Aadi Bioscience (NASDAQ:AADI) President and CEO Dave Lennon used a TD Cowen Oncology Innovation Summit Q&A to outline progress across Whitehawk’s antibody-drug conjugate, or ADC, portfolio, emphasizing the company’s linker-payload technology and upcoming clinical milestones.
In a session hosted by Tara Bancroft, senior biotech analyst at TD Cowen, Lennon said the company was founded around a three-asset ADC transaction completed at the end of 2024. Two of those assets have entered the clinic, while a third is expected to enter clinical development in the third quarter.
Company Highlights CPT113 Linker-Payload Platform
Lennon said the CPT113 system combines a proprietary Topo 1 inhibitor with a linker approach designed to reduce unwanted payload release in circulation. He said the company believes that could improve potency while reducing toxicity, particularly hematologic side effects commonly associated with Topo 1-based ADCs.
He also noted that Whitehawk has expanded its relationship with the originator of the linker-payload technology through an option agreement covering up to five additional ADCs, including dual and novel payload variations.
Discussing the technical basis for the platform, Lennon said the paired linker approach provides two points of attachment to the antibody, which he said is inherently more stable than single-chain linker systems. He also pointed to additional stability measures, including maleimide ring hydrolysis and masking techniques, as contributors to reduced systemic exposure to free payload.
AACR Data Support Three ADC Programs, CEO Says
Lennon reviewed preclinical data presented at the American Association for Cancer Research meeting for the company’s three lead programs: HWK-007, HWK-016 and HWK-206.
HWK-007 targets PTK7, which Lennon described as a large cancer target with potential relevance across multiple tumor types. He said preclinical xenograft studies showed potency down to 1 mg/kg and a highest non-severely toxic dose, or HNSTD, of 60 mg/kg in non-human primates, the highest dose tested.
Lennon said the company has already completed the first clinical dosing cohort for HWK-007 at 2 mg/kg and cleared dose-limiting toxicities. Enrollment has also been completed in a second cohort at 4 mg/kg. He said the company believes it is already in an active dose range for the program.
HWK-016 targets MUC16, a target Lennon said is highly expressed in ovarian cancer. He said the company designed the antibody to bypass a cleaved portion of MUC16 that has historically created an antigen sink and complicated development efforts. Preclinical data for HWK-016 also showed activity at 1 mg/kg and an HNSTD of 60 mg/kg, according to Lennon. The program has started clinical dose escalation at 2.5 mg/kg.
The third program, HWK-206, targets SEZ6, a protein Lennon said is upregulated in neuroendocrine tumors such as small cell lung cancer and other neuroendocrine neoplasias. He said the program uses a biparatopic antibody and is intended to improve on existing approaches against the target, including AbbVie’s ABBV-706 program, which Lennon said has shown promising efficacy but has not balanced safety to the company’s satisfaction.
ASCO Data From Partner Program Seen as Platform Validation
Lennon said Whitehawk is watching upcoming ASCO data from Hangzhou DAC’s CD56-targeting ADC, DXC-006, which uses the CPT113 linker-payload system. According to Lennon, previously released abstract data showed overall response rates in the high 60% range in small cell lung cancer, in the 50% range across all cancers, and 45% in non-small cell lung cancer, with 79 patients in the trial overall.
He said the tolerability profile included less than 30% Grade 3 treatment-related adverse events overall, no Grade 3 neutropenia, no interstitial lung disease and no dose-limiting toxicities during dose escalation.
Lennon noted that Hangzhou DAC’s program uses a DAR4 format, while Whitehawk’s programs use a modified bioconjugation approach intended to achieve DAR6 while maintaining tolerability. He also cited Johnson & Johnson’s disclosed work on an ADC version of amivantamab using CPT113 in the DAR4 format as another vote of confidence in the linker-payload system.
Development Strategy Focuses on Differentiation
For HWK-007, Lennon said the company is taking a focused dose-escalation strategy in non-small cell lung cancer, ovarian cancer and endometrial cancer, where he said there are clear ADC benchmarks. He contrasted the company’s approach with broader solid-tumor strategies, saying Whitehawk wants to demonstrate a best-in-class profile before expanding into other indications.
Lennon said the company’s PTK7 program differs from other U.S. programs he is aware of because it does not use exatecan as a payload. He said exatecan can be associated with gastrointestinal and hematologic toxicity, including Grade 3 neutropenia, which the company hopes to avoid with its heme-sparing payload profile.
For MUC16, Lennon said prior work by Genentech demonstrated that the target could generate strong response rates, but required high dosing that led to intolerable side effects. He said Whitehawk’s design is intended to address the antigen sink issue while using a Topo 1 payload, with the goal of producing a differentiated efficacy and tolerability profile in gynecologic cancers.
For SEZ6, Lennon said the company sees the target as one of the most highly overexpressed tumor targets in neuroendocrine and small cell lung cancer settings. He said Whitehawk plans to present additional expression data at ASCO.
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).
