1 Forward-Looking Statements This presentation contains "forward-looking statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties and are based on our estimates and assumptions. All statements, other than statements of historical facts included in this presentation, are forward-looking statements, including statements concerning: our plans, objectives, goals, strategies or intentions relating to products and markets; whether the commo ...

EQ504: A Novel AhR Modulator for Ulcerative Colitis - Equillium, Inc is developing EQ504, a novel aryl hydrocarbon receptor (AhR) modulator for ulcerative colitis [1] - EQ504 is derived from ITE, a naturally-occurring, endogenous, non-toxic AhR modulator synthesized in the gut & lungs, and is a highly potent and selective modulator of AhR [143][144] - EQ504 has a multi-modal mechanism of action in mucosal homeostasis, modulating immune cell responses and promoting barrier function & tissue repair [148][149][150] - In vitro, EQ504 increases the number and function of suppressive Treg cells that inhibit activity of Th1 and Th17 cells and promote tissue homeostasis [156] - In a DSS colitis animal model, EQ504 blocks weight loss and induces anti-inflammatory cytokines in colon tissue [158][160] Clinical Validation and Market Opportunity - Modulation of AhR has been clinically validated in skin diseases, with up to 34% of patients achieving a PGA-Pso score of 0-1 by week 12 in psoriasis and up to 34% of patients achieving a vIGA-AD score of 0-1 by week 8 in atopic dermatitis [134][136] - Phase 2 trials of Indigo Naturalis in ulcerative colitis showed up to 50% of patients achieved clinical remission with total Mayo score ≤ 2, no individual subscore > 1, and up to 27% of treatment refractory patients achieved clinical remission with total Mayo score < 3, no individual subscore > 1 [138] - Studies of ulcerative colitis patients treated with indigo naturalis demonstrate on-target engagement of AhR through increased intestinal CYP1A1 and high levels of clinical remission [142] - In vivo experiments demonstrate localized delivery of EQ504 directly to the colon of rats, results in >25X greater peak exposures in colon tissues versus blood [167] - The US market for ulcerative colitis treatments is approximately $6 billion, with a substantial unmet need for new oral agents in the pre-biologic setting and opportunities in biologic failure patients and combination therapy [172][173]

Core Insights - Spyre Therapeutics announced positive interim Phase 1 results for SPY003, an investigational extended half-life antibody targeting IL-23, which supports its potential for quarterly or biannual maintenance dosing [1][2][8] Group 1: Clinical Trial Results - SPY003 demonstrated a favorable safety profile in a Phase 1 trial with 59 healthy adult participants, showing it was well tolerated across all dose levels [3][5] - The trial included various dosing cohorts, with the most common treatment-emergent adverse event being headache, and no serious adverse events reported [3][4] - SPY003 exhibited a half-life of approximately 85 days, significantly longer than risankizumab, indicating potential for less frequent dosing [5][8] Group 2: Future Development Plans - The positive results from the Phase 1 trial will allow SPY003 to advance to the ongoing Part A of the SKYLINE Phase 2 platform trial [1][2] - The SKYLINE and SKYWAY trials are expected to yield six proof-of-concept readouts by 2026, further validating the efficacy and safety of SPY003 [1][2] Group 3: Company Overview - Spyre Therapeutics is focused on developing long-acting antibodies and antibody combinations to improve treatment standards for inflammatory bowel disease (IBD) and rheumatic diseases [9] - The company’s pipeline includes investigational therapies targeting α4β7, TL1A, and IL-23, aiming to create a comprehensive IBD portfolio [2][9]

Core Insights - Eli Lilly and Company announced FDA approval for a single-injection, once-monthly maintenance regimen of Omvoh (mirikizumab-mrkz) for adults with moderately to severely active ulcerative colitis, set to be available in early 2026 [1][2][4] Product Details - Omvoh's single-injection dosing replaces the previous two-injection regimen, simplifying the maintenance experience for patients [1][2] - The new formulation is citrate-free and will be available via prefilled pen or syringe [2] - Omvoh is already approved for Crohn's disease and has received three FDA approvals in 2025 [1][4] Clinical Significance - The approval is based on a Phase 1 study demonstrating that the single-injection is bioequivalent to the two-injection regimen, confirming its efficacy [3] - The treatment protocol begins with 300 mg IV infusions every four weeks for three infusions, transitioning to subcutaneous self-injection every four weeks for maintenance [3][15] Market Position - Omvoh is approved in the U.S. for both ulcerative colitis and Crohn's disease, with approvals in 45 countries globally [4][20] - Eli Lilly emphasizes its commitment to improving treatment experiences for patients with inflammatory bowel disease (IBD) [4][21]

Core Viewpoint - AbbVie announced the FDA approval of a supplemental new drug application (sNDA) for RINVOQ (upadacitinib), allowing its use in adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) after one approved systemic therapy when TNF blockers are clinically inadvisable [1][2]. Group 1: Product Information - RINVOQ is now indicated for patients with moderately to severely active UC or CD who have had an inadequate response or intolerance to one or more TNF blockers, and can be prescribed after one approved systemic therapy if TNF blockers are not suitable [2]. - RINVOQ is a JAK inhibitor developed by AbbVie, which is being studied for various immune-mediated inflammatory diseases [9][10]. Group 2: Patient Support and Access - AbbVie offers a patient support program and a co-pay card that may reduce out-of-pocket costs to $0 per month for eligible, commercially insured patients [5]. - The company has a Patient Assistance Program, myAbbVieAssist, for uninsured patients or those unable to afford their medication [5]. Group 3: Company Commitment - AbbVie is dedicated to addressing the needs of patients with inflammatory bowel disease (IBD), aiming to alleviate the physical, emotional, and economic burdens associated with UC and CD [2][8]. - The company is committed to innovative research in gastroenterology, focusing on developing treatments for IBD [32].

Core Insights - The discussion focuses on the UEGW conference in Berlin, highlighting significant updates in the Inflammatory Bowel Disease (IBD) sector [1]. Group 1: Conference Overview - The UEGW conference was described as exciting, with numerous updates relevant to the IBD space [1]. - The session is part of the Wedbush Rewind series, aimed at reviewing key highlights from industry conferences [1]. Group 2: Participants - Key participants include David Nierengarten, Managing Director of the Healthcare Equity Research team at Wedbush, Dr. Marla Dubinsky from Mount Sinai, David De Vries M. Phil, CEO of Tr1X Bio, and Taylor Schreiber, MD, PhD, CEO of Shattuck Labs [2]. - The format encourages audience participation through a Q&A session, enhancing engagement during the discussion [3].

Core Insights - Spyre Therapeutics reported positive interim Phase 1 results for two next-generation TL1A antibodies, indicating they were well-tolerated and supported quarterly or biannual dosing with full TL1A engagement for up to 20 weeks [1][2] - The company initiated the Phase 2 SKYLINE-UC platform study to evaluate three optimized monotherapies and three potentially paradigm-changing combinations for ulcerative colitis [1][3] - Spyre is on track to begin the Phase 2 SKYWAY-RD basket study for TL1A inhibition in rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis in Q3 2025 [1][10] - The company has a strong cash position of $526.6 million as of June 30, 2025, with an expected runway into the second half of 2028 [1][11] Development Pipeline Overview - Spyre's approach combines advanced antibody engineering, dose optimization, and rational therapeutic combinations to enhance efficacy and convenience in treating inflammatory bowel disease (IBD) and other immune-mediated diseases [3][15] - IBD affects approximately 2.4 million individuals in the U.S., while rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) affect over 1.5 million and nearly 3 million individuals, respectively [3][4] Financial Performance - Research and Development (R&D) expenses for Q2 2025 totaled $40.1 million, up from $32.6 million in Q2 2024, primarily due to increased clinical trial expenses [12] - General and Administrative (G&A) expenses were $11.8 million for Q2 2025, slightly higher than $11.5 million in Q2 2024 [12] - The net loss for Q2 2025 was $36.7 million, compared to a net loss of $38.8 million in Q2 2024, including non-cash stock-based compensation expenses [14][24]

Core Insights - Ventyx Biosciences is a clinical-stage biopharmaceutical company focused on developing innovative oral therapies for autoimmune, inflammatory, and neurodegenerative diseases [8] Pipeline Updates and Anticipated Milestones - Ventyx is advancing two novel NLRP3 inhibitors, VTX3232 and VTX2735, through Phase 2 trials targeting neurodegenerative, cardiovascular, and metabolic diseases [2] - The Phase 2 biomarker trial for VTX3232 in Parkinson's disease is expected to complete in Q2 2025, with key endpoints including safety and pharmacokinetics [3] - Results from the Phase 2 trial of VTX3232 in obesity and cardiometabolic risk factors, as well as VTX2735 in recurrent pericarditis, are anticipated in the second half of 2025 [3][4] Financial Overview - As of March 31, 2025, Ventyx reported cash, cash equivalents, and marketable securities of $228.8 million, sufficient to fund operations into at least H2 2026 [11][17] - Research and Development (R&D) expenses for Q1 2025 were $22.9 million, down from $33.7 million in Q1 2024 [11] - General and Administrative (G&A) expenses decreased to $7.2 million in Q1 2025 from $8.0 million in Q1 2024 [11] - The net loss for Q1 2025 was $27.4 million, compared to a net loss of $38.6 million in Q1 2024 [11][15] Inflammatory Bowel Disease (IBD) Portfolio - Ventyx's IBD portfolio includes two Phase 2 compounds: tamuzimod (VTX002), an S1P1R modulator, and VTX958, a TYK2 inhibitor [9] - Tamuzimod has shown robust clinical and endoscopic remission rates compared to placebo, positioning it as a potential backbone for future combination therapies in ulcerative colitis [11] - VTX958 demonstrated a dose-dependent endoscopic response in Crohn's disease, suggesting potential disease-modifying benefits [11]

Core Insights - Spyre Therapeutics reported positive interim pharmacokinetic and safety data for SPY001 in a Phase 1 trial and raised $230 million through a public offering to strengthen its balance sheet [1][12] - The company is on track for multiple milestones, including interim Phase 1 data readouts for SPY002 and SPY003 expected in 2025, and the initiation of a Phase 2 trial for SPY001 in ulcerative colitis planned for mid-2025 [1][2] - The company aims to expand SPY002 into rheumatoid arthritis with a Phase 2 trial initiation also expected in mid-2025 [1][11] Financial Overview - As of December 31, 2024, the company had cash, cash equivalents, and marketable securities totaling $603 million, providing a financial runway into the second half of 2028 [1][12] - Research and development expenses for Q4 2024 were $50.5 million, an increase from $33.7 million in Q4 2023, driven by clinical development and manufacturing costs [13] - General and administrative expenses decreased to $10.8 million in Q4 2024 from $14.1 million in Q4 2023, attributed to higher stock compensation expenses in the previous year [14] Development Pipeline - The company has four programs in development, with three targeting inflammatory bowel disease (IBD) and one undisclosed target [4] - SPY001 is a monoclonal antibody targeting α4β7, showing a favorable safety profile and a half-life greater than 90 days, supporting potential Q6M maintenance dosing [5][6] - SPY002 and SPY003 are also being developed with half-life extension technology, aiming for infrequent subcutaneous maintenance dosing [6][7] Recent Corporate Updates - The company initiated first-in-human trials for SPY002 in December 2024, with interim data expected in Q2 2025 [11] - SPY003 is on track to begin its first-in-human trial in Q1 2025, with interim data anticipated in the second half of 2025 [11] - Spyre was added to the Nasdaq Biotechnology Index in December 2024, reflecting its growing presence in the biotech sector [11]