Swamy Vijayan. Plexium

San Diego up­start de­buts dis­cov­ery en­gine that puts a twist to pro­tein degra­da­tion

For years, the idea of pro­tein degra­da­tion — uti­liz­ing the cell’s nat­ur­al garbage dis­pos­al sys­tem to mark prob­lem­at­ic pro­teins for de­struc­tion — re­mained an el­e­gant but tech­ni­cal­ly dif­fi­cult con­cept. But now es­tab­lished as a promis­ing clin­i­cal strat­e­gy, with ma­jor bio­phar­ma play­ers such as Bay­er, Gilead and Ver­tex try­ing to grab a foothold via part­ner­ship deals, a San Diego start­up is look­ing to ex­ploit it and push its lim­its.

John Boy­lan

While the fron­trun­ners in the bur­geon­ing space such as Arv­inas, Kymera and C4 Ther­a­peu­tics fo­cus on link­ing the tar­get pro­tein with an E3 lig­ase — with drugs that bind to both — Plex­i­um wants to tin­ker with just the ubiq­ui­tin.

“What we are sug­gest­ing is com­plete­ly dif­fer­ent. Most of the tar­gets we’re go­ing af­ter do not have any known binders at all. What we’re sug­gest­ing is we sim­ply bind to the E3 lig­ase, and we mod­i­fy the E3 lig­ase sur­face, and see if any one of those com­pounds that bind to the E3 lig­ase mod­i­fies the E3 lig­ase in­ter­ac­tion suf­fi­cient­ly to redi­rect it to the tar­gets of in­ter­est,” CEO Swamy Vi­jayan told End­points News. “To do what we do, you need the scale.”

The scale de­rives from the plat­form de­vel­oped Vi­jayan, who has a back­ground in di­ag­nos­tics and in­stru­men­ta­tion. It builds on DNA en­cod­ed li­braries — a pop­u­lar screen­ing tool — and in­te­grates cell-based as­says to al­low for deep­er ex­plo­ration of the tests. Drop­ping the DNA-tagged com­pounds in­to mi­nus­cule “pi­co wells,” he is then able to run tests in nano­liter vol­umes.

It is es­sen­tial­ly an en­tire drug dis­cov­ery in­fra­struc­ture in a bench­top de­vice, he said, with the po­ten­tial to iden­ti­fy drugs that hit mul­ti­ple tar­gets through phe­no­typ­ic analy­sis.

“For us to do, say, a 100,000-mem­ber li­brary as­say takes us 15 to 20 mi­crolitres of reagent, where­as for tra­di­tion­al screen­ing that would be a few litre of reagents and plan­ning ahead of time to scale them up,” he said.

Tim Kutzkey

Af­ter prop­ping up the op­er­a­tion in 2018, Plex­i­um said this fund­ing will al­low them to take an ex­per­i­men­tal com­pound through IND en­abling stud­ies, plot­ting a quick flip to the clin­ic to treat sol­id tu­mors. With $28 mil­lion in new fi­nanc­ing, it will al­so lay the ground­work on some neu­rode­gen­er­a­tive dis­eases pro­grams and hunt oth­er po­ten­tial us­es of its plat­form.

The Col­umn Group and DCVC Bio led the Se­ries A and will send their man­ag­ing part­ners, Kier­sten Stead and Tim Kutzkey, on the board. M Ven­tures, CRV and Neotribe Ven­tures are al­so part of the syn­di­cate.

“Plex­i­um is an in­ter­est­ing amal­gam of cut­ting-edge en­gi­neer­ing cou­pled with the lat­est ad­vances in chem­istry and bi­ol­o­gy,” Kutzkey said in a state­ment.

Kier­sten Stead

The ap­proach turns ra­tio­nal drug de­sign on its head, Vi­jayan ad­mit­ted, as the process is akin to test­ing mul­ti­ple tooltips on mul­ti­ple screw­drivers to see what works. But it doesn’t mean they are throw­ing drug de­vel­op­ment ex­per­tise out the win­dow. Ear­li­er this year he re­cruit­ed John Boy­lan from Cel­gene to be CSO, and many on Plex­i­um’s team of 42 are sea­soned phar­ma staffers.

“It’s been a fan­tas­tic cross-pol­li­na­tion of ideas,” Vi­jayan said. “In en­gi­neer­ing and di­ag­nos­tics we’re used to more ag­ile method­olo­gies and cer­tain prod­uct de­vel­op­ment prin­ci­ples and ideas that are very alien to phar­ma be­cause they put the blind­ers on, keep go­ing on a very fixed path, a day at a time. [Ap­ply­ing adap­tive method­olo­gies at Plex­i­um] is pay­ing a lot of div­i­dends.”

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Take­da swoops in to buy lit­tle biotech part­ner and its celi­ac drug poised to 'change stan­dard of care'

Having spent three years carefully grooming PvP Biologics and its drug for celiac disease, Takeda is happy enough with the proof-of-concept data to buy it all.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Bio­gen touts new ev­i­dence from the gene ther­a­py com­pa­ny it wa­gered $800M on

A year ago, Biogen made a big bet on a small gene therapy company. Now they have new evidence one of their therapies could work.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Mi­cro­bio­me Q&A: New study maps the vagi­na's 'op­ti­mal mi­cro­bio­ta' — and its im­pli­ca­tions for bio­phar­ma

The widely-held notion that the “optimal” vaginal microbiota is dominated by one strain of lactic-acid producing bacteria has now been challenged in a new paper, published in Nature Communications on Wednesday, which used advanced gene sequencing methods to map out the most comprehensive gene catalog of the human vaginal microbiome.

Things have changed in the more than 50 years since the concept of vaginal microbiota transplants was proposed and subsequently tainted by a Texas-based gynecologist who transplanted the vaginal fluid of women who had bacterial vaginosis into healthy females, suspecting he had isolated the bacteria responsible for the condition.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

In at least one life-sci hub, gen­der and di­ver­si­ty ini­tia­tives haven’t made a dent

Gender and racial diversity at the top of UK life science companies has hardly budged over the last seven years despite repeated advocacy efforts, according to a new report.

The report, from the recruiting firm Liftstream, found that 14.8% of directors on life sciences boards were women and 21.1% of top executives were women. That’s a modest bump from the 9.8% of directors and 18.1% of executives Liftstream identified in their last report from 2014. The percentage of women CEOs moved from 8% to 9.8%.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 73,100+ biopharma pros reading Endpoints daily — and it's free.

Will a 'risk-of­f' mind­set has­ten cell ther­a­py M&A? Io­vance surges on buy­out chat­ter

Is it time for some cell therapy M&A?

Investors of Iovance Biotherapeutics certainly thought so, sending its stock $IOVA up as much as 40% after Bloomberg reported that the cancer-focused biotech is talking to potential buyers.

While 2019 saw a number of high-profile gene therapy company takeovers — led by Roche’s $4.3 billion bid of Spark as Astellas went for Audentes, Biogen snapped up Nightstar and Vertex absorbed Exonics — large players appeared to prefer partnering on the cell therapy front, particularly when it comes to cancer. Hal Barron put his weight behind Rick Klausner’s startup as he rebuilt GlaxoSmithKline’s cancer pipeline. Takeda turned to MD Anderson to license their natural killer cell therapy.

One less ri­val for Im­muno­vant, as Alex­ion aban­dons FcRn in­hibitor

Less than one year after Alexion parted with $25 million upfront to secure access to a second anti-FcRn asset, it is abandoning the experimental drug. The discontinuation, disclosed at the SVB Leerink Global Healthcare Conference in New York during a fireside chat, bodes well for rival Immunovant.

The drug (ABY-039), partnered for development with Sweden’s Affibody, was forsaken on the basis of early-stage data that was not viewed favorably, Baird and SVB Leerink analysts noted.

Clin­i­cal tri­al spon­sors have to dis­close decade’s worth of un­re­leased da­ta, fed­er­al judge rules

A decade’s worth of unreleased trial data may soon see the light of day.

A New York federal judge ruled this week that the FDA and the NIH have for years misinterpreted a law that would require companies, universities and other clinical trial sponsors to release trial data from studies completed between 2007 and 2017. The ruling covers drugs and medical devices that were experimental when the study was completed but have since been approved, potentially putting hundreds of sponsors out of compliance if they don’t put their results on clinicaltrials.gov.

Laurie Glimcher and Ansbert Gadicke (Justin Knight, Dana-Farber Cancer Institute)

Ty­ing ba­sic sci­ence to spin­outs, Dana-Far­ber de­buts sis­ter funds to­tal­ing $126M with MPM Cap­i­tal

As one of the most prestigious cancer institutes in the US, Dana-Farber has enjoyed considerable support for its entrepreneurial pursuits, spinning out about 30 companies in the past 12 years.

“Now where we’ve always struggled — where every cancer center struggled — is support of basic science,” Barrett Rollins, chief scientific officer emeritus, told Endpoints News.

And then two of its trustees had an idea. What if they tied philanthropy to investment in Dana-Farber startups, requiring a donation to basic science as a condition for accessing its brightest biotech venture ideas?