TRE-515 / Trethera - LARVOL DELTA

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

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=36 | Recruiting | Sponsor: Trethera | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Trethera Phase 1 Solid Tumors Trial Dose Escalates To Fourth Cohort After Safety Review Committee Determines Primary Trial Endpoint Achieved (GlobeNewswire) - P1 | N=36 | NCT05055609 | Sponsor: Trethera | "Trethera Corporation...announces that an independent safety review committee has unanimously recommended further trial advancement following review of the favorable results from the company’s Phase 1a dose escalation clinical trial of TRE-515....The Phase 1a open-label trial was designed to treat up to 24 patients with various solid tumors during the dose escalation portion and is expected to enroll the final patient before the end of 2022....TRE-515 was well tolerated across all patients (N=10). All adverse events were transient and manageable....A secondary endpoint of the study includes signaling for biological activity, although the study is not powered to determine it. However, the reviewing study investigators reported that of the patients who had completed the second staging CT scan (N=6) for the first two dose cohorts (40 mg and 80 mg), 50% showed stable disease per RECIST v1.1 criteria."

DSMB • Enrollment status • P1 data • Oncology • Solid Tumor

Inhibiting deoxycytidine kinase significantly inhibits tumor growth in xenograft models of castration resistant prostate cancer (AACR 2022) - "Taking together these results support the therapeutic potential for TRE-515 to selectively inhibit cancer cells that rely on dCK for DNA synthesis and rapid malignant proliferation. As such, TRE-515 is currently being evaluated in a phase 1 open-label, dose escalation study in solid tumors (NCT #05055609)."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • 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=36; Not yet recruiting; Sponsor: Trethera

New P1 trial • Oncology • Solid Tumor

Trethera Receives FDA Approval To Initiate TRE-515 Phase 1 Clinical Trial in Solid Tumors Monotherapy - "'Receiving regulatory approval to initiate a phase 1, first-in-human clinical trial with an innovative, first-in-class oral inhibitor of deoxycytidine kinase (dCK), the key enzyme in the nucleotide salvage pathway, is a landmark clinical development. It adds another potential weapon to our therapeutic arsenal against solid tumors,' said Dr. Zev Wainberg..."

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