Slide 1: TX45 Phase 1b PH-HFpEF Interim Data Release for Single Dose Hemodynamic Trial
TX45 Phase 1b PH-HFpEF Interim Data Release for Single Dose Hemodynamic Trial 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,” “pot
Slide 3: Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities
3 Tectonic Tx: GPCR-Targeted Therapies for High-Value Opportunities Clinical-Stage TECX focused on discovery & development of GPCR-target biologics with significant unmet need Biotech • Founded in 2019 by Tim Springer and Andrew Kruse, TECX went public via reverse merger (AVROBIO) in June 2024 with
Slide 4: Initial Focus on Group 2 PH due to HFpEF, Enriched for CpcPH Patients
4 Initial Focus on Group 2 PH due to Heart Failure with Preserved EF (PH-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 5: Relaxin Addresses Multiple Organ System Pathologies in PH-HFpEF
5 Relaxin Addresses Multiple Organ System Pathologies in PH-HFpEF Phase 1b data is anticipated to capture the acute impact of vasodilation and LV relaxation Vasodilation RV / LV* Pulmonary & Systemic Afterload NO Endothelin-1 Relaxin LV Relaxation Improved LV Diastolic agonist SERCA2 fun
Slide 6: TX45 Background and Clinical Program Status
6 TX45 Background and Clinical Program Status • TX45 is a human relaxin-2-Fc fusion protein with a potential best in class half-life of 2-3 weeks • The Phase 1b hemodynamic clinical trial is ongoing: • Part A - Enrollment and dosing of PH-HFpEF subjects is completed (N=19) • Efficacy data is availab
Slide 7: Phase 1b (Part A) Trial Design, Single Dose, Open-Label Acute Hemodynamic Trial
7 Phase 1b (Part A) Trial Design, A Single Dose, Open-Label Acute Hemodynamic Trial in IpcPH and CpcPH Subjects Days 2, 15, 29: ECHO Right Heart Catheter is inserted Day 8, 43: Safety Screening and hemodynamic measurements are Follow-ups Day -28 to -2 Admit to Unit captured at the timepoints listed
Slide 8: Key Hemodynamic Measures Assessed in Phase 1b
8 Key Hemodynamic Measures Phase 1b trial results that Assessed in Phase help predict APEX 1b trialTrial success Goal: Treatment for PH-HFpEF needs to both increase LV function and improve pulmonary vascular component of the disease Hemodynamic Definition Significance PCWP • Measure of left atrial p
Slide 9: TX45 Phase 1b Trial Results Expected to Improve Probability of Success in Phase 2
9 TX45 Phase 1b Trial Results Are Expected to Improve Probability of Success of TX45 in Phase 2 Clinical Trial Phase 1b predefined hemodynamic target goals were: • ~15-20% decrease in pulmonary capillary wedge pressure (PCWP) in overall patient population ‒ PCWP provides insight into left ventricula
Slide 10: Phase 1b (Part A) Demographics & Medical History
10 Phase 1b (Part A) Demographics & Medical History All Subjects Key Concomitant All Subjects N = 16 Medications N = 16 Age (mean, SD) 64.3 (9.2) ACEi/ARB [n (%)] 8 (50.0 %) Females [n (%)] 6 (37.5%) MRA [n (%)] 13 (81.3 %) BMI (mean, SD) 28.0 (3.2) SGLT2i [n (%)] 6 (37.5 %) Creatinine (uMol/L; mean
Slide 11: Phase 1b (Part A) - Summary of Baseline Hemodynamics
11 Phase 1b (Part A) - Summary of Baseline Hemodynamics Parameter Baseline Value PVR < 2WU 2 WU ≤ PVR < 3WU PVR ≥3 WU [mean, SD] 7 4 5 Heart Rate (bpm) 68.1 (10.9) Systolic Blood Pressure (mm Hg) 128.8 (11.6) If CpcPH is defined as PVR >3: Diastolic Blood Pressure (mm Hg) 78.5 (6.0) Total IpcPH = 11
Slide 12: Phase 1b (Part A) - Primary Endpoint: TX45 Is Well Tolerated
12 Phase 1b (Part A) - Primary Endpoint: TX45 Is Well Tolerated Treatment-emergent adverse events (# of Subjects) Preferred Term Cohort A Cohort B Cohort C 0.3 mg/kg 1 mg/kg 3 mg/kg Total (n=3) (n=7) (n=6) N=16 Fatigue* 0 0 4 4 (25%) Nasopharyngitis 0 0 1 1 (6.3%) Back pain 0 1 0 1 (6.3%) Gout (wors
Slide 13: Phase 1b (Part A) Results - TX45 Achieved or Exceeded all Hemodynamic Target Goals
13 Phase 1b (Part A) Results - TX45 Achieved or Exceeded all Hemodynamic Target Goals Secondary Endpoints Absolute CFB, Mean [95% CI] Average % CFB, [95% CI] Hemodynamics (Key 2o ) (N = 16) Mean PCWP in all participants - 2.9 [-1.7 to -4.2] mm Hg -17.9% [-9.8% to -26.1%] Mean PVR in CpcPH (PVR ≥
Slide 14: IV Administration of TX45 Resulted in a Transient, Asymptomatic Decrease in Blood Pressure
14 IV Administration of TX45 Resulted in a Transient, Asymptomatic Decrease in Blood Pressure Blood Pressure Mean ± SD Heart Rate Systolic Diastolic Transient, asymptomatic 5-12 mm Hg mean decrease in blood pressure was observed post- IV dosing of TX45 which resolved at subsequent visits
Slide 15: TX45 Decreases PCWP in PH-HFpEF
15 TX45 Decreases PCWP in PH-HFpEF Baseline Treatment Period Absolute CFB Average % CFB, (mm Hg) (mm Hg) (mm Hg) (95% CI) mean (SD) mean (SD) mean (95% CI) All subjects (N = 16) 16.7 (3.2) 13.7 (3.7) -2.9, [-1.7 to -4.2] -17.9% [-9.8 to -26.1] Baseline PVR ≥ 2 WU (n = 9) 16.2 (2.7) 13.0 (3.5) -3.2 [
Slide 16: TX45 Decreases PVR in Patients with CpcPH
16 TX45 Decreases PVR in Patients with CpcPH Baseline Treatment Period Absolute CFB (WU) Average % CFB (WU) (WU) mean [95% CI] mean [95% CI] mean (SD) mean (SD) All subjects (N = 16) * 2.45 (1.12) 1.84 (0.57) -0.61 [-0.22 to -0.99] -12.3% [-38.3 to +13.7] Baseline PVR ≥ 2 WU (n = 9) 3.25 (0.76) 2.19
Slide 17: TX45 Improves Other Relevant Hemodynamics in PH-HFpEF
17 TX45 Improves Other Relevant Hemodynamics in PH-HFpEF All Subjects (N = 16) TPR (WU) Cardiac Output (L/min) mPAP (mm Hg) Baseline (mean, SD) 6.46 (1.65) 4.31 (1.01) 26.6 (4.4) Treatment Period (mean, SD) 4.68 (1.01) 4.96 (0.87) 22.3 (3.8) Absolute CFB (mean, 95% CI) -1.79 [-1.24 to -2.34] +0.65 [
Slide 18: TX45 Decreases TPR and Increase CO in Both the Overall Population and CpcPH
18 TX45 Decreases TPR and Increase CO in Both the Overall Population and CpcPH Total Pulmonary Resistance Baseline Treatment Period Absolute CFB Average % CFB, (WU) (WU) (WU) (95% CI) mean (SD) mean (SD) mean (95% CI) All subjects (N = 16) 6.46 (1.65) 4.68 (1.01) -1.79 [-1.24 to -2.34] -26.3% [-20.1
Slide 19: Combined Decrease in PCWP and PVR Appears to Enhance Improvement in Exercise Capacity
19 Combined Decrease in PCWP and PVR Appears to Enhance Improvement in Exercise Capacity • Decreasing PCWP alone is expected to improve exercise capacity o SGLT2 inhibitor dapagliflozin decreased resting PCWP 20%1 and increased 6MWT by 20m in HFpEF2 • Decreasing both PCWP and PVR appears to further
Slide 20: TX45 Phase 1b Interim Data in PH-HFpEF Met/Exceeded our Expectations
20 TX45 Phase 1b Interim Data in PH-HFpEF Met/Exceeded our Expectations, Increasing Probability of Phase 2 Success • 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 he
Slide 21: APEX Phase 2 Efficacy Trial Design for TX45
21 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 Treatment P
Slide 22: Phase 1a Trial In Healthy Volunteers (IV) Enabled Sub-Q Dose Selection for Phase 2 Trial
22 Phase 1a Trial In Healthy Volunteers (IV) Enabled Sub-Q Dose Selection for Phase 2 Trial • Phase 2 doses provide maximal to near-maximal agonism of RXFP1 throughout the dosing interval • Near maximal agonism at trough provided for maximal effect in preclinical models • 3 mg/kg exposure over two t
Slide 23: TX45 Development Program Clinical Readouts in 2025-2026
23 TX45 Development Program Clinical Readouts in 2025-2026 2024 2025 2026 Phase 1a Healthy Safety, tolerability, PK/PD Volunteers Group 2 PH Q1’25 (Part A) Phase 1b with HFpEF PCWP, PVR in CpcPH, exploring TPR + RHC study to establish hemodynamic additional HD endpoints proof of concept Group 2 PH -