Evrys Bio LLC

Existing investor Sanofi Ventures came back for Escient's series C fundraise, throwing money in the pot to support the ultimate goal of creating new small molecule therapeutics. Escient Pharmaceuticals has scored $120 million, a much heftier sum than its series B haul from a few years ago and once again snagging support from Big Pharma Sanofi’s VC arm. The series C financing round was co-led by new investors New Enterprise Associates, Abingworth and Forge Life Science Partners, with existing investors Sanofi Ventures and 5AM Ventures in tow, among others. The San Diego biotech’s fundraise follows a $77.5 million series B in September 2020, a round that occurred alongside Escient’s first in-human tests. Now, the $120 million will help the biotech push forward investigational small molecule therapeutics for several neurosensory-inflammatory disorders, with a focus on lead candidates EP547 and EP262. The assets are designed to inhibit cell surface receptors called Mas-related G protein-coupled receptors, or MRGPRs, which mediate the neuro-immune overactivation associated with many chronic disorders. By using small molecules to specifically block MRGPRX2 and MRGPRX4 activation, the company aims to develop oral medications for neurosensory-inflammatory diseases without the serious side effects tied to other approaches, Escient CEO Joshua Grass said in a Nov. 28 release. The $120 million financing will help the company advance its pipeline to clinical proof-of-concept in multiple indications. EP547 targets MRGPRX4 with the aim of treating cholestatic and uremic pruritus, a form of severe itching resulting from liver or kidney disease. The asset is being evaluated in phase 2 and phase 1 trials, respectively, and Escient is exploring its potential in other unnamed indications. EP262 is a MRGPRX2 antagonist in preclinical studies for chronic spontaneous urticaria, chronic inducible urticaria and atopic dermatitis.

A precision medicine is only as good as its target. While targeted therapies now address many types of cancer, tumors still frequently develop mutations that help them escape a drug. One strategy to address tumor escape is combining different cancer drugs. Biotech startup IDRx aims to use scientific knowledge of tumor biology to develop new drug combinations that cover cancer escape pathways. It’s now out of stealth backed by $122 million. The Series A financing announced Tuesday was led by Andreessen Horowitz and Casdin Capital. Plymouth, Massachusetts-based IDRx says it takes its inspiration from the various drug combinations that have proven successful in treating diseases such as cystic fibrosis and certain viral infections. Drug combinations are already frequently used in treating cancer. But the toxic effects of multiple drugs means that these combinations are reserved for advanced cancers with limited treatment options. IDRx aims to bring combination therapy into earlier stages of cancer treatment. The first drug in the combo will be engineered to hit the primary mutations that enable a cancer to escape. The goal is for this drug to have a wide therapeutic window, which is the dose range in which a therapy can be used without having dose-limiting toxicity. A wide therapeutic window would enable such a cancer drug to be used as an earlier treatment, the company said. The second part of these drug combinations would consist of molecules that stop the resistance mutations that the first drug does not address. According to IDRx, this approach will shut down a cancer’s escape pathway and enable a durable response to the therapy. In the future, IDRx says its drug cocktails may include more than two drugs in order to address multiple genetic pathways of a cancer. IDRx was founded last year by Alexis Borisy, a serial entrepreneur whose ventures include EQRx, a startup tackling high drug prices. Though IDRx plans to design its own drugs, the startup’s most advanced programs come from outside of its labs. IDRX-42 was licensed from Merck KGaA and IDRX-73 from Blueprint Medicines. Both are small molecules designed to block tyrosine kinases, each addressing different genetic drivers and resistance mutations in gastrointestinal stromal tumor (GIST), a cancer of the gut. IDRx co-founder and CEO Ben Auspitz said in a prepared statement that GIST offers IDRx the opportunity to start with a cancer that has well-known tumor biology but also has a high unmet medical need. The startup’s founders include Nicholas Lydon, a scientist who played a key role in the development of Gleevec, a Novartis cancer drug whose approved uses include GIST. IDRX-42 has begun a Phase 1 study and IDRX-73 is moving toward human testing. Though these drugs are being tested separately, IDRx intends for them to eventually be used together. On its website, the company says IDRX-42 could serve as a base therapy for GIST patients and adding IDRX-73 “may provide a transformative benefit.” Blueprint Medicines disclosed the licensing of its small molecule in its report of second quarter 2022 financial results Tuesday morning. The deal gives the company a 15% equity stake in IDRx as part of the startup’s Series A financing. Blueprint could also receive up to $217.5 million in milestone payments, plus royalties from sales if the drug reaches the market. The other disclosed investors in IDRx are Nextech Invest and Forge Life Science Partners. Photo by Flickr user Ed Uthman via a Creative Commons license Related Stories Alnylam drug succeeds in heart study, setting stage for FDA filing and showdown with Pfizer The power of digital ecosystems to improve pharma supply chain operations AmeriHealth New Jersey, Thyme Care partner to help members through cancer journey

Alex­is Borisy and Ben Aus­pitz want to be in­tel­li­gent with their lat­est biotech, not “stu­pid.” That’s in the words of Borisy, the re­peat biotech en­tre­pre­neur be­hind the likes of Blue­print Med­i­cines and EQRx. He and busi­ness part­ner Aus­pitz, a long-time in­dus­try in­vestor at F-Prime Cap­i­tal, want to bring to­geth­er “in­tel­li­gent­ly de­signed” can­cer drugs, hence their start­up’s name: IDRx. Ben Aus­pitz In launch­ing their lat­est biotech, with a $122 mil­lion Se­ries A, the duo be­lieves it’s brought to­geth­er two drugs that can be “best in class” as a com­bi­na­tion ther­a­py for cer­tain can­cers. At the heart of their new com­pa­ny is an old ven­ture: Blue­print. IDRx has se­cured the li­cense to a Blue­print as­set and a Mer­ck KGaA as­set, with both com­pa­nies re­tain­ing eq­ui­ty stakes in the start­up in ex­change for the trans­fer. An­dreessen Horowitz (a16z) and Cas­din Cap­i­tal led the fi­nanc­ing, which in­clud­ed back­ing from Nex­tech In­vest, Forge Life Sci­ence Part­ners and oth­er undis­closed in­vestors. Blue­print se­cured a 15% eq­ui­ty in­vest­ment and can re­ceive up to $217.5 mil­lion in mile­stone and tiered per­cent­age roy­al­ties, the com­pa­ny said Tues­day in its quar­ter­ly earn­ings. Over a con­ver­sa­tion around Borisy’s firepit, the two dis­cussed what would be­come IDRx, the duo told End­points News . Borisy had been talk­ing with Har­vard med­ical pro­fes­sor George Demetri and Gleevec dis­cov­er­er Nicholas Ly­don about a Mer­ck KGaA mol­e­cule that could be promis­ing in treat­ing KIT-dri­ven gas­troin­testi­nal stro­mal tu­mors, or GIST. But the trio won­dered what could hap­pen if they brought it to­geth­er with an­oth­er mol­e­cule, with the Mer­ck one serv­ing as a base, Borisy said. They pre­sent­ed the idea to Blue­print, who in turn said they were in­trigued and had the right mol­e­cule for the sec­ond half of the com­bo. But Blue­print had a lot al­ready on its plate with a bur­geon­ing pipeline, so even­tu­al­ly the idea turned in­to a new com­pa­ny, Borisy said. Fast for­ward to to­day, IDRx is now in the clin­ic with the Mer­ck KGaA as­set, dubbed IDRX-42, and the ex-Blue­print as­set, IDRX-73, is head­ed to­ward the clin­ic. The first one will be test­ed as a sin­gle agent to serve as the base, and then the Se­ries A funds will bankroll a com­bo study, the ex­ec­u­tives said, in the hopes of prov­ing out their hy­poth­e­sis. The Ply­mouth, MA biotech is work­ing nim­bly with few­er than 10 em­ploy­ees. Aus­pitz serves as CEO. Round­ing out the lead­er­ship team is de­vel­op­ment op­er­a­tions chief Jes­si­ca Chris­to, prod­uct de­vel­op­ment chief Vic Kadambi, VP of reg­u­la­to­ry af­fairs Shrenik De­sai and VP of clin­i­cal op­er­a­tions Deb­bie John­son. IDRx’s vi­sion is built around the com­bo ther­a­py route be­cause pre­ci­sion med­i­cines might be ef­fec­tive on their own, but on­ly for a year or slight­ly more, Borisy said. The biotech wants to de­liv­er a decade or more of sur­vival for pa­tients. To paint a pic­ture, Borisy says to think of No­var­tis’ Gleevec sto­ry of the ear­ly 2000s. “Why are not all drugs like Gleevec in CML (chron­ic myel­oge­nous leukemia), right? Gleevec has trans­formed CML from a dis­ease you died from to a dis­ease you died with, right? That was the promise of pre­ci­sion med­i­cine,” Borisy said. Ly­don has won in­ter­na­tion­al awards for his work help­ing dis­cov­er Gleevec. So, IDRx wants to “hit the core dri­ver very hard,” do the same against by­pass re­sis­tance mech­a­nisms and treat pa­tients ear­li­er in dis­ease. The com­bi­na­tion they found, via the Mer­ck and Blue­print as­sets, is what they dub an in­tel­li­gent­ly de­signed one. In years past, ro­bot­ic high through­put em­pir­i­cal test­ing would go through more than a thou­sand drugs to drum up a mil­lion pos­si­ble com­bi­na­tions, Borisy ex­plained. “That’s a bit of a brute force, stu­pid-type of em­pir­i­cal ap­proach, which is why it may be a lit­tle sort of self-ref­er­en­tial­ly or mak­ing fun of our­selves. We said, ‘Well, this time, it’s ra­tio­nal, right, as op­posed to just brute force. This time it’s in­tel­li­gent­ly de­signed,'” he mused. With the fi­nanc­ing in hand, it’s time for clin­i­cal stud­ies to test that hy­poth­e­sis.