To un­der­stand the new Glax­o­SmithK­line that Em­ma Walm­s­ley is promis­ing to ush­er in, one must see through the old GSK.

“We know this has been a com­pa­ny that has peren­ni­al­ly dis­ap­point­ed when you look at the first half of the last decade,” the CEO said in one of her fi­nal re­marks at the long-an­tic­i­pat­ed in­vestor day.

But af­ter four years of strate­gic trans­for­ma­tion and in­vest­ment, her top team is ready to take the wraps off a shiny new ver­sion of the Big Phar­ma that, among oth­er things, will strive to de­liv­er £33 bil­lion ($46 bil­lion) in an­nu­al sales by 2031. It will start with a planned de­merg­er of the con­sumer health busi­ness in­to a sep­a­rate com­pa­ny in the mid­dle of next year, while the new GSK re­tains a 20% stake as a “short-term fi­nan­cial in­vest­ment.”

Hal Bar­ron

The ma­jor­i­ty of the rev­enue should come from cur­rent late-stage projects, hand­picked by R&D chief Hal Bar­ron in con­sul­ta­tion with chief com­mer­cial of­fi­cer Luke Miels.

The end goal? A “step change” in per­for­mance to re­vi­tal­ize the busi­ness around new vac­cines and spe­cial­ty med­i­cines — two ar­eas that are now in­ter­twined as pre­ven­tion and treat­ment con­verge.

For any­one who’s been fol­low­ing the R&D roadmap that Bar­ron laid out in 2018 af­ter tak­ing over, it can sound like more of the same. Sure, the sep­a­ra­tion of the con­sumer health busi­ness might be the most sig­nif­i­cant change for GSK in two decades; yet the com­pa­ny is stub­born­ly con­sis­tent about what it will take to thrive in the fu­ture. It’s still about the sci­ence of the im­mune sys­tem, the un­der­stand­ing of func­tion­al ge­nomics, some ma­chine learn­ing or ar­ti­fi­cial in­tel­li­gence, as well as a healthy di­et of bolt-on and li­cens­ing deals to en­hance all those ar­eas.

The dif­fer­ence could be that the clock is tick­ing. Amid threats of an ac­tivist at­tack and calls for greater re­form, Walm­s­ley, Bar­ron and oth­ers are un­der se­ri­ous pres­sure to de­liv­er, and every blun­der or set­back could be mag­ni­fied.

But if they suc­ceed, the new GSK will make a mark and cre­ate last­ing fran­chis­es across in­fec­tious dis­ease, HIV, on­col­o­gy and im­munol­o­gy. And they’ve brought in fresh blood to ex­e­cute: Ac­cord­ing to Walm­s­ley, “85% of our top 125 lead­ers are new in roles since 2017, in­clud­ing 30% re­cruit­ed ex­ter­nal­ly.”

Now that they are wrap­ping up a dras­tic re­struc­tur­ing that led to mas­sive lay­offs, she added, there are no near-term plans for an­oth­er round. It’s show­time.

Be­yond Covid-19 vac­cines

GSK may have fall­en be­hind on the glob­al hunt for a Covid-19 vac­cine, but it’s very much look­ing to get in the next-gen game.

Roger Con­nor

Like ri­vals at Pfiz­er (and cur­rent part­ners at Sanofi), GSK wants to be at the fore­front of mR­NA, ac­cord­ing to Roger Con­nor, pres­i­dent of glob­al vac­cines — which is why they’ve re­cruit­ed more than 200 sci­en­tists to fo­cus on this area and teamed up with Ger­many’s Cure­Vac to cre­ate mul­ti­va­lent vac­cines not just for Covid-19 but al­so for in­fluen­za.

De­spite the dis­ap­point­ing re­sults around a Covid-19 vac­cine made from the first gen­er­a­tion of tech­nol­o­gy, the phar­ma clear­ly sees a fu­ture in the sec­ond-gen­er­a­tion ver­sion of the tech.

Said Bar­ron:

I think the key thing to re­mem­ber at least our view is that the fu­ture for mR­NA vac­cines are go­ing to be mul­ti­va­lent. Mul­ti­va­len­cy re­quires a low­er dose be­cause you can’t give a cer­tain amount of mR­NA with­out cre­at­ing re­ac­to­genic­i­ty. So if you’re go­ing to use mul­ti­va­lent vac­cines, you got­ta get the num­ber of mi­cro­grams per va­lence down. What Cure­Vac’s sec­ond-gen­er­a­tion, I think, is telling us is that when you op­ti­mize the un­trans­lat­ed re­gions on each side, the 5’, 3’, you get more ef­fi­cient trans­la­tion, more pro­tein pro­duced.

While Shin­grix cur­rent­ly head­lines the port­fo­lio, GSK is al­so hop­ing its vac­cine for RSV — cre­at­ed from the same plat­form — would do just as well, with broad reach to both old­er adults and preg­nant women (to pre­vent in­fec­tions for their new­borns). As with menin­gi­tis, Con­nor sug­gest­ed that these are ex­am­ples of pathogens where old­er tech­nolo­gies may still have a role to play over mR­NA.

HIV, can­cer, and some wild cards

One thing that the new GSK will like­ly do is to keep drop­ping hints about its in­ter­ests through deals.

Vi­iV Health­care, the HIV-fo­cused sub­sidiary, made its goal clear as it inked a deal with Halozyme ear­li­er this week: to cre­ate ul­tra long-act­ing reg­i­mens that will com­plete­ly change how peo­ple live with the virus.

The first drug to do that is cabote­gravir, the in­te­grase in­hibitor that Vi­iV hopes will be a back­bone for an­ti­retro­vi­ral ther­a­py for the next 10 years the same way that do­lute­gravir — which is los­ing patent pro­tec­tion around 2028 — has.

In can­cer, the most re­cent ex­am­ple came in a pact with iTeos, where GSK paid $625 mil­lion up­front to grab a TIG­IT drug. Even though they’ve en­tered the race lat­er than oth­ers, Bar­ron reck­ons their own ge­nomics da­ta and an­a­lyt­ics point them to things oth­ers can’t see. If TIG­IT plus PD-1 is I/O 2.0, they might be able to add a third ther­a­py tar­get­ing the CD226 ax­is to reach I/O 3.0.

“There’s first to ap­proval, but there’s al­so first in dis­ease,” he said. “We have a re­al­ly ro­bust set of stud­ies that we’re an­tic­i­pat­ing do­ing where we think while we may not be first to mar­ket in lung, where Roche and Mer­ck are prob­a­bly both ahead, we have some par­tic­u­lar­ly in­ter­est­ing in­sights about oth­er dis­eases that we might want to pur­sue, and we can use some da­ta from ex­ter­nal sources to un­gate those tri­als.”

Then there are the in­ter­nal projects you may have to squint hard­er to find, such as Ze­ju­la — which Bar­ron touts as a best-in-class PARP in­hibitor — or the mul­ti­ple myelo­ma drug Blenrep or otil­imab for rheuma­toid arthri­tis or a new an­tibi­ot­ic dubbed gepoti­dacin or dapro­du­s­tat for ane­mia as­so­ci­at­ed with chron­ic kid­ney dis­ease.

As for the lega­cy meds that don’t fit in­to the four new fo­cus ar­eas, mov­ing for­ward GSK will lump them in­to a gen­er­al med­i­cines group that will hap­pi­ly di­vest or part­ner out non-pri­or­i­ty drugs to in­vest in the vac­cines and spe­cial­ty can­di­dates.

“(H)aving the op­por­tu­ni­ty to al­lo­cate cap­i­tal across both phar­ma and vac­cines al­lows us to put mon­ey to where the great projects are,” Bar­ron not­ed.

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.

The National Institutes of Health has again declined to use so-called “march-in” rights to lower the price of Astellas and Pfizer’s prostate cancer drug Xtandi despite being invented at UCLA with grants from the US Army and NIH.

“Given the remaining patent life and the lengthy administrative process involved for a march-in proceeding, NIH does not believe that use of the march-in authority would be an effective means of lowering the price of the drug,” NIH told prostate cancer patients Robert Sachs and Clare Love, in a letter shared with Endpoints News. The institutes’ analyses found Xtandi “to be widely available to the public,” an indication that there was not a pressing need for the US to act.