Pfizer's first-in-class KAT6 inhibitor PF-07248144 has advanced to Phase 3 clinical trials for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, marking a significant milestone for a drug candidate that originated from Australian research discoveries made over two decades ago.
The pharmaceutical giant's KATSIS-1 trial, now published on clinicaltrials.gov with reference ID NCT 07062965, will evaluate PF-07248144 in combination with fulvestrant in patients whose cancer has progressed after prior treatment lines. The international study aims to enroll up to 400 subjects across multiple trial sites, including Australian hospitals and specialty breast cancer units.
Novel Mechanism Targets Cancer Gene Expression
PF-07248144 functions as a selective catalytic inhibitor of KAT6 (KAT6A/B), members of the histone lysine acetyltransferase family of enzymes involved in regulating gene expression. In certain cancers, KAT6A/B gene activity becomes dysregulated, promoting cancer cell growth. The investigational drug suppresses this abnormal gene activity, thereby suppressing cancer growth through a mechanism that essentially "turns off" cancer cells and stops them from multiplying.
Previous clinical trials have demonstrated promise for treating advanced or metastatic hormone receptor positive, HER2-negative breast cancer, positioning the drug as a potential therapeutic in a completely new class of cancer treatments.
Addressing Critical Unmet Medical Need
The advancement addresses a significant clinical need in Australia, where an estimated 10,000-12,000 people are currently living with metastatic breast cancer despite dramatic improvements in overall survival rates through early detection. HR+ HER2- metastatic breast cancer, the most common cancer type in this category, is responsible for approximately 2,500 deaths annually in Australia, equivalent to six deaths per day.
"This investigational drug provides new hope for people whose cancer has failed to respond to all previous lines of treatment," according to the announcement from Oncology One Pty Ltd, the Australian biotechnology company that originally out-licensed the KAT6 inhibitor program to Pfizer.
Collaborative Research Success Story
The drug's development represents a remarkable example of successful research collaboration spanning multiple Australian institutions. The foundational discoveries were made in the early 2000s at the Walter and Eliza Hall Institute (WEHI) by researchers Anne Voss and Tim Thomas, who identified KAT6A as a protein important for controlling gene expression during development and growth of some blood cancers.
Professor Ian Street, Chair of Scientific Advisory Board at Oncology One, highlighted the collaborative nature of the project: "Many CTx research and industry partners - Monash Institute of Pharmaceutical Sciences, SYNthesis Med Chem, Peter MacCallum Cancer Centre, WEHI, CSIRO, Griffith University, St Vincent's Institute of Medical Research, and the Children's Cancer Institute, along with Pfizer, have worked together to develop a new drug that targets KAT6."
Development Timeline and Licensing
The KAT6 project was initially licensed into the Cancer Therapeutics Cooperative Research Centre (CTx) in 2009, Australia's first cooperative drug discovery network funded by the Australian Federal Government and participating organizations. Following further development by CTx, the program was licensed to Pfizer in 2018 by Oncology One, formerly known as CTxONE.
Professor Street expressed gratitude for Pfizer's commitment to advancing the research: "I would like to congratulate the visionary and talented Australian scientists and clinicians who contributed to the discovery and development of PF-07248144 – and of course, share our sincere gratitude to Pfizer for backing this potential cancer therapeutic so quickly into a Phase 3 Clinical Trial."
The progression to Phase 3 represents validation for the multiple research institutes, biotechnology companies, and researchers who participated in translating original Australian research into a promising investigational drug candidate.
