Prelude and Lilly to trial KAT6A degrader PRT13722 in breast cancer

Prelude Therapeutics has signed a clinical trial collaboration and supply agreement with Eli Lilly to evaluate its lead oncology candidate PRT13722 in combination with Lilly's CDK4/6 inhibitor abemaciclib (Verzenio) and oral oestrogen receptor antagonist imlunestrant (Inluriyo) in patients with hormone receptor-positive, HER2-negative breast cancer. The FDA recently cleared the programme under an Investigational New Drug application, and Prelude expects to begin enrolling patients in the fourth quarter of 2026.

PRT13722 is described by Prelude as a highly selective, orally bioavailable KAT6A degrader. The company retains full global development and commercial rights to the asset, meaning Lilly's role is limited to supplying its two approved agents for the combination cohorts. The Phase 1 trial will open with monotherapy dose escalation before advancing to the combination arms.

Preclinical rationale

The deal is underpinned by data Prelude presented at the American Association for Cancer Research Annual Meeting in April 2026. Those preclinical results showed PRT13722 drove durable complete tumour regressions in HR-positive xenograft models, both endocrine therapy-naive and treatment-experienced, at well-tolerated doses. Crucially, the compound demonstrated synergy when combined with endocrine therapies, CDK4/6 inhibitors and PI3K inhibitors, and retained activity in ESR1-mutated and acquired-resistance cell lines.

Sean Brusky, Prelude's Chief Business and Strategy Officer, said the company was "taking a highly differentiated approach to this clinically validated target," arguing that selective KAT6A degradation offers an improved hematological safety profile compared with dual KAT6A/B inhibitors such as prifetrastat. The company believes sparing KAT6B reduces the bone marrow toxicity that has constrained combination use of earlier KAT6 inhibitors.

Market context

HR-positive, HER2-negative breast cancer is the largest and most commercially active breast cancer subtype, and the treatment landscape is already crowded with approved CDK4/6 inhibitor combinations. The competitive question for PRT13722 is whether targeted protein degradation of KAT6A can add meaningful efficacy or tolerability advantages over existing standard-of-care regimens, particularly in the frontline metastatic and early-stage settings where Prelude is positioning the asset.

Several companies have pursued KAT6 as a target following academic validation of its role in oestrogen receptor signalling. Cyclica and a number of university-spinout groups have explored KAT6 biology, though selective degradation rather than dual inhibition remains a relatively novel approach in clinical development. If PRT13722's Phase 1 safety and preliminary efficacy data hold up in patients, the combination readouts with abemaciclib and imlunestrant could provide an early signal on whether the degrader modality genuinely differentiates from the inhibitor class. Investors and clinicians will be watching the dose-escalation data closely, given the ongoing debate about the utility of adding further agents to already active CDK4/6 backbone regimens.