Merck opens its mind to epigenetics with Imago buy
The purchase sets up another showdown with the group’s old rival, Bristol Myers Squibb, in LSD1 inhibition.
Merck & Co seemed to play down its appetite for M&A during its third-quarter results, saying it would only buy assets that appealed in terms of both “science and value”. Bolting on the under-the-radar epigenetics player Imago for just $1.4bn makes sense on the second criteria.
The soundness of Imago’s science will now need to be proven. The group, which floated last year, is focused on LSD1 inhibition and has a phase 3-ready asset, bomedemstat. Only a few other players are active in this space, according to Evaluate Pharma; one is Bristol Myers Squibb, although Merck’s most advanced rival will be Oryzon.
LSD1, or lysine-specific demethylase 1, is an epigenetic protein that regulates gene expression; it is involved in the maturation of bone marrow stem cells and has been shown to be elevated in various cancers.
|Selected LSD1 inhibitors in clinical development for oncology|
|Merck & Co (via Imago Biosciences)||Advanced essential thrombocythemia, myelofibrosis, polycythemia vera & SCLC|
|Oryzon Genomics||Ph2 Alice in 1L elderly AML, final results at Ash 2022; ph2 in SCLC|
|JB-802*||Jubilant Therapeutics||NCT05268666 in solid tumours|
|Seclidemstat||Salarius Pharmaceuticals||Sarcoma study on partial hold following suspected adverse reaction|
|CC-90011||Bristol Myers Squibb (via Celgene)||Solid tumours, "various combinations"|
|TAS1440||Otsuka||NCT04282668 in AML|
|EPI-111||Epiaxis Therapeutics||Epi-Primed completed|
|INCB59872||Incyte||Discontinued ("strategic business decision")|
|GSK2879552||GSK||Discontinued ("risk/benefit does not favour continuation")|
|*LSD1/HDAC6 inhibitor. Source: Evaluate Pharma & clinicaltrials.gov.|
Bomedemstat’s most advanced indication is the slow-growing blood cancer essential thrombocythemia. The project it is also being studied in other blood cancers and small-cell lung cancer; in the latter use it is being given alongside Roche’s checkpoint inhibitor Tecentriq.
However, attempts to inhibit LSD1 have not always gone smoothly: GSK discontinued GSK2879552, with clinicaltrials.gov entries stating that the risk/benefit equation did not support further development.
More recently, Salarius’s seclidemstat was put on partial clinical hold after a patient death following a suspected unexpected serious adverse reaction.
The big concern for Merck, which is paying a 107% premium for Imago, might therefore be avoiding toxicity with bomedemstat. In the project’s phase 2 single-arm trial in essential thrombocythemia, presented at this year’s EHA meeting, there were 19 serious adverse events among 67 patients, with six deemed related to therapy. And 14 patients discontinued the drug, 10 because of adverse events.
More data will feature at this year’s Ash meeting, along with further results from bomedemstat’s phase 2 trial in myelofibrosis.
Ash will also see final data from the Alice trial of Oryzon’s rival LSD1 inhibitor iadademstat; that trial is in another use, acute myeloid leukaemia, making cross-trial comparison even trickier than usual. An investigator-sponsored study of iadademstat in SCLC is also ongoing.
Oryzon also has a “CNS-optimised” LSD1 inhibitor, vafidemstat, in phase 2 for borderline personality disorder and schizophrenia.
|Selected bomedemstat clinical trials|
|Essential thrombocythemia||NCT04254978||Data at EHA 2022; update due at Ash 2022|
|Advanced myelofibrosis||NCT03136185||Data at EHA 2022; update due at Ash 2022|
|Polycythemia vera||NCT05558696||Completes Jun 2024|
|Myelofibrosis (+ Jakafi)||NCT05569538*||Completes Oct 2024|
|SCLC (+ Tecentriq)||NCT05191797*||Completes Jan 2025|
|*Investigator-sponsored trial. Source: Evaluate Pharma & clinicaltrials.gov.|
The first table in this story has been updated to include Jubilant's JB-802.