Dose Escalation Portion of Phase 1 Solid Tumors Trial Produces Favorable Results in Heavily Pretreated Solid Tumor Patients

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Los Angeles, March 15, 2023 — Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, received a unanimous recommendation from the independent safety review committee (“SRC”) to continue clinical trial advancement of Trethera’s lead development asset, TRE-515, its first-in-class deoxycytidine kinase (“dCK”) inhibitor. 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.

The Phase 1a open-label trial enrolled 19 patients with various solid tumors in the planned five dose escalation cohorts.  The study’s primary endpoints were to determine the safety and maximum tolerability of TRE-515 when administered orally once daily as a single agent.  The secondary endpoints were to (i) establish a recommended Phase 2 dose, (ii) characterize the pharmacokinetics/pharmacodynamics, and (iii) evaluate preliminary antitumor activity.  The protocol also included exploratory objectives such as measuring biomarkers of target engagement. 

In the trial, TRE-515 has demonstrated a manageable safety and tolerability profile resulting in an eight-fold increase above the initial starting dose.  While multiple patients remain on therapy today, details of the most recent SRC and clinical data include:

Safety: Patients (N=19) tolerated TRE-515 well, with adverse events being limited, transient and manageable.  No dose-limiting clinical or laboratory toxicities were observed in any treated patient who received daily doses of 40 mg up to 320 mg.  Two patients were dosed continuously for over 200 days while another two for over 100 days with acceptable safety profiles.

Dose: TRE-515 had nearly dose proportional exposure over the 40 mg to 320 mg dose range, displaying favorable pharmacokinetics characterized by rapid absorption (Tmax less than 2 hours) and a plasma half-life of over 6 hours supporting once daily oral administration.  Exposure levels were favorable relative to potency, even at the lowest dose of 40 mg.

Antitumor Activity: A secondary endpoint of the study included signaling for biological effect. Over all dose levels studied, there were five (N=5) cases of stable disease per RECIST v1.1 criteria reported.  The majority of these patients had been heavily pretreated, meaning 5th line therapy or later, with extensive metastases. 

Biomarkers:Plasma nucleoside concentrations, the substrate for the enzyme dCK, provided compelling evidence (p value <0.0001) of target engagement.  Nucleosides potentially represent a readily accessible liquid biomarker for monitoring response during therapy, adjusting dose levels, and detecting a loss of response.

Overall, these data demonstrate that TRE-515 was well tolerated and showed signs of activity in heavily pretreated patients with high tumor burdens. Further, TRE-515 had predictable exposure and proven evidence of on-target activity. Taken together, the data support further evaluation of TRE-515.  Given the promising data, as well as the SRC unanimous recommendation, discussions with the Food and Drug Agency (“FDA”) have initiated to (i) continue dose escalation, (ii) increase the number of patients, and (iii) include new clinical sites, thereby providing the opportunity for additional patients to receive treatment.  After additional dose escalation concludes, the trial will enter dose expansion and dose range finding to further establish the Recommended Phase 2 Dose (RP2D). 

“Based on the first-in-class mechanism of action, we believe TRE-515 has breakthrough potential. We’ve seen strong trial enrollment and remain optimistic for how TRE-515 can impact the future of cancer care,” said Dr. Zev Wainberg, principal investigator of the trial and medical oncologist at the University of California Los Angeles (UCLA).   “We are especially excited that this data set included advanced biomarkers that will enable us to potentially measure drug impact and malignant progression.”

Dr. Tim Donahue, Trethera Board member and UCLA Chief of Surgical Oncology, commented, “These results establish the initial positive data set for safety and tolerability, suggesting that TRE-515 will have a wide therapeutic window, something uncommon for a cancer therapeutic. Moreover, the observations of first antitumor activity, such as those in a high-risk aggressive pancreatic cancer as 6th line therapy, indicate the therapeutic potential of TRE-515 for patients with considerable cancer burden.”

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

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 the requirement for 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 limiting the rapid cell proliferation of cancer cells and aberrant activated lymphocytes, suggesting dCK as a potential therapeutic target with expected enhanced safety.

“We are pleased to successfully complete the dose escalation period, and excited to continue the study in difficult to treat cancers, as it moves us closer to key FDA submissions which are important steps in bringing this novel, first-in-pathway therapy closer to patients,” added Dr. Ken Schultz, Trethera Chairman and CEO.  “Simultaneous with completing the current study, Trethera is optimizing the biomarker assays and manufacturing processes in preparation for Phase 2 proof-of-concept trials.”

Trethera looks forward to presenting the final data package at a future oncology conference.

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 administered 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 Announces Appointment of Laurent Dubois to Board of Directors

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Los Angeles, February 15, 2023 — 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 today the appointment of Laurent Dubois to the Trethera Board of Directors as an independent director.  A healthcare executive veteran with over two decades of experience at McKinsey & Company and GE Healthcare, Mr. Dubois also will chair the Board’s Compensation Committee. 

“We are fortunate to have someone of Laurent’s experience and expertise join our efforts to serve patients with cancer and autoimmune diseases,” said Dr. Ken Schultz, Chairman and Chief Executive Officer of Trethera. “Laurent’s background in commercial pharmaceuticals, drug branding, and hospital care delivery will be highly valued as we expand our multifaceted drug into more advanced proof-of-concept clinical trials and work to deepen our relationships with leading biopharmaceutical companies.”  

“I am pleased to join Trethera’s board as it considers the possible commercial development paths for TRE-515 at this crucial evolution stage with very promising Phase 1 dose escalation data now in hand,” said Mr. Dubois.  “There are strong indications that TRE-515 has the potential to treat a wide array of solid tumors and autoimmune diseases.  This potential and the newly issued composition of matter patent providing exclusivity in the world’s largest market until late 2041, place Trethera in an outstanding position to work towards near-term catalysts and prepare for anticipated growth.”

Mr. Dubois, 53, is the former CEO of GE Healthcare Partners, GE’s hospital solutions, consulting and advanced analytics franchise. While there, he served on the GE Healthcare Global Executive Committee and launched the GEHC Command Centers for hospital operations.  Prior to GE, Mr. Dubois was a Partner at McKinsey & Company, where he was a leader of the Pharmaceuticals and Medical Products practice, and served several of the world’s largest pharmaceutical companies. Laurent is currently the CEO of ADB Safegate, a Carlyle portfolio company and the global leader in airside guidance technology for airports.  He began his career in the oil and gas industry, with roles of increasing responsibility at Texaco and TotalEnergies.   

Mr. Dubois holds an Economics & Business Economics masters degree from the Free University of Brussels. He also served on the selection committee of the Prince Albert Fund, a program of the King Baudouin Foundation. 

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 administered 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 Announces Poster Presentation at the Americas Committee for Treatment and Research in Multiple Sclerosis Annual Meeting

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Los Angeles, January 24, 2023 — 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 an upcoming poster presentation at the 8th Annual Meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).  Dr. Peter M. Clark, of the University of California Los Angeles, will present preclinical research highlighting the use of Trethera’s deoxycytidine kinase (dCK) inhibitor, TRE-515, that suggests a functional role for deoxyribonucleoside salvage and dCK in multiple sclerosis (MS) mouse models.

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

Targeting dCK with first-in-class inhibitor TRE-515 is shown to block symptoms across multiple MS mouse models by specifically limiting activated B and CD4 T cell proliferation.  The ACTRIMS meeting is a specialized gathering of translational science experts highlighting notable, novel and rigorous scientific discoveries made in MS that advance understanding of the clinical care of MS patients.  The work presented by Dr. Clark also has application for optic neuritis, a rare neurologic disease which affects the optic nerve causing visual impairment.  TRE-515 is currently being evaluated in a Phase 1 dose escalation solid tumors study. 

Presentation Details:

  • Poster Title: Clinical Stage Deoxycytidine Kinase Inhibitor TRE-515 Blocks Lymphocyte Proliferation and Disease in Three Mouse Models of Multiple Sclerosis
  • Authors: Peter M. Clark, PhD; Kenneth A. Schultz, MD; Bao Ying Chen, PhD; Jessica R. Salas, PhD; H. Michael Shepard, PhD; Lawrence Steinman, MD
  • Abstract: 422
  • Poster Number: P138
  • Poster Session: 1
  • Date: Thursday, February 23, 2023; 6:30PM – 7:30PM
  • Location: The Marriott Marquis; San Diego, California

TRE-515 is an orally delivered first-in-class therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway.  A common characteristic of MS is the aberrant proliferation of peripheral T and B cells that mistakenly recognize and attack the myelin sheaths surrounding nerves in the central nervous system.  The abnormal clonal expansion of T and B cells during autoimmunity requires elevated levels of nucleotides – including those provided by nucleoside salvage and dCK – to support rapid cellular DNA replication necessary for accelerated division. In contrast, dCK activity is highly restricted in healthy adult human cells. 

By targeting dCK, scientists hope to selectively and effectively deprive abnormally activated immune cells of this needed nucleotide source, thereby ameliorating MS progression and blocking MS symptoms.  Likewise, cancer cells have the capability to upregulate dCK to increase the intracellular nucleotide pool providing the basic DNA precursors for rapid growth and cancer cell division. TRE-515 is twice designated an Orphan Drug by the FDA in demyelinating diseases, in both optic neuritis and acute disseminated encephalomyelitis (ADEM) and is currently being studied in a Phase 1 oncology trial.  This ACTRIMS presentation builds on the research work described earlier in the journal Immunology: 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 administered 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.

About Multiple Sclerosis

MS is an autoimmune neurologic disease that affects almost 1 million Americans.  The National Multiple Sclerosis Society estimates that the total cost of care for MS patients in the US during 2020 was $28 billion, including both direct and indirect healthcare expenses. Patients are typically diagnosed between the ages of 20 and 40 when changes of sensation, coordination, or motor strength occur.  Relapsing remitting multiple sclerosis (RRMS) is the most common form of MS and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. The majority of patients who are diagnosed with RRMS will eventually transition to secondary progressive multiple sclerosis (SPMS), in which they experience steadily worsening disability over time.

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 Announces Appointment of R. Boyd Quinnell to Board of Directors

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Los Angeles, January 18, 2023 — 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 today the appointment of Boyd Quinnell, CPA, MBA, to the Trethera Board of Directors as an independent director.  A veteran healthcare executive with over 30 years of experience in executive and financial leadership, Mr. Quinnell will also chair the Board’s Audit Committee.

“We are pleased to welcome Boyd to the Trethera Board,” said Dr. Ken Schultz, Chairman and Chief Executive Officer of Trethera.  “Boyd’s deep financial expertise in medical technology global businesses with strong regulatory oversight will be invaluable to Trethera as we continue to advance towards first product revenue.  His experience commercializing and scaling innovative technologies to improve health outcomes aligns well with our mission, making him an ideal board addition.”

“I am delighted to join the Board at this exciting time in Trethera’s growth,” said Mr. Quinnell.  “With promising Phase 1 clinical data in oncology and a strong potential to treat a wide array of autoimmune diseases, Trethera is well positioned to execute its mission and clinically advance its lead drug candidate.”

Mr. Quinnell, 61, is the former Chief Financial Officer and General Manager for the US division of Biotronik, a medical device company generating over $400M in annual revenue, where he served from 2015 through 2019.  Prior to Biotronik, Mr. Quinnell worked for 12 years at increasing levels of responsibility at the world’s largest medical device company, Medtronic, exiting as Controller and Senior Director of Finance.  He began his career as a senior consultant at KPMG, one of the Big Four accounting firms. Mr. Quinell received a Bachelor of Arts (BA) degree in business from the University of Hawaii and a Master of Business Administration (MBA) degree from Cornell University.  He holds an active certified public accountant (CPA) license.  He has served on non-profit boards for the American Heart Association and the charity Food on Foot.  Mr. Quinnell remains active in the Los Angeles community in his efforts to alleviate homelessness.

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 administered 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 $1.6 Million National Eye Institute Grant for Continued Advancement of TRE-515 Optic Neuritis Program

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Los Angeles, October 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, announced today that the National Eye Institute (NEI), a division of the National Institutes of Health (NIH), has awarded Trethera a $1.6 million Fast-Track STTR commercialization grant to further develop TRE-515 as a treatment for optic neuritis (ON).  TRE-515 is a novel first-in-class drug, which has been shown to prevent demyelination, and even facilitate remyelination, in multiple demyelinating disease mouse models.  Furthermore, the FDA has designated TRE-515 an Orphan Drug in the treatment of ON.  The grant monies and research activities will be shared in collaboration with scientists at the University of California Los Angeles (UCLA) with support from researchers at Stanford and Harvard. 

TRE-515 preclinical development activities required for an investigational new drug (IND) application as well as dose response studies in mice.  While initial TRE-515 development efforts focused on solid tumors, which has an enrolling Phase 1 clinical trial, preclinical in vivo data along with a growing body of literature supports potential application of TRE-515 in several autoimmune diseases including ON.

“We are excited and grateful for this NEI funding as it allows Trethera to build upon our promising preclinical work conducted to date. New ON treatments fulfill a critical unmet medical need and could benefit the over 100,000 patients in the US who suffer from the disease every year. The last time the FDA approved an ON therapy was over a half century ago,” commented Dr. Ken Schultz, Trethera’s CEO and grant principal investigator.  In addition to the NEI grant, Trethera has also raised over $3 million earlier this year through interim financing involving both existing and new investors. 

 “The use of animal models to evaluate safety and efficacy is essential to the responsible and successful development of novel therapies,” said Dr. Peter M. Clark, Associate Professor in charge of the UCLA-based research.  “The preclinical data generated to date in our ON program is very encouraging, and we believe that the work supported by this new grant will provide important information that will help to optimize the design of human clinical trials for ON.” 

ON is an autoimmune disease caused by inflammatory demyelination of the optic nerve, with the typical patient being a woman in her early 30s.  ON patients experience acute, unilateral, painful vision loss.  Cases of ON have a close association with multiple sclerosis (MS). Although steroids accelerate the initial recovery rate of ON, they have no effect on long-term visual outcomes or whether ON patients develop MS.  ON has been also associated with neuromyelitis optica and systemic disorders such as lupus.

“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.  TRE-515 could potentially provide significant benefit to ON patients beyond the available therapeutic options, especially those taking long-term steroids. Any drug that could improve these outcomes for patients would be game changing,” commented Trethera Scientific Advisory Board member and grant supporter, Dr. Larry Steinman.  Dr. Steinman is a noted immunologist and neurologist; a Professor of Neurology, Pediatrics, and Genetics at Stanford University; and a member of both National Academies of Sciences and Medicine.

A discussion summary from the panel of NIH experts that reviewed Trethera’s proposal stated, “Reviewers were highly enthusiastic … TRE-515 holds FDA Orphan Drug Designation for the treatment of ON, which allows for an accelerated timeline … TRE-515 treatments and dCK knockout are not associated with significant toxicities … a high chance of success, considering the preliminary proof-of-concept data and the parallel Phase 1 clinical development of the same molecule for a different indication.”

“A grant award in the Fast Track category is perhaps the most competitive at the NEI, and a mark of distinction,” stated Dr. Michael Levy, Research Director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital and Trethera grant supporter.  “As an ON treatment has not been approved by the FDA since 1952, I look forward to helping TRE-515 continue its progress to the clinic for this disease.” Dr. Levy is a distinguished  ON specialist, an Associate Professor at Harvard Medical School, and a Fellow of the American Academy of Neurology.

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 accelerated cell division and abnormal activation. Given the rate limiting role of the enzyme dCK in the nucleoside salvage pathway, it is a key target in both malignant cell proliferation and autoimmune lymphocyte activation. In contrast, dCK activity is not required in most healthy adult human cells, suggesting dCK is a highly specific 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, 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 Announces Multiple Sclerosis Treatment Poster Presentation at the American Neurological Association Annual Meeting

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Los Angeles, October 4, 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 an upcoming poster presentation at the 147th Annual Meeting of the American Neurological Association (ANA).  Dr. Peter M. Clark, of the University of California Los Angeles, will present preclinical research highlighting the use of Trethera’s deoxycytidine kinase (dCK) inhibitor, TRE-515, to selectively inhibit symptoms in experimental autoimmune encephalomyelitis (EAE) mouse models of multiple sclerosis (MS).  The ANA meeting is one of the largest annual gatherings of MS researchers and a key venue for presenting noteworthy neurology discoveries.  The work presented by Dr. Clark also has application for optic neuritis, a rare neurologic disease which affects the optic nerve causing visual impairment.  TRE-515 is currently being evaluated in a Phase 1 dose escalation solid tumors study. 

Presentation Details:

  • Poster Title: Inhibiting Deoxycytidine Kinase Significantly Improves Multiple Sclerosis Symptoms in Experimental Autoimmune Encephalomyelitis Mouse Models
  • Authors: Peter M. Clark, PhD; Kenneth A. Schultz, MD; Bao Ying Chen, PhD; H. Michael Shepard, PhD; Lawrence Steinman, MD
  • Abstract: S215
  • Date: Sunday, October 23, 2022; 5:30PM – 7:00PM
  • Location: Riverside East Center; Chicago, Illinois

TRE-515 is an orally delivered first-in-class therapeutic engineered to inhibit dCK, the key enzyme in the nucleoside salvage pathway.  A common characteristic of MS is the aberrant proliferation of peripheral T and B cells that mistakenly recognize and attack the myelin sheaths surrounding nerves in the central nervous system.  The abnormal clonal expansion of T and B cells during autoimmunity requires elevated levels of nucleotides – including those provided by nucleoside salvage and dCK – to support rapid cellular DNA replication necessary for accelerated division. In contrast, dCK activity is highly restricted in healthy adult human cells.  By targeting dCK, scientists hope to selectively and effectively deprive abnormally activated immune cells of this needed nucleotide source, thereby blocking MS symptoms.  TRE-515 is twice designated an Orphan Drug by the FDA in demyelinating diseases, in both optic neuritis and acute disseminated encephalomyelitis (ADEM).  This ANA presentation builds on the  research work described  earlier in the journal Immunology: 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.

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

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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

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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

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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

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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.