Akari Therapeutics Plc

Akari is an oncology company that develops advanced antibody-drug conjugates (ADCs) designed to combat cancer. These ADCs are built using proprietary payloads that leverage powerful biological mechanisms. The company's primary payload, PH1, targets RNA splicing by modulating the spliceosome, a cellular mechanism essential for converting pre-RNA into spliced RNA, which is then translated into proteins vital for cell survival and growth. PH1 disrupts normal RNA splicing, leading to cancer cell death and cytotoxicity. Additionally, this disruption generates neoantigen proteins, which activate both the innate and adaptive immune systems, resulting in robust and lasting cancer-killing activity in preclinical models. AKTX-101 is active against urothelial cancers with FGFR3-fusions, lung cancers with SMARCA4 deletions and BRAF G466V mutations, and K-Ras G12V driven pancreatic cancers. The PH1 payload has also shown activity against metastatic prostate cancer cells driven by AR-v7 and AR-hormone dependent prostate cancer. Akari uses the PH1 payload as a platform to develop a pipeline of ADC candidates, each targeting a different cancer antigen, such as Trop-2 and CEACAM5. Akari's lead candidate, AKTX-101, targets the Trop-2 receptor on cancer cells. It is engineered with a proprietary linker to deliver the PH1 payload directly to tumors, minimizing off-target effects. Preclinical studies have shown AKTX-101 to have significant activity and prolonged survival in animal models compared to ADCs with traditional payloads (topoisomerase1 inhibitors). Due to PH1's unique ability to generate neoantigens, AKTX-101 may also be synergistic with checkpoint inhibitors, demonstrating prolonged survival in combination regimens that exceed the additive efficacy of either treatment alone. The company is advancing AKTX-101 towards clinical trials, having initiated IND-enabling studies with a goal of starting its First-In-Human Phase 1 trial by late 2026/early 2027.