Belinostat

An upcoming trial in patients with colorectal cancer will be the first to test an DNMT inhibitor and an EZH2 inhibitor together in any type of cancer. A pair of epigenetic cancer drugs packs a “one-two punch” against colorectal tumors to knock them out more effectively than either medication alone, a new study in cells suggests.  In a journal article published March 27 in Science Advances, a team of researchers led by scientists from the Van Andel Institute in Grand Rapids, Michigan showed that a low dose of the DNA methyltransferase (DNMT) inhibitor decitabine combined with Tithe EZH2 inhibitor tazemetostat successfully induced changes that would make cancer cells more vulnerable to destruction by the immune system. The chemotherapy decitabine is commercialized by Eisai as Inqovi; tazemetostat is commercialized by Ipsen as Tazverik. Neither company was involved in the study.  While agents in both classes of drugs are FDA approved to treat blood cancer, they haven't had much success in solid tumors such as colorectal cancer, Scott Rothbart, Ph.D., the study’s corresponding author, said in a press release. “Our findings highlight the promise of combination cancer therapies by revealing how these two medications interact, with the DNMT inhibitor priming cancer cells in a way that makes the EZH2 inhibitor more effective.”  “Epigenetic” is a term that refers to typically reversible modifications made to genes that do not directly alter the genes themselves, but rather affect their expression. Cancer progression involves many epigenetic changes both to the cancer cells themselves and to the immune cells that would otherwise destroy them.  Scientists have attempted to destroy cancer by countering these changes pharmacologically and restoring the expression of anti-cancer genes. The most established means of doing so is with histone deacetylase inhibitors, or HDAC inhibitors, such as Merck’s Zolinza (vorinostat) for lymphoma and Acrotech Biopharma’s Beleodaq (belinostat) for myeloma. The only other FDA-approved DNMT inhibitor besides Inquovi is Celgene’s acute myeloid leukemia drug Vidaza (azacitidine). Tazverik is the sole EZH2 inhibitor with FDA approval.  Earlier work by Van Andel Institute researchers showed that DNMT inhibitors cause cancer cells to act as though they’ve been infected by a virus, making them more vulnerable to one’s immune system. For the new study, the researchers hypothesized that because DNMT inhibitors alter the cells in a way that could make EZH2 inhibitors more effective, they would work better together than separately.  To see whether this was the case, the researchers started by testing them against different types of colorectal cancer cells on their own, then looked at them in combination. The results backed up their rationale: EZH2 inhibitors compounded the changes initiated by the DNMT inhibitors, boosting the duo’s effectiveness.   The findings are the basis for an upcoming clinical trial that will evaluate the pair against colorectal cancer in patients. Combinations of DNMT inhibitors and HDAC inhibitors have been tested in clinical trials to mixed results, the study noted. The new trial will be the first to evaluate a DNMT inhibitor and an EZH2 inhibitor.  Future studies should evaluate the pair with immunotherapies, too, Rothbart noted in the release. There’s evidence in preclinical models that the viruslike changes the drugs make in the cells could lead to a better response to drugs that boost the immune system. “These data suggest future directions for testing whether DAC and TAZ treatments might improve tumor response to immunomodulating agents,” the researchers wrote in the study. 

- SLS009 Demonstrated Promising Efficacy in Phase 1 Study with 36.4% Clinical Response (ORR) in r/r Peripheral T-cell Lymphomas (PTCL); ORR in r/r PTCL Patients with Standard of Care is 25.8% - - One Patient with Complete Metabolic Response Continuing Treatment for over 62 weeks and another patient with Complete Response by CT Continuing Treatment for over 24 weeks - - Phase 1b/2 Study in PTCL Ongoing with top line data expected in 1H 2024 - NEW YORK, Dec. 21, 2023 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS’’ or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for SLS009, the Company’s novel and highly selective CDK9 inhibitor, for the treatment of relapsed/refractory (r/r) Peripheral T-cell Lymphomas (PTCL). “We are delighted to announce the FDA’s granting of ODD for SLS009, marking another significant milestone following the recent Fast Track Designation by the FDA for PTCL,” said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. “In the recently completed dose-escalation portion of the Phase 1 trial in r/r hematological malignancies, SLS009 achieved clinical responses in PTCL including two patients reaching complete response. We are excited to see a favorable safety profile, strong initial efficacy signals, and evidence of anti-tumor activity across the Phase 1 study as well as the ongoing Phase 2 studies. With both designations in hand, we look forward to advancing the development of SLS009 and continuing to work closely with regulators with the goal of delivering this treatment to those who may benefit from it.” As it relates to PTCL, SLS009 is currently being evaluated in a Phase 1b/2 trial in patients with r/r PTCL. The open-label, single-arm study will enroll up to 95 patients to evaluate safety and efficacy and, based on the results, may serve as a registrational study. This initial PTCL study is fully funded by GenFleet Therapeutics, Inc. and is being conducted in China. In the recently completed dose-escalation portion of the Phase 1 trial in r/r hematological malignancies, SLS009 demonstrated a favorable safety pro promising clinical efficacy. Complete or partial responses were observed in patients with acute myeloid leukemia as well as lymphoma, including four PTCL patients (36.4%) who achieved clinical responses with one patient with complete metabolic response who is continuing treatment for over 62 weeks, and another patient with complete response by CT scan who is continuing treatment for over 24 weeks. The current standard of care for r/r PTCL, belinostat, an HDAC inhibitor, showed in its pivotal Phase 2 study a 25.8% response rate in a similar patient population to that in the SLS009 Phase 1 clinical trial. The patients who achieved complete response in the SLS009 study were previously treated with regimens containing an HDAC inhibitor. The FDA’s Office of Orphan Products Development grants ODD status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD provides benefits to drug developers designed to support the development of drugs and biologics for small patient populations with unmet medical needs. These benefits include assistance in the drug development process, tax credits for qualified clinical costs, exemptions from certain FDA fees and seven years of marketing exclusivity. About SELLAS Life Sciences Group, Inc. SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S (GPS), is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (formerly GFH009), a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. For more information on SELLAS, please visit Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, forward-looking statements can be identified by terminology such as “plan,” “expect,” “anticipate,” “may,” “might,” “will,” “should,” “project,” “believe,” “estimate,” “predict,” “potential,” “intend,” or “continue” and other words or terms of similar meaning. These statements include, without limitation, statements related to the SLS009 clinical development program, including data therefrom, and regulatory strategy. These forward-looking statements are based on current plans, objectives, estimates, expectations and intentions, and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties with oncology product development and clinical success thereof, the uncertainty of regulatory approval, and other risks and uncertainties affecting SELLAS and its development programs as set forth under the caption “Risk Factors” in SELLAS’ Annual Report on Form 10-K filed on March 16, 2023 and in its other SEC filings. Other risks and uncertainties of which SELLAS is not currently aware may also affect SELLAS’ forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof. SELLAS undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Investor Contact Bruce Mackle Managing Director LifeSci Advisors, LLC SELLAS@lifesciadvisors.com