MLLT-TPD / Dark Blue Therapeutics - LARVOL DELTA

A first-in-class oral clinical candidate targeting MLLT1 and 3 degradation for the treatment of advanced AML and ALL including menin inhibitor resistant / refractory disease (ASH 2025) - "Combination studies were performed in viability assays with menininhibitors and other standard of care (SOC) therapies e.g. venetoclax, azacitidine. We disclose the first-in-class MLLT targeted clinical candidate, which has a TPD mechanism ofaction. This compound has potent anti-cancer activity across a broad panel of acute leukemia cell lines,including those refractory to menin inhibitors, and in mouse models of AML, which supports a strongsingle agent opportunity in late-stage disease. Furthermore, synergistic activity with standard of carechemotherapy and a range of clinically relevant targeted agents, coupled with the compound's benignsafety profile, support potential for our MLLT-TPD to become the backbone for combinations in early linetreatment."

Clinical • Metastases • Acute Myelogenous Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Solid Tumor • CRBN • FLT3 • HOXA9 • KMT2A • MEIS1

MLLT1/3 targeted protein degradation as the best-in-class approach for targeting the super elongation complex (SEC) in acute leukemia, including menin inhibitor refractory disease (ASH 2025) - "Our in vitro and in vivo characterization of MLLT-TPD vs menin inhibition reveals that MLLTdegradation has a broader activity than menin inhibition, including against AML and ALL cells insensitiveto menin inhibitors, and AML cells that carry clinically relevant menin inhibitor resistance mutations.Together these data demonstrate that targeting MLLT1/3, the master regulator of the SEC, is a best-in-class approach with potential for broad, deep and durable clinical responses, including in patients thatare resistant to menin inhibition."

Hematological Malignancies • Leukemia • Targeted Protein Degradation • HOXA9 • KMT2A • MEIS1 • RUNX1