Imaging Endpoints’ novel radiomics technology is assisting Tyme’s Phase II Pancreatic Cancer Study

• TYME launched its multicenter randomized controlled pivotal stage of TYME-88-Panc trial for use of SM-88 in patients with third-line pancreatic cancer based on these clinical outcomes
• SM-88 is an oral, investigational cancer metabolism-based therapy that has demonstrated confirmed clinical responses in 15 different cancers across four separate studies
• SM-88 is a new approach aimed at disrupting cancer metabolism in metastatic pancreatic cancer: ~ 50,000 cases annually in U.S. alone
• Targeted mechanism of action resulted in fewer than 2% of patients experiencing serious adverse events related to SM-88 in clinical trials

NEW YORK, Sept. 30, 2019 (GLOBE NEWSWIRE) — Tyme Technologies, Inc. (NASDAQ: TYME), an emerging biotechnology company developing cancer metabolism based therapies (CMBTs™), announced that its open-label Phase II TYME-88-Panc study evaluating SM-88 (racemetyrosine) as an oral monotherapy in patients with advanced pancreatic cancer continues to demonstrate encouraging overall (OS) results and has a well-tolerated safety profile. TYME also announced encouraging Quality of Life data for this challenging patient population. The supporting data from the study were presented at the European Society of Medical Oncology Congress (ESMO) being held on September 27- October 1, 2019 in Barcelona, Spain. As a result of these clinical outcomes, TYME recently launched the multi-center randomized controlled pivotal stage of the TYME-88-Panc trial for use of SM-88 in patients with third-line pancreatic cancer.

TYME’s lead CMBT candidate, SM-88, was designed to leverage innate changes in cancer metabolism that are fundamental to support the cancer’s proliferation. The Warburg Effect, a process that helps most cancer cells adapt to changing conditions, is prevalent across most solid and hematological malignancies impacting energy production and the uptake of non-essential amino acids for cancer growth. SM-88 is a modified dysfunctional form of the amino acid tyrosine. Tyrosine is required for cancer cell growth and as a result, SM-88 is selectively consumed by the cancer cell, causing a disruption of protein synthesis that leads to catastrophic failure and cancer cell death.

“Given that there are no effective options to treat this poor prognostic patient population, we recently launched our SM-88 pivotal trial for patients with third-line pancreatic cancer. We are increasingly encouraged that SM-88 has the efficacy, safety and quality of life potential to be a new treatment approach for late-stage pancreatic patients,” said Giuseppe Del Priore, M.D., M.P.H., Chief Medical Officer at TYME. “Assessing the potential of emerging biomarkers, such as the evaluation of circulating tumor cells for predicting the outcome and the response to specific investigational medicines, such as SM-88, is an important next step to improve the prognosis of patients with metastatic cancers.”

The results from the multicenter open-label Phase II TYME-88-Panc study involved 49 heavily pretreated patients with radiographically progressive metastatic pancreatic cancer who had significant disease related morbidity before receiving TYME’s investigational agent SM-88. More than 80% of patients had received at least two prior lines of therapy. Of the 49 patients, 38 patients were evaluable for efficacy as defined in the protocol. This study is being performed under a TYME IND with input from the FDA prior to study initiation.

In this study, based on information available as of April 25, 2019, the median overall survival of the 38 evaluable patients was 6.4 months. Certain efficacy indicators correlated with greater OS, including achieving stable disease (SD) or better and decreases in circulating tumor cells (CTCs). Notably, patients achieving stable disease or better demonstrated a statistically significant (p=0.02) improvement in survival with a 92% reduction in risk of death (hazard ratio=0.08).The clinical benefit response (CBR) was durable with the majority of these patients remaining in stable disease or better at more than 7 months after receiving treatment with SM-88.

In the TYME-88-Panc study, baseline CTCs were an average of 142 cells/4ml. Of the 24 evaluable patients treated with SM-88 who had CTC readings available, 66.7% of those patients (16/24) showed a median decrease of 63% in CTC levels falling from baseline CTCs to a median of 21 cells/4ml. 42% of those patients (10/24) with available results reaching an 80% reduction or greater in CTCs demonstrated a 60% decrease in risk of death (hazard ratio=0.40).

A novel radiomics analysis was also conducted. The radiomic analysis of tumor texture correlated with CTCs at baseline (p=0.007). In addition, tumor texture was closely associated with the percentage change in CTCs on treatment (p=0.019) and OS (logrank p=0.001)

Quality of life (QOL) assessments were conducted as part of the TYME-88-Panc study. Generally, patients maintained their QOL throughout their treatment with SM-88. Patients reported low levels of GI-related symptoms (decreased appetite, nausea, vomiting, diarrhea), which are commonly reported in patients undergoing other treatments for pancreatic cancer. Score for pain and fatigue related questions showed that patients reported generally low levels of these symptoms also. Overall stability of weight was also reported. This is a key finding as patients with pancreatic cancer typically experience noticeable, but unintentional weight loss, which is a clinically meaningful indicator of poor prognosis.

As of April 25, 2019, the study reported that SM-88 was well tolerated with only 4.0% of patients (2 of 49) who experienced serious adverse events (SAEs) deemed at least possibly related to SM-88 (abdominal pain, arthralgia, and hypotension). One patient with reported SAEs continued on treatment.

The TYME-88-Panc research results are from an investigational study. SM-88 is not approved for the treatment of patients with any disease condition. Patients and physicians can access www.TYMETRIALS.com for more information about ongoing SM-88 clinical trials.

Details of this study were presented at the ESMO Congress in Barcelona, Spain on Sunday, September 29, 2019, from 12:00 PM CET to 1:00 PM CET during the Poster Display Session 2 in Poster Hall 4. The poster is available on our website (www.tymeinc.com/data-publications).

The SM-88 poster on pancreatic cancer presented at the ESMO Congress in Barcelona is as follows:

Racemetyrosine:
Title: Phase II Monotherapy Efficacy of Cancer Metabolism Targeting SM-88 in Heavily Pre-Treated Poor Prognosis Pancreatic Cancer (PDAC) Patients

Authors: Allyson J. Ocean1, Marcus Smith Noel2, Andrea Wang-Gillam3, Sant Chawla4, Vincent Chung5, Shubham Pant6, Ron Korn7, Giuseppe Del Priore8, Vincent J. Picozzi9

Institutions: 1Weill Cornell Medical College, NY, NY, 2University of Rochester Wilmot Cancer Institute, Rochester, NY,3Washington University Scholl of Medicine, St. Louis, MO,4Sarcoma Oncology Research Center, Santa Monica, CA, 5City of Hope, Duarte, CA, 6MD Anderson Cancer Center, Houston, TX, 7Imaging Endpoints, Scottsdale, AZ, 8Tyme Technologies, Inc., NY, NY, 9Virginia Mason Medical Center, Seattle, WA

Session Title: Poster Display Session 2
Session Date and Time: Sunday, September 29, 2019 12:00 PM CET – 1:00 PM CET
Session Location: Poster Hall 4
Abstract Number: 4283
Poster Number: 719P

About Advanced Pancreatic Cancer
Advanced pancreatic cancer is a difficult-to-treat cancer with the lowest survival rates among all cancer types. Across all patients with pancreatic cancer, relative 5-year survival is 8% and is less than 3% for those with advanced disease.2 The median survival for patients in end-stage of the disease is approximately 3 months. There are two main types of pancreatic cancer – adenocarcinomas, which accounts for approximately 90% of all pancreatic cancer, and neuroendocrine tumors. Pancreatic cancer is relatively uncommon with new cases accounting for only 2.1% of all newly diagnosed cancers. However, pancreatic cancer is the fourth most common cause of cancer death for men and women in the United States.

About SM-88
SM-88 is an oral investigational modified proprietary tyrosine derivative that is hypothesized to interrupt the metabolic processes of cancer cells by breaking down the cells’ key defenses and leading to cell death through oxidative stress and exposure to the body’s natural immune system. Clinical trial data have shown that SM-88 has demonstrated encouraging tumor responses across 15 different cancers, including pancreatic, lung, breast, prostate and sarcoma cancers with minimal serious grade 3 or higher adverse events.

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 therapeutic 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 candidate SM-88 and its clinical potential and non-toxic safety profiles, our drug development plans and strategies, ongoing and planned clinical trials, 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 “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 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, 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 clinical study 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 Phase II data may differ from prior study data or preliminary Phase II 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; 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 June 12, 2019, 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.

1JCO 37, 2019 supp 7S; 83
2Statistics adapted from the American Cancer Society’s (ACS) publication, Cancer Facts & Figures 2018.