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| Item 7.01 | Regulation FD Disclosure. |
On January 13, 2025, Q32 Bio Inc. (the “Company”) updated its corporate presentation for use in meetings with investors, analysts and others. The presentation is available through the Company’s website and a copy is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The information in this Current Report on Form 8-K (including Exhibit 99.1 attached hereto) is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits.
| 99.1 | Corporate presentation, dated as of January 2025 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Q32 BIO INC. | ||||||
| Date: January 13, 2025 | By: | /s/ Jodie Morrison | ||||
| Name: Title: |
Jodie Morrison Chief Executive Officer | |||||
Exhibit 99.1 Building The Future of Immune Therapeutics Company Overview January 2025
Forward Looking Statements This presentation has been prepared by Q32 Bio Inc. (“we”, “us,” “our,” “Q32” or the “Company”) and is made for informational purposes only. The information set forth herein does not purport to be complete or contain all of the information you may desire. Statements contained herein are made as of the date of this presentation unless stated otherwise, and this presentation shall not under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof. This presentation contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” “potential,” and similar expressions regarding future periods. These forward-looking statements include, but are not limited to, our beliefs, observations, expectations and assumptions regarding the topline data from the SIGNAL-AA Phase 2a and the safety, tolerability, clinical activity including biomarker data, potential efficacy and potential benefits of bempikibart, plans and expectations for Part B of the SIGNAL-AA Phase 2a clinical trial statements regarding expected cash and the sufficiency of the Company’s cash to fund operations into mid- 2026, the expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of Q32’s product candidates, including bempikibart and ADX-097, and anticipated milestones, data readouts and timing, among others. Statements that are not historical facts are forward-looking statements. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the Company’s need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of the Company’s development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; Q32’s product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies and clinical trials; the possibility of system failures or security breaches; risks relating to intellectual property and our ability to protect our patents and other proprietary rights; significant costs incurred as a result of operating as a public company; as well as those risk and uncertainties set forth more fully under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 as well as other risks detailed in our subsequent filings with the United States Securities and Exchange Commission. Any forward-looking statement made by us is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Certain information contained in this presentation relates to or is based on studies, publications, analyses, surveys and other data obtained from third-party sources and the Company’s own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research may not have been verified by any independent source. 2
Q32 Mission: Building The Future of Immune Therapeutics • Proof of concept (POC) demonstrated in alopecia areata (AA) in Phase 2a Part A; high unmet need where treatments Bempikibart (ADX-914) include JAK inhibitors which have class-wide safety warnings, a significant limitation for the AA patient demographic IL-7Rα Antagonist Antibody Dual IL-7/TSLP inhibition • Meaningful hair regrowth with evidence of durability after 24-week treatment period with subcutaneous (SC) dosing • Potential to transform AA treatment paradigm with durable effect and favorable tolerability and safety profile • Phase 2a Part B to commence in 1H’25 with data in 1H’26; anticipated final step prior to pivotal trials • Broad expansion opportunity in Th1 and Th2 mediated diseases supported by biomarker and T-cell changes • Platform: Differentiated, targeted approach to address complement dysregulation directly in the tissue Novel Tissue-targeted • ADX-097: Clinical data to date show attainment of dose-dependent target PK/PD, favorable tolerability and good Complement Platform immunogenicity profile with SC dosing Lead Clinical Asset: ADX-097 Inactivates alternative pathway convertases • ADX-097: Phase 2 renal basket trial in IgAN, C3G and Lupus Nephritis ongoing • 1H’25 – Bempikibart: Initiate enrollment in SIGNAL-AA Phase 2a Part B Near Term Value • 1H’26 – Bempikibart: SIGNAL-AA Phase 2a Part B Topline Results Creation Potential • 1H’25 – ADX-097: Renal basket Phase 2 Initial Data Multiple near-term milestones • 2H’25 – ADX-097: Renal basket Phase 2 Topline Results • Management team with extensive public biotech experience Exceptional Team • Deep inflammatory/autoimmune expertise including complement therapeutics 3
Q32 Pipeline: Poised to Deliver Multiple Near-term Clinical Readouts Discovery/ Anticipated Program Indication Phase 1 Phase 2 Preclinical Milestones IL-7/TSLP PROGRAM Bempikibart Alopecia Initiate Part B enrollment 1H’25; 1 (ADX-914) Areata Topline data expected 1H’26 COMPLEMENT INHIBITOR PLATFORM Renal Basket ADX-097 Topline data expected 2H’25 (IgAN, LN, C3G) Note: IgAN = IgA Nephropathy; LN = Lupus Nephritis; C3G = C3 Glomerulopathy. 4
Bempikibart (ADX-914) (IL-7 / TSLP Receptor Inhibitor)
Bempikibart: Bifunctional Antibody for T-cell Mediated I&I Diseases With Demonstrated Activity in AA Bempikibart IL-7Rα antagonist antibody: Biomarker changes and clinical activity in Phase 2a: Blocks IL-7 and TSLP signaling Supports IL-7Rα antagonist approach Biomarker Median Changes Over Time IL-7 receptor TSLP receptor Clinical Data Across Phase 1 and Phase 2a • IL-7 regulates pathogenic T / • TSLP is central regulator of • Favorable PK/RO/PD and minimal ADA eff T cells that suppress T cells dendritic cell differentiation, mem reg • Mechanism demonstrated by changes in Th2 biomarkers and T cells in preclinical models Th2 cytokines supporting additional indication expansion opportunity beyond AA • Blockade of IL-7Rα provides a • Blockade of TSLP function has • Well-tolerated safety profile across 130 subjects to date novel mechanism for potential to inhibit Th2 rebalancing T and T mediated inflammation and eff/mem reg • POC demonstrated with durable hair growth in AA in SIGNAL-AA Part A function eosinophilic disease 24-week treatment and additional 12-week follow-up 6 6
SIGNAL-AA Case Study - Severe AA with 4.5 Year Episode Showing SALT-10 at Week 36: Supports Potential for Durable Hair Regrowth with Bempikibart Treatment Baseline Week 24 Week 36 SALT Score % Change from Baseline 0 -20 -40 -60 -80 -100 111-0010 ❖ 52-year-old female ❖ Duration of episode: 4.5 years ❖ Baseline SALT: 56 ❖ SALT (Week 24): 10.5 ❖ SALT (Week 36): 4 Durable response at Week 36; PI reports continued hair growth following completion of study 7 Day-1 Week 6 Week 12 Week 18 Week 24 Week 26 Week 30 Week 36 SALT % Change from Baseline Last Dose
SIGNAL-AA: Part A SALT Data Through Week 36 Follow-up Showed Continued Benefit Over Time Supporting Potential for Remittive Effect Following Dosing Cessation SALT Percentage Change Over Time SALT Percentage Change Over Time SALT Percentage Change Over Time 1 1 1 (SIGNAL AA, Per Protocol ) (SIGNAL AA, Per Protocol ) (SIGNAL AA, MITT ) 2,3 Week 24 Week 36 10 Updated with complete 10 (EOT) (EOS) Week 36 data SEVERE AND VERY SEVERE 0 0 SALT 50-100 (n=23 at Week 24) Mean SALT % ∆ 16% 21% -10 -10 SALT 30% 17% 39% -20 -20 SALT-20 9% 6% SEVERE ONLY -30 -30 SALT 50-95 (n=15 at Week 24) Mean SALT % ∆ 25% 30% -40 -40 SALT 30% 27% 58% SALT-20 13% 8% Bempikibart 200 mg PP with baseline SALT at 50-95 (N=15) Placebo PP (N=4) Bempikibart 200 mg PP (N=23) mITT as collected Placebo (N=8) Bempi-200 mg mITT as collected (N=33) mITT as collected at SALT baseline 50-95 (N=22) Mean SALT reduction continues after dosing cessation, suggestive of potential for remittive effect. Response relevance supported by multiple inbound patient requests for continued dosing. 1 Analysis excludes 3 placebo subjects from a single site who were major violations of inclusion criteria (AA diagnosis incorrect). Step Down Between mITT to Per Protocol: 10 early terminations, 2 missed week 24 visit, 1 missed 8 2 3 multiple doses, 1 major hairstyle change. 5 LTFU by wk36, 3 LTFU by wk 36 Day-1 Week 6 Week 12 Week 18 Week 24 Week 26 Week 30 Week 36 Day-1 Week 6 Week 12 Week 18 Week 24 Week 26 Week 30 Week 36 SALT % Change from Baseline (Mean) Last Dose SALT % Change from Baseline (Mean) Last Dose End of Dosing
SIGNAL-AA Case Study- Very Severe AA with SALT-10 Response After Dosing Cessation: Supports Potential for Remittive Effect with Bempikibart Treatment Baseline Week 24 Week 36 Week 57 7 months after last dose No additional concomitant treatments ❖ 61-year-old female ❖ Duration of Episode: 3.1 years ❖ Baseline SALT: 98.2 ❖ SALT (Week 24): 98.2 ❖ SALT (Week 36): 88.4 ❖ SALT (Week 54): 8 Achieved near complete hair regrowth ~7 months after last dose; Patient has requested additional dosing 9
SIGNAL-AA First-in-Patient Observations of Durable Response Supported by Broad Literature Describing IL-7 Mechanistic Modulation of T cells eff/mem 10
Preclinical Evidence of Long-Term Durable Effects Following IL-7Rα Antibody Treatment: Models Suggest a Mechanism for Rebalancing T and T function eff/mem reg Type 1 Diabetes Model Collagen Induced Arthritis Model Tuberculin Challenge Model Belarif 2018 Nat. Comm. Days post immunization BMS report BMS report ▪ Anti-IL-7Ra treatment markedly reduces/delays diabetes onset in ▪ Anti-IL-7Ra treatment markedly reduces collagen induced arthritis ▪ One dose of anti-IL-7Ra markedly reduces tuberculin induced DTH NOD1 mice in mice response in baboons ▪ Effect persists 7+ weeks after secession of dosing▪ Effect persists 10+ weeks after secession of dosing▪ Effect persists for 1+ year, BCG vaccine restores response Proposed Mechanism T eff/mem Immune activation Immune suppression Selective T inhibition eff/mem Function amplified T T T T eff/mem reg eff/mem reg IL-7 IL-7Ra Ab T reg Function suppressed Autoimmune Disease Treatment with IL-7Rα Ab Homeostasis Imbalance in T vs T function Restores balance of T vs T function eff/mem reg eff/mem reg 11
Maturing SIGNAL-AA Data Package Supports Potentially Differentiated Profile in AA • Durable hair regrowth observed supports potential for transformative paradigm • Mean SALT scores continued to improve from Week 24 to Week 36 • Multiple reports received of post 36-week hair growth; data collection underway • Long term remittive response post-dosing cessation potential supported by literature • Response observed across hard-to-treat populations • Responses in both severe (SALT 50-95) and very severe (SALT 95-100) patients • Responses in patients with long duration of episodes 1,2,3 • Mean duration of current episode in SIGNAL-AA Phase 2a was 5-6 years vs 2.5-4 years in prior JAK trials 4,5 • Literature shows response rates can be half (or less) in patients with current episode >4 years • Safety profile supports competitive positioning • Potential to drive more patients to treatment, including those ineligible or refusing treatment due to black box safety issues with JAKs Data supports significant potential opportunity in AA based on efficacy and safety profile; Part B to support design of and advancement to pivotal trials 1 2 3 4 King, B. Br J Dermatol 2023; 189:666–673, https://labeling.pfizer.com/ShowLabeling.aspx?id=19638, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217900s000lbl.pdf, Peeva E, et 12 5 al. AAD 2019, S034 Late-breaking Research: Clinical Trials Sponsored by Pfizer, King B. World Congress of Dermatology 2023. Sponsored by Eli Lilly and Company
SIGNAL-AA Phase 2a: Part A Complete Through Week 36 Follow-up Period With Ongoing Expansion for Additional Follow-up Week 24 Part A ✓ Design Elements Primary Endpoint Week 36 Part A Percent change from baseline in SALT score at Week 24 • First exposure in AA patients Bempikibart (n=30) Efficacy and Ongoing expanded 200 mg Q2W (24-weeks) • Severe/Very Severe (SALT 50-100) Safety data collection in Placebo (n=10) • No loading regimen Follow-Up eligible patients Q2W (24-weeks) • Dosing: 24-weeks • Follow-up: 36-weeks Part B Week 36 Primary Objectives Part B Relative and Absolute Efficacy Assessments: • Proportion of subjects achieving ≥30% reduction in SALT vs. baseline at 36-weeks• Severe/Very Severe (SALT 50-100) • Proportion of subjects with absolute SALT ≥20 at 36-weeks Week 52 • Introduces loading regimen: designed to accelerate PK/PD Bempikibart (target n=20 evaluable) dynamics to maximize efficacy Efficacy and Safety • Longer dosing: 36-weeks Follow-Up Loading Regimen Maintenance Dose 200 mg • Longer follow-up: 52-weeks 200 mg Weekly (4-weeks) Q2W (32-weeks) SIGNAL-AA to characterize profile differentiation vs. currently approved AA agents including JAKs 13 Screening with Central Screening Eligibility Review 3:1 Randomization
AA Has Life-Altering Impact and Limited Treatment Options Including JAK Inhibitors Carrying Black Box Warnings 1 700K people living with AA in the U.S. Doctors and patients seek alternatives to currently 2 approved agents including JAK inhibitors which Often manifesting before age 50 carry significant safety risks: • While they have shown efficacy, they are also Psychosocially Severity of disease associated with significant adverse events debilitating; scalp and and long duration face commonly impacted • They require chronic treatment and hair loss of episode each reoccurs with treatment cessation or taper associated with more gradual and Up to 40% become chronic, • Olumiant approved in 2022, Litfulo approved in lower rates of including complete loss of 3 2023: both carry class-wide Black Box Warning 4 5 treatment response scalp and/or body hair Currently available AA treatment options lack desired profile: Providers and patients seek safer alternatives Durable, long-term remission would be transformative 1 2 Benigno M, et al. Clin Cosmet Investig Dermatol. 2020 Apr 1;13:259–266, Source: Wells Fargo Research, “Takeaways from Our Investor Lunch with Management and Alopecia Areata KOL” Oct 31, 2024, 3 4 5 14 https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/207924s006lbl.pdf, https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215830s000lbl.pdf, Alopecia Totalis; Alopecia Universalis
AA is Prevalent, Stigmatizing and Psychologically Burdensome; Unmet Need for New Options with Better Safety and Ability to Provide Durable, Long-Term Remittance Total AA Market Forecast 3 ($ Billions) 1 700K $3.0 US Alopecia Areata (AA) Patients $2.6B $2.5 $2.0 1 300K $1.5 Severe (SALT > 50) $1.0B $1.0 2 $0.5 30K JAK Treated $0.0 2026 2030 1 2 3 Benigno M, et al. Clin Cosmet Investig Dermatol. 2020 Apr 1;13:259–266, Company research; Trinity Life Sciences, Consensus sales forecasts; source: Evaluate Pharma, Jan 2025 15
A Product With Remittive Properties Could Transform the AA Treatment Paradigm: Potential to Differentiate on Safety and Inducing Long-Term Durable Remission [T]he potential to have a side effect profile perhaps closer to biologics we use in atopic dermatitis…is certainly a compelling value proposition. [Patients] would prefer an injection if it was safer in the end. If it has pristine safety, even with lesser efficacy…it could be used first line. – Excerpts from third party Guidepoint KOL call reviewing Bempkibart Phase 2a data, Dec 12, 2024 16
Opportunities Beyond AA: Potential to Expand into a Broad Range of Th1 and Th2 Mediated Diseases SIGNAL Phase 2a SIGNAL Phase 2a Meaningful effect on Results support the Th2 biomarkers potential for long observed term, durable responses Eosiniphils, IgE, TARC Suggestive of T /T impact eff mem Confidential 17
Tissue-Targeted Complement Platform Lead Asset: ADX-097
Q32 Tissue-targeted Platform Value Proposition: Designed to Enable Clinical Profile Superior to Systemic Complement Inhibitors The Unmet Need The Opportunity • Limited activity: • Enhanced activity through tissue targeting: Reliant on systemic blockade for impact on Differentiated approach to driving efficacy by affected organ inactivating convertases directly at site of destruction • High doses, frequent administration required: • R ed u ced tr e a tme nt burden: High abundance, rapid turnover of most target SC route with QW dosing; potential for Q2W complement proteins • Infection risk: • Improved risk/benefit profile: Complement plays critical role in combating Designed to maximize therapeutic index while infection; systemic blockade increases risk maintaining intact immune surveillance; broader indication potential 19
ADX-097 Lead Bivalent Fusion Protein: Designed with Unique MOA to Drive Localized, Complement Re-regulation for Enhanced Activity and Tolerability ADX-097 Design: C3d antibody – fH 1-5 Designed to be held at site of tissue complement Inactivation of alternative pathway convertases activity allowing catalytic degradation of gains control of amplification loop and all 3 alternative pathway convertases complement pathways ADX-097: Fusion protein Humanized anti-C3d mAb linked to two moieties of a negative regulatory protein (fH ) 1-5 20 20
Phase 1 Study: Complete with Primary Goals Achieved Phase 1 SAD/MAD (n= 56 Healthy Volunteers) Explored Single Doses of 0.1 - 30 mg/kg IV and/or SC and 450 mg SC Multiple Dose Cohort (~6 mg/kg) Primary Goals Achieved Results • Attained expected dose-dependent PK/PD Confirm planned Phase 2 • Once weekly SC dosing provided desired exposure for predicted dose/route/schedule complete tissue inhibition with no concomitant systemic inhibition Evaluate proximal POM to • PK levels aligned with predicted Wieslab alternative pathway inhibition establish in-vivo ADX-097 integrity • No serious or severe AEs or discontinuations due to AEs Characterize safety profile • No AEs related to immunogenicity Characterize immunogenicity risk• Minimal anti-drug antibodies (ADA) detected across SAD/MAD; low level titers 21
ADX-097 SPOTLIGHT Phase 2 Renal Basket Clinical Trial: Enrollment Ongoing Details and Timeline Renal Basket (n= up to 30) • Open-label trial designed to assess safety, tissue 26-week treatment pharmacology and magnitude/timing of treatment effect • Key assessments: Drug localization and impact in tissue, biomarkers (including proteinuria and eGFR) for assessment of ADX-097 activity • Anticipated to provide data for key regulatory discussions Trial initiated; topline results expected in 2H’25, with initial open-label data by 1H’25 22 Confidential
ADX-097: Significant Market Opportunity Significant Market Opportunity including in Initial Focus on Renal Diseases (LN, IgAN, C3G) Lupus Nephritis (LN) 1,2 • 6-fold mortality risk increase vs general population • Up to 30% develop kidney failure requiring dialysis or 3,4 kidney transplant within 15 years of diagnosis IgA Nephropathy (IgAN) 5,6 • Up to 40% develop ESRD w/in 20 years of diagnosis , and 7,8 patients have 10 years reduced life expectancy 5,9 • ~70% not adequately controlled w/supportive care C3 glomerulopathy (C3G) • Up to 50% of adult, 70% of pediatric patients progress to 10-13 kidney failure within 10 years • >70% experience recurring disease; ~50% experience 10,14-17 allograft loss w/in 10 years of kidney transplant 1 2 1 2 3 4 5 Watts et al. Nat Rev Rheum 2022; Estimated using U.S. and Norway incidence study results, and Mahajan et al. Lupus 2020; Cervera et al. Medicine 2002; Maroz et al. Am J Med Sci 2013. Ward et al. J Rheumatol 2009; Habas et al. 3 4 6 7 8 Norway prevalence study results as applied to U.S. population; Hoover et al. Kidney Int 2016; Pryor et Medicine (Baltimore) 2022. Berthoux et al. Semin Nephrol 2008; Pitcher et al. Clin Jour of Amer Soc Neph 2023. Hastings et al. Kidney Int Rep 5 6 9 10 11 al. Rheum Dis Clin North Am. 2021; Kwon et al. J Health Econ Outcomes Res. 2021; Swaminathan et 2018; Raun et al. N Engl J Med 2015; Heiderscheit et al. Am J Med Genet C Semin Med Genet 2022. Smith et al. J Am Soc Nephrol 2007; 7 8 12 13 14 15 al. Clin J Am Soc Nephrol 2006; Bomback et al. Kidney Int. 2018. Smith et al. Natur Rev Nephrol. 2019; Servais et al. Kidney Int 2012; Rabasco et al. Kidney Int 2015; Smith et al. Nat Rev Nephrol 2019. Welte et al. BMC Nephrology 2018; 9 10 11 16 17 18 19. Servais et al. Kidney Int 2012; Ronco et al. Nat Rev Dis Primers 2021; Swaminathan et al. Clin J Am Salvadori et al. WJT 2016. Regunathan-Shenk et al. AJKD 2019 Hoover et al. Kidney Int 2016; Pryor et al. Rheum Dis Clin North Am. 2021; 12 13 14 20. 21 22 Soc Nephrol 2006; Hanko et al. Nephrol Dial Transplant 2009;; Umehara et al. Mod Rheum 2012; Braun et al. Int Urol Nephrol 2011; McQuarry et al. Kidney Int 2013; Bomback et al. Kidney Int. 2018. 15 Uchida et al. Int J Rheum 2012; Estimated using Japan prevalence study results as applied to U.S. 23 16 population; Based on 2020 Census population
Summary: Financial Overview and Anticipated Milestones
Q32 Bio Has Significant Potential to Unlock Near-term Value Creation Runway through multiple Phase 2 clinical readouts and into mid-2026 • Q3 cash balance of $89.1M, providing expected cash runway to mid 2026 Financial Overview • Approximately 12.1M shares outstanding • 1H’25 – Bempikibart: Initiate enrollment in SIGNAL-AA Phase 2a Part B Numerous Anticipated Milestones • 1H’26 – Bempikibart: SIGNAL-AA Phase 2a Part B Topline results • 1H’25 – ADX-097: Renal basket Phase 2 Initial data • 2H’25 – ADX-097: Renal basket Phase 2 Topline results 25
APPENDIX
Bempikibart in AA: IL-7 Inhibition is Believed to Block CD8+ T cell-Driven Inflammation Hair Follicle Immune Dysregulation in Alopecia Curr Res Immunol. 2021 27
Bempikibart Shows Potential to be Best in Class IL-7Rα Antibody Bempikibart Lusvertikimab (OSE-127) ZB-168 GSK-2618960 Q32 Bio OSE Zura Bio (formerly Pfizer) GSK (IgG1 Effector-less) (IgG4) (IgG1) (IgG1) 1 Active in development Not currently funded ✓✓û Antagonist -- ✓✓û PK/PD supports current single-injection SC formulation ✓ûûû Fully human ✓û✓û Medarex Rat mAb Murine mAb Antibody generation Phage library (fully human) (humanized) (humanized) 2 IL-7R binding on cells (EC nM) 0.08 0.24 0.04 0.32 50, 2 0.09 0.16 0.13 0.23 IL-7Rα binding affinity, biacore (K , nM) D 2 0.22 0.31 0.37 0.41 Inhibition of IL-7 induced pSTAT5 in T-cells (IC nM) 50 2 Inhibition of TSLP induced signaling in monocytes (IC nM) 2.88 1.07 0.20 7.47 50 3 Bempikibart at 200 mg clinically demonstrated potent IL-7 and TSLP inhibition via changes in Th2 biomarkers and T-cells 1 ,2 Zura Bio, https://investors.zurabio.com/news-events/presentations; development dependent on additional financing and pending topline data from other programs, Company data; data were generated by Q32 3 Bio in side-by-side assay of bempikibart vs comparator IL-7Rα mAb analogues, Results from Phase 2a SIGNAL-AA and SIGNAL-AD clinical trials 28
SIGNAL-AA Part A: Favorable PK and Receptor Occupancy (RO) Achieved 2 1 SIGNAL-AA: PK SIGNAL-AA: RO 100 100 10 10 5 μg/mL 5 μg/mL 1 1 0.1 0.1 Nominal Time After Dose (Days) Nominal Time After Dose (Days) 200 mg 200 mg Bempikibart Phase 2a achieved expected PK and RO, supporting current subcutaneous (SC) dosing 200 mg (SC): ≥5 µg/mL mean concentration and >90% RO in 90% of patients, consistent with Phase 1 results 1 2 Excludes samples impacted by missed dose (PK), Excludes samples impacted by missed dose or assay deviation (RO) 29 0 14 28 42 56 70 84 98 112 126 140 154 168 182 196 210 224 238 252 0 14 28 42 56 70 84 98 112 126 140 154 168 182 196 210 224 238 252 ADX-914 Mean (±SD) Concentration (μg/mL) Last dose ADX-914 Mean (±SD) Concentration (μg/mL) Last dose
SIGNAL-AA Part A: Baseline Characteristics 1 mITT (n=44) Revised Per Protocol (n=27) Bempikibart 200 mg (n=33) Placebo (n=11) Bempikibart 200 mg (n=23) Placebo (n=4) Gender (n, %) Female (27, 81.8%) Female (7, 63.6%) Gender (n, %) Female (18, 78.3%) Female (2, 50.0%) Age 48.8 ± 10.2 47.1 ± 14.2 Age 47.7 ± 11.3 59.8 ± 11.9 (years, Mean ± SD) (years, Mean ± SD) Race (n, %) White White Race (n, %) White White (19, 57.6%) (4, 36.4%) (14, 60.9%) (3, 75.0%) Black /African American Black/African American Black/African American Black/African American (10, 30.3%) (6, 54.5%) (7, 30.4%) (1, 25.0%) American Indian/Alaska Native Asian (1, 9.1%) Other (2, 8.7%) (1, 3.0%) Asian (1, 3.0%) Missing (2, 6.0%) Body weight 82.7 ± 13.9 85.1 ± 16.9 Body weight 81.9 ± 14.2 82.3 ± 12.2 (kg, Mean ± SD) (kg, Mean ± SD) Baseline SALT Scores 75.4 ± 20.7 88.4 ± 22.5 Baseline SALT Scores 75.0 ± 20.3 75.5 ± 21.6 (Mean ± SD) (Mean ± SD) Duration of current episode 58 ± 37.2 36.5 ± 21.2 Duration of current episode 68.5 ± 36.2 51.7 ± 36.5 (months, Mean ± SD) (months, Mean ± SD) 1 Table reflects Revised Per-Protocol Population (defined as pre-specified per-protocol population removing 3 placebo patients from one site excluded for marked protocol violations of entry criteria) 30 30
SIGNAL-AA: Topline Data, as Presented December 10, 2024 KEY FINDINGS: Clinical Activity Observed in SIGNAL-AA • Mean change in SALT 16% vs 2% for placebo (Week 24) Post 24 Week Treatment • Mean change in SALT 18% vs 2% for placebo (Week 26) Updated for Complete • SALT-20 achieved in 9% at Week 24, 13% at Week 26 End-of-Study Data Activity Observed Despite Difficult to Treat Population (See Slide 8) • Mean duration of current episode 58 months (~5 yrs) • Duration of current episode (>4 yrs) associated with more gradual responders, late responders, and lower 1 percentage of patients achieving SALT-20 ds 1 Figure reflects Revised Per-Protocol Population King, B World Congress of Dermatology 2023 31 Last Dose
SIGNAL Phase 2a: Favorable Safety and Tolerability Profile in Phase 2a with No Grade 3 or Higher Related AEs Adverse Events (SIGNAL Trials Through Week 24) Bempikibart 200 mg Placebo (N=96) (N=69) n (%) [E] n (%) [E] Participants with at least one TEAE 55 (57.2) [154] 30 (43.5) [76] Participants with at least one TEAE by greatest reported relationship with study treatment [a] Not related 28 (29.2) [43] 23 (33.3) [47] Related 27 (28.1) [68] 7 (10.1) [12] Participants with at least one TEAE by worst reported severity CTCAE grade [b] Grade 1 - Mild 30 (31.2) [49] 13 (18.8) [27] Grade 2 - Moderate 20 (20.8) [21] 15 (21.7) [22] 1 Grade 3 - Severe 4 (4.1) [6] 2(2.9) [ 2] 2 Grade 4 - Life threatening 1 (1) [ 1] 0 [ 0] Grade 5 - Death 0 [ 0] 0 [ 0] Well-tolerated safety profile 3 Findings consistent through AA Week 36 Low incidence of infections, low incidence of lymphocyte decreases (≤Grade 2) 1 2 3 Bempi arm (all not related): Acute myocardial infraction, supraventricular tachycardia, acute respiratory failure, bone fracture, CPK increase, Coronary Artery Stenosis LAD anaphylactric reaction (nut allergy), Only 3 32 additional non-infection/non-lymphocyte AEs reported in 2 subjects through week 36; n=1 placebo/n=2 treated (all mild)
Substantial Activity on Biomarkers Observed in Clinical Trials Supports Potent Inhibition of TSLP and IL-7 Mediated Signaling 1 2 Th2 Biomarkers: SIGNAL Phase 2a Th1 Biomarkers: SIGNAL Phase 2a Median Changes Over Time (95% CI) Mean Changes Over Time (±SD) + TARC IgE Eosinophils CD3 T cells Placebo Bempikibart Placebo Bempikibart Placebo Bempikibart Placebo Bempikibart + TARC decrease Eos decrease CD3 T cell decrease IgE decrease up to 39% up to 18% up to 57% up to 40% + TARC and eosinophil changes significant at multiple time points (p < .05) CD3 changes significant at multiple time points (p < .05) 1 th Figures depict biomarkers for all enrolled patients in SIGNAL-AD and SIGNAL-AA except samples impacted by missed dose; Patients treated for 12 weeks in SIGNAL-AD, 24 weeks in SIGNAL-AA. Results from SIGNAL-AD and up to Nov 5 , 2024; 2 th 33 Results from SIGNAL-AA and up to Dec 10 , 2024.
ADX-097 Preclinical Data: Desired PK/PD, Favorable Tolerability and Immunogenicity Preclinical data supports ADX-097 as a tissue-targeted complement inhibitor • Durable (>7 days) tissue PK/PD after SC dosing • Reduction in key proof of mechanism/proof of concept biomarkers including proteinuria and sC5b • Over 40x safety margin for planned Phase 2 clinical dosing -/- 1 Potent Tissue PK/PD in CfH Mice Robust Effect on POM/POC Endpoints in Rat PHN Model Proteinuria Urine sC5b-9 Normal Serum 8 75 Anti-Fx1A CVF No disease 6 3 mg/kg (SC) Anti-Fx1A 50 1 mg/kg IV 1 mg/kg (SC) ns ADX-097 4 (single dose) ** * 0.3 mg/kg SC 0.3 mg/kg (SC) * ADX-097 * * 1 mg/kg SC 1 mg/kg (IV) 25 2 3 mg/kg SC ** Start Tx ** 0 *** 0 2 3 4 5 6 7 2 3 4 5 6 7 Day of Study Day of Study Potent inhibition of urine sC5b-9, a non-invasive Potent inhibition equivalent to full systemic approach to monitor complement inhibition in kidney complement depletion 1 1 P Passive Heymann Nephritis 34 34 Pro:Cre (mg/mg) urine C5b-9:Cre (mg/mg)