Devimistat

In the months since Rafael Holdings’ lead drug flunked two Phase III trials — in metastatic pancreatic cancer and acute myeloid leukemia — the little biotech has vowed to carry on with an early-stage pipeline. But the execs in charge are now cutting that off, too. Rafael will curtail its early-stage efforts , including preclinical research, the company disclosed, in a move to reduce spending and focus on finding clinical-stage programs from outside that it could potentially invest in, acquire or in-license. UPDATED: Rafael Holdings guts its top leadership, including short-tenured CEO, as cancer fiasco spurs a shakeup The company wrote in an SEC filing that the move is expected to “ incur severance charges in the amount of approximately $0.5 million,” but didn’t specify how many employees may be laid off. Shares on NYSE $RFL traded up slightly after hours to pass the $2 mark, a fraction of its peak last summer, when it was trading close to $63. Ameet Mallik Rafael Holdings had placed high hopes on devimistat, which was originally developed through its subsidiary Rafael Pharmaceuticals. The drug was designed to target enzymes in cancer cells’ mitochondria, thereby cutting off their energy. In fact, it was so promising that Rafael Holdings wooed Ameet Mallik from Novartis Oncology to become CEO. Bill Conkling The disappointing Phase III results, announced a year ago, triggered a major shakeup at the top of the company. As Mallik returned the reins to founder Howard Jonas, Rafael Holdings bid farewell to a number of top execs, including then-chief commercial and business officer Bill Conkling — before later announcing that Conkling will actually remain with the company and take up the CEO role. Under Conkling, Rafael has sold a building in New Jersey, complete with a garage, for $33 million in cash. That added to its reserves of about $63 million as of July 31. Small biotech whiffs badly in PhIII pancreatic cancer study, prompting halt of another late-stage trial In a statement, Conkling said the “strong balance sheet affords us the opportunity to focus on strategic business development efforts at a time of substantive dislocation in the biotech sector,” with an eye on programs that are near clinical milestones. Rafael Pharmaceuticals, meanwhile, is still developing devimistat for several rare cancer types under a new name, Cornerstone Pharmaceuticals.

September 28, 2022 - Cornerstone Pharmaceuticals, Inc., a company focused on rare cancer therapeutics and formerly known as Rafael Pharmaceuticals, today announced the initiation of a Phase 1 clinical trial evaluating CPI-613® (devimistat) in combination with chemoradiation for the treatment of advanced pancreatic cancer. Devimistat is the company’s first-in-class lead compound designed to target enzymes that are involved in cancer cell energy metabolism found within the mitochondria of cancer cells. “The initiation of this Phase 1 trial is an important milestone for Cornerstone and demonstrates our continued commitment to exploring the potential of devimistat as a novel pancreatic cancer treatment,” said Sanjeev Luther, President and CEO of Cornerstone Pharmaceuticals. “Locally advanced pancreatic cancer is a difficult-to-treat disease associated with high rates of morbidity and mortality and current standards of care have significant limitations. We believe devimistat has the potential to address an unmet need for safer and more effective treatment options for this devastating disease.” The Phase 1 trial is an open-label, dose-escalation study being conducted at the Medical College of Wisconsin in Milwaukee. The objective of the study is to determine the maximum tolerated dose and safety profile of devimistat when used concomitantly with gemcitabine and intensity-modulated radiation (Gem-RT) therapy in adult patients with locally advanced unresectable or metastatic pancreatic cancer. The study will evaluate increasing doses of CPI-613, in combination with Gem-RT therapy, beginning with doses of 500 mg/m^2 and up to 1,500 mg/m^2. The study will enroll up to 24 patients who will receive treatment with devimistat once per week via intravenous infusion. “A hallmark of pancreatic cancer, as well as other cancers, is the pathological reprogramming of cellular metabolism and enhanced mitochondrial function, which can both prevent the efficacy of standard of care therapies and lead to therapeutic resistance,” said Mandana Kamgar, M.D., Assistant Professor at the Medical College of Wisconsin and Principal Investigator for the study. “In previous studies, devimistat has demonstrated low toxicity with a unique mechanism of action that can preferentially target cancer cell energy metabolism. In our pre-clinical studies, done in collaboration with Dr. Asfar Azmi at Karmanos Cancer Institute in Detroit, we have found that devimistat can act as a potent chemo- and radio-sensitizer in pancreatic cancer models. The combination of devimistat with chemoradiation could potentially lead to significant improvements in local control of pancreatic cancer with minimal added toxicity.” The U.S. Food and Drug Administration (FDA) has granted an orphan drug designation for devimistat in pancreatic cancer. Devimistat has also received an orphan drug designation from the European Medicines Agency (EMA) in pancreatic cancer. To learn more about the clinical trial program, please visit ClinicalTrials.gov, using the identifier NCT05325281. About Pancreatic Cancer Pancreatic cancer is the third leading cause of cancer death in the United States with median overall survival of less than 12 months, according to the American Cancer Society. Local tumor progression is the leading cause of hospitalization for those with unresectable pancreatic cancer, a substantial contributor to morbidity, and responsible for mortality in approximately one-third of patients. About CPI-613 (Devimistat) Cornerstone’s first-in-class lead clinical compound, CPI-613 (devimistat), is a selective mitochondrial metabolism inhibitor which targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. Devimistat is designed to target the mitochondrial tricarboxylic acid (TCA) cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat substantially increases cellular stress and the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This synergy allows for potential combinations of devimistat with lower doses of these generally toxic drugs to be more effective with lower patient side effects. Combination therapy with devimistat has the potential to offer a diverse range of opportunities to substantially improve patient outcomes across many different cancers. About Cornerstone Pharmaceuticals, Inc. Cornerstone Pharmaceuticals is committed to the development of therapies for rare cancers that have few to no treatment options available. Cornerstone’s lead compound, CPI-613® (devimistat), is designed to target the mitochondria of cancer cells in order to disrupt their energy production, cutting off the fuel for disease growth. Devimistat is undergoing multiple clinical trials and has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the following indications: Burkitt’s lymphoma, biliary tract cancer, soft tissue sarcoma, myelodysplastic syndrome (MDS), pancreatic cancer and peripheral T-cell lymphoma. In addition, the European Medicines Agency (EMA) has granted orphan drug designation to devimistat for pancreatic cancer and Burkitt’s lymphoma. With science stemming from the world’s most renowned institutions and compassion that runs deep, Cornerstone strives to improve the lives of people with rare cancers, inaugurating a new era of hope. For more information, please visit www.cornerstonepharma.com.