Company: WHWK
Filing Date: 2025-01-31
Form Type: DEFM14A
Source: 0001193125-25-018470
Chunk: 185

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-31
Form: DEFM14A
Chunk 185
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Z6                                                                                                                                                                                                                   
 Seizure-related homolog protein 6 (“SEZ6”) is a transmembrane protein commonly expressed on neurons,                                                                                                                                    
 particularly neuronal dendrites, but minimally expressed in normal tissues outside the central nervous system (“CNS”). SEZ6 plays a role in CNS development and maintenance both during childhood development and in adulthood. SEZ6 is 
 responsible for dendritic branching and synapse formation.   The extracellular                                                                                                                                                          
 portion of the SEZ6 proteins contain three CUB domains and five SCR domains. The presence of multiple CUB and SCR domains suggests potential adhesive or receptor trafficking functions but their binding partners are not yet known.   |

SEZ6 is highly expressed in about 80% of SCLC and also overexpressed in extrapulmonary NETs and CNS tumors. SEZ6 expression is correlated with tumor progression although its role in cancer is not well understood.

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

Emerging Therapies and their Limitations Currently, ABBV-706(developed by AbbVie) is the only clinical stage SEZ6 ADC in development. ABBV-706is 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