Summary of Tectonic Therapeutics FY Conference Call Company Overview - **Company**: Tectonic Therapeutics (NasdaqGM: TECX) - **Focus**: Development of novel therapeutics targeting heart failure and pulmonary hypertension Key Molecule: TX-45 - **Description**: TX-45 is a long-acting relaxin mimetic with potential applications in heart failure and pulmonary hypertension [3][4] - **Mechanisms of Action**: - Acts as a vasodilator for both peripheral and pulmonary circulation [4] - Functions as a leisotropic agent, relaxing heart muscle during diastole [4] - Exhibits antifibrotic properties by increasing metalloproteinases and inhibiting the TGF beta pathway [5] Target Patient Population - **Heart Failure with Preserved Ejection Fraction (HFpEF)**: Estimated 3.5 to 4 million patients in the U.S. [9] - **Specific Subset**: Approximately 1.4 million patients with Class II and III heart failure and elevated pulmonary pressures, with around 700,000 to 1 million having combined pre- and post-capillary pulmonary hypertension (CPCPH) [10] Competitive Landscape - **Lilly's Program**: Competes with a long-acting relaxin designed differently, leading to fluid retention issues in decompensated heart failure patients [12][13] - **AstraZeneca**: Conducting studies in similar patient populations, focusing on pulmonary vascular resistance [24] - **Merck**: Investigating treatments for pulmonary hypertension, with potential data release expected [29] Clinical Trial Updates - **Phase Ib Study**: Showed a 32% to 35% reduction in pulmonary vascular resistance and an 18% to 19% reduction in pulmonary capillary wedge pressure [38] - **Phase II APeX Trial**: Over 30% enrollment, focusing on patients with high pulmonary vascular resistance [42] - **Future Trials**: Plans to initiate a trial for pulmonary hypertension associated with interstitial lung disease (PHILD) in 2026 [50] Additional Program: Hereditary Hemorrhagic Telangiectasia (HHT) - **Target Population**: 70,000 to 75,000 patients in the U.S., focusing on moderate to severe cases with no approved therapies [61] - **Study Timeline**: Phase I study expected to start in Q1 2026 [62] Platform Technology - **G Protein-Coupled Receptors (GPCRs)**: Tectonic's platform enables the development of antibodies against GPCRs, a significant target for drug development [66] Upcoming Milestones - **Data Releases**: Anticipated data from reduced ejection fraction Phase Ib study in October and further updates on clinical trials throughout 2026 [71][72] Conclusion - Tectonic Therapeutics is positioned to address significant unmet needs in heart failure and pulmonary hypertension with innovative therapies and a robust pipeline, while navigating a competitive landscape with ongoing clinical trials and strategic patient targeting.

Summary of Tectonic Therapeutic (TECX) Conference Call Company Overview - **Company**: Tectonic Therapeutic (TECX) - **Event**: 2025 Conference at Cantor Healthcare Conference - **Date**: September 04, 2025 Industry Context - **Industry**: Biopharmaceuticals, specifically focusing on relaxin therapies for heart failure and pulmonary hypertension Key Points and Arguments Eli Lilly's Data Impact - Eli Lilly's recent trial results have negatively impacted Tectonic Therapeutic, referred to as "triple jeopardy" due to three separate impacts from the trial [4][3] - Eli Lilly's trial involved patients with decompensated heart failure, which is a challenging population to treat, leading to concerns about fluid retention and sodium avidity [5][6] - Tectonic's approach differs as they focus on stable patients who are not fluid overloaded, emphasizing the importance of euvolemic status before treatment [7] Tectonic's Phase 1B Data - Tectonic reported positive Phase 1B data showing a **35% reduction in pulmonary vascular resistance** and a **20% reduction in pulmonary artery pressure** [11] - The study indicated a **3 mm drop in pulmonary capillary wedge pressure**, which is significant as it suggests improved hemodynamics [21] - The increase in cardiac output by **almost 20%** was unexpected and indicates effective treatment [21] Future Studies and Patient Population - Tectonic is focusing on a specific patient population with combined pre- and post-capillary pulmonary hypertension (CP-CPH), aiming to reduce pulmonary vascular resistance [37] - The company plans to enrich for patients with high pulmonary vascular resistance (PVR) in their studies, with **70% of patients in the Phase 2 study required to have PVR greater than 3 WU units** [12][13] Competitive Landscape - AstraZeneca has an ongoing relaxin program, which provides reassurance to Tectonic as it indicates continued interest and potential in the relaxin space [16][18] - Tectonic believes that the presence of other therapies, such as Merck's sotatercept, could open the market for their product, as there is currently no approved therapy for CP-CPH [39][40] Regulatory Considerations - The primary endpoint for Tectonic's studies is the **six-minute walk test**, which is considered sufficient for regulatory approval [48] - There is potential for composite endpoints in future studies, including cardiovascular death and hospitalization [48] Upcoming Data and Trials - Tectonic plans to release additional data in the second half of October, focusing on patients with reduced ejection fraction heart failure [30] - A Phase 2 study for pulmonary hypertension associated with interstitial lung disease (PH-ILD) is in the planning stages, with a focus on a small cohort of 20 patients [49][50] Market Positioning - Tectonic aims to be the first systemic therapy for PH-ILD, addressing a significant unmet need in the market [52] - The company is considering testing their therapy in combination with existing treatments if initial studies show efficacy [52] Conclusion - Tectonic Therapeutic is navigating a challenging landscape following Eli Lilly's trial results but remains optimistic about its unique approach and upcoming data releases. The focus on specific patient populations and the potential for regulatory approval through established endpoints positions the company favorably in the biopharmaceutical market.

Core Insights - Tectonic Therapeutic, Inc. is a clinical-stage biotechnology company focused on developing therapeutic proteins and antibodies targeting G-protein coupled receptors (GPCRs) [1][5] - The company will participate in three investor conferences in September 2025, providing opportunities for one-on-one meetings with management [1][4] Conference Details - **Wells Fargo Healthcare Conference** - Date: September 3, 2025 - Location: Boston, MA - Format: Investor Meetings [2] - **Cantor Global Healthcare Conference** - Date: September 4, 2025 - Time: 2:10 PM EDT - Location: New York, NY - Format: Fireside Chat - Presenters: Daniel Lochner (CFO) and Marc Schwabish, PhD (CBO) [2][3] - **Morgan Stanley 23 Annual Global Healthcare Conference** - Date: September 10, 2025 - Time: 3:20 PM EDT - Location: New York, NY - Format: Fireside Chat - Presenter: Alise Reicin, MD (President and CEO) [3] Company Overview - Tectonic utilizes its proprietary GEODe™ technology platform to enhance GPCR-targeted drug discovery, aiming to address significant unmet medical needs [5] - The company is headquartered in Watertown, Massachusetts, and focuses on developing biologic medicines to improve patient quality of life [5]

[Introduction & Disclaimer](index=1&type=section&id=Introduction%20%26%20Disclaimer) 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](index=2&type=section&id=1.1%20Disclaimer%20%26%20Forward-Looking%20Statements) 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](index=2&type=chunk) - 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](index=3&type=chunk) - Estimates and statistical data on market size and growth are subject to assumptions and limitations, and should not be given undue weight[4](index=4&type=chunk) [Company Overview & Strategy](index=3&type=section&id=Company%20Overview%20%26%20Strategy) 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](index=3&type=section&id=2.1%20Tectonic%20Tx%20Highlights) 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](index=5&type=chunk) - The executive team has a strong track record, contributing to **20 'first' approvals**[5](index=5&type=chunk) 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](index=4&type=section&id=2.2%20Leadership%20Team) 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](index=7&type=chunk) - 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](index=7&type=chunk) [Biologics in GPCR Targeting](index=5&type=section&id=2.3%20Biologics%20in%20GPCR%20Targeting) 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](index=9&type=chunk) - Biologics can capture complex ligand/receptor engagement, minimize off-target binding, and be engineered for tissue-specific targeting or bispecific action[9](index=9&type=chunk) [Pipeline Overview: TX45 Program](index=6&type=section&id=Pipeline%20Overview%3A%20TX45%20Program) 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)](index=7&type=section&id=3.1%20TX45%20for%20Group%202%20Pulmonary%20Hypertension%20(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](index=15&type=chunk)[16](index=16&type=chunk) - **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](index=16&type=chunk) [Disease Background: Group 2 PH](index=9&type=section&id=3.1.1%20Disease%20Background%3A%20Group%202%20PH) 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](index=17&type=chunk)[18](index=18&type=chunk) - It is characterized by chronically elevated pulmonary arterial pressures, pulmonary artery narrowing, and can lead to **right heart failure and death**[19](index=19&type=chunk) - There are **no approved therapies** for **Group 2 PH**[19](index=19&type=chunk) 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](index=11&type=section&id=3.1.2%20Market%20Opportunity%3A%20Group%202%20PH%20vs.%20PAH) 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](index=23&type=chunk) - There are **no approved therapies for Group 2 PH**, in contrast to PAH which has multiple approved drugs[23](index=23&type=chunk) - The **5-year survival rate for Group 2 PH** is comparable to or worse than **PAH (~50%)**, highlighting the high unmet need[23](index=23&type=chunk) - The market potential for **Group 2 PH** is estimated to be **multi-billion dollars**, exceeding the current **>$4 billion PAH market**[23](index=23&type=chunk) [TX45 Mechanism of Action](index=12&type=section&id=3.1.3%20TX45%20Mechanism%20of%20Action) 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](index=26&type=chunk) - **TX45** is designed to improve left ventricular diastolic relaxation, reduce RV/LV afterload and preload, decrease fibrosis, and exert anti-inflammatory effects[29](index=29&type=chunk) - 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](index=30&type=chunk) [TX45 PK Optimization](index=15&type=section&id=3.1.4%20TX45%20PK%20Optimization) 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](index=33&type=chunk) - **TX45** was engineered to reduce its net positive charge (**lower pI**), preventing rapid clearance and **extending its half-life**[33](index=33&type=chunk) [TX45 Clinical Development Program Overview](index=16&type=section&id=3.1.5%20TX45%20Clinical%20Development%20Program%20Overview) 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](index=35&type=chunk) - **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](index=35&type=chunk) - A randomized, **6-month Phase 2 study** for **Group 2 PH with HFpEF (enriched for CpcPH)** is planned for **2026**[35](index=35&type=chunk) [Phase 1a Clinical Study Results (Safety & PK/PD)](index=17&type=section&id=3.1.6%20Phase%201a%20Clinical%20Study%20Results%20(Safety%20%26%20PK%2FPD)) 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](index=41&type=chunk) - Single-dose **TX45** demonstrated a potential **best-in-class terminal elimination half-life of 14-20 days**, supporting **monthly dosing**[45](index=45&type=chunk) - 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](index=53&type=chunk) [Phase 1b Part A Clinical Study Results (PH-HFpEF)](index=22&type=section&id=3.1.7%20Phase%201b%20Part%20A%20Clinical%20Study%20Results%20(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](index=72&type=chunk) 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](index=68&type=chunk)[69](index=69&type=chunk)[77](index=77&type=chunk) [APEX Phase 2 Clinical Trial Design (PH-HFpEF)](index=34&type=section&id=3.1.8%20APEX%20Phase%202%20Clinical%20Trial%20Design%20(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](index=79&type=chunk) - The **primary endpoint** is the change from baseline in **Pulmonary Vascular Resistance (PVR)**[79](index=79&type=chunk) - Secondary endpoints include changes from baseline in **Pulmonary Capillary Wedge Pressure (PCWP)**, **6-Minute Walk Distance (6MWD)**, and **Kansas City Cardiomyopathy Questionnaire (KCCQ)**[79](index=79&type=chunk) [Competitive Landscape (Relaxin MoA & Group 2 PH)](index=35&type=section&id=3.1.9%20Competitive%20Landscape%20(Relaxin%20MoA%20%26%20Group%202%20PH)) 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](index=80&type=chunk) [TX45 for Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD)](index=36&type=section&id=3.2%20TX45%20for%20Pulmonary%20Hypertension%20associated%20with%20Interstitial%20Lung%20Disease%20(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](index=83&type=chunk) - The **PH-ILD market potential** is **multi-billion dollars**, driven by unmet need, patient population (**~60K+ in U.S.**), and **orphan drug pricing**[83](index=83&type=chunk) [Disease Background: PH-ILD](index=37&type=section&id=3.2.1%20Disease%20Background%3A%20PH-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](index=83&type=chunk) - It leads to worsening exercise capacity and oxygenation, with a **high 3-year mortality rate of 60% to 77%**[83](index=83&type=chunk) - Only **inhaled treprostinil therapies** are approved for **PH-ILD**, which have side effects like cough and bronchospasm[83](index=83&type=chunk) [Rationale for TX45 in PH-ILD](index=38&type=section&id=3.2.2%20Rationale%20for%20TX45%20in%20PH-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](index=84&type=chunk) - 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](index=85&type=chunk) - **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](index=87&type=chunk) [TX45 Phase 2 PH-ILD Study Design](index=41&type=section&id=3.2.3%20TX45%20Phase%202%20PH-ILD%20Study%20Design) 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](index=88&type=chunk) - Dosing will be **300mg subcutaneous every 2 weeks**[89](index=89&type=chunk) - **Primary efficacy endpoint** is change from baseline in **PVR**, with secondary and exploratory endpoints including **mPAP, CO, 6MWD**, and **quality of life (QoL)**[89](index=89&type=chunk) [Competitive Landscape (PH-ILD)](index=42&type=section&id=3.2.4%20Competitive%20Landscape%20(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](index=44&type=section&id=Pipeline%20Overview%3A%20TX2100%20Program) 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)](index=44&type=section&id=4.1%20TX2100%20for%20Hereditary%20Hemorrhagic%20Telangiectasia%20(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](index=93&type=chunk)[95](index=95&type=chunk) - **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](index=95&type=chunk) [Disease Background: HHT](index=45&type=section&id=4.1.1%20Disease%20Background%3A%20HHT) 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](index=95&type=chunk) - Key symptoms include **nosebleeds (>95%)**, **skin telangiectasias (>90%)**, and **AVMs in lungs (50%), liver (50%), GI tract (20%), and brain (10%)**[95](index=95&type=chunk) - Complications include **iron and transfusion-dependent anemia, high output CHF, stroke, brain abscesses, and pulmonary hypertension**, with **no currently approved therapies**[95](index=95&type=chunk) [Preclinical Rationale & Data](index=46&type=section&id=4.1.2%20Preclinical%20Rationale%20%26%20Data) 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](index=96&type=chunk)[97](index=97&type=chunk) - 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](index=98&type=chunk)[99](index=99&type=chunk) [TX2100 Development Program Overview](index=48&type=section&id=4.1.3%20TX2100%20Development%20Program%20Overview) 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](index=102&type=chunk) - **Phase 1 clinical trial initiation** in healthy volunteers is expected in **Q1'26** to assess safety and tolerability[102](index=102&type=chunk) - A randomized **3-month Phase 2 study** in **HHT patients**, evaluating **hematocrit, epistaxis score, and blood transfusions**, is planned for **early 2027**[102](index=102&type=chunk) [GEODe™ Platform](index=49&type=section&id=GEODe%E2%84%A2%20Platform) 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](index=50&type=section&id=5.1%20GPCR%20Targeted%20Biologics%20Discovery%20Challenges%20%26%20Solutions) 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](index=106&type=chunk) - 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](index=107&type=chunk) [Conclusion & Milestones](index=51&type=section&id=Conclusion%20%26%20Milestones) 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](index=51&type=section&id=6.1%20Value-Creating%20Milestones%20%26%20Financial%20Position) 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](index=108&type=chunk) - **TX2100**, the second pipeline candidate, targets **HHT**, a **rare bleeding disorder** with **no approved therapy**[108](index=108&type=chunk) 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](index=108&type=chunk)

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=4&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) This section presents the company's unaudited condensed consolidated financial statements, including the balance sheets, statements of operations and comprehensive loss, statements of convertible preferred stock and stockholders' equity (deficit), and statements of cash flows, along with detailed notes explaining the basis of presentation, significant accounting policies, and specific financial line items [Condensed Consolidated Balance Sheets as of June 30, 2025 and December 31, 2024](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets%20as%20of%20June%2030,%202025%20and%20December%2031,%202024) The balance sheet shows a significant increase in cash and cash equivalents and total assets as of June 30, 2025, primarily driven by a private placement, while total liabilities remained relatively stable. Stockholders' equity also saw a substantial increase | Metric (in thousands) | June 30, 2025 | December 31, 2024 | Change | % Change | | :-------------------- | :------------ | :---------------- | :----- | :------- | | Cash and cash equivalents | **$287,381** | **$141,239** | **$146,142** | **103.47%** | | Total current assets | **$290,848** | **$146,857** | **$143,991** | **98.05%** | | Total assets | **$295,313** | **$152,905** | **$142,408** | **93.13%** | | Total current liabilities | **$11,361** | **$11,610** | **$(249)** | **-2.14%** | | Total liabilities | **$11,547** | **$12,129** | **$(582)** | **-4.80%** | | Total stockholders' equity | **$283,766** | **$140,776** | **$142,990** | **101.57%** | [Condensed Consolidated Statements of Operations and Comprehensive Loss for the three and six months ended June 30, 2025 and 2024](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss%20for%20the%20three%20and%20six%20months%20ended%20June%2030,%202025%20and%202024) The company reported increased net losses for both the three and six months ended June 30, 2025, compared to the prior year, primarily due to a significant rise in research and development expenses. Interest income also saw a substantial increase | Metric (in thousands) | 3 Months Ended June 30, 2025 | 3 Months Ended June 30, 2024 | Change | % Change | | :-------------------- | :--------------------------- | :--------------------------- | :----- | :------- | | Research and development | **$17,185** | **$7,074** | **$10,111** | **143%** | | General and administrative | **$5,147** | **$4,347** | **$800** | **18%** | | Total operating expenses | **$22,332** | **$11,421** | **$10,911** | **96%** | | Loss from operations | **$(22,332)** | **$(11,421)** | **$(10,911)**| **96%** | | Interest income | **$3,389** | **$318** | **$3,071** | **966%** | | Net loss | **$(19,984)** | **$(12,671)** | **$(7,313)**| **58%** | | Net loss per share, basic and diluted | **$(1.07)** | **$(4.34)** | **$3.27** | **-75%** | | Metric (in thousands) | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | Change | % Change | | :-------------------- | :--------------------------- | :--------------------------- | :----- | :------- | | Research and development | **$30,221** | **$17,892** | **$12,329** | **69%** | | General and administrative | **$10,409** | **$6,497** | **$3,912** | **60%** | | Total operating expenses | **$40,630** | **$24,389** | **$16,241** | **67%** | | Loss from operations | **$(40,630)** | **$(24,389)** | **$(16,241)**| **67%** | | Interest income | **$5,833** | **$574** | **$5,259** | **916%** | | Net loss | **$(35,890)** | **$(27,892)** | **$(7,998)**| **29%** | | Net loss per share, basic and diluted | **$(2.00)** | **$(12.97)** | **$10.97** | **-85%** | [Condensed Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit) for the three and six months ended June 30, 2025 and 2024](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Convertible%20Preferred%20Stock%20and%20Stockholders'%20Equity%20(Deficit)%20for%20the%20three%20and%20six%20months%20ended%20June%2030,%202025%20and%202024) The company's total stockholders' equity significantly increased from **$140.8 million** at January 1, 2025, to **$283.8 million** by June 30, 2025, primarily due to a **$173.1 million** private placement and stock-based compensation, partially offset by net losses | Metric (in thousands) | January 1, 2025 | June 30, 2025 | Change | | :-------------------- | :-------------- | :------------ | :----- | | Additional paid-in capital | **$289,351** | **$468,289** | **$178,938** | | Accumulated deficit | **$(148,586)** | **$(184,476)** | **$(35,890)**| | Total stockholders' equity | **$140,776** | **$283,766** | **$142,990** | - Issuance of common stock in connection with the private placement, net of offering costs, contributed **$173.1 million** to additional paid-in capital[22](index=22&type=chunk) [Condensed Consolidated Statements of Cash Flows for the six months ended June 30, 2025 and 2024](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows%20for%20the%20six%20months%20ended%20June%2030,%202025%20and%202024) For the six months ended June 30, 2025, the company experienced a net increase in cash and cash equivalents of **$146.1 million**, primarily driven by **$174.0 million** from financing activities, largely from a private placement, despite **$27.8 million** used in operating activities | Cash Flow Activity (in thousands) | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | Change | | :-------------------------------- | :--------------------------- | :--------------------------- | :----- | | Net cash used in operating activities | **$(27,802)** | **$(22,655)** | **$(5,147)**| | Net cash provided by investing activities | **$28** | **$0** | **$28** | | Net cash provided by financing activities | **$173,953** | **$179,070** | **$(5,117)**| | Net increase in cash and cash equivalents and restricted cash | **$146,142** | **$156,355** | **$(10,213)**| | Cash and cash equivalents and restricted cash as of end of period | **$287,968** | **$185,711** | **$102,257** | - Financing activities in H1 2025 were primarily driven by **$173.1 million** from a private placement[24](index=24&type=chunk) [Notes to Unaudited Interim Condensed Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Unaudited%20Interim%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed disclosures and explanations for the unaudited interim condensed consolidated financial statements, covering the company's business nature, significant accounting policies, fair value measurements, specific balance sheet accounts, equity incentive plans, net loss per share, license agreements, commitments, contingencies, related party transactions, segment

Company Overview - Tectonic Therapeutic, Inc. is a clinical-stage biotechnology company focused on the discovery and development of therapeutic proteins and antibodies that modulate the activity of G-protein coupled receptors (GPCRs) [4] - The company leverages its proprietary technology platform called GEODe™ (GPCRs Engineered for Optimal Discovery) to develop biologic medicines aimed at overcoming challenges in GPCR-targeted drug discovery [4] - Tectonic targets areas of significant unmet medical need, where therapeutic options are limited or nonexistent, to improve patient quality of life [4] Recent Developments - Tectonic has been added to the Russell 3000 Index following the conclusion of the 2025 Russell US Indexes annual reconstitution, effective after the open of US equity markets on June 30, 2025 [1] - Membership in the Russell 3000 Index results in automatic inclusion in either the large-cap Russell 1000® Index or small-cap Russell 2000® Index, along with the appropriate growth and value style indexes [2]

Core Insights - Tectonic Therapeutic, Inc. announced complete results from Part A of the Phase 1b clinical trial of TX45 for patients with Group 2 Pulmonary Hypertension in Heart Failure with preserved Ejection Fraction (PH-HFpEF) [1][2] - The trial demonstrated that TX45 is well tolerated and showed significant hemodynamic improvements, including a 19.0% reduction in pulmonary capillary wedge pressure (PCWP) and over 30% reduction in pulmonary vascular resistance (PVR) in a specific patient subgroup [2][11] - The results were presented at the European Society of Cardiology Heart Failure 2025 Congress, highlighting the potential of TX45 as a best-in-class therapy for a condition with high morbidity and no approved treatments [3][4] Clinical Trial Results - The Phase 1b trial included a cohort of 19 patients, confirming the tolerability and hemodynamic effects of TX45 previously reported in interim data [2][6] - TX45 treatment resulted in sustained hemodynamic effects for up to 29 days, with improvements in left ventricular function and pulmonary hemodynamics across various left ventricular ejection fractions (LVEF) [4][5] - Specific improvements included a 19.7% reduction in PCWP for patients with LVEF≥50% and an 18.4% reduction for those with LVEF 41-49% [5] Safety Profile - TX45 was well tolerated with no serious or severe adverse events reported during the trial [7][11] - There were no clinically significant changes in vital signs or safety laboratory values, indicating a favorable safety profile for TX45 [11] Mechanism of Action - TX45 is a long-acting Fc-relaxin fusion protein that activates the RXFP1 receptor, providing both pulmonary and systemic vasodilatory effects [13] - The differentiated mechanism of TX45 improves both left ventricular function and pulmonary hemodynamics, particularly beneficial for patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) [11][12] Future Outlook - The topline data from Part B of the Phase 1b study, which will evaluate TX45 in patients with Heart Failure with reduced Ejection Fraction (HFrEF), is expected in the second half of 2025 [3][9] - The ongoing APEX Phase 2 clinical trial is anticipated to provide further insights into the efficacy of TX45 in PH-HFpEF, with topline results expected in 2026 [2][9]

Summary of Tectonic Therapeutics Conference Call Company Overview - Tectonic Therapeutics is focused on the discovery and development of GPCR targeted biologics, founded in 2019 and went public via reverse merger in June 2024 [2][3] Leadership and Experience - The leadership team has led to over 20 drug approvals across various therapeutic areas, allowing for a target-agnostic approach to maximize success probability [3] Key Programs - The primary focus is on a long-acting relaxant program currently in Phase II, with promising Phase Ib data, targeting group two pulmonary hypertension associated with preserved ejection fraction left-sided heart failure (PH HFpEF) [3][4] - The program aims to address a large underserved patient population of over 1 million in the U.S. with high mortality rates and no approved therapies, representing a multibillion-dollar opportunity [5] Competitive Landscape - Competitors include AstraZeneca (AZ), which is also exploring PH HFpEF and PH HFrEF, with Tectonic recently expanding its Phase Ib study into PH HFrEF [5][21] Clinical Data and Efficacy - Phase Ib data showed significant improvements: - 18% decrease in pulmonary capillary wedge pressure, indicating improved left heart function [14] - 32-35% decrease in pulmonary vascular resistance (PVR) [15] - 18% improvement in cardiac output driven by stroke volume [15] - 26% reduction in total pulmonary resistance [15] - The drug was well tolerated with no serious adverse events reported, and the most common adverse event was transient fatigue [17] Future Milestones - Upcoming data from Phase Ib study in PH HFrEF expected later this year, with Phase II data anticipated in 2026 [6] - The design of the Phase II study includes right heart catheterization at baseline, randomization to treatment arms, and evaluation of PVR as the primary endpoint [20] Market Potential - The company has a strong financial position with over $300 million in cash, providing a runway into Q4 2028 [6] - Tectonic is positioned to deliver value-creating milestones with two pipeline candidates targeting significant market opportunities [23] Conclusion - Tectonic Therapeutics is well-capitalized and has a proven leadership team, with a focus on addressing unmet medical needs in pulmonary hypertension, supported by promising clinical data and a clear strategy for future development [23]

Group 1: Stock Performance and Price Targets - Tectonic Therapeutic, Inc. (TECX) closed at $20.71, with a 15.9% gain over the past four weeks, indicating potential upside based on Wall Street analysts' short-term price targets [1] - The mean price target of $74.25 suggests a 258.5% upside potential, with the lowest estimate at $51 (146.3% increase) and the highest at $101 (387.7% increase) [2] - The standard deviation of $20.71 indicates variability in analysts' estimates, with a smaller standard deviation suggesting greater agreement among analysts [2][9] Group 2: Analyst Insights and Earnings Estimates - Analysts show strong agreement on TECX's ability to report better earnings than previously predicted, which supports the view of potential upside [4] - A positive trend in earnings estimate revisions has a strong correlation with near-term stock price movements, indicating a legitimate reason to expect an upside [11] - The Zacks Consensus Estimate for the current year has increased by 9.8%, with one estimate moving higher and no negative revisions in the last 30 days [12] Group 3: Zacks Rank and Investment Considerations - TECX holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While the consensus price target may not be a reliable indicator of the extent of potential gains, it does provide a directional guide for price movement [13]

Financial Performance - Net loss for Q1 2025 was $15,906 thousand, a 5% increase from the net loss of $15,221 thousand in Q1 2024[108] - Cash used in operating activities was $13.1 million for the three months ended March 31, 2025, compared to $9.3 million in the same period of 2024[115] - As of March 31, 2025, the company had $306.2 million in cash and cash equivalents and an accumulated deficit of $164.5 million[114] Expenses - Research and development expenses increased by 21% from $10,818 thousand in Q1 2024 to $13,036 thousand in Q1 2025[108] - General and administrative expenses surged by 145% from $2,150 thousand in Q1 2024 to $5,262 thousand in Q1 2025[108] - Total operating expenses rose by 41% from $12,968 thousand in Q1 2024 to $18,298 thousand in Q1 2025[108] - Total research and development expenses increased by $2.2 million (21%) to $13.0 million for the three months ended March 31, 2025, compared to $10.8 million in the same period of 2024[110] - General and administrative expenses rose by $3.1 million (145%) to $5.3 million for the three months ended March 31, 2025, compared to $2.2 million in the same period of 2024[111] - The company expects to incur significant expenses and operating losses as it advances preclinical and clinical development, necessitating additional capital[113] - The company anticipates additional costs associated with operating as a public company and ongoing research and development activities[123] Revenue Generation - The company has not generated any revenue since inception and does not expect to do so in the foreseeable future[97] - The company has no approved products and has never generated revenue from product sales, relying on funding from various sources[114] Financing Activities - A private placement in February 2025 raised approximately $185.0 million by issuing 3,689,465 shares of common stock[94][95] - Net cash provided by financing activities was $178.1 million for the three months ended March 31, 2025, primarily from the sale of shares in a Private Placement[119] - Interest income increased significantly by 855%, from $256 thousand in Q1 2024 to $2,444 thousand in Q1 2025[108] - Interest income increased by $2.2 million for the three months ended March 31, 2025, primarily due to an increase in cash and cash equivalents following the Merger and Private Placement[112] Clinical Trials and Development - TX45 is currently in a Phase 1b hemodynamic clinical trial, with 19 patients dosed and preliminary data showing improvements in hemodynamics[92] - TX2100 is expected to enter a Phase 1 clinical trial in Q4 2025 or Q1 2026, pending results from IND enabling studies[93] Mergers and Acquisitions - A merger with AVROBIO was completed on June 20, 2024, enhancing the company's operational capabilities[96] Lease Obligations - Minimum lease payments due as of March 31, 2025, are $2.2 million in 2025, $0.5 million in 2026, and $0.1 million in 2027[127]