CEO Virginia Burger (New Equilibrium Biosciences)

Bet­ting ear­ly on an AI niche, RA Cap­i­tal seeds a young founder's quest to un­lock 'Holy Grail' tar­gets

Ar­ti­fi­cial in­tel­li­gence, with its grandiose claims and sweep­ing promis­es to rev­o­lu­tion­ize drug dis­cov­ery, may seem om­nipresent in bio­phar­ma now. But Vir­ginia Burg­er and RA Cap­i­tal be­lieve there are nich­es it has yet to touch.

Pe­ter Tom­pa

Af­ter tak­ing up res­i­den­cy at the star-stud­ded Boston ac­cel­er­a­tor Petri, Burg­er’s start­up — named New Equi­lib­ri­um Bio­sciences — has scored $10 mil­lion in seed cash from the VC firm to prove that by reach­ing in­to those cor­ners, they could un­cov­er drugs against “Holy Grail” tar­gets in every­thing from can­cer to neu­rode­gen­er­a­tive dis­eases.

Specif­i­cal­ly, the biotech is in­ter­est­ed in a class of pro­teins called in­trin­si­cal­ly dis­or­dered pro­teins that doesn’t have a sin­gle fold­ed struc­ture. MYC, for in­stance, is a can­cer-caus­ing IDP.

“They break this par­a­digm of se­quence to struc­ture to func­tion be­cause it’s re­al­ly se­quence to mul­ti­ple of dif­fer­ent con­for­ma­tions which have many dif­fer­ent func­tions,” she told End­points News.

They can al­so range from ful­ly un­struc­tured to par­tial­ly struc­tured ones con­tain­ing a dis­or­dered re­gion, some­thing con­den­sate play­ers like Dew­point are fo­cused on.

Nathaniel Brooks Hor­witz

Crack­ing this spe­cial class, RA Cap­i­tal prin­ci­pal Nathaniel Brooks Hor­witz said, re­quired a new breed of com­pa­ny that in­te­grates AI in physics mod­eel­ing for drug dis­cov­ery, be­yond what the pi­o­neers — he counts Schrödinger, Re­lay, Sil­i­con  Atom­wise, Re­cur­sion and Ex­sci­en­tia among oth­ers — are do­ing.

“What we’re re­al­ly ex­cit­ed about is when a com­pa­ny like New Equi­lib­ri­um can en­able a tar­get about which we can say the fol­low­ing — ‘If on­ly we could de­vel­op a drug for this tar­get’ — we’re con­fi­dent it will be suc­cess­ful,” he said.

As a PhD in Pitts­burgh and lat­er post­doc at MIT, Burg­er would read pa­pers high­light­ing their im­por­tance as drug tar­gets. But they were so hard to tar­get that un­til mid­way through her post­doc, sci­en­tists weren’t even sure if lig­ands could bind to them — they wig­gle around too quick­ly to be even seen in ex­per­i­ments. Even when they did find mol­e­cules that bound weak­ly to the pro­teins, there was no re­al way to op­ti­mize them in­to drug can­di­dates.

Im­mersed in the en­tre­pre­neur­ial en­vi­ron­ment at MIT, it seemed nat­ur­al to build a start­up around the com­pu­ta­tion­al meth­ods she had been de­vel­op­ing to iden­ti­fy the set of con­for­ma­tions the pro­teins would switch be­tween. First, though, she took a job at XtalPi, the US-Chi­na AI biotech start­up backed by Ten­cent and lat­er Soft­Bank and Morn­ing­side.

It was dur­ing that two-year stint that she met Pe­ter Tom­pa, a pro­fes­sor at Flan­ders In­sti­tute for Biotech­nol­o­gy who’s de­vot­ed his ca­reer to study­ing IDP struc­ture and func­tion. He was in­ter­est­ed in start­ing a com­pa­ny to­geth­er.

Two weeks lat­er, she was out.

The first thing she did af­ter re­ceiv­ing fund­ing from Petri — an ac­cel­er­a­tor set up to tai­lor to the needs of young founders — was to buy quan­tum chem­i­cal soft­ware and start gen­er­at­ing their own train­ing da­ta for a new kind of physics mod­el.

Ex­ist­ing com­pu­ta­tion­al mod­els, Burg­er said, were built on what’s al­ready known about fold­ed struc­tures, which ren­ders them the wrong fit for in­trin­si­cal­ly dis­or­dered pro­teins. By us­ing AI to learn quan­tum chem­istry — the en­er­gies and forces on each atom that give rise to a shape at any giv­en mo­ment — New Equi­lib­ri­um’s al­go­rithms can “see,” in sil­i­co, thou­sands or even mil­lions of pos­si­ble struc­tures over time.

“We’re re­do­ing how sim­u­la­tions have been done in the past by re­build­ing the un­der­ly­ing sim­u­la­tion ar­chi­tec­ture to use AI for each step in­stead of in­tro­duc­ing a sin­gle — the stan­dard cal­cu­la­tion for each step,” she said.

The next step is to ze­ro in on the struc­tures that are more sta­ble or ap­pear more fre­quent­ly, screen lig­ands against them in a wet lab, and then fuse the frag­ments bind­ing to dif­fer­ent struc­tures in the same mol­e­cule. Burg­er can’t yet re­veal how many frag­ments they’d need for each drug made this way, but not­ed that the seed fund­ing will get them clos­er to pre­clin­i­cal can­di­dates.

For RA Cap­i­tal, the deal marks an­oth­er move in their shift to­ward ear­li­er stages of ven­ture fi­nanc­ing.

Quan­tum com­put­ing, Hor­witz not­ed, is loom­ing on the hori­zon with hard­ware start­ing to take shape. And the tech­nol­o­gy will ul­ti­mate­ly make it pos­si­ble to “ful­ly mod­el the true bio­phys­i­cal state of even the most com­plex mol­e­c­u­lar in­ter­ac­tions.”

“Which will be the com­pa­nies that are the first to use quan­tum com­put­ing and all the pow­er that brings to ra­tio­nal­ly de­sign med­i­cines for mean­ing­ful tar­gets?” he said. “I think New Equi­lib­ri­um can be that com­pa­ny.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

Sajith Wickramasekara, Benchling via YouTube

Meet Bench­ling, the lat­est uni­corn seek­ing to rev­o­lu­tion­ize the way sci­en­tists do work with the help of the cloud

There’s another unicorn in biotech land, as Benchling and its leading R&D cloud platform pull in a $200 million Series E to help scientists accelerate drug development. In doing so, the company hit a lofty $4 billion valuation — nearly five times what it was worth around this time last year, according to Forbes.

Despite the fact that drug development is becoming significantly more complex, the industry continues to run on paper, emails and spreadsheets, co-founder and CEO Sajith Wickramasekara said in a video on Benchling’s website. The MIT grad sought to change that by creating software that allows scientists to better track, model and forecast their work.

Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Covid-19 roundup: No­vavax shakes up lead­er­ship with two pro­mo­tions and de­par­ture of CFO; Mod­er­na, No­vavax shots added to mix-and-match study in the UK

Novavax has had a busy month, filled with supply chain issues and manufacturing deals that have affected the rollout of its Covid-19 vaccine. Tuesday, the company announced updates to its leadership team.

CFO Greg Covino will step down from that role after just five months for personal reasons, the release said, but take on a new role as executive advisor. John Trizzino, current chief commercial officer and chief business officer, will take the CFO role over in the interim.

Amy­lyx to move for­ward with ALS pro­gram in Eu­rope, but FDA wants an­oth­er look; Hu­ma­cyte adds $50M in debt fi­nanc­ing

Amylyx is one of several companies looking to break through in the tough ALS field, and Wednesday they announced they’re moving forward with regulatory plans.

The Cambridge, MA-based biotech said they’re submitting a marketing application to the EMA for their AMX0035 program by the end of 2021. Wednesday’s news comes a few weeks after they revealed similar plans to move forward with Canadian health regulators by June 30.

Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.