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.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

CDC’s Robert Redfield, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust of the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Laura Shawver (Silverback Therapeutics)

Fol­low­ing a hefty Se­ries B, Sil­ver­back Ther­a­peu­tics quick­ly pulls in $85M for 'an im­por­tant growth phase'

Months after reeling in a $78 million Series B round, Silverback Therapeutics has hooked an even larger Series C.

The Seattle-based company announced Wednesday that it netted $85 million from a slate of new and previous investors. The quick boost could be a sign that an IPO is on the way.

In an email, Silverback CEO Laura Shawver told me she was “not able to provide any additional comments about Silverback” beyond what was shared in the company’s news release. In the prepared statement, she said the company is at “an important growth phase.”

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

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On­ly five months af­ter a Se­ries A launch, Taysha goes pub­lic with $157M IPO

As has been the trend in 2020, Taysha Gene Therapies has become the latest biotech to make a quick ascent from a small, privately-funded company to enjoying its very own Nasdaq ticker.

The Dallas-based biotech raised $157 million for its IPO after pricing shares at $20 apiece Thursday, the high-point of its expected range. Initially pegging $100 million in financing, Taysha offered a little less than 8 million shares and will trade under the $TSHA symbol.

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CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.