Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 187

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 187
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, a glycoprotein often overexpressed in cancers of female                                                                                 
 origin, such as ovarian cancer, endometrial cancer, cervical cancer, or breast cancer. MUC16 has been previously a challenging target because a large part of its extracellular portion is often cleaved and released or “shed” into the      
 bloodstream, often called cancer antigen 125 (“CA125”). mMUC16-CPT113 is specifically designed to bind to the membrane-bound portion, which we believe can enable greater therapeutic effect at lower doses. We plan to develop mMUC16-CPT113 
 initially for the treatment of PROC, with potential expansion to other ovarian cancers, endometrial cancer, and/or cervical cancer, aiming to deliver a potential                                                                             
 best-in-class treatment for these large patient populations.                                                                                                                                                                                  |

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| Our in vitro and in vivo studies show consistent cytotoxic activity by mMUC16-CPT113, including in the presence of CA125,                                                                                                                                                                                                              
 suggesting that our product candidate does bind to the right epitope. Our product candidate also has an optimized linker and improved TOPO1 payload, which we expect can improve response rate and reduce toxicity. We plan to complete IND-enabling studies and submit an IND for the treatment of ovarian cancer by the end of 2025. 
 Target Overview: MUC16                                                                                                                                                                                                                                                                                                                 
 Mucin 16 (MUC16) is a heavily glycosylated type 1 transmembrane protein with a low level of expression in normal bronchial, endometrial, ovarian and corneal                                                                                                                                                                           
 epithelial cells.   MUC16 is upregulated in a number of cancers, including ovarian                                                                                                                                                                                                                                                     
 cancer, endometrial cancer, cervical cancer, or breast cancer, as well as NSCLC, pancreatic and gastric cancers. Overexpression of MUC16 promotes cancer cell proliferation and chemoresistance, while also inhibiting anti-cancer immune                                                                                              |

responses. Knockdown of MUC16 has been shown to reduce tumor growth, motility, and invasiveness, while overexpression enhances these properties. MUC16 interacts with various signaling pathways and proteins, such as the JAK2/STAT3/GR axis, PI3k, EGFR and Src family kinases.

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

MUC16 consists of an O-glycosylated N-terminaldomain, a tandem repeat domain, approximately 56 SEA