Tired of be­ing dumped by phar­ma part­ners, Van­der­bilt’s neu­ro­science team takes a bold aim at the clin­ic

Jeff Conn

As the di­rec­tor of the Van­der­bilt Cen­ter for Neu­ro­science Drug Dis­cov­ery, Jeff Conn has spe­cial­ized in pre­clin­i­cal de­vel­op­ment work on new drugs bio­phar­ma com­pa­nies can take in­to the clin­ic. He’s al­so seen two of the big com­pa­nies he’s part­nered with — Bris­tol-My­ers Squibb and As­traZeneca — make sud­den, un­ex­pect­ed re­treats from the field, which has known a steady di­et of fail­ures and set­backs in re­cent years.

So this time, in­stead of li­cens­ing out his drug and tak­ing the risk of an­oth­er ear­ly dis­ap­pear­ance, Conn and his col­leagues at Van­der­bilt are tak­ing their drug di­rect­ly in­to an ear­ly-stage hu­man study in a rare — per­haps unique — dis­play of aca­d­e­m­ic risk-tak­ing in the clin­ic.

“This drug can­di­date is a pos­i­tive al­losteric mod­u­la­tor of an M1 (mus­carinic) re­cep­tor,” says Conn, re­fer­ring to a neu­ro­trans­mit­ter dis­rupt­ed in Alzheimer’s and schiz­o­phre­nia. This is a well plumbed field, with drugs that have been tried in the clin­ic and failed, says Conn, but no one was able to de­vel­op high­ly se­lec­tive mol­e­cules—at least not un­til now.

“That’s what we are now ad­vanc­ing,” he tells me, fo­cus­ing on cog­ni­tive im­pair­ment in ear­ly to mod­er­ate Alzheimer’s and al­so in schiz­o­phre­nia. And his team is con­cen­trat­ing on some symp­toms that haven’t been ad­dressed so far, in­clud­ing: so­cial with­draw­al, lack of mo­ti­va­tion and a lack of abil­i­ty to ex­pe­ri­ence re­ward.

“The mod­el we fo­cused on has been to part­ner with com­pa­nies rel­a­tive­ly ear­ly, cer­tain­ly be­fore clin­i­cal de­vel­op­ment,” Conn adds. “The shift­ing land­scape in the phar­ma in­dus­try (which in­clud­ed As­traZeneca’s re­cent de­ci­sion to qui­et­ly scut­tle its vir­tu­al iMed mod­el for neu­ro­science) has re­al­ly caused us to re­think that.”

“For this tar­get, we’re tak­ing it through Phase I, make sure there are none of the ad­verse ef­fect li­a­bil­i­ty seen in the ‘90s,” he adds. “That would be a ma­jor step for de-risk­ing, a good point for part­ner­ing with a ma­jor com­pa­ny. We can al­so show we could en­gage the re­cep­tor in the CNS.”

Craig Lind­s­ley

This is no small un­der­tak­ing for an aca­d­e­m­ic group, em­pha­sizes Craig Lind­s­ley, co-di­rec­tor and chief of med­i­c­i­nal chem­istry at the cen­ter.

“We all came from in­dus­try,” he notes. “Do­ing an IND on your own is quite an un­der­tak­ing, in­clud­ing tasks large­ly un­known in aca­d­e­m­ic cir­cles,” such as meet­ing rules on man­u­fac­tur­ing and prod­uct for­mu­la­tion. “It’s an ex­tra day job for every­body. It helped us un­der­stand we could do this. And next time it will be eas­i­er and faster.”

Next time will come soon enough, he says, with an ear­ly stage pipeline in the mak­ing. The NIH and non­prof­its — in­clud­ing The William K. War­ren Foun­da­tion — have pro­vid­ed the ad­di­tion­al fi­nan­cial fire­pow­er need­ed to push ahead in­to the clin­ic. Af­ter they get through Phase I, he and Conn be­lieve that they can go back and do high­er val­ue deals af­ter nail­ing down some sol­id hu­man da­ta on safe­ty and ear­ly ef­fi­ca­cy sig­nals in healthy vol­un­teers. And if Big Phar­ma isn’t in­ter­est­ed, then per­haps a small­er biotech or spin­out can do the job.

The key point, they both say, is that they want their drugs to go as far as pos­si­ble through the clin­ic, and all the way to pa­tients if they can. Next time one of their drugs fails to make it, they don’t want it to be be­cause yet an­oth­er com­pa­ny pulled a sud­den and un­ex­pect­ed left turn in their clin­i­cal strat­e­gy. And for that, they’re will­ing to as­sume some of the added risk that has fright­ened much big­ger play­ers out of the Val­ley of Death.

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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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.

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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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.