Balomenib

CAS 2939850-17-4

MF C33H34F3N7O2 MW617.7 g/mol

4-methyl-1-[[(2S)-5-oxomorpholin-2-yl]methyl]-5-[[2-[6-(2,2,2-trifluoroethyl)quinazolin-4-yl]-2,7-diazaspiro[3.5]nonan-7-yl]methyl]indole-2-carbonitrile

• 1H-Indole-2-carbonitrile, 4-methyl-1-[[(2S)-5-oxo-2-morpholinyl]methyl]-5-[[2-[6-(2,2,2-trifluoroethyl)-4-quinazolinyl]-2,7-diazaspiro[3.5]non-7-yl]methyl]-
• 4-methyl-1-[(2S)-5- oxomorpholin-2- yl]methyl]-5- [[2-[6-(2,2,2- trifluoroethyl) quinazolin-4-yl]-2,7- diazaspiro[3.5]nonan- 7-yl]methyl]indole-2- carbonitrile

4-methyl-1-{[(2S)-5-oxomorpholin-2-yl]methyl}-5-({2-[6-(2,2,2-trifluoroethyl)quinazolin-4-yl]-2,7-diazaspiro[3.5]nonan-7-
yl}methyl)-1H-indole-2-carbonitrile
menin inhibitor, antineoplastic, ZE63-0302, 3BEG4BWN8E

Balomenib (also known as ZE63-0302) is an oral, small-molecule menin inhibitor currently in clinical development for metabolic and oncological conditions. It works by disrupting the protein-protein interaction between menin and KMT2A (formerly MLL), a mechanism that plays a critical role in both pancreatic beta-cell function and certain types of leukemia. 

Key Therapeutic Areas

• Type 2 Diabetes (T2D): Balomenib is being investigated as a potentially disease-modifying treatment to improve pancreatic beta-cell function and survival. As of late 2025, it has advanced into Phase 1b clinical trials specifically for adults with T2D to evaluate its effects on fasting glucose, insulin dynamics, and HbA1c.
• Oncology (AML): It is also a candidate for treating acute myeloid leukemia (AML) with KMT2A rearrangements or NPM1 mutations. Preclinical data suggests it may be more effective against resistance mutations than earlier menin inhibitors. 

Development and Safety

• Corporate Development: The drug was originally developed by Eilean Therapeutics. It is now the lead program for Clywedog Therapeutics, which is merging with Barinthus Biotherapeutics to focus on metabolic diseases.
• Safety Profile: Early trial results indicate a favorable safety profile. Notably, it was designed to minimize QTc prolongation (heart rhythm issues), a side effect common in other menin inhibitors.

• Сlinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of ZE63-0302 in Healthy VolunteersCTID: NCT06780124Phase: Phase 1Status: CompletedDate: 2026-01-22
• Study to Assess Safety, Tolerability, PK, and PD of Multiple Doses of ZE63-0302 Administrated Orally in T2DM Patients.CTID: NCT07234864Phase: Phase 1Status: RecruitingDate: 2026-01-22

SYN

US20250163061,

https://patentscope.wipo.int/search/en/detail.jsf?docId=US456551731&_cid=P10-MNMKG0-25753-1

Example 46. 4-Methyl-1-{[(2S)-5-oxomorpholin-2-yl]methyl}-5-({2-[6-(2,2,2-trifluoroethyl)quinazolin-4-yl]-2,7-diazaspiro[3.5]non-7-yl}methyl)-1H-indole-2-carbonitrile (Compound 102)

Compound was prepared using procedure described in the Example 45 and 5-formyl-4-methyl-1-{[(2S)-5-oxomorpholin-2-yl]methyl}-1H-indole-2-carbonitrile P177 instead of 5-formyl-4-methyl-1-{[(2R)-5-oxomorpholin-2-yl]methyl}-1H-indole-2-carbonitrile P176. Compound 102 was obtained with yield 49%. ¹H NMR (400 MHz, DMSO-d ₆), δ: 8.46 (s, 1H), 7.99 (m, 2H), 7.73 (m, 2H), 7.52 (m, 1H), 7.46 (d, J=5.6 Hz, 1H), 7.31 (d, J=4.8 Hz, 1H), 4.54 (m, 1H), 4.20 (m, 2H), 4.05 (m, 1H), 3.90 (m, 4H), 3.52 (m, 2H), 3.35 (m, 1H), 3.17 (m, 1H), 2.39 (m, 2H), 1.79 (m, 4H). LCMS (ESI) [MH] ⁺: 618.

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US471589031&_cid=P10-MNMKG0-25753-1

Example 46. 4-Methyl-1-{[(2S)-5-oxomorpholin-2-yl]methyl}-5-({2-[6-(2,2,2-trifluoroethyl)quinazolin-4-yl]-2,7-diazaspiro[3.5]non-7-yl}methyl)-1H-indole-2-carbonitrile (Compound 102)

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References

• Inhibitors of menin-mll interactionPublication Number: WO-2023107696-A2Priority Date: 2021-12-09
• Inhibitors of menin-mll interactionPublication Number: US-2025163061-A1Priority Date: 2021-12-09
• Inhibitors of menin-mll interactionPublication Number: EP-4444300-A2Priority Date: 2021-12-09

///////////balomenib, menin inhibitor, antineoplastic, ZE63-0302, 3BEG4BWN8E