Sol­id Bio is hit by an­oth­er set­back as ini­tial biop­sies spot­light a flop for Duchenne MD

Sol­id Bio­sciences has had an­oth­er set­back.

The biotech an­nounced this morn­ing that its dose-as­cend­ing Phase I/II study of its lead gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy flopped, send­ing the com­pa­ny in­to over­drive to hus­tle a high­er dose in­to the clin­ic.

Ilan Gan­ot

The com­pa­ny an­nounced Thurs­day morn­ing that a 3-month biop­sy of a hand­ful of pa­tients “showed low lev­els of mi­crody­s­trophin pro­tein ex­pres­sion.” In 2 of 3 pa­tients, pro­tein ex­pres­sion was un­de­tectable by west­ern blot analy­sis. In the third pa­tient the dy­s­trophin ex­pres­sion hit on­ly 5% by west­ern blot analy­sis, while an­a­lysts and the com­pa­ny were look­ing for 10% or bet­ter.

The com­pa­ny’s shares im­plod­ed, plung­ing 68% by the close. Shares of Sarep­ta, which has the on­ly cus­tom ther­a­py on the mar­ket, jumped about 7% and then slid in­to the red.

Giv­en the safe­ty is­sues that the ther­a­py has al­ready run in­to, Leerink’s Joseph Schwartz ques­tioned the com­pa­ny’s abil­i­ty to pow­er up an ef­fec­tive dose with­out threat­en­ing pa­tients.

Our the­sis that in­vestors should fo­cus not on­ly on the quan­ti­ty of mi­crody­s­trophin ex­pres­sion but al­so on the qual­i­ty of the ex­pressed pro­tein ap­pears to be at sig­nif­i­cant risk based up­on the in­creas­ing­ly un­cer­tain abil­i­ty of SGT-001 (Duchenne mus­cu­lar dy­s­tro­phy/DMD) to be safe­ly dose-es­ca­lat­ed to a lev­el which is suf­fi­cient to achieve com­pet­i­tive mi­crody­s­trophin lev­els. We be­lieve it is pru­dent to wait and see if SLDB can achieve ad­e­quate lev­els of ex­pres­sion in a safe man­ner be­fore con­sid­er­ing whether the mi­crody­s­trophin pro­tein that is ex­pressed by SGT-001 is dif­fer­en­ti­at­ed from that of SRPT and PFE (Bam­boo).

CEO Ilan Gan­ot quick­ly spot­light­ed the com­pa­ny’s cash re­serves, a com­mon strat­e­gy for dis­tressed com­pa­nies.

He not­ed: “This strat­e­gy is fur­ther sup­port­ed by our scal­able man­u­fac­tur­ing process, from which we have suf­fi­cient drug prod­uct avail­able to dose es­ca­late with­out de­lay. We have the fi­nan­cial re­sources to ex­e­cute on our plan and look for­ward to com­mu­ni­cat­ing ad­di­tion­al da­ta lat­er this year.”

Gan­ot — a for­mer JP Mor­gan in­vest­ment banker — has made much of the fact that he’s a Duchenne MD dad out to find a gene ther­a­py that could cure the lethal, rare dis­ease. By in­tro­duc­ing a syn­thet­ic dy­s­trophin trans­gene con­struct, called mi­crody­s­trophin, via a vi­ral vec­tor, the com­pa­ny has en­cour­aged hopes it can do what Sarep­ta and oth­ers have been grop­ing for with one de­ci­sive in­ter­ven­tion. And he had at­tract­ed some heavy­weight back­ers, in­clud­ing RA Cap­i­tal and their col­leagues at Bain.

The com­pa­ny ran in­to ear­ly trou­ble, though.

The very first pa­tient to be treat­ed with SGT-001 ex­pe­ri­enced a se­ri­ous ad­verse event, trig­ger­ing alarm bells af­ter in­ves­ti­ga­tors saw a “de­crease in platelet count fol­lowed by a re­duc­tion in red blood cell count, tran­sient re­nal im­pair­ment and ev­i­dence of com­ple­ment ac­ti­va­tion.” That trig­gered a clin­i­cal hold that last­ed sev­er­al months.

It wasn’t the first brush with trou­ble.

In the lead up to its IPO Gan­ot ne­glect­ed to tell in­vestors about an ini­tial clin­i­cal hold on the pro­gram, post­ing that news just ahead of the list­ing. The biotech was al­so forced to note that gene ther­a­py pi­o­neer James Wil­son from Penn had re­signed from their sci­en­tif­ic ad­vi­so­ry board due to ris­ing safe­ty con­cerns re­lat­ed to high dos­ing us­ing the vec­tor he had de­vel­oped.

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