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.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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Andrew Phillips, Nexo Therapeutics CEO

Scoop: Ver­sant, NEA launch new biotech helmed by ex-CEO of pro­tein de­grad­er C4 Ther­a­peu­tics

Long-time biotech venture firms Versant and New Enterprise Associates are backing a new startup run by former C4 Therapeutics chief executive Andrew Phillips.

The fledgling biotech has raised at least $30 million so far, according to paperwork filed with the SEC this week. The round could balloon to $60 million.

Phillips, who left protein degradation startup C4 in 2020 to be a managing director at Cormorant Asset Management, is running the show of the new venture as president, the SEC filing outlines. He also served as interim CEO of Cormorant-backed and Hansoh Pharmaceutical-partnered Blossom Bioscience last year.

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J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.

Dermavant Sciences' first consumer TV ad for its Vtama psoriasis med shows people ready for a new topical treatment.

Roivant’s Der­ma­vant de­buts first-ever TV com­mer­cial for pso­ri­a­sis cream Vta­ma

Dermavant Sciences has been marketing its first product, psoriasis med Vtama, to dermatologists for months, but on Tuesday it rolled out its first consumer campaign. The debut DTC effort including a streaming TV commercial encourages patients to a “Topical Uprising” in a nod to Vtama being a topical cream.

In the new commercial, a swell of people discards scarves and jacket coverings, gathering in the street to converge on a pharmacy to demand a steroid-free prescription. A moment of levity follows when a pharmacist says, “You know you can just talk to your doctor, right?” The gathered crowds collectively says, “Oh.”

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FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.