An ADC with a novel RNA spliceosome modulating payload PH1 paired with a KRAS inhibitor demonstrates synergistic cytotoxic activity against KRAS G12D and G12C- driven pancreatic cancer models
Data supports the broader applicability of targeting RNA splicing to attack difficult-to-treat KRAS-driven cancers
Findings featured in ASCO 2026 online abstract further differentiate AKTX-101 from TROP2 ADCs utilizing Topoisomerase I inhibitor payloads
TAMPA, Fla. and LONDON, May 21, 2026 (GLOBE NEWSWIRE) — Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing antibody drug conjugates (ADCs) with a novel RNA splicing modulator payload, today announced positive preclinical data featured in an online abstract released in connection with the American Society of Clinical Oncology (ASCO) Annual Meeting 2026 highlighting synergistic cytotoxic activity of AKTX-101 in combination with KRAS inhibition in KRAS-mutated pancreatic cancer models. Access the abstract here.
The data further expands the potential opportunity for Akari’s lead TROP2-targeting ADC, AKTX-101, and its proprietary RNA spliceosome-modulating payload beyond the Company’s current Phase 1 development plan and supports the broader applicability of targeting RNA splicing as a potential way to treat difficult-to-treat KRAS-driven cancers.
The ASCO abstract evaluated the activity of AKTX-101 in combination with adagrasib, a KRAS inhibitor, across pancreatic cancer cell lines harboring KRAS G12D and KRAS G12C. In these studies, the combination of AKTX-101 and adagrasib demonstrated synergistic cell killing in KRAS mutant cell lines driven by G12C and G12D. This synergistic inhibition was not observed with the comparator first-in-class topoisomerase I-targeting TROP2 ADCs. Instead, these ADCs exhibited antagonism when paired with adagrasib. These results suggest that AKTX-101 synergy with KRAS inhibitor may be linked to the novel biology of PH1 targeting RNA splicing. The synergy was explained by PH1’s unique ability target pre-mRNA transcripts for degradation, including those bearing KRAS mutations driving these cancer models.
“KRAS has long been considered one of oncology’s most important but difficult targets, and while recent KRAS inhibitors have represented meaningful progress, there remains a significant opportunity to further enhance activity and broaden therapeutic impact,” said Abizer Gaslightwala, President and Chief Executive Officer of Akari Therapeutics. “These data suggest that our PH1 RNA splicing modulator payload may offer a fundamentally differentiated mechanism capable of enhancing KRAS inhibitor activity in ways not observed with conventional ADC payloads. We believe this represents an exciting opportunity not only for AKTX-101, but potentially for RNA splicing modulation as a new therapeutic strategy across KRAS-driven tumors.”
Dr. Satyajit Mitra, Executive Director and Head of Oncology, stated, “Historically, KRAS mutations have been incredibly difficult to drug, and one may need to approach this problem with drugs of different modalities and mechanisms of action. AKTX 101 synergy with an approved drug, like adagrasib, in an unapproved KRAS setting offers exciting combination possibilities. The PH1 spliceosome modulator payload ADC has the potential to unlock efficacy of cancer therapeutics in cancers with oncogene dependency. We have previously demonstrated combination with AR-v7 oncogenes with enzalutamide and now KRAS oncogenes with adagrasib.”
The data featured in the ASCO 2026 online abstract build upon Akari’s previously reported AACR 2026 findings demonstrating differentiated cytotoxicity and superior potency of AKTX-101 versus current TROP2 ADCs utilizing Topoisomerase I inhibitor payloads across multiple tumor models, including bladder, lung (including KRAS G12V mutated NSCLC) and breast cancers.
Akari’s lead program, AKTX-101, is a TROP2-targeting ADC powered by the Company’s proprietary PH1 RNA spliceosome-modulating payload. Unlike traditional ADC payloads that primarily rely on microtubule or DNA-damaging mechanisms, PH1 is designed to disrupt RNA splicing within cancer cells while also activating innate and adaptive immune responses.
Akari has initiated IND-enabling studies for AKTX-101 and is targeting initiation of a Phase 1 first-in-human clinical trial by mid-2027.
For more information about the ASCO Annual Meeting 2026, please visit www.asco.org.
About Akari Therapeutics
Akari Therapeutics is an oncology biotechnology company developing next-generation antibody drug conjugates (ADCs) with a unique payload, PH1, which targets RNA splicing. Utilizing its innovative ADC discovery platform, the Company has the ability to generate ADC candidates and optimize them based on the desired application to any antigen target of interest. Akari’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells with a proprietary linker, enabling it to deliver its novel PH1 payload directly into the tumor with minimal off-target effects. Unlike current ADCs that use microtubule inhibitors and DNA-damaging agents as their payloads, PH1 is a novel payload that is a spliceosome modulator designed to disrupt RNA splicing within cancer cells. This splicing modulation has been shown in preclinical animal models to induce cancer cell death while activating both the innate and adaptive immune systems to drive robust and durable activity. In preclinical studies, AKTX-101 has been shown to have significant activity and prolonged survival relative to ADCs with traditional payloads. Additionally, AKTX-101 has the potential to be synergistic with checkpoint inhibitors and has demonstrated prolonged survival as both a single agent and in combination with checkpoint inhibitors. The PH1 payload has also been demonstrated to be very active against cancer cells with key oncogenic drivers such as KRAS, BRAF, ARV7, FGFR3 fusions, and others. The Company has initiated IND enabling studies for AKTX-101 with a goal of starting its First-In-Human trial by mid-2027. Akari is also developing AKTX-102, an ADC candidate targeting CEACAM5 (Carcinoembryonic Antigen-related Cell Adhesion Molecule-5), a well-validated tumor antigen broadly expressed across multiple solid tumors. AKTX-102 is designed to leverage Akari’s proprietary PH1 spliceosome-modulating payload and a novel antibody construct to enable differentiated tumor cell killing and immune activation.
For more information about the Company, please visit www.akaritx.com and connect on X and LinkedIn.
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