Aadi Bioscience (NASDAQ:AADI) was the focus of a Jefferies Global Healthcare Conference discussion in which Dave Lennon, chief executive officer of Whitehawk Therapeutics, outlined progress across an antibody-drug conjugate, or ADC, pipeline that includes three programs.
Lennon said Whitehawk is developing three ADCs, two of which entered the clinic earlier this year. He also said the company recently announced an $87.5 million financing that extends its cash runway into 2028 as it advances the programs through Phase 1 dose escalation. A third program is expected to enter the clinic in the third quarter, with data updates anticipated in the first half of 2027, he said.
Two Clinical ADC Programs Target PTK7 and MUC16
For HWK-007, Lennon said the company is pursuing non-small cell lung cancer, ovarian cancer and endometrial cancer in a focused Phase 1 dose-escalation program. He said Whitehawk has already enrolled a 2 mg cohort and is enrolling a 4 mg cohort. The company’s efficacy benchmarks include about a 40% overall response rate in lung cancer and about 50% in gynecological cancers, while maintaining low rates of Grade 3 adverse events, particularly hematologic events.
For HWK-016, Lennon said the MUC16-directed program is focused on ovarian and endometrial cancer, with similar expectations for efficacy and tolerability benchmarks.
Company Highlights Safety Rationale Behind Platform
Lennon said preclinical data presented at AACR showed the highest non-severely toxic dose, or HNSTD, for all three ADCs reached 60 mg/kg in non-human primate studies, which he characterized as high for the ADC field. He said that result gives the company confidence in the potential therapeutic index of the platform.
He also pointed to clinical data from a partner’s China-based program using a related CPT113 linker-payload approach. Lennon said that program reported safety data in about 100 patients, including no Grade 3 neutropenia, very low thrombocytopenia rates and about 18% Grade 3 anemia. He cautioned that the data are not from Whitehawk’s programs and that there are differences between the partner’s DAR4 construct and Whitehawk’s DAR6 approach.
Lennon said Whitehawk will monitor overall tolerability as it escalates doses, noting that ADC development is increasingly defined less by dose-limiting toxicities and more by the balance between cumulative toxicity and efficacy.
PTK7 Program Aims to Improve on Earlier ADC Efforts
Lennon said PTK7 is broadly expressed across tumors and has been seen in up to about 70% of tumors. He cited prior clinical experience with cofetuzumab pelidotin, a PTK7-directed ADC developed by Pfizer and AbbVie, which showed response rates in the 20% to 40% range in small groups of patients across non-small cell lung cancer, ovarian cancer and triple-negative breast cancer before being discontinued.
Whitehawk’s goal, Lennon said, is to build on that precedent by using a Top1-based payload and a higher-stability construct. He said the company selected EGFR wild-type adenocarcinoma within non-small cell lung cancer to create a more homogeneous study population and because the company sees an opportunity in a setting where ADCs have generally topped out around 30% overall response rates.
Lennon said Whitehawk is requiring tissue from non-small cell lung cancer patients and screening for PTK7 expression, which could later allow the company to evaluate whether response rates correlate with target expression.
MUC16 and SEZ6 Programs Address Gynecologic and Neuroendocrine Tumors
Discussing MUC16, Lennon said the target is highly expressed in ovarian and endometrial cancers and is the source molecule for CA125, a blood-based biomarker commonly used by gynecologic oncologists. He said the challenge with targeting MUC16 has been circulating CA125, which can create an antigen sink. Whitehawk’s approach, he said, targets epitopes below the cleavage site in the juxtamembrane region to avoid the circulating CA125 portion.
Lennon said MUC16 is often expressed at levels three to 10 times higher than targets such as FR-alpha, CDH6, B7-H4 and NaPi2b, making it an attractive ADC target if the CA125 challenge can be addressed.
The company’s third program targets SEZ6, or seizure protein six, which Lennon said is expressed in certain neuronal cells and is highly upregulated in neuroendocrine tumors such as small cell lung cancer. He said the SEZ6 program is expected to enter the clinic in the third quarter and initially focus on small cell lung cancer, with dose-escalation data expected in the second half of next year.
Lennon compared the program with AbbVie’s SEZ6-targeting ADC, ABBV-706, which he said has shown greater than 50% overall response rates in small cell lung cancer but also meaningful hematologic toxicity, including 40% Grade 3 anemia at an expansion dose. Lennon said Whitehawk believes its molecule may improve tolerability and dose intensity, citing a biparatopic antibody that he said is more potent in internalization and cell killing than AbbVie’s antibody.
Additional ADC Options and Partnering Outlook
Lennon said Whitehawk has signed an extension deal with Hangzhou DAC covering up to five additional ADCs. He said the company is not seeking to fill its pipeline for its own sake, but is evaluating programs that could add differentiated value. He said any new programs would likely arrive in the second half of 2027, after data from the first two clinical programs.
On partnering, Lennon said the company’s current focus is execution and reaching clinical inflection points. “We’ll tackle partnering after we have data,” he 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).
