Tectonic Therapeutic, Inc. · NASDAQ:TECX
Tectonic Therapeutic — Investor Presentation (August 2025)
52 slides from Tectonic Therapeutic's investor presentation, Aug 7, 2025
Slide 1: Innovating GPCR-Targeted Therapies to Reach Large Untapped Market Opportunities
AUGUST 2025 Innovating GPCR-Targeted Therapies to Reach Large Untapped Market Opportunities Exhibit 99.2
Slide 2: Forward-Looking Statements
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,” "pro
Slide 3: Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities
Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities TECX focused on discovery & development of GPCR-target biologics with significant unmet need Founded in 2019 by Tim Springer and Andrew Kruse Executive team with numerous accomplishments, resulting in 20 “first” approvals Long-acting
Slide 4: This Accomplished Team Has Delivered for Patients and Investors
This Accomplished Team Has Delivered for Patients and Investors Alise Reicin, M.D. CEO, Director Daniel Lochner CFO Peter McNamara, Ph.D. CSO Anthony Muslin, M.D. CDO Marcella Ruddy, M.D. CMO Marc Schwabish, Ph.D. CBO Timothy Springer, Ph.D. Co-Founder FOUNDED MULTIPLE SUCCESSFUL COMPANIES GPCR EXPE
Slide 5: Biologics Offer Advantages Over Small Molecules in Targeting GPCRs
Of the approved drugs that target GPCRs only three are antibodies Biologics Offer Advantages Over Small Molecules in Targeting GPCRs, Hold Potential to Transform Therapeutic Landscape When difficult to target with small molecule, biologic captures complexity of ligand/receptor engagement Biologic mi
Slide 6: Unique Pipeline of GPCR-Targeted Biologics Underpinned By TX45
Unique Pipeline of GPCR-Targeted Biologics Underpinned By TX45 TX45 TX2100 TX45 AUGUST 2025 * Subject to positive Phase 1 data
Slide 7: TX45: Long-acting relaxin to address large, unmet need in Group 2 PH
TX45: Long-acting relaxin to address large, unmet need in Group 2 PH RXFP1 agonist with differentiated profile
Slide 8: TX45: Potential Best-in-class Treatment for Group 2 PH-HFpEF
Mechanism appears ideal to address disease pathology TX45: Potential Best-in-class Treatment for Group 2 PH-HFpEF High unmet need Streamlined and differentiated clinical strategy Potential to expand opportunity Relaxin with optimized PK Protein engineering has extended pharmacologic half-life to sup
Slide 9: TX45 Initial Indication: Group 2 Pulmonary Hypertension
Pulmonary hypertension consists of 5 distinct diseases, or groups TX45 Initial Indication: Group 2 Pulmonary Hypertension (PH) * Heart Failure with reduced Ejection Fraction ** CAD: Coronary Artery Disease, HTN: Hypertension, T2DM: Type 2 Diabetes Mellitus Group 1 PAH Idiopathic, hereditary or drug-
Slide 10: Initial Focus on Group 2 PH-HFpEF, Enriched for CpcPH Patients
Clinical program designed to enable evaluation of efficacy in overall population and CpcPH Initial Focus on Group 2 PH due to Heart Failure with Preserved EF (PH-HFpEF), Enriched for CpcPH Patients PH-HFpEF (~1.4M)1 HFpEF (~4M)1 IpcPH (700K-1M) CpcPH2 (400-700K) Normal HFpEF Heart IpcPH (Isolated, p
Slide 11: Significant opportunity for a first-in-indication therapy
Significant opportunity for a first-in-indication therapy Highly motivated physicians and patients Group 2 PH vs. PAH (Group 1) US Prevalence >> PAH 5-Year Survival £ PAH4 No Therapeutic Options For Group 2 PH Multiple drugs/ mechanisms approved ET1R antagonists PDE5 inhibitors GC stimulators Prosta
Slide 12: Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy
Hemodynamic and Anti-fibrotic Properties of Relaxin Demonstrated by its Role in Pregnancy Facilitates Gestation PULMONARY AND SYSTEMIC VASODILATOR Increases cardiac output to accommodate the increased demand from developing fetus ANTIFIBROTIC Prepares musculoskeletal tissues for pregnancy and childb
Slide 13: Relaxin Addresses Multiple Organ System Pathologies in PH-HFpEF
“ Vasodilation Pulmonary & Systemic “ NO ” Endothelin-1 ” Fibrosis Anti-Inflammatory “ MMPs ” TGFb “ Renal Blood Flow ” RV / LV* Afterload RV / LV and Pulmonary Artery Reverse Remodeling “ Na+ Excretion ” RV / LV Preload Relaxin Addresses Multiple Organ System Pathologies in PH-HFpEF * RV: right ven
Slide 14: Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification
Heart and vascular dysfunction contribute to disease pathology Renal dysfunction also present in many of these patients Relaxation and Anti-Fibrotic Effects of Relaxin Have Potential for Disease Modification in PH-HFpEF CHARACTERISTICS OF PH-HFpEF ANTICIPATED RELAXIN EFFECTS Pulmonary artery narrowi
Slide 15: TX45 is Engineered to Solve a Critical PK Problem
TX45 is Engineered to Solve a Critical PK Problem Observed With Other Relaxin Molecules pI >9, Comparator pI >9, TX early pI <9, TX-45 TX45 Exhibits Superior Profile vs. Parent Compound and Comparator Molecules 2,3 Preclinical Rat Pharmacokinetic Data Half-life extended relaxins have steep decline i
Slide 16: TX45 Group 2 PH Development Program Overview
Phase 1b RHC study to establish hemodynamic proof of concept - Part A (PH-HFpEF); Part B (PH-HFrEF) Group 2 PH with HFpEF (enriched for CpcPH) Group 2 PH with HFpEF Healthy Volunteers TX45 Group 2 PH Development Program Overview Phase 1a Safety, tolerability, PK/PD Phase 2 Randomized, 6-month study
Slide 17: Robust Design of TX45 Phase 1a Clinical Study
Positive results support on-going development Phase 1a Clinical Study Complete 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 Enables more r
Slide 18: TX45 Shows Favorable Safety Profile
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 TX45: 23% Not asso
Slide 19: TX45 Single Dose Demonstrates Extended Half-Life in Subjects
TX45 Single Dose Demonstrates Extended Half-Life in Subjects Single Dose TX45 Pharmacokinetics TX45 Pharmacokinetics (PK) Profile Potential best-in-class terminal elimination half life of 14-20 days PK was dose proportional with subcutaneous bioavailability of ~50% Modeled accumulation at steady sta
Slide 20: Preclinical PK/PD from Acute Renal Blood Flow Model Informs Target Levels
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 rat renal bl
Slide 21: Robust Human-Exposure Model Allows for Phase 2 Dose Selection
Robust Human-Exposure Model Allows for Phase 2 Dose Selection Phase 1a Renal Plasma Flow (RPF) 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 post dose resulted in a modeled
Slide 22: Phase 1b RHC study to establish hemodynamic proof of concept
Phase 1b RHC study to establish hemodynamic proof of concept - Includes Part A (PH-HFpEF) & Part B (PH-HFrEF) Group 2 PH with HFpEF (enriched for CpcPH) Group 2 PH with HFpEF Healthy Volunteers Planned readouts in 2025 and 2026 TX45 Group 2 PH Development Program Overview Phase 1a Safety, tolerabili
Slide 23: Phase 1b Clinical Trial Design
Hemodynamic data was prespecified to be pooled across all doses. After IV administration, all dose levels result in exposures which are in the predicted efficacious range during the 8-hour assessment period (i.e. above trough exposure of 2 ug/ml) Phase 1b Clinical Trial Design: A Single Dose, Open-L
Slide 24: Key Hemodynamic Measures Assessed in Phase 1b Trial
Phase 1b trial results that help predict APEX trial success Goal: Treatment for PH-HFpEF needs to both increase LV function and improve pulmonary vascular component of the disease Key Hemodynamic Measures Assessed in Phase 1b Trial Hemodynamic Definition Significance PCWP (Pulmonary Capillary Wedge
Slide 25: Phase 1b PH-HFpEF (Part A): Baseline Characteristics and Medications
Phase 1b PH-HFpEF (Part A): Baseline Characteristics and Medications are Consistent with Target Population All Subjects N = 19 Age (mean, SD) 65.1 (8.7) Females [n (%)] 7 (36.8%) BMI (mean, SD) 28.9 (3.6) Creatinine (uMol/L; mean, SD)* 82.7 (18.9) NT-proBNP (pg/mL; mean, SD) 1347 (1146) Comorbiditie
Slide 26: Phase 1b PH-HFpEF (Part A): Baseline Hemodynamics
Phase 1b PH-HFpEF (Part A): Baseline Hemodynamics Are Consistent with Target Population PVR < 2WU 2 WU ≤ PVR < 3WU PVR ≥3 WU 10 4 5 If CpcPH is defined as PVR >2: Total IpcPH = 10 Total CpcPH = 9 If CpcPH is defined as PVR >3: Total IpcPH = 14 Total CpcPH = 5 Parameter Baseline Value [mean, SD] Hear
Slide 27: Phase 1b (Part A) Results - TX45 Improved Cardiac and Pulmonary Hemodynamics
Secondary Endpoints CFB* Mean [95% CI] Average % CFB* Mean [95% CI] Hemodynamics (Key 2o ) (N = 19) Mean D PCWP in all participants -3.2 [-4.3 to -2.1] mm Hg -19.0% [-26.1% to -11.9%] Mean D PVR in CpcPH (PVR ≥ 2 WU) (n= 9) -1.06 [-1.34 to -0.78] WU -32.0% [-35.9% to -28.1%] Mean D PVR in CpcPH (PVR
Slide 28: TX45 Consistently Reduced PCWP in Both IpcPH and CpcPH Patients
Phase 1b (Part A) Results - TX45 Consistently Reduced PCWP in Both IpcPH and CpcPH patients and Improved PVR in CpcPH Patients * Group averages reported as mean [95% CI]. Parameter vs. time plots show mean ± SD. Spaghetti plots show average baseline values and average of Hours 1-8 for each participa
Slide 29: TX45 Changes in PVR, PCWP & CO in Group 2 PH-HFpEF Patients
TX45 Changes in PVR, PCWP & CO in Group 2-PH-HFpEF Patients PVR Baseline (WU) mean (SD) Treatment Period (WU) mean (SD) Absolute CFB** (WU) mean [95% CI] Average % CFB** mean [95% CI] All subjects (N = 19) * 2.33 (1.06) 1.74 (0.59) -0.60 [-0.93 to -0.27] -15.3% [-37.4% to +6.8%] Baseline PVR ≥ 2 WU
Slide 30: Echo Results Suggest Sustained Improvement in Hemodynamic Effects
Phase 1b (Part A) Results - Echo Results Suggest Sustained Improvement in Hemodynamic Effects with TX45 *Nominal P<0.05, **Nominal P<0.01 for treated (Day 29) versus baseline (Day -1) 1 RVFAC is a measure of right heart function and TAPSE/SPAP is a surrogate for PVR TX45 administration increased tri
Slide 31: Phase 1b (Part A) - TX45 was Well-tolerated
Phase 1b (Part A) - TX45 was Well-tolerated Preferred Term Cohort A 0.3 mg/kg (n=3) Cohort B 1 mg/kg (n=7) Cohort C 3 mg/kg (n=9) Total N=19 Fatigue 0 0 4 4 (21.1%) Back pain 0 1 1 2 (10.5%) Nasopharyngitis 0 0 1 1 (5.3%) Gout (worsening) 0 1 0 1 (5.3%) Viral infection 0 0 1 1 (5.3%) Procedural pain
Slide 32: Combined Decrease in PCWP and PVR Appears to Enhance Exercise Capacity
Combined Decrease in PCWP and PVR Appears to Enhance Improvement in Exercise Capacity Decreasing PCWP alone is expected to improve exercise capacity PCWP provides insight into left ventricular function and correlates with exercise capacity in HFpEF, HFrEF1 and Group 2 pulmonary hypertension (CpcPH)2
Slide 33: TX45 Phase 1b Part A Results Met/Exceeded Expectations
TX45 was well-tolerated Transient asymptomatic decreases in BP were observed over the first 24 hours after an IV dose TX45 observed to improve left heart function and pulmonary hemodynamics, which together should increase probability of success of APEX Phase 2 Trial TX45 has a differentiated profile
Slide 34: APEX Phase 2 Efficacy Clinical Trial Design for TX45
End of Study Week 30 End Treatment Hemodynamics Week 24 Clinical trial in subjects with PH-HFpEF enriched for subjects with CpcPH subgroup APEX Phase 2 Efficacy Clinical Trial Design for TX45 Randomization Day 1 RHC Baseline Hemodynamics Day -21 to -7 Double-blind Sub Q 24 Week Treatment Period TX45
Slide 35: Pharma Has Interest In The Relaxin MoA and Group 2 PH Patients
Pharma Has Interest In The Relaxin MoA and Group 2 PH Patients Company Format Formulation Half Life in NHV Dosing* Patient Population Phase 2 Endpoints*** Est. Data Read-Out Fc-Relaxin Fusion (TX45) Sub Q 14-20 days Q4 Weeks Group 2 PH / HFpEF (enriched for CpcPH) ∆PVR Ph 2 - 2026 Fc-Relaxin Fusion
Slide 36: TX45 PH-ILD Program
TX45 PH-ILD Program Potential differentiated treatment of Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD)
Slide 37: TX45 Preclinical and Clinical Data Support PH-ILD Indication
TX45 Preclinical and Clinical Data Support PH-ILD Indication TX45: Overview and Rationale in PH-ILD (WHO Group 3 PH) TX45 Phase 2 PH-ILD Trial Planned to Initiate in 2026 High Unmet Medical Need 60K+ PH-ILD patients in U.S.** High mortality: 3-year mortality rate of 60% to 77%*** (5x higher than ILD
Slide 38: Strong Rationale for TX45 in PH-ILD
Strong Rationale for TX45 in PH-ILD -Pulmonary Vasodilation, Anti-inflammatory and Anti-Fibrotic Effects of Relaxin: -Potential for Increased Exercise Capacity and Disease Modification CHARACTERISTICS OF PH-ILD ANTICIPATED RELAXIN EFFECTS Pulmonary vascular constriction due to underlying lung diseas
Slide 39: TX45 Clinical Hemodynamic Changes and Preclinical Effects on Histopathology
TX45 Demonstrates Clinical Hemodynamic Changes and Preclinical Effects on Histopathology Important for PH-ILD TX45 improves abnormal hemodynamics in PH-HFpEF patients also seen in PH-ILD patients *Mouse Fc-fusion with TX45 relaxin sequence TX45* has remodeling effects in animal models of PH relevant
Slide 40: Why Have Inhaled Therapies Succeeded in PH-ILD?
Why Have Inhaled Therapies Succeeded in PH-ILD And Systemic Pulmonary Vasodilatory Compounds Have Failed? Success of inhaled treprostinil treatments: Targeted pulmonary hemodynamic effects while avoiding prostacyclin-specific systemic side effects Clinical trials in focused population of confirmed P
Slide 41: TX45 PH-ILD Study: Overview of Design and Rationale
TX45 Phase 2 PH-ILD Study: Overview of Design and Rationale Size: ~20 subjects with PH-ILD Baseline right heart catheterization (RHC) to diagnose PH Dosing: 300mg Q2 weeks subcutaneous Endpoints: ∆ from baseline in the following: Safety: oxygenation and systolic blood pressure (sBP) Primary Efficacy
Slide 42: TX45: A Differentiated Therapy for PH-ILD
TX45: A Differentiated Therapy for PH-ILD Offering Potential Efficacy, Safety and Convenience ∆ = change in, 6MWD = Six Minute Walk Distance, PVR = Pulmonary Vascular Resistance head-to-head comparison trials have not been conducted Company Format Administration Dosing MOA Clinical Stage Primary End
Slide 43: Summary: Strong Rationale for TX45 in PH-ILD
Summary: Strong Rationale for TX45 to Bring a Differentiated Treatment Approach to Address Unmet Needs in PH-ILD PH-ILD is a disease with high morbidity/mortality and insufficient therapeutic options Preclinical PH data and clinical hemodynamic data in PH-HFpEF suggest that TX45 is well suited as a
Slide 44: TX2100 HHT program
TX2100 HHT program Potential first-in-class and indication opportunity for Hereditary Hemorrhagic Telangiectasia (HHT), the 2nd most common genetic bleeding disorder
Slide 45: Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT) Autosomal dominant disease that causes abnormal blood vessel formation >95% Nose (epistaxis) >90% Skin (telangiectasia) 50% Lungs (pulmonary AVMs*) 50% Liver (hepatic AVMs) 20% Gastrointestinal tract 10% Brain (cerebral AVMs) Iron and transfusion dependent
Slide 46: Anti-VEGF: Mouse HHT Model Predictive of Efficacy in Patients
Anti-VEGF: Mouse HHT Model Predictive of Efficacy in Patients Angiogenesis. 2014 Oct; 17(4): 823–830 Incisional wounds Anti-VEGF ab Decreases Vessel Growth Anti-VEGF ab Improves Hemoglobin Levels Anti-VEGF mAb suppresses AVM formation, visceral hemorrhage in HHT model Haematologica. 2021 Aug 1; 106(
Slide 47: Effects of anti-GPCR3 antagonist mAb in mouse HHT model
Effects of anti-GPCR3 antagonist mAb in mouse HHT model generated by immuno-blocking of BMP9 and BMP101,2 A GPCR3 Antagonist Significantly Reduces AVM Formation and Bleeding in Animal Model of HHT Hemoglobin Levels AVM Formation Retinal Bleeding n=14 1. Ruiz, S. et. al., Scientific Reports, 2016; 6:
Slide 48: TX2100 Development Program Overview
Phase 1 TX2100 Development Program Overview Patients with HHT Phase 1 IND Enabling Studies and CMC Finalize Development Candidate (DC) Phase 2 Safety and Tolerability Initiation Expected Q1’26 Randomized 3-Month Study Hematocrit, Epistaxis Score Blood Transfusions Planned early 2027 2024 2025 2026 2
Slide 49: Platform
Platform Proprietary platform enables reproducible discovery and optimization of GPCR targeted biologics
Slide 50: Solving Key Challenges in GPCR Targeted Biologics Discovery
Solving Key Challenges in GPCR Targeted Biologics Discovery Challenges RETAIN endogenous GPCR structure to enable screening against relevant form of receptor PURIFY target in sufficient quantities to power screening campaign INDUCE immune response to human GPCR in animals if immunization strategy is
Slide 51: Tectonic Tx: Positioned to Deliver on Value-Creating Milestones
Tectonic Tx: Positioned to Deliver on Value-Creating Milestones Lead candidate, TX45, long-acting relaxin in Phase 2 supported by Phase 1b trial results TX45 has best-in-class potential for >1M+ patients with Group 2 Pulmonary Hypertension (PH) with HFpEF; potential to expand to Group 2 PH-HFrEF and
Slide 52: Thank You
Thank You info@tectonictx.com www.tectonictx.com LinkedIn: TectonicTx
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