Los Angeles, September 5, 2023 — Trethera Corporation, 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 Michael Levy, MD, PhD, to its Scientific Advisory Board.  Dr. Levy will have a particular focus on evaluating the clinical development of Trethera’s lead asset, TRE-515, in demyelinating autoimmune diseases.  A demyelinating disease is any condition that causes damage to the protective covering (myelin sheath) that surrounds nerve fibers in the brain, spinal cord, and peripheral nervous system.  When the myelin sheath is damaged, nerve impulses slow or even stop, causing neurological problems.

Dr. Levy is currently an Associate Professor of Neurology at Harvard Medical School and Research Director for the Division of Neuroimmunology at Massachusetts General Hospital, where he leads a team focused on rare autoimmune diseases of the central nervous system. His efforts focus on seeking to understand the causes and to develop treatments for rare autoimmune demyelinating diseases, including optic neuritis, a condition in which inflammation of the optic nerve affects vision, and acute disseminated encephalomyelitis (ADEM), a neural inflammation that primarily impacts children. Dr. Levy will advise Trethera regarding the potential of its first-in-class compound, TRE-515, to treat optic neuritis and ADEM as well as other more common neurologic diseases such as multiple sclerosis (MS).

“We are honored to have Dr. Levy join our advisory board,” said Dr. Ken Schultz, Chairman and CEO of Trethera. “He is a leading authority on rare neurologic autoimmune diseases and has expertise in both early and late-stage clinical trials. His knowledge is especially well suited and valuable given that TRE-515 has achieved FDA Orphan Drug Designations for both optic neuritis and ADEM.”

“I am delighted to support Trethera as it advances TRE-515 as a treatment option for patients with optic neuritis and ADEM,” said Dr. Levy. “Supporting these efforts is especially compelling given the high unmet need.  Both conditions are frequently treated with high-dose corticosteroids, which can be associated with significant side effects and incomplete symptom resolution.  With no approved therapies, and a real mortality risk in a vulnerable pediatric patient population, treating ADEM remains complex on multiple levels.”   

Dr. Levy received his Doctor of Medicine and Philosophy (MD, PhD) from Baylor College of Medicine, completing his neurology residency training at Johns Hopkins Hospital.  He also holds a Bachelor of Arts (BA) degree from the University of Pennsylvania.  He is a fellow of the American Academy of Neurology.

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 TRE-515

TRE-515 is an orally delivered, once daily, 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 enabling the rapid cell proliferation of cancer cells and aberrant activated lymphocytes, suggesting dCK as a potential therapeutic target with expected enhanced safety.

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.

Los Angeles, June 27, 2023 — Trethera Corporation, a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announced today that it was awarded a $0.6M Small Business Technology Transfer (STTR) grant from the National Institute for Allergy and Infectious Diseases (NIAID).  The grant will fund Investigational New Drug (IND) enabling activities using TRE-515 to treat systemic lupus erythematosus (SLE), a chronic autoimmune disease with significant morbidity and mortality. Trethera’s lead asset, TRE-515, is a first-in-class deoxycytidine kinase (dCK) inhibitor.

“The potential TRE-515 has to treat a broad spectrum of diseases creates a pipeline in a product that reduces overall development risk,” said Dr. Ken Schultz, principal investigator and Trethera CEO. “We are grateful that the NIH also recognizes this, providing $4.2M in overall grant funding since September for optic neuritis, solid tumors, and now lupus.  We look forward to using these grants to continue working with our UCLA research partners on this first-in-class drug.”  

The NIAID grant follows favorable results announced earlier this year from Trethera’s Phase 1 clinical trial in high risk, heavily pretreated patients with solid tumors. In the all comers designed (i.e., unselected) dose escalation trial for TRE-515, the once daily capsule demonstrated a superb safety profile, wide therapeutic window, biomarkers of target engagement, and early evidence of clinical benefit.

Trethera Scientific Advisory board member, UCLA Associate Professor and co-investigator, Dr. Peter Clark commented, “With this funding, we intend to further showcase the broad therapeutic promise of disrupting the nucleoside salvage pathway to treat autoimmune diseases.

This Phase I grant will serve as proof-of-concept that TRE-515 has potential as a new SLE therapy and possibly lead to advanced studies that expand into mechanistic work and additional SLE models.” A discussion summary from the panel of NIAID experts that reviewed Trethera’s proposal stated, “if successful, the proposal has high potential to impact the SLE field from a drug and biomarker perspective… dCK biomarkers could identify patients likely to respond and confirm drug-target engagement over time… commercialization potential is also high, as this treatment could have broad applicability to other autoimmune diseases.”

SLE is a disease driven by autoreactive immune cells.  SLE can affect vital organs including the kidneys, brain, and lungs, where approximately 35–50% of patients develop organ damage within 5 years of diagnosis.  Patients undergo periods of stable disease interspersed with flares that can cause irreversible organ damage. Current treatments can be effective but not curative, with response rates of less than 50% or below 6 months durability, while being associated with strong side effects.

Sources: Ann Rheum Dis.2021 Jan;80(1); Lancet.2019 8;393(10188); NatureMed.2008 14(783)

About TRE-515

TRE-515 is an orally delivered, once daily, 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 enabling the rapid cell proliferation of cancer cells and aberrant activated lymphocytes, suggesting dCK as a potential therapeutic target with expected enhanced safety.

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.

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:

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.

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.

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.