Im­mu­nic's lead drug fails to im­press in 2 sep­a­rate tri­als — and it's blam­ing some of its woes on the pan­dem­ic

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.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

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.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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