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    ACELYRIN Inc (SLRN)

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    Business Description

    ACELYRIN, INC. (Nasdaq: SLRN) is a late-stage clinical biopharmaceutical company focused on developing and commercializing transformative medicines to address unmet medical needs. Headquartered in the Los Angeles area with additional operations in the San Francisco Bay area, the company specializes in identifying and accelerating the development of innovative therapies. ACELYRIN does not currently have any approved products for commercial sale and is primarily engaged in clinical development activities.

    1. Izokibep - A small protein therapeutic designed to inhibit IL-17A, currently in late-stage clinical trials for hidradenitis suppurativa, psoriatic arthritis, and uveitis, with plans for axial spondyloarthritis.
    2. Lonigutamab - A monoclonal antibody targeting the IGF-1 receptor, being developed for the treatment of Thyroid Eye Disease (TED).
    3. SLRN-517 - A monoclonal antibody targeting c-KIT, under development for chronic urticaria.

    Q3 2024 Summary

    Initial Price$4.37July 1, 2024
    Final Price$5.09October 1, 2024
    Price Change$0.72
    % Change+16.48%

    What went well

    • Acelyrin reported a strong financial position with $562.4 million in cash at the end of Q3 2024, and updated year-end cash guidance to $435 million to $450 million, providing operational runway to at least mid-2027.
    • They completed a positive end of Phase II meeting with the FDA for their lead product candidate, lonigutamab, in thyroid eye disease (TED), with alignment on the Phase III program and plan to initiate Phase III trials in the first quarter of 2025.
    • Upcoming top-line results for izokibep in uveitis are expected in December, with potential for superior clinical outcomes compared to existing treatments and the possibility for accelerated approval due to high unmet need and orphan disease status.

    What went wrong

    • Potential Challenges in Demonstrating Superior Efficacy Over Adalimumab: The company acknowledges that their uveitis study includes patients who are biologic-experienced, including those who have previously failed treatment with adalimumab (Humira). Such patients may respond less favorably, potentially impacting the ability to show superior efficacy over adalimumab, which the company has set as a benchmark for success. ,
    • High Bar for Uveitis Program to Continue: Management has stated that if the upcoming uveitis data does not demonstrate a profile that is better than adalimumab, they may choose not to proceed with further development in this indication. This reliance on achieving superior results introduces significant risk to the continuation of the uveitis program. ,
    • Safety Concerns Regarding Hearing Impairment with Lonigutamab: There are potential safety liabilities associated with hearing-related events in the development of lonigutamab for thyroid eye disease. Despite efforts to mitigate these risks through dosing strategies, the possibility of hearing impairment remains a concern, which could affect the drug's competitiveness against existing therapies.

    Q&A Summary

    1. Izokibep vs. Humira in Uveitis
      Q: If izokibep data matches Humira, is it still interesting?
      A: Management suggested that if izokibep's efficacy in uveitis only matches Humira (adalimumab), it may not warrant further development. They aim for a superior clinical profile to address unmet needs, given the presence of Humira biosimilars. The trial includes patients who failed prior biologics, and stratification at randomization allows assessment of efficacy in these subpopulations.

    2. Lonigutamab Phase III Dosing
      Q: Is 70 mg the Phase III dose for lonigutamab?
      A: The Phase III dose for lonigutamab has not been confirmed. Doses ranging from 25 mg to 100 mg, including a 70 mg dose and a potential 100 mg loading dose, have been tested in cohorts. Detailed dosing information and trial design will be announced in early 2025.

    3. Funding for Uveitis Phase III
      Q: What is the funding plan for uveitis Phase III?
      A: The company has a financial runway extending to mid-2027, providing flexibility to develop izokibep in uveitis without additional capital. Specific cost estimates were not disclosed, but they feel confident in proceeding after reviewing upcoming data.

    4. Partnerships for Izokibep in HS and PSA
      Q: Any BD discussions for izokibep in HS and PSA?
      A: Management plans to update on potential partnerships for izokibep after the uveitis data release. They have not included assumptions about partnering or new investments in their financial guidance.

    5. Impact of Biologic-Experienced Patients
      Q: How does including biologic-experienced patients impact data?
      A: The uveitis trial includes patients who have previously used biologics like Humira, unlike earlier studies. Patients are stratified at randomization to balance groups and understand the efficacy in those who failed prior treatments.

    Executive Team

    NamePositionStart DateShort Bio
    Shao-Lee LinFounder, Chief Executive Officer, DirectorJuly 2020Founder and CEO of SLRN since July 2020. Previously held leadership roles at Horizon Therapeutics, AbbVie, Gilead Sciences, and Amgen. Holds an M.D. and Ph.D. from Johns Hopkins.
    Gil LabrucherieChief Financial OfficerAugust 17, 2023CFO of SLRN since August 17, 2023, after serving as interim CFO from August 2, 2023. Previously CFO and COO at Nektar Therapeutics. Holds a J.D. from UC Berkeley and is a CFA charterholder.
    Melanie GloriaChief Operating OfficerNovember 2021COO of SLRN since November 2021. Former SVP of Development Operations at Horizon Therapeutics. Holds a B.S. in nursing from the University of Illinois, Chicago.
    Mina KimChief Legal and Administrative OfficerNovember 2022Chief Legal and Administrative Officer since November 2022. Former Chief Legal Officer at Zymergen and held senior roles at Atara Biotherapeutics and Sunrun. Holds a J.D. from Harvard Law School.
    Ron OystonChief People OfficerSeptember 2022Chief People Officer since September 2022. Previously SVP and Head of HR at SLRN and VP of HR at Horizon Therapeutics. Holds an M.B.A. from the University of Edinburgh.
    Shephard MpofuChief Medical OfficerSeptember 2023CMO of SLRN since September 2023. Former CMO of Novartis’ Gene Therapy franchise and Global Lead for secukinumab, advancing it to multiple approvals.
    Mina KimChief Executive OfficerMay 9, 2024Appointed CEO effective May 9, 2024. Previously Chief Legal and Administrative Officer at SLRN. Held senior roles at Zymergen, Atara Biotherapeutics, and Sunrun. Holds a J.D. from Harvard Law School.
    Sanam PangaliChief Legal Officer and Head of PeopleMay 9, 2024Promoted to Chief Legal Officer and Head of People effective May 9, 2024. Previously served as Senior Vice President, Corporate Legal at SLRN.

    Questions to Ask Management

    1. Given the potential for hearing-related adverse events with anti-IGF-1R agents like lonigutamab, can you elaborate on how your Phase III dosing strategy aims to mitigate these risks, and what thresholds for hearing impairment are acceptable for regulatory approval?
    2. With biologic-experienced patients included in your izokibep uveitis trial—unlike the VISUAL I study for adalimumab—how might this affect the efficacy outcomes, and how will you interpret the data in the context of these differing patient populations?
    3. Considering your cash runway projections to mid-2027 exclude new investments in izokibep, what specific criteria will you use to decide whether to advance izokibep into a Phase III uveitis trial, and how would this impact your financial guidance?
    4. How do you plan to balance further development of izokibep, given the $35.7 million manufacturing credit voucher, with your primary focus on lonigutamab, and what factors would trigger renewed investment in the izokibep program?
    5. As you plan to extend dosing of lonigutamab to 52 weeks in both active and inactive TED patients, what evidence supports the long-term safety and efficacy over this extended period, and how have regulators responded to this approach compared to standard treatment durations?

    Past Guidance

    Q3 2024 Earnings Call

    • Issued Period: Q3 2024
    • Guided Period: FY 2024
    • Guidance:
      1. Year-End 2024 Cash Position: Updated guidance of $435 million to $450 million, including a $31 million license option payment in Q4 to acquire global rights to lonigutamab.
      2. Cash Runway: Cash position provides an operational runway to at least mid-2027, covering the entire Phase III development program for lonigutamab (development and manufacturing activities through to a potential BLA filing). This excludes new investments in izokibep, including uveitis.
      3. Manufacturing Credit Utilization: The $35.7 million manufacturing credit voucher will be utilized in 2025 and Q1 2026 to offset cash outflows for manufacturing services, including lonigutamab supply.
      4. Lonigutamab Phase III Program: Expected to start in Q1 2025.
      5. Izokibep in Uveitis: Top-line results for the Phase IIb/III trial expected in December 2024. Future development plans will be decided after reviewing the data.
      6. Investor Event: Planned for early 2025, to share details on the Phase III program for lonigutamab and updates on hearing-related safety considerations.

    Q2 2024 Earnings Call

    • Issued Period: Q2 2024
    • Guided Period: FY 2024
    • Guidance:
      1. Cash Runway Guidance: Cash runway projected to extend to mid-2027, covering the completion of the ongoing uveitis study, HS and PsA studies, the Phase II program in lonigutamab, two Phase III trials for lonigutamab, and BLA-enabling activities. This excludes proceeds from additional financing or partnering.
      2. Year-End Cash Position: Projected to range between $420 million and $450 million.
      3. Cash Used in Operations: Expected to increase substantially in the second half of 2024.
      4. Restructuring Charges: Approximately $4.5 million in cash-based restructuring charges related to workforce reduction.
      5. Costs for Ongoing Studies: Estimated costs for completing the ongoing uveitis study, HS, and PsA studies range between $30 million and $35 million.
      6. CMC Activities and Commitments: Costs for ongoing izokibep CMC activities and commitments expected to range between $55 million and $85 million.
      7. Development Timeline for Lonigutamab: Phase III program expected to start before the end of Q1 2025, with the first top-line readout in 2026 and a potential BLA filing thereafter.

    Q1 2024 Earnings Call

    • Issued Period: Q1 2024
    • Guided Period: N/A
    • Guidance: The documents do not provide information about the guidance given in the Q1 2024 earnings call.

    Q4 2023 Earnings Call

    • Issued Period: Q4 2023
    • Guided Period: N/A
    • Guidance: The documents do not contain information about the Q4 2023 earnings call or any guidance provided during that period.

    Summary Table

    Earnings Call TitleIssued PeriodGuided PeriodGuidance
    Q3 2024Q3 2024FY 2024Year-end cash position: $435M-$450M; Cash runway to mid-2027; Manufacturing credit utilization in 2025-Q1 2026; Lonigutamab Phase III start in Q1 2025; Izokibep uveitis results in Dec 2024; Investor event in early 2025.
    Q2 2024Q2 2024FY 2024Year-end cash position: $420M-$450M; Cash runway to mid-2027; Restructuring charges: $4.5M; Costs for ongoing studies: $30M-$35M; CMC activities: $55M-$85M; Lonigutamab Phase III start by Q1 2025, top-line readout in 2026, potential BLA filing thereafter.
    Q1 2024Q1 2024N/ANo information available.
    Q4 2023Q4 2023N/ANo information available.