Milademetan as a
Precision Therapeutic

Rain's approach to precision oncology uses molecularly targeted therapy with genetic eligibility screening and optimized pharmacology to translate advances in science to advances in patient care.

milademetan

Milademetan is an oral, selective, small molecule inhibitor that is currently in clinical development for the treatment of patients with TP53 wildtype cancers.1

The MDM2-p53 Interaction

When a cell’s DNA is damaged beyond repair, tumor suppressor protein p53 triggers cell death to prevent tumor development. If TP53 is mutated or suppressed, this protection is lost.2,3

MDM2 is a key negative regulator of p53 responsible for controlling and limiting p53 levels. If MDM2 levels are high, p53 levels may be significantly suppressed, aiding in tumor growth.3,4 Milademetan may reactivate p53, restoring the protection it provides.1

Dosing Regimen

One of the historic challenges in developing a drug that inhibits the MDM2-p53 complex has been to deliver a benefit to patients while reducing toxicity.1,5 Rain is hopeful that milademetan’s pharmacological characteristics may support a dosing schedule that will reduce toxicity while allowing patients to experience potential benefits from the drug.

Biomarker-driven Patient Identification*

Rain is using in vitro diagnostics to confirm the presence of predictive biomarkers to help identify patients who may benefit from milademetan treatment.

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*Dedifferentiated liposarcoma biomarker testing is not required for participation in the MANTRA trial.
†Annual incidence in the United States.7
References
1. Gounder MM, Bauer TM, Schwartz GK, et al. A first-in-human phase 1 study of milademetan, an MDM2 inhibitor, in patients with advanced liposarcoma, solid tumors or lymphomas. J Clin Oncol. 2023. doi:10.1200/CO.22.01285. 2. Hernández Borrero LJ, El-Deiry WS. Tumor suppressor p53: biology, signaling pathways, and therapeutic targeting. Biochim Biophys Acta Rev Cancer. 2021 1876:188556. doi: 10.1016/j.bbcan.2021.188556. Epub 2021 Apr 29. 3. Chène P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat Rev Cancer. 2003;3:102-109. 4. Dembla V, Somaiah N, Barata P, et al. Prevalence of MDM2 amplification and coalterations in 523 advanced cancer patients in the MD Anderson phase 1 clinic. Oncotarget. 2018;9:33232-33243. 5. Wang S, Chen FE. Small-molecule MDM2 inhibitors in clinical trials for cancer therapy. Eur J Med Chem. 2022;236:114334. doi: 10.1016/jejmech.2022.114334. 6. Zhang C, Liu J, Xu D, et al. Gain-of-function mutant p53 in cancer progression and therapy. J Mol Cell Biol. 2020;12:674-687. 7. Data on file. Rain Oncology, 2023.

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