Tectonic Therapeutic, Inc. · NASDAQ:TECX
Tectonic Therapeutic — AVROBIO — Merger or Acquisition (April 2024)
33 slides from Tectonic Therapeutic's merger presentation, Apr 4, 2024
Slide 1: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR- Targeted Therapies Apri l 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 AVROBIO, Tectonic and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from stockholders in connection with the proposed Merger. Information about the directors and executive offi
Slide 4: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR-Targeted Therapies Apri l 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: AVRO) OVERVIEW • 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: This Team Has Delivered for Patients and Investors
7 This 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, CFO CSO CDO CMO CBO FOUNDED MULTIPLE GPCR EXPERT, SUCCESSFUL COMPANIES FORBES ”30 under 30” Timothy
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 remain When difficult to drug with small molecules drugs target unexploited Biologic captures complexity of ligand / receptor engagement 100 GPCRs 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 2 2 Potential Best-in-Class GPCR Antagonist GPCR Antagonist 1 (anti-angioge
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 Phase 1a • Ph 1b hemodynamic proof of concept data: 2025 Agonist • Randomized Ph 2 data: 2026 (TX45 – Fc-relaxin) GPCR • St
Slide 11: GEODe Platform Designed to Solve Key Challenges in GPCR Targeted Biologics Discovery
11 GEODe GEODe Designed to Solve Key Challenges in GPCR Targeted Biologics Discovery GEODe™ Platform Features Challenges Designed for Success RETAIN 1. endogenous GPCR structure to enable Receptor Engineering, and Purification Technology screening against relevant form of receptor 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 Role in Pregnancy
13 TX45 Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation AGONIST PULMONARY AND SYSTEMIC VASODILATOR Increases cardiac output to Natural Ligand of RXPF1 accommodate the Receptor increased demand from developing fetus No RXFP1
Slide 14: Evidence of Serelaxin's Safety and Benefit in Acute Heart Failure
14 TX45 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
15 TX45 TX45 is Engineered to Solve a Critical PK Problem Observed with Other Relaxin Molecules TX45 EXHIBITS SUPERIOR PROFILE vs. PARENT COMPOUND 2 3 AND COMPARATOR MOLECULE Preclinical Rat Pharmacokinetic Data Relaxin has very short in vivo half-life Fc-fusion needed to improve PK Relaxin Fc-fusio
Slide 16: TX45 Reflects Significant Protein Engineering to Optimize Its Pharmacology
16 TX45 TX45 Reflects Significant Protein Engineering to Optimize Its Pharmacology 1 TX45 results in ~10x greater in vivo potency by dose over comparator molecule than predicted 2 based on PK and in vitro activity – potentially from reduced trapping of drug in glycocalyx, resulting in increased free
Slide 17: TX45 – Optimized RXFP1 Agonist for Group 2 PH in HFpEF
17 TX45 TX45 – Optimized RXFP1Agonist for Group 2 PH in HFpEF ü Potential Best-in-Class Relaxin • Protein engineering has extended pharmacologic half-life to support monthly dosing Agonist with Optimized PK • No approved therapy ü High Unmet Need in Group 2 • >600,000 patients in US 1 PH with HFpEF
Slide 18: Pulmonary Hypertension Consists of Distinct Diseases
18 TX45 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 1 (>600,000 ) (“CTEPH”) (Misc.) 1 (~25,000 ) • Idiopathic • Due to left heart • Due to lung disease • Chronic thrombo- • Mis
Slide 19: Our Focus is on the Group 2 PH Subset of HFpEF
19 TX45 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 Ô HFpEF 1,2 Increased Pulmonary Venou
Slide 20: Relaxin Multimodal MOA Addresses Pathways Implicated in Group 2 PH
20 TX45 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(*) Activation of TGFβ pathway 3 (*) Most active in CpcPH subset Effects of RXFP1 Activation by Relaxin ü Pulmon
Slide 21: Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification
21 TX45 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
22 TX45 Group 2 PH vs. PAH • Significant opportunity for a first-in-indication therapy • Highly motivated physicians and patients 6 US PREVALENCE >> PAH 5 YEAR SURVIVAL ≤ PAH NO THERAPEUTIC OPTIONS 1-3 >600,000 50% 50% ~ No approved Multiple drugs/ therapies mechanisms approved … ET1R antagonists Ip
Slide 23: PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin
23 TX45 PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin PDE5 inhibitors demonstrated (1-3) benefits across 3 studies including: üReduction in PVR üImprovement in exercise capacity PDE5i Effects üDecrease in heart failure hospitalizations TX45 anticipated to be beneficial in
Slide 24: Relaxin Improves Hemodynamics in Heart Failure
24 TX45 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 mP
Slide 25: TX45 Development Program Overview
25 TX45 TX45 Development Program Overview Planned readouts in mid-2024, 2H 2025, 2026 2024 2026 2025 Mid-2024 Phase 1A Healthy • Safety Safety, Volunteers • PK tolerability, (ongoing) • PD (Renal Blood Flow) PK/PD Phase 1B 2025 Group 2 PH • mPAP RHC study to establish with HFpEF • PVR hemodynamic pr
Slide 26: Preliminary PK/PD Analysis After TX45 Administration in Healthy Volunteers
Preliminary PK/PD Analysis After TX45 Administration in Healthy Volunteers April 2024
Slide 27: Summary of Preliminary Data from TX45 SAD Study
27 TX45 1 Summary of preliminary data from TX45 SAD study Cohort A (0.3 mg/kg IV) and Cohort C (150 mg SC) • Well tolerated with minimal adverse events, TX45 SAD Dose Escalation Plan no drug-related SAEs • Pharmacokinetics – Low intersubject variability in serum concentrations (≤ 20%) – No evidence
Slide 28: Phase 1A Study Preliminary Single Dose TX45 PK/PD Data
28 TX45 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 A 0.3 mg/kg IV TX45 Dosed on Day 1 - Cohort A 0.3 mg/kg IV 0.3 mg/ kg IV PK in humans 100. 100 0 Predicted predicted from NHP data
Slide 29: PK Modeling Suggests TX45 Can be Given Monthly
29 TX45 PK Modeling based on Preliminary Data Suggests TX45 Can be Given Monthly 150 mg SC q4w Target (1.7 μg/mL) 1 Mo Target (0.6 μg/mL) 16 • 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 t is
Slide 30: Significant Pharma Interest in Relaxin
30 TX45 Significant Pharma Interest in Relaxin Tectonic has Potential Best-in-Class Molecule Expected Dosing Company Format Formulation Frequency Fc-Fusion SubQ Engineered for optimal PK, Q4 Weeks biodistribution, high [C] High [C] achievable formulation Fc-Fusion SubQ Q2 Weeks SubQ h-Albumin-mAb-Fu
Slide 31: Summary
31 Summary
Slide 32: Uniquely Positioned to Deliver on Value Creating Milestones
32 Uniquely Positioned to Deliver on Value Creating Milestones Strong Balance Sheet Accomplished Team Pipeline of Uniquely Anticipated Post World-leader Founders Differentiated Assets Transaction st 20 1 Approvals ~$165 Million Multiple Inflection Points >$50 Billion in Annual Sales >3 Year Runway 2
Slide 33: Transforming the Discovery of Novel GPCR-Targeted Therapies
Transforming the Discovery of Novel GPCR-Targeted Therapies Apri l 2024