, the most optimistic analyst ...

Live audio webcasts and replays of these events will be available on the Spyre investor events website at https://ir.spyre.com/events-and-presentations. WALTHAM, Mass., May 28, 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 announ ...

Shares of Spyre Therapeutics (SYRE) have gained 14.7% over the past four weeks to close the last trading session at $14.93, but there could still be a solid upside left in the stock if short-term price targets of Wall Street analysts are any indication. Going by the price targets, the mean estimate of $53.50 indicates a potential upside of 258.3%.The mean estimate comprises 10 short-term price targets with a standard deviation of $16.36. While the lowest estimate of $21 indicates a 40.7% increase from the c ...

Exhibit 99.1 Spyre Therapeutics Reports First Quarter 2025 Financial Results and Provides Corporate Update On track for mid-year initiations of planned Phase 2 studies in ulcerative colitis ("UC") and rheumatoid arthritis ("RA"), providing for 7+ proof-of-concept readouts in 2026 & 2027 Reported extended follow-up Phase 1 data for SPY001, supporting that the molecule is well tolerated, has a pharmacokinetic ("PK") profile enabling quarterly or biannual dosing, and provides complete target engagement at expe ...

On track for mid-year initiations of planned Phase 2 studies in ulcerative colitis ("UC") and rheumatoid arthritis ("RA"), providing for 7+ proof-of-concept readouts in 2026 & 2027Reported extended follow-up Phase 1 data for SPY001, supporting that the molecule is well tolerated, has a pharmacokinetic ("PK") profile enabling quarterly or biannual dosing, and provides complete target engagement at expected Phase 2 trough concentrationsRemain on track to report interim Phase 1 data for SPY002 later this quart ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 ____________________________ FORM 10-Q ____________________________ (Mark One) x QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 OR o TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-37722 SPYRE THERAPEUTICS, INC. (Exact Name of Registrant as Specified i ...

Core Insights - SPY001 is a novel, half-life extended α4β7 antibody in development for the treatment of Inflammatory Bowel Disease (IBD) with a pharmacokinetic profile supporting a potential best-in-class status [1][3] - The company plans to initiate a Phase 2 trial in mid-2025, which will include SPY001 and other candidates, with initial data expected in 2026 [1][2] Group 1: SPY001 Development - SPY001 has shown a human half-life of approximately 80 days, which is more than three times that of vedolizumab, allowing for potential quarterly or biannual dosing [3][4] - Interim data from the Phase 1 trial indicates that SPY001 is well tolerated and maintains target engagement at expected Phase 2 trough concentrations [4] Group 2: Clinical Trials and Future Plans - The Phase 2 platform trial will test SPY001 as a monotherapy and in combination with other therapies for ulcerative colitis patients, expected to begin mid-2025 [2][3] - Initial monotherapy data from the Phase 2 trial is anticipated in 2026 [1] Group 3: Preclinical and Clinical Data - Preclinical studies indicate that combined inhibition of α4β7 integrin and TL1A cytokine is superior to either monotherapy in mouse models of colitis [4] - The pharmacodynamic data supports rapid and sustained saturation of α4β7 receptors with a single dose of SPY001 [1][4] Group 4: Company Overview - Spyre Therapeutics focuses on developing next-generation therapies for IBD and other immune-mediated diseases through advanced antibody engineering and therapeutic combinations [5] - The company's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23 [5]

Core Insights - Spyre Therapeutics has initiated a Phase 1 clinical trial for SPY003, an investigational anti-IL-23 monoclonal antibody, which is expected to offer improved dosing convenience and efficacy compared to first-generation therapies [1][2][3] - The company anticipates interim pharmacokinetic and safety data from the trial in the second half of 2025, which will inform the progression to a Phase 2 study in ulcerative colitis [1][2][3] Company Overview - Spyre Therapeutics is focused on developing next-generation therapies for Inflammatory Bowel Disease (IBD) and other immune-mediated diseases through advanced antibody engineering and therapeutic combinations [4] - The company’s pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23, with SPY003 being a key candidate [4] Clinical Trial Details - The Phase 1 trial of SPY003 is a double-blind, placebo-controlled study involving approximately 56 healthy adult participants, primarily assessing safety as the primary endpoint and pharmacokinetics as a secondary endpoint [2][3] - SPY003 has shown equivalent potency to risankizumab in preclinical studies, with a significantly longer half-life, potentially allowing for dosing as infrequently as once every six months [3]

Clinical Trial Timelines and Data Expectations - SPY001 (α4β7) Phase 1 interim data expected by November 2024, with full Phase 1 data expected by 2H 2025[22] - SPY002 (TL1A) Phase 1 interim data expected by 2Q 2025, with full Phase 1 data expected by 2H 2025[22] - SPY003 (IL-23) Phase 1 interim data expected by 2H 2025, with full Phase 1 data expected by 2H 2025[22] - SPY002 Phase 1 study initiated in Q4 2024, with high-concentration (200 mg/mL) citrate-free SC formulations developed for clinical studies[136] - SPY002 Phase 1 study initiated in 4Q 2024 with interim FIH data expected in 2Q 2025[143][146] - SPY003 Phase 1 study initiation expected in 1Q 2025 with interim FIH data expected in 2H 2025[156][167] - SPYRE plans Ph1 readouts for TL1A and IL-23 programs in 2025, with multiple Ph2 initiations expected[99] Half-Life and Pharmacokinetics - SPY001 (α4β7) has a half-life of >90 days, significantly longer than Vedolizumab's ~25 days[15] - SPY002 (TL1A) has a half-life of ~24 days, compared to Tulisokibart's ~12 days[15] - SPY003 (IL-23) has a half-life of ~30 days, compared to Risankizumab's ~9 days[15] - SPY001 Phase 1 interim data shows a half-life of >90 days, exceeding expectations and supporting potential for twice-yearly maintenance dosing[118][134] - SPY001 demonstrated dose-proportional pharmacokinetics between 300 mg and 1000 mg, with a half-life of >100 days in SAD cohorts[123] - SPY002 candidates exhibit >2-3x increased half-life in NHPs compared to first-generation anti-TL1As, with t1/2 of ~24 days for DC1 and ~28 days for DC2[141] - SPY002 human half-life targets ~65 days in humans based on PK modeling, supporting Q3M-Q6M maintenance dosing[149] - SPY003 exhibits >3x the half-life of risankizumab in NHPs (~30 days vs. ~9 days)[161][162] - SPY003 human half-life targets ~60 days in humans based on PK modeling, supporting Q3M-Q6M maintenance dosing[171] In Vitro Efficacy and Potency - SPY002 (TL1A) shows 100% inhibition at 10 nM concentration in vitro, comparable to Tulisokibart[12] - SPY001 (α4β7) shows 60% inhibition at 10 nM concentration in vitro, comparable to Vedolizumab[12] - SPY003 (IL-23) shows 80% inhibition at 10 nM concentration in vitro, comparable to Risankizumab[12] - SPY002 candidates target distinct TL1A epitopes, showing superior or comparable potency in multiple assays compared to synthesized comparator antibodies[138] - SPY003 targets a similar epitope as risankizumab with comparable potency in vitro[158][159] Safety and Tolerability - SPY001 Phase 1 trial interim data indicates a favorable safety profile, with no serious adverse events reported across all dose levels[115] - SPY003 completed IND-enabling tox studies with NOAEL at the highest dose tested[157] Dosing and Formulation - Spyre's monotherapies and combinations offer Q3M & Q6M dosing profiles, significantly reducing annual injections compared to competitors like Entyvio (26x SC) and Skyrizi (6x OBI)[42] - Spyre's coformulations allow for dose optimization and extended dosing intervals, potentially improving immunogenicity profiles[55] - SPY001 saturated α4β7 receptors through ~12 weeks of follow-up after a single dose, demonstrating sustained target engagement[131] - SPY003 developed a high-concentration (180 mg/mL) citrate-free SC formulation for clinical studies[157] Financial and Operational Highlights - The company has a cash runway lasting into the second half of 2028, with approximately $903 million as of December 31, 2024[3] - Preliminary cash as of December 31, 2024, is $603M, with an expected runway into the second half of 2028[103] - Spyre's leadership team includes experienced executives in clinical development, corporate strategy, and operations, supporting its pipeline advancement[92] Preclinical and Clinical Efficacy - Spyre's portfolio shows potential for best-in-class efficacy with SPY230 combinations, achieving up to 40% clinical remission rates[44] - Spyre's TL1A antibody demonstrates superior efficacy vs. anti-TNF in rat models of rheumatoid arthritis (RA), with comparable efficacy in therapeutic models[81][82] - Spyre's TL1A antibody has shown efficacy in reducing arthritis scores and hind paw erosions in preclinical models[76][78] - Tulisokibart showed clinical remission rates of 48% at 250 mg Q4W in ARTEMIS-UC and 56% at 250 mg Q4W in APOLLO-CD[152] Platform and Trial Design - Spyre's platform trial design enables multiple placebo-controlled readouts, with a planned initiation in mid-2025 and a target population of ~600 patients[47] - Spyre's platform trial design is expected to reduce costs by up to 40% compared to individual Phase 2 trials[54] - SPY002 and SPY003 both utilize single-ascending and multiple-ascending dose cohorts in Phase 1 studies[145][166] Disease Targets and Therapeutic Areas - Spyre's portfolio targets multiple diseases, including ulcerative colitis, Crohn's disease, and rheumatoid arthritis, with TL1A implicated in inflammation and fibrosis[61][62] - Spyre anticipates initiating a Phase 2 trial for TL1A in RA by mid-2025, with topline data expected in 2H26[86]