dichloroacetate (SL-1009) / Saol Therap, University of Florida, Medosome Biotec - LARVOL DELTA

Saol Therapeutics Has Been Granted a Type A Meeting with the FDA to Determine the Path Forward for SL1009 in Pyruvate Dehydrogenase Complex Deficiency (PDCD) (PRNewswire) - "In the two months since receiving an unexpected Complete Response Letter (CRL), Saol has collected additional data and performed new analyses to help address the clinical deficiencies raised by the FDA. Saol's objective is to collaborate with the FDA on a pathway to approval without the need for a new clinical trial, which is not feasible."

FDA event • Metabolic Disorders

Safety, pharmacokinetics, and pharmacodynamic effects of dichloroacetate in patients with recurrent glioblastoma (SNO 2025) - "PDK expression and lactate levels are associated with worse cancer outcomes. Combining DCA with standard radiation and chemotherapy could improve outcomes of newly diagnosed GBM patients."

Clinical • PK/PD data • Brain Cancer • Glioblastoma • Metabolic Disorders • Solid Tumor • PCNA • PDHA1 • PDK4 • PGK1

Safety, pharmacokinetics, and pharmacodynamic effects of dichloroacetate in patients with recurrent glioblastoma (WFNOS 2025) - "PDK expression and lactate levels are associated with worse cancer outcomes. Combining DCA with standard radiation and chemotherapy could improve outcomes of newly diagnosed GBM patients."

Clinical • PK/PD data • Brain Cancer • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor • PCNA • PDHA1 • PDK4 • PGK1

Pyruvate Dehydrogenase Complex Stimulation with Dichloroacetate May Improve Septic Cardiac Dysfunction. (PubMed, Shock) - "Our findings revealed that sepsis decreased PDH activity in cardiac tissue. Rebalancing PDH activity with DCA improved cardiac performance after CLP. While imaging mass spectrometry identified changes in itaconate concentration and enabled detection of tricarboxylic acid cycle metabolites, further investigation is necessary to determine whether DCA is an effective therapeutic agent for septic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock

Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice. (PubMed, Geroscience) - "Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents to the list of interventions identified by the ITP that extend lifespan, this report continues the strong male bias in the efficacy of life-extending drugs identified so far."

Heterogeneity • Journal • Preclinical

Saol Therapeutics Receives Complete Response Letter from FDA for SL1009 (DCA) for the Treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD) (PRNewswire) - "The FDA provided specific observations within the CRL that Saol will need to address to clarify the path forward. These observations did not include any findings regarding the manufacturing of SL1009. To address the deficiencies as the FDA requested, it would take several years and require significant financial resources."

CRL • Metabolic Disorders

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM) (clinicaltrials.gov) - P2 | N=40 | Active, not recruiting | Sponsor: University of Florida | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: (clinicaltrials.gov) - P3 | N=34 | Active, not recruiting | Sponsor: Saol Therapeutics Inc | Trial completion date: Mar 2025 ➔ Aug 2025 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Metabolic Disorders

Expanded Access Treatment Protocol With DCA for Patients With PDCD (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Saol Therapeutics Inc

New trial • Metabolic Disorders

Trial of Dichloroacetate (DCA) in Glioblastoma Multiforme (GBM) (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: University of Florida | Trial completion date: Jun 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Clinical Physiology and Pharmacology of GSTZ1/MAAI. (PubMed, Biochem Pharmacol) - "MAAI is identical to the zeta 1 family isoform of GST, which biotransforms the investigational drug dichloroacetate (DCA) to the endogenous compound glyoxylate. Gene association studies have linked GSTZ1 or its protein product to various physiological traits and pathologies. Haplotype variations in GSTZ1 influence the rate of DCA metabolism, enabling a genotyping strategy to allow potentially safe, precision-based drug dosing in clinical trials."

Journal • Review

Dichloroacetate as a novel pharmaceutical treatment for cancer-related fatigue in melanoma (AACR 2023) - "Moreover, we found that DCA could relieve treatment-worsened CRF in murine YUMMER1.7 melanoma (treated with anti-PD1 immunotherapy) and MC38 colon cancer (treated with 5-fluorouracil chemotherapy) without affecting the efficacy of these treatments. The abnormal increase of muscle mitochondrial membrane potential, which may enhance reactive oxygen species production, was also reversed in DCA-treaded mice. In all, this study provides evidence for DCA as the first potential adjuvant pharmaceutical treatment to maintain physical function and motivation in cancer patients experiencing CRF."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor

Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: (clinicaltrials.gov) - P3 | N=34 | Active, not recruiting | Sponsor: University of Florida | Trial completion date: May 2023 ➔ Mar 2025 | Trial primary completion date: Apr 2023 ➔ Mar 2025

Trial completion date • Trial primary completion date • Metabolic Disorders

In-vivo magnetic resonance spectroscopy of lactate as a non-invasive biomarker of dichloroacetate activity in cancer and non-cancer central nervous system disorders. (PubMed, Front Oncol) - "This difference is most striking in focal impairments of lactate metabolism suggesting that MRS might provide data not captured by solely monitoring blood. In summary, our findings corroborate the feasibility of MRS as a pharmacokinetic/pharmacodynamic biomarker of DCA delivery in the CNS, that is ready to be integrated into currently ongoing and future human clinical trials using DCA."

Journal • Preclinical • Review • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Glioma • Metabolic Disorders • Oncology • Solid Tumor

Saol Therapeutics enhances its IP portfolio for Dichloroacetate (DCA; SL-1009) in Glioblastoma and Rare Pediatric Cancers (PRNewswire) - "Saol Therapeutics...announced today the signing of an agreement with Medosome Biotec to provide Saol the rights to use their patented genotype test for all potential indications where SL-1009 might be used as a therapy.... 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."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioblastoma • Oncology