Merck KGaA offloads clinical-phase cancer drugs to Day One

Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer of Day One (Day One Biopharmaceuticals)

Merck KGaA has out-licensed two oral MEK inhibitors to Day One Biopharmaceuticals. The agreement positions Day One to test pimasertib in combination with its pan-RAF kinase inhibitor in a subset of solid tumor patients. 

Pimasertib, a small-molecule inhibitor of MEK1/2 on the MAPK pathway, entered the clinic more than a decade ago. From 2007 to 2013, Merck initiated a series of studies to assess the molecule as both a single agent and in combination therapy in multiple cancers. Merck took another MEK1/2 inhibitor, MSC2015103B, into the clinic around the same time.

Neither program advanced past phase 2. Merck delivered data on pimasertib in multiple cancers but opted against taking the asset deeper into the clinic. The Big Pharma terminated the only clinical trial of MSC2015103B for “an administrative reason.”

Day One sees reasons to restart development. The California-based biotech plans to run a phase 1/2 clinical trial that will test pimasertib, a drug given to around 900 patients to date, in combination with its existing type II pan-RAF kinase inhibitor DAY101. The study will enroll patients aged 12 years and older with recurrent, progressive or refractory solid tumors with MAPK pathway aberrations.

“Data have shown DAY101 to selectively inhibit both RAF monomers and dimers which may broaden its potential clinical application in combination with MEK inhibition in solid tumors driven by non-BRAF V600 mutations and RAF fusions,” Samuel Blackman, M.D., Ph.D., co-founder and chief medical officer of Day One, said in a statement. Day One plans to start the combination trial this year.  

Day One has put together a financial package of undisclosed size to secure exclusive rights to the two Merck drugs. The deal features an upfront payment, plus regulatory, approval and sales milestone payments. Day One has raised $190 million since breaking cover last year, enabling it to secure the rights to the ex-Takeda pan-RAF drug before adding the Merck assets to its pipeline. 

Blackman and his colleagues identified the molecules as good fits with their vision for Day One. While most oncology R&D focuses on adults, Day One is developing drugs to treat both children and adults.