Tectonic Therapeutic, Inc. · NASDAQ:TECX
Tectonic Therapeutic — Investor Presentation (January 2025)
39 slides from Tectonic Therapeutic's investor presentation, Jan 13, 2025
Slide 1: Innovating GPCR-Targeted Therapies to Reach Large Untapped Market Opportunities
Exhibit 99.1 Innovating GPCR-Targeted Therapies to Reach Large Untapped Market Opportunities JANUARY 2025
Slide 2: Disclaimer
2 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,”
Slide 3: Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities
3 Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities TECX focused on discovery & development of GPCR-target biologics with significant unmet need Clinical-Stage Biotech • Founded in 2019 by Tim Springer and Andrew Kruse, TECX went public via reverse merger (AVROBIO) in June 2024 with
Slide 4: This Accomplished Team Has Delivered for Patients and Investors
4 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 5: Biologics Offer Advantages Over Small Molecules in Targeting GPCRs
5 Biologics Offer Advantages Over Small Molecules in Targeting GPCRs, Hold Potential to Transform Therapeutic Landscape Of the approved drugs that target GPCRs only three are antibodies When difficult to target with small >18%* >470 ~12% molecule, biologic captures complexity remain approved drugs u
Slide 6: Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of GPCRs
6 Our Unique Pipeline Opportunities are Enabled by Biologic Targeting of GPCRs Group 2 Pulmonary Hypertension Long-Acting Relaxin Potential Best-in-Class Profile (PH) due to HFpEF in Phase 2 1 to Target RXFP1 Positive Phase 1a clinical data Hereditary Hemorrhagic 2 GPCR Antagonist Potential First-in
Slide 7: Unique Pipeline of GPCR-Targeted Biologics Underpinned By TX45
7 Unique Pipeline of GPCR-Targeted Biologics Underpinned By TX45 Targeting PH-HFpEF with P1b Results Expected Q1’25 PROGRAM / INDICATION DISCOVERY IND ENABLING PHASE 1 PHASE 2 ANTICIPATED MILESTONES • Phase 1b hemodynamic PH-HFpEF GROUP 2 PH-HFpEF results expected in Q1’25, with PH- TX45 Potential B
Slide 8: TX45: Long-acting relaxin to address large, unmet need in Group 2 PH
8 TX45: Long-acting relaxin to address large, unmet need in Group 2 PH RXFP1 agonist with differentiated profile
Slide 9: TX45: Potential Best-in-class Treatment for Group 2 PH-HFpEF
9 TX45 TX45: Potential Best-in-class Treatment for Group 2 PH-HFpEF • Protein engineering has extended pharmacologic half-life to support monthly dosing Relaxin with optimized PK • Rigorous Phase 1 PK/PD model enabled robust Phase 2 dose selection * • Group 2 PH-HFpEF has no approved therapy High un
Slide 10: Significant Pharma Interest in Relaxin
10 TX45 Significant Pharma Interest in Relaxin Tectonic has potential best-in-class molecule Half Life Patient Phase 2 Company Format Formulation Dosing* in NHV Population Endpoints Group 2 PH / Change in pulmonary Fc-Fusion Sub Q 14-20 days Q4 Weeks HFpEF (enriched vascular resistance (TX45) for Cp
Slide 11: Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by Its Role in Pregnancy
11 TX45 Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy Pharmacology Facilitates Gestation AGONIST PULMONARY AND Natural Ligand of SYSTEMIC VASODILATOR RXFP1 Receptor Increases cardiac output to accommodate the Relaxin-2 increased demand from No RXFP1 develo
Slide 12: The First Recombinant Relaxin (Serelaxin) Demonstrated Safety and Benefit in AHF
12 TX45 The First Recombinant Relaxin (Serelaxin) Demonstrated Safety and Benefit in Acute Heart Failure (AHF) in Trials of >11,000 Patients Background • Program sponsored by Novartis META ANALYSIS: Serelaxin was Efficacious in AHF • Serelaxin half life <9 hours, a major hurdle for development for c
Slide 13: TX45 is Engineered to Solve a Critical PK Problem
13 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 Molecules Preclinical Rat Pharmacokinetic Data Relaxin has very short in vivo half-life Fc-fusion needed to improve PK Half-life exten
Slide 14: TX45 Initial Indication: Group 2 Pulmonary Hypertension
14 TX45 TX45 Initial Indication: Group 2 Pulmonary Hypertension (PH) Pulmonary hypertension consists of 5 distinct diseases, or groups • Idiopathic, hereditary or drug-induced Group 1 • Connective tissue disease-associated PAH Group 2 PH is chronic, progressive • Congenital heart disease-associated
Slide 15: Initial Focus on Group 2 PH due to HFpEF, Enriched for CpcPH Patients
15 TX45 Initial Focus on Group 2 PH due to Heart Failure With Preserved EF (HFpEF), Enriched for CpcPH Patients 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
Slide 16: Group 2 PH vs. PAH (Group 1)
16 TX45 Group 2 PH vs. PAH (Group 1) Significant opportunity for a first-in-indication therapy Highly motivated physicians and patients No Therapeutic Options 4 US Prevalence >> PAH 5-Year Survival ≤ PAH For Group 2 PH 1 ~1,400,000 Group 2 PH PAH ~ 50% 50% No approved Multiple drugs/ IpcPH therapies
Slide 17: Relaxin Agonism of RXFP1 Elicits Changes in Multiple Organs
17 TX45 Relaxin Agonism of RXFP1 Elicits Changes in Multiple Organs and Organ Systems Important in PH-HFpEF “ Vasodilation ” RV / LV* Pulmonary & Systemic Afterload “ NO ” Endothelin-1 Relaxin “ LV Relaxation Improved LV agonist Diastolic Function “ SERCA2 function ” Fibrosis RV / LV and Pulmonary A
Slide 18: Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification
18 TX45 Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification in PH-HFpEF • Heart and vascular dysfunction contribute to disease pathology • Renal dysfunction also present in many of these patients CHARACTERISTICS OF PH-HFpEF ANTICIPATED RELAXIN EFFECTS Pulmonary Va
Slide 19: In AHF, Serelaxin Improves LV Function and Lowers Pulmonary Pressures
19 TX45 In Acute Heart Failure (AHF), Serelaxin Improves LV Function (Lowering 1 PCWP), and Lowers Pulmonary Pressures and Resistance (mPAP, PVR) Furosemide given 4h prior to serelaxin infusion, and 8h after initiation of serelaxin PCWP mPAP PVR Lung capillary pressure – Pulmonary (lung) Blood flow
Slide 20: TX45 Development Program Overview
20 TX45 TX45 Development Program Overview 2026 2024 2025 Healthy Phase 1a Toplined Sept ’24 Volunteers Safety, PK, PD (Renal Blood Flow) Safety, tolerability, PK/PD Group 2 PH Phase 1b with HFpEF RHC study to establish hemodynamic proof of concept Group 2 PH - Part A (PH-HFpEF); Part B (PH-HFrEF) wi
Slide 21: Phase 1a Clinical Study Complete
21 TX45 Phase 1a Clinical Study Complete Positive results support on-going development Robust Design of TX45 SAD Study Benefits of the Study Design • Exposure-response model developed with over 200 data points • Overcomes impact of outlier values on mean values based on 6 patients per dose cohort •
Slide 22: TX45 Shows Favorable Safety Profile
22 TX45 TX45 Shows Favorable Safety Profile • No discontinuations or treatment-related SAEs • No observed injection site reactions, immunogenicity, or detection of anti-drug antibodies • Most common AE was transient orthostatic tachycardia (increases in heart rate with standing) ‒ Placebo: 17% vs TX
Slide 23: TX45 Single Dose Demonstrates Extended Half-Life in Subjects
23 TX45 TX45 Single Dose Demonstrates Extended Half-Life in Subjects TX45 Pharmacokinetics (PK) Profile Single Dose TX45 Pharmacokinetics • Potential best-in-class terminal elimination half life of 14-20 days • PK was dose proportional with subcutaneous bioavailability of ~50% • Modeled accumulation
Slide 24: Preclinical PK/PD from Acute Renal Blood Flow Model Informs Target Plasma Concentration
24 TX45 Preclinical PK/PD from Acute Renal Blood Flow (RBF) Model Informs Target Plasma Concentration Levels at Trough for Maximum Therapeutic Effect RBF Model • Used to assess pharmacodynamic response to TX45 administration based on acute vasodilatory effects of relaxin, as measured by increased ra
Slide 25: Robust Human-Exposure Model Allows for Phase 2 Dose Selection
25 TX45 Robust Human-Exposure Model Allows for Phase 2 Dose Selection Phase 1a Renal Plasma Flow (RPF) TX45-RPF E model max • Mean dose cohort effects (n=6 per cohort) demonstrated increased renal plasma flow of up to 42% • Incorporation of all exposure-response data across all doses and time points
Slide 26: TX45 Development Program Overview: Planned readouts in 2025 and 2026
26 TX45 TX45 Development Program Overview Planned readouts in 2025 and 2026 2024 2026 2025 Healthy Phase 1a Volunteers Safety, tolerability, PK/PD Expected Q1’25 (Part A) Group 2 PH PCWP, PVR in CpcPH, exploring TPR + Phase 1b with HFpEF additional HD endpoints RHC study to establish hemodynamic pro
Slide 27: TX45 Phase 1b Trial Design (Part A)
27 TX45 TX45 Phase 1b Trial Design (Part A) Open label single dose safety and hemodynamics trial in PH-HFpEF Study Goals: • Primary Endpoint: Safety and Tolerability • Establish single dose safety in patients • Demonstrate relevant acute hemodynamic • Key Secondary Endpoints: PCWP in all changes con
Slide 28: Phase 1b Trial Expected to Improve Probability of Success
28 TX45 Positive TX45 Phase 1b Trial Expected to Improve Probability of Success of TX45 in Later Stage Development GOAL: Treatment for PH-HFpEF needs to both increase LV function and improve pulmonary vascular component of the disease • Decrease (~15-20%) in pulmonary capillary wedge pressure (PCWP)
Slide 29: APEX Phase 2 Efficacy Trial Design for TX45
29 TX45 APEX Phase 2 Efficacy Trial Design for TX45 Clinical trial in subjects with PH-HFpEF enriched for subjects with CpcPH subgroup • Global multicenter, double-blind, randomized, placebo-controlled proof-of-concept clinical trial to evaluate the efficacy of TX45 Double-blind Sub Q 24 Week Treatm
Slide 30: HHT program: Potential first-in-class and indication
30 HHT program Potential first-in-class and indication nd opportunity for 2 most common genetic bleeding disorder
Slide 31: Hereditary Hemorrhagic Telangiectasia (HHT)
31 HHT Hereditary Hemorrhagic Telangiectasia (HHT) Autosomal dominant disease that causes abnormal blood vessel formation • Rare, autosomal dominant disease: ~ 75,000 patients in US No currently ‒ Mutations in the BMP9/10 pathway approved AVMs Telangiectasias therapies for HHT • High degree of pheno
Slide 32: Anti-VEGF: Mouse HHT Model Predictive of Efficacy in Patients
32 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 33: A GPCR3 Antagonist Significantly Reduces AVM Formation and Bleeding in Animal Model
33 HHT A GPCR3 Antagonist Significantly Reduces AVM Formation and Bleeding in Animal Model of HHT Effects of anti-GPCR3 antagonist mAb in mouse HHT model generated by immuno-blocking 1,2 of BMP9 and BMP10 Hemoglobin Levels AVM Formation Retinal Bleeding n=14 1. Ruiz, S. et. al., Scientific Reports,
Slide 34: Projected HHT Development Program Overview
34 HHT Projected HHT Development Program Overview 2024 2025 2026 2027 Finalize IND Enabling DC selected Development Studies and CMC November ’24 Candidate (DC) Safety and Tolerability Phase 1a PHASE 1a Initiation Planned Q4’25/Q1’26 Randomized 3-Month Study Patients Hematocrit, Epistaxis Score PHASE
Slide 35: Platform: Proprietary, validated platform enables discovery of GPCR targeted biologics
35 Platform Proprietary, validated platform enables reproducible discovery and optimization of GPCR targeted biologics
Slide 36: GEODe Solving Key Challenges in GPCR Targeted Biologics Discovery
36 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 37: Tectonic Tx: Positioned to Deliver on Value-Creating Milestones
37 Tectonic Tx: Positioned to Deliver on Value-Creating Milestones Two pipeline candidates addressing untapped markets with significant market potential • Lead candidate, TX45, long-acting relaxin in Phase 2, with de-risking Phase 1b trial results expected in Q1’25 • TX45 has best-in-class potential
Slide 38: Thank You
38 Thank You info@tectonictx.com www.tectonictx.com LinkedIn: TectonicTx
Slide 39: Results of Serelaxin Pre-specified Substudy of RELAX-AHF-2
39 TX45 Results of Serelaxin Pre-specified Substudy of RELAX-AHF-2 Demonstrated Multi-Organ Protection Background • In RELAX-AHF-2, no benefit shown on 5-day heart failure worsening or 180d mortality with 48h IV serelaxin treatment • Recent prospective, pre-specified substudy of RELAX- AHF-2 of 1,02
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