Markus Warmuth (Monte Rosa)

Monte Rosa pulls in $95M to test its 'mol­e­c­u­lar glues,' and the first tar­get is GSPT1

Pro­tein degra­da­tion has been a fundrais­ing hotbed in re­cent years, with in­vestors drool­ing over the po­ten­tial to drug the “un­drug­gable.” Al­ready an in­vestor dar­ling, Monte Rosa Ther­a­peu­tics and its “mol­e­c­u­lar glues” are go­ing back to the well with the clin­ic on the hori­zon — and the biotech’s fi­nal­ly re­veal­ing its first tar­get.

Monte Rosa hauled in a $95 mil­lion Se­ries C to pave the way for its lead pro­tein de­grad­er pro­gram to make a run to the clin­ic and flesh out its pipeline, the biotech said Fri­day. The round was led by Avoro Cap­i­tal Ad­vi­sors.

Un­like oth­er small mol­e­cule de­graders such as PRO­TAC that func­tion much like in­hibitors, Monte Rosa’s de­graders help bind E3 lig­as­es — an en­zyme laden with ubiq­ui­tin, a key reg­u­la­to­ry pro­tein in the degra­da­tion process — with tar­get­ed dis­ease-caus­ing pro­teins. The re­sult­ing “glue” avoids the need for avail­able bind­ing sites, which are im­pos­si­ble to hit on the so-called “un­drug­gable” pro­teins.

Monte Rosa’s lead pro­gram, which the biotech hopes to take in­to IND en­abling stud­ies by the mid­dle of the year, will tar­get GSPT1, a reg­u­la­to­ry pro­tein im­pli­cat­ed in the syn­thet­ic lethal­i­ty of sol­id tu­mor cells, CEO Markus War­muth told End­points News. It’s the first time the com­pa­ny is show­ing its hand in terms of an ini­tial tar­get af­ter stay­ing mum through two pri­or fund­ing rounds.

The biotech plans to use the pro­ceeds to scale its drug dis­cov­ery plat­form for nov­el tar­gets as well as build its trans-At­lantic team in Boston and Basel, Switzer­land, War­muth said. Since the biotech last closed its $96 mil­lion Se­ries B in Sep­tem­ber, Monte Rosa has worked out the kinks in its dis­cov­ery plat­form and is ready to keep build­ing.

“The big break­throughs over the last six months have re­al­ly been on plat­form,” he said. “We now have good val­i­da­tion that our com­pu­ta­tion­al ap­proach … has worked out, and we’re look­ing to re­al­ly scale the plat­form ag­gres­sive­ly now.”

Pro­tein degra­da­tion has turned in­to a hotbed of in­vest­ment in re­cent years, but “mol­e­c­u­lar glues” them­selves aren’t brand new. Lep­rosy ther­a­py thalido­mide, first ap­proved way back in 1998, func­tions the same way but found its mech­a­nism of ac­tion large­ly by ac­ci­dent. Mean­while, oth­er pro­tein de­graders such as PRO­TAC look to ac­com­plish the same thing by act­ing as a func­tion­al link­er be­tween the pro­tein re­cep­tor and ubiq­ui­tin en­zyme.

That struc­ture makes PRO­TAC larg­er than mol­e­c­u­lar glues, which can lim­it its drug-like prop­er­ties and low­er its op­ti­miza­tion for spe­cif­ic tar­gets, War­muth said.

With its dis­cov­ery plat­form grow­ing, War­muth re­mained mum on where his team was look­ing for its next tar­gets, but did point specif­i­cal­ly to tran­scrip­tion fac­tor pro­teins that bind to DNA to turn cer­tain genes “on” or “off.” Those pro­teins are an ob­vi­ous tar­get due to the vast ma­jor­i­ty of them be­ing und­drug­gable.

“In our pool of tar­gets we have dis­cov­ered, there’s a clear en­rich­ment for tran­scrip­tion fac­tors,” War­muth said. “We’re not lim­it­ed to tran­scrip­tion fac­tors, but that’s a fam­i­ly that is par­tic­u­lar­ly at­trac­tive.”

Monte Rosa will have a hard time dif­fer­en­ti­at­ing it­self in a mol­e­c­u­lar glue field packed with com­peti­tors. In De­cem­ber, Neo­morph, a Dana-Far­ber-backed play at the field, snared a $105 mil­lion Se­ries A. Ear­li­er in the month, Ab­b­Vie placed a $55 mil­lion up­front bet on Fron­tier Med­i­cines to de­vel­op drug can­di­dates tar­get­ing E3 lig­as­es. Fron­tier will al­so be scout­ing small mol­e­cule binders to tar­get, Ab­b­Vie said.

Oth­er drug­mak­ers, in­clud­ing Sanofi, Roche, Bay­er, Gilead and Ver­tex, have all inked their own pro­tein degra­da­tion pacts in the re­cent past.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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CEO Lex Rovner (64x Bio)

A George Church spin­out fight­ing the vi­ral vec­tor bot­tle­neck in cell and gene ther­a­py lands $55M

A synthetic biology company spun out of George Church’s lab is set to tackle the gene therapy manufacturing bottleneck, and it just landed $55 million in a Series A financing round to do so.

64x Bio comes out of the Harvard Department of Genetics. CEO Lex Rovner and her team — which right now, sits around 10 people — are looking to tackle a key hurdle for major companies: manufacturing cell and gene therapies.