Full Press Release Details
Hemodynamic Trial January 2025
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," projects," "would" and future or similar expressions are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could
cause actual results to differ significantly from those expressed or implied by such forward- looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding: the design,
objectives, initiation, timing, progress and results of current and future preclinical studies and clinical trials of our product candidates, including the ongoing Phase 1b and Phase 2 clinical trial for TX45, in Group 2 Pulmonary Hypertension; the
expected timing of program updates and data disclosures; the timing of filing INDs and other regulatory documents; the timing and likelihood of seeking regulatory approval for our product candidates including TX45; the competitive landscape for and
market potential of our product candidates; and our ability to identify and develop additional product candidates as well as pursue additional indications. These forward-looking statements reflect our current beliefs and expectations. Many factors
may cause differences between current expectations and actual results, including the early stage of our development efforts; success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same
results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidates; clinical site activation rates or clinical trial enrollment rates that are lower than expected; changes in expected or existing competition;
changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; the impact of macroeconomic conditions, including the conflict in Ukraine and the conflict in the Middle East, heightened inflation and uncertain
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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 a concurrent
private placement of approximately $131 million Tenured Team Executive team with numerous accomplishments, resulting in 20 "first" approvals Long-acting relaxin in Phase 2 trial, supported by Phase 1b interim results TX45 Lead Pipeline
Asset Initial indication targeting Group 2 Pulmonary Hypertension (PH) associated with Heart Failure with Preserved Ejection Fraction (HFpEF), or PH-HFpEF, with Phase 2 trial enriched for CpcPH Positive Phase 1a clinical trial
results support best-in-class potential, including favorable safety profile Positive interim Phase 1b clinical trial results achieved or exceeded all hemodynamic goal targets, supporting Phase 2 trial Relaxin Potentially Relaxin physiologic
and hemodynamic effects further demonstrated in prior clinical studies Ideal for PH-HFpEF Prior clinical development of relaxin by Novartis adds to clinical rationale for TX45 targeting PH-HFpEF * PH-HFpEF Significant ~1.4M+ Group 2 PH-HFpEF
patients in the U.S. with no approved therapy ; high 5-year mortality * Market Potential Potential peak multi-billion-dollar revenue potential for Group 2 PH-HFpEF patients with EF > 40% Astra Zeneca is pursuing a Group 2 PH
relaxin program targeting both HFpEF and HFrEF patients Targeting rare bleeding disorder called Hereditary Hemorrhagic Telangiectasia (HHT) TX2100 Second Pipeline Asset Significant market potential, no approved therapies for HHT, estimated
~75K patients in the U.S. alone (15-20% severe) Phase 1 clinical trial initiation expected in Q4'25 / Q1'26 Potential to Broaden TX45 Phase 1b, hemodynamic topline results in PH-HFrEF subjects expected in 2H'25 TX45 to
HFrEF Patients * Positive PH-HFrEF results could potentially expand the addressable TX45 patient population by ~1.1M patients in the U.S. ~$159 million in cash as of 9/30/24, expected to provide a cash runway into mid-2027 Well-Capitalized *
Estimates based on company sponsored market analysis conducted by Health Advances
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 HFpEF 1
Increased Pulmonary Venous Pressures (~4M) Passive Pressure Backflow Pulmonary Hypertension PH-HFpEF 1 (~1.4M) IpcPH CpcPH (Combined, pre- and post capillary PH) 2 CpcPH (700K-1M) (400-700K) Chronic PH, HF, and/or Other Drivers
Pulmonary Vasculature Permanent Vascular Changes, e.g. Pulmonary Artery Remodeling Increased Vascular Resistance Normal PAH-like Right Heart Failure 1 Group 2 PH-HFrEF could add ~1.1M on top of the ~1.4M for PH-HFpEF 1. US
prevalence numbers for Class 2 and 3, estimates based on company sponsored market analysis conducted by Health Advances 2. 400K CpCPH and 1M IpcPH assumes diagnosis based on PVR>3; 700K CpCPH and 700K IpcPH assumes diagnosis based on
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
Function SERCA2 function Fibrosis RV / LV and Pulmonary Artery Anti-Inflammatory MMPs TGF Reverse Remodeling RXFP1 + Na Excretion Renal Blood Flow RV / LV Preload * RV: right ventricle; LV: left
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
available for 16 of 19 subjects 3 Hemodynamic data on the last 3 subjects are in line with the findings on the first 16 Last 3 patients all have IpcPH, therefore the CpcPH cohort data is final Safety data is available on 16
patients, 15 of whom have completed the full 43-day safety follow-up 2 Part B - Enrollment in PH-HFrEF subjects is expected to initiate near term with data in 2H'25 1 TX45 is currently enrolling in a Phase 2 trial for subjects
with PH-HFpEF enriched for CpcPH with results expected in 2026 1 PH-HFpEF = Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction (LVEF 40%) 2 PH-HFrEF = Pulmonary Hypertension due to Heart Failure with Reduced
Ejection Fraction 3 Based on data available to date
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 Day 8, 43: Safety Right Heart Catheter is inserted Screening Follow-ups and hemodynamic measurements are Admit to Unit Day -28 to -2 captured at the timepoints listed above Day -1
Day 1 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
8 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 Hemodynamic Definition Significance PCWP Measure of left atrial pressure
Key marker of left ventricular (LV) function (Pulmonary Capillary Wedge Pressure) PVR Measure of resistance to blood flow in Health of the pulmonary vessels (Pulmonary Vascular pulmonary vessels Resistance) PVR =
(mPAP - PCWP)/CO Measure of right ventricular afterload Key marker of resistance, how hard must the TPR (Total Pulmonary TPR = mPAP/CO right ventricle (RV) work Resistance) Amount of blood heart pumps
How well is the heart working (both RV and LV) CO (Cardiac Output) (volume/time) CO = heart rate x stroke volume SV Amount of blood ejected from ventricle Effectiveness of the heart at pumping blood (Stroke Volume) per beat
(both RV and LV) Note: mPAP = mean Pulm. Artery Pressure = average pressure required to pump blood through the lungs
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 1 PCWP provides insight into left ventricular
function and correlates with exercise capacity in HFpEF, HFrEF and Group 2 2 pulmonary hypertension (CpcPH) a ~15-20% decrease in pulmonary vascular resistance (PVR) in patients with CpcPH b PVR is normal in IpcPH , so a floor effect
is likely in this subgroup 3 In PAH, lowering of PVR is associated with improvement in 6MWD 2 - In Group 2 PH (CpcPH), lowering of PVR is correlated with increased 6MWD Reduction in total pulmonary resistance (TPR) in overall patient
population No bar set for Cardiac Output as Cardiac Output is normal at rest in patients with HFpEF 1.Wolsk E et al. Eur. J. Heart Fail. 2018 2.Zhang H et al. JACC: Cardiovascular Interventions. 2019
3.www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209279Orig1s000MedR.pdf a CpcPH = Combined Pre- and Post-Capillary Pulmonary Hypertension b IpcPh = Isolated Post-Capillary Pulmonary Hypertension
10 Phase 1b (Part A) Demographics & Medical History All Subjects
Key Concomitant All Subjects N = 16 Medications N = 16 ACEi/ARB [n (%)] 8 (50.0 %) Age (mean, SD) 64.3 (9.2) MRA [n (%)] 13 (81.3 %) Females [n (%)] 6 (37.5%) SGLT2i [n (%)] 6 (37.5 %) BMI (mean, SD) 28.0 (3.2) Loop Diuretic [n (%)] 11 (68.8 %)
Creatinine (uMol/L; mean, SD)* 80.8 (18.7) Beta-blocker 12 (75.0 %) Comorbidities Digoxin [n (%)] 5 (31.3 %) Hypertension [n (%)] 13 (81.3%) Atrial fibrillation [n (%)] 10 (62.5%) Diabetes mellitus [n (%)] 5 (31.3%) Coronary artery disease [n (%)]
10 (62.5%) NYHA Class [n (%)] NYHA Class II 9 (56.3%) *Creatinine normal range (uMol/L): Males: 61.9-114.9 NYHA Class III 7 (46.8%) Females: 53.0 to 97.2
11 Phase 1b (Part A) - Summary of Baseline Hemodynamics PVR < 2WU 2
WU PVR < 3WU PVR 3 WU Parameter Baseline Value [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: Total IpcPH = 11 Diastolic Blood Pressure (mm Hg) 78.5
(6.0) Total CpcPH = 5 Mean Pulmonary Artery Pressure (mm Hg) 26.6 (4.4) Pulmonary Capillary Wedge Pressure (mm Hg) 16.7 (3.2) If CpcPH is defined as PVR >2: Pulmonary Vascular Resistance (Woods Units) 2.45 (1.1) Total IpcPH = 7 Cardiac Output
(L/min) 4.3 (1.0) Total CpcPH = 9 Stroke Volume mL 65 (18) Total Pulmonary Resistance (Woods Units) 6.5 (1.6)
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 (worsening) 0 1 0
1 (6.3%) Viral infection 0 0 1 1 (6.3%) Procedural pain (catheter) 0 0 1 1 (6.3%) There were 9 treatment-emergent adverse events (TEAEs) in 7 patients There were no serious or severe adverse events, discontinuations, infusion
reactions or drug related adverse events There were no clinically significant changes in vital signs, physical exam or safety laboratory values *4 participants reported fatigue in the evening of D1; all reports of fatigue were brief
(< 3 hours) and self-limited; there were no reports of fatigue after D1
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] o Hemodynamics (Key 2 ) (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
2 WU) (n= 9) - 1.06 [-0.78 to -1.34] Woods Units -32.0% [-28.1% to -35.9%] Mean PVR in CpcPH (PVR 3 WU) (n= 5) - 1.35 [-1.15 to -1.55] Woods Units -35.5% [-32.5% to -38.6%] Other Hemodynamic Effects Mean Cardiac Output in
all participants +0.65 [0.34 to 0.96] L/min +17.4% [8.9% to 25.9%] +7 [2 to 12] mL Mean Stroke Volume in all participants +13.8% [5.3% to 22.3%] Mean TPR in all participants -1.79 [-1.24 to -2.34] Woods Units -26.3% [-20.1% to -32.5%]
-4.33 [-3.02 to -5.65] mmHg Mean mPAP in all participants -15.9% [-11.2% to -20.6%]
14 IV Administration of TX45 Resulted in a Transient, Asymptomatic
Decrease in Blood Pressure Mean SD Blood Pressure 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
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 [-2.0 to -4.4]
-20.6% [-12.5 to -28.6] Baseline PVR 3 WU (n = 5) 16.0 (2.4) 13.3 (2.7) -2.7 [-1.3 to -4.1] -17.1% [-7.8 to -26.4] All Subjects (mean SD) PCWP (mm Hg)
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 (0.44) -1.06
[-0.78 to -1.34] -32.0% [-28.1 to -35.9] Baseline PVR 3 WU (n = 5) 3.81 (0.46) 2.46 (0.34) -1.35 [-1.15 to -1.55] -35.5% [-32.5 to -38.6] All Subjects Subjects with baseline PVR 2 WU Subjects with baseline PVR 3 WU (N = 16;
mean SD) (N = 5; mean SD ) (N = 9; mean SD) * All subjects include both IpcPH and CpcPH subjects PVR (Woods Units)
17 TX45 Improves Other Relevant Hemodynamics in PH-HFpEF TPR (WU)
Cardiac Output (L/min) mPAP (mm Hg) All Subjects (N = 16) 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 [0.34 to 0.96]
-4.3 (-3.0 to -5.7) Average % CFB (mean, 95% CI) -26.3% [-20.1 to -32.5] +17.4% [8.9 to 25.9] -15.9% [-11.2 to -20.6] Mean Pulmonary Artery Pressure Total Pulmonary Resistance Cardiac Output (N = 16; mean SD) (N = 16; mean SD) (N = 16;
mean SD) TPR (Woods Units) CO (L/min) mPAP (mm Hg)
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 to -32.5]
Baseline PVR 2 WU (n = 9) 7.34 (1.50) 4.97 (0.89) -2.37 [-1.68 to -3.06] -31.5% [-25.2 to -37.9] Baseline PVR 3 WU (n = 5) 8.31 (1.11) 5.51 (0.77) -2.80 [-1.89 to -3.71] -33.5% [-25.8 to -41.1] Cardiac Output Baseline Treatment
Period Absolute CFB Average % CFB, (L/min) (L/min) (L/min) (95% CI) mean (SD) mean (SD) mean (95% CI) All subjects (N = 16) 4.31 (1.01) 4.96 (0.86) +0.65 [0.34 to 0.96] +17.4% [8.9 to 25.9] Baseline PVR 2 WU (n = 9) 4.08 (1.19) 4.79 (0.93)
+0.70 [0.30 to 1.10] +20.5% [7.3 to 33.6] Baseline PVR 3 WU (n = 5) 3.62 (0.94) 4.46 (1.00) +0.84 (0.35 to 1.32) +24.5% [7.4 to 41.5]
19 Combined Decrease in PCWP and PVR Appears to Enhance Improvement in
Exercise Capacity Decreasing PCWP alone is expected to improve exercise capacity 1 o SGLT2 inhibitor dapagliflozin decreased resting PCWP 20% and increased 6MWT by 20m in 2 HFpEF Decreasing both PCWP and PVR appears to further
increase in exercise capacity o CpcPH patients undergoing pulmonary artery denervation surgery achieved a treatment- adjusted average decrease of 19% in PCWP and 32% in PVR, and increased 6MWT distance 3 69m [NOTE: This was a severe population of
CpcPH patients (mean PVR>6 WU) and we expect impact on 6MWD will be clinically important but not as large as demonstrated in this study] 1 Borlaug B et al. Circulation 2023 2 Lewis GD et al. Circ. Heart Failure 2023 3 Zhang H et al. JACC
Cardiovasc. Interv. 2019
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