Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 184

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 184
---
, including NSCLC and PROC, in the second half of 2025.   Target                                                                                                                                                                 
 Overview: Protein tyrosine kinase 7 (PTK7)   Protein tyrosine kinase 7                                                                                                                                                                       
 (“PTK7”) is an oncofetal pseudokinase also known as colon carcinoma kinase 4 (“CCK-4”). PTK7 is a transmembrane protein with an extracellular region comprised of 7 Ig domains and an                                                        
 intracellular domain that is non-catalytic.                                                                                                                                                                                                  |

PTK7 drives embryonic early development by regulating cell polarity, movement and development of hematopoietic and somatic progenitor cells often interacting with ligands, co-receptorsand intracellular transducers in the Wnt signaling pathway. PTK7 is subsequently down-regulated in adult tissues and is known as - 121 -

a catalytically inactive receptor tyrosine kinase (“RTK”). PTK7 is commonly upregulated across a broad spectrum of cancers, being found in tumors associated with endometrial, prostate, cervical, head and neck, breast, colorectal, esophageal, lung, ovarian and gastric intestinal cancers, as shown in the figure below. In fact, PTK7 is almost exclusively re-expressedin primary and metastatic tumor cells and cancer associated fibroblasts (“CAFs”) in the tumor microenvironment. PTK7 is known to promote cancer growth and invasion. Overexpression of PTK7 is associated with poor prognosis, tumor metastasis and reduced overall survival.

| 1. | Aadi analysis based on Human Protein Atlas, Gepia, and literature review. |

PTK7 is a clinically validated tumor target. In a Phase 1 trial in patients with advanced solid tumors, including PROC, NSCLC or triple-negative breast cancer (“TNBC”), Cofe-Pdemonstrated clinical activity with ORR ranging from 16 to 27% in all evaluable patients and 23 to 46% in the subgroup with moderate or high expression of PTK7 (“PTK7 mod-high”),as confirmed by immunohistochemistry (“IHC”) analysis of tumor tissues. In patients treated every three weeks (“Q3W”) cohort, ORR was up to 46% compared to 27% in patients with PROC compared to patients with PTK7 mod-highPROC, 25% compared to 16% in patients with NSCLC compared to patients with PTK7 mod-highNSCL