Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 191

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 191
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 a TOPO1-based ADC (DAR 6) with a cleavable linker. In a Phase 1 trial in patients with SCLC and neuroendocrine neoplasms (“NEN”), ABBV-706demonstrated an overall ORR of 44% (21/48, excludes n=5 with glioblastoma multiforme (“GBM”)), with 60.9% ORR in SCLC and 28% ORR in NENs. ABBV-706demonstrated a manageable safety profile with no on-targetneurotoxicity. The promising results with ABBV-706 - 128 -

validated SEZ6 as a target and demonstrated clinical improvement by switching to a cleavable TOPO1 inhibitor linker-payload.

Of note, 77% (41/53) of patients experienced Grade 3 or higher treatment-emergent adverse events (“TEAEs”) with
cytopenias being the most frequent. 32% of patients experienced severe adverse events (“SAEs”), with pneumonia being the most common. Anemia (60%) and fatigue (66%) were the most common any-grade
hematologic and non-hematologic TEAEs, respectively. The 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