Tectonic Therapeutic, Inc. · NASDAQ:TECX
Tectonic Therapeutic — Investor Presentation (September 2024)
56 slides from Tectonic Therapeutic's investor presentation, Sep 19, 2024
Slide 1: Transforming and Innovating the Discovery and Development of GPCR-Targeted Therapies
Exhibit 99.2 Transforming and Innovating the Discovery and Development of Novel, Class Leading GPCR-Targeted Therapies S e p t e m b e r 2 0 2 4
Slide 2: Disclaimer
DISCLAIMER Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as anticipates, believes, expects, intends, “plans,” “potential,” p
Slide 3: Agenda
3 Agenda I. Company Overview TM II. GEODe Platform III. TX45 Relaxin in Group 2 Pulmonary Hypertension i. Overview of Target and Indication ii. Patient Journey iii. Clinical Data iv. Preclinical Data v. Clinical Program IV. HHT Program V. Summary
Slide 4: Tectonic Therapeutic – Transforming the Discovery of GPCR-Targeted Therapies
4 Tectonic Therapeutic – Transforming the Discovery of Novel GPCR-Targeted Therapies, Innovating in Their Development • Validated platform to discover and optimize biologics that target GPCRs Validated GEODe Platform• Prioritizing high value GPCR targets, where small molecules are not the right moda
Slide 5: This Accomplished Team Has Delivered for Patients and Investors
5 This Accomplished Team Has Delivered for Patients and Investors Alise Daniel Peter Anthony Marcella Marc Reicin, M.D. McNamara, Ph.D. Muslin, M.D. Ruddy, M.D. Schwabish, Ph.D. Lochner CEO, Director CSO CDO CMO CBO CFO FOUNDED MULTIPLE GPCR EXPERT, SUCCESSFUL COMPANIES FORBES ”30 under 30” Timothy
Slide 6: Team Track Record: >20 Approvals with >$50B In Annual Sales
6 st Team Track Record: >20 1 Approvals with >$50B In Annual Sales st 1 approvals and indication expansions shown below ONCOLOGY/ IMMUNOLOGY/ CARDIO/ RESPIRATORY OTHER IO INFLAMMATION METABOLISM / ALLERGY
Slide 7: Biologics Offer Advantages Over Small Molecules in Targeting GPCRs
7 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 8: Unique Pipeline Opportunities Enabled by Biologic Targeting of GPCRs
8 Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of GPCRs GROUP 2 PULMONARY HEREDITARY HEMORRHAGIC FIBROSIS f HYPERTENSION (Group 2 PH) TELANGIECTASIA (HHT) IN PHASE 2 First in Class & Indication Bi-specific Approach 2 2 GPCR Antagonist GPCR Modulator Potential Best-in-Class (an
Slide 9: Pipeline of GPCR-Targeted Biologics with Multiple Value Inflection Points
9 Pipeline of GPCR-Targeted Biologics with Multiple Potential Value Infection Points Ahead Phase 1 Phase 2 Indication Program Preclinical Phase 3 (1) Group 2 PH in Phase 2 Initiated Phase 1b (ongoing) Patients with Heart RXFP1 Agonist in August ‘24 Hemodynamic data Failure with Randomized (TX45 – Fc
Slide 10: GEODe Platform
10 GEODe PLATFORM Proprietary, validated platform, enables reproducible discovery and optimization of GPCR targeted biologics
Slide 11: GEODe Solving Key Challenges in GPCR Targeted Biologics Discovery
11 GEODe Solving 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 receptor reagent
Slide 12: GEODe Platform Spans Three Enabling Technologies
12 GEODe Proprietary GEODe platform spans three enabling technologies to identify and optimize potent GPCR targeted biologics 1. 2. 3. EXPRESSION AND IN-VITRO YEAST PROTEIN ENGINEERING PURIFICATION TECHNOLOGY DISPLAY LIBRARIES • Optimize Protein Pharmacology Produce Sufficient Quantities Efficiently
Slide 13: GEODe Discovery Capabilities Deliver Selective Orthosteric Antagonists
13 GEODe GEODe Platform Discovery Capabilities Deliver Selective, Ligand Competitive Orthosteric Antagonists PURIFIED ANTIBODIES ARE OPTIMIZATION IMPROVES SELECTIVE * FUNCTIONAL ANTAGONISTS ORIGINAL POTENCY BY ~20X (NO EFFECT ON OFF-TARGET GPCR) Receptor Signaling Assay (Mammalian Cells) 125 200 TX7
Slide 14: Proprietary Antigen Formats Enable Screening for Agonist Activity
14 GEODe Our Proprietary Antigen Formats Enable Screening for Biologics with Agonist Activity Active Inactive GPCR GPCR Proprietary Ga Mimetics Membrane Designs Driven by Machine Cytosol Learning and Energy Prediction Algorithms Proprietary Gα mimetic
Slide 15: Design of Proprietary Gα Mimetics Driven by Machine Learning
15 GEODe Design of Our Proprietary Ga Mimetics Is Driven by the Latest in Machine Learning and Energy Prediction Algorithms Nucleotide-bound In-silico Deep Mutational Mutations Predicted to Stabilize the Confirmation Scanning for Receptor-bound GPCR Bound Conformation of G⍺ s Stabilizing Mutations a
Slide 16: End-to-end Capabilities in Place at Tectonic
16 GEODe End-to-end Capabilities in Place at Tectonic for Continued Discovery of Optimal DCs Suite of Ab Discovery, Optimization and Characterization Capabilities • GPCR structural and mechanistic know-how Target Prep for GPCR Biochemistry • Overexpression & stabilization of target TARGET Discovery
Slide 17: TX45: Fc-Relaxin Fusion Protein
TX45: Fc-RELAXIN FUSION PROTEIN RXFP1 agonist with differentiated profile
Slide 18: Hemodynamic and Anti-fibrotic Properties of Relaxin in Pregnancy
18 TX45 Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation PULMONARY AND AGONIST SYSTEMIC VASODILATOR Increases cardiac output to Natural Ligand of RXFP1 accommodate the Receptor increased demand from developing fetus No RXFP1
Slide 19: Serelaxin Demonstrated Safety and Benefit in Acute Heart Failure
19 TX45 The First Recombinant Relaxin (serelaxin) Demonstrated Safety and Benefit in Acute Heart Failure (AHF) in Trials of >11,000 Patients -Note: trials only included a two-day relaxin infusion Study (WHF Day 5) Relative Risk [95% CI] N(drug) N(pbo) PK limitations of relaxin a Pre-RELAX AHF 0.56 [
Slide 20: TX45 Engineered to Solve a Critical PK Problem
20 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 21: TX45 Reflects Significant Protein Engineering to Optimize Pharmacology
21 TX45 TX45 Reflects Significant Protein Engineering to Optimize Its Pharmacology 1 TX45 results in ~10x greater in vivo potency over comparator molecule than predicted based on PK 2 and in vitro activity – potentially from reduced trapping of drug in glycocalyx, resulting in increased free drug av
Slide 22: TX45 – Optimized RXFP1 Agonist for Group 2 PH in HFpEF
22 TX45 TX45 – Optimized RXFP1 Agonist for Group 2 PH in HFpEF ✓ Potential Best-in-Class Relaxin • Protein engineering has extended pharmacologic half-life to support monthly dosing Agonist with Optimized PK • No approved therapy ✓ High Unmet Need in Group 2 • >600,000 patients in US 1 PH with HFpEF
Slide 23: Pulmonary Hypertension Consists of Distinct Diseases
23 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-• Misce
Slide 24: Focus on Group 2 PH Subset of HFpEF
24 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 Overall Population and CpCPH IpcPH (Isolated, post capillary PH) Heart Increased Left Ventricle Filling Pressures HFpEF Normal Ô HFpEF 1,2 Increased
Slide 25: Group 2 PH: Patient Journey
25 Group 2 PH: Patient Journey
Slide 26: Key Hemodynamic Measures in Pulmonary Hypertension
26 TX45 Key Hemodynamic Measures in Pulmonary Hypertension Measure Definition Detection Method(s) / Formulas Clinical Significance mPAP Directly measured by RHC Fluid pressure in the Key parameter for diagnosing pulmonary Mean Pulmonary Arterial lung arteries hypertension of all causes (Groups I-V)
Slide 27: Group 2 Pulmonary Hypertension Patient Journey
27 TX45 Group 2 Pulmonary Hypertension (PH) Patient Journey Patient with HF Symptoms Echocardiography (LVEF, SPAP) Cardiologist 2 Treat HF (HFpEF , SPAP > 30 3 (pulmonary hypertension) HFrEF ) No RH Catheterization Yes mPAP > 20 mPAP > 20 mPAP > 20 PVR ≥ 3 PVR < 3 PVR ≥ 3 PCWP ≥ 15 PCWP ≥ 15 PCWP <
Slide 28: Treatment of PH in the Setting of HFpEF
28 Treatment of Pulmonary Hypertension (PH) in the Setting of Heart Failure with Preserved Ejection Fraction (HFpEF) Patient Diagnosed with PH-HFpEF (LVEF ≥ 50%, PCWP ≥ 15, mPAP > 20) Treat Co-Morbidities Start SGLT2 inhibitor (HTN, AFib, Diabetes, Obesity, Sleep Apnea) Repeat echo Consider Mineralo
Slide 29: Relaxin Multimodal MOA Addresses Pathways in Group 2 PH
29 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 ✓ Pulmon
Slide 30: Relaxation and Anti-Fibrotic Effects Have Potential for Disease Modification
30 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 31: Group 2 PH vs. PAH
31 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 No approved Multiple drugs/ ~ 50% 50% therapies mechanisms approved … IpcPH Limited (>500
Slide 32: PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin
32 TX45 PDE5 Inhibitors Affect Only One of Several Pathways Addressed by Relaxin PDE5 inhibitors demonstrated (1-3) efficacy across 3 studies including: ✓Reduction in PVR ✓Improvement in exercise capacity PDE5i Effects ✓Decrease in heart failure hospitalizations TX45 anticipated to be effective in b
Slide 33: PDE5 Inhibitors Show Benefit in CpcPH and HFpEF
33 TX45 PDE5 Inhibitors Show Significant Benefit in CpcPH and HFpEF Despite Limited Mechanism of Action Compared with Relaxin Expected to Increase POS of Relaxin in HFpEF and CpcPH PDE5i TREATMENT DECREASES (3) HOSPITALIZATIONS Patients with HF Hospitalizations PDE5i Post-treatment LOWERS (1) PVR Pr
Slide 34: Relaxin Improves Hemodynamics in Heart Failure
34 TX45 Relaxin Improves Hemodynamics in Heart Failure Balanced pulmonary and peripheral vasodilation, and improved heart function (decreased PCWP) relevant to Group 2 PH mPAP PVR (Pulmonary (lung) artery pressure) (Blood flow resistance in pulmonary arteries) p<0.0001 • Panels: serelaxin infusion f
Slide 35: TX45 and Other Relaxin Preclinical Data
35 TX45 and Other Relaxin Preclinical Data Preclinical validation Anti-fibrotic effects of relaxin observable across broad range of studies
Slide 36: TX45 Efficacy in Monocrotaline-Induced Model of PH in Rats
36 TX45 TX45 Efficacy in Monocrotaline-Induced Model of Pulmonary Hypertension in Rats TX45 Significantly Reduces Right Ventricular Systolic Pressure, Fulton’s Index and Muscularization of Small Pulmonary Arteries in Tx Model of PH Reduced Histological Reduced Pulmonary Improved Pulmonary Reduced Ca
Slide 37: TX45 Reduces Collagen and TNFa in Mouse Renal Fibrosis Model
37 TX45 TX45 Significantly Reduces Collagen and TNFa levels in Mouse UUO Model of Renal Fibrosis Sham TNFa Collagen IV IHC Quantification in Kidney Cortex 0.010 25 p = 0.02 0.008 20 0.006 UUO + Vehicle 15 0.004 10 5 0.002 UUO + TX45 0 0.000 Sham UUO + Vehicle UUO + TX45 Sham UUO + Vehicle UUO + TX45
Slide 38: TX45 Reduces Cardiac Hypertrophy and Fibrosis in Mouse Model
38 TX45 TX45 Reduces Cardiac Hypertrophy and Fibrosis in the Mouse Isoproterenol Induction Model Heart Weight/Body Weight Collagen content Vehicle Isoproterenol Isoproterenol Vehicle Isoproterenol Isoproterenol + TX45 +TX45
Slide 39: Relaxin Prevents Diastolic Dysfunction in a Model of HFpEF
39 TX45 Relaxin Prevents Diastolic Dysfunction in a Model of HFpEF and Reverse Cardiac Fibrosis Relaxin Prevents TAC (transverse aortic constriction) -Induced Cardiac Diastolic Dysfunction in Rats & Reverses Diabetes-Induced Cardiac Fibrosis and Diastolic Dysfunction in mRen-2 Rats. Human relaxin-2
Slide 40: Additional Anti-Fibrotic Effects of Relaxin in Heart Failure Models
40 TX45 Additional Anti-Fibrotic Effects of Relaxin Demonstrated in Preclinical Animal Models of Heart Failure In other rodent models of heart failure, Relaxin has been shown to also: 1 ✓Inhibit TGFb or ANG-II induced collagen synthesis in cardiac fibroblasts 2 ✓Prevent interstitial and perivascular
Slide 41: TX45 Clinical Program and Preliminary Phase 1a Data
41 TX45 Clinical Program and Preliminary Phase 1 Data
Slide 42: TX45 Development Program Overview
42 TX45 TX45 Development Program Overview Planned readouts in 2025 and 2026 2024 2026 2025 Healthy Toplined Sept ’24 Phase 1a Safety, PK, PD (Renal Blood Flow) Volunteers Safety, tolerability, PK/PD Phase 1b Group 2 PH Expected Q2-2025 RHC study to establish hemodynamic with HFpEF mPAP, PVR, PCWP, C
Slide 43: TX45 Phase 1a Single Ascending Dose Study
43 TX45 TX45 Phase 1a Single Ascending Dose Study • Study has completed TX45 SAD Dose Escalation Plan • TX45 was well tolerated with minimal adverse events, no drug-related SAEs • Pharmacokinetics – PK is dose proportional – No evidence of immune mediated clearance • Pharmacodynamics from 0.3 mg/kg
Slide 44: Phase 1a Preliminary Single Dose PK/PD Data
44 TX45 Phase 1a Study: Preliminary Single Dose TX45 Pharmacokinetic/Pharmacodynamic Data (lowest dose) 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 15 m0 mg g/kg IV SC PK in humans 100.0
Slide 45: Preclinical PK/PD from Acute RBF Model Informs Target Plasma Levels
45 TX45 Preclinical PK/PD from Acute RBF Model Informs Target Plasma Concentration Levels at Trough for Therapeutic Effect RBF Model Used to assess pharmacodynamic response to TX45 administration based on acute vasodilatory effects of relaxin, as measured by increased rat renal blood flow (RBF) * *
Slide 46: Summary of Planned TX45 Phase 2 Study Design
46 TX45 Summary of Planned TX45 Phase 2 Study Design TX000045 – 300mg Q4W SC (n=60) Screening RHC prior to randomization TX000045 – 300mg Q2W SC (n=60) (n=60)
Slide 47: Significant Pharma Interest in Relaxin
47 TX45 Significant Pharma Interest in Relaxin Tectonic has Potential Best-in-Class Molecule Expected Dosing Company Format Formulation Population Timing Frequency Fc-Fusion Group 2 PH / Start in August ’24 SubQ Engineered for optimal Q4 Weeks HFpEF (enriched PK, biodistribution, high High [C] achie
Slide 48: HHT Program
48 HHT Program nd First-in- indication opportunity for 2 most common genetic bleeding disorder
Slide 49: Hereditary Hemorrhagic Telangiectasia (HHT)
49 HHT Hereditary Hemorrhagic Telangiectasia (HHT) Autosomal Dominant Disease that Causes Abnormal Blood Vessel Formation No currently • Rare, autosomal dominant disease: ~ 75,000 patients in US approved • Mutations in the BMP9/10 pathway AVMs Telangiectasias therapies for HHT • High degree of pheno
Slide 50: Anti-VEGF: Mouse HHT Model Predictive of Efficacy in Patients
50 HHT Anti VEGF: Mouse HHT Model Predictive of Efficacy in Patients ANTI-VEGF mAb SUPPRESSES AVM FORMATION, ANTI-VEGF THERAPY REDUCES EPISTAXIS SEVERITY, VISCERAL HEMORRHAGE IN HHT MODEL IMPROVES HEM. PARAMETERS IN PATIENTS ALK-1 Conditional Knock-Out Wound-induced vascular response Decreases Impro
Slide 51: GPCR3 Antagonist Reduces AVMs and Retinal Vascular Density in Animal Model
51 HHT A GPCR3 Antagonist Significantly Reduces AVMs and Retinal Vascular Density in Animal Model of HHT (1,2) Effects of anti-GPCR3 antagonist mAb in mouse HHT model generated by immunoblocking of BMP9 and BMP10 8 **** 6 ns AVM Number **** Plexus Vascular (per Retina, Density 4 4 2 n=7) (x10 µm ) 2
Slide 52: Projected HHT Development Program Overview
52 HHT Projected HHT Development Program Overview 2024 2026 2025 2027 Finalize IND Enabling DC selection Development Studies and CMC Expected 2H’24 Candidate Safety and Tolerability Phase I PHASE 1a Initiation Planned Q4’25/Q1’26 Randomized 3-Month Study Patients Hematocrit, Epistaxis Score PHASE 2
Slide 53: Tectonic Therapeutic
=CTONIC Therapeutic
Slide 54: Financial Overview
54 Financial Overview Company Ticker NASDAQ: TECX Major mutual fund, TAS Partners, 5AM Ventures, EcoR1 Capital, Polaris Investor Participation from Partners, Farallon Capital June 2024 Private Placement (managed funds), Vida Ventures, Pags Group and other investors 1 ~$185 million Cash as of 6/30/24
Slide 55: Uniquely Positioned to Deliver on Value Creating Milestones
55 Uniquely Positioned to Deliver on Value Creating Milestones Strong Balance Sheet Pipeline of Uniquely Accomplished Team Post Transaction Differentiated Assets World-leader Founders st ~$185 Million* (as of 6/30/24) Multiple Inflection Points 20 1 Approvals 2025, 2026, 2027 Runway Into Mid-2027 >$
Slide 56: Thank you
56 Thank you info@tectonictx.com www.tectonictx.com LinkedIn: TectonicTx
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