Whitehawk Therapeutics CEO Dave Lennon outlined the company’s strategy and near-term milestones at the Inaugural Life Sciences Conference in Miami, describing a three-program antibody-drug conjugate (ADC) pipeline built around a shared linker-payload system and focused on targets the company believes can support broad activity across multiple tumor types.
Company reset and runway
Lennon said the current incarnation of Whitehawk Therapeutics began about a year ago following a transaction that closed in March of last year, which “reset the company” from its prior identity as Aadi Bioscience (NASDAQ:AADI). The transaction centered on a three-asset ADC portfolio in-licensed from WuXi Biologics and included a financing that, according to Lennon, left the company with about $200 million in cash at inception.
ADC approach: topo-1 payload with a focus on stability
Lennon described Whitehawk as building its ADCs around a topoisomerase 1 (topo-1) inhibitor payload, noting the field’s shift away from earlier payload classes such as PBD and MMAE. He characterized topo-1 payloads as generally falling into two groups—exatecan-like and deruxtecan-like—with exatecan described as more potent but associated with greater hematologic toxicity, and deruxtecan described as somewhat less potent with fewer side effects.
Whitehawk’s platform uses a deruxtecan-like payload and aims to improve potency through engineering, Lennon said. The company’s linker-payload system, called CPT-113, was licensed from Hangzhou DAC. Lennon said the key differentiator is stability and circulation exposure designed to maximize payload delivery at the tumor site. He also said the same technology is used across all three ADC programs.
HWK-007: PTK7-directed ADC enters dose escalation
Whitehawk’s lead program is HWK-007, a PTK7-directed ADC that Lennon said is enrolling “very quickly” as it approaches dose escalation. He described PTK7 as a developmental protein downregulated in adult tissues but upregulated in tumors, where it may support migration and metastasis. Lennon said PTK7 is expressed in up to 70% of tumors, making it a broadly expressed target.
He pointed to prior clinical validation from a Pfizer and AbbVie co-development program against PTK7, which he said showed overall response rates in the 20% to 40% range depending on expression and indication, including signals in non-small cell lung cancer, ovarian cancer, and triple negative breast cancer. Lennon said the prior program was ultimately discontinued “largely for safety,” attributing the issues to payload-related toxicities tied to earlier ADC generations.
Discussing Whitehawk’s preclinical criteria, Lennon highlighted antibody binding and internalization (including a “slow off rate”), along with linker stability. He said Whitehawk evaluates premature payload release in circulation and cited a payload release ratio of 0.01% on a molar basis, which he described as 10x to 100x more stable than typical ADCs. He also said animal work showed potency “down to about 1 mg/kg on average,” which the company uses as a threshold for anticipated minimally effective human dosing, and added that the company started dosing its clinical programs at levels higher than that threshold.
Whitehawk plans to release initial HWK-007 clinical data in the first half of 2027, with Lennon anticipating at least 20 to 30 patients enrolled for readout. He said the team intends to take a disciplined approach to pipeline decisions, noting the company has about 25 people and is “not beholden” to pursuing technology that does not show differentiation.
HWK-016: MUC16-directed ADC designed to bypass CA-125 sink
The company’s second clinical program is HWK-016, a MUC16-directed ADC that entered the clinic recently and, according to Lennon, is also enrolling well. Lennon described MUC16 as highly expressed in gynecologic tissues and “massively overexpressed” in ovarian and endometrial cancers, with expression also noted in pancreatic cancer, mesothelioma, and some non-small cell lung cancers.
He emphasized that MUC16 is cleaved into the circulating biomarker CA-125, widely used to track disease and response in gynecologic cancers. Lennon said this cleavage has historically created an “antigen sink” problem for MUC16-targeted therapies. He cited Genentech’s prior efforts, saying Genentech used an antibody directed to the cleaved, glycosylated portion of MUC16 and had to dose at nearly 2x typical levels to overcome the sink, achieving a reported 42% overall response rate in ovarian cancer in Phase 1 but with significant side effects including ocular toxicity and peripheral neuropathy in an MMAE-based construct.
Lennon said Whitehawk designed its antibody to bind below the CA-125 cleavage site to avoid binding circulating antigen. He said preclinical testing showed the antibody does not bind CA-125 and that head-to-head comparisons on the same linker-payload system outperformed the Genentech antibody at lower doses.
Across the portfolio, Whitehawk uses a drug-antibody ratio (DAR) of 6, which Lennon said is optimized for exposure and payload release for the construct. Whitehawk expects HWK-016 data in the first half of 2027. Lennon added that in gynecologic cancers, he views 50% overall response rate as a current benchmark for ADCs, and said the company believes 50% “should be quite reasonable,” with potential for 60% or better, based on the prior Genentech response rate and Whitehawk’s design changes.
HWK-206: SEZ6 biparatopic ADC planned for Phase 1 in Q3
Whitehawk’s third program, HWK-206, targets SEZ6 (seizure protein 6), which Lennon described as a CNS-delimited protein overexpressed in cancers of neuroendocrine origin, including small cell lung cancer and other neuroendocrine tumors. He said SEZ6 is more highly expressed than targets such as DLL3 and B7-H3 and has a “clean” expression profile relative to normal tissues in those cancers.
Lennon pointed to an AbbVie SEZ6 ADC, ABBV-706, as a key comparator, saying it has shown strong response rates but carries toxicity consistent with an exatecan-type payload, including Grade 3 neutropenia and other cytotoxic effects such as nausea and vomiting. Whitehawk’s approach uses a biparatopic antibody—binding two epitopes on the same molecule—to drive receptor clustering and improved internalization. Lennon said Whitehawk demonstrated 2x to 3x greater potency versus ABBV-706’s monoclonal antibody when linked to the same payload, and that when paired with Whitehawk’s less potent but safer payload, the company sees equivalent efficacy in preclinical comparisons, with the goal of improved tolerability and combination potential.
Lennon said Whitehawk is on track for an IND submission and plans to start Phase 1 in Q3 of this year, enrolling patients with neuroendocrine and small-cell tumors.
Upcoming milestones and data catalysts
Looking ahead, Lennon said Whitehawk plans to release preclinical data on all three programs at an upcoming congress in the spring, including potency, stability, pharmacokinetics, and other comparative metrics. He also flagged a Hangzhou DAC program, DXC006, which uses the same chemical structure as Whitehawk’s linker-payload system (with a different bioconjugation approach) and may provide additional read-through on potency and safety when that program presents data later this year.
Whitehawk’s own initial clinical readouts remain targeted to the first half of 2027 for HWK-007 and HWK-016, with HWK-206 expected later given its later start, Lennon said.
About Aadi Bioscience (NASDAQ:AADI)
Aadi Bioscience, Inc is a clinical-stage biopharmaceutical company focused on developing precision medicines for genomically defined cancers. Headquartered in Redwood City, California, Aadi Bioscience was founded in 2012 and went public in 2019 on the Nasdaq Stock Market under the ticker AADI. The company’s research strategy centers on identifying molecular drivers of tumor growth and designing small-molecule inhibitors that target these pathways.
The company’s lead product candidate, fimepinostat (CUDC-907), is a novel dual inhibitor of histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K).
