Core Viewpoint - Spyre Therapeutics (SYRE) has shown a 0.9% increase in share price over the past four weeks, closing at $22.65, with analysts projecting a potential upside of 158.9% based on a mean price target of $58.63 [1][12]. Price Targets - The average price target consists of eight estimates ranging from a low of $40 to a high of $71, with a standard deviation of $12.36, indicating variability among analysts [2]. - The lowest estimate suggests a 76.6% increase from the current price, while the highest estimate indicates a 213.5% upside [2]. Analyst Sentiment - There is strong agreement among analysts regarding SYRE's ability to exceed previous earnings predictions, which supports the expectation of a stock price increase [4][9]. - Over the last 30 days, the Zacks Consensus Estimate for the current year has risen by 2%, with one estimate increasing and no negative revisions [10]. Zacks Rank - SYRE holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors, suggesting a strong potential for upside in the near term [11].

Core Viewpoint - Pomerantz LLP is investigating claims of potential securities fraud and unlawful business practices involving Spyre Therapeutics, Inc. following the company's disclosure of issues with its financial statements [1][2]. Financial Reporting Issues - On November 18, 2024, Spyre announced that its previously issued audited financial statements for the year ending December 31, 2023, and interim periods should no longer be relied upon due to a misapplication of Generally Accepted Accounting Principles [2]. - The misapplication involved the exclusion of Series A and Series B non-voting convertible preferred stock in the calculation of basic and diluted net loss per share, along with a finding of material weakness in internal control over financial reporting [2]. - Spyre plans to amend its Annual Report on Form 10-K and Quarterly Reports on Form 10-Q for the affected periods to correct the net loss per share figures [2]. Stock Market Reaction - Following the announcement of the financial reporting issues, Spyre's stock price experienced a significant decline during intraday trading on November 19, 2024 [2]. Legal Context - Pomerantz LLP is recognized for its expertise in corporate, securities, and antitrust class litigation, having a long history of fighting for victims of securities fraud and corporate misconduct [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]

Core Insights - Spyre Therapeutics is advancing its clinical pipeline with multiple antibody candidates targeting inflammatory bowel disease (IBD) and rheumatoid arthritis (RA), with significant milestones expected in 2025 and 2026 [2][3][11] Clinical Development - Phase 1 interim results for SPY002 and SPY003 are anticipated in 2Q2025 and 2H2025 respectively [1][6] - A Phase 2 platform trial for ulcerative colitis (UC) is set to begin in mid-2025, involving SPY001, SPY002, SPY003, and their combinations, with initial results expected in 2026 [1][11] - The SPY002 program is expanding into RA, with a Phase 2 trial expected to start in mid-2025 and topline results projected for 2026 [1][3][11] Financial Position - The company reported a strong balance sheet with over $600 million in cash, cash equivalents, and marketable securities as of December 31, 2024, providing operational runway into the second half of 2028 [2][8] Product Pipeline - SPY001 is a highly potent anti-α4β7 monoclonal antibody with a half-life exceeding 90 days, supporting potential quarterly to semi-annual dosing [6][11] - SPY002 consists of two extended half-life anti-TL1A antibodies, with Phase 1 studies initiated in Q4 2024 [6][11] - SPY003 targets the p19 subunit of IL-23, with Phase 1 initiation on track for Q1 2025 [6][11] Market Opportunity - The expansion into RA addresses a significant unmet need for effective treatments, with evidence supporting the efficacy of anti-TL1A in RA [3][11]

Group 1 - Spyre Therapeutics, Inc. has been added to the Nasdaq Biotechnology Index, effective December 23, 2024 [1] - The Nasdaq Biotechnology Index tracks the performance of biotechnology and pharmaceutical securities listed on The Nasdaq Stock Market, with specific eligibility requirements [2] - Spyre Therapeutics focuses on developing next-generation products for Inflammatory Bowel Disease (IBD) using advanced antibody engineering and precision medicine [4] Group 2 - The company's pipeline includes extended half-life antibodies targeting α4β7, TL1A, and IL-23 [4]

NEW YORK, Dec. 03, 2024 (GLOBE NEWSWIRE) -- Bragar Eagel & Squire, P.C., a nationally recognized stockholder rights law firm, is investigating potential claims against Spyre Therapeutics, Inc. (“Spyre” or the “Company”) (NASDAQ:SYRE) on behalf of Spyre stockholders. Our investigation concerns whether Spyre has violated the federal securities laws and/or engaged in other unlawful business practices. Click here to participate in the action. On November 18, 2024, Spyre disclosed in a filing with the U.S. Secur ...

Spyre is concurrently advancing two anti-TL1A molecules into first-in-human studiesPreclinical data for both SPY002 molecules demonstrate picomolar potency and potential for quarterly or twice-yearly dosing, suggesting opportunity for improved efficacy and convenience over first-generation anti-TL1As which are dosed every two to four weeksInterim pharmacokinetic, pharmacodynamic, and safety data from healthy volunteers for both SPY002 molecules anticipated in the second quarter of 2025Spyre expects to intro ...

WALTHAM, Mass., Nov. 18, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ: SYRE), 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 the pricing of its previously announced underwritten public offering of 7,275,000 shares of its common stock at a price to the p ...

WALTHAM, Mass., Nov. 18, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ: SYRE), 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 commenced an underwritten public offering of up to $200.0 million of shares of its common stock or, in lieu of issui ...

Exhibit 99.1 Spyre Therapeutics Reports Third Quarter 2024 Financial Results and Provides Corporate Update Continued execution towards expected milestones across portfolio, with SPY001 on-track for interim Phase 1 data by year-end 2024, and SPY002 on-track for initiation of first-in-human trials in the fourth quarter of 2024 Presented new data on SPY003, a potential best-in-class half-life extended anti-IL-23 antibody, demonstrating robust preclinical potency and a greater than three-fold increase in non-hu ...