Company: WHWK
Filing Date: 2025-01-31
Form Type: DEFM14A
Source: 0001193125-25-018470
Chunk: 186

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-31
Form: DEFM14A
Chunk 186
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 maximum tolerable dose (“MTD”) was 3.0 mg/kg, with hematological dose limiting toxicities (“DLTs”) occurring in 2 patients: one
Grade 4 leukopenia and neutropenia lasting >7 days and one Grade 4 thrombocytopenia. All gastrointestinal toxicities were Grade 1 or 2 and no neurotoxicity or GBM was observed suggesting that there is no intracranial penetration. While ABBV-706 represents important progress for SCLC, we believe there are opportunities to apply novel ADC engineering to provide a path to even greater gains.

Our Product Candidate: biSEZ6-CPT113

We plan to
investigate a biparatopic ADC approach. Biparatopic antibodies (which bind two different epitopes of the same protein) can allow for concentration of surface receptors as multiple antibodies can bind to the same antigen, and the same antibody can
bind to multiple antigens. This can lead to concentration of surface receptors, and ultimately result in the formation of large receptor clusters on the cell surface, which can improve receptor internalization and increase payload release. We
believe this target specificity, binding and the internalization can translate into great efficacy and/or safety gains for patients treated with ADCs.

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Source:
Weisser et al. Nat Commun. 2023;14(1):1394.

There are several biparatopic molecules that provide precedent for demonstrating increased therapeutic
benefit compared to their single epitope counterparts. For example, zanidatamab, a biparatopic HER2 Ab (Jazz Pharmaceuticals) binds the same epitopes as trastuzumab (Herceptin) and pertuzumab (Perjeta). Zanidatamab demonstrated approximately 20%
increase in ORR compared to monoparatopic trastuzumab while maintaining a tolerable safety profile.

Our biparatopic SEZ6 ADC, biSEZ6-CPT113, is the only
biparatopic ADC in development for small cell lung cancer, and shows potential to outperform the available treatment approaches and the single epitope ADCs in development.

Preclinical models suggest the biSEZ6 antibody shows superior binding and internalization compared to single epitope SEZ6 antibody counterparts, including the
antibody used in ABBV-706, with increased mean fluorescence intensity (MFI).

Clinical Development Plan

We plan to explore this potential in our planned Phase 1