U.S. Patent Office Issues Trethera Composition of Matter Patent Covering TRE-515, Extending Market Exclusivity to Late 2041

Los Angeles, September 20, 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 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.  

Figure 1. Co-crystal 3D structure of the drug bound to the target enzyme, dCK, at the deoxycytidine binding site.

 “We are extremely pleased with this addition to the TRE-515 patent portfolio,” said Dr. Ken Schultz, Trethera CEO and patent co-inventor. “The patent issue is significant, not only by adding more than 19 years of exclusivity from today in the world’s largest market, but also encompassing claims that cover TRE-515’s unique  chemical structure, whether used in the treatment of cancer, multiple sclerosis, or other diseases.  Succeeding in this patent application demonstrates Trethera’s strong overall commitment to protecting the innovation and commercialization of our lead asset.”   

Trethera is currently enrolling a Phase 1 dose escalation trial to evaluate TRE-515 monotherapy in patients with various solid tumors. Once a day oral doses have escalated from an initial 40mg dose to the current 320mg dose level.  As reported in June 2022 and continuing through today, TRE-515 was well tolerated by all enrolled patients with adverse events being transient and manageable.  Furthermore, 50% of the patients who completed their second staging CT scan (N=6) in the first two cohorts, meaning 40mg and 80mg dose levels, showed stable disease.  The dose escalation portion of the trial is expected to enroll the final patient before year end.

Trethera’s outside intellectual property counsel, Wilson Sonsini Goodrich & Rosati, led the  patent prosecution (USPTO number 11,446,307) and similar patent application efforts are underway globally, including the major pharmaceutical markets of Europe and Japan.  Trethera’s TRE-515 patent portfolio includes other granted US and global patents and pending applications directed to specialized methods of use for cancer and autoimmune diseases.  TRE-515 is a highly selective, potent small molecule inhibitor of the enzyme dCK in nucleotide metabolism. 

About Trethera

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, and certain autoimmune diseases, such as multiple sclerosis, 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 ir@trethera.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. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.

Trethera and UCLA Publish Data Demonstrating TRE-515 Ability to Control and Improve Multiple Sclerosis Symptoms in Mouse Models

Los Angeles, September 7, 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 the publication of new results in the peer-reviewed journal Immunology demonstrating that TRE-515 improved multiple sclerosis (MS) symptoms in mouse models. TRE-515 is a clinical stage drug being developed by Trethera that targets the enzyme deoxycytidine kinase (dCK) in the deoxyribonucleoside salvage pathway.

In a collaboration between Trethera and the Peter Clark Lab at UCLA, the authors studied dCK and TRE-515 in the MOG35-55 and MOG1-125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS using positron emission tomography (PET) molecular imaging, efficacy studies, and Cytometry by Time of Flight (CyTOF) cellular analyses. Their results demonstrated that dCK activity is necessary for the development of clinical symptoms in both EAE models of MS. Targeting dCK with TRE-515 limited disease severity when treatments were started prophylactically at disease induction or therapeutically after symptoms appear. Remarkably, therapeutic treatment with TRE-515 resulted in neurorestoration in multiple cases.

T and B cells aberrantly activated against myelin cause disease in these MS models. Pharmacological inhibition of dCK with TRE-515 was shown to selectively block the proliferation of these CD4 T and B cells. Unlike many available MS therapies, TRE-515 does this without affecting the levels of other immune cell populations such as naïve T and B cells and 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.

“Inflammation damaging the protective myelin nerve sheath causes loss of function. These data provide key validation to suggest targeting dCK with TRE-515 could have a broad role in treating T-cell and B-cell mediated demyelinating diseases such as MS, optic neuritis, and ADEM. Any drug that could improve outcomes for these patients would be game changing,” said Trethera Scientific Advisory Board member and paper co-author, Dr. Larry Steinman.  Dr. Steinman is a noted immunologist and neurologist, a professor of pediatrics at Stanford University, and a member of the National Academy of Sciences.

Figure 1: PET scans showing mouse brain before (left) and after (right) MS induction (brain encircled in a dashed white line). The salvage pathway becomes upregulated during MS disease.

Reference: Chen et al. (2022), Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis. Immunology. https://doi.org/10.1111/imm.13569.

About Trethera

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, and certain autoimmune diseases, such as multiple sclerosis, 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 ir@trethera.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. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.

Trethera Receives U.S. Patent Office Notice of Allowance Covering TRE-515 Structural Claims, Extending Protections to Late 2041

Los Angeles, August 17, 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 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.

“We are extremely pleased with this expansion of the TRE-515 patent portfolio,” said Dr. Ken Schultz, Trethera CEO and patent co-inventor. “Trethera’s ownership of this patent is another major step in the commercialization of TRE-515, providing 19 years of composition of matter patent life when our final dose escalation patient enrolls this year.  The patent claims cover the unique TRE-515 chemical structure, whether used in the treatment of cancer, autoimmune, or other diseases.”   

Trethera is currently enrolling patients in a Phase 1 dose escalation trial to evaluate TRE-515 monotherapy in patients with various solid tumors. Once a day oral doses have escalated from an initial 40mg dose to the current 240mg dose level.   Trethera reported in June 2022 that TRE-515 was well tolerated by all enrolled patients (N=10) with adverse events being transient and manageable.  Furthermore, 50% of the patients who completed their second staging CT scan (N=6) before June showed stable disease.  The dose escalation portion of the trial is expected to enroll the final patient before year end.

Trethera’s outside intellectual property counsel, Wilson Sonsini Goodrich & Rosati, led the patent prosecution. This Notice of Allowance concludes the substantive examination period of the patent application and will result in the issuance of a patent after USPTO administrative fees and processes are completed in the coming months. Similar patent application efforts are underway globally, including the major pharmaceutical markets of Europe and Japan.  Trethera’s TRE-515 patent portfolio includes other granted US and global patents and pending applications directed to specialized methods of use for cancer and autoimmune diseases. 

About Trethera

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, and certain autoimmune diseases, such as multiple sclerosis, 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 ir@trethera.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. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.

Trethera Phase 1 Solid Tumors Trial Dose Escalates To Fourth Cohort After Safety Review Committee Determines Primary Trial Endpoint Achieved

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. 

About Trethera

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 ir@trethera.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.

Trethera Scientific Founder Dr. Caius Radu To Present Research At Los Angeles Bioscience Ecosystem Summit 2022

Los Angeles, May 19, 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 a forthcoming presentation by scientific founder Dr. Caius Radu at the Los Angeles Bioscience Ecosystem Summit 2022 (“LABEST”).

Presentation Details:

Title: Development of a first-in-class/first-in-human inhibitor of deoxycytidine kinase with cancer and autoimmune disease indications
Location: Main Ballroom, Luskin Conference Center
Date: Thursday, May 26, 2022 at 10AM
Track: UCLA Professor Spotlight

Dr. Radu is a Professor in the Departments of Molecular and Medical Pharmacology and Surgery at the University of California Los Angeles (UCLA). He also serves as a Vice Chairman of the Department of Molecular and Medical Pharmacology, Co-Director of the Cancer Molecular Imaging, Nanotechnology, and Theranostics Research Program at the UCLA Jonsson Comprehensive Cancer Center, and Chairman of the Trethera Scientific Advisory Board. 

LABEST 2022 is the premier showcase for bioscience innovation in Los Angeles County and is produced by the UCLA Technology Development Group.  It is intended to promote awareness of the growing life science entrepreneurial ecosystem in Los Angeles and to foster partnerships with the biotechnology and life science industry. 

TRE-515 is an orally delivered therapeutic engineered to inhibit deoxycytidine kinase (“dCK”), the key enzyme in the nucleoside salvage pathway.  A common characteristic of solid tumors and autoimmune diseases is that they require elevated nucleotide levels to support abnormal and accelerated cell division.  In contrast, dCK activity is highly restricted in healthy adult human cells.  Mediated by the rate limiting kinase, dCK, the nucleoside salvage pathway plays a pivotal role in rapid cell proliferation of  cancer cells and aberrant activated lymphocytes, suggesting dCK as a potential therapeutic target.

About Trethera 

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.

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.

Trethera Announces Completion of $3.8 Million Seed Funding Round From Current Investors

Los Angeles, May 11, 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 the completion of a follow-on seed financing of $3.8 million from its existing investors.  Funds will be used for working capital purposes.

“This capital raise signals the continued momentum of our lead asset TRE-515, which has received Orphan Drug designation by the FDA for significant demyelinating diseases.  Part of the funding will also support our ongoing first-in-class Phase 1 solid tumors dose escalation trial, ” said Dr. Ken Schultz, Chairman and CEO of Trethera. “Equally as important, this round demonstrates the dedication of the cadre of experienced and committed investors who have continued to support this program over the long term and commitment to the company vision.”

Over the last two years, Trethera stockholders have invested in excess of $6.5 million to fund the creation of a highly attractive and differentiated approach for the treatment of cancers and autoimmune diseases by focusing on novel targets in the pathways of nucleotide metabolism.  TRE-515 is a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK) in the evaluation of patients with various solid tumor malignancies.  TRE-515 also potentially limits the autoinflammatory symptoms seen in multiple sclerosis and optic neuritis. 

About Trethera 

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.

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.

Trethera Announces Prostate Cancer Poster Presentation at the American Association for Cancer Research Annual Meeting

Los Angeles, March 22, 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, announced an upcoming poster presentation at the American Association for Cancer Research (AACR) Annual Meeting.  Dr. Caius Radu, of the University of California Los Angeles, will present preclinical research highlighting the use of the deoxycytidine kinase (dCK) inhibitor, TRE-515, to selectively inhibit the growth of prostate cancer cells in xenograft mouse models that rely on dCK for DNA synthesis and rapid malignant proliferation.  AACR is one of the largest annual meetings of cancer researchers and a key venue for presenting noteworthy oncology discoveries.  Accordingly, the first-in-class molecule TRE-515 is currently being evaluated in a Phase 1 open-label, dose escalation study in solid tumors. 

Presentation Details:

Title: Inhibiting deoxycytidine kinase significantly inhibits tumor growth in xenograft models of castration resistant prostate cancer
Authors: Caius G. Radu, MD; Kenneth A. Schultz, MD; Katharina Lückerath, PhD; H. Michael Shepard, PhD; Johannes Czernin, MD
Date: Tuesday, April 12, 2022; 9:00 AM – 12:30 PM
Abstract: 2635

TRE-515 is an orally delivered therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway.  A common characteristic of solid tumors is that they require elevated levels of nucleotides to support rapid cellular DNA replication necessary for accelerated malignant growth.  Cancer cells overexpress dCK to help maintain these elevated nucleotide levels.  In contrast, dCK activity is highly restricted in healthy adult human cells.  By targeting dCK, scientists hope to selectively and effectively deprive cancer cells of this needed nucleotide source, thereby blocking tumor growth.

About Trethera

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.

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.

Safety Review Committee Advances Trethera Phase 1 Solid Tumors Trial to Next Dose After First Patient Cohort Achieves Primary Endpoint

Los Angeles, December 9, 2021 — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announced that the first patient cohort completed their full dose cycle with no serious adverse events (SAEs) in its multi-site Phase 1 oncology trial. The safety and tolerability of TRE-515, a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK), is being evaluated in up to 36 patients with various solid tumor malignancies.

No SAEs and no drug-related treatment-emergent adverse events were observed during the administration of TRE-515 as a monotherapy treatment. The independent safety review committee (SRC) evaluated the first cohort data and unanimously supported study continuation and dose escalation. The clinical trial will now proceed to the second of five dose levels, and interim data is expected by the end of next year. “We are pleased to have the SRC endorsement for dose escalation and to reach this milestone in TRE-515 development,” said Dr. Ken Schultz, Trethera Chairman and CEO. “We are grateful to the patients and clinical sites for their participation and look forward to continued collaboration as we commence enrollment of the second cohort.”

TRE-515 is an orally delivered therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway. A common characteristic of solid tumors is that they require elevated levels of nucleotides to support rapid cellular DNA replication and accelerated malignant growth. Cancer cells overexpress dCK to help maintain these elevated nucleotide levels. In contrast, dCK activity is highly restricted in healthy adult human cells. By targeting dCK, scientists hope to selectively and effectively deprive cancer cells of this needed nucleotide source, thereby blocking tumor progression.

About Trethera

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.

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.

Trethera Announces FDA Orphan Drug Designation Granted to TRE-515 for the Treatment of Demyelinating Optic Neuritis

Los Angeles, November 12, 2021 — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Status (ODS) to TRE-515 for the treatment of optic neuritis (ON). ON is a rare autoimmune disease where patients rapidly lose vision in one or both eyes with 1 in 10 patients never fully recovering their eyesight. TRE-515 is a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK).

“The FDA designation for the treatment of ON complements our existing exclusive ODS for acute disseminated encephalomyelitis (ADEM) and provides key external validation that continues to showcase the strength of our scientific data,” said Dr. Ken Schultz, Trethera Chairman and CEO. “TRE-515 is developing an impressive resume for potential treatments of demyelinating autoimmune diseases.” ADEM is an autoimmune disease in which the immune system damages myelin in the central nervous system, leading patients to become paralyzed and causing death in some cases.

Over 100,000 cases of ON occur annually in the US and have a close association with multiple sclerosis (MS). Although steroids accelerate the rate of ON recovery and limit conversion to MS in the first two years, steroids have no effect on long-term visual outcomes or conversion to MS as measured after 5 years. “Inflammation damaging the protective myelin coating around the optic nerve causes ON, leading to pain and vision loss. Targeting dCK with TRE-515 could limit this inflammation,” said Dr. Peter Clark, member of the Trethera Scientific Advisory Board.

“For some patients, ON can be self-resolving, but for others ON can lead to lifelong disability. In all ON cases, the threat of future conversion to MS remains. Any drug that could improve these outcomes for patients would be game changing. TRE-515 could potentially significantly benefit ON patients beyond the available therapeutic options, especially those taking long-term steroids,” said Trethera Scientific Advisory Board member Dr. Larry Steinman.

The FDA’s Orphan Drug program is designed to advance the development of drugs that treat a condition affecting 200,000 or fewer US patients annually. ODS is given to medicinal products that represent a significant benefit over existing treatments and are intended for the treatment of a disease that is life-threatening or chronically debilitating. The ODS designation qualifies Trethera for certain incentives, which include FDA assistance in designing clinical trials, access to the FDA Orphan Drug Grants Program, exemption from the drug approval application fee and eligibility for seven years of marketing exclusivity.

Sources: Bennett 2019; Cleveland Clinic 2021; Yang 2017; Wilhelm 2015

About Trethera

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 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 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 cells or autoimmune diseases that will transform outcomes for patients.

For more information, please visit us at trethera.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. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.

Trethera Doses First Patient in Landmark Clinical Trial for the Treatment of Solid Tumors With First-In-Class Drug TRE-515

Los Angeles, October 15, 2021 — Trethera Corporation (“Trethera”), a biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announced that the first patient has been treated with TRE-515, a first-in-class inhibitor of deoxycytidine kinase (dCK). Trethera’s multi-site Phase 1 study will evaluate TRE-515 monotherapy in up to 36 patients with various solid tumors.

“I am thrilled to announce the world’s first clinical stage dCK inhibitor, TRE-515” said Dr. Ken Schultz, Trethera Chairman and CEO. “This study will assess the safety and tolerability of TRE-515, as well as utilize multiple biomarkers to measure target engagement, a valuable tool for predicting antitumor activity in the clinic. We look forward to sharing future updates as the clinical trial progresses.”

“The first patient dosed marks a significant milestone toward delivering on the promise and potential of an exciting new clinical treatment strategy targeting dCK,” said Dr. Michael Shepard, Lasker Laureate and member of the Trethera Scientific Advisory Board. “TRE-515 is a one-of-a-kind small molecule inhibitor that has the potential to durably treat devastating diseases such as cancer and multiple sclerosis.”

Trethera’s US-based clinical trial evaluates the safety and tolerability of TRE-515 in patients with various solid tumor malignancies. A common characteristic of solid tumors is the rapid cellular DNA replication necessary to enable accelerated malignant growth. TRE-515 is an orally delivered therapeutic engineered to inhibit dCK, the key enzyme in a nucleotide metabolism pathway shown to be overexpressed in cancer cells. By targeting dCK, scientists hope to selectively and effectively deprive cancer cells of a needed additional source of nucleotides, thereby blocking DNA replication and halting tumor progression.

“For years, Trethera has had an unwavering commitment to advancing nucleotide metabolism treatments,” said Dr. Caius Radu, co-founder and primary inventor. “With the first patient treated in this historic clinical trial, we mark a significant step in advancing the TRE-515 clinical program and move closer to our goal of developing a game-changing medicine for patients with cancer and autoimmune diseases.”

“TRE-515 is intelligently designed and on target, knocking out dCK, which could be a key to stopping the growth of certain tumors or modulating select autoimmune diseases,” said Dr. Owen Witte, co-founder and Scientific Advisory Board member. “Advancing a first-in-class drug from bench to bedside represents a remarkable scientific achievement.”

About Trethera

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 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 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 cells or autoimmune diseases that will transform outcomes for patients.

For more information, please visit us at trethera.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. The Company intends that all forward-looking statements be subject to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995.