Tectonic Therapeutic Announces Favorable Phase 1a Safety, Tolerability and PK/PD Results for Lead Program TX45
Tectonic Therapeutic (NASDAQ: TECX) announced favorable Phase 1a topline data for its lead asset TX45, a long-acting relaxin being developed for Group 2 PH-HFpEF treatment. The trial demonstrated TX45's safety, tolerability, and favorable PK/PD profile with no observed immunogenicity. Doses of 0.3, 1, and 3 mg/kg (IV) and 150, 300, and 600 mg (SC) were tested. Based on these results, Tectonic has selected doses for its global Phase 2 randomized clinical trial.
The company also reported progress in its Phase 1b single-dose hemodynamic proof-of-concept trial, which has escalated to the highest dose of TX45 (3 mg/kg). Topline results for this trial are expected in Q2 2025. Tectonic has initiated screening for the Phase 2 APEX clinical trial, with topline results anticipated in 2026.
Tectonic Therapeutic (NASDAQ: TECX) ha annunciato dati positivi preliminari della Fase 1a per il suo principale candidato TX45, un rilassante a lunga durata d'azione in fase di sviluppo per il trattamento della PH-HFpEF di Gruppo 2. Lo studio ha dimostrato la sicurezza, la tollerabilità e il profilo PK/PD favorevole di TX45 senza alcuna immunogenicità osservata. Sono state testate dosi di 0,3, 1 e 3 mg/kg (IV) e 150, 300 e 600 mg (SC). Sulla base di questi risultati, Tectonic ha selezionato le dosi per il suo studio clinico randomizzato di Fase 2 globale.
La società ha anche riportato progressi nel suo trial di prova di concetto emodinamico a dose singola di Fase 1b, che è stato portato alla dose più alta di TX45 (3 mg/kg). I risultati preliminari di questo studio sono attesi nel secondo trimestre del 2025. Tectonic ha avviato lo screening per il trial clinico di Fase 2 APEX, con risultati preliminari attesi nel 2026.
Tectonic Therapeutic (NASDAQ: TECX) anunció datos preliminares favorables de Fase 1a para su activo principal TX45, un relajante de acción prolongada que se está desarrollando para el tratamiento de PH-HFpEF Grupo 2. El ensayo demostró la seguridad, la tolerabilidad y el perfil PK/PD favorable de TX45 sin observarse inmunogenicidad. Se probaron dosis de 0.3, 1 y 3 mg/kg (IV) y 150, 300 y 600 mg (SC). Basado en estos resultados, Tectonic ha seleccionado dosis para su ensayo clínico aleatorio global de Fase 2.
La compañía también informó avances en su ensayo de prueba de concepto hemodinámico de dosis única de Fase 1b, que ha escalado a la dosis más alta de TX45 (3 mg/kg). Se esperan resultados preliminares para este ensayo en el segundo trimestre de 2025. Tectonic ha iniciado el cribado para el ensayo clínico de Fase 2 APEX, con resultados preliminares anticipados para 2026.
테크토닉 테라퓨틱(Tectonic Therapeutic) (NASDAQ: TECX)은 주요 자산 TX45의 1상a 임상 결과가 긍정적임을 발표했습니다. TX45는 그룹 2 PH-HFpEF 치료를 위해 개발 중인 장기 작용성 릴락신입니다. 시험 결과 TX45의 안전성, 내약성 및 유리한 PK/PD 프로필이 확인되었으며 면역원성은 관찰되지 않았습니다. 0.3, 1, 3 mg/kg (IV)와 150, 300, 600 mg (SC)의 용량이 시험되었습니다. 이 결과를 바탕으로 테크토닉은 글로벌 2상 무작위 임상 시험을 위한 용량을 선택했습니다.
회사는 또한 1상b 단일 용량 혈역학적 개념 검증 임상 시험에서 진행 상황을 보고했으며, 이 시험은 TX45(3 mg/kg)의 최고 용량으로 진행되고 있습니다. 이 시험의 결과는 2025년 2분기에 발표될 예정입니다. 테크토닉은 2상 APEX 임상 시험을 위한 선별 과정을 시작했으며, 결과는 2026년으로 예상됩니다.
Tectonic Therapeutic (NASDAQ: TECX) a annoncé des données préliminaires favorables de la Phase 1a pour son actif principal TX45, un relaxin à action prolongée en développement pour le traitement de la PH-HFpEF de groupe 2. L'essai a démontré la sécurité, la tolérabilité et le profil PK/PD favorable de TX45 sans immunogénicité observée. Des doses de 0,3, 1 et 3 mg/kg (IV) et 150, 300 et 600 mg (SC) ont été testées. Sur la base de ces résultats, Tectonic a séléctionné les doses pour son essai clinique randomisé mondial de Phase 2.
L'entreprise a également rapporté des progrès dans son essai de preuve de concept hémodynamique à dose unique de Phase 1b, qui a été porté à la dose la plus élevée de TX45 (3 mg/kg). Les résultats préliminaires de cet essai sont attendus au deuxième trimestre 2025. Tectonic a lancé le dépistage pour l'essai clinique de Phase 2 APEX, avec des résultats préliminaires anticipés pour 2026.
Tectonic Therapeutic (NASDAQ: TECX) hat positive vorläufige Daten aus der Phase 1a für sein führendes Produkt TX45 angekündigt, ein langwirksames Relaxin, das zur Behandlung von PH-HFpEF der Gruppe 2 entwickelt wird. Die Studie hat die Sicherheit, Verträglichkeit und das günstige PK/PD-Profil von TX45 gezeigt, ohne dass eine Immunogenität beobachtet wurde. Dosen von 0,3, 1 und 3 mg/kg (IV) und 150, 300 und 600 mg (SC) wurden getestet. Basierend auf diesen Ergebnissen hat Tectonic Dosen für seine globale randomisierte klinische Studie der Phase 2 ausgewählt.
Das Unternehmen berichtete auch über Fortschritte bei seiner Phase 1b Einzeldosen-Hämodynamik-Konzeptstudie, die auf die höchste Dosis von TX45 (3 mg/kg) erhöht wurde. Die vorläufigen Ergebnisse dieser Studie werden im 2. Quartal 2025 erwartet. Tectonic hat das Screening für die klinische Studie der Phase 2 APEX initiiert, wobei vorläufige Ergebnisse für 2026 erwartet werden.
- TX45 demonstrated favorable safety and tolerability profile in Phase 1a trial
- No observed immunogenicity in TX45 administration
- Successful translation of preclinical model to clinical results
- Phase 1b trial progressed to highest dose (3 mg/kg) due to favorable tolerability
- Screening initiated for Phase 2 APEX clinical trial
- FDA cleared Investigational New Drug application for TX45
- Topline results for Phase 2 APEX trial not expected until 2026
- No currently available commercialized treatments for the target patient population
Insights
The Phase 1a results for TX45 are promising for Tectonic Therapeutic. The drug demonstrated favorable safety, tolerability and PK/PD profiles across multiple doses and administration routes. Notably, there was no observed immunogenicity, which is important for a long-acting biologic. The robust PK/PD relationship established will guide dosing in future trials, potentially streamlining development.
The translation of preclinical data to clinical outcomes is particularly encouraging, as it validates Tectonic's modeling approach. This could increase confidence in future preclinical-to-clinical translations for their pipeline. The advancement to a Phase 2 trial with optimized dosing based on these results suggests a strong foundation for efficacy studies in PH-HFpEF patients.
The development of TX45 for Group 2 PH-HFpEF is significant in addressing an unmet medical need. With over 600,000 estimated patients and no current commercialized treatments, a successful therapy could have substantial market potential. The choice of subcutaneous administration for the Phase 2 trial could offer a more convenient option for chronic treatment compared to IV infusion.
The ongoing hemodynamic study, now escalated to 3 mg/kg, will provide important insights into TX45's acute effects on key parameters like pulmonary capillary wedge pressure and pulmonary vascular resistance. Positive results here could strongly support TX45's mechanism of action in the target patient population. The faster-than-expected recruitment for this trial suggests high interest from both patients and clinicians, potentially facilitating future larger-scale studies.
Tectonic's progress with TX45 represents a significant milestone in their pipeline development. The positive Phase 1a results and advancement to Phase 2 de-risk the program to some extent, potentially increasing investor confidence. However, it's important to note that efficacy in the target population remains to be demonstrated.
The large addressable market of over 600,000 patients with no current approved treatments presents a substantial commercial opportunity if TX45 proves successful. The expected timelines for data readouts (Q2 2025 for the hemodynamic study and 2026 for Phase 2) provide clear catalysts for potential stock movement. Investors should monitor these closely, as positive results could significantly impact Tectonic's valuation. However, as with all early-stage biotech companies, risks remain high until efficacy is definitively proven in larger trials.
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 profile observed 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) profile of 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
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 profile at 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 www.tectonictx.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 www.tectonictx.com 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
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