Akari Therapeutics Plc announced the filing of a US provisional patent (No. 63/958,508) covering its second antibody-drug conjugate (ADC) program, AKTX-102, which is designed to target CEACAM5-expressing solid tumors, expanding the company’s next-generation ADC pipeline and intellectual property estate.
AKTX-102 is being developed as a first-in-class ADC combining a novel CEACAM5-directed antibody construct with Akari’s proprietary PH1 spliceosome-modulating payload, an innovative cytotoxic agent intended to induce direct tumor cell death while also engaging both innate and adaptive immune responses.
The patent filing extends Akari’s ADC platform composition-of-matter protection to include novel antibody constructs and ADC architectures built around the PH1 payload and antibody design, further strengthening the company’s intellectual property position.
Akari is also advancing its lead ADC program, AKTX-101, which targets Trop2, toward IND/CTA submission and first-in-human studies expected in late 2026 or early 2027, with regulatory interactions planned in the first half of 2026.
Research context
CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule-5) is a well-validated tumor-associated antigen that is frequently expressed across multiple high-unmet-need cancers, including gastrointestinal malignancies (80–90% expression), bladder cancer (~30%), lung adenocarcinoma (25%), and luminal A breast cancer (up to 50%). Despite its prevalence, CEACAM5 has historically proven to be a challenging therapeutic target.
The clinical landscape for CEACAM5-directed therapies is evolving, with current development efforts focused primarily on ADCs, alongside emerging modalities such as bispecific antibodies and cell therapies. Sanofi suffered a notable setback in 2023 when its CEACAM5-targeting ADC SAR408701 failed to meet Phase III endpoints in non-small cell lung cancer. As a result, the field is currently led by Merck KGaA’s Phase III-stage precemtabart tocentecan, while Pfizer’s Seagen-originated SGN-CEACAM5C (PF-08046050) remains in Phase I/II development.
Notably, both Merck and Pfizer employ topoisomerase I (Topo-1) inhibitor payloads, in contrast to Akari’s differentiated strategy using a PH1 spliceosome-modulating payload. PH1, a thailanstatin analog, disrupts pre-mRNA splicing, leading to mRNA decay, depletion of essential proteins, and accumulation of mis-spliced proteins that act as neoepitopes. This mechanism is designed to drive both direct cytotoxicity and immune-mediated tumor cell killing.
By comparison, Topo-1 inhibitor payloads—such as those used in approved ADCs Enhertu and Trodelvy—induce DNA damage–mediated cell death but are associated with established resistance mechanisms and toxicity profiles. Akari is applying PH1 payloads with the aim of overcoming resistance inherent to DNA-damaging agents and has indicated that PH1 may confer immune-mediated anti-tumor effects while potentially reducing certain toxicities, including neutropenia and peripheral neuropathy.