Since our last clinical update in 2020 two new fragment-derived drugs, asciminib and sotorasib, have been approved, bringing the total to six.
The current list contains 52 molecules, with 22 approved or in active trials. As always, this table includes compounds whether or not they are still in development (indeed, some of the companies no longer even exist). Because of this, the Phase 1 list contains a higher proportion of compounds that are no longer progressing.
The current list contains 52 molecules, with 22 approved or in active trials. As always, this table includes compounds whether or not they are still in development (indeed, some of the companies no longer even exist). Because of this, the Phase 1 list contains a higher proportion of compounds that are no longer progressing.
Drugs reported
as still active in clinicaltrials.gov, company websites, or other sources are in bold, and those that have been discussed on Practical Fragments are hyperlinked to the most relevant post. The list is almost certainly
incomplete, particularly for Phase 1 compounds. If you know of any others (and can
mention them) please leave a comment.
| Drug | Company | Target |
|---|---|---|
| Approved! | ||
| Asciminib | Novartis | BCR-ABL1 |
| Erdafitinib | Astex/J&J | FGFR1-4 |
| Pexidartinib | Plexxikon | CSF1R, KIT |
| Sotorasib | Amgen | KRASG12C |
| Vemurafenib | Plexxikon | B-RAFV600E |
| Venetoclax | AbbVie/Genentech | Selective BCL-2 |
| Phase 3 | ||
| Capivasertib | AstraZeneca/Astex/CR-UK | AKT |
| Lanabecestat | Astex/AstraZeneca/Lilly | BACE1 |
| Pelabresib (CP-0610) | Constellation | BET |
| Verubecestat | Merck | BACE1 |
| Phase 2 | ||
| ASTX029 | Astex | ERK1,2 |
| ASTX660 | Astex | XIAP/cIAP1 |
| AT7519 | Astex | CDK1,2,4,5,9 |
| AT9283 | Astex | Aurora, JAK2 |
| AUY-922 | Vernalis/Novartis | HSP90 |
| AZD5991 | AstraZeneca | MCL1 |
| DG-051 | deCODE | LTA4H |
| eFT508 | eFFECTOR | MNK1/2 |
| Indeglitazar | Plexxikon | pan-PPAR agonist |
| LY2886721 | Lilly | BACE1 |
| LY3202626 | Lilly | BACE1 |
| LY517717 | Lilly/Protherics | FXa |
| LYS006 | Novartis | LTA4H |
| MAK683 | Novartis | PRC2 EED |
| Navitoclax (ABT-263) | Abbott | BCL-2/BCLxL |
| Onalespib | Astex | HSP90 |
| PF-06650833 | Pfizer | IRAK4 |
| PF-06835919 | Pfizer | KHK |
| PLX51107 | Plexxikon | BET |
| S64315 | Vernalis/Servier/Novartis | MCL1 |
| VK-2019 | Cullinan Oncology / Wistar | EBNA1 |
| Phase 1 | ||
| AG-270 | Agios/Servier | MAT2A |
| ABBV-744 | Abbott | BD2-selective BET |
| ABT-518 | Abbott | MMP-2 & 9 |
| ABT-737 | Abbott | BCL-2/BCLxL |
| AT13148 | Astex | AKT, p70S6K, ROCK |
| AZD3839 | AstraZeneca | BACE1 |
| AZD5099 | AstraZeneca | Bacterial topoisomerase II |
| BI 691751 | Boehringer Ingelheim | LTA4H |
| ETC-206 | D3 | MNK1/2 |
| GDC-0994 | Genentech/Array | ERK2 |
| HTL0014242 | Sosei Heptares | mGlu5 NAM |
| IC-776 | Lilly/ICOS | LFA-1 |
| LP-261 | Locus | Tubulin |
| LY2811376 | Lilly | BACE1 |
| Mivebresib | AbbVie | BRD2-4 |
| Navoximod | New Link/Genentech | IDO1 |
| PLX5568 | Plexxikon | RAF |
| SGX-393 | SGX | BCR-ABL |
| SGX-523 | SGX | MET |
| SNS-314 | Sunesis | Aurora |
| TAK-020 | Takeda | BTK |
With only two phase 3 molecules in active development it may be some time before the next fragment-derived drug is approved. Then again, in 2020 sotorasib was only in phase 2. While long timelines are common in our industry, good drugs can make remarkably rapid progress.
I just learned at the ACS meeting that LY3372689, Lilly's OGA inhibitor, has fragment origins and is now in Phase 2.
ReplyDeleteTo this list can be added five more compounds:
ReplyDeleteBI 1823911, Boehringer Ingelheim, Phase 1, KRAS G12C inhibitor
CFTX-1554, Confo Therapeutics, Phase 1, angiotensin II type 2 receptor antagonist
HTL9936, Sosei Heptares, Phase 1, M1-receptor partial agonist (discussed here)
HTL0018318, Sosei Heptares, Phase 2, M1-receptor partial agonist (mentioned here)
MRTX1719, Mirati, Phase 1, PRMT5•MTA inhibitor (profiled here)