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 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]
Spyre Therapeutics(SYRE) - 2024 Q4 - Annual Results