Akari Therapeutics Builds Momentum for AKTX-101 with Compelling Urothelial Cancer Data Supporting Differentiated ADC Strategy

AKTX-101 demonstrated robust anti-tumor activity across multiple clinically relevant urothelial cancer preclinical models

Data supports the potential of Akari’s novel PH1 RNA spliceosome-modulating payload to overcome payload-specific resistance

Results strengthen the rationale for a differentiated ADC sequencing strategy as ADC use expands across oncology and more patients require treatment following relapse

Akari advancing IND-enabling activities for AKTX-101 toward planned Phase 1 clinical development in mid-2027

TAMPA, Fla. and LONDON, Aug. 18, 2026 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing antibody drug conjugates (ADCs) with novel RNA splicing modulator payloads, today announced new preclinical data demonstrating the potential of AKTX-101, the Company's proprietary TROP2-targeted ADC utilizing its novel PH1 RNA spliceosome modulating payload, as a differentiated therapeutic approach for urothelial cancer in disease settings where currently available ADC therapies may have limited clinical benefit.

The findings demonstrated meaningful anti-tumor activity across multiple clinically relevant urothelial cancer preclinical models including advanced urothelial cancer with limited response to currently approved ADC therapy, and tumors with acquired resistance following treatment with a first-generation TROP2-directed ADC. Collectively, the data provide additional validation for Akari's strategy of developing ADCs with a differentiated payload mechanism designed to address emerging limitations associated with existing ADC payload classes, such as microtubule and topoisomerase 1 inhibitors.

"ADC therapies have transformed the treatment landscape across oncology, but the next wave of innovation will require advances beyond conventional payloads classes used with currently approved ADCs," said Abizer Gaslightwala, President and Chief Executive Officer of Akari Therapeutics. "As ADCs continue moving earlier in the treatment paradigm, more patients will ultimately require additional treatment following relapse, thus creating an urgent need for differentiated payload technologies capable of overcoming resistance and enabling effective ADC payload sequencing strategies. We believe our proprietary PH1 RNA spliceosome modulating payload has the potential to address this important challenge, and these new preclinical findings further strengthen our confidence in AKTX-101 as we advance the program toward Phase 1 development."

Urothelial cancer has become one of the fastest-growing categories for ADC therapy, with Padcev® (enfortumab vedotin) representing > $3.5B in annual sales. Despite these advances, patients that relapse after receiving PADCEV® continue to face significant unmet medical needs and limited treatment options. As the use of ADCs expands, developing novel payload mechanisms capable of maintaining anti-tumor activity following prior ADC exposure has become an increasingly important priority across the oncology field.

In Akari’s most recent preclinical studies, AKTX-101 demonstrated encouraging activity across multiple urothelial cancer models designed to evaluate its potential therapeutic profile across different clinical settings, including:

• Demonstrated statistically significant anti-tumor activity in the UM-UC-14 advanced urothelial carcinoma model, which represents metastatic urothelial cancer, a setting where Padcev® (enfortumab vedotin) is currently approved as first-line therapy. While Padcev® had limited responsiveness on the tumor in this model, AKTX-101 achieved statistically significant tumor growth inhibition compared with vehicle, supporting the potential of its differentiated payload mechanism in settings where current ADC payloads may have reduced effectiveness.
• Demonstrated encouraging activity following acquired resistance to the first-generation TROP2-directed ADC Trodelvy® (sacituzumab govitecan). Tumors initially treated with Trodelvy subsequently developed resistance and resumed growth. When these resistant tumors were switched from Trodelvy to AKTX-101, tumor growth was again slowed, suggesting that resistance was associated with the Topoisomerase I payload, and that the AKTX-101 PH1 payload mechanism of disrupting RNA splicing can be effective in this resistant setting. These findings support the potential for AKTX-101's novel PH1 payload to provide therapeutic benefit following prior treatment with first-generation TROP2 ADCs in several areas where these ADCs are currently approved, including potentially breast and lung cancers.
  
  

"One of the most important questions facing the ADC field today is how best to treat patients after progression on prior ADC therapies," said Satyajit Mitra, Ph.D., Head of Oncology R&D at Akari Therapeutics. "The activity we observed in tumors that have developed resistance to Trodelvy is particularly encouraging because it suggests resistance may be driven by the payload rather than loss of the TROP2 target itself. These findings provide compelling support for our hypothesis that introducing a differentiated payload mechanism may overcome payload-specific resistance while preserving target tumor engagement, reinforcing the potential of our PH1 platform to address an increasingly important unmet need in oncology."

Akari continues to advance IND-enabling activities for AKTX-101 with the goal of initiating a Phase 1 clinical trial in mid-2027. The Company is also expanding development opportunities for its proprietary PH1 payload platform through additional tumor-specific programs and strategic collaborations designed to maximize the platform's long-term clinical and commercial potential.

About Akari Therapeutics

Akari Therapeutics is an oncology biotechnology company developing next-generation antibody drug conjugates (ADCs) with a unique payload, PH1, which targets RNA splicing. 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 antigen target of interest. Akari’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells with a proprietary linker, enabling it to deliver its novel PH1 payload directly into the tumor with minimal off-target effects. Unlike current ADCs that use microtubule 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 both the innate and adaptive immune systems to drive robust and durable activity. In preclinical studies, AKTX-101 has been 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. The PH1 payload has also been demonstrated to be very active against cancer cells with key oncogenic drivers such as KRAS, BRAF, ARV7, FGFR3 fusions, and others. The Company has initiated IND enabling studies for AKTX-101 with a goal of starting its First-In-Human trial by mid-2027. Akari is also developing AKTX-102, an ADC candidate targeting CEACAM5 (Carcinoembryonic Antigen-related Cell Adhesion Molecule-5), a well-validated tumor antigen broadly expressed across multiple solid tumors. AKTX-102 is designed to leverage Akari’s proprietary PH1 spliceosome-modulating payload and a novel antibody construct to enable differentiated tumor cell killing and immune activation.

For more information about the Company, please visit www.akaritx.com and connect on X and LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release includes express or implied forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, about the Company that involve risks and uncertainties relating to future events and the future performance of the Company. Actual events or results may differ materially from these forward-looking statements. Words such as “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “future,” “opportunity” “will likely result,” “target,” variations of such words, and similar expressions or negatives of these words are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. Examples of such forward-looking statements include, but are not limited to, express or implied statements regarding the ability of the Company to advance its product candidates for the treatment of cancer and the timing of commencement of a Phase I clinical trial. These statements are based on the Company’s current plans, estimates and projections. By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific. A number of important factors, including those described in this communication, could cause actual results to differ materially from those contemplated in any forward-looking statements. Factors that may affect future results and may cause these forward-looking statements to be inaccurate include, without limitation: the Company’s need for additional capital; the potential impact of unforeseen liabilities, future capital expenditures, revenues, costs, expenses, earnings, synergies, economic performance, indebtedness, financial condition and losses on the future prospects, business and management strategies for the management, expansion and growth of the business; risks related to global as well as local political and economic conditions, including interest rate and currency exchange rate fluctuations; potential delays or failures related to research and/or development of the Company’s programs or product candidates; risks related to any loss of the Company’s patents or other intellectual property rights; any interruptions of the supply chain for raw materials or manufacturing for the Company’s product candidates, including as a result of potential tariffs; the nature, timing, cost and possible success and therapeutic applications of product candidates being developed by the Company and/or its collaborators or licensees; the extent to which the results from the research and development programs conducted by the Company, and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; uncertainty of the utilization, market acceptance, and commercial success of the Company’s product candidates; risks related to competition for the Company’s product candidates; and the Company’s ability to successfully develop or commercialize its product candidates. While the foregoing list of factors presented here is considered representative, no list should be considered to be a complete statement of all potential risks and uncertainties. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company’s filings with the SEC, copies of which may be obtained from the SEC’s website at www.sec.gov. The Company assumes no, and hereby disclaims any, obligation to update the forward-looking statements contained in this press release except as required by law.

Investor Relations Contact

JTC Team, LLC
Jenene Thomas
908-824-0775
AKTX@jtcir.com