Soley Therapeutics Unveils Preclinical AACR 2026 Data Highlighting Selective Anti-Tumor Activity of First-in-Class CKAP2 Modulator STX-6398
Soley Therapeutics, a biotechnology company focused on developing innovative therapies rooted in integrated cell stress biology, has announced the presentation of new preclinical findings at the American Association for Cancer Research (AACR) Annual Meeting 2026. The data showcase the therapeutic potential of STX-6398, a first-in-class, orally available small-molecule modulator targeting cytoskeleton-associated protein 2 (CKAP2), and highlight its selective anti-tumor activity across a range of cancer models.
The newly presented findings underscore a growing body of evidence supporting CKAP2 as a promising yet historically challenging therapeutic target. CKAP2 is an intrinsically disordered protein that plays a critical role in cell division, cytoskeletal organization, and tumor progression. Due to its structural properties, CKAP2 has long been considered “undruggable,” making Soley Therapeutics’ progress in identifying a small-molecule modulator particularly noteworthy. The company’s discovery platform, which integrates insights from cell stress biology, has enabled the rapid identification of STX-6398 and other potential first-in-class candidates.
According to Yerem Yeghiazarians, M.D., Co-Founder and Chief Executive Officer of Soley Therapeutics, the data presented at AACR provide strong validation for both the company’s scientific approach and the therapeutic potential of CKAP2 modulation. He emphasized that CKAP2 is implicated in multiple aspects of malignant progression and is expressed across a wide range of tumor types, making it an attractive and broadly relevant target. The preclinical profile of STX-6398, including its biomarker-linked activity, oral bioavailability, and favorable tolerability, supports its continued development as a potential treatment option for patients with CKAP2-expressing cancers.
The preclinical studies highlighted several key findings that collectively demonstrate the promise of STX-6398. In vitro experiments conducted across a panel of approximately 300 tumor cell lines revealed that sensitivity to the compound strongly correlates with CKAP2 protein abundance. This relationship suggests that CKAP2 expression levels could serve as a predictive biomarker, enabling a more targeted therapeutic approach. Notably, this correlation was observed across both hematologic malignancies and solid tumors, indicating the potential for broad clinical applicability.
Mechanistic investigations provided further insight into how STX-6398 exerts its anti-tumor effects. The compound was shown to modulate CKAP2-associated signaling pathways, including focal adhesion kinase (FAK) signaling, which is known to play a role in cell adhesion, migration, and survival. By disrupting these pathways, STX-6398 effectively reduces cancer cell migration and invasiveness. Additionally, the compound interferes with microtubule dynamics, a critical component of cell division, leading to cell cycle arrest. This multi-faceted mechanism of action contributes to its ability to inhibit tumor growth and progression.
Beyond its effects on cell proliferation and migration, STX-6398 also demonstrated anti-angiogenic properties. Angiogenesis, the process by which new blood vessels form to supply nutrients and oxygen to tumors, is a key driver of cancer progression. In preclinical models, treatment with STX-6398 resulted in the inhibition of angiogenesis, further limiting tumor growth. Importantly, the compound maintained its activity under hypoxic conditions, which are commonly found within the tumor microenvironment and often contribute to treatment resistance. This ability to remain effective in low-oxygen conditions highlights the robustness of STX-6398’s therapeutic potential.
In vivo studies provided additional support for the efficacy of STX-6398. Oral administration of the compound in multiple xenograft models, including lung and colon cancer, resulted in significant anti-tumor activity. Researchers observed dose-dependent tumor growth inhibition, with some models demonstrating tumor regression. These findings are particularly encouraging, as they indicate that STX-6398 can achieve meaningful therapeutic effects when administered orally, a route that is generally more convenient and patient-friendly compared to intravenous therapies.
Equally important is the safety and tolerability profile of STX-6398. In preclinical efficacy studies, the compound was well tolerated, with no significant adverse effects observed at therapeutically relevant doses. Additional safety assessments further supported its favorable profile, suggesting that STX-6398 may offer a viable balance between efficacy and safety—a critical consideration in oncology drug development.
The poster presentation at AACR 2026, titled “CKAP2 Modulation With a Novel Small Molecule Results in Excellent In Vitro and In Vivo Anti-Tumor Activity,” provides a comprehensive overview of these findings. Scheduled for presentation on April 20 from 2:00 PM to 5:00 PM PDT in Poster Section 15 (Poster Number 3043), the session offers an opportunity for the scientific community to engage with Soley Therapeutics’ research and explore the implications of CKAP2 modulation as a novel therapeutic strategy.
The broader significance of this work lies in its potential to open new avenues in cancer treatment. Targeting intrinsically disordered proteins like CKAP2 has long been a challenge in drug discovery, but advances in molecular understanding and innovative discovery platforms are beginning to overcome these barriers. By successfully identifying and advancing a small-molecule modulator of CKAP2, Soley Therapeutics is contributing to a paradigm shift in how previously intractable targets can be approached.
Moreover, the biomarker-driven nature of STX-6398’s activity aligns with the growing emphasis on precision medicine in oncology. By identifying patients whose tumors exhibit high CKAP2 expression, clinicians may be able to tailor treatment strategies more effectively, potentially improving outcomes while minimizing unnecessary exposure to therapies that are less likely to be beneficial.
Looking ahead, the encouraging preclinical results for STX-6398 support further development and eventual clinical evaluation. Future studies will likely focus on confirming its safety and efficacy in human patients, as well as refining patient selection strategies based on CKAP2 expression and other relevant biomarkers. If successful, STX-6398 could represent a new class of targeted therapies that address unmet needs across a range of cancer types.
In summary, the data presented by Soley Therapeutics at AACR 2026 highlight the potential of STX-6398 as a first-in-class CKAP2 modulator with selective anti-tumor activity. Through a combination of biomarker-linked efficacy, multi-mechanistic action, and favorable tolerability, the compound demonstrates promise as a novel therapeutic approach in oncology. These findings not only validate the company’s innovative discovery platform but also underscore the broader potential of targeting intrinsically disordered proteins in cancer treatment.
About Soley Therapeutics
Soley Therapeutics is a science-first, tech-enabled drug discovery and development company using cells as the world’s most powerful sensors to uncover first-in-class medicines. Soley’s platform translates the cellular information of stress biology into mechanistic insight, revealing novel drug candidates that otherwise would be missed. Soley deploys full-stack AI via its collaboration with Oracle, including Oracle Cloud Infrastructure AI infrastructure and NVIDIA Blackwell GPUs. By combining foundational biology, proprietary imaging, first-in-class automation, and integrated AI tools, Soley has rapidly built a pipeline that spans oncology, neurodegenerative disorders, metabolic diseases, and other areas. Soley is headquartered in South San Francisco
