Heart Failure, Diastolic

TX45 advances into Phase 2 clinical trial for patients with Group 2 PH-HFpEF with first site activated and screening open in August 2024Received U.S. Investigational New Drug (IND) clearance for lead program, TX45 in July 2024Completed reverse merger with AVROBIO in June 2024, including concurrent private placement of $130.7 millionCash and cash equivalents were $185.1 million as of June 30, 2024, prior to the payment of accrued transaction and related expenses of approximately $14.4 million, are expected to provide cash runway into mid-2027 WATERTOWN, Mass., Aug. 14, 2024 (GLOBE NEWSWIRE) -- Tectonic Therapeutic, Inc. (NASDAQ: TECX) (“Tectonic”, or “the Company”), 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 its financial results for the second quarter ending June 30, 2024, and provided an overview of recent business highlights. “The second quarter of 2024 was transformational for Tectonic as we transitioned from a private to a public company, completed a significant concurrent capital raise, and continued to advance TX45, our novel Fc-relaxin fusion protein,” commented Alise Reicin, M.D., President and Chief Executive Officer of Tectonic. “Today, we announced the start of our global Phase 2 “APEX” clinical trial of TX45 for patients with Group 2 PH-HFpEF. Looking forward, this September, we expect to report topline results from our Phase 1a clinical trial evaluating single dose TX45 in healthy volunteers and dose the first subject in our Phase 2 clinical trial of TX45.” Recent Business Highlights TX45 Phase 2 Clinical Trial Open for Screening: This August, the Company activated the first clinical trial site for the global, 24-week Phase 2 clinical trial (named the APEX trial) evaluating TX45 administered subcutaneously in subjects with Group 2 Pulmonary Hypertension (PH) due to Heart Failure with Preserved Ejection Fraction (PH-HFpEF). PH-HFpEF is a serious condition estimated to affect over 600,000 people in the United States alone, currently with no approved therapies.U.S. IND Clearance for TX45: On July 30, 2024, the Company announced the U.S. Food and Drug Administration cleared its IND application for TX45.Closed Reverse Merger with AVROBIO and Concurrent Financing: On June 20, 2024, the Company announced the closing of its reverse merger with AVROBIO along with a concurrent private placement financing of $130.7 million.Appointed New CFO: On June 3, 2024, Tectonic appointed Dan Lochner, who has nearly 20 years of biotechnology experience, as the Company’s Chief Financial Officer. Upcoming Milestones APEX Phase 2 Clinical Trial to Dose First Subject with TX45: The Company expects to dose its first subject in its global, 24-week APEX Phase 2 clinical trial this September. The trial is a placebo-controlled study designed to evaluate the safety and efficacy of TX45 administered subcutaneously in subjects with PH-HFpEF. Topline trial results from this trial are expected in 2026.Phase 1a Clinical Trial Results: Topline results for the TX45 Phase 1a clinical trial in healthy volunteers are expected to be released this September, with detailed data to be subsequently presented at a scientific meeting.Ongoing Phase 1b Hemodynamic Clinical Trial: The TX45 Phase 1b hemodynamic clinical trial evaluating single doses of TX45 in subjects with PH-HFpEF continues to enroll as planned, with topline trial results from this trial are expected in mid-2025.Selection of Development Candidate for Second Program: The Company’s second program is evaluating Hereditary Hemorrhagic Telangiectasia (HHT), the second-most common genetic bleeding disorder, representing a potential first-in-indication opportunity. The Company plans to select a development candidate in the second half of 2024 and anticipates initiating a Phase 1 clinical trial beginning in the fourth quarter of 2025 or the first quarter of 2026. HHT is the second most common genetic bleeding disorder, and it is estimated to affect approximately 70,000-75,000 people in the United States alone, with up to 10-20% of those patients expected to have severe disease. Overview of Financial and Operating Results Cash Position: As of June 30, 2024, cash and cash equivalents were $185.1 million, compared to $18.7 million as of March 31, 2024. Tectonic anticipates that its current cash and cash equivalents as of the date hereof, will provide a cash runway into mid-2027, including through key Phase 1b and Phase 2 readouts for TX45, and the progression of the HHT program into clinical development.Research and Development Expenses: Research and development expenses were $7.1 million for the three months ended June 30, 2024, as compared to $8.8 million for the three months ended June 30, 2023. The decrease was primarily due to a reduction in Contract Manufacturing Organization (CMO) costs as a result of fewer batches of clinical trial supply produced during the three months ended June 30, 2024 compared to the three months ended June 30, 2023, due to the completed production of drug substance for the TX45 program in 2023 for planned Phase 1 and Phase 2 studies, and a reduction in preclinical Contract Research Organization (“CRO”) costs. This was partially offset by an increase in consulting and professional services fees, as well as an increase in clinical CRO costs.General and Administrative Expenses: General and administrative expenses were $4.3 million for the three months ended June 30, 2024, as compared to $1.9 million for the three months ended June 30, 2023. The increase was primarily the result of increases in professional and consulting fees to support merger-related activities as well as increases in personnel related costs.Other Expense, Net: Other expense, net was $1.3 million for the three months ended June 30, 2024, as compared to $0.2 million of other income, net for the three months ended June 30, 2023. The $1.4 million change was primarily the result of a SAFE liabilities loss of $1.5 million due to a remeasurement of the SAFE liabilities to fair value during the three months ended June 30, 2024 as compared to the three months ended June 30, 2023.Net Loss: For the three months ended June 30, 2024, the Company had a net loss of $12.7 million, compared to a net loss of $10.5 million for the three months ended June 30, 2023. About TX45, a long-acting Fc-relaxin fusion protein Tectonic’s lead program, TX000045 (TX45), is an Fc-relaxin fusion protein with optimized pharmacokinetics and biophysical properties that activates the RXFP1 receptor, the GPCR target of the hormone relaxin. Relaxin is an endogenous protein, expressed at low levels in both men and women. In normal human physiology, relaxin is upregulated during pregnancy where it exerts vasodilative effects, reduces systemic and pulmonary vascular resistance and increases cardiac output to accommodate the increased demand for oxygen and nutrients from the developing fetus. Relaxin also exerts anti-fibrotic effects on pelvic ligaments to facilitate delivery of the baby. TX45’s pharmacological profile, with an extended half-life compared with native relaxin, is a direct result of applying Tectonic’s protein engineering capabilities. It has the potential to address patients with Group 2 PH-HFpEF as the initial disease setting. Treatment with TX45 could potentially improve hemodynamics through effects on pulmonary and systemic vasodilation, cardiac diastolic dysfunction and potential remodeling in both the pulmonary vessels and the heart, which could translate into a clinically meaningful improvement in exercise capacity in these patients. The Phase 1a clinical trial of TX45 in healthy volunteers was designed as a single ascending dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (including renal blood flow) of TX45 administered intravenously (IV) (four doses ranging from 0.3 mg/kg to 10 mg/kg) and SC (three doses, 150 mg, 300 mg and 600 mg). Topline results are expected to be reported from this trial this September, followed by more detailed data at a later scientific meeting. The Phase 1b clinical trial of TX45 in patients with Group 2 PH-HFpEF is a single dose, open-label trial to evaluate safety, tolerability and acute hemodynamic effects of IV administration of TX45, with study results expected in mid-2025. The trial will evaluate the change from baseline in pulmonary vascular resistance (PVR) as determined by right heart catheterization, as well as improvement in mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), cardiac output, and systemic vascular resistance (SVR). About Group 2 Pulmonary Hypertension in HFpEF The World Health Organization has defined 5 groups of PH. Tectonic is focused on the Group 2 subtype, a condition that develops as a consequence of left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (PH-HFpEF). There are an estimated 6 million patients with heart failure in the United States, with HFpEF representing up to ~50% of heart failure cases. Tectonic estimates the combined Group 2 PH population with HFpEF at over 600,000. In patients with PH-HFpEF, chronic heart failure leads to increased blood pressure in the pulmonary arteries, exerting severe strain on the right side of the heart, which adapts poorly to the increased pressure. This increased pulmonary pressure gradually causes worsening exercise capacity, shortness of breath and right-sided heart failure which can lead to death. Although several Group 1 PH (Pulmonary Arterial Hypertension, PAH) medications have been explored in Group 2 PH, to date, no medications have been approved for its treatment. About Tectonic Tectonic Therapeutic 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). Leveraging its proprietary technology platform called GEODe™ (GPCRs Engineered for Optimal Discovery), Tectonic is focused on developing biologic medicines that overcome the existing challenges of GPCR-targeted drug discovery and harness the human body to modify the course of disease. Tectonic focuses on areas of significant unmet medical need, where therapeutic options are poor or nonexistent, and new medicines have the potential to improve patient quality of life. Tectonic is headquartered in Watertown, Massachusetts. For more information, please visit www.tectonictx.com and follow @TectonicTx on X (formerly Twitter) and LinkedIn. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements”. These statements may be identified by words such as “aims”, “anticipates”, “believes”, “could”, “estimates”, “expects”, “forecasts”, “goal”, “intends”, “may”, “plans”, “possible”, “potential”, “seeks”, “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the design, objectives, initiation, timing, progress and results of current and future clinical trials of Tectonic’s product candidate, TX45, including the ongoing Phase 1a and Phase 1b clinical trial in Group 2 PH-HFpEF; the proposed initiation of the Phase 2 clinical trial of TX45 in Group 2 PH-HFpEF including anticipated clinical trial design and study endpoints; the anticipated market opportunity of TX45 to address the unmet needs of patients living with PH-HFpEF; the Company’s plans to select a development candidate for its second program in HHT and anticipated market opportunity; and the Company’s expected cash runway. These forward-looking statements are based on Tectonic’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause Tectonic’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets, on Tectonic’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; Tectonic’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause Tectonic’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled "Risk Factors" in the final prospectus on Form 424(b)(3) filed by AVROBIO with the SEC on May 3, 2024, and in subsequent filings that Tectonic makes and will make with the SEC in the future. Tectonic expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. For more information, please visit www.tectonictx.com and follow @TectonicTx on X (formerly Twitter) and LinkedIn. Contacts: Investors: Dan Ferry LifeSci Advisors daniel@lifesciadvisors.com (617) 430-7576 Media: Karen SharmaCG Lifeksharma@cglife.com(617) 571-2733 Tectonic Therapeutic, Inc.Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except per share data) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development $7,074 $8,766 $17,892 $21,751 General and administrative 4,347 1,865 6,497 3,411 Total operating expenses 11,421 10,631 24,389 25,162 Loss from operations (11,421) (10,631) (24,389) (25,162)Other income (expense), net: Change in fair value of SAFE liabilities (1,535) — (3,610) — Interest income 318 224 574 352 Interest expense (28) (40) (59) (82)Other expense (5) (8) (408) (8)Total other (expense) income, net (1,250) 176 (3,503) 262 Net loss (12,671) (10,455) (27,892) (24,900)Net loss per share attributable to common stockholders, basic and diluted $(4.34) $(8.51) $(12.97) $(20.60)Weighted-average common shares outstanding, basic and diluted 2,919,872 1,228,778 2,150,160 1,208,447 Other comprehensive loss: Foreign currency translation adjustment (8) — (50) — Comprehensive loss $(12,679) $(10,455) $(27,942) $(24,900) Tectonic Therapeutic, Inc.Condensed Consolidated Balance Sheets(in thousands) June 30, December 31, 2024 2023 (unaudited) Cash and cash equivalents $185,124 $28,769 Working capital 161,387 (10,004)Total assets 193,910 39,399 Total stockholders’ equity (deficit) 166,367 (84,636)

Semaglutide, a medication initially developed for type 2 diabetes and obesity, significantly improves symptoms in men and women with a common type of heart failure that has had few therapeutic options. Women experienced greater weight loss and the same symptom benefits compared with men. Semaglutide, a medication initially developed for type 2 diabetes and obesity, significantly improves symptoms in men and women with a common type of heart failure that has had few therapeutic options. Women experienced greater weight loss and the same symptom benefits compared with men, according to research presented today by Dr. Subodh Verma (St. Michael's Hospital, University of Toronto) at the American Diabetes Association's 2024 Scientific Sessions and published in the Journal of the American College of Cardiology (JACC). This secondary analysis of the STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) program reveals that semaglutide provides benefits for men and women that do not track directly with weight loss, suggesting the drug may also have weight-loss independent effects on the cardiovascular system. The study (which included two trials) compared semaglutide with a placebo over 52 weeks in 1,145 participants, highlighting intriguing sex differences. The analysis sought to determine whether phenotypic features and treatment effects of semaglutide vary by sex in obesity-related heart failure (HF) with preserved ejection fraction (HFpEF). It evaluated the influence of sex on the disease's baseline characteristics and compared the effects of semaglutide versus placebo on key trial endpoints in the STEP-HFpEF program (comprised of STEP-HFpEF and STEP-HFpEF DM Trials). "Understanding the sex differences in obesity-related HFpEF is of great importance. Obesity and visceral adiposity are key drivers of HFpEF development and progression, and this may be even more amplified in women, who represent the majority of people with the disease, and bear a heavier burden of symptoms and physical limitations due to HFpEF" said Mikhail Kosiborod, MD, FACC, senior author of the study and a cardiologist at Saint Luke's Mid-America Heart Institute in Kansas City, Missouri. "Our study sheds light on these differences and the consistent benefits of semaglutide for women and men." Lead author, Dr. Subodh Verma commented that "women living with obesity and heart failure with a preserved ejection fraction were also found to have higher BMI's compared to men, and were much more symptomatic at baseline." "Females had more systemic inflammation and compared to previous HfpEF studies, females with obesity-related HfpEF were also younger," Verma said. The study analyzed the effects of semaglutide 2.4 mg administered to participants once weekly vs placebo on the STEP-HFpEF program's dual primary and confirmatory secondary, and exploratory outcomes by sex. A total of 1,145 participants with obesity-related HFpEF were evaluated over 52 weeks, of which 570 were females. Semaglutide, compared with placebo, similarly improved HF-related symptoms, physical limitations, exercise function, and reduced inflammation and natriuretic peptides regardless of sex. Semaglutide-mediated improvements in HF-related symptoms and physical limitations were consistent in both male and female participants across key subgroups including age and BMI. It also lowered their systolic blood pressure and waist circumference. However, there were sex differences in the treatment effects in terms of the reduction in body weight with semaglutide. Female participants experienced greater weight loss than males, with a mean difference of -9.6% vs -7.2%. Even though there was a significant reduction in body weight in both sexes, it was greater in females (a statistically significant interaction). At baseline, females had higher left ventricular ejection fraction, presented with worse symptoms and physical limitations, and had higher levels of inflammation at baseline, but similar rates of hypertension and diuretic use and less atrial fibrillation compared with males, despite their higher BMI. Researchers note that this may indicate that more female participants had a typical obesity phenotype of HFpEF compared with males who may also have left atrial myopathy HFpEF complicated by an increase in BMI. In an accompanying editorial, Anuradha Lala, MD, a cardiologist at the Mount Sinai School of Medicine and Director of Heart Failure Research for the NHLBI Cardiothoracic Surgery Network, said there is a need for further studies to illuminate the mechanism by which this drug provides benefits and continued attention to sex-specific differences in treatment responses.

Study to evaluate TX45 impact on cardiopulmonary hemodynamics in patients with Group 2 Pulmonary Hypertension, a patient population in urgent need of novel therapies TX45 clinical program advancing on track based on promising initial Phase 1A data; confirmatory Phase 1A data expected mid-2024 and topline Phase 1B data expected in 2025 WATERTOWN, Mass.--(BUSINESS WIRE)-- Tectonic Therapeutic, Inc. (“Tectonic”), a privately-held biotechnology company developing GPCR (G-protein coupled receptor)-targeted therapeutic proteins, co-founded by Timothy A. Springer and Andrew C. Kruse of Harvard Medical School, today announced the initiation of enrollment in the Phase 1B study for TX45, an investigational long-acting relaxin-Fc fusion molecule. The study will evaluate the safety and hemodynamic effects of single-dose TX45 in patients with Group 2 Pulmonary Hypertension secondary to Heart Failure with preserved Ejection Fraction (Group 2 PH with HFpEF). Group 2 PH with HFpEF impacts over 600,000 patients in the US and is associated with significant morbidity and mortality. Importantly, there are no approved therapies for this condition. “Our goal is to leverage relaxin’s vasodilatory, anti-fibrotic and anti-inflammatory properties to provide improved treatment outcomes for patients with Group 2 PH,” said Alise Reicin, MD, President and CEO at Tectonic. “It has long been hypothesized that the unique biology of relaxin may offer substantial therapeutic potential in the treatment of cardiovascular disease. This study will provide us with valuable TX45 pharmacology and hemodynamic data in patients.” Demonstrating a durable treatment effect with the native relaxin protein can be challenging due to its intrinsic short half-life; however, initial data from Tectonic’s ongoing Phase 1A study suggests that TX45 has the potential to overcome previous challenges and to be a best-in-class therapy. Topline results from the Phase 1A study are expected to be reported in mid-2024, followed by results from the Phase 1B study in Group 2 PH with HFpEF patients in 2025. A randomized Phase 2 study is planned to begin in H2 2024. Phase 1B study overview The Phase 1B study with TX45 in patients with Group 2 PH with HFpEF is a single dose, open-label study to evaluate safety, tolerability and acute hemodynamic effects of intravenous administration of TX45. The study will evaluate the effect of TX45 on hemodynamic parameters, as determined by right heart catheterization and echocardiography. About TX45, a long-acting Fc-relaxin fusion protein Known as a “pregnancy hormone,” relaxin is upregulated during pregnancy to help the expectant mother’s cardiovascular system meet the increased demand from the developing fetus, and to remodel tissues and musculoskeletal structures involved in childbirth. Because of these features, it offers a similarly broad range of potential therapeutic applications with significant benefits expected in cardio-pulmonary diseases. Tectonic’s TX45 Fc-relaxin fusion protein is a potential best-in-class agent, resulting from protein engineering efforts to overcome limitations associated with the natural human hormone and achieve both optimal in vitro (biophysical and developability), as well as in vivo (pharmacokinetic and pharmacodynamic, or “PK/PD”) properties. Tectonic is leveraging relaxin’s vasodilatory and anti-fibrotic properties with the goal of improving treatment outcomes for patients with Group 2 PH. About Pulmonary Hypertension and HFpEF The World Health Organization has defined 5 groups of pulmonary hypertension (PH). Tectonic is focused on the Group 2 subtype, a condition that develops as a consequence of left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (PH-HFpEF). There are an estimated 6 million patients with heart failure in the United States, with HFpEF representing up to ~50% of heart failure cases. Tectonic estimates the combined Group 2 PH population with HFpEF at over 600,000. In this condition, chronic heart failure leads to increased blood pressure in the pulmonary arteries, exerting severe strain on the right side of the heart, which adapts poorly to the increased pressure. This increased pulmonary pressure gradually causes worsening exercise capacity, shortness of breath and right-sided heart failure which can lead to death. Although several Group 1 PH (PAH) medications have been explored in Group 2 PH, no medications have yet demonstrated consistent efficacy, and to date, none have been approved for its treatment. About Tectonic Therapeutic Tectonic Therapeutic, co-founded by Andrew Kruse and Tim Springer of Harvard Medical School, is transforming the discovery of antibodies and other biologic drugs targeting GPCRs to develop novel therapies for patients inadequately served by current treatments. With its proprietary GEODe™ platform, Tectonic aims to unlock the therapeutic utility of some of the most difficult receptors in the class, where small molecule pharmacology may be intractable. In January 2024, Tectonic entered into a definitive agreement to merge with AVROBIO, Inc. (Nasdaq: AVRO). Tectonic is headquartered in Watertown, Massachusetts. Learn more at and follow us @TectonicTx. View source version on businesswire.com: Contacts Tectonic Therapeutic: Investors: Dan Ferry LifeSci Advisors daniel@lifesciadvisors.com (617) 430-7576 Media: Karen Sharma MacDougall ksharma@macdougall.bio (781) 235-3060 Source: Tectonic Therapeutic, Inc. View this news release online at: