Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 189

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 189
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 et al. Gynecol Oncol. 2021;163(3):473-480; Liu J, et al. Ann Oncol. 2016;27(11):2124-2130; Chen Y, et al. Cancer Res.2007;67(10):4924-4932. ORR, objective response rate.

Emerging Therapies and their Limitations

Currently,
there are no approved or actively developing ADCs targeting MUC16. Regeneron is developing two MUC16 bispecific T cell-engaging antibodies; a limitation of this approach, however, includes the modest ORRs observed to date. While several ADCs
targeting other antigens in PROC are under development, none offer the combined advantages of high target expression in both depth and frequency, along with the potential for a matched blood-based biomarker like CA125.

Our Product Candidate: mMUC16-CPT113

Our product
candidate is designed to bind to a different region than the targets of prior MUC16 therapies in development. mMUC16-CPT113 targets membrane-bound MUC16 below the site of cleavage, so that even if MUC16 is cleaved and release of CA125 occurs, the
ADC can stay bound to the cell surface permitting internalization of the TOPO1 inhibitor payload. This allows mMUC16-CPT113 to bypass the antigen sink of circulating CA125, and directly target the tumor surface.

Preclinical data shows that mMUC16-CPT113 demonstrates superior tumor growth inhibition in vivo compared to DMUC4064A in a high CA125-shedding model of
ovarian cancer. In vitro and in vivo data suggest that this

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next wave approach has the potential for improved response rates in ovarian cancer and other gynecological cancers. For example, our product candidate mMUC16-CPT113, along with DMUC and mMUC16
antibodies conjugated to DXd and MMAE payloads, were tested in an in vivo OVCAR-3 CDX model. Nude mice bearing the OVCAR-3 tumor xenograft were treated with a
single dose of ADC at 1 mg/kg. mMUC16 ADCs displayed significantly increased in vivo antitumor activity compared to DMUC ADCs, regardless of the cytotoxic payload. No obvious weight loss was observed in any group.

Clinical Development Plan

We plan to complete IND-enabling studies and linker-payload process development in 2025 with IND submission