Tectonic Therapeutic, Inc. · NASDAQ:TECX
Tectonic Therapeutic — Merger or Acquisition (January 2024)
33 slides from Tectonic Therapeutic's merger presentation, January 2024
Slide 1: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR- Targeted Therapies JANUARY 2024
Slide 2: Disclaimer
DISCLAIMER This communication contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including but not limited to, express or implied statements regarding the structure, timing and completion of the proposed M
Slide 3: Disclaimer (continued)
DISCLAIMER (continued) Participants in the Solicitation This communication relates to the proposed merger transaction involving AVROBIO and Tectonic and may be deemed to be solicitation material in respect of the proposed merger transaction. In connection with the proposed merger transaction, AVROBI
Slide 4: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR-Targeted Therapies JANUARY 2024
Slide 5: Merger of Tectonic Therapeutic and AVROBIO
5 Merger of Tectonic Therapeutic and AVROBIO • Tectonic Therapeutic, a privately-held biotechnology company focused on discovering and developing GPCR-targeted therapies, intends to merge with AVROBIO, Inc. (Nasdaq: OVERVIEW AVRO) • Supported by the Board of Directors of both companies and subject t
Slide 6: Tectonic Therapeutic – Transforming the Discovery of Novel GPCR-Targeted Therapies
6 Tectonic Therapeutic – Transforming the Discovery of Novel GPCR-Targeted Therapies, Innovating in Their Development • Validated platform to discover and optimize biologics that target GPCRs • Prioritizing high value GPCR targets, where small molecules are not the right modality • First two assets
Slide 7: Our Team Has Delivered for Patients and Investors
7 Our Team Has Delivered for Patients and Investors Alise Christian Peter Anthony Marcella Marc Reicin, M.D. Cortis, Ph.D. McNamara, Ph.D. Muslin, M.D. Ruddy, M.D. Schwabish, Ph.D. CEO, Director COO CSO CDO CMO CBO FOUNDED MULTIPLE GPCR EXPERT, SUCCESSFUL COMPANIES FORBES ”30 under 30” Timothy Andre
Slide 8: Biologics Offer Advantages Over Small Molecules in Targeting GPCRs
8 Biologics Offer Advantages Over Small Molecules in Targeting GPCRs in Multiple Settings ~12% >18%* Approved drugs target remain When difficult to drug with small molecules 100 GPCRs unexploited Biologic captures complexity of ligand / receptor engagement If target site similar to domains of differ
Slide 9: Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of GPCRs
9 Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of GPCRs GROUP 2 PULMONARY HEREDITARY HEMORRHAGIC FIBROSIS HYPERTENSION (Group 2 PH) TELANGIECTASIA (HHT) First in Class & Indication Bi-specific Approach Potential Best-in-Class GPCR Antagonist2 GPCR Antagonist2 RXFP1 Agonist1 (a
Slide 10: Post Close Cash to Support Pipeline Progression Into Mid-2027
10 Post Close Cash to Support Pipeline Progression Into Mid-2027 and Several Key Inflection Points Tectonic Pipeline and Expected Readouts RXFP1 • Complete PK/PD Data: mid 2024 Agonist Phase 1a • Ph 1b hemodynamic proof of concept data: 2025 (TX45 – Fc-relaxin) • Randomized Ph 2 data: 2026 GPCR Deve
Slide 11: GEODe Designed to Solve Key Challenges in GPCR Targeted Biologics Discovery
GEODe 11 GEODe Designed to Solve Key Challenges in GPCR Targeted Biologics Discovery GEODe™ Platform Features Challenges Designed for Success RETAIN endogenous GPCR structure to enable 1. screening against relevant form of receptor Receptor Engineering, and Purification Technology delivers abundant
Slide 12: TX45: Fc-Relaxin Fusion Protein
TX45: Fc-RELAXIN FUSION PROTEIN RXFP1 agonist with differentiated profile
Slide 13: Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy
TX45 13 Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation AGONIST PULMONARY AND SYSTEMIC VASODILATOR Natural Ligand of RXPF1 Increases cardiac output to Receptor accommodate the increased demand from developing fetus No RXFP1
Slide 14: Evidence of Serelaxin's Safety and Benefit in Acute Heart Failure
TX45 14 Evidence of Serelaxin’s Safety and Benefit in Acute Heart Failure (AHF) • A meta-analysis of 6 studies and >11,000 patients demonstrated that a 2-day infusion of serelaxin was safe and resulted in a 23% decrease in 5-day worsening heart failure • One of two pivotal studies include in meta-an
Slide 15: TX45 is Engineered to Solve a Critical PK Problem
TX45 15 TX45 is Engineered to Solve a Critical PK Problem Observed with Other Relaxin Molecules TX45 EXHIBITS SUPERIOR PROFILE vs. PARENT COMPOUND AND COMPARATOR2 MOLECULE3 Preclinical Rat Pharmacokinetic Data Relaxin has very short in vivo half-life Fc-fusion needed to improve PK Concentration Rela
Slide 16: TX45 Reflects Significant Protein Engineering to Optimize Its Pharmacology
TX45 16 TX45 Reflects Significant Protein Engineering to Optimize Its Pharmacology TX45 results in ~10x greater in vivo potency over comparator1 molecule than predicted based on PK and in vitro activity2 – potentially from reduced trapping of drug in glycocalyx, resulting in increased free drug avai
Slide 17: TX45 – Optimized RXFP1 Agonist for Group 2 PH in HFpEF
TX45 17 TX45 – Optimized RXFP1Agonist for Group 2 PH in HFpEF ✓ Potential Best-in-Class Relaxin • Protein engineering has extended pharmacologic half-life to Agonist with Optimized PK support monthly dosing • No approved therapy ✓ High Unmet Need in Group 2 • >600,000 patients in US PH with HFpEF1 •
Slide 18: Pulmonary Hypertension Consists of Distinct Diseases
TX45 18 Pulmonary Hypertension Consists of 5 Distinct Diseases Group 2 PH is of Greatest Interest for TX45’s Initial Indication Group 1 Group 2 Group 4 Group 5 (“PAH”) Group 3 (>600,0001) (“CTEPH”) (Misc.) (~25,0001) • Idiopathic • Due to left heart • Due to lung disease • Chronic thrombo- • Miscell
Slide 19: Our Focus is on the Group 2 PH Subset of HFpEF
TX45 19 Our Focus is on the Group 2 PH Subset of Heart Failure with Preserved EF (HFpEF) Clinical Program Designed to Enable Evaluation of Efficacy in Each Subgroup IpcPH (Isolated, post capillary PH) Heart Increased Left Ventricle Filling Pressures HFpEF Normal HFpEF (Several million pts.)1,2 Inc
Slide 20: Relaxin Multimodal MOA Addresses Pathways Implicated in Group 2 PH Pathophysiology
TX45 20 Relaxin Multimodal MOA Addresses Pathways Implicated in Group 2 PH Pathophysiology Mechanisms Implicated in Group 2 PH 1 Activation of ET-1 pathway(*) 2 Reduced NO pathway activity(*) 3 Activation of TGFβ pathway (*) Most active in CpcPH subset Effects of RXFP1 Activation by Relaxin ✓ Pulmon
Slide 21: Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification
TX45 21 Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification in Group 2 PH • Heart, and vascular dysfunction contribute to disease pathology • Renal dysfunction also present in many of these patients CHARACTERISTICS OF GROUP 2 PH IpcPH CpcPH ANTICIPATED RELAXIN EFF
Slide 22: Group 2 PH vs. PAH
TX45 22 Group 2 PH vs. PAH • Significant opportunity for a first-in-indication therapy • Highly motivated physicians and patients US PREVALENCE >> PAH 5 YEAR SURVIVAL < PAH6 NO THERAPEUTIC OPTIONS >600,0001-3 50% No approved Multiple drugs/ therapies mechanisms 45% approved … ET1R IpcPH Limited anta
Slide 23: PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin
TX45 23 PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin PDE5 inhibitors demonstrated efficacy across 3 studies (1-3) including: ✓Reduction in PVR PDE5i Effects ✓Improvement in exercise capacity ✓Decrease in heart failure hospitalizations TX45 anticipated to be effective in b
Slide 24: Relaxin Improves Hemodynamics in Heart Failure
TX45 24 Relaxin Improves Hemodynamics in Heart Failure Balanced pulmonary and peripheral vasodilation, and increased cardiac output relevant to Group 2 PH p<0.0001 • Above: serelaxin infusion for 20hrs in Acute Heart Failure patients with elevated pulmonary artery pressure (PAP) rapidly lowered mPAP
Slide 25: TX45 Development Program Overview
TX45 25 TX45 Development Program Overview Planned readouts in mid-2024, 2H 2025, 2026 2024 2025 2026 Phase 1A Healthy Mid-2024 Safety, • Safety Volunteers • PK tolerability, (ongoing) PK/PD • PD (Renal Blood Flow) Phase 1B 2025 RHC study to establish Group 2 PH • mPAP hemodynamic proof of with HFpEF
Slide 26: Preliminary PK/PD Analysis After TX45 Administration in Healthy Volunteers
Preliminary PK/PD Analysis After TX45 Administration in Healthy Volunteers January 2024
Slide 27: Summary of preliminary data from TX45 SAD study
TX45 27 Summary of preliminary data from TX45 SAD study1 Cohort A (0.3 mg/kg IV) and Cohort C (150 mg SC) • Well tolerated with minimal adverse events, no drug-related SAEs TX45 SAD Dose Escalation Plan • Pharmacokinetics – Low intersubject variability in serum concentrations (≤ 20%) – No evidence o
Slide 28: Phase 1A Study Preliminary Single Dose TX45 PK/PD Data
TX45 28 Phase 1A Study Preliminary Single Dose TX45 PK/PD Data (0.3 mg/kg) TX45 Serum Concentrations from Phase 1A Subjects Renal Plasma Flow in Phase 1A Subjects Cohort 0.3150 A mg/kg mg0.3 SCmg/kg IV IV TX45 Dosed on Day 1 - Cohort A 0.3 mg/kg IV 100.0 PK in humans 100 Predicted predicted from NHP
Slide 29: PK Modeling Suggests TX45 Can be Given Monthly
TX45 29 PK Modeling based on Preliminary Data Suggests TX45 Can be Given Monthly 150 mg SC q4w Target (1.7 μg/mL) 1 Mo 16 Target (0.6 μg/mL) • A model was constructed using observed data from both 0.3 mg/kg IV and 150 mg SC cohorts to predict 14 trough concentrations of 150 mg SC Q4W • Terminal t1/2
Slide 30: Significant Pharma Interest in Relaxin
TX45 30 Significant Pharma Interest in Relaxin Tectonic has Potential Best-in-Class Molecule Expected Dosing Company Format Formulation Frequency Fc-Fusion Engineered for optimal PK, SubQ Q4 Weeks biodistribution, high [C] High [C] achievable formulation Fc-Fusion SubQ Q2 Weeks h-Albumin-mAb-Fusion
Slide 31: Summary
TECTONIC Therapeutic
Slide 32: Uniquely Positioned to Deliver on Value Creating Milestones
32 Uniquely Positioned to Deliver on Value Creating Milestones Strong Balance Sheet Pipeline of Uniquely Accomplished Team Anticipated Post Differentiated Assets World-leader Founders Transaction 20 1st Approvals ~$165 Million Multiple Inflection Points 2024, 2025, 2026 >$50 Billion in Annual Sales
Slide 33: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR-Targeted Therapies JANUARY 2024
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