2023 Year End Report

As we bid farewell to 2023, it is with great enthusiasm that we share with you the accomplishments and progress that the Thryv team has achieved over the past year.

Thryv has grown to include 17 full-time employees, and we are grateful for the dedication and talent that each team member brings to our mission.

Long QT Syndrome

In the realm of Long QT Syndrome, our progress has been substantial. The completion of our Phase 1 healthy volunteer study demonstrated that LQT-1213 was well tolerated, with good bioavailability and predictable pharmacokinetics. Furthermore, the data from our WAVE I Part 1 clinical proof of efficacy study was particularly encouraging. It showed that LQT-1213 rapidly and significantly reduces the QTc interval in individuals with prolonged QTc induced by dofetilide, mimicking Long QT Syndrome Type 2. Thanks to the extraordinary efforts of our team, the WAVE I Part 2 study is underway, now focusing not only on evaluating safety, tolerability, and pharmacokinetics of LQT-1213, but providing a glimpse of efficacy in patients diagnosed with Long QT Syndrome Type 2 or Type 3. We would like to extend our appreciation to the teams at the Sudden Arrhythmia Death Syndromes Foundation (SADS), Mayo Clinic, and the University of Rochester for their pivotal roles in facilitating our efforts to provide patients with Long QT Syndrome a potential new therapeutic choice.

In addition to these clinical developments, our team has made significant contributions to the scientific community this year. We have published three influential papers related to Long QT Syndrome research. The first, titled "SGK1 Inhibition Attenuates Action Potential Duration in Reengineered Heart Cell Models of Drug-Induced QT Prolongation," and second titled “SGK1 inhibition attenuated the action potential duration in patient- and genotype-specific re-engineered heart cells with congenital long QT syndrome” were featured in the Heart Rhythm Society Journal. The first study demonstrated the efficacy of two novel SGK1 inhibitors in IPSC-CM models displaying dofetilide-induced action potential duration prolongation, and the second study sought to test the efficacy of novel, selective SGK1 inhibitors in induce pluripotent stem cell–derived cardiomyocyte (iPSC-CM) models of LQTS. Our third paper, "Gene- and Variant-Specific Efficacy of Serum/Glucocorticoid-Regulated Kinase 1 Inhibition in Long QT Syndrome Types 1 and 2," was published by the European Society of Cardiology. This study showed that SGK1 inhibition shortens action potential duration in individuals with Long QT Syndrome Types 1 and 2.

Atrial Fibrillation and Heart Failure

Our endeavors in atrial fibrillation and heart failure have been equally promising. We successfully demonstrated the preventive effect of an SGK1 inhibitor in an animal model of high-fat diet-induced atrial fibrillation and our abstract, A Novel SGK1 Inhibitor (SGK1-I), Prevents Obesity-Related Atrial Fibrillation, was selected for an oral presentation at the American Heart Association Annual Scientific Sessions. We would like to thank our collaborator, Dr. Aneesh Bapat, Cardiac Electrophysiologist at Massachusetts General Hospital and Instructor in Medicine, Harvard Medical School, who served as this study’s investigator.

In the realm of Heart Failure, to further understand the cardiometabolic benefit of SGK-1 inhibition, two new preclinical studies for heart failure with preserved ejection fraction (HFpEF) have been initiated, with data expected in early 2024.

Furthermore, the preclinical studies required for human dosing are now completed and we are gearing up for a healthy volunteer Phase 1 study early next year for our third novel SGK1 inhibitor.

Oncology

In the field of oncology, we have made impressive strides. Our research team demonstrated the efficacy of THRV-1257 in delaying and reversing resistance to standard-of-care treatment in a mouse xenograft model of anaplastic thyroid cancer. Perhaps the most significant milestone was the FDA clearance we received for an Investigational New Drug (IND) application for THRV-1257 in anaplastic thyroid cancer (ATC). This achievement paves the way for clinical studies in humans, which we anticipate commencing in 2024.

We attended the American Thyroid Cancer Annual meeting held in October and presented a poster titled "The SGK1 Inhibitor THRV-1257: Robust Tumor Regression and Overcoming Resistance to Standard of Care Dabrafenib Plus Trametinib in a Mouse Model of Anaplastic Thyroid Cancer (ATC) with BRAFV600E Mutation”. This presentation demonstrated the ability of THRV-1257 to induce significant tumor regression and successfully combat resistance when combined with the standard of care treatment, dabrafenib + trametinib. These results provide support for the clinical evaluation of THRV-1257 in patients with Anaplastic Thyroid Cancer and the BRAFV600E mutation.  THRV-1257 also promoted a significant increase in tumor growth inhibition when combined with the standard of care treatment in a mouse xenograft model of colorectal cancer, which could enable future study in this indication as well.

The Thryv team would like to express its gratitude to the International Thyroid Oncology Group (ITOG) for their continuous support in providing guidance and recommendations for our clinical development. We would like also to thank our collaborator, Dr. Antonio Di Cristofano, at the NCI-designated Montefiore Einstein Comprehensive Cancer Center, for a great year of results that should culminate in the publication of two research papers highlighting the potential of SGK1 inhibition in ATC.

Advisory Boards

In 2023, Thryv convened three advisory board meetings featuring Key Opinion Leaders (KOLs) in their respective fields. The inaugural meeting was the Commercial Advisory Board Meeting, where participants engaged in discussions regarding our strategic commercial roadmap, encompassing all three of our programs. Additionally, we reconvened our Long QT Syndrome Advisory Board and organized dedicated advisory board meetings for oncology and atrial fibrillation, where attending physicians and KOLs provided guidance on our clinical pathways for all three programs.

Thanks for a Great Year

These achievements are the result of relentless dedication, rigorous research, and unwavering commitment to improving the lives of those affected by these conditions. We want to extend our gratitude to the entire Thryv community. A special thank you goes out to our Board of Directors and our Investors for their invaluable contributions. 

As we venture into 2024, we do so with optimism and determination. The past 12 months have been a whirlwind of activity, and we are excited about what’s to come in the new year.

Wishing all our supporters, patients, and families a healthy and happy new year!

Sincerely,

Debra Odink

President & Chief Development Officer