Seclidemstat Modulates Tumor Microenvironment to Help Genetically Mutated Cancer Types Overcome Resistance to Checkpoint Inhibitors in Preclinical Study

Data Supports Continued Study of Seclidemstat with Checkpoint Inhibitors

HOUSTON, Feb. 04, 2020 (GLOBE NEWSWIRE) -- Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage biotechnology company targeting cancers caused by mis-regulated gene expression, today announced the publication of a scientific paper entitled, “The Novel Reversible LSD1 Inhibitor SP-2577 Promotes Anti-Tumor Immunity in SWItch/Sucrose-NonFermentable (SWI/SNF)1,” available in preprint at bioRxiv.com. The paper highlights data from in vitro studies conducted by Sunil Sharma, M.D., Salarius’ scientific founder, and his team at the Translational Genomic Institute (TGen) in Phoenix, AZ that demonstrate the potential for SP-2577, also known as Seclidemstat, Salarius’ lead clinical drug candidate, to be used in combination with checkpoint inhibitors to treat cancers with identifiable (i.e., SWI/SNF) mutations.

Dr. Sharma’s group used 3-D in vitro organoids to investigate the ability of Seclidemstat, a potent reversible inhibitor of the LSD1 enzyme, to promote anti-tumor immunity and T-cell infiltration in two types of ovarian cancer – small cell carcinoma of the ovary hypercalcemic type (SCCOHT) and ovarian clear cell carcinoma (OCCC) -- that both carry mutations in proteins of the SWI/SNF complex. The SWI/SNF complex plays an important role in modulating gene expression, and when proteins of the complex are mutated, it can result in cancer growth and progression. Mutations in the SWI/SNF complex occur in roughly 20% of human cancers, including ovarian cancer, which is one of the most lethal cancers affecting women.

Checkpoint inhibitors are designed to unleash an immune attack on cancer cells. However, checkpoint inhibitor therapies do not work in about 70% of cancer patients, and even patients who do show an initial response, many suffer a return of the disease. In this study, Seclidemstat modulated the tumor microenvironment to help overcome the resistance to checkpoint inhibitors.

“Dr. Sharma’s research represents a significant potential advancement for Salarius and Seclidemstat as it demonstrates the potential for the drug to be utilized in combination with checkpoint inhibitors in the treatment of a readily identifiable patient population with specific mutations,” stated David Arthur, Chief Executive of Salarius Pharmaceuticals. “Seclidemstat is already the subject of a Phase 1/2 study in Ewing sarcoma, for which it has been granted Fast Track Designation by the FDA, and a second Phase 1/2 study is also underway in advanced solid tumors. It is our wish to explore the use of Seclidemstat in multiple indications, and we are excited by the potential opportunity to combine our LSD1 inhibitor with checkpoint inhibitors and develop cancer treatments for patients who need them most.”

Dr. Sharma commented, “Transcriptome analysis of SCCOHT cell lines show that LSD1 is a highly expressed gene in tumors with SWI/SNF mutations which makes tumors with SWI/SNF mutations attractive tumor types for an LSD1 inhibitor. In addition, our data shows that Seclidemstat stimulates interferon pathways that cause an increase in cytokines and T-cell recruitment, which has a pronounced effect on cancers with these very mutations. Seclidemstat could be effective in patients with SWI/SNF mutations.”

A renowned cancer researcher, Dr. Sharma has led significant research with anti-cancer agents and co-founded several biopharmaceutical startups, including Salarius. During his time as a researcher at the University of Utah’s Huntsman Cancer Institute, Dr. Sharma developed the LSD1 inhibitor technology Salarius licensed from the university, which is now the Company's Seclidemstat program. 

More information on this research paper, is available at the link: https://www.biorxiv.org/content/10.1101/2020.01.10.902528v1

1 Raffaella Soldi, Tithi Ghosh Halder, Alexis Weston, Trason Thode, Kevin Drenner, Rhonda Lewis, Mohan R. Kaadige, Shreyesi Srivastava, Sherin Daniel Ampanattu, Ryan Rodriguez del Villar, Jessica Lang, Hariprasad Vankayalapati, Bernard Weissman, Jeffrey M. Trent, William P.D. Hendricks, Sunil Sharma

About Dr. Sunil Sharma
Dr. Sunil Sharma is currently a Deputy Director, professor and head of Applied Cancer Research and Drug Discovery at the Translational Genomics Research Institute (TGen), where he pursues drug development and patient clinical trials in concert with TGen’s research alliance with City of Hope in California and TGen’s clinical partnership with the HonorHealth Research Institute in Scottsdale. Before arriving at TGen in 2017, Dr. Sharma served briefly as Deputy Director of the Huntsman Cancer Institute (HCI) in Salt Lake City, UT, following an eight-year span as Senior Director of Clinical Research and Director of the Center for Investigational Therapeutics at HCI, where he also held a Jon and Karen Huntsman Presidential Professorship in Cancer Research and taught at the University of Utah School of Medicine. Dr. Sharma helped HCI receive a coveted Comprehensive Cancer Center designation from the NCI in 2015. Dr. Sharma co-founded Salarius Pharmaceuticals in 2011, as well as Iterion Therapeutics and Stingray Therapeutics, and he currently serves as Stingray Therapeutics’ chief medical officer. In 2004, Dr. Sharma founded the GI Investigational Program at the Nevada Cancer Institute in Las Vegas and served as director until 2008. He previously held the position of vice president at Novartis in charge of the Swiss drug giant’s early clinical oncology program and worked as an oncologist at Sloan Kettering Memorial Hospital. During the past 15 years, Dr. Sharma has served as the primary investigator on more than 150 Phase 1 and Phase 2 oncology clinical trials.

About Seclidemstat
Seclidemstat is a first-in-class, oral, small molecule designed for the reversible and noncompetitive inhibition of the LSD1 enzyme. Seclidemstat is based on the research of Dr. Sunil Sharma, Salarius’ co-founder, into LDS1 inhibition during his tenure at the University of Utah’s Huntsman Cancer Institute. As a reversible inhibitor, Seclidemstat could offer more efficacy, more flexible dosing and less toxicity. Salarius expects to release early cohort data early next year from its Ewing sarcoma study and a second Phase 1 clinical study in advanced solid tumors, including prostate, breast and ovarian cancers. A preclinical program in glioblastoma is underway at the Barrow Neurological Institute ‘s Ivy Brain Tumor Center.

More information about Salarius’ ongoing Ewing sarcoma trial is available at ClinicalTrials.gov and on the company website, salariuspharma.com. Active clinical trial sites include, Memorial Sloan Kettering Cancer Center in New York City, Nationwide Children’s Hospital in Columbus, OH, Johns Hopkins All Children’s Hospital in St. Petersburg, FL; Children’s Hospital of Los Angeles in Los Angeles, CA; Moffitt Cancer Center in Tampa, FL; Dana-Farber Cancer Institute in Boston, MA; MD Anderson Cancer Center in Houston, TX; and the Sarcoma Oncology Center in Santa Monica, CA.

About Salarius Pharmaceuticals
Salarius Pharmaceuticals, Inc. is a clinical-stage oncology company targeting the epigenetic causes of cancers and is developing treatments for patients that need them the most. Epigenetics refers to the regulatory system that affects gene expression. In some cancers, epigenetic regulators often become dysregulated and incorrectly turn genes on or off leading to cancer progression. Drugs that can safely modify the activity of these epigenetic regulators may correct the gene changes that are driving the disease. The company’s lead candidate, Seclidemstat, is currently in clinical development for treating Ewing sarcoma, for which it has Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. Salarius believes that Seclidemstat is one of only two reversible inhibitors of the epigenetic modulator LSD1 currently in human trials, and that it could have potential for improved safety and efficacy compared to other LSD1-targeted therapies. Salarius is also developing Seclidemstat for several cancers with high unmet medical need, with a second Phase 1 clinical study in advanced solid tumors, including prostate, breast and ovarian cancers. Salarius receives financial support from the National Pediatric Cancer Foundation to advance the Ewing sarcoma clinical program and is also the recipient of an $18.7 million Product Development Award from the Cancer Prevention and Research Institute of Texas (CPRIT). For more information, please visit salariuspharma.com.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These forward-looking statements may be identified by terms such as “will,” “can,”” “could,” “believe,” “feel,” “plan,” “allow,” “will,” “expect,” “provide,” “able to,” “position,” “anticipate,” “progress,” “potential,” “target,” and similar terms or expressions or the negative thereof. Examples of such statements include, but are not limited to, statements regarding: Dr. Sharma’s research representing a significant potential advancement for the company and Seclidemstat as it demonstrates the potential for the drug to be utilized in combination with checkpoint inhibitors in the treatment of a readily identifiable patient population with specific mutations; the company’s plans to explore the use of Seclidemstat in multiple indications, and the potential opportunity to combine the company’s LSD1 inhibitor with checkpoint inhibitors and develop cancer treatments for patients who need them most; anticipated milestones from the company’s clinical development pipeline, which is led by Seclidemstat; the ongoing Seclidemstat Phase 1/2 clinical trial; the study of  Seclidemstat in a second Phase 1 clinical trial in advanced solid tumors; the company’s plans to release early cohort data and expected timing thereof; the company’s belief that Seclidemstat is one of only two reversible inhibitors of the epigenetic modulator LSD1 currently in human trials, and that it could have potential for improved safety and efficacy compared to other LSD1-targeted therapies, more flexible dosing and less toxicity; and the company’s development of Seclidemstat for several cancers with high unmet medical need, with a second Phase 1 clinical study in advanced solid tumors, including prostate, breast and ovarian cancers. Salarius may not actually achieve the plans, carry out the intentions or meet the expectations or objectives disclosed in the forward-looking statements. You should not place undue reliance on these forward-looking statements. These statements are subject to risks and uncertainties which could cause actual results and performance to differ materially from those discussed in the forward-looking statements. These risks and uncertainties include, but are not limited to, the following: the ability of the company to raise additional capital to meet the company’s business operational needs and to achieve its business objectives and strategy; the company’s ability to project future capital needs and cash utilization; available sources of cash, including from CPRIT and its equity line; future clinical trial results; that the results of studies and clinical trials may not be predictive of future clinical trial results; the sufficiency of Salarius’ intellectual property protection; risks related to the drug development and the regulatory approval process; the competitive landscape and other industry-related risks; market conditions which may impact the ability of Salarius access capital under its equity line; the possibility of unexpected expenses or other uses of Salarius’ cash resources; and other risks described in Salarius’ filings with the Securities and Exchange Commission, including those under the heading “Risk Factors.” The forward-looking statements contained in this press release speak only as of the date of this press release and are based on management’s assumptions and estimates as of such date. Salarius disclaims any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made

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