Akari Therapeutics’ Preclinical Data Demonstrates the Potential of its Novel ADC Spliceosome Modulating Payload, PH1
Akari Therapeutics (NASDAQ: AKTX) has announced promising preclinical data for its novel ADC spliceosome modulating payload, PH1, targeting hormone refractory prostate cancer. The data demonstrates PH1's ability to suppress AR-V7 receptor levels, which drives metastatic castration resistant prostate cancer (mCRPC) progression.
The research showed PH1's effectiveness in both hormone-refractory and hormone-sensitive prostate cancer models. In hormone-sensitive cases, PH1 showed additive effects when combined with existing treatments like Xtandi and Erleada. This suggests potential for developing first-line combination therapies and addressing the significant unmet need in ARPI-resistant cases, where current treatment options are limited.
Akari Therapeutics (NASDAQ: AKTX) ha annunciato dati preclinici incoraggianti sul suo nuovo payload di modulazione dello spliceosoma ADC, PH1, mirato al cancro della prostata resistente agli ormoni. I dati mostrano che PH1 è in grado di ridurre i livelli del recettore AR-V7, che guida la progressione del cancro della prostata metastatico resistente alla castrazione. La ricerca ha dimostrato l’efficacia di PH1 sia in modelli di cancro prostatico resistenti agli ormoni sia sensibili agli ormoni. Nei casi sensibili agli ormoni, PH1 ha mostrato effetti additivi quando combinato con trattamenti esistenti come . Questo suggerisce potenzialità per terapie di prima linea in combinazione e per rispondere al significativo bisogno insoddisfatto nelle casistiche ARPI-resistant, dove le opzioni di trattamento attuali sono limitate.
Akari Therapeutics (NASDAQ: AKTX) ha anunciado datos preclínicos prometedores sobre su nuevo payload de modulación del espliceosoma ADC, PH1, dirigido al cáncer de próstata resistente a hormonas. Los datos muestran que PH1 puede suprimir los niveles del receptor AR-V7, que impulsa la progresión del cáncer de próstata metastásico resistente a la castración (mCRPC). La investigación demostró la efectividad de PH1 en modelos de cáncer de próstata tanto hormonodependientes como hormonoindependientes. En casos sensibles a hormonas, PH1 mostró efectos aditivos al combinarse con tratamientos existentes como Xtandi y Erleada. Esto sugiere potencial para terapias de primera línea en combinación y abordar la considerable necesidad insatisfecha en casos ARPI-resistentes, donde las opciones de tratamiento actuales son limitadas.
Akari Therapeutics(NASDAQ: AKTX)는 호르몬에 의한 저항성을 가진 전립선암을 겨냥한 새로운 ADC 스플라이소좀 조절 페이로드 PH1에 대한 초기 동물/세포 데이터가 유망하다고 발표했다. 데이터는 AR-V7 수용체 수준을 억제하는 PH1의 능력을 보여주며, 이는 전이성 거세저항성 전립선암(mCRPC)의 진행을 주도한다. 연구는 PH1의 호르몬 저항 및 호르몬 민감 전립선암 모델 모두에서 효과를 확인했다. 호르몬 민감한 경우 PH1은 Xtandi와 Erleada와 같은 기존 치료제와 병용 시 보완 효과를 보였다. 이는 1차 치료 조합 요법 개발과 ARPI 저항 사례에서의 큰 미충족 수요를 해결할 수 있는 치료 옵션의 확장 가능성을 시사한다.
Akari Therapeutics (NASDAQ: AKTX) a annoncé des données précliniques prometteuses pour son nouveau payload ADC modulant le spliceosome, PH1, ciblant le cancer de la prostate résistant aux hormones. Les données démontrent la capacité de PH1 à diminuer les niveaux du récepteur AR-V7, qui stimule la progression du cancer de la prostate métastatique résistant à la castration (mCRPC). La recherche a montré l’efficacité de PH1 dans des modèles de cancer de la prostate à la fois résistants et sensibles aux hormones. Dans les cas sensibles, PH1 a montré des effets additifs lorsqu’il est combiné avec des traitements existants tels que Xtandi et Erleada. Cela suggère un potentiel pour des thérapies de première ligne en association et pour répondre au besoin important non satisfait dans les cas résistants aux ARPI, où les options de traitement actuelles sont limitées.
Akari Therapeutics (NASDAQ: AKTX) hat vielversprechende präklinische Daten zu seinem neuartigen ADC-Spleißosom-Modulierungs-Payload PH1 vorgelegt, der auf hormonaversagenen Prostatakrebs abzielt. Die Daten zeigen PH1s Fähigkeit, AR-V7-Rezeptor-Niveaus zu unterdrücken, die das Fortschreiten des metastasierenden kastrationsresistenten Prostatakrebs (mCRPC) antreiben. Die Forschung zeigte die Wirksamkeit von PH1 sowohl in hormonresistenten als auch hormonempfindlichen Prostatakrebsmodellen. In hormonempfindlichen Fällen zeigte PH1 additive Effekte, wenn es mit bestehenden Behandlungen wie Xtandi und Erleada kombiniert wird. Dies deutet auf Potenzial für eine Erstlinien-Kombinationstherapie hin und angesichts des signifikanten ungedeckten Bedarfs bei ARPI-resistenten Fällen, in denen aktuelle Behandlungsoptionen begrenzt sind.
أعلنت Akari Therapeutics (بورصة ناسداك: AKTX) عن بيانات ما قبل السريرية واعدة للحمولة الجديدة ADC التي تعدل مقطع spliceosome، PH1، المستهدفة لسرطان البروستاتا المقاوم للهرمونات. تُظهر البيانات قدرة PH1 على خفض مستويات مستقبل AR-V7، الذي يدفع تقدم سرطان البروستاتا النقيلي المقاوم للإخصاء. أظهرت الدراسة فعاليتها في نماذج سرطان البروستاتا التي تتسم بالاعتماد على الهرمونات وبغيرها على حد سواء. في الحالات الحساسة للهرمونات، أظهر PH1 تأثيرات تضايفية عند الجمع مع علاجات حالية مثل Xtandi و Erleada. وهذا يوحي بإمكانية تطوير علاجات من الخط الأول في حالات الجمع ومعالجة النقص الكبير في الاحتياج غير الملبّى في حالات ARPI-المقاومة حيث الخيارات العلاجية الحالية محدودة.
Akari Therapeutics（纳斯达克股票代码：AKTX）宣布其新型ADC剪接体调控载荷PH1在针对激素难治性前列腺癌方面的前临床数据乐观。数据表明PH1有能力抑制AR-V7受体水平，该受体推动着转移性去势抵抗性前列腺癌（mCRPC）的进展。研究还显示PH1在激素抵抗和激素敏感的前列腺癌模型中均有效。在激素敏感病例中，PH1与现有治疗如Xtandi和Erleada联用时显示出叠加效应。这表明未来有望开发一线联合治疗，并解决在ARPI耐药病例中的显著未满足需求——现有治疗选择有限。
- Demonstrated ability to suppress AR-V7 receptor levels in hormone-refractory prostate cancer
- Showed effectiveness as single agent and additive effects with existing treatments in hormone-sensitive cases
- Potential to develop first-line combination therapies with major drugs like Xtandi ($6B/year) and Erleada ($3B/year)
- Addresses significant unmet need in ARPI-resistant hormone refractory patients
- Still in preclinical stage, requiring extensive further testing
- Data yet to be presented at scientific conference for peer review
- Potential competition from existing treatments in hormone-sensitive cases
Insights
Akari's PH1 payload shows promising activity against AR-V7 in prostate cancer, addressing a significant treatment gap in a multi-billion dollar market.
Akari Therapeutics has unveiled compelling preclinical data for their novel antibody drug conjugate (ADC) payload, PH1, which targets a critical gap in prostate cancer treatment. The data demonstrates PH1's ability to suppress AR-V7 receptor expression in hormone-refractory prostate cancer models - a significant finding as AR-V7 is a major driver of metastatic castration-resistant prostate cancer (mCRPC) progression and treatment resistance.
The clinical significance cannot be overstated. When prostate cancer patients develop resistance to first-line Androgen Receptor Pathway Inhibitors (ARPIs) like
What's particularly intriguing is PH1's versatility. In hormone-sensitive models, PH1 demonstrated efficacy both as a monotherapy and when combined with existing ARPIs, suggesting potential applications in earlier treatment lines. This dual functionality could position Akari's technology as both a rescue therapy for ARPI-resistant patients and as part of combination regimens to potentially delay resistance development.
The preclinical results support two potential development pathways: a first-line combination therapy with existing ARPIs or a second-line therapy for patients who have failed ARPI treatment. Given that no current therapies effectively target AR-V7-driven tumors, Akari is addressing a significant unmet medical need in a market where existing therapies generate billions in annual revenue.
However, these findings remain preclinical, and the typical drug development timeline suggests that clinical validation remains years away. The company plans to present more detailed data at an upcoming scientific conference, which will provide greater insight into PH1's potential clinical applications.
Data highlights ability of Akari’s ADC payload, PH1, to suppress the levels of the AR-V7 receptor that is responsible for driving hormone refractory prostate cancer progression
No current therapies have proven to be effective in AR-V7 driven tumors
BOSTON and LONDON, Sept. 24, 2025 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), an oncology biotechnology company developing novel payload antibody drug conjugates (ADCs), today announced key preclinical data demonstrating the potential of its novel antibody drug conjugate (ADC) spliceosome modulating payload, PH1, for the treatment of tumors fueled by alternative splicing-drivers, such as the Androgen Receptor splice variant 7 (AR-V7) in prostate cancer.
AR-V7 is a key driver for progression of metastatic castration resistant prostate cancer (mCRPC). During progression of hormone-sensitive prostate cancer, many patients fail to respond to current first-line therapies known as Androgen Receptor Pathway Inhibitors (ARPIs), which include enzalutamide (Xtandi,
As referenced in the Company’s recent patent filing, preclinical data demonstrated that Akari’s ADC payloadPH1 is able to suppress the expression levels of the AR-V7 receptor in a hormone-refractory mCRPC model called 22Rv1. As a control, ARPIs had no effect on AR-V7 receptor expression in these experiments, which was expected given the refractory nature of these prostate cancer cell lines.
Surprisingly, in a different model, of hormone-sensitive LnCAP cells that express high levels of normal Androgen Receptor (i.e. ARPI sensitive) and lack AR-V7, PH1 demonstrated a benefit as a single agent, and additive effect when combined with either Xtandi or Erleada. The Company believes this combined efficacy data may potentially lead to the development of robust first-line combination regimens of Xtandi or Erleada with a PH1 payload conjugated ADC (PH1 ADC) to target prostate cancer that is sensitive to ARPIs. As progression is often linked to AR-V7 expression, and PH1 reduces AR-V7 expression, it is hypothesized that the combination of ARPI plus PH1 ADCs may slow the development of resistance and AR-V7-driven tumor progression which typically occurs after patients progress on Xtandi or Erleada. Akari has plans to test this hypothesis using PH1 ADCs against different prostate cancer targets in future research.
Abizer Gaslightwala, President and Chief Executive Officer of Akari Therapeutics commented, “We believe these compelling preclinical data support the rationale for Akari to develop a novel ADC with our PH1 spliceosome-modulating payload targeting prostate cancer either alone or in partnership with potential partners. Our goal is to develop the first ADC therapeutic in prostate cancer, either as a first-line combination therapy with ARPIs or a second-line therapy post ARPI failures in tumors driven by AR-V7. We are excited to continue to advance this novel spliceosome modulating payload to drive robust anti-cancer biological mechanisms to treat difficult alternative splicing-driven tumors, for which there are currently no effective treatment options today.”
The Company plans to present the preclinical data at an upcoming scientific conference.
About Akari Therapeutics
Akari Therapeutics is an oncology biotechnology company developing next-generation spliceosome payload antibody drug conjugates (ADCs). 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 target of interest. Akari’s lead candidate, AKTX-101, targets the Trop2 receptor on cancer cells and with a proprietary linker, delivers its novel PH1 payload directly into the tumor. Unlike current ADCs that use tubulin 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 immune cells to drive robust and durable activity. In preclinical studies, AKTX-101 has 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, as compared to appropriate controls. The Company is generating validating data on its novel payload PH1 to continue advancing its lead asset, as well as other undisclosed targets with this novel payload.
For more information about the Company, please visit www.akaritx.com and connect on X and LinkedIn.
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Investor Relations Contact
JTC Team, LLC
Jenene Thomas
908-824-0775
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