Company: WHWK
Filing Date: 2025-01-21
Form Type: PREM14A
Source: 0001193125-25-009599
Chunk: 181

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-21
Form: PREM14A
Chunk 181
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otherapies, particularly for cancer such as solid tumors, as it can deliver potent
antibody-directed payloads directly to the tumor cells. This targeted approach can limit off-target toxicities of the chemotherapy and/or allow for greatly improved potency against cancer. With these
improvements in cancer outcomes, the ADC market of an estimated $11 billion in sales at the end of 2023 is expected to grow to over $50 billion by 2030.

As of the end of 2024, 13 ADCs have been approved by the FDA (mostly first generation; two have been withdrawn) against multiple cancers, including blood,
breast, and lung cancers. Despite benefit seen with first generation ADCs, there continues to be significant need for improved ADCs with safer payloads, improved stability and optimized pharmacokinetics. For example, first generation ADCs often use
tubulin inhibitor-based payloads, such as MMAE-based payloads, that have been associated with a class effect of dose-limiting toxicities, like peripheral neuropathy, ocular toxicities and neutropenia.

Next wave ADCs

Recent advances in ADCs have included
replacing the tubulin inhibitor-based payloads with Topoisomerase I (“TOPO1”) inhibitor payloads to reduce toxicity, improving linker stability to reduce circulating free payload, and increasing and optimizing the drug-to-antibody ratio (“DAR”) to improve pharmacokinetics and antitumor activity. In a number of ADC programs, next generation ADCs were shown to have improved ORR
by 20-40% over their first generation precursors. For example, the ORR for ABBV-011, a calicheamicin-based ADC with a DAR of 2 and a
non-cleavable linker, in small cell lung cancer (“SCLC”) was 19%, while the ORR for

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ABBV-706,a next wave ADC with a TOPO1 inhibitor payload and a DAR of 6, was 61%, representing a 42% higher response rate compared to ABBV-011.

| 1 | Overall response rate in indicated Phase I patients; exception, Elahere phase III data in ovarian cancer                                                                                                                                     
 FRa, Folate receptor alpha; DM4, Ravtansine (tubulin inhibitor); TOPO1, Topoisomerase I inhibitor; MMAE, Monomethyl Auristatin E (tubulin inhibitor) OvCa, Ovarian Cancer; TN