Q32 Bio Inc. · NASDAQ:QTTB
Q32 Bio — Investor Presentation (December 2024)
36 slides from Q32 Bio's investor presentation, Dec 11, 2024
Slide 1: Building The Future of Immune Therapeutics: Company Overview
Exhibit 99.2 Building The Future of Immune Therapeutics Company Overview December 2024
Slide 2: Forward Looking Statements
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 contai
Slide 3: Q32 Mission: Building The Future of Immune Therapeutics
Q32 Mission: Building The Future of Immune Therapeutics • Bempikibart (ADX-914): Dual inhibitor of IL-7 and TSLP signaling; potent inhibition observed by clinical biomarkers, with potential to treat both Th1 and Th2 mediated diseases • Ph2a data show attractive PK/PD profile, favorable safety and to
Slide 4: Q32 Pipeline: Poised to Deliver Multiple Near-term Clinical Readouts
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 1 Initiate Part B enrollment 1H’25 (ADX-914) Areata COMPLEMENT INHIBITOR PLATFORM Renal Basket Topline results
Slide 5: Bempikibart (ADX-914) (IL-7 / TSLP Receptor Inhibitor)
Bempikibart (ADX-914) (IL-7 / TSLP Receptor Inhibitor)
Slide 6: Bempikibart: Investigational Therapy for T-cell Mediated Inflammatory and Autoimmune Diseases
Bempikibart: Investigational Therapy for T-cell Mediated Inflammatory and Autoimmune Diseases With Demonstrated Clinical Activity Bempikibart: IL-7Rα antagonist antibody blocks IL-7 and TSLP signaling IL-7 • Potent regulator of pathogenic T / T survival and proliferation eff mem • Suppresses T cells
Slide 7: IL-7 and TSLP are Central Drivers of Inflammation and Autoimmunity
IL-7 and TSLP are Central Drivers of Inflammation and Autoimmunity Pathogenic Immune Response Ligand/Receptor Activation Preclinical Evidence • Induction of pathogenic T-eff/ • Elevated IL-7 and sIL-7Rα in disease• Overexpression of IL-7 or TSLP T-mem and ILC2 cells recapitulates disease pathology I
Slide 8: Bempikibart Shows Potential to be Best in Class IL-7Rα Antibody
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
Slide 9: Favorable PK and Receptor Occupancy Achieved in Phase 2a Clinical Trials
Favorable PK and Receptor Occupancy (RO) Achieved in Phase 2a Clinical Trials SIGNAL-AD SIGNAL-AA 100 100 10 10 5 μg/mL 5 μg/mL 1 PK PK 1 0.1 0.1 Nominal Time After Dose (Days) 200 mg Nominal Time After Dose (Days) 120 200 mg 100 90% RO 100 90% RO 80 60 50 RO RO 40 20 0 0 -20 Nominal time after dose
Slide 10: Biomarker Results in SIGNAL-AD: Substantial Reductions Observed
Biomarker Results in SIGNAL-AD: Substantial Reductions Observed in Phase 2a Clinical Trials Suggesting Potent Inhibition of TSLP and IL-7 Mediated Signaling Th2 Biomarkers: SIGNAL-AD Th1 Biomarkers: SIGNAL AD and AA Median Changes Over Time (95% CI) Median Changes Over Time (95% CI) Absolute Lymphoc
Slide 11: SIGNAL-AA: Bempikibart Phase 2a Clinical Trial in Alopecia Areata
SIGNAL-AA: Bempikibart Phase 2a Clinical Trial in Alopecia Areata Alopecia Areata Design/Timeline Alopecia Areata is common, and psychosocially debilitating; scalp and Part A and B face commonly impacted • Part A (n=44) Key Assessments: 200mg SC Q2W vs placebo (3:1) • Autoimmune disease, often assoc
Slide 12: SIGNAL-AA: Baseline Characteristics
SIGNAL-AA: 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 ±
Slide 13: SIGNAL-AA: Key Efficacy Findings
SIGNAL-AA: Key Efficacy Findings Endpoint (Post-Hoc Analysis) Bempikibart 200 mg (N=23) Placebo (N=4) 1 Mean reduction in SALT score (Week 24) 16% 2% 2 Wilcoxon Rank Sum p-value 0.045 SALT-20 (Week 24) 9% 0% SALT-20 (Week 26) 13% 0% 1 Table reflects Revised Per-Protocol Population. Results for Revis
Slide 14: SIGNAL-AA: SALT Improvement Over Time
SIGNAL-AA: SALT Improvement Over Time KEY FINDINGS: Clinical Activity Observed in SIGNAL-AA Dosed through 24 Weeks • Mean change in SALT 16% vs 2% for placebo (Week 24) • Mean change in SALT 18% vs 2% for placebo (Week 26) • SALT-20 achieved in 9% at Week 24, 13% at Week 26 Activity Observed Despite
Slide 15: SIGNAL-AA: Change in SALT Score by Patient at Week 24
SIGNAL-AA: Change in SALT Score by Patient at Week 24 Achieved SALT-20 at Week 24 Achieved SALT-20 at Week 24 Achieved SALT-20 at Week 26 Figure reflects Revised Per-Protocol Population 15
Slide 16: SIGNAL-AA and SIGNAL-AD: Favorable Safety and Tolerability Profile
SIGNAL-AA and SIGNAL-AD: Favorable Safety and Tolerability Profile 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 relate
Slide 17: SIGNAL-AA and SIGNAL-AD: Adverse Events of Special Interest (Infections)
SIGNAL-AA and SIGNAL-AD: Adverse Events of Special Interest (Infections) SIGNAL-AD PART A & B SIGNAL-AA Bempikibart Placebo Bempikibart Placebo N=63 N=58 N=33 N=11 Not Related Related Not Related Not Related Related Not Related Related n (%) n (%) n (%) Related n (%) n (%) n (%) n (%) n (%) Infectio
Slide 18: Current Landscape of Marketed Agents for AA
Current Landscape of Marketed Agents for AA • Olumiant (baricitinib) approved in 2022, Litfulo (ritlecitinib) approved in 2023 • Both carry classwide Black Box Warning: • Olumiant approved recommended dose for AA: 2mg once daily 1 • Phase 3 SALT-20 at Week 24: 13% (BRAVE-AA1: 7% placebo-adjusted, BR
Slide 19: Tissue Targeted Platform: Building The Future of Complement Therapeutics
Tissue Targeted Platform: Building The Future of Complement Therapeutics
Slide 20: Proprietary Tissue-targeted Platform: Building The Future of Complement Therapeutics
Proprietary Tissue-targeted Platform: Building The Future of Complement Therapeutics The Evolution of Complement Therapeutics The Future: Tissue Targeted nd 2 Gen: Continued Systemic Applications Apellis InflaRx Kira st 1 Gen: UCB Novartis Omeros Pioneer Akari Sanofi Alnylam Alexion 20
Slide 21: Q32 Tissue-targeted Platform Value Proposition
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 drivin
Slide 22: ADX-097 (C3d targeted antibody – fH 1-5 fusion protein)
ADX-097 (C3d targeted antibody – fH 1-5 fusion protein)
Slide 23: ADX-097: A Novel Tissue-Targeted Approach to Regulating the Complement System
ADX-097: A Novel Tissue-Targeted Approach to Regulating the Complement System ADX-097 Design: C3d antibody – fH 1-5 ADX-097 Construct: humanized anti-C3d mAb linked to two moieties of a negative regulatory protein (fH ) 1-5 • Designed to be active at the site of complement activation in the tissue w
Slide 24: ADX-097 Lead Bivalent Fusion Protein: Unique MOA for Localized Complement Re-regulation
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
Slide 25: ADX-097 Preclinical and Ph1 Data: Robust Data Package
ADX-097 Preclinical and Ph1 Data: Robust Data Package Supports Desired PK and PD with Favorable Tolerability and Immunogenicity Profile Preclinical Data • Tissue distribution and target binding • Durable (>7 days) tissue PK/PD after SC dosing • Reduction in key proof of mechanism (POM)/proof of conc
Slide 26: ADX-097 Preclinical Data: Supports POM, POC, PK/PD Dosing Model
ADX-097 Preclinical Data: Supports POM, POC, PK/PD Dosing Model and Indication Rationale 1 Milestone Organ System Species Model ✓ Kidney IHC of human disease biopsies Target validation in human disease✓ Skin✓ Human (multiple disease-types for ✓ Liver kidney, skin & liver) ✓ Kidney✓ Mouse fH -/- mice
Slide 27: fH-/- Mouse Model of Human C3G
fH -/- Mouse Model of Human C3G with Uncontrolled Complement Activation: Showed Robust and Durable Tissue PK/PD in Absence of Circulating Inhibition of Complement Potent Tissue PK/PD ✓ Robust tissue PK/PD and activity at doses of 1 – 3 mg/kg, SC or IV ✓ Tissue PD EC90 = circulating concentration of
Slide 28: Passive Heymann Nephritis Rat Model of Human Membranous Nephropathy
Passive Heymann Nephritis Rat Model of Human Membranous Nephropathy: Showed Robust Effect on POM and POC Endpoints Proteinuria Podocyte Structures Normal Serum 75 Potent Vehicle ADX-097 Anti-Fx1A inhibition of CVF * 3 mg/kg (SC) proteinuria 50 * 1 mg/kg (SC) equivalent to * ADX-097 (single dose) **
Slide 29: ADX-097-001 Phase 1 Study: Complete with Primary Goals Achieved
ADX-097-001 Phase 1 Study: Complete with Primary Goals Achieved ADX-097-001 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 Ph
Slide 30: ADX-097 Phase 1 PK Data: Weekly SC Dosing Met Desired Exposures
ADX-097 Phase 1 PK Data: Weekly SC Dosing Met Desired Exposures for Predicted Complete Tissue Inhibition With No Concomitant Systemic Inhibition Phase 2 Dose Identified: 450 mg SC Met Key Exposure Goals 50% systemic complement inhibition 450mg SC achieved exposures below systemic inhibition and abov
Slide 31: ADX-097: Significant Market Potential in Priority High Unmet Need Indications
ADX-097: Significant Market Potential in Priority High Unmet Need Indications 10,11 13-15 IgA Nephropathy: 185K C3 glomerulopathy: 3K ~30% of those with Up to 50% of adult and proteinuria >1g/day develop 70% of pediatric patients kidney failure progress to kidney failure 7,8 Lupus nephritis: 100K 12
Slide 32: LN, IgAN, C3G Basket: Building Blocks for Renal Expansion
LN, IgAN, C3G Basket: Designed to Provide Building Blocks for Renal Expansion Renal Disease (LN, IgAN, C3G) Design/Timeline Basket design (n= up to 30), 24-week treatment Lupus Nephritis (LN) 1,2 • Designed to assess safety, tissue pharmacology and magnitude/timing 6-fold mortality risk increase vs
Slide 33: Q32 Bio Has Significant Potential to Unlock Near-term Value Creation
Q32 Bio Has Significant Potential to Unlock Near-term Value-creation Runway through multiple Phase 2 clinical readouts and into mid-2026 Financial • Q3 cash balance of $89.1M, providing expected cash runway to mid 2026 Overview • Approximately 12.1M shares outstanding • 1H25: Bempikibart AA Ph2 Part
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Slide 35: Bempikibart in AA: IL-7 Inhibition is Believed to Block CD8+ T cell-Driven Inflammation
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 35
Slide 36: Bempikibart Phase 2a Clinical Trial in Atopic Dermatitis Topline Results
Bempikibart Phase 2 Clinical Trial in Atopic Dermatitis Topline Results ADX-914-202 SIGNAL-AD Part A Part B 12-week treatment (n= 15 patients in Part A), 12-week follow-up 12-week treatment (n= ~100 patients in B), 12-week follow-up • Part A Key Assessments • Part B Key assessments: 200mg SC Q2W vs