Re­gen­eron, Sanofi make their case for an­oth­er PD-1 drug — and they’re not set­tling for sixth place

Jo Lager, Sanofi

CHICA­GO — The two top im­muno-on­col­o­gy in­ves­ti­ga­tors for Re­gen­eron $REGN and Sanofi, Is­rael ‘Izzy’ Lowy and Jo Lager, came to Chica­go to of­fer a very promis­ing snap­shot of the ear­ly da­ta they’ve reaped from a study of their PD-1 drug REGN2810 for cu­ta­neous squa­mous cell car­ci­no­ma — the sec­ond dead­liest form of skin can­cer be­hind melanoma.

Like No­var­tis or In­cyte or some of the oth­er com­pa­nies work­ing on PD-(L)1 ther­a­pies in the large sec­ond wave form­ing in the pipeline fol­low­ing the first 5 that have been ap­proved, these two ma­jor league play­ers see this as a key build­ing block for the com­bos they want to de­vel­op. But it would be a mis­take, they say, to sim­ply write this one off as the lat­est check­point of this stripe look­ing to line up for the mar­ket.

Is­rael Lowy, Re­gen­eron

“I don’t think we’re the sixth,” Lowy told me in a con­ver­sa­tion over the week­end. “We’re the third.”

Re­gen­eron has some of the best an­ti­body spe­cial­ists in the busi­ness, which they’ve proved with a string of new drug ap­provals. Lowy says he’s learned a lot about PD-(L)1 while they’ve been work­ing on REGN2810. And some of their in­sights have ma­jor im­pli­ca­tions for every­one work­ing in the field.

One of the biggest lessons is that PD-1 is a sig­nif­i­cant­ly bet­ter path­way to fol­low than PD-L1, says Lowy.

The team cre­at­ed a PD-L1 as a com­ple­men­tary pro­gram in case their work on PD-1, but they feel now that PD-1 ther­a­pies of­fer a much more ef­fec­tive way to  un­leash an im­mune at­tack, some­thing that’s been un­der­scored by the dom­i­nance of Keytru­da and Op­di­vo  as well as Roche’s re­cent stun­ning set­back with the PD-L1 drug Tecen­triq.

And that’s why Re­gen­eron and Sanofi feel they can leapfrog ahead of some of the ear­ly en­tries.

Re­gen­eron and Sanofi al­so didn’t set out to cre­ate a bet­ter PD-1 than Keytru­da or Op­di­vo.

“One of the things was a ma­jor re­quire­ment for it to be at least as good as any­one else’s,” says Lowy, “not as­sum­ing that we could make an an­ti­body that was bet­ter. That be­ing said, we’re very hap­py with it. We screened many an­ti­bod­ies to pick the one that was our bet­ter can­di­date.”

Not on­ly is the first cut of the da­ta very good, this check­point is al­ready in a po­ten­tial­ly piv­otal Phase II tri­al.

Here’s what they found:

REGN2810 de­liv­ered an im­pres­sive over­all re­sponse rate of 46.2% — 12 of 26 pa­tients — which in­cludes 2 com­plete re­spons­es, 9 par­tial re­spons­es and 1 un­con­firmed par­tial re­sponse. The dis­ease con­trol rate hit 69.2%, cov­er­ing 18 of 26 pa­tients with 12 ORR and 6 with sta­ble dis­ease. The me­di­an pro­gres­sion-free sur­vival and over­all sur­vival rate were not reached at the da­ta cut­off date with a me­di­an fol­low-up of 6.9 months. Ten pa­tients re­main in re­sponse as of the da­ta cut­off date, with a range of 8 to 40 weeks du­ra­tion of re­sponse.

Ge­of­frey Porges, Leerink

Leerink’s Ge­of­frey Porges called the re­sults “com­pelling,” not­ing that the Re­gen­eron/Sanofi team could have a $300 mil­lion peak sales op­por­tu­ni­ty in the US alone. “(T)he com­pa­ny will al­most cer­tain­ly file an ap­pli­ca­tion with the two tri­als, and then take the risk of a pos­si­ble ad­vi­so­ry com­mit­tee re­view (new drug/new in­di­ca­tion for PD-1) about the clin­i­cal sig­nif­i­cance of the re­sult and the im­por­tance of the in­di­ca­tion.”

“We rec­og­nized long ago that block­ade of the PD-1 path­way is an es­sen­tial com­po­nent of any im­muno-on­col­o­gy pro­gram,” Lowy tells me. “Al­though a fab­u­lous ad­vance, it’s re­al­ly just the first chap­ter, or a pref­ace.”

“We want to have our own to fa­cil­i­tate the abil­i­ty to de­vel­op nov­el com­bi­na­tions with­out hav­ing to re­ly on any­one else’s agent,” he adds.

Re­gen­eron and Sanofi are well on their way. The rest of the in­dus­try might want to pay more at­ten­tion.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

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In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

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Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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New safe­ty da­ta ex­pose po­ten­tial weak­ness as Pfiz­er's abroc­i­tinib takes on Dupix­ent in eczema

Last September, when Pfizer celebrated positive data from a second Phase III study of abrocitinib, many watchers applauded the efficacy but were still waiting to see whether the JAK1 inhibitor is “safe enough to be a formidable competitor to Dupixent,” the clear leader in the atopic dermatitis field. The full slate of safety data are now out and, according to one analyst, the answer is: probably not.

José Basel­ga finds promise in new class of RNA-mod­i­fy­ing can­cer tar­gets, lock­ing in 3 pre­clin­i­cal pro­grams with $55M

Having dived early into some of the RNA breakthroughs of the last decades — betting on Moderna’s mRNA tech and teaming up with Silence on the siRNA front — AstraZeneca is jumping into a new arena: going after proteins that modify RNA.

Their partner of choice is Accent Therapeutics, which is receiving $55 million in upfront payment to steer a selected preclinical program through to the end of Phase I. After AstraZeneca takes over, the Lexington, MA-based startup has the option to co-develop and co-commercialize in the US — and collect up to $1.1 billion in milestones in the long run. The deal also covers two other potential drug candidates.

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