Sodium Dichloroacetate

Cancer-related fatigue is a debilitating yet all-too-common condition, which can severely affect quality of life for patients undergoing treatment. For those struggling with CRF, there have been no effective pharmaceutical treatments for the constellation of symptoms that together define the syndrome. Researchers found that a metabolism-targeting drug called dichloroacetate (DCA) helped alleviate CRF in mice, without interfering with cancer treatments. Cancer-related fatigue (CRF) is a debilitating yet all-too-common condition, which can severely affect quality of life for patients undergoing treatment. For those struggling with CRF, there have been no effective pharmaceutical treatments for the constellation of symptoms that together define the syndrome. In a new study led by Yale Cancer Center researchers at Yale School of Medicine, the team found that a metabolism-targeting drug called dichloroacetate (DCA) helped alleviate CRF in mice, without interfering with cancer treatments. The findings are a pathway for future CRF research that may someday lead to a new therapy for patients. The results were published in American Journal of Physiology-Endocrinology and Metabolism on Oct. 2. "This study identifies dichloroacetate, an activator of glucose oxidation, as the first intervention, and particularly the first metabolism-focused intervention, to prevent the whole syndrome of cancer-related fatigue in preclinical models," said senior author Rachel Perry, who is a member of Yale Cancer Center. Researchers used tumor-bearing mouse models to investigate the effectiveness of DCA in treating cancer-related fatigue for patients living with melanoma. The group found that DCA did not affect the rates of tumor growth or compromise the effectiveness of immunotherapy or chemotherapy in two mouse cancer models. DCA also significantly preserved physical function and motivation in mice with late-stage tumors. The data suggests that DCA treatment may have several positive effects, including reducing oxidative stress in muscle tissue of tumor-bearing mice. The researchers said DCA could be a practice-changing approach in the future, when used as an adjuvant therapy to treat cancer-related fatigue. "We hope that this research will provide the bedrock for future clinical trials using dichloroacetate -- an FDA-approved drug for another indication (lactic acidosis) -- to treat the debilitating syndrome of cancer-related fatigue," said Perry, who is also an assistant professor of medicine (endocrinology) and of cellular and molecular physiology at Yale School of Medicine.

By signing an agreement with Medosome Biotec By providing support for clinical trial treatment of GBM at the University of Florida By starting a collaborative research project in rare pediatric cancers with a leading cancer center ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, March 16, 2023 /PRNewswire/ -- Saol Therapeutics ("Saol"), a privately held, clinical-stage pharmaceutical company, announced today the signing of an agreement with Medosome Biotec, LLC to provide Saol the rights to use their patented genotype test for all potential indications where SL-1009 might be used as a therapy. The test is performed to identify potential mutations at GSTZ1 (glutathione S-transferase zeta 1 human enzyme) that categorize individuals as fast or slow metabolizers of DCA (SL-1009). Utilization of the genotype testing enables individual dosing, potentially reducing the incidence of treatment related adverse events. Prior to this agreement Saol only had rights to the patented genotype test for the indication of Pyruvate Dehydrogenase Complex Deficiency (PDCD). "We are pleased to have executed these agreements to support our pursuit of expanded opportunities beyond PDCD" As part of the agreement Saol will aid patient recruitment efforts for the Phase IIA Trial of DCA in Glioblastoma Multiforme (GBM) by providing additional funding and resource support. Glioblastoma is aggressive and the most common type of primary brain cancer in adults. GBM is difficult to treat and there is no known cure. This study, sponsored by the University of Florida and the Food and Drug Administration (FDA) (NCT05120284), is further supported in partnership with Medosome Biotec and Saol. Dr. Peter Stacpoole is Principal Investigator for the PDCD trial and the GBM trial and is Professor of Medicine at University of Florida. Dr. Stacpoole stated, "We are pleased to expand our partnership with Saol Therapeutics. Our partnership has led to over-enrollment of our Phase III study in PDCD (NCT02616484) and we mutually see the broader potential application of DCA as the prototypic inhibitor of Pyruvate Dehydrogenase Kinases (PDKs) that, in turn, inhibit PDC enzymatic activity. We look forward to collaborating with Saol on potential additional indications for DCA. Expansion of our collaboration on the GBM trial will result in the addition of more study sites, allowing for quicker recruitment of patients. We are hopeful that DCA will be an important addition to the treatment of GBM." Saol also recently signed a sponsored research agreement with a leading cancer center to evaluate DCA in rare pediatric solid tumors. The preclinical research will investigate DCA alone and in combination with chemotherapy in several different pediatric tumor models, such as Wilms, Neuroblastoma, Rhabdoid Tumor, Osteosarcoma, Ewing Sarcoma, and Rhabdomyosarcoma. Literature suggests that DCA could be effective in several rare, pediatric, solid tumors. The rationale for the pediatric tumor screening includes the fact that DCA has been widely studied in animals and humans and has a mechanism of action that might override the Warburg effect seen in cancer cells1,2,3,4. Saol is currently studying this medicine in children using a proprietary formulation developed for pediatric use (NCT02616484). "If the pre-clinical assessment provides encouraging data, the work already conducted in pediatric patients may allow us to quickly transition toward clinical investigation", commented Dr. Virinder Nohria, Chairman and Chief Medical Officer at Saol. These agreements, and the additional investments behind them, represent an important next step in the evolution of Saol Therapeutics as an emerging pharmaceutical company. "Now that we have completed enrollment in the PDCD trial we are rapidly transitioning to other important therapeutic areas, and are evaluating the utility of DCA (SL-1009) in adult and pediatric oncology indications with limited treatment options", said Saol CEO David Penake. "We are pleased to have executed these agreements to support our pursuit of expanded opportunities beyond PDCD". Saol expects to have topline data in the PDCD trial in the 3rd quarter of 2023. Should the results of the trial support a subsequent FDA approval, it will be the first and only medicine approved for this rare, pediatric indication. References Aminzadeh S, Vidali S, Sperl W, Kofler B, Feichtinger RG. Energy metabolism in neuroblastoma and Wilms tumor. Transl Pediatr. 2015 Jan;4(1):20-32. doi: 10.3978/j.issn.2224-4336.2015.01.04. Guo JQ, Tang HY, Wang CD, Sang BT, Liu X, Yi FP, Liu GL, Wu XM. Influence of Dichloroacetate on Wilms' Tumor in vitro. Ann Clin Lab Sci. 2022 Jan;52(1):101-108. PMID: 35181623. Kankotia S, Stacpoole PW. Dichloroacetate and cancer: new home for an orphan drug? Biochim Biophys Acta. 2014 Dec;1846(2):617-29. doi: 10.1016/j.bbcan.2014.08.005. Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019 Nov 14;2019:8201079. doi: 10.1155/2019/8201079. PMID: 31827705. About Dichloroacetate (DCA; SL-1009) DCA, a pan- PDK inhibitor, has the potential to be the 1st approved medication for the mitochondrial disease PDCD and will be available as an oral solution. Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. However, PDC is also inhibited by PDKs, that may be over-expressed in PDCD. DCA inhibits PDKs to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. DCA dosing is based on a proprietary genetic test that dichotomizes subjects into "fast" and "slow" drug metabolizers, providing individualized dosing. About Saol Therapeutics Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit . About Medosome Biotec Medosome Biotec, LLC is a privately held, preclinical and early-stage clinical pharmaceutical company with operations in Alachua, FL and Bloomington, IN. The Company focuses on pediatric diseases with an emphasis on developing and offering genetic tests for diagnosing rare diseases and providing personalized dosing of pharmaceutical drugs. For more information, visit Media contact: Brian Nappi, Senior Vice President Strategy, bnappi@saolrx.com