TRE-515 / Trethera - LARVOL DELTA

FDA Grants Fast Track Designation for TRE-515 in Combination with KRAS G12C Inhibitors for the Treatment of Non-Small Cell Lung Cancer (GlobeNewswire) - "The FDA Fast Track decision builds on Trethera’s $2.7 million NIH grant awarded in 2025 to evaluate TRE-515 with KRASi therapies and marks the second FDA Fast Track designation, following its prior designation in metastatic castration-resistant prostate cancer."

Fast track • Non Small Cell Lung Cancer

Trethera Announces Massachusetts General Hospital Clinical Trial Collaboration to Evaluate TRE-515 in ALS Patients (GlobeNewswire) - "During the collaboration, up to six patients with advanced ALS will be enrolled in a trial conducted by MGH. The trial will evaluate the safety and tolerability of TRE-515 while tracking disease trajectory over time. In parallel, investigators will collect pharmacodynamic biomarkers reflecting TRE-515 pathway activity alongside established ALS disease biomarkers such as neurofilament light chain (NfL)...This integrated clinical and biomarker approach may help (i) inform the biological activity of TRE-515 in ALS patients, (ii) guide future patient selection, and (iii) serve as a platform for larger clinical trials."

Commercial • Amyotrophic Lateral Sclerosis

Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Genetic contexts such as BRCA2 loss and mutant p53 further heighten this vulnerability. This review synthesizes mechanistic evidence linking dCK to stress-adaptive nucleotide metabolism, summarizes progress in small-molecule dCK inhibitor development, and highlights dCK inhibitor TRE-515 as the first clinically tested agent, alongside plasma nucleoside profiling and PET imaging as translational pharmacodynamic biomarkers."

Journal • Oncology • BRCA2 • DCK • TP53

Trethera to Highlight Clinical Momentum and Indication Expansion at Biocom Global Partnering & Investor Conference (GlobeNewswire) - "Biocom selected Trethera as a featured presenter following a strong close to 2025, highlighted by the successful completion of its Phase 1 solid tumor dose escalation trial and FDA Fast Track designation for prostate cancer. A favorable safety profile has been established with evidence of target engagement and early clinical activity. These results position Trethera’s lead drug, TRE-515, to advance as a multi-indication program across both oncology and autoimmune diseases. Ongoing preclinical, clinical and translational work is expected to inform upcoming indication expansion and next stage clinical trials."

Clinical • Immunology • Prostate Cancer

Trethera Receives $2.7 Million NIH Grant, Validating the Potential of First-in-Class TRE-515 to Overcome KRAS Inhibitor Resistance in Lung Cancer (GlobeNewswire) - "The grant will fund testing TRE-515 with standard of care KRAS inhibitors (KRASi) in NSCLC mouse models to inform future clinical trials."

Financing • Preclinical • Non Small Cell Lung Cancer

Trethera Corporation…announced today that the National Institutes of Health (NIH) awarded Trethera a $1.8 million grant for preclinical studies of TRE-515 as a Crohn’s disease treatment (GlobeNewswire) - "This award follows Trethera’s prior $400,000 NIH Crohn’s research grant and builds on the encouraging findings presented at the 2025 Crohn’s & Colitis Congress. The presentation highlighted compelling preclinical data demonstrating that TRE-515 outperformed Johnson & Johnson’s market-leading drug, Stelara. TRE-515 blocked inflammatory bowel disease symptoms in mice by selectively limiting activated CD4 T-cell proliferation."

Financing • Preclinical • Crohn's disease • Inflammatory Bowel Disease

Trethera Awarded $2.3 Million NIH Grant to Study TRE-515 Combined with Radiation Therapy in Prostate Cancer Preclinical Models (GlobeNewswire) - "Because dCK is relatively conserved in the regulated cell division of healthy cells, inhibiting dCK with TRE-515 has demonstrated a favorable safety profile and clinical benefit in ongoing first-in-human trials. Based on these observations, the NIH award will expand development into additional preclinical prostate cancer models and in combination with radiation therapy."

Financing • Castration-Resistant Prostate Cancer

Trethera Awarded $3 Million NIH Grant to Advance First-In-Class Drug, TRE-515, for the Treatment of Lupus (GlobeNewswire) - "Trethera will leverage the funding to complete advanced studies, including toxicology, pharmacology, and efficacy testing, with the goal of initiating trials in lupus patients after the award conclusion."

Financing • Systemic Lupus Erythematosus

FDA Grants Fast Track Designation for TRE-515 in Combination with Radiation Therapy for the Treatment of Metastatic Castration Resistant Prostate Cancer (GlobeNewswire) - "Trethera Corporation...announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for its novel drug, TRE-515, in the treatment of prostate cancer....The designation covers the treatment of a type of advanced prostate cancer referred to as PSMA-positive mCRPC that has spread to other parts of the body (metastatic) by combining TRE-515 with Pluvicto (lutetium Lu 177 vipivotide tetraxetan), an FDA approved radiopharmaceutical....The FDA’s Fast Track decision was supported by encouraging results from Trethera’s first-in-human Phase 1 trial in cancer patients as well as a growing body of preclinical data, including findings presented at the American Association for Cancer Research annual meeting."

Evidence highlight • Fast track • Castration-Resistant Prostate Cancer • Oncology • PSMA1 • PSMA2

Trethera Secures New License, Strengthening TRE-515 Intellectual Property Portfolio and Extending Market Exclusivity to 2045 (The Manila Times) - "Trethera Corporation...today announced it entered an exclusive, worldwide licensing agreement with the University of California, Los Angeles (UCLA). The license expands Trethera's intellectual property (IP) estate for TRE-515, its lead deoxycytidine kinase (dCK) inhibitor, to include new therapeutic uses in autoimmune and inflammatory diseases....When combined with existing granted patents and filings, the new IP asset potentially secures market exclusivity for TRE-515 through at least February 2045 - supporting a long-term commercial strategy."

Commercial • Immunology • Inflammation

Trethera Treats a Late Stage, Heavily Pretreated Amyotrophic Lateral Sclerosis (ALS) Patient with TRE 515 (GlobeNewswire) - P1 | N=85 | NCT05055609 | Sponsor: Trethera | "Trethera Corporation...announced clinical results from treating a patient with ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease) with TRE-515 under the FDA Expanded Access program....In the four months leading up to the trial, the patient’s forced vital capacity—a key measure of lung function—declined from 60% to 37%, despite receiving multiple drugs and experimental stem cells to fight the disease. Over a three month dosing period with TRE-515, objective measures demonstrated disease stabilization, including forced vital capacity as well as the Revised ALS Functional Rating Scale (ALSFRS-R). The patient reported gain in body weight, improved neck tone, and increased arm strength over the three month period. Importantly, no adverse events occurred over the treatment duration and the multicenter medical review group voted unanimously to increase the TRE-515 dose and extend the trial."

P1 data • Amyotrophic Lateral Sclerosis

Trethera and UCLA Publish Data Demonstrating TRE-515 Ability to Control Immune Cell Activation That Causes Multiple Sclerosis Symptoms in Mice (GlobeNewswire) - "These results were translated into the proteolipid protein (PLP139-151) mouse models of MS where the researchers found dCK was activated during disease and pharmacological inhibition of dCK with TRE-515 led to fewer autoreactive T and B cells and less disease. Unlike many available MS therapies, TRE-515 accomplishes this without affecting the levels of other immune cell populations such as naïve T and B cells or innate immune cells. These results suggest that dCK represents a potential new target for treating patients and modulating symptoms in MS and other demyelinating diseases."

Preclinical • Multiple Sclerosis

FIRST-IN-CLASS CLINICAL STAGE DEOXYCYTIDINE KINASE INHIBITOR TRE-515 BLOCKS INFLAMMATORY BOWEL DISEASE SYMPTOMS IN AN ADOPTIVE CD4 T CELL TRANSFER MOUSE MODEL (CCCongress 2025) - "Here, TRE-515 treatment of ACT mice limited weight loss and increased the percent of naïve CD4 T cells in the mesenteric lymph nodes. Our results in a preclinical model suggest that TRE-515 may have efficacy in treating IBD."

Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology • Solid Tumor • CD4 • DCK • IL12A • IL23A

Trethera Announces Inflammatory Bowel Disease Poster Presentation at the Annual Crohn’s & Colitis Foundation Congress (GlobeNewswire) - "Trethera Corporation...will present preclinical research highlighting the use of Trethera’s deoxycytidine kinase (dCK) inhibitor, TRE-515, that suggests a functional role for nucleoside salvage and dCK in inflammatory bowel disease (IBD) mouse models."

Preclinical • Inflammatory Bowel Disease

Trethera Announces Inflammatory Bowel Disease Poster Presentation at the Annual Crohn’s & Colitis Foundation Congress (GlobeNewswire) - "Drs. Peter M. Clark, of the University of California Los Angeles, and Kenneth A. Schultz, of Trethera, will present preclinical research highlighting the use of Trethera’s deoxycytidine kinase (dCK) inhibitor, TRE-515, that suggests a functional role for nucleoside salvage and dCK in inflammatory bowel disease (IBD) mouse models. Targeting dCK with first-in-class inhibitor TRE-515 is shown to block symptoms in an IBD mouse model by specifically limiting activated CD4 T cell proliferation."

Preclinical • Inflammatory Bowel Disease

Blocking Deoxycytidine Kinase in Activated Lymphocytes Depletes Deoxycytidine Triphosphate Pools and Alters Cell Cycle Kinetics to Yield Less Disease in a Mouse Multiple Sclerosis Model. (PubMed, Immunology) - "TRE-515 decreases deoxycytidine triphosphate (dCTP) and deoxythymidine triphosphate (dTTP) pools and increases the length of time cells spend in S phase of the cell cycle without inducing a replication stress response in B cells. Our results suggest that dCK activity is required to supply needed dNTPs and to enable rapid cell division following lymphocyte activation against autoantigens in EAE mouse models."

Journal • Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor • CD4 • DCK

Open-Label, Dose-Escalation With Expansion to Assess the Safety, Tolerability, and PK of TRE-515 in Subjects With Solid Tumors (clinicaltrials.gov) - P1 | N=85 | Recruiting | Sponsor: Trethera | Trial completion date: Jul 2023 ➔ Jun 2027 | Trial primary completion date: May 2023 ➔ Dec 2026 | N=36 ➔ 85

Enrollment change • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

National Institute of Health to Fund Preclinical Development of Trethera Lead Drug, TRE-515, for Treatment of Crohn’s Disease (GlobeNewswire) - "Trethera Corporation...announced today that it was awarded a Small Business Technology Transfer (STTR) grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) division of the National Institute of Health (NIH). The award provides $400,000 to translate proof-of-principle early research findings of Trethera’s clinical stage first-in-class drug, TRE-515, as an oral therapy for Crohn’s disease."

Financing • Crohn's disease • Immunology

Trethera Receives Grant from National Institute of Allergy and Infectious Diseases for the Advancement of TRE-515 in Lupus (GlobeNewswire) - "Trethera Corporation…announced today that it was awarded a $0.6M Small Business Technology Transfer (STTR) grant from the National Institute for Allergy and Infectious Diseases (NIAID). The grant will fund Investigational New Drug (IND) enabling activities using TRE-515 to treat systemic lupus erythematosus (SLE), a chronic autoimmune disease with significant morbidity and mortality."

Financing • Immunology • Systemic Lupus Erythematosus

Trethera Receives $2 Million National Cancer Institute Grant for Advancement of Clinically Relevant Biomarkers in Phase 1 Trial (GlobeNewswire) - "Trethera Corporation...announced today that it was awarded a $2 million Small Business Innovative Research ('SBIR') grant from the National Cancer Institute ('NCI'). The grant will fund additional patient dosing studies to identify predictive biomarkers of activity and target engagement of TRE-515 in solid tumors."

Financing • Oncology • Solid Tumor

Dose Escalation Portion of Phase 1 Solid Tumors Trial Produces Favorable Results in Heavily Pretreated Solid Tumor Patients (GlobeNewswire) - P1 | N=36 | NCT05055609 | Sponsor: Trethera | "Trethera Corporation...received a unanimous recommendation from the independent safety review committee ('SRC') to continue clinical trial advancement of Trethera’s lead development asset, TRE-515...This recommendation follows favorable results from the company’s Phase 1a dose escalation clinical trial in high risk, heavily pretreated, patients with solid tumor malignancies....In the trial, TRE-515 has demonstrated a manageable safety and tolerability profile resulting in an eight-fold increase above the initial starting dose....No dose-limiting clinical or laboratory toxicities were observed in any treated patient who received daily doses of 40 mg up to 320 mg."

DSMB • P1 data • Oncology • Solid Tumor

Clinical Stage Deoxycytidine Kinase Inhibitor TRE-515 Blocks Lymphocyte Proliferation and Disease in Three Mouse Models of Multiple Sclerosis (ACTRIMS Forum 2023) - "Background: Nucleotide metabolism has been exploited for over a decade in the treatment of MS as exemplified by the success of teriflunomide and cladribine. Targeting dCK with first-in-class inhibitor TRE-515 blocks symptoms across multiple EAE mouse models by specifically limiting activated B and CD4 T cell proliferation. TRE-515 has been well tolerated in dose escalation Phase I clinical trials. TRE-515 could represent a new once a day oral treatment drug class for relapsing forms of MS with strong efficacy and predicable safety."

Preclinical • CNS Disorders • Multiple Sclerosis • Oncology • Solid Tumor • CD4 • DCK

Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis. (PubMed, Immunology) - "EAE mice treated with TRE-515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE-515 blocks activation-induced B and T cell proliferation and MOG -specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG -specific lymphocyte activation-induced proliferation."

Journal • Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • DCK

U.S. Patent Office Issues Trethera Composition of Matter Patent Covering TRE-515, Extending Market Exclusivity to Late 2041 (GlobeNewswire) - "Trethera Corporation...announces today that the United States Patent and Trademark Office (USPTO) entered a Notice of Issue for a composition of matter patent covering the polymorphic form of TRE-515. The resulting US patent extends the patent protection for TRE-515 in the United States by at least seven years through November 2041. TRE-515 is a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK) and currently in Phase 1 clinical trials."

Patent • Oncology • Solid Tumor

Trethera Receives U.S. Patent Office Notice of Allowance Covering TRE-515 Structural Claims, Extending Protections to Late 2041 (GlobeNewswire) - "Trethera Corporation...announces today that the United States Patent and Trademark Office (USPTO) issued a Notice of Allowance for a composition of matter patent covering the polymorphic form of TRE-515. The resulting US patent will extend the patent protection for TRE-515 in the United States by seven years through November 2041. TRE-515 is a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK) and currently in Phase 1 clinical trials....'The patent claims cover the unique TRE-515 chemical structure, whether used in the treatment of cancer, autoimmune, or other diseases'."

Patent • Oncology