Molecular Glues - Competitive landscape, 2025

DelveInsight’s, “Molecular Glues - Competitive landscape, 2025,” report provides comprehensive insights about 50+ companies and 65+ drugs in Molecular Glues Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

Global coverage

Molecular Glues: Understanding

Molecular Glues: Overview

Molecular glue (MG) compounds are a type of unique small molecule that can change the protein–protein interactions (PPIs) and interactomes by degrading, stabilizing, or activating the target protein after their binging. These small-molecule MGs are gradually being recognized for their potential application in treating human diseases, including cancer. Evidence suggests that small-molecule MG compounds could essentially target any proteins, which play critical roles in human disease etiology, where many of these protein targets were previously considered undruggable. Intriguingly, most MG compounds with high efficacy for cancer treatment can glue on and control multiple key protein targets. On the other hand, a single key protein target can also be glued by multiple MG compounds with distinct chemical structures. The high flexibility of MG–protein interaction profiles provides rich soil for the growth and development of small-molecule MG compounds that can be used as molecular tools to assist in unraveling disease mechanisms, and they can also facilitate drug development for the treatment of human disease, especially human cancer.

They can be classified into different types based on their mechanisms and targets. One type includes immunomodulatory imide drugs (IMiDs) like thalidomide, which recruit E3 ligases to degrade specific substrates. Another type encompasses synthetic small molecules designed to induce proximity between target proteins and ubiquitin ligases, effectively marking the target for degradation. Additionally, natural product-derived molecular glues, such as rapamycin, function by binding to specific proteins and bridging their interaction with other cellular machinery. These diverse types of molecular glues have significant potential for therapeutic applications, especially in targeting undruggable proteins.

Molecular glues exhibit significant potential in treating a variety of diseases by modulating protein interactions. In cancer therapy, molecular glues such as IMiDs (e.g., thalidomide and its derivatives) have been employed to induce the degradation of oncogenic proteins, providing a strategy to eliminate cancer cells selectively. These molecules target transcription factors and other proteins crucial for cancer cell survival and proliferation. In the realm of neurodegenerative diseases, molecular glues can be designed to promote the degradation of misfolded or aggregated proteins, such as tau or alpha-synuclein, which are implicated in conditions like Alzheimer's and Parkinson's disease. By altering protein-protein interactions, molecular glues offer a novel therapeutic approach to mitigate the accumulation of toxic proteins, thereby potentially slowing disease progression and alleviating symptoms. These applications underscore the versatility and promise of molecular glues in addressing complex diseases through targeted protein modulation.

Report Highlights

In May 2024, Takeda Pharmaceuticals announced an exclusive licensing deal with China-based Degron Therapeutics to develop novel molecular glue degraders for various oncology, neuroscience and inflammatory disease targets.

In May 2024, NEOsphere Biotechnologies GmbH announced a collaboration with Kymera Therapeutics, Inc. focused on unlocking undrugged or poorly drugged disease-causing protein targets that can be only or best addressed by Targeted Protein Degradation. Under the agreement, NEOsphere Biotechnologies will utilize its target- and E3-agnostic platform to screen molecular glue compounds on a proteome-wide level and in a native context.

In March 2024, Nurix Therapeutics, Inc. announced that the US Food and Drug Administration (FDA) had lifted the partial clinical hold on the U.S. Phase Ia/Ib study evaluating NX-2127 in adults with relapsed/refractory B-cell malignancies. The partial clinical hold on the study was announced by Nurix on November 1, 2023, following the company’s communication to the FDA of its intention to transition to an improved manufacturing process.

In February 2024, Neomorph, Inc. announced about collaboration and licensing agreement with global healthcare company Novo Nordisk to discover, develop and commercialize molecular glue degraders. Under the terms of the deal, Neomorph will lead discovery and preclinical activities against unnamed selected targets. Novo Nordisk will then have the option to exclusively pursue further clinical development and commercialization of the compounds.

In September 2023, Orionis Biosciences, a privately held life sciences company with an integrated drug discovery and chemical biology platform, announced a multi-year collaboration with Genentech, a member of the Roche Group, to discover novel small molecule medicines for challenging targets in major disease areas, including oncology and neurodegeneration. Under the terms of the agreement, Orionis will be responsible for the discovery and optimization of molecular glues for Genentech’s designated targets, while Genentech will be responsible for subsequent later-stage preclinical, clinical development, regulatory filing, and commercialization of such small molecules.

Molecular Glues: Company and Product Profiles (Marketed)

1. Company Overview: Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company that focuses on discovering, developing, and delivering innovative medicines to patients with serious diseases. Headquartered in New York City, the company specializes in areas such as oncology, immunology, cardiovascular diseases, and fibrosis. Through extensive research and development efforts, Bristol Myers Squibb aims to address unmet medical needs and improve the quality of life for patients around the world. The company collaborates with various partners and employs advanced scientific methods to advance its pipeline of therapeutics.

Product Description: REVLIMID

REVLIMID is a prescription medicine, used to treat adults with multiple myeloma (MM) in combination with the medicine dexamethasone, or as maintenance treatment after autologous hematopoietic stem cell transplantation (a type of stem cell transplant that uses your own stem cells). REVLIMID should not be used to treat people who have chronic lymphocytic leukemia (CLL) unless they are participants in a controlled clinical trial. It is not known if REVLIMID is safe and effective in children.

Product Description: POMALYST

POMALYST is a prescription medicine used to treat adults with Multiple myeloma, taken along with the medicine dexamethasone, in patients who have previously received at least 2 medicines to treat multiple myeloma, including a proteasome inhibitor and lenalidomide, and whose disease has become worse during treatment or within 60 days of finishing the last treatment. It is not known if POMALYST is safe and effective in children.

Molecular Glues: Company and Product Profiles (Pipeline)

1. Company Overview: Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company that focuses on discovering, developing, and delivering innovative medicines to patients with serious diseases. Headquartered in New York City, the company specializes in areas such as oncology, immunology, cardiovascular diseases, and fibrosis. Through extensive research and development efforts, Bristol Myers Squibb aims to address unmet medical needs and improve the quality of life for patients around the world. The company collaborates with various partners and employs advanced scientific methods to advance its pipeline of therapeutics.

Product Description: Golcadomide

Golcadomide (CC-99282) is an oral molecular glue that promotes degradation of IKZF1/3 transcription factors (Ikaros/Aiolos) by engaging the cereblon E3 ubiquitin ligase complex. Structurally golcadomide is a novel thalidomide analogue (known as a CELMoD/cereblon E3 ligase modulator). It has immunomodulatory actions, with enhanced antiproliferative and proapoptotic activities. Currently, Golcadomide is in Phase III stage of development for the treatment of B-cell Lymphoma.

2. Company Overview: Revolution Medicines, Inc.

Revolution Medicines is a biopharmaceutical company focused on developing targeted cancer therapies that inhibit frontier oncology targets, particularly RAS proteins. The company's mission is to revolutionize treatment for patients with RAS-addicted cancers, which account for a significant portion of lung, colorectal, and pancreatic cancer cases. Revolution Medicines has a pipeline of novel RAS(ON) inhibitors and RAS companion inhibitors designed to permanently disengage the ""ON"" switch of mutated RAS proteins and suppress cooperating pathways that sustain RAS-addicted cancers.

Product Description: RMC 6291

RMC-6291 is an orally active and covalent inhibitor of KRASG12C(ON). RMC-6291 forms a tri-complex within tumor cells between KRASG12C(ON) and cyclophilin A (CypA). Thus, RMC-6291 prevents KRASG12C(ON) from signaling via steric blockade of RAS effector binding. RMC-6291 inhibits ERK signaling and induced apoptosis in KRASG12C-mutant H358 cells. RMC-6291 also inhibits the proliferation of KRASG12C mutant cells with a median IC50 of 0.11 nM. RMC-6291 may address an area of high unmet need for patients with KRAS G12C–mutant advanced non–small cell lung cancer (NSCLC) and colorectal cancer (CRC), including patients with NSCLC whose disease has progressed on prior treatment with other KRAS G12C(OFF) inhibitors. Currently, RMC-6291 is in Phase I/II stage of development for the treatment of Solid tumors including NSCLC and SCLC.

3. Company Overview: Nested Therapeutics

Nested Therapeutics is a biotechnology company focused on discovering and developing novel, targeted, small molecule precision medicine therapies for patients with cancer by using mutation clusters to identify druggable pockets. With a platform that utilizes insights from genomics, computational chemistry, proteomics and AI, Nested is working to reach untapped mutations with the potential to improve outcomes of patients.

Product Description: NST-628

NST-628 is a fully brain-penetrant, mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway. NST-628 was developed based on Nested's proprietary structural insights of how signaling complexes form and function in cancer and addresses common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of resistance via signaling pathway reactivation. It is currently being evaluated in Phase I for the treatment of Solid tumors.

4. Company Overview: Nurix Therapeutics

Nurix Therapeutics, Inc. is a biopharmaceutical company focused on developing novel therapies that control protein levels by harnessing the body's natural process of ubiquitination. Founded in 2009 and based in San Francisco, Nurix is led by President and CEO Arthur T. Sands, M.D., Ph.D., who previously co-founded Lexicon Pharmaceuticals.

Product Description: NX-2127

NX-2127 is an orally bioavailable protein degrader molecule. It reduces levels of both Bruton's tyrosine kinase (BTK) and the IKZF transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) through targeted ubiquitination and proteasomal degradation. NX-2127 acts as a dual PROTAC (through recruitment of cereblon) and molecular glue (degradation of the neosubstrate transcription factors). It is predicted that this approach can achieve clinical efficacy, even in the presence of BTK mutations that confer resistance to clinically used kinase inhibitor drugs. It is currently being evaluated in Phase I for the treatment of B-cell malignancies.

5. Company Overview: Plexium

Plexium is an innovative biotechnology company focused on targeted protein degradation (TPD) to develop novel small molecule drugs for treating various diseases, including cancer and neurodegenerative disorders. Founded in 2017 and based in San Diego, Plexium employs a proprietary drug discovery platform that utilizes high-throughput screening to identify compounds capable of selectively degrading disease-causing proteins. This approach aims to overcome the limitations of traditional therapies, enhancing the efficacy of treatments.

Product Description: PLX-4545

PLX-4545 is designed to destabilize highly suppressive regulatory T cells (Tregs) by inducing the degradation of IKZF2. This mechanism aims to convert Tregs into effector-like T cells, potentially enhancing the immune response against tumors. The drug is administered orally and has shown promising preclinical efficacy, comparable to pembrolizumab, particularly when combined with checkpoint inhibitors.

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