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Myricx's Dual-action NMT Inhibitor ADCs for Enhanced Cancer Therapy

Tuesday, November 28, 2023

Myricx Bio, a biotechnology company based in the UK, is delighted to announce the publication of groundbreaking research in Nature Cell Biology by collaborators at the MRC-LMS (Laboratory of Medical Sciences). The research reveals the central role of N-Myristoyltransferase (NMT) inhibition in senescence, a process where cells cease dividing and undergo physiological changes with implications for various diseases.

Cellular senescence is associated with many diseases, as senescent cells, also known as 'zombie' cells, can negatively impact tissue function by persisting and secreting proteins. In tumors, these proteins contribute to chronic inflammation, metastasis, drug resistance, and tumor growth. Senolytics, which selectively eliminate senescent cells, offer a promising strategy for treating diseases such as cancer, fibrotic diseases, and age-related conditions.

The collaborative research, funded by UKRI MRC and CRUK, involved a study led by Professor Jesús Gil and Professor Ed Tate, along with 18 other scientists. The study found that small molecule NMTis can selectively kill senescent cancer cells.

The research demonstrated that senescent cells rely on a hyperactive secretory apparatus, and inhibiting NMT kills these cells, offering potential treatments for senescence-associated diseases, including cancer.

At a more detailed cellular level, the study revealed that COPI vesicle formation in senescent cells is a targetable process. However, existing senolytic drugs targeting COPI have poor pharmacological properties. Myricx's proprietary NMTis were shown to be non-toxic senolytics, selectively eliminating senescent cells with improved outcomes in different in vivo proof-of-concept cancer models. Specifically, NMTi targets ARF1, a key regulator of COPI vesicle formation requiring myristoylation to be functional.

Professor Jesús Gil highlighted the collaborative success, stating, "Our team has long been looking into senolytic targets that effectively and selectively kill senescent cells. In this study, we expanded our selection pool to be much larger, revealing previously unknown vulnerabilities of senescent cells. This opens up new possibilities for treating age-related diseases and cancer."

Professor Ed Tate added, "Our findings suggest that NMT inhibition could be a game-changer in senolytic therapy. Our potent, selective, in vivo active small molecule NMTis open exciting avenues for further research and development, as the first senolytic targeting protein lipidation."

Myricx Bio, emphasized the potential of the research for their NMTi-ADCs, stating, "The senolytic properties demonstrated give our NMTi-ADCs the potential for a highly differentiated profile not addressed by any other ADCs. We look forward to exploring this as we advance our drugs into clinical trials."

Myricx has pending patents and exclusive IP rights for the development of NMTis as novel drugs, including in senescence applications. The company has validated its NMTi payload platform, demonstrating in vivo pre-clinical efficacy for three NMTi-ADCs in its pipeline (B7-H3-NMTi, TROP2-NMTi, HER2-NMTi), showing complete and durable tumor regressions in multiple cancer models.



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