TAMPA, Fla. and LONDON — November 10, 2025 — Leads & Copy — Akari Therapeutics, Plc (Nasdaq: AKTX) has announced data from its novel antibody drug conjugate (ADC) payload, PH1, that was presented at the 40th Annual Society for Immunotherapy of Cancer (SITC) Meeting. The data showed that the spliceosome targeting payload can induce both cancer cell cytotoxicity and activation of anti-tumor immunity through multiple mechanisms.
According to the data, treatment with a Trastuzumab-PH1 ADC monotherapy drove macrophages to polarize into an anti-tumor/inflammatory state and caused expansion of B cell clones and subsequent IgM antibodies. In preclinical experiments, the combination of Trastuzumab PH1 + anti-PD1 outperformed the combination of Kadcyla® + anti-PD1 with a statistically significantly greater rate of complete responses (74% v 42%, p<0.05).
When combined with anti-PD1 therapy, additional effects included expansion of Gamma-Delta T cell clones demonstrating that the combined regimen drives innate, adaptive, and humoral immunity against the tumor. Akari Therapeutics, an oncology biotechnology company developing novel payloads for ADCs, plans to host a live webcast on Tuesday, November 18th at 11:00 AM ET to discuss the data presented at the SITC Meeting.
Satyajit Mitra Ph.D., Executive Director, Head of Oncology at Akari Therapeutics, presented the abstract titled, A Novel Splicing-Targeted ADC Payload Drives Immune Activation, Synergy with Checkpoint Inhibitors, and Enhanced Therapeutic Potential Beyond Cytotoxicity in oral and poster presentations at the 40th Annual SITC Meeting.
Dr. Mitra stated that he was excited to showcase the unique mechanism of action of Akari’s novel ADC payload PH1 at the annual meeting for SITC. He added that it is not often that one gets to introduce a novel ADC payload class with the unique data Akari presented. Dr. Mitra said he was thrilled to see Akari’s work being received extremely well and the excitement from colleagues to see further clinical development of the PH1 payload as Akari continues to advance its lead ADC molecule, a Trop2 PH1 ADC.
The data outlined Akari’s investigation of multiple mechanisms behind preclinical colon tumor regressions induced by a Trastuzumab PH1 ADC as a single agent or in combination with an anti-PD-1 therapy compared to a first-in-class ADC with a microtubule inhibitor payload, Kadcyla®, also tested as a monotherapy or in combination with anti-PD1 therapy.
The company reported that a higher rate of complete tumor regressions was seen with Trastuzumab PH1 combined with anti-PD1 therapy (74%) when compared to Kadcyla®, combined with anti-PD1 therapy (42%), with statistical significance of p < 0.05.
According to Akari, these differentiated results are attributed to a multi-faceted immune response activated by neoantigens induced by the PH1 payload’s ability to disrupt normal RNA splicing. These neoantigens likely trigger the observed multi-modal immune response including a polarization of macrophages to the pro-inflammatory phenotype, an increase in the presence of neutrophils, and importantly, expansion of both B cell clones to produce polyclonal IgM antibodies, and gamma-delta T-cell clones.
The company reported that these immune system responses were not as prominent in the comparator test arm utilizing Kadcyla®, in combination with anti-PD1 therapy. Akari’s data also highlights a synergy between the PH1 ADC payload and the anti-PD1 checkpoint inhibitor.
Akari stated that the induction of gamma-delta T-cells by the combination of Trastuzumab PH1 and anti-PD1 is particularly interesting because this subpopulation of T-cells is known to attack cancer through a rapid response and has high cytotoxic activity.
The unique results seen with both the single agent ADC Trastuzumab-PH1 and the combination therapy with an anti-PD1 agent open up the possibility of creating a new paradigm of an ADC/checkpoint inhibitor therapy that goes beyond today’s regimens using ADCs with traditional payloads, Akari reported. The company believes this new potential combination of ADC’s using the PH1 payload with checkpoint inhibitors has the opportunity to set a new standard of care and the chance to dramatically improve outcomes for cancer patients.
Akari is advancing a new class of immuno-oncology ADCs built on the platform of a novel PH1 payload, specifically designed to target and disrupt the action of the spliceosome. Akari’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells with a proprietary linker and delivers its novel PH1 payload directly into the tumor. Akari is currently initiating IND-enabling studies with the plan to advance this lead ADC into clinical trials in the near future.
Akari stated that members from the Akari management team will host a live webcast to discuss the presented data for investors, analysts and other interested parties on Tuesday, November 18, 2025 at 11:00 AM ET. Interested participants can access the webcast here or on the Presentations page under the Investors section of the Company’s website, akaritx.com. A replay of the webcast will be accessible two hours after the live event and archived for 90 days.
Akari Therapeutics is an oncology biotechnology company developing next-generation spliceosome payload antibody drug conjugates (ADCs). The Company can generate ADC candidates and optimize them based on the desired application to any target of interest.
Akari also reported that AKTX-101 has shown to have significant activity and prolonged survival, relative to ADCs with traditional payloads and the potential to be synergistic with checkpoint inhibitors, as both a single agent and in combination with checkpoint inhibitors, as compared to appropriate controls.
Investor Relations Contact:
JTC Team, LLC
Jenene Thomas
908-824-0775
AKTX@jtcir.com
Source: Akari Therapeutics, Plc
