Whitehawk Therapeutics CEO Dave Lennon outlined the company’s antibody-drug conjugate (ADC) strategy and pipeline during an Annual Healthcare Conference presentation, highlighting two clinical-stage programs that are currently enrolling patients and a third candidate expected to enter the clinic later this year.
Lennon said Whitehawk launched in early 2025 after in-licensing a three-asset ADC portfolio from WuXi Biologics and building the company around those assets, an experienced leadership team, and what he described as the “capital strength” to advance development. He added that Whitehawk had $160 million in cash as of the end of the third quarter of the prior year, which he said provides a runway into 2028.
Company focus: engineering “better ADCs”
- Targeting: Lennon said the company aims to use high-affinity antibody selection and “clever target selection” focused on clinically validated tumor targets. He also highlighted use of an attenuated Fc portion on its monoclonal antibodies to reduce nonspecific uptake by immune cells, which he said could help limit toxicities often associated with ADCs, including interstitial lung disease (ILD).
- Bioconjugation: Lennon argued that conventional ADC construction can create liabilities because standard approaches often require breaking disulfide bonds in the antibody, which may contribute to instability and free payload in circulation. Whitehawk’s approach uses what he described as a “paired carbon-bonded linker payload” and a dual-chain (paired-chain) bioconjugation method intended to stabilize the ADC and reduce free payload release.
- Linker/payload: Lennon said Whitehawk uses PEG masking to “hide” the cytotoxic payload in circulation and release it only after intracellular cleavage. He described the payload as a proprietary Topo-1 agent based on exatecan-like molecules, designed to minimize toxicity while maximizing tumor killing.
On non-clinical benchmarks, Lennon said Whitehawk’s platform demonstrated 3–10x greater tumor potency versus the “average Topo 1 inhibitor ADC,” 5–25x improved stability, and a 2–3x higher safety margin in non-human primate testing, which he said supports an improved therapeutic index.
Lead program HWK-007 targets PTK7
Whitehawk’s first clinical program, HWK-007, is a PTK7-directed ADC. Lennon described PTK7 as broadly expressed across multiple cancers and said it compares favorably with other ADC targets in development such as HER3, HER2, Trop-2, c-Met, and B7H3.
He cited clinical precedent from Pfizer’s first-generation PTK7 ADC, cofetuzumab pelidotin, which used an MMAE (tubulin inhibitor) payload. Lennon said Pfizer’s program showed “really interesting initial efficacy” in phase I studies, including a 46% overall response rate in ovarian cancer among patients with high PTK7 expression, but was limited by toxicities associated with MMAE and ultimately discontinued as Pfizer and its partner AbbVie prioritized other programs.
Lennon also presented preclinical head-to-head xenograft data in small cell lung cancer models comparing HWK-007 with cofetuzumab pelidotin, stating HWK-007 drove significant regressions at lower doses and appeared more potent in that setting.
HWK-016 targets MUC16 in gynecologic cancers
The second clinical program, HWK-016, targets MUC16 and is intended for gynecological cancers. Lennon said the company submitted an IND in December 2025 and is now recruiting patients into a phase I dose-escalation trial, with an initial focus on ovarian and endometrial cancers.
He described MUC16 as highly expressed in ovarian cancer and said its expression can be 3–10x higher than other ovarian cancer ADC targets such as NaPi2b and FR-alpha. Lennon also noted potential expansion opportunities for MUC16 beyond gynecologic cancers, including mesothelioma, non-small cell lung cancer, and pancreatic cancer.
Lennon pointed to Genentech’s prior MUC16 ADC (DMUC4064A) as clinical validation, saying it showed a 42% response rate at an intended dose of 5.2 mg/kg in phase I ovarian cancer studies, but development was limited by ocular and other toxicities and was ultimately discontinued due to its safety profile.
He highlighted a biological challenge for MUC16 targeting: the molecule is cleaved to produce the circulating biomarker CA125. Lennon said Genentech’s antibody targeted the cleaved portion, creating an “antigen sink” as circulating CA125 bound the ADC and reduced tumor delivery—potentially requiring higher doses that contributed to toxicity. Whitehawk, he said, designed an antibody to bind a different portion of MUC16 that remains membrane-bound below the cleavage site. Lennon described preclinical ovarian cancer models with high circulating CA125 in which the Whitehawk antibody showed tumor suppression at low dose and, when combined with Whitehawk’s Topo-1 platform, produced further suppression and regressions in mice.
Third program HWK-206 to enter clinic in Q3
Whitehawk’s third program, HWK-206, is a biparatopic SEZ6-directed ADC. Lennon said biparatopic binding enables clustering of the target and improved internalization. He referenced a competing SEZ6 program, AbbVie’s ABBV-706, and said Whitehawk designed an improved targeting approach with better binding and internalization, which he believes could translate into improved efficacy. Lennon said an IND filing is expected by mid-year, with a phase I start planned for Q3.
Timeline and upcoming disclosures
Lennon said Whitehawk is enrolling patients in phase I dose-escalation studies for HWK-007 (in non-small cell lung cancer, ovarian cancer, and endometrial cancer) and HWK-016 (in ovarian and endometrial cancer). He said the company anticipates clinical readouts in the first half of 2027.
During a Q&A with Oppenheimer biotech analyst Jeff Jones, Lennon also said Whitehawk plans to release additional preclinical data packages supporting all three programs in the spring of 2026, “over the next few months,” as the company continues advancing the portfolio in what he characterized as a highly competitive ADC landscape.
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).
