Even as researchers discover more links between specific proteins and human disease, it’s still hard to find small molecules or antibodies that can bind to those drug targets.
San Diego biotech Plexium is the latest addition to the growing number of startups aiming to use technology to devise new drugs that can target those currently “undruggable” proteins.
The new company, which debuted Thursday, has attracted $28 million in venture financing from investors that believe in its approach, which involves taking advantage of a built-in cellular mechanism known as protein degradation—the process by which cells recycle misfolded or otherwise damaged proteins.
Plexium’s technology pulls from discoveries in molecular biology—including the 2004 Nobel Prize-winning discovery of the degradation process—and from advances in chemistry to identify molecules that can bind to proteins called E3 ligases, which play a key role in the cellular recycling apparatus. The idea is to find small molecules that can bind to E3 ligases that are known to interact with those as-of-yet undrugged targets of interest.
“Every one of these ‘undruggable’ proteins is already inside the cells, modulated by other proteins … Could we hijack the E3 ligase and modulate it to interact with our target of interest?” says founder and CEO Swamy Vijayan.
Plexium contends its engineering know-now differentiates its technology from others taking a protein degradation approach to drug discovery. The company has figured out to how to miniaturize the process of scanning what are known as DNA-encoded libraries for potential drug candidates. With only nanoliter volumes, it can screen millions of compounds, each tagged with a unique DNA identifier, as a mixture, rather than one by one. That means Plexium can more quickly identify promising compounds.
A physicist by training, Vijayan is a serial entrepreneur with extensive experience in sequencing. After working for a time at the San Diego-based sequencing machine maker Illumina (NASDAQ: ILMN), he left in 2013 to launch Omniome, a sequencing startup. (Now headed by CEO Dave Mullarkey, the company last year announced it had raised $60 million in Series B financing to continue developing its technology.)
Vijayan says the realization that some diseases had no treatment options, even with better diagnostics, prompted him to start Plexium.
“I stuck with sequencing because I believed that was the most powerful diagnostic tool, and I thought diagnostics were the primary requirement for healthcare: You diagnose a disease, there’s always a drug that could be given,” he says. “Over time I started realizing that that was not true, there was not always a drug that one could give. … I started getting interested in how I could use my diverse background in computation, physics, and engineering to build tools and techniques for drug development.”
Vijayan says the platform, called DELPhe for DNA-encoded library phenotypic screening, has already identified some small molecules. Plexium will use the Series A funding to advance those molecules toward clinical testing. The compounds are potential treatments for solid-tumor cancers and a neurodegenerative disease, Vijayan says.
“Our chemical matter seems to have unique activity in targets involving solid tumors, so we pursued that actively,” he says. Solid tumors, in comparison to so-called liquid tumors, are an area in which some new cancer treatments, such as CAR-T cell therapy, haven’t made as much headway.
The company’s Series A round was led by two San Francisco Bay Area venture capital firms: The Column Group (TCG), a biotech VC firm, and Data Collective, which also goes by DCVC. DCVC, which has historically invested in high-tech startups, last year formed its first life science-focused fund named DCVC Bio, for which it has since raised about $208 million, according to a May securities filing.
San Francisco Bay Area-based early-stage VC firms CRV and Neotribe Ventures and M Ventures, the venture arm of Germany’s Merck KGaA, also participated in the Series A financing. DCVC Bio managing partner Kiersten Stead and TCG managing partner Tim Kutzkey joined Plexium’s board of directors as part of the deal.
A number of pharmaceutical companies have made early bets on protein-degradation drugs. German life sciences giant Bayer this year inked a $115 million deal with New Haven, CT-based Arvinas (NASDAQ: ARVN) to discover and develop compounds for pharmaceutical and agricultural applications. Foster City, CA-based Gilead Sciences (NASDAQ: GILD) kicked in $45 million up front to start an alliance with San Francisco startup Nurix Therapeutics; Celgene (NASDAQ: CELG) has partnered with Nurix, too, for drug discovery work focused on certain inflammatory and immunological diseases.