Zaf­gen's sec­ond try at Prad­er-Willi syn­drome trig­gers an­oth­er safe­ty alarm in pre­clin­i­cal tox study

Zaf­gen’s $ZFGN lat­est shot at cre­at­ing the first ther­a­py to treat pa­tients with rare cas­es of obe­si­ty brought on by Prad­er-Willi syn­drome has hit a safe­ty alarm be­fore the drug even man­aged to make it in­to the clin­ic.

The suc­ces­sor to be­lo­ranib — which blew up with spec­tac­u­lar ef­fect sev­er­al years ago fol­low­ing a clin­i­cal hold by the FDA — ZGN-1258 was sup­posed to be the biotech’s come­back drug in the field. In­stead, the biotech re­port­ed af­ter the mar­ket closed on Mon­day that it is sus­pend­ing plans for an IND af­ter re­searchers tracked mus­cle de­te­ri­o­ra­tion in a ro­dent mod­el of the dis­ease.

Zaf­gen’s stock shriv­eled at the men­tion of a new safe­ty alert. The shares plum­met­ed 35% af­ter the bell.

From their state­ment to­day:

Non­clin­i­cal da­ta showed de­gen­er­a­tion and oth­er anom­alies in rat mus­cle tis­sue to dif­fer­ent de­grees in both ve­hi­cle and dose arms of the stud­ies. The ef­fects were ab­sent from oth­er an­i­mal species in long term mod­els, and im­por­tant­ly, this find­ing has not been ob­served in any of the Com­pa­ny’s oth­er MetAP2 in­hibitors or clin­i­cal tri­als and ap­pears to be spe­cif­ic to ZGN-1258. Zaf­gen will pro­vide an up­date on plans for ZGN-1258 at a lat­er time, if war­rant­ed, fol­low­ing fur­ther eval­u­a­tion.

The move to shelve the IND came af­ter Zaf­gen re­port­ed in an SEC fil­ing late last year that every­thing had been lined up to ini­ti­ate clin­i­cal tri­als ex­cept for 1 last pre­clin­i­cal tri­al, which had to be re­done by a new CRO af­ter the first CRO had con­duct­ed it “im­prop­er­ly.”

Any fresh hint of a safe­ty warn­ing is tox­ic to Zaf­gen, which had to re­or­ga­nize and ul­ti­mate­ly re­place the se­nior ex­ecs who went on to oth­er en­deav­ors af­ter the first big crash. The biotech re­cent­ly re­port­ed what it called en­cour­ag­ing ear­ly da­ta about their lead drug, ZGN-1061 for obe­si­ty re­lat­ed to di­a­betes. Re­searchers re­port­ed pos­i­tive im­prove­ments in weight loss and blood sug­ar lev­els for di­a­bet­ics.

The lead drug, though, has al­so been un­der a cloud since the FDA dropped a clin­i­cal hold on the pro­gram last No­vem­ber, cit­ing CV safe­ty con­cerns. Leerink’s Joseph Schwartz has re­mained fo­cused on a key bio­mark­er for CV risk, even as the com­pa­ny pur­sued a risky ex-US tri­al.

Di­a­betes is a field with a huge pa­tient pop­u­la­tion, and even a hint of a safe­ty is­sue could prove lethal for any drug in de­vel­op­ment for this group.

And obe­si­ty drugs in gen­er­al are al­ways un­der a mi­cro­scope at the FDA, even af­ter the lat­est gen­er­a­tion hit the mar­ket, though they proved dra­mat­i­cal­ly un­suc­cess­ful as a com­mer­cial prod­uct.

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.

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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The fu­ture of mR­NA, J&J's vac­cine ad­comm, Mer­ck­'s $1.85B au­toim­mune bet and more

Welcome to the third installment of 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.

If this report was helpful in recapping it all for you, please do share it with your colleagues.

Get ready for FDA’s third Covid-19 vaccine

On the heels of a ringing endorsement from FDA reviewers earlier in the week, J&J‘s single-dose vaccine — which proved 66% effective at preventing symptomatic Covid-19, and 85% effective at stopping severe disease 28 days after administration — the advisory committee convened by the agency voted unanimously to recommend its emergency use authorization. It was “a relatively easy call,” according to one of the committee members — although that doesn’t mean they didn’t have questions. Jason Mast has the highlights from the discussion, including new information from the company, on this live blog.

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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.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Roche and Genen­tech re­searchers plot $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Roche and Genentech have committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Researchers from both Roche and its big South San Francisco hub — mixing teams from gRED and pRED this time — will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

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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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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