Q32 Bio Inc. · NASDAQ:QTTB
Q32 Bio — Homology Medicines — Merger or Acquisition (January 2024)
41 slides from Q32 Bio's merger presentation, Jan 26, 2024
Slide 1: Building The Future of Immune Therapeutics: Company Overview
Exhibit 99.1 Building The Future of Immune Therapeutics Company Overview January 2024
Slide 2: Disclaimers
Disclaimers Important Information for Investors This confidential presentation (Presentation) is for informational purposes only and is being provided to interested parties solely in their capacity as potential investors for the purpose of evaluating a potential private offering of securities (the P
Slide 3: Disclaimers (cont.)
Disclaimers (cont.) Important Information about the Proposed Transaction and Where to Find It In connection with the Proposed Transaction, Homology filed a registration statement on Form S-4 that includes a proxy statement of Homology and that constitutes a prospectus with respect to shares of Homol
Slide 4: Risk Factors
Risk Factors Both Homology and Q32 are subject to various risks associated with their businesses and their industries. In addition, the Proposed Transaction, including the possibility that the Proposed Transaction may not be completed, poses a number of risks to each company and its respective secur
Slide 5: 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, designed to provide broad control of T cell- mediated pathological processes in autoimmune diseases IL-7Rα Antagonist Antibody • Ph1 data show attractive PK/PD profile, favorab
Slide 6: Transaction Summary: Q32 Bio Merger with Homology Medicines
Transaction Summary: Q32 Bio Merger with Homology Medicines (NASDAQ: FIXX) •Homology Medicines, Inc. (NASDAQ: FIXX) to acquire 100% of the outstanding equity interests of Q32 Bio Inc., structured as a tax- free reorganization and by means of a reverse triangular merger of a wholly-owned subsidiary o
Slide 7: Q32 Management Team
Q32 Management Team: Experienced Public Company Leadership Team with Deep Drug Development Experience Executive Team Jodie Morrison Lee Kalowski, MBA Shelia Violette, PhD Jason Campagna, MD, PhD Maria Marzilli, MPH Saul Fink, PhD CEO Interim CFO CSO, President of CMO EVP, Corporate Strategy CTO Rese
Slide 8: 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 Phase 3 Preclinical Milestones IL-7/TSLP PROGRAM Atopic Topline Ph2 Dermatitis Bempikibart 1 results 2H24 1 (ADX-914) Alopecia Areata COMPLEMENT INHIBITOR PLATFORM Basket: L
Slide 9: ADX-914 (IL-7 / TSLP Receptor Inhibitor)
ADX-914 (IL-7 / TSLP Receptor Inhibitor)
Slide 10: Bempikibart (ADX-914): Novel Investigational Therapy for T-cell Mediated Diseases
Bempikibart (ADX-914): Novel Investigational Therapy for T-cell Mediated Inflammatory and Autoimmune Diseases Delivering Two Phase 2 Readouts in 2024 Bempikibart: IL-7Rα antagonist antibody blocks IL-7 and TSLP signaling IL-7 • Potent regulator of pathogenic T / T survival and proliferation eff mem
Slide 11: 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
Slide 12: Re-Acquisition of Bempikibart (ADX-914)
Re-Acquisition of Bempikibart (ADX-914) • In November 2023, Q32 regained full worldwide rights to Bempikibart (ADX-914) from Amgen • Per the terms of the agreement: • Q32 retains the initial consideration and all development funding received (total $55M) • Q32 will pay Amgen a milestone upon the fir
Slide 13: ADX-914: Phase 1 Clinical Data Support Rapidly Advancing Clinical Development
ADX-914: Phase 1 Clinical Data Support Rapidly Advancing Clinical Development IL7 Receptor Occupancy Observed 100 Generally well tolerated up to 4 mg/kg 50 Full RO & pSTAT5 inhibition at 1 mg/kg SC 0 dosing Q2W in NHV Pooled Placebo -50 SAD1: -914 .1 mg/kg PK/PD profile evaluated in patients; 2 8 15
Slide 14: ADX-914 Phase 2 AD Part A Data Supports Development Program
ADX-914 Phase 2 AD Part A Data Supports Development Program Part A Evaluated 2 mg/kg and 3 mg/kg Q2W SC for 12 weeks • PK/Dosing: Both dose groups maintained target PK threshold > 5 ug/ml (dose predicted to achieve full target engagement in tissue); 1 supports administration of 200 mg SC flat dosing
Slide 15: Dual MOA Potential to Modulate Immune Cells in AD Pathogenesis
By Virtue of its Dual MOA, We Believe ADX-914 Has the Potential to Modulate Immune Cells Important in Both Acute and Chronic AD Pathogenesis ADX-914: Intended to block TH2 and TH1 driven disease pathology in AD Existing therapies focused on early AD, providing inadequate response as the disease prog
Slide 16: ADX-914-202 SIGNAL-AD: Phase 2 Atopic Dermatitis POC Clinical Trial
ADX-914-202 SIGNAL-AD: Phase 2 Atopic Dermatitis POC Clinical Trial Atopic Dermatitis Design/Timeline 12-week treatment (n= ~102 patients) Atopic dermatitis is the most common chronic inflammatory skin disease 1,2,3 • Prevalence in children ranges from 2%-20% • PK Run in completed: Dose selected for
Slide 17: ADX-914: Evaluating Potential to Block TH1 and TH2 Driven Pathology In AA
ADX-914: Evaluating Potential to Block TH1 and TH2 Driven Disease Pathology In AA Hair Follicle Immune Dysregulation in Alopecia Curr Res Immunol. 2021 ADX-914 is designed to inhibit IL-7 signaling and could potentially benefit alopecia areata patients by blocking CD8+ T cell-driven inflammation 17
Slide 18: ADX-914-202 SIGNAL-AA: Phase 2 Alopecia Areata POC Clinical Trial
ADX-914-202 SIGNAL-AA: Phase 2 Alopecia Areata POC Clinical Trial Alopecia Areata Design/Timeline 24-week treatment (n= ~40 patients) Alopecia Areata is common, and psychosocially debilitating; scalp and face commonly impacted • SC dosing, placebo controlled • Approximate prevalence of 2%, most befo
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: The Evolution 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 Lead Bivalent Fusion Protein: Unique MOA
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 24: ADX-097 Preclinical and Ph1 Data
ADX-097 Preclinical and Ph1 Data: Robust data package supports desired PK and PD with favorable tolerability and good 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
Slide 25: 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 ü Kidney IHC of human disease biopsies Target validation in human diseaseü Skinü Human (multiple disease-types for ü Liver kidney, skin & liver) ü Kidneyü Mouse fH -/- mice
Slide 26: 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 ü Robust tissue PK/PD and activity at doses of 1 – 3 mg/kg, SC or IV ü Tissue PD EC90 = circulating concentration of
Slide 27: Passive Heymann Nephritis Rat Model of 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 Anti-Fx1A inhibition of CVF 3 mg/kg (SC) proteinuria 50 1 mg/kg (SC) equivalent to ADX-097 (single dose) ** 0.3 mg/kg (SC) full sy
Slide 28: 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 29: 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 30: 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 31: LN, IgAN, C3G Basket: Building Blocks for Renal Expansion
LN, IgAN, C3G Basket: Designed to Provide Building Blocks for Renal Expansion LN, IgAN, C3G Unmet Need Planned Design 1,2 6-fold mortality risk increase vs general population Basket design (n= up to 30) Up to 30% develop kidney failure requiring dialysis or • Designed to assess safety, tissue pharma
Slide 32: AAV Two-part Phase 2
AAV Two-part Phase 2: Expected to Deliver Key Biomarker Data & Evaluation of Reduction of Steroids AAV Unmet Need Planned Design Ph2 design informed by avacopan Ad Com roadmap More effective induction and maintenance 1-3 • With treatment, 5-year mortality 10-30% overall Part A (funded FPI 1Q25) : 12
Slide 33: Looking Ahead
Looking Ahead
Slide 34: Merger Positions Q32 Bio to Unlock Significant Near-term Value-creation
* Merger Positions Q32 Bio to Unlock Significant Near-term Value-creation Pro forma runway through multiple value-driving Phase 2 clinical readouts Use of • To fund the continued development of pipeline candidates, other ongoing research and development activities, and for general corporate purposes
Slide 35: 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, designed to provide broad control of T cell- mediated pathological processes in autoimmune diseases IL-7Rα Antagonist Antibody • Ph1 data show attractive PK/PD profile, favorab
Slide 36: Thank You!
@32BlO Thank You!
Slide 37: Appendix: ADX-097
Appendix: ADX-097
Slide 38: Several Disease Models Establish Drug Levels for Maximal Tissue PD & Activity
Several Disease Models (Mouse, Rat and NHP) Establish Drug Levels Anticipated for Maximal Tissue PD & Activity Preclinical Disease Model Studies Establishing Dose Response and PoM/PoC 3 mg/kg SC = circ. conc of 0.3 ug/ml Several disease models demonstrate maintaining drug levels of 0.3 - 3.2 ug/ml 3
Slide 39: ADX-097-101: Plasma Concentrations and Wieslab AP Activity After Single Dose IV
ADX-097-101: Plasma ADX-097 Concentrations and % of Baseline Wieslab AP Activity After Single Dose IV ADX-097 IV Dosing PK % of Baseline AP Activity LLOQ Corrected • C increased dose-proportionally following 0.1 to 30 mg/kg IV dosing; Tmax achieved within 80 minutes after IV infusion max • 30 mg/kg
Slide 40: ADX-097-101: Plasma Concentrations and Wieslab AP Activity After SC Dose
ADX-097-101: Plasma ADX-097 Concentrations and % of Baseline Wieslab AP Activity After Single/Multiple Dose SC of ADX-097 SC Dosing PK % of Baseline AP Activity LLOQ Corrected • Tmax achieved within 1-3 days after SC dosing • After single dose 10 mg/kg SC ADX-097, AP activity decreased to 65% of bas
Slide 41: ADX-097-101: Key Pharmacology Takeaways
ADX-097-101: Key Pharmacology Takeaways ADX-097 showed nonlinear PK with a saturable clearance mechanism • Detectable plasma ADX-097 concentrations in all PK-evaluable participants • T achieved within 80 minutes after IV infusion and within 1 to 3 days after SC injection max • C increased dose-propo
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