Akari's Novel ADC Aims to Reshape Cancer Therapy with Dual-Action Payload

TAMPA, Fla. and LONDON – January 09, 2026 – Akari Therapeutics is charting an ambitious course to transition from a preclinical research firm to a clinical-stage oncology company, a pivotal move underpinned by a novel class of cancer-fighting agents. In a recent corporate update, President and CEO Abizer Gaslightwala detailed the company's significant scientific and operational progress throughout 2025, outlining a clear path toward initiating human trials for its lead candidate by late 2026.

At the heart of Akari's strategy is its innovative antibody-drug conjugate (ADC) platform, which utilizes a proprietary payload known as PH1. This technology aims to deliver a one-two punch to tumors, combining direct cancer cell destruction with a simultaneous activation of the body's own immune system, a dual-action mechanism that could set it apart in the highly competitive landscape of cancer therapeutics.

A New Weapon in the ADC Arsenal

Antibody-drug conjugates have been hailed as “guided missiles” in oncology, designed to deliver potent toxins directly to cancer cells while sparing healthy tissue. Historically, these ADCs have relied on payloads that act as tubulin inhibitors, disrupting cell division, or as DNA-damaging agents. While effective, these mechanisms face challenges, including the development of drug resistance and limited efficacy against certain tumor types.

Akari is pioneering a different approach. Its PH1 payload is a spliceosome modulator, a new class of agent for ADCs. The spliceosome is a cellular machine responsible for editing messenger RNA (mRNA) before it is translated into proteins. In many cancers, this process is altered or hyperactive, making the spliceosome an attractive therapeutic target.

By inhibiting this process, the PH1 payload causes a cascade of events inside the cancer cell. First, it disrupts the production of essential proteins, leading directly to cell death—a potent cytotoxic effect. But its action doesn't stop there. The faulty splicing process also leads to the creation of abnormal, mis-spliced proteins. These malformed proteins are then presented on the cancer cell's surface as neoantigens, effectively acting as red flags that alert the immune system to the presence of a threat. This unique feature transforms the ADC from a simple cytotoxic agent into an immuno-oncology therapy, activating both innate and adaptive immune responses to mount a broader attack against the tumor.

Preclinical data presented by the company has been compelling, showing that this dual mechanism can be effective against cancer cells with notorious oncogenic drivers like KRAS and BRAF, which have long frustrated drug developers. Furthermore, the PH1 payload appears to be resistant to common efflux pumps, a cellular defense mechanism that cancer cells use to expel drugs and a major cause of acquired resistance to existing therapies.

The Path to Human Trials

With promising science in hand, Akari is now focused on the complex operational and regulatory steps required to bring its technology to patients. The company’s lead candidate, AKTX-101, combines the PH1 payload with an antibody that targets Trop2, a receptor that is highly expressed across a wide range of solid tumors, including breast, lung, and urothelial cancers.

To advance AKTX-101, Akari has initiated critical IND (Investigational New Drug)-enabling studies and the associated Chemistry, Manufacturing, and Controls (CMC) activities. A cornerstone of this strategy is a strategic manufacturing partnership established in 2025 with WuXi Biologics, a global leader in ADC development. This collaboration is vital for producing the highly complex, clinical-grade GMP (Good Manufacturing Practice) material required for human trials, a step that often represents a significant hurdle for smaller biotech firms.

According to the company, these advancements position it to potentially initiate a First-in-Human clinical trial for AKTX-101 as early as the end of 2026 or early 2027. Beyond its lead program, Akari is also advancing a second candidate, AKTX-102, which uses the same PH1 payload but targets a different, undisclosed receptor relevant in gastrointestinal and lung cancers, demonstrating the platform's potential breadth.

Navigating a Crowded and Competitive Field

The target selected for AKTX-101, Trop2, is a well-validated but intensely competitive space. Gilead Sciences' Trodelvy, a Trop2-ADC with a topoisomerase inhibitor payload, is already approved for multiple cancer types. Another formidable competitor, datopotamab deruxtecan (Dato-DXd) from Daiichi Sankyo and AstraZeneca, is in late-stage trials and has shown strong results.

In this crowded arena, Akari is betting that its payload, not its target, will be the key differentiator. The ability to activate the immune system offers a distinct advantage over payloads that are purely cytotoxic. Preclinical studies presented by Akari at the 2025 Society for Immunotherapy of Cancer (SITC) meeting provided evidence for this. In a head-to-head model, an ADC using the PH1 payload combined with an anti-PD1 checkpoint inhibitor showed a statistically significant higher rate of complete tumor regressions compared to the established ADC Kadcyla combined with the same checkpoint inhibitor. This suggests a powerful synergy that could unlock new combination therapy strategies and improve outcomes for patients.

The Business of Biotech: Investment and Milestones

For Akari Therapeutics, the transition to a clinical-stage company is not just a scientific milestone but a critical business inflection point. Like many development-stage biotech companies, its financial journey has been volatile. However, the promise of its novel platform has attracted positive attention from some industry analysts. H.C. Wainwright recently reiterated a “Buy” rating on the company, and Maxim Group initiated coverage with a similar positive outlook, signaling confidence from some corners of Wall Street in the long-term potential of the PH1 technology.

The high cost of clinical development remains a significant factor, and the company's ability to fund its ambitious plans will be closely watched by investors. Successfully entering the clinic would serve as a major de-risking event, potentially unlocking new value and attracting further investment or partnership opportunities.

The journey from a promising preclinical concept to an approved therapy is long and fraught with uncertainty. However, Akari's innovative approach to ADC design, which cleverly turns a tumor’s own cellular machinery against it while simultaneously flagging it for immune destruction, represents a compelling new strategy. The upcoming clinical trials for AKTX-101 will be the definitive test of whether this sophisticated scientific approach can translate into meaningful clinical benefits for patients battling some of the most difficult-to-treat cancers.