Avenzo Therapeutics announced today that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for AVZO-023, a novel cyclin-dependent kinase 4 (CDK4) selective inhibitor. The company has also exercised its exclusive option to secure global development, manufacturing, and commercialization rights for the drug from Allorion Therapeutics Inc., excluding Greater China.
The San Diego-based clinical-stage biotechnology company plans to initiate a Phase 1/2 first-in-human, open-label clinical study in the third quarter of 2025. This trial will evaluate AVZO-023 (formerly ARTS-023) in patients with advanced or metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer and select other advanced solid tumors.
"The clearance of our IND for AVZO-023 represents an important milestone on our journey to transform cancer treatment," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "We believe AVZO-023 has the potential to be a best-in-class oncology therapy for patients with HR+/HER2- breast cancer."
Dual CDK Inhibitor Strategy
The upcoming clinical trial will assess AVZO-023 as both a single agent and in combination with endocrine therapy. Notably, the study will also evaluate AVZO-023 in combination with AVZO-021, Avenzo's CDK2 selective inhibitor that is currently being studied in HR+/HER2- metastatic breast cancer and other advanced solid tumors.
This dual CDK inhibitor approach represents a novel strategy in targeting the cell cycle regulation pathway, which is frequently dysregulated in cancer cells. By selectively inhibiting CDK4 with AVZO-023 and CDK2 with AVZO-021, Avenzo aims to provide more effective and potentially less toxic treatment options for cancer patients.
Promising Preclinical Profile
Preclinical data for AVZO-023 were presented for the first time at the American Association for Cancer Research (AACR) Annual Conference in April 2025. The results highlighted several promising characteristics of the compound:
- Sub-nanomolar potency against CDK4
- High selectivity over other CDKs, particularly CDK6
- Efficacy in in vivo xenograft models as both a single agent and in combination with AVZO-021
The high selectivity over CDK6 is particularly significant, as CDK6 inhibition is associated with hematologic toxicity in currently approved CDK4/6 inhibitors. By sparing CDK6, AVZO-023 may potentially offer an improved safety profile while maintaining efficacy.
Addressing Unmet Needs in HR+/HER2- Breast Cancer
HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancer cases. While CDK4/6 inhibitors have transformed the treatment landscape for this disease in recent years, challenges remain, including the development of resistance and management of side effects.
AVZO-023's selective inhibition of CDK4 represents a potential advancement in targeting the cell cycle more precisely. If successful in clinical trials, this approach could provide new options for patients who have progressed on current therapies or who experience significant toxicities with existing treatments.
Clinical Development Timeline
The Phase 1 portion of the upcoming trial will focus on safety, tolerability, and preliminary clinical activity assessments. If successful, the Phase 2 portion would likely expand to larger patient populations and potentially explore additional combination strategies.
Avenzo's development of both a CDK4 selective inhibitor (AVZO-023) and a CDK2 selective inhibitor (AVZO-021) positions the company to explore multiple therapeutic approaches in cell cycle-targeted cancer therapy, potentially addressing resistance mechanisms that limit the effectiveness of current treatments.
As the company prepares to initiate the clinical trial in the coming months, the oncology community will be watching closely to see if AVZO-023's promising preclinical profile translates to clinical benefit for patients with advanced breast cancer and other solid tumors.
