On August 18, 2026 Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing antibody drug conjugates (ADCs) with novel RNA splicing modulator payloads, reported 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.

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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.

(Press release, Akari Therapeutics, AUG 18, 2026, View Source [SID1234670205])