Los Angeles, June 1, 2022 — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, 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, its first-in-class deoxycytidine kinase (“dCK”) inhibitor.
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. The study’s primary endpoints are to determine the safety and maximum tolerability of TRE-515 when administered orally once daily as a single agent. The secondary endpoints are to (i) establish a recommended Phase 2 dose, (ii) characterize the pharmacokinetics/pharmacodynamics, and (iii) evaluate preliminary antitumor activity. The protocol also includes exploratory objectives such as measuring plasma deoxycytidine (dC), the dCK substrate and a potential liquid biomarker, as well as utilizing a specialized PET probe in select cases to measure intracellular dCK as the drug target.
In the trial thus far, TRE-515 demonstrated a manageable safety and tolerability profile resulting in authorization to increase the daily dose to 240 mg for the fourth cohort. Details of the most recent safety committee review include:
Safety: TRE-515 was well tolerated across all patients (N=10). All adverse events were transient and manageable. No dose-limiting clinical or laboratory toxicities were observed in any treated patient who received daily doses of 40 mg, 80 mg, or 160 mg. One patient has had continued daily therapy for over 200 days with an acceptable safety profile.
Dose: TRE-515 displayed favorable pharmacokinetics across dose levels, with a plasma half-life supporting once daily oral dosing as well as a Tmax of less than 2 hours, reflecting rapid gastrointestinal absorption. Exposure levels were favorable relative to potency, even at the lowest dose cohort.
Antitumor Activity: 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.
Overall, these data suggest tolerability with first antitumor activity in heavily pretreated patients with high tumor burden at early phases of dose escalation consistent with potential biological activity. This supports further evaluation of TRE-515. The Phase 1a dose escalation portion remains ongoing, with exploration of additional higher doses in order to find the Maximum Tolerated Dose (MTD), reach dose expansion, and establish the Recommended Phase 2 Dose (RP2D).
Dr. Michael Shepard, Trethera Scientific Advisory Board member and Lasker laureate, commented, “These results hold importance in several ways. First, they allow us to continue the study safely to its conclusion, which indicates a positive trend toward safety and tolerability, the primary focus of this and any Phase 1a clinical trial. However, these unexpected observations of first antitumor activity indicate the therapeutic potential for TRE-515 in solid tumor patients with considerable cancer burden. We look forward to completing dose escalation and sharing first data at target dose next year.”
TRE-515 is an orally delivered therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway. A common characteristic of tumor cells in solid malignancies and pathological immune cells in autoimmune diseases is that they require elevated nucleotide levels to support abnormal and accelerated cell division. In contrast, dCK activity is not required in most healthy adult human cells. Mediated by the rate limiting enzyme, dCK, the nucleoside salvage pathway may play a pivotal role in rapid cell proliferation of cancer cells and aberrant activated lymphocytes, suggesting dCK as a potential therapeutic target.
“The rationale for use of TRE-515 in patients with difficult to treat cancers is scientifically attractive and we continue to be optimistic regarding the clinical development. The balance of our trial enrollment, whether by gender or ethnicity, adds to the possible broad applicably of TRE-515. We look forward to continuing to provide data results of these outcomes as the trial concludes,” added Dr. Ken Schultz, Trethera Chairman and CEO.
Trethera is a clinical stage privately held biopharmaceutical company dedicated to pioneering the development of novel treatments for autoimmune diseases and cancers. Founded by prominent UCLA scientists, Trethera is led by experienced management and board members. Trethera’s innovative approach to targeting nucleotide metabolism led to the development of TRE-515, an orally taken capsule twice designated by the FDA as an Orphan Drug. TRE-515 is a first-in-class clinical stage drug that inhibits deoxycytidine kinase (dCK), the rate-limiting enzyme in the nucleoside salvage pathway, one of two biosynthetic pathways that generate DNA precursors. It is believed that some forms of cancer may be preferentially dependent on the salvage pathway to support tumor growth. Certain autoimmune diseases might also respond to TRE-515 treatment. Trethera is developing TRE-515 for use as a monotherapy or in combination, to precisely target a metabolic vulnerability of cancer or autoimmune diseases that will transform outcomes for patients.
For more information, please visit us at trethera.com or e-mail Investor Relations at email@example.com.
Note on Forward-Looking Statements
All statements other than statements of historical facts included in this press release that address activities, events or developments that Trethera believes or anticipates will or may occur in the future are “forward-looking statements,” which may often, but not always, be identified by the use of such words as “may,” “might,” “will,” “will likely result,” “would,” “should,” “estimate,” “plan,” “project,” “forecast,” “intend,” “expect,” “anticipate,” “believe,” “seek,” “continue,” “target” or the negative of such terms or other similar expressions. Although Trethera has a reasonable basis for the forward-looking statements contained herein, Trethera cautions that such statements are based on current expectations about future events and are subject to risks, uncertainties and factors relating to medical and scientific research, all of which are difficult to predict and many of which are beyond Trethera’s control, that may cause actual results to differ materially from those expressed or implied by the forward-looking statements in this press release. These potential risks and uncertainties include, without limitation: the extent to which development of any novel cancer therapies or therapies for autoimmune diseases succeeds; whether Trethera would obtain the necessary regulatory approvals to commence human trials or commercialize TRE-515 or any novel therapies resulting from such research; Trethera successfully implementing its growth strategy, including that relating to its disease therapies; the effects of the global Covid-19 pandemic; changes in economic conditions; competition; and risks and uncertainties applicable to the business of Trethera. The statements in this press release speak only as of the date hereof and Trethera does not undertake any obligation to update, amend or clarify these forward-looking statements whether as a result of new information, future events or otherwise. Trethera intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.