TAMPA, Fla. and LONDON, UK — Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing novel payload antibody drug conjugates (ADCs), today announced key preclinical data demonstrating the therapeutic potential of its novel ADC targeting Trop2, AKTX-101, in pancreatic cancer driven by K-Ras mutations, one of the deadliest and most treatment-resistant forms of cancer.
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that approximately 60,000 people will be diagnosed annually with pancreatic cancer2, and about 50,000 people will die from this aggressive disease. The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) and its variants, account for the vast majority of cases3 and have few effective treatment options, particularly for tumors driven by the K-Ras G12V mutation.
Current standard of care in K-Ras G12V-driven PDAC are 5-fluorouracil (5-FU) containing chemotherapy regimens such as FOLFIRINOX (Overall Survival = 1.5 years) or gemcitabine plus nab-paclitaxel (Overall Survival = 1.3 years), which offer poor outcomes, significant toxicities, and poor quality of life. Currently, there is a real void of targeted therapies for K-Ras driven PDAC, making this still one of the highest unmet need cancers. Current K-Ras inhibitors, such as Lumakras® and Krazati®, are only approved in K-Ras G12C mutated non-small cell lung cancer and colorectal cancer further emphasizing the void and the significant unmet need for K-Ras G12V targeted therapy options in PDAC patients.
AKTX-101 is an antibody-drug conjugate that delivers a novel RNA spliceosome modulating payload, PH1, into cancer cells that express Trop2 which is a protein commonly found at high levels in pancreatic and other hard-to-treat solid tumors. Once inside the tumor, the PH1 payload disrupts normal RNA splicing, a fundamental process cancer cells depend on to survive, grow, and spread. Trop2 is a ubiquitously expressed protein at high levels in PDAC and potentially a good ADC target4 in pancreatic cancer, and has been validated in other solid tumors including lung and breast cancers. Within pancreatic cancer, K-Ras mutated PDAC is associated with higher levels of Trop2 protein4 compared to PDAC with normal K-Ras, making a Trop2 ADC like ATKX-101 a potential precision therapeutic in this specific tumor mutation.
The latest data for AKTX-101 in KRas-G12V PDAC builds on preclinical evidence disclosed earlier in a patent filing. In this new study, AKTX-101 exhibited single digit nanomolar cytotoxic potency in all K-Ras G12V PDAC cell lines tested. Of significance, AKTX-101 also outperformed daraxonrasib in multiple PDAC cell lines (daraxonrasib is an investigational therapy being developed by Revolution Medicines to treat patients with cancers driven by K-Ras mutations).
bizer Gaslightwala, President and Chief Executive Officer of Akari Therapeutics commented, “These preclinical data provide a rationale for Akari to develop AKTX-101 in areas of severe unmet need and historically very difficult cancers, such as K-Ras mutant PDAC. We aspire to tackle hard-to-treat cancers and are excited to see our novel spliceosome-modulating payload PH1, conjugated to an ADC, demonstrate activity against aggressive cancers like K-Ras mutant tumors.”
From this early data, the Company believes that AKTX-101 may have therapeutic potential to control an aggressive form of untreatable pancreatic cancer and its preliminary data support K-Ras G12V-mutated PDAC as another high unmet need opportunity for AKTX-101. These data continue to demonstrate the promise of the PH1 payload in treating some of the most difficult cancers like K-Ras mutant tumors.
The Company plans to present this preclinical data at an upcoming scientific conference and is currently advancing AKTX-101 towards a first-in-human trial, expected to initiate in late 2026, and preliminary safety and efficacy data in 2027. In parallel, the Company is pursuing discussions with potential partners on developing the PH1 payload for new ADCs targeting other antigens expressed in a range of cancer tumors.
About Akari Therapeutics
Akari Therapeutics is an oncology biotechnology company developing next-generation spliceosome payload antibody drug conjugates (ADCs). 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 target of interest. Akari’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells and with a proprietary linker, delivers its novel PH1 payload directly into the tumor. Unlike current ADCs that use tubulin 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 immune cells to drive robust and durable activity. In preclinical studies, AKTX-101 has 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, as compared to appropriate controls. The Company is generating validating data on its novel payload PH1 to continue advancing its lead asset, as well as other undisclosed targets with this novel payload.
For more information about the Company, please visit www.akaritx.com and connect on X and LinkedIn.
Investor Relations Contact
JTC Team, LLC
Jenene Thomas
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References
1 Ebia et al 2025, https://doi.org/10.1200/PO-24-00684
2 Siegel RL, et al. CA Cancer J Clin. 2024;74:12-49
3 Hallbrook CJ, et al. Cell. 2023;186:1729-1754
4 Mas et al 2023, https://doi.org/10.1016/j.clinre.2023.102108