Core Insights - Q32 Bio has sold its Phase 2 complement inhibitor, ADX-097, to Akebia Therapeutics, which allows the company to focus on advancing bempikibart for alopecia areata [1][2][3] - The transaction is expected to provide $12 million in upfront payments and potential total payments of up to $592 million based on future milestones [3][4] - Q32 Bio retains its tissue-targeted complement inhibitor platform, including ADX-096 and other early-stage assets, and is evaluating strategic options for these programs [1][2] Financial Implications - The sale of ADX-097 is projected to extend Q32 Bio's cash runway into the second half of 2027, supporting ongoing clinical trials [2][4] - The upfront payment structure includes $7 million at signing, $3 million at the 6-month anniversary, and $2 million upon achieving a milestone or by the end of 2026 [3] Product Development Focus - Q32 Bio is concentrating on bempikibart (ADX-914), a fully human anti-IL-7R antibody, for the treatment of alopecia areata, with topline data from the SIGNAL-AA Phase 2a trial expected in mid-2026 [2][6] - The company’s tissue-targeted complement platform aims to inhibit complement activation while minimizing systemic effects, differentiating it from current therapies [2][3]

Core Insights - Q32 Bio has completed enrollment in Part B of the SIGNAL-AA Phase 2a clinical trial, increasing the trial size to 33 patients due to high patient demand, with topline data expected in mid-2026 [1][5][2] - The company reported cash and cash equivalents of $49.0 million as of September 30, 2025, which is anticipated to fund operations into 2027 [1][4][11] - The third quarter of 2025 showed a significant reduction in research and development expenses, totaling $3.6 million compared to $14.3 million in the same quarter of 2024 [4][6][11] Clinical Development - The SIGNAL-AA Phase 2a clinical trial is evaluating bempikibart, a fully human anti-IL-7R antibody, in patients with severe alopecia areata (AA) [5][7] - The trial includes a loading regimen of 200mg bempikibart weekly for four doses, followed by a maintenance dose every other week for a total of 36 weeks [5] - Preliminary pharmacokinetic data indicates that steady state drug concentration is achieved at least nine weeks earlier in Part B compared to Part A, suggesting potential for earlier clinical responsiveness [5][2] Financial Performance - Q32 Bio reported a net loss of $7.4 million for the quarter ended September 30, 2025, a decrease from a net loss of $17.6 million in the same quarter of 2024 [11][13] - General and administrative expenses decreased to $4.0 million from $4.5 million year-over-year, primarily due to lower personnel-related costs [11][4] - Total operating expenses for the third quarter of 2025 were $7.6 million, down from $18.8 million in the same period of 2024 [11][4] Market Context - Approximately 700,000 individuals in the United States are affected by alopecia areata, highlighting a significant market need for effective treatments [7] - Q32 Bio aims to provide a differentiated therapeutic option for AA patients, addressing the demand for safer and more durable treatment alternatives [2][5]

Core Insights - Q32 Bio has completed enrollment in Part B of the SIGNAL-AA Phase 2a clinical trial for bempikibart, exceeding the initial target of approximately 20 patients, with a total of 33 patients enrolled due to high demand [1][3] - Bempikibart is a fully human anti-IL-7R antibody aimed at treating severe alopecia areata (AA) by re-regulating adaptive immune function [1][3] - The trial is designed to evaluate the efficacy of bempikibart over a 36-week treatment period, with follow-up extending to 52 weeks, and aims to support advancement into pivotal trials based on the results [2][3] Company Overview - Q32 Bio is a clinical stage biotechnology company focused on developing therapies for alopecia areata and other autoimmune diseases, targeting the adaptive immune system [3] - Approximately 700,000 individuals in the United States are affected by alopecia areata, highlighting the need for new treatment options [3] Clinical Trial Details - Part B of the SIGNAL-AA trial includes a loading regimen of 200mg of bempikibart administered weekly for four doses, followed by a maintenance dose every other week for a total of 36 weeks [2] - Efficacy will be assessed using the Severity of Alopecia Tool (SALT) scores, with the goal of observing significant improvements in patients' conditions [2] Future Expectations - Preliminary data from early-enrolling patients in Part B indicate emerging signs of clinical activity, with a faster achievement of steady-state drug concentration compared to Part A [2] - Q32 Bio anticipates reporting topline data from Part B in mid-2026, which could lead to further development of bempikibart pending positive results [3]

Financial Data and Key Metrics Changes - The company has extended its cash runway into Q1 2027, providing sufficient margin to allow ongoing trials to complete [47][48] - The company reported a 20% reduction in SALT score at week 36 in part A, with expectations to improve upon this in part B [28][29] Business Line Data and Key Metrics Changes - The company is advancing bempikibart, focusing on alopecia areata, with ongoing enrollment in phase 2 part B after positive results from part A [5][36] - In part A, statistically significant hair improvement was observed at week 24, with no grade 3 or higher related events reported [8][12] Market Data and Key Metrics Changes - The competitive landscape includes other IL-7 receptor alpha programs, with the company believing it has a best-in-class asset due to its pharmacology and dosing advantages [43][44] Company Strategy and Development Direction - The company is focusing on immunomodulating agents rather than immunosuppressants, aiming for clinically meaningful efficacy with durable responses [31][32] - Future trials may include registrational studies, with potential for seamless phase 2 part B/3 trials [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the differentiated profile of bempikibart, emphasizing its safety and potential for durable effects [49][51] - Early signs in part B indicate improved responsiveness compared to part A, suggesting that changes made to the trial design are effective [52][53] Other Important Information - The company has made significant changes to trial design in part B, including a loading dose regimen and modified inclusion criteria to enhance patient responsiveness [9][25] - Management noted that the atopic dermatitis trial did not yield expected results, but it provided valuable insights for future indications [42] Q&A Session Summary Question: What are the next steps for bempikibart? - The next steps could include registrational trials, with various options being considered for the trial design [36] Question: How does the company plan to fund operations moving forward? - The company has sufficient cash runway into 2027 and is exploring strategic options for further funding [47][48] Question: What differentiates bempikibart from competitors? - The company believes its pharmacology and dosing regimen provide a competitive edge over other IL-7 receptor alpha programs [43][44] Question: What are the expectations for part B results? - Management hopes to see improved efficacy and responsiveness in part B compared to part A, with a focus on clinically meaningful outcomes [52][53]

Core Viewpoint - Q32 Bio reported a significantly reduced GAAP net loss of $0.78 per share for Q2 2025, with no revenue, reflecting its pre-commercial status and a focus on its lead drug candidate, bempikibart [1][5][10] Financial Performance - The net loss (GAAP) decreased to $9.5 million in Q2 2025 from $17.0 million in Q2 2024, primarily due to an $8.2 million reduction in research and development expenses [5] - Research and development expenses were $5.2 million in Q2 2025, down 61.2% from $13.4 million in Q2 2024 [2] - General and administrative expenses decreased to $4.0 million in Q2 2025 from $4.5 million in Q2 2024, reflecting lower staffing and legal costs [2][5] - Cash and cash equivalents at the end of the period were $54.8 million, expected to fund operations into 2027 [2][7] Business Focus and Strategy - Q32 Bio is concentrating on bempikibart, an experimental therapy for autoimmune diseases, and has halted development on its ADX-097 project [3][4] - The company underwent a restructuring in February 2025 to conserve resources and accelerate progress on bempikibart [4] Clinical Development - The bempikibart program is currently in the SIGNAL-AA Phase 2a trial, with ongoing enrollment and topline results expected in the first half of 2026 [6][10] - Bempikibart received Fast Track designation from the U.S. FDA for alopecia areata, which may expedite its development and review process [8] Future Outlook - Management does not anticipate revenue in the near term and has prioritized completing the SIGNAL-AA trial [10]

Clinical Trial Results - The SIGNAL-AA Phase 2a trial studied bempikibart in patients with severe or very severe Alopecia Areata [1] - The study included patients with SALT scores between 50 and 100 [15] - At Week 24, patients with baseline SALT 50-100 showed a mean SALT score change of 163% with bempikibart treatment [20] - In patients with baseline SALT 50-95, the mean SALT score change at Week 24 was 245% with bempikibart [20] - Some patients experienced continued response even 7 months post last dose [23, 24] Safety and Tolerability - In the bempikibart group, 70% of participants experienced at least one treatment-emergent adverse event (TEAE) [27] - In the placebo group, 38% of participants experienced at least one TEAE [27] - No Grade 3 or higher related adverse events were reported in the bempikibart group [27] Study Design and Demographics - The study randomized patients in a 3:1 ratio to bempikibart (n=33) or placebo (n=81) [15] - The mean baseline SALT score in the bempikibart group was 749, while in the placebo group it was 819 [16]

Core Insights - Q32 Bio has made significant progress in its clinical trials for bempikibart, receiving Fast Track designation and initiating dosing in both parts of the SIGNAL-AA Phase 2a clinical trial [2][3][4] - The company reported a net loss of $11.0 million for Q1 2025, compared to a net income of $1.0 million in Q1 2024, indicating a shift in financial performance [9][13] - Cash and cash equivalents stood at $65.5 million as of March 31, 2025, which is expected to fund operations into the second half of 2026 [9][12] Clinical Development - The first patient has been dosed in Part B of the SIGNAL-AA Phase 2a clinical trial, with topline data readout anticipated in the first half of 2026 [3][4] - Part B will evaluate bempikibart in approximately 20 patients with severe or very severe alopecia areata (AA) over a 36-week treatment period [3][4] - An open-label extension (OLE) for Part A has been initiated to allow for longer-term follow-up of patients who completed the initial trial [3][4] Fast Track Designation - Bempikibart has received Fast Track designation from the FDA, which aims to expedite the development and review of drugs for serious diseases [3][4] - This designation may allow for more frequent communication with the FDA and eligibility for Accelerated Approval and Priority Review [3] Financial Performance - Research and development expenses decreased to $7.1 million in Q1 2025 from $9.8 million in Q1 2024, reflecting a focus on clinical development [9][13] - General and administrative expenses remained stable at $5.1 million for Q1 2025, consistent with the previous year [9][13] - The company reported a basic and diluted net loss per share of $(0.90) for Q1 2025, compared to a net income per share of $1.03 in Q1 2024 [9][13] Market Context - Approximately 700,000 individuals in the United States are affected by alopecia areata, highlighting the significant unmet medical need in this area [6] - Q32 Bio is focused on developing therapies that target the adaptive immune system, particularly for autoimmune and inflammatory diseases [6]

Table of Contents As filed with the Securities and Exchange Commission on April 19, 2024 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Q32 BIO INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code No.) Delaware 2834 47-3468154 (I.R.S. Employer Identification Number) 830 Winter Str ...