Whitehawk Therapeutics CEO Dave Lennon presented at TD Cowen’s 46th Annual Healthcare Conference, outlining the company’s strategy to develop a portfolio of next-generation antibody-drug conjugates (ADCs) and discussing early priorities for its first-in-human studies. Lennon said Whitehawk has advanced two ADC programs into the clinic since launching last year and is working toward initiating a third program in 2026.
Portfolio built around three ADC targets
Lennon said Whitehawk is advancing three ADC programs built on clinically validated tumor targets that the company believes are not yet “inundating,” leaving an opportunity to compete for first-in-class or best-in-class positioning. The company’s targets are:
- PTK7 (HWK-007), which Lennon described as broadly expressed across tumors
- MUC16 (HWK-016), described as highly expressed in gynecological cancers
- SEZ6, which Lennon associated with small cell, neuroendocrine neoplasias, and some CNS tumors
Platform differentiation: stability, safety, and payload design
Lennon emphasized Whitehawk’s technology platform as a key differentiator, highlighting antibody design, bioconjugation chemistry, and payload selection. He said the company engineers high-affinity antibodies and benchmarks them against reference monoclonal antibodies from prior and current ADC programs. He also said Whitehawk uses an attenuated Fc region to help reduce undesired immune-mediated uptake, particularly in lung-resident macrophages—an approach he believes can help reduce the risk of interstitial lung disease (ILD) associated with some topoisomerase I (TOP1) ADCs.
On bioconjugation, Lennon contrasted Whitehawk’s approach with what he described as a common industry method used in many TOP1 ADCs, where disulfide bonds are broken and single-chain linker-payloads are attached. He argued that this can compromise antibody structural integrity and increase vulnerability to premature payload release in circulation. Whitehawk instead uses a carbon-bridge cysteine re-pairing method intended to restore a more natural antibody state and improve stability, followed by an additional “linker hydrolysis” step to further lock the structure.
Lennon also discussed Whitehawk’s payload strategy, stating the company uses a proprietary modified exatecan payload rather than “pure exatecan.” He said pure exatecan can be retained in bone marrow and contribute to hematological toxicity such as grade 3 neutropenia, while Whitehawk’s modified payload is intended to retain potency with reduced hematological impact.
In non-clinical benchmarking, Lennon said Whitehawk’s platform demonstrates 5–25x greater stability in circulation, 3–10x improved potency, and a 2–3x higher safety margin in non-primate studies compared with what he characterized as an average TOP1 ADC platform.
PTK7 program: clinical objectives and safety watchpoints
During Q&A, Lennon said historical understanding of PTK7 as an ADC target largely comes from Pfizer’s cofetuzumab pelidotin program (a Pfizer-AbbVie collaboration), which showed initial signals in non-small cell lung cancer (NSCLC) and ovarian cancer. Whitehawk’s initial clinical trials include those indications, and Lennon said the Phase 1 dose escalation will focus on whether the company can reach an efficacious dose range while limiting dose-limiting toxicities—particularly hematological toxicities.
He said Whitehawk’s initial goal is not primarily to prove pharmacokinetics (PK) or stability in humans, noting the ADCs are designed with a half-life supportive of every-three-week dosing.
Asked about safety events of particular interest, Lennon highlighted:
- Hematological toxicity, including grade 3/4 events and potential febrile neutropenia
- ILD/pneumonitis, which he said may be mitigated by Fc attenuation and is a concern in NSCLC and in combinations with immuno-oncology agents
- Inflammatory headaches, which he said were observed as potential on-target toxicity in the historical cofetuzumab program and are treatable with corticosteroids
On efficacy benchmarks that would support expansion into additional indications, Lennon said internal decision-making thresholds include roughly 35%–40% objective response rate (ORR) and 5.5–6 months progression-free survival (PFS) in NSCLC, and around 50% ORR and more than six months PFS in gynecologic cancers.
MUC16 program: targeting strategy designed to bypass circulating CA-125
Lennon described MUC16 as a “super expresser” in gynecological cancers, and said it can be expressed at levels three to 10 times higher than other targets in the space. He noted that MUC16 is cleaved into the circulating biomarker CA-125, which is commonly used to track tumor progression, and said a challenge has been that targeting the wrong portion of the molecule can prevent effective tumor binding. Whitehawk’s approach targets the membrane-retained portion of MUC16, which he characterized as a design intended to bypass circulating CA-125.
He said the company expects the HWK-016 study to recruit quickly due to the target’s prevalence in ovarian and endometrial cancer and investigator interest. While he did not disclose specific starting doses, he said the company is starting above what it believes is the minimally effective range and expects to escalate quickly into an efficacious dose range, enabling early assessment of responses.
Lennon also said MUC16 expression is broad in ovarian cancer and that even low MUC16 expressers can have high absolute expression. He noted that MUC16 and FR-alpha expression are “not terribly correlated” as biomarkers, and said the trial allows patients regardless of FR-alpha status, provided they have received standard of care.
Capital runway and strategy: three programs in parallel
Lennon said Whitehawk ended Q3 2025 with over $160 million in cash, providing runway into 2028 and enabling the company to reach anticipated clinical milestones across all three programs. He said the company’s quarterly cash burn is roughly $15 million to $17 million.
On prioritization, Lennon said investment decisions will be driven by clinical data as it emerges, framing the company’s approach around whether each program demonstrates a best-in-class profile. He also said a potentially underappreciated aspect of Whitehawk is that it has “three clinical shots on goal in parallel” as an early-stage ADC company, which he believes could create meaningful value inflection as data read out.
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).
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