TYME’s Oncology Research Reveals Potential New Oral Therapy TYME-19 in the Fight Against COVID-19

• TYME-19 is an oral synthetic bile acid that has demonstrated broad spectrum antiviral activity as well as efficacy against COVID-19 in preclinical studies
• Initiating proof-of-concept RESPOnD trial to investigate TYME-19 for safety and efficacy in recently diagnosed, symptomatic COVID-19 patients
• RESPOnD trial is being led in collaboration with investigators from Massachusetts General Hospital and Weill Cornell Medical Center
• Trial is targeted to begin as soon as customary clinical trial site approvals are completed
• TYME-19 is intended to be a well-tolerated therapeutic that could be used at earlier stages of COVID-19 infection and in future viral outbreaks

BEDMINSTER, N.J.–(BUSINESS WIRE)–$TYME—Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism-based therapies (CMBTs^TM), announced a potential new approach to treating COVID-19 using a metabolic agent, TYME-19. TYME-19 is a synthetic bile acid, a family of metabolic agents that the Company also uses in its anticancer product, TYME-18. Because of its expertise in metabolic therapies, the Company was able to quickly identify TYME-19 as a potent, well characterized antiviral bile acid and has performed preclinical experiments establishing effectiveness against COVID-19. Bile acids have primarily been used for liver disease; however, they represent a family of critical cellular regulators across cardiovascular, neurologic, and metabolic systems, with some also having antiviral properties.

TYME has partnered with physicians from Massachusetts General Hospital and the Weill Cornell Medical Center to design a trial for recently diagnosed, symptomatic patients. The proof-of-concept trial is expected to start as soon as customary trial site approvals are completed.

“There is an enormous unmet medical need for patients after diagnosis for a safe treatment that would alleviate their symptoms and eliminate the need for them to go to a hospital. Currently, most of therapeutic drug development is focused on hospitalized patients,” said Curtis L. Cetrulo, Jr., M. (Read more…)D. of Massachusetts General Hospital and Harvard Medical School. “We are encouraged with this new approach to fight COVID-19, especially one in a class of therapies that has a well understood safety profile and considerable research behind it. We are also hopeful that TYME-19’s potential broad antiviral properties could help us prepare for future outbreaks.”

In preclinical testing, TYME-19 repeatedly prevented COVID-19 viral replication without attributable cytotoxicity to the treated cells. Previous preclinical research has also shown select bile acids like TYME-19 have had broad antiviral activity. TYME-19 is part of a family of metabolic agents called bile acids that have formerly been associated with liver disease but are becoming recognized for their potential utility to treat multiple diseases. Bile acids are important regulators for many cellular functions throughout the central nervous, cardiovascular and metabolic systems^1,2. TYME is a leader in the development of bile acids as potential therapies for cancer, COVID-19 and other diseases.

TYME and its collaborating partners at Massachusetts General Hospital and Weill Cornell Medical Center are initiating a proof-of-concept study to evaluate TYME-19 versus placebo in newly diagnosed, symptomatic patients with defined high-risk factors. The trial will measure specific indicators of safety and efficacy, including time to resolution of symptoms, changes in viral load, rate of hospitalization and others. Positive results from the proof-of-concept study could lead to a development program in which TYME-19 is studied as a potential new oral treatment for patients with COVID-19 before they require hospitalization, and/or as prophylaxis for high-risk individuals and front-line workers.

Viruses hijack a cell’s ability to make proteins and lipids and divert these processes to make viral proteins and lipids in order to reproduce. Viruses accomplish this by inducing stress in the endoplasmic reticulum (ER), where cells process proteins, which enables the virus to remodel protein and lipid synthesis. In preclinical testing, TYME-19 has been shown to counteract these effects, preventing viral replication, by reducing ER stress^3,4. In addition, TYME-19 is believed to physically degrade viruses by solubilizing the protective lipid layer and other structural components, which prevent a virus from binding to and infecting a cell.

“The demonstrated tolerability of this agent, the multiple antiviral mechanisms of TYME-19, and the recent finding that certain bile acids occur naturally as part of our response to viral infection, make it an exceptional potential treatment against a virus that spreads rapidly, like COVID-19,” said Dr. John Rothman, Executive Vice President, Product Development at TYME. “Although bile acids have traditionally been developed for hepatic disease, they have recently been recognized as steroid hormones with broad metabolic functions in the body including neuro- and cardio-protective roles, as well as antiviral properties. TYME-19 is a synthetic bile acid with numerous therapeutic effects, including broad spectrum antiviral activity that has yet to be exploited. Its ability to inhibit viral replication leaves open the question of whether it may not just be a potential therapy for early stage disease but may also be a prophylactic therapy.”

Beyond TYME-19, TYME is utilizing its experience in cell metabolism to identify a pipeline of proprietary oral compounds that are designed to have improved antiviral efficacy for use against COVID-19 and future viral outbreaks.

“We hope that TYME-19 can soon be an important treatment alternative for doctors in the fight against COVID-19,” said Steve Hoffman, TYME’s Chairman and CEO. “We chose TYME-19 because of its similarity to our metabolic cancer agent TYME-18, the breadth of research, its ease of manufacturing and oral administrability. Moreover, we believe metabolic agents have been largely overlooked for their potential as innovative therapies that could save lives, change the course of care and ultimately reduce the burden on healthcare systems. At the same time, we remain committed to our cancer metabolism-based development programs and we will continue to follow the science to where we can improve the lives of patients in need.”

About Tyme Technologies

Tyme Technologies, Inc., is an emerging biotechnology company developing cancer therapeutics that are intended to be broadly effective across tumor types and have low toxicity profiles. Unlike targeted therapies that attempt to regulate specific mutations within cancer, the Company’s cancer metabolism-based approach is designed to take advantage of a cancer cell’s innate metabolic weaknesses to compromise its defenses, leading to cell death through oxidative stress and exposure to the body’s natural immune system. For more information, visit www.tymeinc.com. Follow us on social media: @tyme_Inc, LinkedIn, Instagram, Facebook and YouTube.

Forward-Looking Statements/Disclosure Notice

In addition to historical information, this press release contains forward-looking statements under the Private Securities Litigation Reform Act that involve substantial risks and uncertainties. Such forward-looking statements within this press release include, without limitation, statements regarding our drug candidates, including SM-88 and TYME-18, and their clinical potential and non-toxic safety profiles, our drug development plans and strategies, ongoing and planned preclinical and clinical trials, including the proposed TYME-19 proof-of-concept study, preliminary data results and the therapeutic design and mechanisms of our drug candidates; and readers can identify forward-looking statements by sentences or passages involving the use of terms such as “believes,” “expects,” “hopes,” “may,” “will,” “plan,” “intends,” “estimates,” “could,” “should,” “would,” “continue,” “seeks,” or “anticipates,” and similar words including their use in the negative or by discussions of future matters such as effect of the novel coronavirus (COVID-19) pandemic and the associated economic downturn and impacts on the Company’s ongoing clinical trials and ability to analyze data from those trials, the cost of development and potential commercialization of our lead drug candidate and of other new products, expected releases of interim or final data from our clinical trials, possible collaborations, the timing, scope and objectives of our ongoing and planned clinical trials and other statements that are not historical. The forward-looking statements contained in this press release are based on management’s current expectations, which are subject to uncertainty, risks and changes in circumstances that are difficult to predict and many of which are outside of TYME’s control. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance or achievements to be materially different from any historical results and future results, performances or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, the severity, duration, and economic impact of the COVID-19 pandemic; that the information is of a preliminary nature and may be subject to change; uncertainties inherent in the cost and outcomes of research and development, including the cost and availability of acceptable-quality clinical supply and the ability to achieve adequate clinical study design and start and completion dates; the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing data; risks associated with early, initial data, including the risk that the final data from any clinical trial may differ from prior or preliminary study data; final results of additional clinical trials that may be different from the preliminary data analysis and may not support further clinical development; that past reported data are not necessarily predictive of future patient or clinical data outcomes; whether and when any applications or other submissions for SM-88 may be filed with regulatory authorities; whether and when regulatory authorities may approve any applications or submissions; decisions by regulatory authorities regarding labeling and other matters that could affect commercial availability of SM-88; the ability of TYME and its collaborators to develop and realize collaborative synergies; competitive developments; and the factors described in the section captioned “Risk Factors” of TYME’s Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission on May 22, 2020, as well as subsequent reports we file from time to time with the U.S. Securities and Exchange Commission available at www.sec.gov.

The information contained in this press release is as of its release date and TYME assumes no obligation to update forward-looking statements contained in this release as a result of future events or developments.

¹Marin, J.J., et al., Bile Acids in Physiology, Pathology and Pharmacology. Curr Drug Metab, 2015.17(1): p. 4-29.

²Claudel, T., B. Staels, and F. Kuipers, The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol, 2005. 25(10): p. 2020-30.

³Yang, X, et al., Activation of autophagy by unfolded proteins during endoplasmic reticulum stress. The Plant Journal (2016) 85, 83–95

⁴Umut O¨ zcan, U., et al., Chemical Chaperones Reduce ER Stress and Restore Glucose Homeostasis in a Mouse Model of Type 2 Diabetes. Sciencemag.org/cgi/content/full/313/5790/1137/DC1

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