Whitehawk Therapeutics Validates PTK7 as Third Most Abundant ADC Target Across 157,000 Tumor Samples
核心洞察
Whitehawk Therapeutics (搜索) presented real-world analysis of over 157,000 tumor samples confirming PTK7 (搜索) as the third most highly expressed tumor marker among ADC targets, present in approximately 70% of solid tumors (搜索).
The study revealed stable PTK7 (搜索) expression across disease stages and metastatic status, with highest expression levels observed in endometrial, ovarian, head and neck, and non-small cell lung cancers.
The findings support development of HWK-007 (搜索), Whitehawk's PTK7 (搜索)-directed ADC candidate, with the company planning to submit an IND application by year-end for initial evaluation in NSCLC, ovarian, and endometrial cancers.
Whitehawk Therapeutics (搜索) presented compelling real-world evidence at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, establishing Protein Tyrosine Kinase 7 (PTK7 (搜索)) as a broadly expressed and clinically relevant target for antibody-drug conjugate (ADC) development. The analysis, conducted in collaboration with Tempus AI, represents the first robust characterization of PTK7 expression across a massive dataset of over 157,000 tumor samples.
Comprehensive Analysis Reveals PTK7's Pan-Tumor Potential
The large-scale RNA analysis evaluated data from the Tempus AI database and the Clinical Proteomic Tumor Analysis Consortium, with nearly half of the samples derived from metastatic lesions. The study confirmed PTK7 (搜索) as one of the most broadly and highly expressed targets across solid tumors (搜索), ranking as the third most highly expressed tumor marker among clinically validated and emerging ADC targets, trailing only HER2 (搜索) and HER3 (搜索).
PTK7 (搜索), an oncofetal transmembrane pseudokinase that drives early embryonic development, demonstrates restricted expression in adult tissues but frequent overexpression across a wide range of cancers. Notably, there are currently no approved PTK7-directed ADCs, presenting a significant therapeutic opportunity.
The analysis revealed that PTK7 (搜索) is expressed in approximately 70% of solid tumors (搜索), with the highest median PTK7 mRNA expression observed in endometrial cancers (7.4), ovarian cancers (7.2), head and neck cancers (7.1), non-small cell lung cancer (搜索) (6.9), and breast cancers (6.7).
Stable Expression Across Disease Stages and Histologies
A critical finding of the study was PTK7 (搜索)'s stable expression across histologic subtypes, disease stages, and metastatic status, underscoring its relevance in both early- and late-stage disease. This consistency is particularly important for ADC development, as it suggests the target remains viable throughout disease progression.
The expression levels proved comparable to or exceeded those of clinically validated and emerging ADC targets across key cancer types. In lung cancer, PTK7 (搜索) expression was comparable to HER2 (搜索), HER3 (搜索), Trop-2 (搜索), and cMET. For ovarian cancer (搜索), PTK7 levels matched HER2 and FRα while markedly exceeding CDH6, B7-H4, and CLDN6. In endometrial cancer (搜索), PTK7 expression was comparable to Trop-2 and markedly higher than FRα, B7-H4, and HER2.
"These results emphasize the translational potential of PTK7 (搜索) as a broadly expressed and stable target across solid tumors (搜索)," said Grace Dy, MD, Chief of Thoracic Oncology and Professor of Oncology at Roswell Park Comprehensive Cancer Center. "By demonstrating consistent expression across histologies, disease stages and sample types, this analysis builds on the foundational rationale for developing next-generation ADCs that have the potential to reach a wide range of patients."
HWK-007 Development Program Advances
Based on these findings, Whitehawk is advancing HWK-007 (搜索), a PTK7 (搜索)-targeting ADC that leverages an advanced technology platform consisting of a highly stable yet cleavable linker delivering a Topoisomerase I (搜索) (TOPO1) inhibitor payload. The company plans to submit an Investigational New Drug application to the U.S. Food and Drug Administration for HWK-007 by year-end, with initial clinical evaluation planned in NSCLC, ovarian, and endometrial cancers.
"These findings reinforce PTK7 (搜索)'s promise as one of the most compelling and underexplored ADC targets in oncology," said Dave Lennon, PhD, President and Chief Executive Officer of Whitehawk Therapeutics (搜索). "As the third most abundant tumor marker across all cancer patients – present in approximately 70% of solid tumors (搜索) – the opportunity for HWK-007 (搜索) has never been clearer. We believe we are well positioned to develop a differentiated ADC that could have a meaningful impact for the nearly 750,000 patients in the US with PTK7-expressing cancers."
Strategic Partnership and Technology Platform
The analysis was conducted as part of a previously announced collaboration between Whitehawk and Tempus AI, demonstrating the value of leveraging real-world data to validate therapeutic targets. Whitehawk's advanced three-asset ADC portfolio is engineered to overcome the limitations of first-generation predecessors, with assets in-licensed from WuXi Biologics under an exclusive development and global commercialization agreement.
The comprehensive dataset and robust findings position PTK7 (搜索) as a clinically meaningful pan-tumor ADC target, potentially addressing a substantial patient population across multiple solid tumor types. The stable expression profile across disease stages suggests HWK-007 (搜索) could benefit patients throughout their treatment journey, from early-stage disease through advanced metastatic settings.