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.

A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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David Grainger [file photo]

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Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

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