Benzinga | Oct 7, 2021 10:01AM EDT

Rain Therapeutics Presents Data On Milademetan (RAIN-32) At 2021 AACR-NCI-EORTC Virtual International Conference

Rain Therapeutics Inc., (NASDAQ:RAIN), ("Rain"), a late-stage company developing precision oncology therapeutics, today announced data on its oral mouse double minute 2 (MDM2) inhibitor, milademetan, presented at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics held virtually October 7-10, 2021.



Three poster presentations detailed: 1) in vivo and in vitro activity of milademetan using a rationally-derived MDM2 copy number threshold as a predictive biomarker for patient selection, 2) in vivo and in vitro activity of milademetan in Merkel cell carcinoma (MCC) models and 3) results demonstrating milademetan induces synthetic lethality of (ER)-positive breast tumors with GATA3 mutations.

Key findings from Rain's presentations include:

* Milademetan demonstrated anti-tumor activity in patient-derived organoid models and xenograft models consisting of genetically selected tumors, representing many different histologies, using MDM2 gene amplification (amp) and wild-type (WT) p53 as selection criteria. Robust induction of p53 target genes including MIC-1, p21 and PUMA was observed following milademetan treatment indicating re-activation of p53 by milademetan.

* Milademetan inhibited MCC cell lines in patient-derived xenograft models that lack TP53 mutations, representing the majority of MCC cases, for which no approved targeted therapies are available. MCC has low rates of p53 mutation and MDM2 dependence in MCC is driven by polyoma virus-induced MDM2 expression in the majority of cases.

* Milademetan inhibited proliferation of GATA3 frameshift (fs) mutant ER+ breast cancers, demonstrating significant activity and the potential to treat ER+, GATA3 mutant breast cancers that have been unresponsive to the current standard of care. GATA3 fs mutations are mutually exclusive of p53 mutations in ER+ breast cancer and are associated with higher expression of MDM2 and other genes in the MDM2/p53 axis associated with p53 inactivation.

"These data further support the potential of milademetan as a targeted therapy in genetically pre-defined cancer patients beyond our lead indication in liposarcoma," said Robert Doebele, M.D., Ph.D., co-founder, president and chief scientific officer of Rain Therapeutics. "These therapeutic opportunities represent areas of unmet need where the tumors may exhibit MDM2 dependency and for which milademetan therapy alone or in combination may lead to clinically meaningful outcomes."

Copies of each poster will be available by visiting the "Events & Presentations" section of the Rain website.