VAV1

iStock, JHVEPhoto Biogen touted strong Q3 sales of its Alzheimer’s drug Leqembi a day after announcing a deal worth up to $1.45 billion with Neomorph to discover and develop molecular glue degraders. Biogen came out on top in the third quarter, exceeding revenue expectations overall and beating Wall Street expectations for Alzheimer’s drug Leqembi, which is slowly beginning to pick up steam after a slow start. The Cambridge, Mass.–based biotech reported $2.5 billion for the third quarter and raised its guidance for the year, expecting earnings per share (EPS) between $16.10 and $16.60, up from between $15.75 and $16.25, according to its report released Wednesday. In June and July 2024, Biogen hit $237 per share, but since then, its shares have been consistently falling. In premarket trading Wednesday morning, the company’s shares were down more than 1%, sitting at $180 per share. Sales of Biogen’s multiple sclerosis drugs were down across the board compared to Q3 2023, with Tecfidera falling to $232.8 million from $239.5 million and Tysabri down to $406.1 million from $456.3 million. On Biogen’s fourth-quarter 2023 earnings call, CEO Chris Viehbacher noted the company’s pivot away from its “legacy multiple sclerosis franchise” as one of five key primary objectives aimed at returning the company to growth. Biogen predicts total 2024 sales to decline by a low-single-digit percentage compared with last year but said it expects these decreases in multiple sclerosis product revenue to be offset by new product launches. One key product launch is that of Leqembi, which received full FDA approval in July 2023 but has struggled to gain traction in the market, in part due to delays in building intravenous infusion infrastructure, diagnostic test requirements and regular brain scans. However, sales have been increasing over the last few quarters, CNBC reported . The anti-amyloid antibody brought in $67 million in sales in the third quarter, exceeding Wall Street predictions of $50 million. Also on the neuro front, Biogen and partner Sage announced they will not pursue further development of recently approved postpartum depression (PPD) drug Zurzuvae in major depressive disorder (MDD). This news was revealed by Sage in its third-quarter earnings report on Tuesday. The companies won approval for Zurzuvae in August 2023 as the first pill for PPD but had hoped to capture a piece of the much broader MDD space. Meanwhile, Biogen became the latest biopharma company to ink a deal in the molecular glue space, tying up with Neomorph in a multi-target research collaboration. The deal, which will see Biogen lay down up to $1.45 billion, is aimed at discovering and developing molecular glue degrader clinical candidates in Alzheimer’s, rare neurological and immunological diseases. The partnership will marry Neomorph’s “leading molecular glue discovery platform” with Biogen’s “deep expertise” in these therapeutic spaces, according to a Tuesday press release . This is the second significant deal struck in molecular glues this week after Novartis announced Monday it would pay Monte Rosa Therapeutics $150 million upfront for the rights to that company’s VAV1-targeting molecular glue degraders. Under the agreement, Monte Rosa is eligible for up to $2.1 billion in development, regulatory and sales milestones.

Agreement expected to accelerate MRT-6160 clinical development and broadly explore therapeutic opportunities across multiple indications Monte Rosa to receive up-front payment of $150 million and is eligible to receive milestone payments, U.S. profit and loss share, and tiered royalties on ex-U.S. net sales BOSTON, MA, USA I October 28, 2024 I Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs, including MRT-6160. MRT-6160 is currently in an ongoing Phase 1, single ascending dose (SAD)/multiple ascending dose (MAD) healthy volunteer study for immune-mediated conditions. Under the terms of the agreement, Novartis will obtain exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs and will be responsible for all clinical development and commercialization, starting with Phase 2 clinical studies. Monte Rosa remains responsible for completion of the ongoing Phase 1 clinical study of MRT-6160. i “We are thrilled to announce this agreement with Novartis, a key player in immune-mediated conditions, and we are excited about the transformative potential it provides for Monte Rosa and MRT-6160. We expect this will accelerate and broaden the scope of clinical development of MRT-6160 to advance this unique, orally bioavailable modality while retaining substantial value for Monte Rosa. We believe the transaction validates our unique and industry leading QuEEN™ discovery engine, and it further increases our conviction to rationally design and develop highly selective and safe MGDs for undruggable targets, including in the areas of immunology and inflammation, metabolism, and genetic diseases,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “The financial resources provided by this agreement are expected to extend our operational runway, enable us to advance our pipeline to potential value-creating milestones and anticipated proof-of-concept readouts, and further leverage our QuEEN™ discovery engine.” “Novartis has had a long-standing interest in molecular glue degraders, which offer the potential to tackle challenging biological targets. We are excited about their application in immunology and the early progress we have seen by Monte Rosa in this space and with MRT-6160. We look forward to advancing MRT-6160 and learning more about its potential to provide a new therapeutic option for people living with a range of immune-mediated conditions,” said Fiona Marshall, President of Biomedical Research at Novartis. “Novartis is committed to bringing forward new therapeutic options for these patients, and we are happy to be working with Monte Rosa to harness the potential of this approach to address unmet medical needs.” MRT-6160 is a potent, highly selective, and orally bioavailable investigational degrader of VAV1, a key signaling protein downstream of both the T- and B-cell receptors. Preclinical studies have demonstrated deep degradation of VAV1, resulting in a significant decrease in cytokines linked to immune-mediated conditions, with no detectable effects on other proteins. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. ii,iii Agreement Details and Financial Terms Under the terms of the agreement, Novartis has agreed to pay Monte Rosa $150 million up front. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies, as well as tiered royalties on ex-U.S. net sales. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S. The agreement is subject to customary closing conditions including regulatory clearance. Monte Rosa plans to provide further information regarding its updated cash position and runway in its third quarter 2024 earnings update. About Monte Rosa Monte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond, and has a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com . i Details about the study, MRT-6160 in a First-in-human Study in Healthy Subjects, can be found at ClinicalTrials.gov under the identifier NCT06597799. ii Cartwright A et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model. Poster presented at: Digestive Disease Week 2024; May 21, 2024; Washington, DC. iii Cartwright A et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Colitis Model Concomitant with Reduced Calprotectin Expression. Poster presented at: EULAR 2024 – Annual European Congress of Rheumatology; June 14, 2024; Vienna, Austria. SOURCE: Monte Rosa Therapeutics

Novartis is getting a hold of one of Monte Rosa Therapeutics’ clinical-stage molecular glues, and it’s putting more than $2.2 billion on the table. That includes $150 million upfront for MRT-6160, according to Monday’s announcement. Novartis will get full global rights to the drug, which is currently in a Phase 1 healthy volunteer study for immune-mediated conditions, and it will assume development responsibilities beginning in Phase 2. Monte Rosa remains responsible for all Phase 1 work. MRT-6160 is a VAV1-targeting molecule that was first dosed in the Phase 1 trial several months ago. That signaling receptor works downstream of T cell and B cell receptors, according to Monte Rosa, and may reduce cytokine proteins that fuel autoimmune conditions when modulated. Monte Rosa CEO Markus Warmuth said in an interview that the specificity of the compound sets it apart. “We really get very deep, and in many cases, also prolonged pathway modulation,” he said, underscoring that it’s also important that the asset demonstrates clear safety. “I think with ‘6160 we’ve landed one of those.” Novartis research chief Fiona Marshall said in a statement that the company was excited about the molecular glue’s “potential to provide a new therapeutic option for people living with a range of immune-mediated conditions.” It’s the second major deal in the molecular glue category this month. About two weeks ago, Pfizer paid $49 million upfront to Triana Biomedicines for multiple drug targets, with more than $1.5 billion in biobucks available as well. Other large pharmas like Takeda , Eisai and Novo Nordisk have also bought into the space. Warmuth said the deal with Novartis was a competitive process, and there were “certainly a few others looking as well.” Back in May, Monte Rosa raised $100 million, which extended the biotech’s runway into the first half of 2027. Warmuth declined to specify if the new money extends that any further. It also expects to have more data this year on its lead asset, MRT-2359, which will include the planned Phase 2 dose. Toxicity was an issue at a higher dose range based on data presented a year ago , with three patients reporting grade 4 side effects, though each case resolved with dose reductions.