The pan­dem­ic has posed a se­ri­ous chal­lenge to the way drug­mak­ers do busi­ness, which has made it an easy scape­goat for clin­i­cal tri­al duds. Once look­ing to solve Covid-19, Im­mu­nic’s lead drug has now flopped one study and failed to im­press in an­oth­er — is it fair to blame the pan­dem­ic for that?

On Wednes­day, the biotech re­vealed a study for its lead pro­gram in Covid-19 could not be eval­u­at­ed for its pri­ma­ry and sec­ondary end­points. Then on Thurs­day, Im­mu­nic said the same pro­gram hit sta­tis­ti­cal sig­nif­i­cance in pri­ma­ry scle­ros­ing cholan­gi­tis — though on­ly bare­ly — while not­ing the study pop­u­la­tion end­ed up much small­er than ex­pect­ed be­cause of pan­dem­ic re­stric­tions.

The Covid-19 news from Wednes­day sent Im­mu­nic $IMUX shares down about 20%, while Thurs­day’s PSC up­date left a more mut­ed im­pres­sion on Wall Street: in ear­ly morn­ing trad­ing, the com­pa­ny stock was flat.

The Im­mu­nic pro­gram in ques­tion is an oral treat­ment called IMU-838, which aims to block the en­zyme di­hy­drooro­tate de­hy­dro­ge­nase, or DHODH, and in­hib­it the in­tra­cel­lu­lar me­tab­o­lism of ac­ti­vat­ed T and B cells. DHODH in­hibitors can al­so pro­duce a host-based an­tivi­ral ef­fect re­gard­less of spe­cif­ic virus pro­teins and struc­ture, and Im­mu­nic is hope­ful this can lead to use as the treat­ment of sev­er­al dif­fer­ent virus­es.

Im­mu­nic large­ly pinned the Covid-19 tri­al miss on the way the treat­ment land­scape has changed through­out the pan­dem­ic. Re­searchers launched the study al­most a year ago — back in March, to be ex­act — when there was near­ly ze­ro sci­en­tif­ic con­sen­sus on how to treat the dis­ease.

As a re­sult, Im­mu­nic went af­ter ven­ti­la­tion in mod­er­ate Covid-19 cas­es. They sought to mea­sure how well its pro­gram could re­duce the need for in­va­sive ven­ti­la­tion af­ter four weeks in mod­er­ate cas­es. But over the course of the study, they found that less than 1% of hos­pi­tal­ized Covid-19 pa­tients with mod­er­ate cas­es need­ed ven­ti­la­tors at all, es­sen­tial­ly pre­vent­ing them from mea­sur­ing how ef­fec­tive their pro­gram is in this pop­u­la­tion.

Sim­i­lar mis­cal­cu­la­tions oc­curred in the sec­on­daries as well. Go­ing for 28-day mor­tal­i­ty, sur­vival with­out res­pi­ra­to­ry fail­ure and re­duc­ing ICU ad­mis­sions in mod­er­ate cas­es, Im­mu­nic again found in­ci­dence rates that were too low to con­duct analy­ses. Their study found mor­tal­i­ty to be un­der 2% and less than 4.5% of pa­tients re­quired an ICU stay.

Giv­en how lit­tle was known about the nov­el coro­n­avirus at the out­set of the pan­dem­ic, it’s cer­tain­ly pos­si­ble that Im­mu­nic is far from the on­ly biotech to shoot for these ag­gres­sive end­points and come up short. But they tried to pull a pos­i­tive out of the da­ta, high­light­ing that the pro­gram showed a nu­mer­ic ad­van­tage in time to re­cov­ery over place­bo: in pa­tients who were 90% like­ly to re­cov­er from Covid-19, those tak­ing IMU-838 felt bet­ter af­ter 18.9 days as op­posed to the 26.8 days need­ed in the place­bo arm.

Daniel Vitt

Im­mu­nic al­so pre­sent­ed da­ta that the ther­a­py could be help­ful against “long Covid,” where pa­tients who have suc­cess­ful­ly flushed the virus from their sys­tems con­tin­ue to suf­fer from symp­toms and an over­ac­tive im­mune sys­tem, some­times for months. A post-hoc analy­sis of 27 pa­tients saw low­er nu­mer­ic lev­els of long Covid-re­lat­ed fa­tigue in the drug arm.

CEO Daniel Vitt said in a con­fer­ence call Thurs­day morn­ing that the com­pa­ny ex­pects to speak with reg­u­la­tors about how to pro­ceed in Covid-19 and can hope­ful­ly plan a Phase III tri­al, but isn’t sure what that tri­al might look like yet.

The pan­dem­ic al­so af­fect­ed the pro­gram’s study in PSC, as much of the treat­ments were ad­min­is­tered at the Mayo Clin­ic in Min­neso­ta. Pa­tients had to trav­el to the site, which some­times proved chal­leng­ing over the last sev­er­al months, Vitt said. Orig­i­nal­ly plan­ning to en­roll 30 pa­tients, Im­mu­nic end­ed up on­ly be­ing able to ad­min­is­ter the ex­per­i­men­tal drug to 18 pa­tients while on­ly 11 fin­ished the 24-week treat­ment course. And in late 2020 the prin­ci­pal in­ves­ti­ga­tor de­ter­mined the tri­al need­ed to be stopped.

Look­ing to re­duce serum ALP in adults with PSC af­ter 24 weeks, re­searchers found IMU-838 de­creased lev­els by an av­er­age of 5.76 IU/L every 30 days in these 11 pa­tients. That was good for a p-val­ue of p=0.041, hit­ting sta­tis­ti­cal sig­nif­i­cance but com­ing close to the p=0.05 bor­der.

The pro­gram did not hit sta­tis­ti­cal sig­nif­i­cance in the 18-pa­tient pop­u­la­tion that in­clud­ed those who didn’t fin­ish the study, reg­is­ter­ing an av­er­age base­line change of -2.11 and hit­ting a p-val­ue of 0.578. Both stud­ies found the can­di­date to be safe and well-tol­er­at­ed, and Im­mu­nic is plan­ning to move for­ward with an­oth­er tri­al in PSC as well.

In ad­di­tion to Covid-19 and PSC, the can­di­date is al­so be­ing stud­ied to treat mul­ti­ple scle­ro­sis, ul­cer­a­tive col­i­tis and Crohn’s dis­ease. Last Au­gust, the com­pa­ny re­leased topline da­ta in re­laps­ing-re­mit­ting MS pa­tients, say­ing the ex­per­i­men­tal drug re­duced the cu­mu­la­tive num­ber of com­bined unique ac­tive MRI le­sions af­ter 24 weeks com­pared to place­bo.

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.