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.”

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Antoine Papiernik, Sofinnova managing director (Business Wire)

Sofinno­va Part­ners stays fo­cused on late-stage deals with a new, $540M crossover fund

One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies.

The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.”

They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management.

Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Presage teams with Mer­ck on its Phase 0 test­ing; Kem­Pharm AD­HD drug wins ap­proval in chil­dren aged 6 and up

Seattle-based Presage Biosciences, which approaches drug development through its microdosing platform, has some new partnerships and cash to come with them.

Presage closed a $13 million financing round Tuesday, aiming to expand its network of clinical trial sites and advance development of its microdosing injection devices. They also closed partnership deals with Merck and Maverick Therapeutics.

The financing included $7 million from new investors, including the LabCorp Venture Fund, Bristol Myers Squibb, and InHarv Partners. An additional $6 million convertible note from Takeda Ventures will convert to equity.

Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,400+ biopharma pros reading Endpoints daily — and it's free.

CEO David Campbell (Janux)

Fresh off $1B+ Mer­ck deal, Janux locks down first pri­vate fundraise for its T cell en­gagers

Janux Therapeutics had kept a relatively low profile since being founded back in 2017 but burst onto the scene late last year when Merck plunked down more than $1 billion in promised milestones for its T cell engagers. Now, less than three months later, the small biotech has clinched its first round of private funding led by some prominent backers.

As it prepares its first programs for INDs, Janux completed a $56 million Series A on Wednesday morning, with Jay Lichter’s Avalon Ventures joining forces with new investors OrbiMed and RA Capital Management to fund the company. Janux will use the cash to primarily advance its T cell engagers targeting PSMA and TROP2, which are expected to hit the clinic in the first and second quarters of 2022, respectively.