On November 10, 2025 Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing novel payloads for antibody drug conjugates (ADCs), reported the presentation of immune mechanism-of-action data for its novel ADC payload, PH1. The Company will host a live webcast to discuss the presented data on Tuesday, November 18th (details below).

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The abstract titled,A Novel Splicing-Targeted ADC Payload Drives Immune Activation, Synergy with Checkpoint Inhibitors, and Enhanced Therapeutic Potential Beyond Cytotoxicity was presented in oral and poster presentations at the recently held 40th Annual SITC (Free SITC Whitepaper) Meeting by Satyajit Mitra Ph.D., Executive Director, Head of Oncology at Akari Therapeutics.

Dr. Mitra commented, "We were excited to showcase the unique mechanism of action of our novel ADC payload PH1 at the annual meeting for SITC (Free SITC Whitepaper), a premier global immunotherapy conference. It’s not often that one gets to introduce a novel ADC payload class with the unique data we presented. I was thrilled to see our 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 presented 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, tested also as a monotherapy or in combination with anti-PD1 therapy. 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. 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. Notably, these immune system responses were not as prominent in the comparator test arm utilizing Kadcyla, in combination with anti-PD1 therapy. Importantly, these Trastuzumab PH1 results also highlight a synergy between the PH1 ADC payload and the anti-PD1 checkpoint inhibitor. 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.

Key Highlights:

Payload diversification is key in the current ADC landscape dominated by 2 ADC payload classes, microtubule inhibitors, and topoisomerase inhibitors.
A payload that disrupts the actions of the spliceosome demonstrates multiple modes of actions to attack cancer, including cytotoxicity and broad immuno-oncology effects.
An ADC of Trastuzumab PH1 induces RNA mis-splicing and subsequently increases neoantigen generation in cancer cells and a subsequent increase in anti-cancer immune cells in the tumor microenvironment.
Trasutuzmab-PH1 in combination with an anti-PD1 agent outperformed Kadcyla in combination with an anti-PD1 agent in complete tumor regressions with statistical significance (74% vs. 42%, p < 0.05) in an immune-competent, HER2-positive colon cancer model.
When combined with anti-PD1 therapy, the MOAs of the two agents complemented each other: Trastuzumab PH1 increased neoantigens, driving an increase in pro-inflammatory macrophages, an increase in pro-inflammatory neutrophils, and the expansion of B cells and resulting IgM antibodies. The anti-PD1 therapy specifically expanded alpha-beta T cell clones as expected, and together, the combination of both therapies drove the unique expansion of gamma-delta T cell clones. The synergy of the Trastuzumab PH1+ anti-PD-1 agent is likely due to each agent’s unique and complementary impact on the immune system.

These 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. 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.

Utilizing its innovative ADC payload platform, Akari is advancing a new class of immuno-oncology ADCs built on the platform of a novel PH1 payload. This payload is designed specifically to target and disrupt the action of the spliceosome and has a unique preclinical efficacy and safety profile with the potential to address an unmet need for oncology patients as a monotherapy or used in combination with checkpoint inhibitors. 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. For more information, visit www.akaritx.com.

Webcast Details

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.

(Press release, Akari Therapeutics, NOV 10, 2025, View Source [SID1234659702])