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.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Covid-19 roundup: Mer­ck­'s $356M sup­ply deal on hold as FDA asks for more da­ta; UK stud­ies of­fer more in­for­ma­tion on ef­fi­ca­cy of Pfiz­er/BioN­Tech vac­cine af­ter one dose

Merck is pushing back plans to supply the US government with a Covid-19 drug after the FDA asked for more data to support an emergency use authorization.

The antibody, MK-7110, had looked promising in a Phase III study conducted by OncoImmune before Merck came along and bought the biotech for $425 million. At the interim analysis, investigators looked at data from 203 patients and concluded that a single dose of the drug cut the risk of death or respiratory failure by more than 50% among severe patients. And those taking the drug had a 60% higher chance of improvement in clinical status compared to placebo.

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CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

Fatty liver conceptual image, 3D illustration showing fatty liver silhouette made from micrograph of liver steatosis (Shutterstock)

The path to NASH: un­der­stand­ing the role of se­vere obe­si­ty in a com­plex, mul­ti-sys­tem dis­ease

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We often think a person’s transition from a healthy to a diseased state is binary. But that’s often not the case. In reality, the onset of a disease is not something that occurs overnight, and the majority lie on a continuum that is impacted by a multitude of factors. Some of these factors are in a patient’s control. Others are not.

This is the case in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), two of the most complex diseases that “live” on this proverbial continuum. The clinical onset of NAFLD — and ultimately NASH — is a complex process that is closely related to obesity, insulin resistance and impaired adipose tissue metabolism.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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