PRMT5 Inhibitors for MTAP-Deleted Cancers
As of November 6, 2026, Drugnews tracks 12 MTA-cooperative PRMT5 inhibitors: 11 in clinical development and 1 discontinued, with none approved; 5 are from Asia.
About 10% to 15% of cancers have lost a gene called MTAP, and the share is higher in pancreatic cancer. Without it, a metabolite called MTA builds up inside the cancer cell, and the cell becomes especially dependent on the enzyme PRMT5.
First-generation PRMT5 inhibitors did not distinguish normal cells from cancer cells, and blood toxicity capped their doses. The new generation is "MTA-cooperative": the drug grips PRMT5 only together with MTA, so it works mainly in MTAP-deleted cancer cells.
This page tracks 12 assets: 11 in clinical development and 1 discontinued; none is approved yet. Five come from Asian companies or Asian licensors, and Taiwan's entry is PharmaEngine's PEP08.
01 | The leader: Bristol Myers Squibb has opened two Phase 2/3 trials
Bristol Myers Squibb acquired Mirati for about US$4.8 billion in 2023 and with it navlimetostat (MRTX1719).
- First-line lung cancer: with pembrolizumab and chemotherapy, a 590-patient Phase 2/3 started in January 2026.
- Pancreatic cancer: with gemcitabine plus nab-paclitaxel, a 470-patient Phase 2/3 started in October 2025.
- Another Phase 2 (254 patients) adds Rasonque to the combinations.
Amgen's anvumetostat (AMG 193) has closed enrollment in a 329-patient Phase 1/2, and AstraZeneca's AZD3470 has two Phase 1/2 trials, one combined with the ADC Datroway.
02 | Pancreatic cancer: "RAS plus PRMT5" is the hottest combination
In August 2026 the FDA approved Revolution Medicines' Rasonque (daraxonrasib) for metastatic pancreatic cancer. The next step is pairing it with a PRMT5 inhibitor.
Tango's vopimetostat plus Rasonque produced a 92% response rate in 12 evaluable pancreatic patients in June 2026. At ESMO in October, 22 second- and third-line MTAP-deleted patients had an 82% response rate, with 88% progression-free at nine months. Tango plans to start a first-line Phase 3 in the first half of 2027.
In Rasonque's Phase 3 RASolute 302, second-line chemotherapy shrank tumors in only 11% of patients; this combination pushes the figure above 80%.
In August 2026 BeOne Medicines took partial Asian rights to four Revolution RAS drugs and plans to combine its own PRMT5 inhibitor, BGB-58067, with Rasonque. Bristol Myers Squibb's Phase 2 also includes Rasonque.
03 | Late entrants crowd into Phase 1
- IDEAYA's IDE892, combined with its own MAT2A inhibitor, began a 260-patient Phase 1 in March 2026.
- Bayer licensed a PRMT5 program globally from China's Puhe BioPharma in 2025 and is running a 450-patient Phase 1/2.
- In China, Abbisko's ABSK131 and CytosinLab's CTS3497 are in Phase 1 or Phase 1/2.
- Tango's TNG456 is designed to cross into the brain, targeting brain tumors and brain metastases.
Tango terminated its first-generation TNG908 and moved on to vopimetostat and TNG456. When a company retires its own first drug, late entrants survive only on real differences in the molecule.
04 | Taiwan: where PharmaEngine's PEP08 stands
PharmaEngine's PEP08 is an MTA-cooperative PRMT5 inhibitor discovered with XtalPi's AI platform. It was cleared for clinical testing in June 2025 and is in a 40-patient Phase 1 in Australia and Taiwan.
- Preclinical data show synergy with PharmaEngine's own CHK1 inhibitor, PEP07.
- PharmaEngine also holds rights to the pancreatic cancer chemotherapy Onivyde; the first-line NALIRIFOX regimen joined Taiwan's National Health Insurance in December 2025.
PEP08 is aimed at the hottest direction but is still in Phase 1, at least one stage behind Bristol Myers Squibb's Phase 2/3 trials and Tango's planned first-line Phase 3. Its Phase 1 safety and differentiation data will decide whether it earns combination or licensing opportunities.
05 | Timeline
- 1H 2027: Tango's first-line Phase 3 of vopimetostat plus Rasonque in pancreatic cancer is expected to start.
- Ongoing: Bristol Myers Squibb's two navlimetostat Phase 2/3 trials in lung and pancreatic cancer.
- Ongoing: PharmaEngine's PEP08 Phase 1 in Australia and Taiwan.
Development stage
Country / region
Drug landscape
| Drug | Company | Country | Mechanism | Route | Stage | Indication | Trial ID | Deal | Latest progress and date | Sources |
|---|---|---|---|---|---|---|---|---|---|---|
| navlimetostat (BMS-986504 / MRTX1719) | Bristol Myers Squibb (originally Mirati) | US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 2/3 | MTAP-deleted first-line NSCLC, pancreatic cancer, mesothelioma, glioblastoma and others | NCT07063745 NCT07076121 NCT07492680 | BMS acquired Mirati for about US$4.8B in 2023 | Two Phase 2/3 trials: first-line NSCLC with pembrolizumab and chemo (590, from Jan 2026) and pancreatic cancer with gemcitabine plus nab-paclitaxel (470, from Oct 2025); plus a Phase 2 including daraxonrasib combinations (254, Jul 2026)2026-07-27 | 1 2 3 4 |
| anvumetostat (AMG 193) | Amgen | US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-null solid tumors; pancreatic cancer with chemotherapy | NCT05094336 NCT06360354 NCT06333951 | — | Phase 1/2 (329, including a docetaxel comparator part) closed to enrollment; Phase 1 in pancreatic cancer with gemcitabine/nab-paclitaxel or mFOLFIRINOX (120)2024-05-29 | 1 2 |
| vopimetostat (TNG462) | Tango Therapeutics | US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-deleted solid tumors; with RAS(ON) inhibitors in pancreatic and lung cancer | NCT05732831 NCT06922591 NCT07897734 | — | With daraxonrasib (Rasonque): 92% ORR in 12 evaluable pancreatic patients (Jun 2026); at ESMO 2026, 82% ORR in 22 second/third-line MTAP-deleted pancreatic patients with 88% progression-free at 9 months; first-line Phase 3 targeted to start in 1H 20272026-10-23 | 1 2 3 4 |
| TNG456 | Tango Therapeutics | US | Brain-penetrant MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-deleted solid tumors (brain-penetrant); with abemaciclib | NCT06810544 | — | Phase 1/2 (191) enrolling2025-03-24 | 1 |
| AZD3470 | AstraZeneca | UK | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-deficient solid tumors; with pembrolizumab or datopotamab deruxtecan | NCT06137144 NCT06130553 | — | Two Phase 1/2 trials (161 and 334) enrolling2024-01-23 | 1 2 |
| BAY 3713372 | Bayer (licensed from Puhe BioPharma) | Germany / China | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-deleted solid tumors | NCT06914128 | Bayer licensed Puhe's PRMT5 program globally in 2025 (terms undisclosed) | Phase 1/2 (450) enrolling2025-03-21 | 1 2 |
| CTS3497 | CytosinLab Therapeutics | China | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 | MTAP-deficient solid tumors | NCT06971523 | — | China Phase 1/2 (224) enrolling since Dec 20242024-12-25 | 1 |
| BGB-58067 | BeOne Medicines | China / US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1 | MTAP-deleted solid tumors; with RAS(ON) inhibitors; newly diagnosed glioblastoma | NCT06589596 NCT07485049 | Aug 2026: BeOne took partial Asian rights to four Revolution Medicines RAS drugs and will combine with Rasonque | Phase 1 (695) enrolling, including RAS(ON) combination arms2026-08-10 | 1 2 |
| IDE892 | IDEAYA Biosciences | US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1 | MTAP-deleted solid tumors; with the MAT2A inhibitor IDE397 | NCT07277413 | — | Phase 1 (260) began enrolling in Mar 20262026-03-04 | 1 |
| ABSK131 | Abbisko Therapeutics | China | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1 | Advanced or metastatic solid tumors | NCT07288957 | — | China Phase 1 (266) enrolling since Jul 20252025-07-22 | 1 |
| PEP08 | PharmaEngine (TPEx: 4162) | Taiwan | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1 | MTAP-deleted advanced or metastatic solid tumors | NCT06973863 | Discovered with XtalPi's AI platform under a milestone-sharing partnership | Cleared for clinical testing in Jun 2025; Phase 1 (40) enrolling in Australia and Taiwan; preclinical synergy with the CHK1 inhibitor PEP072026-05-04 | 1 2 3 |
| TNG908 | Tango Therapeutics | US | MTA-cooperative PRMT5 inhibitor | Oral | Phase 1/2 (terminated) | MTAP-deleted solid tumors | NCT05275478 | — | Phase 1/2 terminated; Tango moved on to vopimetostat and TNG4562022-03-23 | 1 |
Frequently asked questions
What is an MTA-cooperative PRMT5 inhibitor?
First-generation PRMT5 inhibitors did not distinguish normal cells from cancer cells, and blood toxicity capped their doses. The new generation is "MTA-cooperative": the drug grips PRMT5 only together with MTA, so it works mainly in MTAP-deleted cancer cells.
Which PRMT5 inhibitor is furthest along?
navlimetostat (BMS-986504 / MRTX1719) — Phase 2/3. Two Phase 2/3 trials: first-line NSCLC with pembrolizumab and chemo (590, from Jan 2026) and pancreatic cancer with gemcitabine plus nab-paclitaxel (470, from Oct 2025); plus a Phase 2 including daraxonrasib combinations (254, Jul 2026)
Where does PharmaEngine’s PEP08 stand?
Cleared for clinical testing in Jun 2025; Phase 1 (40) enrolling in Australia and Taiwan; preclinical synergy with the CHK1 inhibitor PEP07.