Company: WHWK
Filing Date: 2025-01-31
Form Type: DEFM14A
Source: 0001193125-25-018470
Chunk: 176

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-31
Form: DEFM14A
Chunk 176
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 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; TNBC, Triple negative breast cancer; SCLC, Small cell lung cancer |

Source: Published data; Aadi Analysis Our Approach: CPT113-based ADC platform Each of the three ADC assets utilizes Hangzhou DAC’s CPT113 platform, which consists of a highly stable yet cleavable linker with proprietary carbon-bridge technology that delivers a TOPO1 inhibitor payload. We believe that the CPT113 platform’s linker stability and payload has the potential to be highly competitive among the next generation ADC platforms. Hangzhou DAC selectively designed and synthesized an advanced linker and payload design that supports stability, limits free payload release and improves the pharmacokinetic characteristics for the associated ADCs. Separately from ADC Programs we are licensing, Hangzhou DAC has two internally developed programs utilizing the same platform, DXC006 and DXC1002, that are currently in dose-escalating Phase 1 clinical trials in China. A critical feature of the CPT113 platform is its stability. First generation ADCs were challenged by high free payload release in circulation. Many approved and marketed ADCs have 1 to 20 percent free payload released into the circulation, which limits their therapeutic windows because the high amounts of free payload can generate off-targetside effects. Next generation ADC platforms in development generally seek to lower the