Zaf­gen stakes out a PhI beach­head for its next weight drug as it fights for a come­back

Last sum­mer Zaf­gen $ZFGN ex­pe­ri­enced one of the worst biotech dis­as­ters the in­dus­try wit­nessed for all of last year — the kind of night­mare that CEOs dread. Af­ter the FDA put their lead drug be­lo­ranib on clin­i­cal hold in late 2015 — link­ing it to the death of a pa­tient from a pul­monary em­bolism linked with the ther­a­py — the biotech had lit­tle choice but to kill the pro­gram in Ju­ly and slash its staff af­ter reg­u­la­tors spelled out what they would have to do to qual­i­fy for a mar­ket­ing OK.

Tom Hugh­es

But with its share price dec­i­mat­ed, Zaf­gen still didn’t throw in the tow­el. And now in an ef­fort to make a come­back, Zaf­gen’s team has re­leased Phase I da­ta that shows its sole clin­i­cal drug hope, ZGN-1061, a fol­lowup MetAP2 drug, was able to knock about a pound a week off of obese and over­weight pa­tients for four weeks, with­out any signs of throm­bot­ic risk.

Zaf­gen shares surged 15% on the news Thurs­day evening, in post-mar­ket trad­ing.

Break­ing down the da­ta, pa­tients treat­ed with ZGN-1061 for four weeks lost sig­nif­i­cant­ly more weight rel­a­tive to place­bo-treat­ed pa­tients, drop­ping 4.6 lbs, 2.2 lbs and 3.8 lbs for 0.2 mg, 0.6 mg, and 1.8 mg dos­es, re­spec­tive­ly, com­pared to a 0.51 lb loss for the place­bo arm. And that’s what they were hop­ing to see as they po­si­tion them­selves for a run at obe­si­ty and Type 2 di­a­betes, two of the most dif­fi­cult mass mar­ket con­di­tions any biotech ever tack­led.

That’s not the kind of sud­den and mas­sive weight loss that be­lo­ranib could trig­ger in the first few weeks, CEO Tom Hugh­es con­cedes, but cu­mu­la­tive­ly it’s sig­nif­i­cant­ly bet­ter than the dis­ap­point­ing trio of weight drugs that hit a few years ago. This drug, he em­pha­sized, is on the right track for a Phase I, bless­ed­ly free of any sur­pris­es for the re­searchers in­volved.

“We’ve been work­ing in this area for quite some time,” Hugh­es told me ear­li­er Thurs­day. That gives the team at Zaf­gen a chance to care­ful­ly eval­u­ate the phar­ma­co­ki­net­ic qual­i­ties of  ZGN-1061, tar­get en­gage­ment and the dose ef­fect, con­firm­ing the “good be­hav­ior” of the drug in an ad­mit­ted­ly small num­ber of sub­jects.

Hugh­es was def­i­nite­ly up­beat about the re­sults, but al­so per­haps a lit­tle more sub­dued than in past dis­cus­sions about be­lo­ranib as that drug head­ed through the clin­ic be­fore im­plod­ing in Phase III.

“I don’t know if you can tell by our tone,” he said at one point, “but we are re­al­ly, re­al­ly pleased with the re­sult….It’s good to have a well-be­haved mol­e­cule.”

And how.

Phase I is a rel­a­tive­ly small step in the obe­si­ty/di­a­betes R&D world, with ma­jor de­mands that ul­ti­mate­ly have to be met on safe­ty and ef­fi­ca­cy that have be­dev­iled oth­er de­vel­op­ers over the years and forced in­vestors to di­rect their cash else­where.

Phase II, slat­ed to get un­der­way lat­er this year, will re­cruit about 120 pa­tients with Type 2 di­a­betes, says CMO Den­nis Kim, prob­a­bly look­ing at he­mo­glo­bin A1c lev­els — a clas­sic mea­sure of ef­fi­ca­cy — as the pri­ma­ry end­point. The com­pa­ny still prob­a­bly hasn’t es­tab­lished the low­est most ef­fec­tive dose of the drug, which they should be able to shine a light on as mid-stage da­ta comes through.

Lat­er on, adds Hugh­es, it’s pos­si­ble that Zaf­gen could take on a part­ner as it an­gles for a Phase III. And cer­tain­ly on­ly a ma­jor play­er could ex­pect to mar­ket a drug like this if it even­tu­al­ly wins an OK. But if things con­tin­ue to go the biotech’s way this time, Hugh­es feels that the cap­i­tal will be there for what’s need­ed.

Now it’s time to con­cen­trate on step 2 in their re­hab pro­gram.


Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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