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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

Tillman Gerngross, Adagio CEO

Q&A: Till­man Gern­gross ex­plains why his Covid mAb will have an edge over an al­ready crowd­ed field

If anyone knows about monoclonal antibodies, it’s serial entrepreneur, Adimab CEO, and Dartmouth professor of bioengineering Tillman Gerngross.

Even the name of Gerngross’ new antibody startup Adagio Therapeutics is meant to reflect his vision behind the development of his Covid-19 mAb: slowly, he said, explaining that “everyone else, whether it’s Regeneron, Lilly, or AstraZeneca, Vir, they all valued speed over everything.”

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Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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