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.

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

Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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IPOs abound in the time of coro­n­avirus, as For­ma Ther­a­peu­tics pen­cils in $150M Nas­daq de­but

The IPO engine is thriving, never mind the rampage of the coronavirus crisis on R&D timelines.

On Friday, along with synthetic lethality-focused biotech Repare Therapeutics, another Bristol Myers partner Forma Therapeutics also unveiled its plans to vault on to the Nasdaq — penciling in a target of $150 million.

The Watertown, Massachusetts-based company — which poached senior Genentech executive Frank Lee to take over the reins last year after more than a decade under founder Steve Tregay — raised a plump $100 million late last year, while shepherding its sickle cell disease (SCD) drug through an early-stage trial.

Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid August.

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Roche nabs front­line OK for Avastin/Tecen­triq in com­mon liv­er can­cer, best­ing an old Bay­er drug

For the first time in 12 years, the FDA has approved a new frontline treatment for the most common form of liver cancer.

The agency okayed a combination of Roche’s anti-VEGF antibody Avastin and their immunotherapy Tecentriq for patients with unresectable or metastatic hepatocellular carcinoma (HCC). The approval comes two weeks after Roche and their big biotech sub Genentech published Phase III results showing the combo improved both progression-free survival and, crucially, helped patients live longer than the long-running standard-of-care, Bayer’s Nexavar.

Jean-Jacques Bienaime, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Lynn Seely, Myovant CEO

My­ovant’s re­l­u­golix wins a piv­otal prostate can­cer show­down with an old stan­dard — com­ing down to the wire on ap­provals

Myovant $MYOV has rounded the final turn in its development race to get relugolix down to the regulatory wire at the FDA. And the biotech joined the virtual crowd at ASCO with the kind of data needed to keep the investor crowd’s attention.

Much of the attention on the drug has been focused on uterine fibroids, where AbbVie just scored a regulatory win for their rival drug Oriahnn (elagolix) as the biotech posted results in prostate cancer at the ASCO meeting.

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