Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a break­through.

The Stan­ford neu­rol­o­gist, a soft-spo­ken de­mi-prodi­gy who be­came a pro­fes­sor while still a res­i­dent, had been ob­sessed for a decade with how to bet­ter de­fine psy­chi­atric dis­or­ders. Drugs for de­pres­sion or bipo­lar dis­or­der didn’t work for many pa­tients with the con­di­tions, and he sus­pect­ed the rea­son was how tra­di­tion­al di­ag­noses didn’t ac­tu­al­ly get at the heart of what was go­ing on in a pa­tient’s brain.

He had shown in 2006 that some pa­tients with dif­fer­ent di­ag­noses — PTSD vs. de­pres­sion, for ex­am­ple — looked re­mark­ably sim­i­lar un­der brain imag­ing, sug­gest­ing clin­i­cians drew dis­tinc­tions in the wrong places. And in 2014, he showed that one could de­fine pa­tients by look­ing at in­di­vid­ual dis­crete be­hav­iors, such as at­ten­tion or sleep.

But the big ad­vance came in 2017, when his team demon­strat­ed it could pre­dict PTSD pa­tients’ re­sponse to ther­a­py by just look­ing at their brain­waves. Sim­i­lar pre­dic­tions, aid­ed with a bit of AI, fol­lowed for oth­er dis­or­ders.

“So those are the tools that re­al­ly got us ex­cit­ed,” Etkin told End­points News. “And then of course, the main ques­tion that you can’t an­swer in the lab is, how do you de­vel­op new ther­a­peu­tics around this?”

So Etkin left the lab, turn­ing his back on a bur­geon­ing aca­d­e­m­ic ca­reer to found and a run a start­up around his pre­dic­tive tech­nol­o­gy. The com­pa­ny, known as Al­to Neu­ro­science, an­nounced a $32 mil­lion Se­ries A Thurs­day, with plans to launch three Phase IIa tri­als for treat­ment-re­sis­tant de­pres­sion and PTSD with­in the next year and have its first da­ta by 2023.

With the launch, Al­to joins a grow­ing boom in neu­ro­science R&D, a field that much of big phar­ma aban­doned over the last decade.

Amit Etkin with a stu­dent

Click on the im­age to see the full-sized ver­sion

This resur­gence has been pred­i­cat­ed in part on new tech­nolo­gies, in­clud­ing the abil­i­ty to bet­ter di­vide and clas­si­fy pa­tients by their bi­ol­o­gy. Last week, ARCH, Am­gen and a long list of oth­er in­vestors threw $500 mil­lion be­hind Neumo­ra, a biotech that promis­es to use a host of dif­fer­ent met­rics and datasets to come up with so-called “pre­ci­sion phe­no­types” — pop­u­la­tions most like­ly to re­spond to a giv­en mol­e­cule.

Al­to will try to do some­thing sim­i­lar with Etkin’s tech­nol­o­gy. The pro­fes­sor-turned-CEO and his team have spent more than a year go­ing through 200-plus mol­e­cules that have been ap­proved or put in clin­i­cal de­vel­op­ment for psy­chi­atric dis­or­ders.

They did deep dili­gence on 21 of them, look­ing for those that had gone through Phase I for safe­ty and shown the right kind of bi­o­log­i­cal ac­tiv­i­ty. They in-li­censed 11 and plan to even­tu­al­ly push each in­to a psy­chi­atric sub-pop­u­la­tion that, ei­ther be­cause of a giv­en be­hav­ior or EEG pat­tern or oth­er bio­mark­er, they think will re­spond.

Etkin views the hun­dreds of failed psy­chi­a­try drugs from the last few decade as sim­ply “tools that ma­nip­u­late the brain in some use­ful way.” His goal is to find the best place to use them.

“We have all of these tools sit­ting around that we don’t quite know how to use, and we have all this bi­ol­o­gy that we’ve been flesh­ing out over these years,” he said. “This is re­al­ly how we struc­tured Al­to in terms of the strat­e­gy: to take all that knowl­edge from the past 30 years in phar­ma and biotech, and put it to work in a tar­get­ed and mean­ing­ful way.”

Etkin found his main backer in a pro­tag­o­nist of the new neu­ro boom: Chris­t­ian Anger­may­er, the Ger­man bil­lion­aire who found­ed and large­ly fund­ed ATAI, the now-$2 bil­lion com­pa­ny try­ing to de­vel­op psy­che­delics for a panoply of psy­chi­atric dis­or­ders. His firm Ape­iron led the Se­ries A.

Chris­t­ian Anger­may­er

“Al­to is well-po­si­tioned to rev­o­lu­tion­ize the treat­ment of psy­chi­atric dis­or­ders by align­ing the right pa­tient with the right drug,” he said. “At Ape­iron, we have seen re­cent ad­vance­ments at­tempt­ing to ex­pand the toolk­it for men­tal well-be­ing but con­tin­ue to rec­og­nize the dire need to im­prove the way drugs are de­vel­oped in this space.”

The com­pa­ny is keep­ing its 11 mol­e­cules un­der wraps for now, in­clud­ing the three it plans to soon put in­to Phase IIa tri­als. Those stud­ies, Etkin said, will hope­ful­ly let Al­to prove they can de­vel­op bio­mark­ers to pre­dict the best pa­tients to re­spond, al­low­ing them to de­sign piv­otal tri­als just around that group.

It’s the be­gin­ning of what Etkin hopes will be a sea change across the field, to­ward some­thing that looks a lot clos­er to where on­col­o­gy is to­day.

“In five years, in our mind, we’ve com­plete­ly changed psy­chi­a­try, we’ve changed in­to a much more pre­cise prac­tice,” he said. “And the frus­tra­tion of tri­al and er­ror for both pa­tients and clin­i­cians is — if not gone — is cer­tain­ly on the way to get­ting there.”

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Luc Boblet, Egle Therapeutics CEO

A new Treg play­er emerges with $46M and back­ing from Take­da

In recent years, the chorus of biotechs and Big Pharma backers targeting regulatory T cells — also known as “Tregs” — for cancer and autoimmune diseases has only grown louder.

The newest voice is from Egle Therapeutics, which sang out a $46.4 million Series A round on Friday led by LSP and Bpifrance through their InnoBio 2 fund. Takeda’s venture arm also chipped in, about a year after the pharma struck a research pact with the Paris-based upstart.

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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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