Company: WHWK
Filing Date: 2025-01-31
Form Type: DEFM14A
Source: 0001193125-25-018470
Chunk: 175

Company: Whitehawk Therapeutics, Inc.
Filing Date: 2025-01-31
Form: DEFM14A
Chunk 175
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ization and effectiveness of the ADC. |

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We believe that improving ADC architecture can increase treatment efficacy in solid tumors. Each of the
three ADC assets utilizes the advanced CPT113 linker-payload technology from Hangzhou DAC, which consists of a highly stable yet cleavable linker that delivers a TOPO1 inhibitor payload, and high affinity antibodies designed using the
industry-leading antibody capability of Wuxi Biologics. We believe these assets have greater target binding, improved linker-payload stability, optimized pharmacokinetic parameters, together which can increase tumor cell killing and reduce off-target effects and can potentially overcome the limitations that hindered the first generation ADC therapies against these targets to deliver improved results for patients. Under the License Agreement, we have
worldwide development and commercialization rights to all of our product candidates. See “The PIPE Financing and License Agreement—The License Agreement.” We intend to develop each of our programs as a monotherapy and
also in combination with other therapies.

Industry Background

Antibody-Drug Conjugates

An antibody-drug conjugate
(“ADC”) consists of an antibody that is connected to a drug (the payload) via a linker. An ADC can be a preferred alternative to systemic chemotherapies, 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As of the end of 2024, 13 ADCs have been approved by the FDA (mostly first generation; two have been withdrawn) against multiple cancers, including blood,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