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.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Mathai Mammen (Rob Tannenbaum, Endpoints News at BIO 2018)

Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck five years ago, where the soft-spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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Samantha Du, Zai Lab CEO

Any­one still look­ing for a CD47? Zai Lab shelves PhI pro­gram af­ter re­view­ing 'com­pet­i­tive land­scape'

Over the past few years, the promise of blocking CD47 — a “don’t eat me” signal co-opted by cancer cells — has sent drugmakers big and small into a frenzy. But one biotech is now bowing out.

Zai Lab is deprioritizing ZL-1201, its CD47 inhibitor, scrapping plans for a Phase II trial. It will now “pursue out-licensing opportunities,” the company said in its Q2 update. The decision was based on a review of the competitive landscape, it added, without going into further details.

Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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HHS Secretary Xavier Becerra (Patrick Semansky/AP Images)

US weighs new route of ad­min­is­tra­tion for mon­key­pox vac­cine as cas­es climb — re­port

Less than a week after HHS Secretary Xavier Becerra declared monkeypox a national health emergency, reports have emerged that the US plans to extend its vaccine supply by opting for a different route of administration.

Officials are expected to call for intradermal injection of Bavarian Nordic’s Jynneos vaccine — the only shot approved specifically for monkeypox in the US — as opposed to subcutaneous injection, unnamed sources told both the New York Times and Washington Post on Tuesday.

'Messy at best': Is the US re­peat­ing the same Covid mis­steps with mon­key­pox mes­sag­ing?

When Kyle Planck first suspected he might have monkeypox in late June, he went to the CDC website and found six photos of different types of lesions. And that was about it for general public information.

Planck, who is a sixth-year PhD pharmacology researcher at Weill Cornell, kept looking though and found a separate part of the CDC website meant for healthcare professionals. There he found a medical slide deck with more pictures, professional journal articles and more details about symptoms and diagnosis.

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Andy Jassy, Amazon CEO (Isaac Brekken/AP Images for NFL, File)

Up­dat­ed: FDA slaps Ama­zon with a warn­ing let­ter for sell­ing OTC mole re­moval prod­ucts

The FDA’s Center for Drug Evaluation and Research on Tuesday released a warning letter sent last week to Amazon CEO Andy Jassy in Seattle for selling mole removal products over-the-counter, or, as the FDA explains, “introducing, delivering, or causing the introduction or delivery into interstate commerce of products that are unapproved new drugs.”

“There are no over-the-counter (OTC) drugs that can be legally sold for mole or skin tag removal, and FDA has safety concerns about drugs marketed OTC directly to consumers for these uses,” the agency said in its Aug. 4 warning.

Craig Thompson, Cerevance CEO

UP­DAT­ED: Mer­ck makes first big splash for Alzheimer’s drug R&D since 2017 fail, ink­ing re­search pact with Cere­vance

For the first time since discontinuing its late-stage Alzheimer’s program, Merck has found promise on the path forward in the memory-robbing disease.

After a Phase III flop of its drug verubecestat, the New Jersey Big Pharma axed the study in early 2018. More than four years later, the company is ready to sign up for another pact to test the waters of the befuddling disease.

This time, there’s $1.1 billion in biobucks on the line and a target that its partner says no other biopharma is looking at en route to finding the next treatment for Alzheimer’s, a neuroscience field that has hit hurdle after hurdle for decades.

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