A First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study To Assess the Safety, Tolerability, Pharmacokinetics, and Food Effect of Thrv-1268 in Healthy Adult Subjects

This is a single-center, randomized, double-blind, placebo-controlled study to be conducted in 2 parts: single ascending dose (SAD) incorporating a food effect arm and multiple ascending dose (MAD). Potential participants for each part will undergo screening procedures within 28 days of enrollment.

开始日期2024-06-06

申办/合作机构

Thryv Therapeutics, Inc.初创企业

NCT05906732 / Recruiting临床1/2期

A Phase 1b/2a, 2-Part Study; Part 1: Randomized, Double-Blind, Crossover, Dose-Escalation, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SGK-1 Kinase Inhibition by LQT-1213 on Dofetilide-Induced QTc Prolongation in Healthy Adult Subjects. Part 2: Single-Blind, Multiple-Dose, Safety Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LQT-1213 in Patients Diagnosed With Type 1, 2 or 3 Long QT Syndrome

Part 1: This is a Phase 1b, randomized, double-blind, crossover, dose escalation, placebo-controlled study to evaluate the effect of oral LQT-1213 on dofetilide-induced QTc prolongation in healthy adult subjects. This is a 2-treatment, 2-period crossover study with approximately up to 28 healthy subjects, with screening procedures within 28 days of enrolment.
Part 2: This is a Phase 2a, single-blind, placebo run-in, multiple-dose safety study to evaluate the safety, tolerability, and PK of LQT-1213 in patients diagnosed with LQT1, LQT2 or LQT3. Up to 12 participants with LQT1, up to 20 participants with LQT2 and up to 12 participants with LQT3 will be recruited.

开始日期2023-03-12

申办/合作机构

Thryv Therapeutics, Inc.初创企业

NCT05759962 / Completed临床1期

A Phase 1, Randomized, Double-blinded, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluated the Safety, Tolerability, Pharmacokinetics, Food Effect, and Pharmacodynamics of LQT-1213 in Healthy Adult Participants

开始日期2022-09-14

申办/合作机构

Thryv Therapeutics, Inc.初创企业

100 项与 Thryv Therapeutics, Inc. 相关的临床结果

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0 项与 Thryv Therapeutics, Inc. 相关的专利（医药）

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项与 Thryv Therapeutics, Inc. 相关的文献（医药）

2023-05-19·Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2.

Article

作者: Wilde, Arthur A M ; Sager, Philip T ; Casini, Simona ; Remme, Carol Ann ; Louradour, Julien ; Srinivasan, Dinesh ; Giannetti, Federica ; Mura, Manuela ; Pradhananga, Sabindra ; Sala, Luca ; Nimani, Saranda ; Crotti, Lia ; Odening, Katja E ; Koren, Gideon ; Shiti, Assad ; Das, Saumya ; Brink, Paul ; Schwartz, Peter J ; Zaza, Antonio ; Barbieri, Miriam ; Zehender, Manfred ; Gepstein, Lior ; Gnecchi, Massimiliano ; Alerni, Nicolò

AIMS:

Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2.

METHODS AND RESULTS:

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM-10 µM) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 µM) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3-10 µM (by 20-32%/25-30%/44-45%). Importantly, in LQT2 rabbit CMs, 3 µM SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 µM (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 µM (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3-3 µM.

CONCLUSION:

A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS.

2023-04-01·Heart rhythm O2

SGK1 inhibition attenuated the action potential duration in patient- and genotype-specific re-engineered heart cells with congenital long QT syndrome

Article

作者: Pradhananga, Sabindra ; Das, Saumya ; Hamrick, Samantha K ; Srinivasan, Dinesh ; Kim, Maengjo ; Ackerman, Michael J ; Gao, Xiaozhi ; Sager, Philip T ; Tester, David J

Background:

Long QT syndrome (LQTS) stems from pathogenic variants in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3) and is characterized by action potential duration (APD) prolongation. Inhibition of serum and glucocorticoid regulated kinase-1 (SGK1) is proposed as a novel therapeutic for LQTS.

Objective:

The study sought to test the efficacy of novel, selective SGK1 inhibitors in induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) models of LQTS.

Methods:

The mexiletine (MEX)-sensitive SCN5A-P1332L iPSC-CMs were tested initially compared with a CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 SCN5A-P1332L variant-corrected isogenic control (IC). The SGK1-I1 therapeutic efficacy, compared with MEX, was tested for APD at 90% repolarization (APD90) shortening in SCN5A-P1332L, SCN5A-R1623Q, KCNH2-G604S, and KCNQ1-V254M iPSC-CMs using FluoVolt.

Results:

The APD90 was prolonged in SCN5A-P1332L iPSC-CMs compared with its IC (646 ± 7 ms vs 482 ± 23 ms; P < .0001). MEX shortened the APD90 to 560 ± 7 ms (52% attenuation, P < .0001). SGK1-I1 shortened the APD90 to 518 ± 5 ms (78% attenuation, P < .0001) but did not shorten the APD90 in the IC. SGK1-I1 shortened the APD90 of the SCN5A-R1623Q iPSC-CMs (753 ± 8 ms to 475 ± 19 ms compared with 558 ± 19 ms with MEX), the KCNH2-G604S iPSC-CMs (666 ± 10 ms to 574 ± 18 ms vs 538 ± 15 ms after MEX), and the KCNQ1-V254M iPSC-CMs (544 ± 10 ms to 475 ± 11ms; P = .0004).

Conclusions:

Therapeutically inhibiting SGK1 effectively shortens the APD in human iPSC-CM models of the 3 major LQTS genotypes. These preclinical data support development of SGK1 inhibitors as novel, first-in-class therapy for patients with congenital LQTS.

项与 Thryv Therapeutics, Inc. 相关的新闻（医药）

2024-11-20

·PRNewswire

Thryv Therapeutics Announces the Appointment of Esteemed Executive Leader Amy Sehnert, MD, as Chief Medical Officer

MONTREAL, Nov. 20, 2024 /PRNewswire/ - Thryv Therapeutics Inc., a clinical-stage biotechnology company pioneering novel therapies for cardiovascular diseases, is pleased to announce the appointment of Amy Sehnert, MD, as Chief Medical Officer (CMO). Dr. Sehnert will lead the clinical development and strategy for Thryv Therapeutics' expanding cardiometabolic product portfolio targeting serum glucocorticoid inducible kinase 1 (SGK1) – a kinase implicated in adverse electrical and structural remodeling of the heart. Dr. Sehnert is a pediatric cardiologist with 20 years of experience as a serial and founding medical lead at innovative biotech companies introducing precision diagnostics and therapeutics to the clinic. Dr. Sehnert joins Thryv Therapeutics from Bristol Myers Squibb (BMS), where she held leadership roles of increasing responsibility and most recently served as Vice President and Global Program Lead for cardiovascular assets transitioning from early to late development. Prior to her time at BMS, Dr. Sehnert served as Vice President, Clinical Science at MyoKardia, Inc., where she played a pivotal role in the development and approval of Camzyos® - a groundbreaking treatment for hypertrophic cardiomyopathy (HCM) - contributing to the $14 billion acquisition of MyoKardia by BMS in 2020. "I am thrilled to join Thryv Therapeutics at such an important time in the company's journey," said Dr. Sehnert. "Thryv Therapeutics' cutting-edge approach to cardiovascular diseases aligns with my passion for advancing precision medicine, and I look forward to working with the team to deliver transformative therapies to patients worldwide." Dr. Sehnert has also made notable contributions in other fields of medicine, such as maternal-fetal health, oncology, and genomics, leading early efforts in non-invasive prenatal testing (NIPT) and cell-free DNA applications now in wide clinical use. She holds a Doctor of Medicine degree from the University of Minnesota, completed Pediatrics Residency at University of Colorado, and Fellowship in Pediatric Cardiology at UCSF followed by faculty appointments at UCSF and Stanford University. In 2022 she was recognized as one of the Most Influential Women in Business by the San Francisco Business Times and among the Top 25 Healthcare Technology Leaders of San Francisco. She has co-authored over 60 peer-reviewed publications and has been involved in numerous international collaborations, making her an internationally recognized expert in her field. "On behalf of Thryv Therapeutics, I am excited to welcome Amy to the team," said Paul F. Truex, CEO of Thryv Therapeutics. "Dr. Sehnert brings a wealth of medical and clinical development knowledge in the field of cardiometabolic and genetic diseases. Her extensive experience in designing and executing late-stage clinical trials for genetic and broader cardiovascular diseases and leadership qualities will be invaluable as we enter the next phase of clinical development of our SGK1 portfolio." Dr. Philip Sager, Thryv Therapeutics' founding Chief Medical Officer, will continue to provide strategic clinical and regulatory guidance as the company's portfolio advances into later stage clinical studies. "Philip and his collaborators originally developed unique insights into the clinical potential for SGK1 in various cardiometabolic diseases and in particular, Long QT Syndrome. His tireless leadership and relentless passion for exploring these initial ideas advanced Thryv Therapeutics' portfolio to its current stage," said Paul F. Truex. "We're thankful for his continued, on-going contributions in his new role to all of our clinical programs and we are inspired by his commitment to finding treatments for these patient communities." About Thryv Therapeutics Thryv Therapeutics Inc. is a privately owned company based in Montreal, Quebec, Canada. Thryv Therapeutics is pioneering a precision medicine approach to develop potent and highly selective serum glucocorticoid inducible kinase 1 (SGK1) inhibitors to treat heart failure, atrial fibrillation, Long QT Syndrome and other cardiometabolic and cardiorenal diseases. Numerous animal models have demonstrated that activation of SGK1 leads to inappropriate electrical and structural remodeling of the heart contributing to adverse outcomes in heart failure, atrial fibrillation, and genetic channelopathies, such as Long QT Syndrome. For more information, please visit . SOURCE Thryv Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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2024-11-06

·PRNewswire

Thryv Therapeutics Announces Participation in Four Major Upcoming Investor Conferences

MONTREAL, Nov. 6, 2024 /PRNewswire/ - Thryv Therapeutics Inc., a clinical-stage biotechnology company pioneering novel therapies for cardiovascular diseases, is pleased to announce its participation in four prominent healthcare investor conferences over the coming weeks, providing critical updates on its advancements in precision medicine. Stifel Healthcare Conference 2024 Format: Presentation and one-on-one investor meetings Date: Monday, November 18, 2024, from 1:50 p.m. to 2:20 p.m. ET Location: Lotte New York Palace Hotel, New York, NY At the Stifel Healthcare Conference, Thryv Therapeutics will present key updates on its precision medicine approach, targeting novel treatments for Long QT Syndrome, heart failure and atrial fibrillation. Thryv's management team will also be available for one-on-one meetings throughout the day on Monday, November 18. To arrange a meeting, please contact [email protected]. Jefferies London Healthcare Conference 2024 Dates: November 19-21, 2024 Location: London, UK To arrange a meeting at Jefferies, please contact [email protected]. Piper Sandler 36th Annual Healthcare Conference Format: One-on-one investor meetings Dates: December 3-5, 2024 Location: New York, NY To arrange a meeting at Piper Sandler, please contact [email protected]. Wells Fargo Virtual Private Biotech Symposium Format: One-on-one investor meetings Date: December 12, 2024 To arrange a virtual meeting, please contact [email protected]. About Thryv Therapeutics Inc. Thryv Therapeutics Inc. is a privately owned company based in Montreal, Quebec, Canada. Thryv Therapeutics is pioneering a precision medicine approach to develop potent and highly selective inhibitors of serum glucocorticoid inducible kinase 1 (SGK1) to treat Long QT Syndrome, heart failure and atrial fibrillation. For more information, please visit . SOURCE Thryv Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2024-11-04

·PRNewswire

Thryv Therapeutics to Sponsor and Participate in the 2024 International SADS Foundation Family Conference in Chicago

MONTREAL, Nov. 4, 2024 /PRNewswire/ - Thryv Therapeutics Inc., a clinical-stage biotechnology company, is proud to announce its sponsorship and active participation in the 2024 International Sudden Arrhythmia Death Syndromes (SADS) Foundation Family Conference, taking place in Chicago, Illinois from November 8th to 9th, 2024. This highly anticipated event, organized in partnership with Northwestern University and Ann & Robert H. Lurie Children's Hospital, unites leading global experts in inherited arrhythmias, along with patients and families affected by conditions such as Long QT Syndrome (LQTS). The conference serves as a vital forum for sharing cutting-edge research, advancements in treatment, and personal stories from the SADS community. "We are honored to sponsor and participate in this important gathering," said Paul Truex, Chairman and CEO of Thryv Therapeutics. "Our mission is to offer meaningful solutions for patients with Long QT Syndrome, and we look forward to connecting with the SADS community, sharing our progress, and learning from the invaluable experiences of patients and families." As part of its sponsorship, Thryv Therapeutics will deliver a 10-minute presentation, followed by a Q&A session, during both the healthcare professional and family sessions. In addition, Paul Truex will participate in a live interview during the reception, engaging directly with attendees. David Hutton, a renowned advocate for Long QT Syndrome (LQTS) patients, will also be attending on behalf of Thryv. David Hutton works closely with patients and their families, sharing their stories to raise awareness and strengthen community support for those living with inherited cardiac conditions. The International SADS Foundation Family Conference offers an unparalleled opportunity for patients, caregivers, and healthcare providers to exchange insights, discuss the latest advances in treatment, and collaborate on strategies for improving patient outcomes. It fosters a supportive environment where families and medical professionals can connect and ensure that those affected by these conditions receive the care and information they need from the SADS Foundation and its experts. For more details about the conference, visit the SADS Foundation website. About SADS Foundation The Sudden Arrhythmia Death Syndromes (SADS) Foundation is committed to saving lives and providing support to families affected by genetic predispositions to sudden cardiac death caused by heart rhythm abnormalities. The Foundation supports individuals living with inherited channelopathies and cardiomyopathies, including conditions such as Long QT Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), Brugada Syndrome, Short QT Syndrome, and Arrhythmogenic Cardiomyopathy (ACM). For more information, visit the SADS Foundation website. About Thryv Therapeutics Thryv Therapeutics Inc. is a privately owned company based in Montreal, Quebec, Canada. Thryv Therapeutics is pioneering a precision medicine approach to develop potent and highly selective inhibitors of serum glucocorticoid inducible kinase 1 (SGK1) to treat Long QT Syndrome, atrial fibrillation and heart failure. For more information, please visit . SOURCE Thryv Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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