The PC­SK9 of NASH? Re­gen­eron and Al­ny­lam join forces to tack­le a promis­ing tar­get for se­vere liv­er dis­eases

The Re­gen­eron Ge­net­ics Cen­ter $REGN rou­tine­ly sifts through a moun­tain of se­quenc­ing da­ta. And every now and then, the re­searchers there will pan out a glit­ter­ing find­ing that looks like it could rank right up there with PC­SK9.

Here’s one.

John Maraganore

This evening, in a study pub­lished in the New Eng­land Jour­nal of Med­i­cine, they are point­ing to one such dis­cov­ery that they be­lieve has some big im­pli­ca­tions for se­vere liv­er dis­eases, in­clud­ing the Holy Grail of NASH. And with­out a log­i­cal an­ti­body strat­e­gy to put in­to play — giv­en an in­tra­cel­lu­lar tar­get in the spot­light — they’ve en­list­ed an ex­pe­ri­enced crew at Al­ny­lam to bring their RNAi gene si­lenc­ing plat­form in­to the game to find the most ef­fi­cient way to pro­vide the key to coun­ter­ing a raft of ail­ments.

“We ob­vi­ous­ly saw the da­ta and we were blown away,” says Al­ny­lam $AL­NY CEO John Maraganore, who’s now in wait-and-see mode as their lead drug patisir­an rolls up to an Au­gust PDU­FA date. “This tar­get  — HSD17B13 — from a hu­man ge­net­ics per­spec­tive it re­al­ly is the  PC­SK9 of NASH.”

Aris Baras

Re­gen­eron prides it­self on mov­ing ag­gres­sive­ly when they find some­thing promis­ing for clin­i­cal de­vel­op­ment. And in Al­ny­lam, they feel they are work­ing with close kin in that re­spect.

“These guys at Al­ny­lam have a sim­i­lar ap­proach and track record,” says Aris Baras, head of the RGC. And he feels this tar­get de­serves speed and care, which in­spired a 50/50 deal on re­search costs and any com­mer­cial po­ten­tial that comes out of the pre­clin­i­cal align­ment.

How fast can Al­ny­lam move here? “We’re not giv­ing guid­ance,” says Maraganore, but he says you shouldn’t be sur­prised if there’s a pro­gram in the clin­ic next year. (Yes, that is fast.)

The deal, he adds, calls for shared eco­nom­ics in de­vel­op­ment, with Al­ny­lam do­ing the crit­i­cal ear­ly de­vel­op­ment and Re­gen­eron pick­ing up the late-stage work. That will be their first RNAi study of their own, says Maraganore, but there’s no re­al mys­tery in how that works. And they’ll stay close­ly in­volved through­out.

The study of hu­man ge­net­ics in these cen­ters is be­gin­ning to have a re­al im­pact on R&D ef­fi­cien­cy, says Baras. And this project in par­tic­u­lar, he be­lieves, high­lights the promise of the field in quick­ly ze­ro­ing in on a vi­able drug pro­gram.

By set­ting up a large pile of ge­net­ic da­ta on thou­sands of pa­tients with liv­er dis­ease and com­par­ing it with se­quenc­ing da­ta on a group of tens of thou­sands of healthy peo­ple, Baras tells me, the re­searchers at Re­gen­eron’s ge­net­ics arm nar­rowed down pos­si­ble ge­net­ic trig­gers for dis­ease to a loss-of-func­tion ge­net­ic vari­a­tion in HSD17B13.

Ful­ly shut down by the vari­a­tion, the in­ves­ti­ga­tors found that eclips­ing the gene re­duced en­zy­mat­ic ac­tiv­i­ty:

— Cut­ting the risk of al­co­holic cir­rho­sis by 73%.

— Low­er­ing the risk of non­al­co­holic cir­rho­sis by 49%.

— And cut­ting the risk of al­co­holic liv­er dis­ease by 53%, and non­al­co­holic liv­er dis­ease by 30%, with an as­so­ci­at­ed re­duc­tion in risk of NASH.

Re­gen­eron is al­so go­ing af­ter some small mol­e­cule pro­grams in the process.

“We think this is big bi­ol­o­gy and there are dif­fer­ent shots on goal with dif­fer­ent modal­i­ties,” says Baras.

We’ll stay fo­cused here at End­points on this one to see whether it lives up to the pre­clin­i­cal promise. Tra­di­tion sug­gests that any pro­gram that goes in­to the clin­ic will have at best around a 1 in 10 shot at an ap­proval. Ge­net­ics aims to change those odds for the bet­ter.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bris­tol My­ers Squibb sues No­var­tis for roy­al­ties sur­round­ing the use of trans­genic mice

Two Big Pharma companies are going to the mat over genetically modified mice in a licensing dispute.

Bristol Myers Squibb is suing Novartis in New York over a dispute concerning an evaluation, research and commercialization agreement stretching back to the late ’90s initially inked between Novartis and BMS’ predecessor Medarex. The deal in question allowed Novartis to use Medarex’s patented transgenic mice to develop therapeutic drugs. Novartis agreed to pay Medarex – and subsequently BMS – a royalty on sales of drugs it developed using the mice.

Anthony Fauci (AP Images)

West Vir­ginia man faces prison time for threat­en­ing emails to Fau­ci, oth­er health of­fi­cials

NIAID director Anthony Fauci gained hero status amid the pandemic, earning Americans’ trust and even Time magazine’s Guardian of the Year title. But he and other federal health officials have also faced intense threats, according to charges brought by the US Department of Justice.

A West Virginia man is facing up to 10 years in prison after threatening Fauci, former NIH director Francis Collins, and HHS assistant secretary for health Rachel Levine via email, the DOJ said on Monday. Thomas Patrick Connally, Jr., pleaded guilty on Monday to using an anonymous email address to threaten the officials for performing their official duties, including discussing Covid-19 testing and prevention.