Emma Walmsley (GSK via investor day livestream)

Mul­ti­va­lent mR­NA vac­cines, I/O 3.0, long-act­ing HIV drugs: The $46B game is on for the new Glax­o­SmithK­line

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.

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.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; 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.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).