Covid-19 roundup: Gilead touts pre­clin­i­cal promise for oral remde­sivir; Roche pre­pares for virus to be­come en­dem­ic

With remde­sivir still stand­ing as the on­ly an­tivi­ral ap­proved to treat Covid-19, Gilead has been ex­plor­ing new ways to ex­pand its use. Now its re­searchers, in col­lab­o­ra­tion with a team from the Uni­ver­si­ty of Car­oli­na in Chapel Hill, have come up with pre­clin­i­cal re­sults back­ing up an oral can­di­date.

And they have their sights set be­yond Covid-19.

GS-621763, a pro­drug of the parental nu­cle­o­side of remde­sivir, ap­peared promis­ing in both in vit­ro ex­per­i­ments in cell cul­tures and in vi­vo ex­per­i­ments in­volv­ing mice. No­tably, the sci­en­tists al­so com­pared GS-621763 against Mer­ck’s mol­nupi­ravir, an­oth­er oral nu­cle­o­side ana­log an­tivi­ral cur­rent­ly be­ing test­ed in hu­mans, and found both drugs to be “sim­i­lar­ly ef­fi­ca­cious.”

They start­ed the pa­per, post­ed on bioRx­iv, by not­ing that lag­ging vac­ci­na­tion rates, cou­pled with wan­ing im­mu­ni­ty and break­through in­fec­tions by SARS-CoV-2 vari­ants, high­light the need for sec­ond-gen­er­a­tion treat­ments — but ther­a­peu­tic op­tions are lim­it­ed. The ones that are avail­able, such as remde­sivir and the mon­o­clon­al an­ti­bod­ies, large­ly have to be in­fused in­tra­venous­ly, hin­der­ing wide­spread use, not to men­tion that some an­ti­bod­ies are show­ing signs of di­min­ished ef­fi­ca­cy against vari­ants.

By tar­get­ing a high­ly con­served RNA-de­pen­dent RNA poly­merase, GS-621763 is tout­ed as an al­ter­na­tive can­di­date that can fight through all those mu­ta­tions. Across stud­ies, it showed “sig­nif­i­cant an­tivi­ral ac­tiv­i­ty in lung cell lines and two dif­fer­ent hu­man pri­ma­ry lung cell cul­ture sys­tems” and trig­gered “dose-de­pen­dent an­tivi­ral ac­tiv­i­ty in mice in­fect­ed with SARS-CoV-2” with re­gards to vi­ral load, lung pathol­o­gy and pul­monary func­tion, they re­port­ed in a preprint.

Gilead has al­so pro­posed the op­tion of in­tranasal de­liv­ery, with tri­als for an in­haled for­mu­la­tion of remde­sivir un­der­way.

“Next-gen­er­a­tion oral coro­n­avirus (CoV) an­tivi­rals, if wide­ly dis­sem­i­nat­ed and giv­en ear­ly in in­fec­tion, could cur­tail the du­ra­tion of dis­ease, re­duce long-term se­que­lae of COVID-19, min­i­mize house­hold trans­mis­sions, and lessen hos­pi­tal­iza­tions, thus hav­ing a broad im­pact on pub­lic health,” they wrote.

The goal, though, is not just to fight Covid-19, but any oth­er coro­n­avirus that emerges in the years to come.

The da­ta pro­vid­ed here­in sup­ports the fu­ture eval­u­a­tion of oral­ly bioavail­able pro­drugs of GS-441524 in hu­mans with COVID-19. If safe and ef­fec­tive, this class of RdRp in­hibitors could be­come part of the ar­se­nal of ex­ist­ing oral an­tivi­rals that are des­per­ate­ly need­ed to ad­dress a glob­al un­met need for the COVID-19 pan­dem­ic and CoV pan­demics of the fu­ture.

Pre­dict­ing 200M-500M cas­es each year, Roche vows to keep up Covid-19 R&D

Roche doesn’t see Covid-19 go­ing away any time soon, if ever.

That’s why the phar­ma gi­ant will keep work­ing on treat­ments and di­ag­nos­tics against the coro­n­avirus, said Bar­ry Clinch, glob­al head of in­fec­tious dis­ease clin­i­cal de­vel­op­ment, on a con­fer­ence call with an­a­lysts, per Bloomberg.

On top of mak­ing Covid-19 di­ag­nos­tics and help­ing Re­gen­eron man­u­fac­ture its an­ti­body cock­tail, Roche is al­so de­vel­op­ing an an­tivi­ral to tack­le the in­fec­tion.

The way Roche sees it, the dis­ease will most like­ly be­come sea­son­al and en­dem­ic, with 200 mil­lion to 500 mil­lion new in­fec­tions each year — not just an­oth­er com­mon cold.

While the virus will “be­come eas­i­er to man­age over time,” it will still call for man­age­ment, Clinch was quot­ed as say­ing, rep­re­sent­ing a mid­dle ground be­tween the best-case sce­nario of it dis­ap­pear­ing and a worst-case sce­nario of it be­com­ing un­pre­dictable due to con­stant mu­ta­tions.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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WIB22: Lead­ing NK cell re­searcher re­flects on roots in Iran, the UK and Texas

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

In a small but widely-cited 11-person study published in NEJM in 2020, seven patients saw signs of their cancer completely go away after getting a new therapy made from natural killer cells. The study was one of the earliest to provide clinical proof that the experimental treatment method had promise.

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WIB22: Chas­ing af­ter ever-evolv­ing sci­ence takes a drug hunter across the pond

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Like many scientists, Fiona Marshall would tell you that she loved the natural world growing up — going to look at crabs running around the beach near her childhood home, pondering about the tides. But one thing about biology, in particular, stood out: It was constantly changing, and changing very quickly.

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