Merck pays $30M to buy ‘chameleon’ approach to deadly brain cancers

Mer­ck is ac­quir­ing a start­up spun out of Yale called Mod­i­fi Bio, which has de­vel­oped a suite of mol­e­cules against chemother­a­py-re­sis­tant glioblas­toma, a dev­as­tat­ing and of­ten dead­ly dis­ease.

Mer­ck will pay $30 mil­lion up­front, and the deal could be worth as much as $1.3 bil­lion based on po­ten­tial fu­ture pay­ments.

Mod­i­fi Bio was found­ed in 2021 in hopes of turn­ing the aca­d­e­m­ic find­ings from Yale sci­en­tists in­to a new treat­ment for brain can­cers. That re­search, pub­lished in Sci­ence when the com­pa­ny launched in 2022, showed that a so-called DNA mod­i­fi­er could es­sen­tial­ly link two strands of DNA in a way slow enough that healthy cells could re­verse any dam­age, but can­cer cells couldn’t, lead­ing on­ly can­cer cells to die.

Ran­jit Bindra, co-di­rec­tor of the Yale Brain Tu­mor Cen­ter and Mod­i­fi Bio co-founder, said the sci­en­tists called the mol­e­cules “chameleon-like” be­cause the DNA mod­i­fi­ca­tions are tox­ic to glioblas­toma cells, but ap­pear to­tal­ly dif­fer­ent to nor­mal cells. “The mol­e­cules ‘look’ and be­have to­tal­ly dif­fer­ent based on the mol­e­c­u­lar sur­round­ings in the DNA,” he said.

It’s akin to pre­ci­sion chemother­a­py. The treat­ment method was in­spired by temo­zolo­mide, a chemother­a­py that many brain can­cer pa­tients first re­ceive. “Why is [temo­zolo­mide] the on­ly thing that works?” said Mod­i­fi Bio co-founder King­son Lin, who com­plet­ed his MD/PhD at Yale and is now do­ing his res­i­den­cy at the Har­vard Ra­di­a­tion On­col­o­gy Pro­gram. He said that many re­searchers in the past had at­tempt­ed to make ana­logues of temo­zolo­mide, but that re­search didn’t re­al­ly lead any­where.

The Yale team stud­ied how temo­zolo­mide worked in cer­tain glioblas­toma cells that are what’s called MGMT-de­fi­cient and set out to de­sign mol­e­cules that could like­wise link DNA in a lethal fash­ion but over­come re­sis­tance from the tu­mor.

The com­pa­ny had raised $10.7 mil­lion in seed fund­ing. In seek­ing a Se­ries A, the start­up founders not on­ly faced a frigid biotech mar­ket, but al­so the chal­lenge of pitch­ing a treat­ment for glioblas­toma, a less com­mon can­cer that doesn’t com­mand huge re­turns, Bindra said.

He not­ed that some in­vestors they spoke to had been more in­ter­est­ed in the ap­pli­ca­tions of the com­pa­ny’s plat­form out­side of CNS in­di­ca­tions, but Mod­i­fi was de­ter­mined to de­vel­op the drug for the can­cer they set out to treat. And that’s where Mer­ck came in to buy the com­pa­ny in a deal that closed last Tues­day.

Mod­i­fi has se­lect­ed a de­vel­op­ment can­di­date dubbed MOD-246, which Bindra said has been op­ti­mized com­pared to the ini­tial com­pound that the group pub­lished in their Sci­ence pa­per. Mer­ck is ac­quir­ing that com­pound as well as its re­lat­ed ana­logues.