Zaf­gen has some­thing to cheer as di­a­betes drug makes the cut in PhII study

Af­ter be­ing plagued by a laun­dry list of set­backs that cul­mi­nat­ed in the de­ser­tion of its obe­si­ty drug and the de­par­ture of its CEO, Zaf­gen fi­nal­ly has some good news to re­port. Da­ta from a co­hort of a mid-stage study sug­gest­ed that its now-lead di­a­betes drug in­duced sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in blood sug­ar lev­els and weight loss.

The Boston-based com­pa­ny’s shares $ZFGN rose about 7% in pre-mar­ket trad­ing on Thurs­day.

More than two years ago Zaf­gen aban­doned de­vel­op­ing be­lo­ranib af­ter the ex­per­i­men­tal obe­si­ty drug was linked to pa­tient deaths in a late-stage study. The FDA, wor­ried about ex­pos­ing more pa­tients to harm, slapped a clin­i­cal hold on Zaf­gen’s sec­ond-gen­er­a­tion di­a­betes drug ZGN-1061 last No­vem­ber, wary that the car­dio threat posed by be­lo­ranib was still in play. At the time, Zaf­gen said ex-US Phase II clin­i­cal tri­al of ZGN-1061 would con­tin­ue as planned, and that it would talk to the FDA staff to de­ter­mine the path for­ward.

Den­nis Kim

On Thurs­day, the com­pa­ny re­port­ed en­cour­ag­ing da­ta from the two high­est dos­es of the di­a­betes drug, fol­low­ing up on ear­li­er pos­i­tive re­sults with small­er dos­es. Ac­cord­ing to US clin­i­cal tri­als data­base, the Phase II proof-of-con­cept study in­clud­ed two groups of pa­tients. In the first co­hort, 120 pa­tients would get ei­ther 0.05, 0.3, or 0.9 mg of ZGN-1061 or place­bo, while in the sec­ond co­hort, 40 pa­tients would re­ceive 0.9 or 1.8 mg of ZGN-1061 or place­bo.

No treat­ment-re­lat­ed se­ri­ous side-ef­fects and no car­dio­vas­cu­lar safe­ty sig­nals were ob­served in the sec­ond co­hort of the study, the com­pa­ny said.

Leerink’s Joseph Schwartz did not let the com­pa­ny off the hook, how­ev­er, say­ing al­though Zaf­gen did not ob­serve any clin­i­cal­ly mean­ing­ful el­e­va­tions in mean D-dimer con­cen­tra­tions — a key bio­mark­er for CV risks — he was cau­tious ahead of phase III stud­ies in­volv­ing larg­er and het­ero­ge­neous type 2 di­a­betes pa­tient pop­u­la­tion on mul­ti­ple oth­er agents.

The com­pa­ny did not dis­close how the drug en­ters and ex­its en­dothe­lial cells, Schwartz not­ed, in ref­er­ence to con­cerns he had pre­vi­ous­ly high­light­ed re­gard­ing pre­clin­i­cal da­ta on the com­pound, which sug­gests it has the propen­si­ty to in­duce clot­ting fac­tors if it is not cleared from en­dothe­lial cells, and the po­ten­tial for drug-drug in­ter­ac­tions.

In terms of ef­fi­ca­cy, 12-week da­ta sug­gest­ed that the 1.8 mg dose sur­passed the glycemic con­trol in­duced by the 0.9 mg dose, but both dos­es con­ferred a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in A1C — a blood test that mea­sures av­er­age lev­els of blood glu­cose (p<0.0001 and p=0.0003, re­spec­tive­ly). The high­est dose caused a 1.1% re­duc­tion in A1C rel­a­tive to place­bo.

“The re­sults we’ve seen…with this lat­est 1.8 mg dose co­hort, ap­pear very com­pet­i­tive with the cur­rent­ly avail­able best-in-class an­ti-di­a­betes ther­a­pies,” Zaf­gen CMO Den­nis Kim said in a state­ment. “All of the phar­ma­co­log­i­cal ac­tions of ZGN-1061 im­prove at the 1.8 mg dose lev­el and, with its in­sulin-sen­si­tiz­ing ef­fects, we be­lieve there is a clear op­por­tu­ni­ty for even greater ben­e­fit with longer treat­ment du­ra­tion giv­en the ef­fect we are see­ing at just 12 weeks.”

Sig­nif­i­cant­ly, treat­ment with the 1.8 mg dose al­so trig­gered a place­bo-cor­rect­ed weight loss of 2.3 kg (5.1 pounds) that was sta­tis­ti­cal­ly sig­nif­i­cant (p=0.0002), Zaf­gen said, adding that there was no ev­i­dence of a wan­ing ef­fect.

“These re­sults in con­junc­tion with meta­bol­ic ben­e­fits along­side a pro­gres­sive re­duc­tion in weight po­si­tion ZGN-1061 com­pet­i­tive­ly with those agents al­ready ap­proved,” Schwartz added in a note.

Di­a­betes and obe­si­ty are close­ly linked — some drugs to treat the lat­ter have been pulled off the mar­ket due to safe­ty con­cerns, and those that have man­aged to re­main on shelves have seen mea­ger adop­tion, due to their lim­it­ed ef­fec­tive­ness, bun­gled launch­es and re­im­burse­ment hur­dles.

Last year, Zaf­gen saw big man­age­ment changes, in­clud­ing the ex­its of CEO Tom Hugh­es, who had led the com­pa­ny for 9 years, and board mem­ber Bruce Booth, who made his de­par­ture af­ter a dozen years.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?

Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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