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.”

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Rep. Buddy Carter (R-GA) (Bill Clark/CQ Roll Call via AP Images).

US House as­sem­bles bi­par­ti­san cau­cus on do­mes­tic phar­ma man­u­fac­tur­ing

The US House of Representatives is taking a further interest in domestic pharma manufacturing by creating the Domestic Pharmaceutical Manufacturing Caucus, led by Reps. Buddy Carter (R-GA), Elissa Slotkin (D-MI), Gus Bilirakis (R-FL) and Chrissy Houlahan (D-PA).

As the supply chain increasingly is outsourced to China and India, particularly on the active pharmaceutical ingredient side, the caucus will aim to focus on moving forward legislation that incentivizes greater domestic manufacturing of medicines. Carter said the caucus will try to reduce US reliance on “foreign adversaries,” try to ensure an adeqate supply of pharmaceuticals and try to halt supply chain disruptions.

Cy­to­ki­net­ics’ ALS drug fails PhI­II, leav­ing the biotech with a sin­gle late-stage prospect

Cytokinetics’ candidate for the muscle disease amyotrophic lateral sclerosis, or ALS, failed a Phase III trial, the Bay Area biotech announced Friday morning.

At a second interim analysis of the trial, an independent review committee recommended that Cytokinetics discontinue its COURAGE-ALS trial for reldesemtiv, as it “found no evidence of effect” compared to placebo on the primary or key secondary endpoints.

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Sar­to­rius to ac­quire French man­u­fac­tur­er for $2.6B+ in cell and gene ther­a­py play

The German life science group Sartorius will be picking up French contract manufacturer Polyplus for the price of €2.4 billion, or $2.6 billion.

On Friday, Sartorius announced the acquisition through its French subgroup, Sartorius Stedim Biotech, which will be acquiring Polyplus from private investors ARCHIMED and WP GG Holdings IV. Polyplus has 270 employees and produces materials and components that go into making viral vectors that are used in cell and gene therapies. This includes DNA/RNA reagents as well as plasmid DNA. Polyplus has locations in France, Belgium, China and the US.

CHMP gives thumbs-up for We­govy use in ado­les­cents, along with nine new drug rec­om­men­da­tions

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended nine drugs for approval this week while also giving thumbs up for six expanded indications, including Novo Nordisk’s approved obesity medication Wegovy for younger people. Wegovy is already approved as an obesity treatment in the EU for adults, and the new indication would allow prescriptions for adolescents aged 12 and older.

Green­Light re­ceives buy­out of­fer; Apol­lomics com­pletes SPAC merg­er

RNA biotech GreenLight Biosciences has been handed an offer for potential acquisition.

GreenLight said in a release that it has received a non-binding “indication of interest” from Fall Line Endurance Fund to acquire GreenLight’s capital stock for $0.60 per share in cash. The release said any potential agreement between the two parties would depend on certain conditions.

Through a special committee, the biotech will evaluate the offer but added there’s no certainty a deal will go forward. GreenLight will also not make any more announcements until a deal comes through or “otherwise determines” a statement is necessary.

TScan Therapeutics' departing CEO David Southwell and CSO/COO Gavin MacBeath

TCR up­start an­nounces CEO ex­it, with CSO now act­ing re­place­ment

A public T cell biotech’s chief executive has decided to leave the company.

TScan Therapeutics said Friday morning that CEO David Southwell stepped down earlier this week, leaving both his chief executive and board member roles. Filling in is Gavin MacBeath, the company’s CSO and COO. He became the acting CEO on Tuesday, and will continue to remain CSO and COO, TScan’s announcement read.

Sen­ate Fi­nance Com­mit­tee lobs more bi­par­ti­san pres­sure on­to PBMs

Congress is honing in on how it wants to overhaul the rules of the road for pharmacy benefit managers, with a Senate Finance Committee hearing Thursday serving as the latest example of the Hill’s readiness to make changes to how pharma middlemen operate.

While pledging to ensure patients and pharmacies “don’t get a raw deal,” Finance Committee Chair Ron Wyden (D-OR) laid out the beginning of what looks like a major bipartisan effort — moves the PBM industry is likely to challenge vigorously.

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