Vanquish Oncology, Inc.

A phase I clinical trial of PAC-1, a drug that spurs programmed cell death in cancer cells, found only minor side effects in patients with end-stage cancers. The drug stalled the growth of tumors in the five people in the trial with neuroendocrine cancers and reduced tumor size in two of those patients. It also showed some therapeutic activity against sarcomas, scientists and clinicians report. A phase I clinical trial of PAC-1, a drug that spurs programmed cell death in cancer cells, found only minor side effects in patients with end-stage cancers. The drug stalled the growth of tumors in the five people in the trial with neuroendocrine cancers and reduced tumor size in two of those patients. It also showed some therapeutic activity against sarcomas, scientists and clinicians report in the British Journal of Cancer. The drug was first identified and developed as an anti-cancer agent by scientists at the University of Illinois Urbana-Champaign. The findings from the clinical trial are noteworthy because the drug was tested in a small number of patients with advanced disease, said study clinical director Dr. Arkadiusz Dudek, an oncologist with the HealthPartners Cancer Center at Regions Hospital in St. Paul, Minnesota, and at Mayo Clinic in Rochester, Minnesota. Phase I clinical trials are designed to test whether a new drug compound has worrisome side effects or toxicities in human patients, Dudek said. But scientists also can look for early evidence of therapeutic benefits. The trial enrolled cancer patients with advanced disease who had run out of other treatment options. "We had patients with colon cancer, breast cancer, pancreatic cancer, adenocarcinoma, melanoma and others," he said. The clinical trial -- and another testing PAC-1 against brain cancer -- involves patients and clinicians at three institutions: Regions Hospital, the University of Illinois Chicago and Johns Hopkins University. Phase I clinical trials track side effects in patients who first are given very low doses of the compound being tested. If the drug is well tolerated and causes no discernible toxicities over the course of a month, the dose is incrementally increased. This process can take several months before a potentially therapeutic dose is given, said Dr. Oana Danciu, a medical oncologist and associate director for clinical research at the University of Illinois Cancer Center in Chicago, who led the clinical trial. Researchers at the U. of I. first identified PAC-1 as a potential anti-cancer compound in the early 2000s when they discovered that it could switch on a pathway that is suppressed in cancer cells. The first step of this pathway involves the conversion of procaspase-3, a protein found in most cells, into caspase-3, an enzyme that, when activated, initiates programmed cell death. Led by chemistry professor Paul Hergenrother, the U. of I. team also recognized that procaspase-3 occurs in greater abundance in many cancer cells relative to healthy tissues. That characteristic, along with its tendency to not be activated in cancer cells, made it a good target for anti-cancer therapies. In animal trials involving pet dogs with spontaneously occurring lymphomas, meningiomas and osteosarcomas, Hergenrother and Dr. Timothy Fan, a U. of I. professor of veterinary clinical medicine, found that an early formulation of PAC-1 had anti-cancer effects. Their work in cells and in animals set the stage for the human clinical trials, which were initiated several years ago with funding from an anonymous angel investor. Hergenrother founded biotechnology company Vanquish Oncology to lead the effort. The clinicians are currently seeking further funding to move the drug into phase II clinical trials, which would involve many more, much healthier patients with very similar cancer profiles to one another. "Our strategy is to figure out which tumor type will be the most sensitive and pursue that," Dudek said. "So we are very excited about the results in neuroendocrine tumors because there are not many drugs available for that disease." More results are expected soon from a phase I clinical trial of PAC-1 in patients with glioblastoma multiforme, an aggressive form of brain cancer that has only one drug available to treat it. In the new clinical trial, the team combined PAC-1 with this drug, temozolomide. In previous studies, the researchers discovered that PAC-1 crosses the blood-brain barrier, which is essential for any brain cancer treatment. They also saw promising results of PAC-1 in combination with the drug temozolomide and radiation in pet dogs with brain cancer. If clinical trials reveal that PAC-1 is therapeutic against one or more cancer type and the drug is approved for use in those populations, it will make it less costly to test it against other cancers, the researchers said. An approved drug also can be prescribed for "off-label use" by doctors who think their patients might benefit from adding it to their cancer-treatment protocols. It can take many years for the results of new clinical trials to be available, and longer still before a new drug like PAC-1 is approved for cancer treatment, the researchers said. Hergenrother and Fan are affiliates of the Carl R. Woese Institute for Genomic Biology at the U. of I. and members of the Cancer Center at Illinois. Vanquish Oncology, the University of Illinois Cancer Center, the National Institutes of Health and the Engdahl Family Foundation supported this research.

JERSEY CITY, N.J., June 23, 2022 (GLOBE NEWSWIRE) -- SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug-resistant infections, today announced the initiation and first patient enrolled in a new Phase 3b, open-label, multicenter study (VANQUISH) to evaluate the efficacy, safety and tolerability of oral ibrexafungerp as a treatment for complicated vulvovaginal candidiasis (VVC) in patients who have failed treatment with fluconazole, based on mycological and clinical outcomes. The VANQUISH study will enroll approximately 150 difficult-to-treat complicated VVC patients who will receive 600 mg of oral ibrexafungerp for one, three or seven consecutive days determined by their underlying complicating condition including immunocompromised state. Complicated patients include patients with recurrent VVC, those with VVC caused by non-albicans Candida species and those with diabetes, immunocompromising conditions (e.g., HIV), or immunosuppressive therapy (e.g., corticosteroids). “After seeing the strong positive results of patients in the CANDLE Sub-study who had failed fluconazole and the refractory or relapsed VVC cases in our ongoing FURI study, we decided to conduct additional research to explore the efficacy of ibrexafungerp specifically in patients with the most challenging yeast infection cases that have not responded to azole treatments,” said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. “This is another step in our efforts to advance this important non-azole antifungal treatment for VVC that provides an alternative for women with severe, difficult-to-treat fungal infections. Once completed, we believe the results of this study could further demonstrate ibrexafungerp’s ability to treat multiple types of complicated cases.” Of the 14 patients in the Phase 3 open-label, single-arm FURI study (NCT03059992) with refractory or relapsed cases of VVC treated with ibrexafungerp, 10 (71.4%) had successful clinical outcomes as judged by an independent Data Review Committee. In the nested sub-study of the CANDLE Phase 3 trial, 24 patients who failed to respond to the initial three-day regimen of fluconazole received a one-day open-label treatment course of ibrexafungerp (300 mg BID), and 71% successfully achieved a significant reduction or elimination of signs and symptoms. In both studies, ibrexafungerp was generally safe and well-tolerated with findings consistent with the existing approved label. “There is a significant need of treatment alternatives for patients with complicated VVC, including those with underlying conditions such as immunosuppression,” said Nkechi Azie, M.D., Vice President of Clinical Development and Medical Affairs. “The VANQUISH study will allow us to evaluate various dose regimens of ibrexafungerp in women with complicated VVC who have failed fluconazole therapy, to deepen the scientific data on additional dosing options of ibrexafungerp in these challenging complicated VVC scenarios. We thank our advisors and investigators for the strong interest shown in participating in this study, which highlights the need and the opportunity for ibrexafungerp to play a key role in the treatment of women suffering for these burdensome conditions.” For more information on VANQUISH, please visit ClinicalTrials.gov (NCT05399641). About Ibrexafungerp Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids. This agent combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and intravenous (IV) formulations. Ibrexafungerp is in late-stage investigation and development for multiple indications, including life-threatening fungal infections caused primarily by Candida (including C. auris) and Aspergillus species in hospitalized patients. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains. The U.S. Food and Drug Administration (FDA) approved BREXAFEMME® (ibrexafungerp tablets) on June 1, 2021. The FDA also granted Qualified Infectious Disease Product (QIDP) and Fast Track designations for the oral and IV formulations of ibrexafungerp for the indications of invasive candidiasis (IC), including candidemia, and invasive aspergillosis (IA) and has granted Orphan Drug Designation for the IC and IA indications. The European Medicines Agency (EMA) has granted ibrexafungerp Orphan Medicinal Product designation for the indication of IC. Ibrexafungerp is formerly known as SCY-078. INDICATION BREXAFEMME is a triterpenoid antifungal indicated for the treatment of adult and postmenarchal pediatric females with vulvovaginal candidiasis (VVC). DOSAGE AND ADMINISTRATION The recommended dosage of BREXAFEMME is 300 mg (two tablets of 150 mg) twice a day for one day, for a total treatment dosage of 600 mg. BREXAFEMME may be taken with or without food. IMPORTANT SAFETY INFORMATION BREXAFEMME is contraindicated during pregnancy and in patients with a history of hypersensitivity to ibrexafungerp BREXAFEMME administration during pregnancy may cause fetal harm based on animal studies. Prior to initiating treatment, verify pregnancy status in females of reproductive potential and advise them to use effective contraception during treatment When administering BREXAFEMME with strong CYP3A inhibitors, the dose of BREXAFEMME should be reduced to 150 mg twice a day for one day. Administration of BREXAFEMME with strong CYP3A inducers should be avoided Most common adverse reactions observed in clinical trials (incidence ≥2%) were diarrhea, nausea, abdominal pain, dizziness, and vomiting To report SUSPECTED ADVERSE REACTIONS, contact SCYNEXIS, Inc. at 1-888-982-SCYX (1-888-982-7299) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For more information, visit www.brexafemme.com. Please click here for Prescribing Information. About SCYNEXIS SCYNEXIS, Inc. (NASDAQ: SCYX) is a biotechnology company pioneering innovative medicines to help millions of patients worldwide overcome and prevent difficult-to-treat infections that are becoming increasingly drug-resistant. SCYNEXIS scientists are developing the company’s lead asset, ibrexafungerp (formerly known as SCY-078), as a broad-spectrum, systemic antifungal for multiple fungal indications in both the community and hospital settings. SCYNEXIS has initiated the launch of its first commercial product in the U.S., BREXAFEMME® (ibrexafungerp tablets). The U.S. Food and Drug Administration (FDA) approved BREXAFEMME on June 1, 2021. In addition, late-stage clinical investigation of oral ibrexafungerp for the prevention of recurrent vulvovaginal candidiasis (VVC) and the treatment of life-threatening invasive fungal infections in hospitalized patients is ongoing. For more information, visit www.scynexis.com. CONTACT: Investor RelationsIrina KofflerLifeSci AdvisorsTel: (646) 970-4681ikoffler@lifesciadvisors.com Media RelationsBrett WhelanLifeSci CommunicationsTel: (339) 368-0466bwhelan@lifescicomms.com