Akari Therapeutics Reports Breakthrough Preclinical Data Demonstrating Synergistic Activity of AKTX-101 with KRAS Inhibition in KRAS-Mutated Pancreatic Cancer Models
Akari Therapeutics, Plc, 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.
Study Details and Findings
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.”
Building on Previous Discoveries
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.
