Myricx Pharma, an oncology drug discovery company specializing in precision medicines based on its N-myristoyltransferase (NMT) platform, has recently presented positive pre-clinical proof of concept data at the American Association for Cancer Research's Annual Meeting (AACR 2023). The company unveiled its novel antibody drug conjugate (ADC) programme, demonstrating the potential of Myricx's NMT inhibitors (NMTi) as a unique ADC payload.
Previously, NMTi had been shown to inhibit the viability and growth of hematological cancers. Myricx's potent NMTi have demonstrated selective cytotoxicity in multiple cancer cell lines and tumor regression in both hematological and solid cancer in vivo models. The company has also developed a transcriptional signature that predicts cancer cell sensitivity to NMTi with high accuracy.
Myricx's advanced chemistry allows for the development of NMTi as a novel payload for a wide range of existing linker and antibody ADC technologies. NMTi-ADCs offer two targeting mechanisms: a monoclonal antibody (mAb) that directs the payload to antigen-positive cancer cells and selectivity for specific cancers with high intrinsic sensitivity to NMTi.
MYX2449, Myricx's most advanced ADC, is a selective and ultrapotent NMTi conjugated via a cleavable linker to trastuzumab (HER2+ mAb). Positive in vitro and in vivo data presented at AACR demonstrate MYX2449's cytotoxic potency in selective cancer cell lines and its anti-tumor efficacy in both high and low HER2-expressing cancers. The data also show tolerability greater than ten times its efficacious dose in in vivo models.
As a proof of concept, Myricx tested its MYX2449 trastuzumab-NMTi ADC in in vivo models of gastric cancer (GC) and breast cancer (BC), which frequently express both HER2 and the NMTi sensitivity signature. MYX2449 exhibited differentiated activity and improved efficacy compared to the gold standard ADC trastuzumab-deruxtecan in a GC model, demonstrating excellent tumor shrinkage and tolerability at the highest dose.
Encouraged by these positive results, Myricx is now investigating a range of ADCs for further hard-to-treat solid cancers that express both the NMTi sensitivity signature and ADC-compatible antigens.
Dr. Robin Carr, CEO of Myricx, presented the ADC-NMTi poster at AACR and said, "NMT inhibitors represent a novel class of ADC payloads that can be exploited as targeted therapies in cancer. Based on our positive PoC data, we believe that ADC-NMTi offers huge potential for selective cancer cell killing via its unique mechanism of action."
Myricx, a startup from two of London's leading biomedical research organizations, Imperial College London and the Francis Crick Institute, is developing NMTi as small molecule drugs and novel selective cytotoxic payloads for ADCs. The company's scientists and founding collaborators were the first to identify that NMT inhibition is highly effective in treating MYC-driven cancer models, acting through the unfolded protein response (UPR).
These discoveries, along with the massive potential of NMTi as a selective ADC payload, pave the way for novel and highly efficacious treatments for patients in the near future.
Topics: Novel Therapeutics