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Novel Drug Candidates Target Diverse Diseases: Malaria, Gastroparesis, and Cancer

• Novartis unveils NVP-FVP954, a fast-acting IV antimalarial for severe malaria, addressing the urgent need for new treatments due to rising resistance and high infection rates. • Altos Therapeutics and Takeda collaborate on TAK-906, a peripherally-restricted D2/D3 receptor antagonist, to treat gastroparesis by targeting the stomach and vomiting center. • Revolution Medicines advances RMC-9805, a covalent KRAS(G12D)(ON) molecular glue inhibitor, showing promise in synergizing with PD-1 inhibitors for cancer treatment.

The pharmaceutical landscape is witnessing the emergence of innovative drug candidates targeting a range of critical diseases, from infectious diseases like malaria to chronic conditions such as gastroparesis and various forms of cancer. These novel therapies, presented at recent scientific meetings, offer potential improvements over existing treatments and address significant unmet medical needs.

Novartis's NVP-FVP954: A Novel Antimalarial

Malaria, caused by the parasite Plasmodium falciparum, remains a major global health challenge, with over 240 million infections and 600,000 deaths annually, predominantly in sub-Saharan Africa. The rise of resistance against current antimalarial drugs underscores the urgent need for new therapeutic options. At the ACS Fall 2024 meeting in Denver, CO, Novartis disclosed NVP-FVP954, a novel, fast-acting intravenous antimalarial designed for severe malaria cases. Its rapid action and novel mechanism offer a potential breakthrough in combating this deadly disease.

TAK-906: Targeting Gastroparesis

Gastroparesis, a chronic condition characterized by delayed gastric emptying, leads to debilitating symptoms such as nausea, vomiting, pain, and anorexia. Altos Therapeutics and Takeda are collaborating on TAK-906, a peripherally-restricted D2/D3 receptor antagonist, to address this condition. Unlike other treatments, TAK-906 does not penetrate the blood-brain barrier, focusing its action on the stomach and the vomiting center in the area postrema. This targeted approach aims to reduce side effects while effectively managing gastroparesis symptoms.

Revolution Medicines' RMC-9805: A KRAS(G12D) Inhibitor

Revolution Medicines is developing RMC-9805, a first-in-class, covalent KRAS(G12D)(ON) molecular glue inhibitor. This innovative therapy uses a cyclophilin A (CypA)-recruiting tricomplex mechanism combined with an aziridine covalent handle to inhibit the KRAS(G12D) mutant, previously considered “undruggable.” Presented at the AACR 2024 meeting in San Diego, the discovery story detailed how structural and modeling insights were key to engaging a poorly nucleophilic mutant Asp. RMC-9805 has demonstrated synergistic effects with PD-1 inhibitors, marking significant progress in cancer treatment. The company is currently evaluating the compound in clinical trials.
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