08 November 2021

Fragments in the clinic: 2021 edition

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. 
 
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.

DrugCompanyTarget
Approved!

AsciminibNovartisBCR-ABL1
ErdafitinibAstex/J&JFGFR1-4
PexidartinibPlexxikonCSF1R, KIT
Sotorasib
Amgen KRASG12C
VemurafenibPlexxikonB-RAFV600E
VenetoclaxAbbVie/GenentechSelective BCL-2
Phase 3

Capivasertib
AstraZeneca/Astex/CR-UKAKT
LanabecestatAstex/AstraZeneca/LillyBACE1
Pelabresib (CP-0610)
ConstellationBET
VerubecestatMerckBACE1
Phase 2

ASTX029AstexERK1,2
ASTX660AstexXIAP/cIAP1
AT7519AstexCDK1,2,4,5,9
AT9283 AstexAurora, JAK2
AUY-922Vernalis/NovartisHSP90
AZD5991AstraZenecaMCL1
DG-051deCODELTA4H
eFT508eFFECTORMNK1/2
IndeglitazarPlexxikonpan-PPAR agonist
LY2886721LillyBACE1
LY3202626LillyBACE1
LY517717Lilly/ProthericsFXa
LYS006Novartis
LTA4H
MAK683NovartisPRC2 EED
Navitoclax (ABT-263)AbbottBCL-2/BCLxL
OnalespibAstexHSP90
PF-06650833PfizerIRAK4
PF-06835919PfizerKHK
PLX51107PlexxikonBET
S64315Vernalis/Servier/NovartisMCL1
VK-2019
Cullinan Oncology / Wistar
EBNA1
Phase 1

AG-270
Agios/Servier
MAT2A
ABBV-744AbbottBD2-selective BET
ABT-518AbbottMMP-2 & 9
ABT-737AbbottBCL-2/BCLxL
AT13148AstexAKT, p70S6K, ROCK
AZD3839AstraZenecaBACE1
AZD5099AstraZenecaBacterial topoisomerase II
BI 691751Boehringer IngelheimLTA4H
ETC-206D3MNK1/2
GDC-0994Genentech/ArrayERK2
HTL0014242Sosei HeptaresmGlu5 NAM
IC-776Lilly/ICOSLFA-1
LP-261LocusTubulin
LY2811376LillyBACE1
MivebresibAbbVieBRD2-4
NavoximodNew Link/GenentechIDO1
PLX5568PlexxikonRAF
SGX-393SGXBCR-ABL
SGX-523SGXMET
SNS-314SunesisAurora
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.

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