Core Insights - Tectonic Therapeutic, Inc. announced a late-breaking oral presentation at the ESC Heart Failure 2025 Congress, focusing on Phase 1b data for TX45, a long-acting relaxin therapy targeting Group 2 PH-HFpEF patients [1][2] Group 1: Company Overview - Tectonic Therapeutic is a clinical-stage biotechnology company specializing in the discovery and development of therapeutic proteins and antibodies that modulate GPCR activity [5] - The company utilizes its proprietary GEODe™ technology platform to develop biologic medicines aimed at addressing significant unmet medical needs [5] Group 2: Product Information - TX45 is an Fc-relaxin fusion protein designed to activate the RXFP1 receptor, exhibiting pharmacokinetics and biophysical properties that enhance its therapeutic potential [3] - Relaxin, the hormone targeted by TX45, functions as a pulmonary and systemic vasodilator with additional anti-fibrotic and anti-inflammatory properties [3] Group 3: Disease Focus - Tectonic is concentrating on Group 2 pulmonary hypertension, specifically PH-HFpEF, which arises from left-sided heart disease and leads to increased pulmonary artery pressure and right-sided heart failure [4] - Approximately one third to one half of the 1.4 million PH-HFpEF patients in the U.S. are affected by the more severe Combined pre- and post-capillary PH (CpcPH) [4]

PART I [Business](index=4&type=section&id=Item%201.%20Business) Tectonic Therapeutic, Inc. is a clinical-stage biotechnology company developing GPCR-targeted biologics using its GEODe™ platform, with lead asset TX45 in Phase 2 for PH-HFpEF and a pipeline including TX2100 for HHT - On June 20, 2024, the company completed a merger with AVROBIO, Inc., changing its name to Tectonic Therapeutic, Inc. and focusing on the business of Legacy Tectonic, a clinical-stage biotech developing GPCR-targeted biologics[14](index=14&type=chunk) - The company's proprietary GEODe™ technology platform is designed to overcome historical challenges in discovering and developing biologic therapeutics for GPCR targets[16](index=16&type=chunk)[18](index=18&type=chunk) Development Pipeline Summary | Program | Target/Mechanism | Indication | Development Stage | | :--- | :--- | :--- | :--- | | **TX45** | Fc-relaxin fusion (RXFP1 agonist) | Group 2 PH in HFpEF (PH-HFpEF) | Phase 2 Initiated | | **TX2100** | GPCR3 Antagonist | Hereditary Hemorrhagic Telangiectasia (HHT) | Preclinical (IND-enabling studies planned) | | **Fibrosis Program** | GPCR Modulator Bispecific | Fibrotic Diseases | Discovery | [Pipeline and Clinical Development](index=5&type=section&id=1.1%20Pipeline%20and%20Clinical%20Development) The company's pipeline features lead asset TX45 in Phase 2 for PH-HFpEF, TX2100 advancing to Phase 1 for HHT, and a discovery-stage fibrosis program, all supported by the GEODe™ platform - The lead asset, TX45, is an Fc-relaxin fusion molecule being developed for Group 2 PH in HFpEF. A Phase 2 trial (APEX) was initiated in Q4 2024, with data expected in 2026[21](index=21&type=chunk)[26](index=26&type=chunk) TX45 Phase 1b Interim Hemodynamic Data (16 of 19 patients) | Endpoint | Result | p-value | | :--- | :--- | :--- | | **Mean Δ PCWP (all participants)** | -2.9 mm Hg | <0.05 | | **Mean Δ PVR (CpcPH, PVR ≥ 3 WU)** | -1.35 Woods Units | <0.05 | | **Mean Δ Cardiac Output (all)** | +0.65 L/min | <0.05 | - The second program, TX2100, is a VHH-Fc fusion antagonist for HHT. The company plans to start IND-enabling toxicology studies in Q2 2025 and initiate a Phase 1 trial in Q4 2025 or Q1 2026[27](index=27&type=chunk)[29](index=29&type=chunk) - The GEODe™ platform has been significantly modified and improved over the last few years, enhancing its success rate in generating high-affinity, potent GPCR-targeted antibodies[19](index=19&type=chunk)[79](index=79&type=chunk) [Collaboration and Manufacturing](index=19&type=section&id=1.2%20Collaboration%20and%20Manufacturing) Tectonic relies on third-party CDMOs like WuXi Biologics for manufacturing and CROs for clinical services, underpinned by a core technology license from Harvard - The company in-licensed core technology from Harvard, paying a one-time fee and stock, with future obligations for annual maintenance fees, low single-digit royalties on net sales, and a percentage of sublicensing income[85](index=85&type=chunk)[86](index=86&type=chunk) - Tectonic does not own manufacturing facilities and relies on third-party CDMOs. A key relationship is with WuXi Biologics for the development and manufacturing of its product candidates in compliance with CGMPs[107](index=107&type=chunk)[108](index=108&type=chunk)[109](index=109&type=chunk) [Intellectual Property and Competition](index=22&type=section&id=1.3%20Intellectual%20Property%20and%20Competition) The company protects its proprietary technology and product candidates, including TX45, through patents expiring no earlier than 2041, while facing competition from major biotech and pharmaceutical firms - The patent portfolio for Fc-relaxin fusion compositions (including TX45) consists of in-licensed and owned applications with expected 20-year expiry dates not earlier than May 2041, November 2042, and May 2044 for different families[102](index=102&type=chunk) - The company faces competition from AstraZeneca, which is also developing a relaxin agonist, and from companies like Vaderis and Diagonal Therapeutics in the HHT space[111](index=111&type=chunk)[112](index=112&type=chunk) [Government Regulation](index=25&type=section&id=1.4%20Government%20Regulation) The company's products are subject to extensive FDA and international regulation, requiring multi-phase clinical trials and BLA submission for approval, with ongoing compliance and potential impacts from biosimilar pathways and drug pricing laws - To gain marketing approval in the U.S., the company must complete preclinical testing, submit an IND, conduct adequate and well-controlled clinical trials (Phases 1-3) under GCP, and submit a BLA to the FDA[117](index=117&type=chunk)[121](index=121&type=chunk) - The BPCIA creates an abbreviated approval pathway for biosimilars, but a reference product like Tectonic's, if approved, could be eligible for a 12-year period of marketing exclusivity in the U.S[150](index=150&type=chunk)[152](index=152&type=chunk) - The Inflation Reduction Act of 2022 (IRA) includes provisions for Medicare to negotiate drug prices for certain biologics after 11 years on the market and imposes rebates for price increases faster than inflation, which may impact future revenue[160](index=160&type=chunk) [Risk Factors](index=41&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including limited operating history, ongoing net losses, funding needs, uncertain clinical development, reliance on third parties, intense competition, and regulatory challenges - **Financial Risk:** The company has a history of net losses (**$58.0 million** in 2024) and will require substantial additional funding to continue operations, which may not be available on favorable terms[187](index=187&type=chunk)[190](index=190&type=chunk) - **Development Risk:** All product candidates are in early development. Clinical trials are expensive and uncertain, and may fail to demonstrate safety or efficacy, preventing regulatory approval[198](index=198&type=chunk)[202](index=202&type=chunk)[207](index=207&type=chunk) - **Reliance on Third Parties:** The company depends on third parties for manufacturing (sole-source for TX45 with WuXi Biologics), conducting clinical trials (CROs), and for licensed intellectual property (Harvard), the loss of which could harm the business[300](index=300&type=chunk)[341](index=341&type=chunk)[344](index=344&type=chunk) - **Regulatory and Commercial Risk:** The company faces a lengthy and unpredictable regulatory approval process and, if approved, must build a commercial organization and achieve market acceptance and reimbursement, which is not guaranteed[227](index=227&type=chunk)[253](index=253&type=chunk)[259](index=259&type=chunk) - **Political and Supply Chain Risk:** Reliance on a Chinese manufacturer (WuXi Biologics) exposes the company to geopolitical risks, such as the proposed BIOSECURE Act, which could disrupt the supply chain for its lead product candidate[284](index=284&type=chunk)[285](index=285&type=chunk)[343](index=343&type=chunk) [Cybersecurity](index=118&type=section&id=Item%201C.%20Cybersecurity) The company manages cybersecurity risks through its IT Department and audit committee oversight, employing threat assessment, mitigation strategies, and vendor management processes - Cybersecurity risk management is handled by the IT Department, led by the VP of IT, and is integrated into the company's overall enterprise risk management program[437](index=437&type=chunk)[440](index=440&type=chunk) - Governance is provided by the board of directors' audit committee, which oversees the cybersecurity risk management processes and receives periodic reports from the VP of IT[445](index=445&type=chunk)[449](index=449&type=chunk) - The company uses vendor management processes to manage cybersecurity risks associated with third-party providers, such as CROs and CDMOs, which may include risk assessments and contractual obligations[442](index=442&type=chunk)[443](index=443&type=chunk) PART II [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=122&type=section&id=Item%207.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) For 2024, Tectonic reported a **$58.0 million net loss**, driven by increased R&D and G&A expenses, with **$141.2 million** cash on hand, deemed sufficient for the next 12 months Results of Operations Summary (in millions) | | Year Ended Dec 31, 2024 | Year Ended Dec 31, 2023 | $ Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $41.4 | $37.0 | $4.4 | 12% | | General and administrative | $16.7 | $7.7 | $9.0 | 117% | | **Loss from operations** | **($58.0)** | **($44.6)** | **($13.4)** | **30%** | | **Net loss** | **($58.0)** | **($42.8)** | **($15.2)** | **35%** | - R&D expenses increased by **$4.4 million**, primarily due to a **$4.0 million** increase in costs for the TX2100 program, while TX45 program costs remained stable[486](index=486&type=chunk) - G&A expenses increased by **$9.0 million**, driven by a **$4.8 million** rise in professional and consulting fees for merger activities and public company support, and a **$3.9 million** increase in employee-related costs[487](index=487&type=chunk)[488](index=488&type=chunk) - As of December 31, 2024, the company had **$141.2 million** in cash and cash equivalents and an accumulated deficit of **$148.6 million**. Management believes current cash is sufficient to fund operations for at least the next 12 months[492](index=492&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=134&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity on its **$141.2 million** cash and equivalents, though a 10% rate change is not expected to be material, and inflation impact is immaterial - The primary market risk is interest rate sensitivity related to the company's **$141.2 million** in cash and cash equivalents. A 10% change in interest rates is not expected to have a material effect[517](index=517&type=chunk)[518](index=518&type=chunk) - The effects of inflation on the company's results of operations and financial condition are believed to have been immaterial[519](index=519&type=chunk) [Financial Statements and Supplementary Data](index=136&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) The consolidated financial statements for 2024 and 2023, reflecting the AVROBIO merger, show a **$58.0 million net loss** in 2024, with Deloitte & Touche LLP providing an unqualified opinion and noting critical audit matters Consolidated Balance Sheet Data (in millions) | | Dec 31, 2024 | Dec 31, 2023 | | :--- | :--- | :--- | | Cash and cash equivalents | $141.2 | $28.8 | | Total assets | $152.9 | $39.4 | | Total liabilities | $12.1 | $43.4 | | Total stockholders' equity (deficit) | $140.8 | ($84.6) | Consolidated Statement of Operations Data (in millions) | | Year Ended Dec 31, 2024 | Year Ended Dec 31, 2023 | | :--- | :--- | :--- | | Research and development | $41.4 | $37.0 | | General and administrative | $16.7 | $7.7 | | **Loss from operations** | **($58.0)** | **($44.6)** | | **Net loss** | **($58.0)** | **($42.8)** | | **Net loss per share** | **($6.83)** | **($33.76)** | - The independent auditor, Deloitte & Touche LLP, identified two critical audit matters: (1) the estimation of accrued and prepaid contract research and development expenses, and (2) the evaluation of the accounting for the merger with AVROBIO as a reverse recapitalization[562](index=562&type=chunk)[565](index=565&type=chunk) [Controls and Procedures](index=137&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2024, with no material changes reported - Management concluded that as of December 31, 2024, the company's disclosure controls and procedures were effective[523](index=523&type=chunk) - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2024, based on the COSO 2013 framework[524](index=524&type=chunk) PART III [Directors, Executive Compensation, Security Ownership, and Related Transactions](index=138&type=section&id=Items%2010-14) Information for Items 10-14, covering directors, executive compensation, security ownership, and related transactions, is incorporated by reference from the upcoming 2025 proxy statement - Information regarding Directors, Executive Officers, Corporate Governance, Executive Compensation, Security Ownership, Certain Relationships and Related Transactions, and Principal Accounting Fees and Services is incorporated by reference from the definitive proxy statement to be filed within 120 days of December 31, 2024[531](index=531&type=chunk)[533](index=533&type=chunk)[534](index=534&type=chunk)[535](index=535&type=chunk)[536](index=536&type=chunk) PART IV [Exhibits, Financial Statement Schedules](index=139&type=section&id=Item%2015.%20Exhibits,%20Financial%20Statement%20Schedules) This section lists exhibits filed with the Form 10-K, including the Merger Agreement, Subscription Agreement, equity plans, and material contracts like the Harvard license and WuXi Biologics manufacturing agreement - The exhibits include key corporate and transactional documents, such as the Merger Agreement, Subscription Agreement, and various equity and compensation plans[541](index=541&type=chunk) - Material contracts filed as exhibits include the license agreement with Harvard College and the manufacturing services agreement with WuXi Biologics[542](index=542&type=chunk)

Financial Performance - Tectonic experienced a net loss of $12.4 million for Q4 2024, compared to a net loss of $7.9 million for the same period in 2023[11]. - Net loss for Q4 2024 was $12,373,000, compared to a net loss of $7,869,000 in Q4 2023, reflecting a 57.5% increase in losses[18]. - Comprehensive loss for the year ended December 31, 2024, was $57,973,000, compared to $42,834,000 in 2023[18]. - Net loss per share for Q4 2024 was $0.84, compared to $5.01 in Q4 2023[18]. Cash and Assets - Tectonic reported cash and cash equivalents of $141.2 million as of December 31, 2024, with an additional $185.0 million raised in a private placement in February 2025, providing a cash runway into Q4 2028[6]. - Cash and cash equivalents increased significantly to $141,239,000 in 2024 from $28,769,000 in 2023[20]. - Total assets grew to $152,905,000 in 2024, up from $39,399,000 in 2023[20]. - Working capital improved to $135,247,000 in 2024, compared to a negative working capital of $(10,004,000) in 2023[20]. - Total stockholders' equity improved to $140,776,000 in 2024, compared to a deficit of $84,636,000 in 2023[20]. Expenses - Research and development expenses increased to $9.2 million for Q4 2024, up from $7.1 million in Q4 2023, primarily due to higher costs associated with clinical trials[11]. - General and administrative expenses rose to $4.8 million in Q4 2024, compared to $2.3 million in Q4 2023, driven by increased audit, legal, and professional service costs[11]. - Total operating expenses for Q4 2024 were $13,989,000, a 49.5% increase from $9,372,000 in Q4 2023[18]. - Research and development expenses rose to $9,155,000 in Q4 2024, up 29.3% from $7,081,000 in Q4 2023[18]. - Interest income for Q4 2024 was $1,735,000, a significant increase from $132,000 in Q4 2023[18]. Clinical Trials and Research - The TX45 Phase 1b trial interim analysis showed a 17.9% reduction in Pulmonary Capillary Wedge Pressure (PCWP) and over 30% reduction in Pulmonary Vascular Resistance (PVR) in patients with Group 2 Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF)[7]. - The APEX Phase 2 trial for TX45 is ongoing, with topline results expected in 2026[6]. - The first patient for the TX45 Phase 1b Part B trial was enrolled in March 2025, with results anticipated in the second half of 2025[11]. - Tectonic plans to initiate a Phase 1 clinical trial for TX2100, a GPCR-targeting biotherapeutic for Hereditary Hemorrhagic Telangiectasia (HHT), in Q4 2025 or Q1 2026[11]. - Tectonic presented positive TX45 Phase 1a results at the AHA 2024 Scientific Sessions in November 2024[7]. Events and Engagement - The company hosted a Key Opinion Leader webinar in December 2024 discussing the treatment landscape for patients with Group 2 PH-HFpEF[7].

WATERTOWN, Mass., March 20, 2025 (GLOBE NEWSWIRE) -- Tectonic Therapeutic, Inc. (NASDAQ: TECX) ("Tectonic"), 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"), today announced financial results for the fourth quarter and full year ended December 31, 2024, and provided an overview of recent business highlights. "2024 was an important year for Tectonic as we transitioned to ...

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 two investor conferences in March 2025, providing opportunities for engagement with investors [1][4] Conference Details - Tectonic will present at the TD Cowen 45 Annual Health Care Conference on March 5, 2025, at 9:50 AM EST in Boston, MA, with Alise Reicin, MD, as the presenter [2] - The company will also participate in the Leerink Partners Global Healthcare Conference on March 11, 2025, at 11:20 AM EDT in Miami, FL, featuring Daniel Lochner and Marc Schwabish, PhD, as presenters [3] - Both conferences will include live webcasts accessible on Tectonic's website, with replays available for approximately 90 days post-event [3] Company Overview - Tectonic utilizes its proprietary GEODe™ technology platform to enhance GPCR-targeted drug discovery, aiming to develop biologic medicines for significant unmet medical needs [5] - The company is headquartered in Watertown, Massachusetts, and focuses on areas where therapeutic options are limited, aiming to improve patient quality of life [5]

Core Insights - Tectonic Therapeutics (NASDAQ: TECX) announced positive interim results from its phase 1b study of Fc-fusion protein TX45 for treating patients with Group 2 pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF) [2] Company Overview - Tectonic Therapeutics is involved in developing innovative treatments for pulmonary hypertension, specifically targeting heart failure patients with preserved ejection fraction [2] Research and Analysis - The Biotech Analysis Central service provides in-depth analysis of various pharmaceutical companies, including a library of over 600 biotech investing articles and a model portfolio of more than 10 small and mid-cap stocks [2]

Core Viewpoint - Tectonic Therapeutic, Inc. has announced a private investment in public equity (PIPE) financing expected to generate approximately $185.0 million in gross proceeds [1]. Financing Details - Tectonic will issue a total of 3,689,465 shares of common stock at a price of $50.00 per share for fund investors and $54.14 per share for individual investors who are officers or directors of the company [2]. - The PIPE financing includes participation from both new and existing investors, such as Adage Capital Partners LP, Ally Bridge Group, and others [3]. Use of Proceeds - The net proceeds from the PIPE will be utilized for the clinical development of TX45 and TX2100, discovery platform development, working capital, and other general corporate purposes [5]. Company Overview - Tectonic is a biotechnology company focused on discovering and developing therapeutic proteins and antibodies that modulate G-protein coupled receptors (GPCRs) [8]. - The company leverages its proprietary technology platform, GEODe™, to develop biologic medicines aimed at addressing significant unmet medical needs [8].

Core Insights - Tectonic Therapeutic, Inc. announced positive interim data from the Phase 1b clinical trial of TX45, showing significant improvements in left ventricular function and pulmonary hemodynamics in patients with Group 2 Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF) [1][6][8] Group 1: Clinical Trial Results - TX45 achieved a 17.9% reduction in pulmonary capillary wedge pressure (PCWP) in the overall study population, which correlates with exercise capacity, morbidity, and mortality in heart failure patients [2][6][14] - In patients with combined pre- and post-capillary pulmonary hypertension (CpcPH), TX45 demonstrated over a 30% reduction in pulmonary vascular resistance (PVR), indicating a significant improvement in a more severe disease subgroup [2][9][14] - The trial enrolled 16 out of 19 patients, with 9 patients having CpcPH, and evaluated hemodynamic endpoints similar to the ongoing APEX Phase 2 clinical trial [4][10] Group 2: Safety and Tolerability - TX45 was well tolerated, with no serious or severe adverse events reported, and no significant changes in vital signs or safety laboratory values observed [5][7][9] - Transient asymptomatic decreases in blood pressure were noted within the first 24 hours post-dosing, but no clinically significant issues arose [7][9] Group 3: Future Prospects - The interim results are expected to accelerate the clinical program for TX45, with topline results from the ongoing APEX Phase 2 trial anticipated in 2026 [3][10] - The company plans to enrich the Phase 2 trial with CpcPH patients, who may benefit the most from TX45 based on the interim findings [9][12] Group 4: Product Overview - TX45 is a long-acting Fc-relaxin fusion protein that activates the RXFP1 receptor, showing potential as a therapeutic option for patients with PH-HFpEF, a condition currently lacking approved treatments [13][16] - The unique mechanism of TX45 improves both left ventricular function and pulmonary hemodynamics, differentiating it from other pulmonary arterial hypertension (PAH) drugs [8][14]

Group 1 - Tectonic Therapeutics focuses on discovering antibody therapeutics for GPCRs (G-protein coupled receptors) [1] - The company was founded in 2019 by Andrew Kruse and Timothy Springer [1] - Tectonic Therapeutics utilizes its GEODe platform to engineer biologics aimed at challenging targets [1]

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 GEODe™ technology platform 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] Upcoming Event - Alise Reicin, MD, President and Chief Executive Officer of Tectonic, will present at the Piper Sandler 36th Annual Healthcare Conference in New York from December 3-5, 2024 [1] - The presentation is scheduled for December 3rd, 2024, at 12:30 PM ET [2] - A live webcast of the presentation will be available on Tectonic's website, with a replay accessible for approximately 90 days post-conference [3]