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.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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#ES­MO20: Alk­er­mes of­fers their first snap­shot of a ben­e­fit for their next-gen IL-2 drug. But why did 1 pa­tient starve to death?

Everyone in the cancer R&D arena is looking to build new franchises around better drugs and combos. And one busy pocket of that space is centered entirely on creating an IL-2 drug that can be as effective as the original without the toxicity that damned it to the sidelines.

Alkermes $ALKS formally tossed its hat into the ring of contenders at virtual ESMO today, highlighting the first glimpse of efficacy for their candidate, ALKS 4230, as both a monotherapy as well as in combination with Merck’s Keytruda.

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Albert Bourla, Pfizer CEO (Steven Ferdman/Getty Images)

Pfiz­er ex­ecs con­fi­dent­ly tap their top 10 block­busters-to-be. But what are the chances of sur­viv­ing PhI­II, let alone hit­ting these big peak sales es­ti­mates?

Pfizer’s top executive team doesn’t lack for confidence.

Where many Big Pharmas would be reluctant to put a peak sales figure on their late-stage drugs, Pfizer CEO Albert Bourla has shrugged off the usual diffidence to outline where the pharma giant expects to get $15 billion-plus.

The list, outlined this week during their investor presentations, is topped by 3 drugs in the $3 billion-plus peak sales category. They are:

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

Pfiz­er match­es Mod­er­na with their full Covid-19 tri­al blue­print — As­traZeneca says it will un­veil its pro­to­col 'short­ly'

Yesterday, after sustained public pressure as Moderna released its Phase III Covid-19 trial blueprint, Pfizer released its own full trial design for their vaccine trials. The move was designed to boost transparency and shore up public trust in the vaccines, but it also revealed differences in how the two companies are approaching the much-watched studies while failing to satisfy the demands of the fiercest advocates for transparency.

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#ES­MO20: Re­gen­eron, Sanofi eye an­oth­er first for their PD-1 con­tender Lib­tayo with promis­ing da­ta for on­col­o­gy niche

Regeneron and Sanofi took another step forward in the long march towards a greatly expanded market for their late-bloomer PD-1 checkpoint Libtayo.

The two occasional allies posted an objective response rate of 31% for Libtayo among 84 patients suffering from advanced cases of basal cell carcinoma at virtual ESMO. That spotlights progress for 26 patients, 5 of whom had a complete response. The data also reflect a boost in the number of responses seen from the last cut of the numbers.

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Christian Itin, Autolus CEO (Autolus)

#ES­MO20: Au­to­lus pro­vides glimpse of next-gen­er­a­tion CAR-T pro­gram, show­ing ear­ly pos­i­tive safe­ty da­ta

CAR-T therapies were hailed as a breakthrough when Novartis received the first FDA approval for Kymriah back in 2017. Though highly effective at treating certain types of blood cancers, CAR-Ts are also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome.

With this in mind, Autolus Therapeutics is looking to take a crack at a safer CAR-T and presented Phase II cohort data for its AUTO3 program at virtual ESMO 2020. The data showed that, among the 35 patients in the cohort being treated for r/r diffuse large B cell lymphoma, there were no instances of Grade 3 or higher CRS. Eight individuals saw Grade 1 inflammation while another four patients reached Grade 2.

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Seat­tle Ge­net­ic­s' Astel­las-part­nered ADC nails con­fir­ma­to­ry PhI­II in urothe­lial can­cer

Nine months after Seattle Genetics nabbed an accelerated approval for its Astellas-partnered antibody-drug conjugate Padcev, the partners said the therapy has nailed a confirmatory Phase III, proving its worth in locally advanced or metastatic urothelial cancer.

Padcev, which has widely been tapped as a potential blockbuster, scored improvements in both overall survival and progression-free survival compared to chemotherapy, causing a 30% reduction in risk of death (p = 0.001) and 39% reduction in risk of disease progression or death (p<0.00001).

Stronger to­geth­er? Boehringer and Mi­rati team to put first KRAS-KRAS com­bo in the clin­ic

Researchers are still waiting to see how much any of the vaunted KRAS drugs now in the clinic can, after decades of preclinical research and some early human studies, help patients. But while they do, two of the leading developers will look to see whether a KRAS-KRAS combo might pose a better shot than any KRAS alone.

Boehringer Ingelheim and Mirati have signed a collaboration to combine Mirati’s closely-watched lead KRAS inhibitor, MRTX849, in a clinical trial with the pan-KRAS blocker that Boehringer has quietly developed with high expectations behind their flashier contenders.

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Sean Bo­hen's break from bio­phar­ma is over. The ex-As­traZeneca CMO has re­tired his Big Phar­ma jer­sey and is now — hap­pi­ly — run­ning a lit­tle biotech

The last I had heard about Sean Bohen, he had stepped out of his high-profile job as chief medical officer at AstraZeneca at the beginning of 2019 as CEO Pascal Soriot triggered a broad-ranging R&D shakeup. And then, earlier this week, I got a chance to catch up.

It turns out that Bohen decided at the time that he would not just jump into a new job in the booming biopharma business. As an oncologist, he had worked on the big programs at AstraZeneca, and before that he was at Genentech. That was good for a ticket to just about anyplace in the big biopharma world. But he felt it was time to stop and think things through.

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