Core Insights - Tectonic Therapeutic, Inc. announced favorable Phase 1a results for TX000045 (TX45), a long-acting Fc-relaxin fusion protein, supporting its further development for Group 2 Pulmonary Hypertension in HFpEF [1][2] - The Phase 1a trial demonstrated a favorable safety profile with no severe adverse events or immunogenicity observed [1][3] - Upcoming topline results from the ongoing clinical program include Phase 1b hemodynamic trial data expected in late Q1 or early Q2 2025, and APEX Phase 2 clinical trial data anticipated in 2026 [1][2] Phase 1a Clinical Trial Results - The Phase 1a trial assessed safety and tolerability in 55 healthy volunteers, showing TX45 was well tolerated with no drug-related severe adverse events [2][3] - The most common adverse event was transient orthostatic tachycardia, not linked to blood pressure drops [3] - No clinically meaningful changes in laboratory values, ECG intervals, or blood pressure were observed [3] Pharmacokinetic and Pharmacodynamic Findings - TX45 exhibited approximately 50% subcutaneous bioavailability and a half-life of 14-20 days [4] - Administration of TX45 resulted in increased renal plasma flow (RPF) across all doses, leading to the development of a robust exposure-response model for Phase 2 dose selection [5][6] - The exposure-response model indicated a maximum effect (Emax) of 33% on RPF, with mean dose cohort effects showing increases of up to 42% [6] APEX Phase 2 Clinical Trial Overview - The APEX Phase 2 trial aims to evaluate TX45's efficacy in a broad population of patients with Group 2 PH-HFpEF, enrolling up to 180 subjects [7] - The trial will assess changes in pulmonary vascular resistance (PVR) and six-minute walk distance as primary and secondary endpoints [7] - TX45 is expected to address physiological abnormalities in PH-HFpEF, potentially improving exercise capacity [7] About TX45 and Its Mechanism - TX45 is designed to activate the RXFP1 receptor, a target of the hormone relaxin, which has vasodilative, anti-fibrotic, and anti-inflammatory properties [8] - Relaxin is naturally expressed at low levels and is upregulated during pregnancy, facilitating increased cardiac output and reduced vascular resistance [8] Context of Group 2 Pulmonary Hypertension - Group 2 PH-HFpEF is characterized by increased pulmonary artery pressure due to left-sided heart disease, leading to severe strain on the right heart and worsening exercise capacity [9] - Currently, no medications have been approved specifically for the treatment of Group 2 PH, highlighting a significant unmet medical need [9] Company Overview - Tectonic Therapeutic focuses on developing therapeutic proteins and antibodies targeting G-protein coupled receptors (GPCRs) [10] - The company leverages its proprietary GEODe™ platform to address significant unmet medical needs in areas with limited therapeutic options [10]

Financial Performance - Cash and cash equivalents were $159.1 million as of September 30, 2024, down from $185.1 million as of June 30, 2024, providing a cash runway into mid-2027[4] - Research and development expenses increased to $14.3 million for Q3 2024, compared to $8.1 million for Q3 2023, primarily due to higher external research costs[4] - General and administrative expenses rose to $5.3 million for Q3 2024, up from $2.0 million for Q3 2023, driven by increased personnel-related costs and professional fees[4] - The net loss for Q3 2024 was $17.7 million, compared to a net loss of $10.1 million for Q3 2023[4] - Cash and cash equivalents increased to $159,095 thousand as of September 30, 2024, compared to $28,769 thousand on December 31, 2023[11] - Working capital improved to $145,278 thousand from a deficit of $(10,004) thousand[11] - Total assets rose to $168,717 thousand, up from $39,399 thousand[11] - Total stockholders' equity increased to $150,361 thousand from a deficit of $(84,636) thousand[11] Clinical Trials and Development - The first subject was dosed with TX000045 in the APEX Phase 2 clinical trial in early October 2024, with topline results expected in 2026[2] - Favorable Phase 1a topline trial results for TX45 were announced in September 2024, showing good tolerability and a favorable pharmacokinetic profile[2] - TX2100 was selected as the development candidate for the HHT program, with plans to initiate a Phase 1 clinical trial in Q4 2025 or Q1 2026[2] - The ongoing Phase 1b hemodynamic clinical trial for TX45 is enrolling ahead of plan, with topline results expected in late Q1 2025 or early Q2 2025[3] - Tectonic anticipates that its current cash will support key Phase 1b and Phase 2 readouts for TX45 and the progression of the HHT program into clinical development[4] - The APEX Phase 2 clinical trial is a 24-week placebo-controlled study designed to evaluate the safety and efficacy of TX45 in subjects with PH-HFpEF[2]

Table of Contents As filed with the Securities and Exchange Commission on July 19, 2024 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Tectonic Therapeutic, Inc. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code No.) Delaware 2836 81-0710585 (I.R.S. Employer Identification Number) 4 ...