The molecular glues pipeline and clinical trial analysis report delivers important insights on ongoing research, clinical strategies, upcoming therapeutics, and commercial analysis.
LAS VEGAS, July 11, 2024 /PRNewswire/ — DelveInsight’s ‘Molecular Glues Competitive Landscape – 2024‘ report provides comprehensive global coverage of available, marketed, and pipeline molecular glues in various stages of clinical development, major pharmaceutical companies working to advance the pipeline space, company assessment, comparative assessment, and future growth potential of the molecular glues competitive domain.
Key Takeaways from the Molecular Glues Competitive Landscape Report
- Over 10+ companies are evaluating 12+ molecular glues in various stages of development, and their anticipated acceptance in the oncology market would significantly increase market revenue.
- Key molecular glues companies such as Bristol Myers Squibb, Monte Rosa Therapeutics Inc., Revolution Medicines Inc., Nurix Therapeutics, Nested Therapeutics, DeuteRx, and others are evaluating new molecular glues to improve the treatment landscape.
- Promising molecular glues such as Mezigdomide, Golcadomide, Iberdomide, MRT-2359, RMC 6291, NX-2127, NST-628, SP-3164, and others are under different phases of molecular glues clinical trials.
- 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 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 November 2023, Kymera Therapeutics shared promising results from the Phase I clinical trial of its lead program, KT-474, marking a significant milestone in the field of targeted protein degradation (TPD).
- 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.
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Molecular Glues Overview
Molecular glues are a novel class of small molecules that facilitate the interaction between proteins, leading to the degradation or modulation of target proteins that are typically difficult to drug. Unlike traditional inhibitors that block active sites of enzymes, molecular glues work by binding to two different proteins, often an E3 ubiquitin ligase and a target protein, bringing them into close proximity. This interaction results in the ubiquitination and subsequent proteasomal degradation of the target protein. The mechanism offers a unique therapeutic approach, particularly in oncology, where it can selectively degrade proteins essential for cancer cell survival. The specificity and efficacy of molecular glues have shown promise in preclinical and clinical studies, indicating their potential to address previously “undruggable” targets.
The discovery and development of molecular glues involve sophisticated techniques in chemical biology and proteomics. Researchers use high-throughput screening and structure-based drug design to identify compounds that can act as molecular glues. One of the most well-known examples is thalidomide and its derivatives, which act as molecular glue by promoting the degradation of specific transcription factors. The field is rapidly evolving, with ongoing research aimed at expanding the repertoire of targetable proteins and improving the specificity and potency of these compounds. As our understanding of protein-protein interactions and the ubiquitin-proteasome system deepens, molecular glues are poised to become a transformative modality in the treatment of various diseases.
Find out more about molecular glues @ Molecular Glues Treatment
Molecular Glues Pipeline Analysis: Drug Profile
Golcadomide : Bristol Myers Squibb
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.
RMC 6291: Revolution Medicines, Inc.
RMC-6291 is an orally active, covalent inhibitor targeting KRAS G12C(ON). It forms a tri-complex in tumor cells between KRAS G12C(ON) and cyclophilin A (CypA), thereby preventing KRAS G12C(ON) from signaling through steric hindrance of RAS effector binding. This inhibition blocks ERK signaling and induces apoptosis in KRAS G12C-mutant H358 cells. Additionally, RMC-6291 effectively inhibits the proliferation of KRAS G12C mutant cells, with a median IC50 of 0.11 nM. Currently, RMC-6291 is in Phase I/II stage of development for the treatment of Solid tumors including NSCLC and SCLC.
NST-628: Nested Therapeutics
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.
A snapshot of the Molecular Glues Pipeline Drugs mentioned in the report:
|
Molecular Glues |
Company |
Phase |
Indication |
MoA |
|
Mezigdomide |
Phase III |
Multiple myeloma |
Apoptosis stimulants; CRBN protein modulators; Ubiquitin protein ligase modulators |
|
|
Golcadomide |
Phase III |
Lymphoma |
CRBN protein modulators; Ubiquitin protein ligase modulators |
|
|
Iberdomide |
Phase III |
Multiple Myeloma |
Ubiquitin protein ligase complex modulators |
|
|
MRT-2359 |
Monte Rosa Therapeutics, Inc |
Phase I/II |
Solid tumors |
Peptide-chain-release factor 3 degraders |
|
RMC 6291 |
Revolution Medicines, Inc. |
Phase I/II |
Solid tumors |
KRAS protein inhibitors |
|
NX-2127 |
Nurix Therapeutics |
Phase I |
B-cell malignancies |
Agammaglobulinaemia tyrosine kinase degraders; Agammaglobulinaemia tyrosine kinase inhibitors; IKZF1 protein degraders; IKZF3 protein degraders |
|
NST-628 |
Nested Therapeutics |
Phase I |
Solid tumors |
Mitogen-activated protein kinase inhibitors; Ras protein modulators |
|
SP-3164 |
DeuteRx |
Phase I |
Non-Hodgkin’s Lymphoma |
CRBN protein modulators; IKZF1 protein degraders; IKZF3 protein degraders |
Learn more about the emerging molecular glues @ Molecular Glues Clinical Trials
Scope of the Molecular Glues Competitive Landscape Report
- Coverage: Global
- Key Molecular Glues Companies: Bristol Myers Squibb, Monte Rosa Therapeutics Inc., Revolution Medicines Inc., Nurix Therapeutics, Nested Therapeutics, DeuteRx, and others
- Key Pipeline Molecular Glues: Mezigdomide, Golcadomide, Iberdomide, MRT-2359, RMC 6291, NX-2127, NST-628, SP-3164, and others
- Company Analysis, Therapeutic Assessment, Pipeline Assessment, Inactive drugs assessment, Unmet Needs
Dive deep into rich insights for new molecular glues, visit @ Molecular Glues
Table of Contents
|
1. |
Molecular Glues Pipeline Report Introduction |
|
2. |
Molecular Glues Pipeline Report Executive Summary |
|
3. |
Molecular Glues Pipeline: Overview |
|
4. |
Molecular Glues Marketed Drugs |
|
4.1. |
REVLIMID: Bristol Myers Squibb |
|
5. |
Molecular Glues Clinical Trial Therapeutics |
|
6. |
Molecular Glues Pipeline: Late-Stage Products (Pre-registration) |
|
7. |
Molecular Glues Pipeline: Late-Stage Products (Phase III) |
|
8. |
Molecular Glues Pipeline: Mid-Stage Products (Phase II) |
|
8.1. |
Drug Name: Company Name |
|
9. |
Molecular Glues Pipeline: Early-Stage Products (Phase I) |
|
9.1. |
NST-628: Nested Therapeutics |
|
10. |
Molecular Glues Pipeline Therapeutics Assessment |
|
11. |
Inactive Products in the Molecular Glues Pipeline |
|
12. |
Company-University Collaborations (Licensing/Partnering) Analysis |
|
13. |
Unmet Needs |
|
14. |
Molecular Glues Market Drivers and Barriers |
|
15. |
Appendix |
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