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TX45 was well-tolerated with no observed immunogenicity, and demonstrated a favorable PK/PD relationship which was used to identify doses for the Phase 2 clinical trial Results to be presented at the American Heart Association (AHA) Scientific Sessions in November 2024 Phase 1b single dose hemodynamic proof-of-concept clinical trial in Group 2 Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF) escalated to the highest dose of TX45 (3 mg/kg) based on favorable tolerability pro at lower doses, with topline trial results expected in the second quarter of 2025 WATERTOWN, Mass., Sept. 19, 2024 (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 favorable Phase 1a topline data for its lead asset TX45, a long-acting, potentially best-in-class relaxin. TX45 is being developed for the treatment of Group 2 PH-HFpEF. “These topline Phase 1a findings for TX45 validate the preliminary data previously presented at lower doses, and we look forward to sharing the full trial results at the AHA Scientific Sessions later this year,” said Alise Reicin, M.D., President and Chief Executive Officer of Tectonic. “Furthermore, the Phase 1a data reveal the successful translation of a robust preclinical model into the clinic. This allowed us to select doses for our global Phase 2 randomized, 6-month clinical trial evaluating the effect of TX45 on PH-HFpEF patients, enriched for those with combined pre- and post-capillary PH.” The Phase 1a clinical trial is a single ascending dose study in healthy volunteers designed to assess the safety and tolerability of TX45 in addition to the pharmacokinetic (PK) and pharmacodynamic (PD) pro TX45 based upon relaxin’s known ability to increase renal plasma flow. TX45 doses of 0.3, 1 and 3 mg/kg administered intravenously (IV) and 150, 300 and 600 mg given subcutaneously (SC) were examined. The trial demonstrated that TX45 had minimal adverse events and no evidence of immune-mediated clearance. By assessing the change in renal plasma flow from baseline at several timepoints after dosing, a robust PK/PD relationship was established to identify the Phase 2 doses and dosing regimens. In a preclinical model of chronic pulmonary hypertension, trough exposures associated with maximal activity also demonstrated near peak increases in renal plasma flow. The PK/PD model created from the Phase 1a clinical data had a high concordance, when adjusted for differences in potency between species, with the PK/PD relationship observed in the preclinical studies. Tectonic has chosen dose regimens for the Phase 2 proof of concept clinical trial in patients with PH-HFpEF based upon these models. In the Phase 2 clinical trial, patients will be randomized to 300 mg SC (2ml injection) once monthly of TX45, 300 mg SC every other week of TX45, or placebo. There are an estimated 6 million patients with heart failure in the U.S., with HFpEF representing up to approximately 50% of heart failure cases. The combined Group 2 PH population with HFpEF is conservatively estimated at over 600,000, and there are no currently available commercialized treatments. Tectonic recently announced the U.S. Food and Drug Administration cleared its Investigational New Drug application for TX45. Screening for the Phase 2 APEX clinical trial has been initiated and topline results are anticipated in 2026. In addition, Tectonic has an ongoing, single dose IV, open-label clinical trial evaluating the safety, tolerability and acute hemodynamic effects of TX45 in patients with PH-HFpEF. TX45 has already been administered at doses of 0.3 mg/kg and 1 mg/kg and is now being dosed at 3 mg/kg, based upon the favorable tolerability pro lower doses. This trial is currently assessing TX45’s acute effects on pulmonary capillary wedge pressure and pulmonary vascular resistance in addition to other hemodynamic assessments by right heart catheterization. Recruitment for this clinical trial has been better than expected and topline results are expected in the second quarter of 2025. 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 G-protein coupled receptor (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. 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 due to left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (PH-HFpEF). 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 is a 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, often where therapeutic options are poor or nonexistent, as these are areas where new medicines have the potential to improve patient quality of life. Tectonic is headquartered in Watertown, Massachusetts. For more information, please visit com and follow @TectonicTx on X 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 preclinical studies and clinical trials of Tectonic’s product candidates, including the ongoing Phase 1a and Phase1b clinical trial for its lead program, TX45, in Group 2 PH-HFpEF; the initiation of the Phase 2 clinical trial of TX45 in Group 2 PH-HFpEF including clinical trial design and endpoints; the anticipated market opportunity of TX45 to address the unmet needs of patients living with PH-HFpEF. 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 under the heading “Risk Factors” in Tectonic’s quarterly report on Form 10-Q filed with the SEC on August 14, 2024, and in other 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 and follow @TectonicTx on X (formerly Twitter) and LinkedIn. Contacts: Investor: Dan Ferry LifeSci Advisors daniel@lifesciadvisors.com (617) 430-7576 Media: Lia Dangelico Deerfield Group lia.dangelico@deerfieldgroup.com (540) 303-0180 Source: Tectonic Therapeutic

▎药明康德内容团队报道 8月30日，中国国家药监局药品审评中心（CDE）官网最新公示，礼来（Eli Lilly and Company）申报的LY3540378注射液获批临床，拟开发用于治疗慢性肾脏疾病（CKD）患者。公开资料显示，LY3540378（volenrelaxin）是礼来在研的长效松弛素家族肽受体1（RXFP1）的有效激动剂，目前在国际范围内处于2期临床研究阶段。 截图来源：CDE官网 松弛素（Relaxin）是一种人类多肽激素，可以在怀孕期间调节心血管、肾脏和肺部的适应性，最初因其能够软化产道为分娩做准备而得名。随后研究已经证明了松弛素在心肾系统中的作用。研究表明，松弛素及其受体RXFP1均在肾脏中表达，松弛素已被证明在肾脏血管扩张、钠排泄和抗纤维化中发挥作用。 Volenrelaxin是一种半衰期延长的重组人松弛素蛋白，由人松弛素类似物和血清白蛋白VHH结构域组成，被研发用于改善肾脏灌注和心肾功能。 根据今年5月发表的一篇文献报道，一项1期研究评估了volenrelaxin单次和多次给药（SAD和MAD）后的安全性、耐受性、药代动力学和药效学。在这项健康参与者的四部分随机双盲安慰剂对照SAD和MAD研究中，SAD参与者以剂量递增的方式接受静脉注射或皮下剂量的volenrelaxin或安慰剂，MAD参与者接受volenrelaxin或安慰剂皮下注射，每周一次，持续5周。 研究结果表明，Volenrelaxin耐受性良好，安全，适合每周皮下给药。此外，该产品在重复给药后显示肾脏灌注持续改善，支持慢性肾脏疾病和慢性心力衰竭的进一步临床开发。 根据ClinicalTrials官网，礼来目前正在开展volenrelaxin治疗射血分数保留型心力衰竭（HFpEF）的2期临床研究。本次在中国获批治疗慢性肾脏疾病IND，意味着其将在中国针对这一适应症开展临床。 参考资料： [1]中国国家药监局药品审评中心官网. Retrieved Aug 31， 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]Lai San Tham,  et al. Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial, Nephrology Dialysis Transplantation, 2024;, gfae112, https://doi.org/10.1093/ndt/gfae112 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。