Tectonic Therapeutic, Inc.(TECX) - 2025 Q2 - Quarterly Results

Introduction & Disclaimer This section outlines the forward-looking nature of statements, highlighting substantial risks and uncertainties that could cause actual results to differ Disclaimer & Forward-Looking Statements This section outlines the forward-looking nature of statements made in the presentation, highlighting substantial risks and uncertainties that could cause actual results to differ - Statements regarding future preclinical studies, clinical trials (including Phase 1b and Phase 2 for TX45, and Phase 1 for TX2100), regulatory approvals, market potential, cash runway, and pipeline expansion are considered forward-looking[2] - Actual results may differ due to factors such as early development stage, clinical trial success rates, competitive changes, regulatory environment, macroeconomic conditions, and litigation[3] - Estimates and statistical data on market size and growth are subject to assumptions and limitations, and should not be given undue weight[4] Company Overview & Strategy Tectonic Tx, founded in 2019, focuses on GPCR-targeted biologics, leveraging a strong leadership team and a proprietary platform to address unmet medical needs Tectonic Tx Highlights Tectonic Tx, founded in 2019, is focused on discovering and developing GPCR-targeted biologics for significant unmet medical needs - Founded in 2019 by Tim Springer and Andrew Kruse, Tectonic Tx specializes in GPCR-targeted biologics[5] - The executive team has a strong track record, contributing to 20 'first' approvals[5] Key Financial and Pipeline Highlights | Metric | Detail | | :--- | :--- | | Lead Candidate | TX45 (long-acting relaxin) in Phase 2 trial for Group 2 Pulmonary Hypertension (PH-HFpEF) | | TX45 Market Potential | ~1.4M+ Group 2 PH-HFpEF patients in U.S. with no approved therapy; potential peak multi-billion-dollar revenue | | Second Pipeline Asset | TX2100 targeting Hereditary Hemorrhagic Telangiectasia (HHT), ~75K patients in U.S. with no approved therapies | | Cash Position (as of 06/30/25) | $287.4 million in cash and cash equivalents | | Cash Runway | Into Q4'28 | Leadership Team Tectonic Tx is led by an accomplished executive team and co-founders with extensive experience in the pharmaceutical and biotech industries, including contributions to major drug approvals and successful company formations - The executive team includes Marcella Ruddy (CEO), Marc Reicin (CMO), Alise Lochner (CBO), Daniel McNamara (CSO), Peter Muslin (CDO), and Anthony Schwabish (CFO), with backgrounds from Novartis, Merck, Regeneron, Celgene, and Goldman Sachs[7] - Co-founders Timothy Springer, Ph.D., and Andrew Kruse, Ph.D., are highly recognized scholars, with Springer being a 2022 Lasker Award recipient and Kruse a GPCR expert[7] Biologics in GPCR Targeting Biologics offer significant advantages over small molecules in targeting G protein-coupled receptors (GPCRs), which are a vast and largely unexploited therapeutic landscape - Over 18% of approved drugs target GPCRs, but only three are antibodies, indicating a large unexploited opportunity for biologics[9] - Biologics can capture complex ligand/receptor engagement, minimize off-target binding, and be engineered for tissue-specific targeting or bispecific action[9] Pipeline Overview: TX45 Program The TX45 program focuses on developing a long-acting relaxin for Group 2 Pulmonary Hypertension (PH-HFpEF) and Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD), addressing significant unmet medical needs TX45 for Group 2 Pulmonary Hypertension (PH-HFpEF) TX45 is a long-acting relaxin, an RXFP1 agonist, being developed as a potential best-in-class treatment for Group 2 Pulmonary Hypertension (PH) associated with Heart Failure with Preserved Ejection Fraction (HFpEF) - TX45 is a long-acting relaxin (RXFP1 agonist) with optimized pharmacokinetics for monthly dosing, aiming to be a best-in-class treatment for Group 2 PH-HFpEF[15][16] - Group 2 PH-HFpEF has no approved therapy, affects over 1 million patients in the US, and is associated with high 5-year mortality[16] Disease Background: Group 2 PH Pulmonary hypertension (PH) is categorized into five distinct groups, with Group 2 PH being the largest category, characterized by chronic, progressive elevated blood pressure in the pulmonary arteries due to left heart failure - Group 2 PH is the largest category of pulmonary hypertension, caused by left heart failure (HFpEF, HFrEF) or valvular heart disease[17][18] - It is characterized by chronically elevated pulmonary arterial pressures, pulmonary artery narrowing, and can lead to right heart failure and death[19] - There are no approved therapies for Group 2 PH[19] Group 2 PH Subtypes and Prevalence | Subtype | Description | US Prevalence (approx.) | | :--- | :--- | :--- | | IpcPH (Isolated, post capillary PH) | Increased Left Ventricle Filling Pressures, Passive Pressure Backflow | 700K-1M | | CpcPH (Combined, pre- and post capillary PH) | Chronic PH, HF, and/or Other Drivers, Permanent Vascular Changes, Increased Vascular Resistance | 400K-700K | | Total PH-HFpEF | | ~1.4M | | Potential Expansion to PH-HFrEF | | ~1.1M additional patients | Market Opportunity: Group 2 PH vs. PAH Group 2 PH represents a significant market opportunity due to its high prevalence compared to PAH (Group 1) and the complete lack of approved therapeutic options, despite similar or worse 5-year survival rates - Group 2 PH has a US prevalence of ~1.4 million patients, significantly higher than PAH (~25,000 patients)[23] - There are no approved therapies for Group 2 PH, in contrast to PAH which has multiple approved drugs[23] - The 5-year survival rate for Group 2 PH is comparable to or worse than PAH (~50%), highlighting the high unmet need[23] - The market potential for Group 2 PH is estimated to be multi-billion dollars, exceeding the current >$4 billion PAH market[23] TX45 Mechanism of Action TX45, as a relaxin agonist, leverages the natural hemodynamic and anti-fibrotic properties of relaxin, which are crucial during pregnancy - Relaxin is a natural ligand of the RXFP1 receptor, acting as a pulmonary and systemic vasodilator and an anti-fibrotic agent[26] - TX45 is designed to improve left ventricular diastolic relaxation, reduce RV/LV afterload and preload, decrease fibrosis, and exert anti-inflammatory effects[29] - Anticipated relaxin effects include pulmonary and peripheral vasodilation, improved cardiac relaxation, left ventricular remodeling, and improvement in kidney function, addressing key characteristics of PH-HFpEF[30] TX45 PK Optimization TX45 has been engineered to overcome the critical pharmacokinetic (PK) limitations of other relaxin molecules, specifically their very short in vivo half-life - Natural relaxin has a very short in vivo half-life, and previous Fc-fusion relaxins with high pI experienced rapid clearance due to glycocalyx binding[33] - TX45 was engineered to reduce its net positive charge (lower pI), preventing rapid clearance and extending its half-life[33] TX45 Clinical Development Program Overview The TX45 development program includes Phase 1a (completed), Phase 1b (Part A completed, Part B expected early Q4'25), and a planned Phase 2 trial for Group 2 PH-HFpEF (enriched for CpcPH) expected in 2026 - Phase 1a (Healthy Volunteers) for safety, tolerability, PK/PD was toplined in Sept '24[35] - Phase 1b (Group 2 PH with HFpEF/HFrEF) is a RHC study for hemodynamic proof of concept; Part A (PH-HFpEF) is complete, Part B (PH-HFrEF) results expected early Q4'25[35] - A randomized, 6-month Phase 2 study for Group 2 PH with HFpEF (enriched for CpcPH) is planned for 2026[35] Phase 1a Clinical Study Results (Safety & PK/PD) The Phase 1a study demonstrated a favorable safety profile for TX45 with no serious adverse events and an extended half-life of 14-20 days, supporting monthly dosing - TX45 showed a favorable safety profile in Phase 1a, with no discontinuations, treatment-related SAEs, injection site reactions, or immunogenicity. The most common AE was transient orthostatic tachycardia (17% placebo vs 23% TX45)[41] - Single-dose TX45 demonstrated a potential best-in-class terminal elimination half-life of 14-20 days, supporting monthly dosing[45] - Human-exposure modeling based on Phase 1a Renal Plasma Flow (RPF) data (Emax = 33%) supports Phase 2 dose selection, with 300 mg SC monthly predicted to achieve a steady-state trough of 2.6 ug/ml (EC80), slightly higher than the preclinical predicted maximal efficacy exposure of 2 ug/ml[53] Phase 1b Part A Clinical Study Results (PH-HFpEF) Phase 1b Part A results in PH-HFpEF patients met or exceeded expectations, demonstrating that TX45 was well-tolerated and significantly improved both left heart function (reduced PCWP) and pulmonary hemodynamics (reduced PVR, increased Cardiac Output) - TX45 was well-tolerated in Phase 1b Part A, with all 10 treatment-emergent adverse events (TEAEs) in 8 patients being mild/moderate and self-limited, and no serious or severe adverse events[72] Phase 1b Part A Hemodynamic Results (N=19) | Hemodynamic Measure | Absolute Change from Baseline (Mean [95% CI]) | Average % Change from Baseline (Mean [95% CI]) | | :--- | :--- | :--- | | Mean Δ PCWP (all participants) | -3.2 [-4.3 to -2.1] mm Hg | -19.0% [-26.1% to -11.9%] | | Mean Δ PVR (CpcPH, PVR ≥ 2 WU, n=9) | -1.06 [-1.34 to -0.78] WU | -32.0% [-35.9% to -28.1%] | | Mean Δ Cardiac Output (all participants) | +0.73 [0.39 to 1.08] L/min | +18.5% [10.2% to 26.9%] | | Mean Δ TPR (all participants) | -1.89 [-2.42 to -1.36] WU | -28.7% [-34.1% to -22.1%] | | Mean Δ mPAP (all participants) | -4.63 [-5.77 to -3.48] mmHg | -16.8% [-20.8% to -12.8%] | | Mean Δ SVR (all participants) | -3.95 [-5.82 to -2.08] mmHg | -16.6% [-24.4% to -8.8%] | - Echocardiographic analyses suggested sustained improvements in hemodynamics with a single dose of TX45, including increased TAPSE/SPAP and RVFAC[68][69][77] APEX Phase 2 Clinical Trial Design (PH-HFpEF) The APEX Phase 2 trial for TX45 will be a global, multicenter, double-blind, randomized, placebo-controlled study in PH-HFpEF subjects, enriched for the CpcPH subgroup - The Phase 2 trial will be a 24-week, double-blind, randomized, placebo-controlled study with two active TX45 arms (300mg Q2W and 300mg Q4W) and a placebo arm, each with 60 subjects[79] - The primary endpoint is the change from baseline in Pulmonary Vascular Resistance (PVR)[79] - Secondary endpoints include changes from baseline in Pulmonary Capillary Wedge Pressure (PCWP), 6-Minute Walk Distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ)[79] Competitive Landscape (Relaxin MoA & Group 2 PH) Tectonic Tx's TX45 stands out in the competitive landscape for Group 2 PH due to its Fc-Relaxin Fusion format, subcutaneous administration, and a longer half-life (14-20 days) compared to AstraZeneca's Fc-Relaxin Fusion (7-9 days), allowing for less frequent dosing Competitive Landscape for Group 2 PH | Company | Format | Formulation | Half Life (in NHV) | Dosing* | Patient Population | Phase 2 Endpoints | Readout | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | TECTONIC | Fc-Relaxin Fusion (TX45) | Sub Q | 14-20 days | Q4 Weeks | Group 2 PH / HFpEF (enriched for CpcPH) | ΔPVR | Ph 2 | | AstraZeneca | Fc-Relaxin Fusion (AZD3427) | Sub Q | 7-9 days ** | Q2 Weeks* | Group 2 PH / HFpEF and HFrEF | ΔPVR | 2H'25 | | AstraZeneca | Small Molecule Relaxin (AZD5462) | Oral | 3-6 hours | QD* | CHF | ΔEcho Parameters | 1H'25 | | MERCK | ActRIIA-Fc (ACE-011) | Sub Q | n/a | Q3 Weeks | Group 2 PH (CpcPH) / HFpEF | VLAK | Q4'25 | | TENAX | Levosimendan (TNX-103) | Oral | n/a | BID/TID | Group 2 PH / HFpEF | Δ6MWD | Mid '25 | - TX45's half-life of 14-20 days supports a Q4W (monthly) dosing frequency, offering a potential advantage over competitors requiring more frequent administration[80] TX45 for Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD) Tectonic Tx is expanding the TX45 program to include Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD), a WHO Group 3 PH with high unmet medical need and mortality - TX45 is being developed for PH-ILD (WHO Group 3 PH), a condition with high mortality (3-year rate of 60-77%) and limited approved therapies (only inhaled treprostinil)[83] - The PH-ILD market potential is multi-billion dollars, driven by unmet need, patient population (~60K+ in U.S.), and orphan drug pricing[83] Disease Background: PH-ILD PH-ILD is a subgroup of Group 3 Pulmonary Hypertension, diagnosed by right heart catheterization in the context of Interstitial Lung Disease - PH-ILD is a subgroup of Group 3 PH, diagnosed by RHC in patients with Interstitial Lung Disease, characterized by increased PVR and mPAP with reduced CO[83] - It leads to worsening exercise capacity and oxygenation, with a high 3-year mortality rate of 60% to 77%[83] - Only inhaled treprostinil therapies are approved for PH-ILD, which have side effects like cough and bronchospasm[83] Rationale for TX45 in PH-ILD TX45's pulmonary vasodilation, anti-inflammatory, and anti-fibrotic effects, demonstrated in preclinical models and Group 2 PH patients, provide a strong rationale for its use in PH-ILD - TX45's relaxin effects include pulmonary vasodilation (via NO pathway, antagonizing ET-1), anti-inflammatory effects, and inhibition of TGFβ pathway, which can heal abnormal histologic changes and attenuate lung fibrosis[84] - Clinical hemodynamic data from PH-HFpEF patients (e.g., -32.0% PVR reduction in CpcPH) and preclinical remodeling effects in animal models of PH are relevant to PH-ILD[85] - TX45 has the potential to improve pulmonary hemodynamics without systemic hypotension or worsening hypoxemia, differentiating it from systemic pulmonary vasodilatory compounds that have failed in PH-ILD[87] TX45 Phase 2 PH-ILD Study Design Tectonic Tx plans to initiate an open-label, repeat-dose, 16-week Phase 2 trial for TX45 in approximately 20 PH-ILD subjects in 2026 - The planned Phase 2 PH-ILD trial is an open-label, repeat-dose, 16-week study with approximately 20 subjects[88] - Dosing will be 300mg subcutaneous every 2 weeks[89] - Primary efficacy endpoint is change from baseline in PVR, with secondary and exploratory endpoints including mPAP, CO, 6MWD, and quality of life (QoL)[89] Competitive Landscape (PH-ILD) In the PH-ILD competitive landscape, TX45 offers a differentiated approach as an Fc-Relaxin Fusion administered subcutaneously every 2 or 4 weeks, contrasting with approved inhaled prostacyclin therapies and other investigational inhaled or oral compounds Competitive Landscape for PH-ILD | Company | Format | Administration | Dosing | MOA | Clinical Stage | Primary Endpoint | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | TECTONIC | Fc-Relaxin Fusion (TX45) | Sub-Q | Every 2 or 4 Weeks | Relaxin | Planned Phase 2 in 2026 | ΔPVR at Week 16 | | United Therapeutics | Tyvaso (Treprostinil) | Inhaled (nebulizer / dry powder) | 4x Daily | Prostacyclin | Approved | Δ6MWD at Week 16 | | Liquidia | Yutrepia (Treprostinil) | Inhaled (dry powder) | 3-5x Daily | Prostacyclin | Approved | Δ6MWD at Week 12 | | Insmed | Treprostinil Palmitil Inhalation Powder (TPIP) | Inhaled (dry powder) | 1x Daily | Prostacyclin | Phase 3 initiation before end of 2025 | Not available | | Gossamer Bio | Seralutinib (GB002) | Inhaled (dry powder) | 2x Daily | Tyrosine Kinase Inhibitor | Pending Phase 3 initiation in Q4'25 | Δ6MWD at Week 24 | | PulmoVasc | Mosliciguat (BAY 1237592) | Inhaled (dry powder) | 1x Daily | sGC Activator | Phase 2 | ΔPVR at Week 16 | | Hall | Hymecromone (HB-1614) | Oral | 2x Daily | Hyaluronan Inhibitor | Phase 2a | ΔPVR at Week 24 | | Foresee Pharmaceuticals | Mirivadelgat (FP-045) | Oral | 1x Daily | ALDH2 Activator | Phase 2 | ΔPVR at Week 12 | Pipeline Overview: TX2100 Program The TX2100 program targets Hereditary Hemorrhagic Telangiectasia (HHT), a rare genetic bleeding disorder with no approved therapies, representing a potential first-in-class treatment TX2100 for Hereditary Hemorrhagic Telangiectasia (HHT) TX2100 is Tectonic Tx's second pipeline asset, targeting Hereditary Hemorrhagic Telangiectasia (HHT), a rare genetic bleeding disorder with no approved therapies - TX2100 is a potential first-in-class therapy for Hereditary Hemorrhagic Telangiectasia (HHT), the second most common genetic bleeding disorder, with no approved therapies[93][95] - HHT affects approximately 75,000 patients in the US, caused by mutations in the BMP9/10 pathway, leading to abnormal blood vessel formation (AVMs and telangiectasias) and increased mortality risk[95] Disease Background: HHT HHT is a rare, autosomal dominant disease caused by mutations in the BMP9/10 pathway, resulting in abnormal blood vessel formations (AVMs and telangiectasias) throughout the body - HHT is a rare, autosomal dominant disease affecting ~75,000 patients in the US, caused by mutations in the BMP9/10 pathway[95] - Key symptoms include nosebleeds (>95%), skin telangiectasias (>90%), and AVMs in lungs (50%), liver (50%), GI tract (20%), and brain (10%)[95] - Complications include iron and transfusion-dependent anemia, high output CHF, stroke, brain abscesses, and pulmonary hypertension, with no currently approved therapies[95] Preclinical Rationale & Data Preclinical studies, including an HHT mouse model, have shown that anti-VEGF antibodies can suppress AVM formation and improve hemoglobin levels, although clinical studies have been limited - Anti-VEGF monoclonal antibodies have shown efficacy in mouse HHT models, suppressing AVM formation and visceral hemorrhage, and reducing epistaxis severity in patients, but rigorous clinical studies are lacking due to patent expiration and side effect concerns[96][97] - A GPCR3 antagonist mAb (TX1351) significantly reduced AVM formation, retinal bleeding, and improved hemoglobin levels in an HHT mouse model generated by immuno-blockade of BMP9 and BMP10[98][99] TX2100 Development Program Overview The TX2100 development program is progressing with IND-enabling studies and CMC finalized in November '24 - IND-enabling development studies and CMC were finalized in November '24[102] - Phase 1 clinical trial initiation in healthy volunteers is expected in Q1'26 to assess safety and tolerability[102] - A randomized 3-month Phase 2 study in HHT patients, evaluating hematocrit, epistaxis score, and blood transfusions, is planned for early 2027[102] GEODe™ Platform The proprietary GEODe™ Platform addresses key challenges in GPCR-targeted biologics discovery through advanced receptor engineering and optimized antibody discovery GPCR Targeted Biologics Discovery Challenges & Solutions Tectonic Tx's proprietary GEODe™ Platform is designed to overcome key challenges in GPCR-targeted biologics discovery - The GEODe™ Platform addresses challenges such as retaining endogenous GPCR structure, purifying targets in sufficient quantities, inducing immune responses to human GPCRs, and stabilizing receptors in active conformations[106] - Key features include Receptor Engineering and Purification Technology for abundant native receptor reagent, In-vitro Yeast Display Antibody Discovery with optimized libraries, and Protein Engineering to optimize pharmacology and enable agonist/antagonist screening[107] Conclusion & Milestones Tectonic Tx is well-positioned to achieve significant value-creating milestones for its pipeline candidates, supported by a strong financial position and experienced leadership Value-Creating Milestones & Financial Position Tectonic Tx is well-positioned to deliver value-creating milestones with two pipeline candidates addressing significant untapped markets - TX45, the lead candidate, is a long-acting relaxin in Phase 2, with best-in-class potential for over 1 million patients with Group 2 PH-HFpEF, and potential expansion to PH-HFrEF and PH-ILD[108] - TX2100, the second pipeline candidate, targets HHT, a rare bleeding disorder with no approved therapy[108] Upcoming Milestones | Year | Milestone | | :--- | :--- | | 2025 | TX45 Phase 1b Part B hemodynamic topline results in PH-HFrEF subjects (expected early Q4'25) | | 2026 | TX2100 Phase 1 initiation (expected Q1'26) | | 2026 | Initiation of Phase 2 PH-ILD trial (expected 2026) | | 2026 | TX45 APEX Phase 2 topline results in PH-HFpEF (expected 2026) | - The company is well-capitalized with $287.4 million in cash and cash equivalents as of June 30, 2025, providing a cash runway into Q4'28[108]