- New antibody drug conjugate (ADC) programme unveiled, with demonstration of positive pre-clinical proof of concept for Myricx N-myristoyltransferase inhibitors (NMTi) as a completely novel ADC payload (see poster 2635)2
- New biology reveals mode of action (MoA) for NMTi via unfolded protein response (UPR) stress pathways in cancer cells (see poster 4871)3 and ability of NMTi to re-programme tumour-associated macrophages into anti-cancer phenotype (see poster 439)1
LONDON, UK I April 17, 2023 I Myricx Pharma (‘Myricx’), an oncology drug discovery company focused on developing precision medicines based on its N-myristoyltransferase (NMT) platform has unveiled its antibody drug conjugate (ADC) programme, presenting promising in vivo data at the American Association for Cancer Research’s Annual Meeting, AACR 2023, April 14-19, Florida.
NMT inhibitors (NMTi) have previously been shown to inhibit viability and growth of haematological cancers. Myricx’s novel highly potent NMTi are selectively cytotoxic in multiple cancer cell lines as well as exhibiting tumour regression in in vivo models of both haematological and solid cancers. Myricx has also developed a transcriptional signature which predicts cancer cell sensitivity to NMTi with high confidence.
Myricx’s advanced chemistry offers the potential for the development of NMTi as a novel payload on a wide range of existing linker and antibody ADC technologies. A unique feature of NMTi-ADCs is that they contain two targeting mechanisms: a monoclonal antibody (mAb) that targets the payload to antigen positive cancer cells; and selectivity for specific cancers with high intrinsic sensitivity to NMTi. Myricx has data elucidating the mechanism of this sensitivity.
Myricx’s most advanced ADC, MYX2449, is a selective and ultrapotent NMTi conjugated via a cleavable linker to trastuzumab (HER2+ mAb). Positive in vitro and in vivo data presented at AACR2 demonstrate MYX2449 cytotoxic potency in selective cancer cell lines, anti-tumour efficacy in both high and low HER2 expressing cancers, with tolerability >10 times its efficacious dose in in vivo models.
As a proof of concept (PoC) for its NMTi-ADC approach, Myricx tested MYX2449 trastuzumab-NMTi ADC in in vivo models of gastric cancer (GC) and breast cancer (BC), as many of these cancers express HER2 and also express the NMTi sensitivity signature. MYX2449 delivered differentiated activity and improved efficacy compared to the gold standard ADC trastuzumab-deruxtecan in a GC model with excellent tumour shrinkage at 5mpk in the xenograft and excellent cyno tolerability at the highest dose, 20mpk. Similar efficacy was obtained in a BC xenograft model.
Encouraged by these positive PoC results, Myricx is now exploring a range of ADCs in further hard-to-treat solid cancers that express both the NMTi sensitivity signature and ADC-compatible antigens.
Myricx CEO Dr Robin Carr who presented the ADC-NMTi poster at AACR 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 offer huge potential for selective cancer cell killing via its unique mechanism of action.”
Myricx is a start-up from two of London’s leading biomedical research organizations, Imperial College London and the Francis Crick Institute. Myricx scientists and founding collaborators were the first to identify that inhibition of NMT is highly effective in the treatment of MYC-driven cancer models acting through the unfolded protein response (UPR). UPR stress is a known vulnerability of cancer and Myricx is now using its discoveries to build a proprietary pipeline of targeted cancer therapies. The company is developing NMTi as small molecule drugs as well as novel selective cytotoxic payloads for ADCs.
In addition to the poster on its lead ADC programme, scientists from Myricx’s collaborators presented two posters on Myricx’s small molecule programmes and NMT biology, including in vivo reprogramming of tumour-associated macrophages to an anticancer phenotype by modulating NMT activity1 and how deregulation of MYC-family proteins sensitizes cancers to NMT inhibition, resulting in the identification of NMTi sensitivity and mechanism.3
Professor Ed Tate, Myricx co-founder and lead author of the posters presented by the Imperial College London/Francis Crick Institute teams, said, “NMT is a hot emerging drug target in cancer and Myricx has developed high-quality proprietary chemical inhibitors of NMT that have led to breakthrough discoveries and unlocked an unexpected and unique mechanism of cancer cell killing, specific to cancers with vulnerabilities associated with the unfolded protein response. Furthermore, we have recently shown that NMTi has the potential to drive anti-tumour innate immune responses, including the reprogramming of tumour-associated macrophages in the tumour microenvironment.
“These discoveries alongside the massive potential of NMTi as a selective ADC payload pave the way for novel and highly efficacious treatments for patients.”
- Poster number: 439: From foe to friend: In vivo reprogramming of tumour-associated macrophages to an anti-cancer phenotype by modulating N-myristoyltransferase activity – presented by @Wouter Kallemeijn, Francis Crick Institute/Imperial College London
New Drug Targets 16 April 1:30 PM Section 16 board 3
- Poster number: 2635: N-Myristoyltransferase (NMT) inhibitors as novel potent payloads for antibody drug conjugates – presented by our CEO @Robin Carr
Antibody Technologies session 17 April, 1:30 PM Section 13 board 3
- Poster number: 4871: Dysregulation of MYC-family proteins sensitizes cancers to NMT inhibition: identification of NMTi sensitivity and mechanism – presented by @James Zhang, ICR/Imperial College London
Anticancer Approaches Targeting Signal Transduction Pathways 18 April 1:30 PM Section 13 board 14
Copies of these posters will be available on our website after they have been presented – HERE
Notes to Editors:
About Myricx Pharma – www.myricxpharma.com
Myricx Pharma Ltd (“Myricx”) is a small molecule drug discovery company engaged in developing novel proprietary inhibitors of human N-myristoyltransferases (NMT) for the treatment of cancer, both directly and as selective cytotoxic payloads for antibody drug conjugate (ADC) drugs.
Operating as a mainly virtual company based in London, UK, Myricx was founded in 2019 based on discoveries made at Imperial College London and the Francis Crick Institute by its co-founders Prof Ed Tate, Dr Andrew Bell and Dr Roberto Solari. The Company has raised an initial £4.5million in seed investment from Sofinnova Partners and Brandon Capital Partners. Myricx has the rights to key NMT discoveries, and composition-of-matter and use patents of its scientific co-founders through exclusive license agreements with Imperial College London.
Follow us on LinkedIn.
About Myristoylation
Myristoylation is a lipid modification to a specific group of target proteins in a cell. It involves the attachment of myristic acid, a 14-carbon fatty acid, to a protein’s N-terminal glycine residue. This process is catalyzed by the ubiquitous eukaryotic enzyme, N-myristoyltransferase (NMT), which uses myristoyl-coenzyme A (CoA) as a substrate.
Myristoylation is an irreversible change to proteins and plays a vital role in protein–protein interactions, targeting proteins to cytoplasmic and plasma membranes, and regulating cellular signaling pathways in several biological processes. It is also known to be involved in a range of diseases including cancer.
SOURCE: Myricx Pharma
Post Views: 330
- New antibody drug conjugate (ADC) programme unveiled, with demonstration of positive pre-clinical proof of concept for Myricx N-myristoyltransferase inhibitors (NMTi) as a completely novel ADC payload (see poster 2635)2
- New biology reveals mode of action (MoA) for NMTi via unfolded protein response (UPR) stress pathways in cancer cells (see poster 4871)3 and ability of NMTi to re-programme tumour-associated macrophages into anti-cancer phenotype (see poster 439)1
LONDON, UK I April 17, 2023 I Myricx Pharma (‘Myricx’), an oncology drug discovery company focused on developing precision medicines based on its N-myristoyltransferase (NMT) platform has unveiled its antibody drug conjugate (ADC) programme, presenting promising in vivo data at the American Association for Cancer Research’s Annual Meeting, AACR 2023, April 14-19, Florida.
NMT inhibitors (NMTi) have previously been shown to inhibit viability and growth of haematological cancers. Myricx’s novel highly potent NMTi are selectively cytotoxic in multiple cancer cell lines as well as exhibiting tumour regression in in vivo models of both haematological and solid cancers. Myricx has also developed a transcriptional signature which predicts cancer cell sensitivity to NMTi with high confidence.
Myricx’s advanced chemistry offers the potential for the development of NMTi as a novel payload on a wide range of existing linker and antibody ADC technologies. A unique feature of NMTi-ADCs is that they contain two targeting mechanisms: a monoclonal antibody (mAb) that targets the payload to antigen positive cancer cells; and selectivity for specific cancers with high intrinsic sensitivity to NMTi. Myricx has data elucidating the mechanism of this sensitivity.
Myricx’s most advanced ADC, MYX2449, is a selective and ultrapotent NMTi conjugated via a cleavable linker to trastuzumab (HER2+ mAb). Positive in vitro and in vivo data presented at AACR2 demonstrate MYX2449 cytotoxic potency in selective cancer cell lines, anti-tumour efficacy in both high and low HER2 expressing cancers, with tolerability >10 times its efficacious dose in in vivo models.
As a proof of concept (PoC) for its NMTi-ADC approach, Myricx tested MYX2449 trastuzumab-NMTi ADC in in vivo models of gastric cancer (GC) and breast cancer (BC), as many of these cancers express HER2 and also express the NMTi sensitivity signature. MYX2449 delivered differentiated activity and improved efficacy compared to the gold standard ADC trastuzumab-deruxtecan in a GC model with excellent tumour shrinkage at 5mpk in the xenograft and excellent cyno tolerability at the highest dose, 20mpk. Similar efficacy was obtained in a BC xenograft model.
Encouraged by these positive PoC results, Myricx is now exploring a range of ADCs in further hard-to-treat solid cancers that express both the NMTi sensitivity signature and ADC-compatible antigens.
Myricx CEO Dr Robin Carr who presented the ADC-NMTi poster at AACR 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 offer huge potential for selective cancer cell killing via its unique mechanism of action.”
Myricx is a start-up from two of London’s leading biomedical research organizations, Imperial College London and the Francis Crick Institute. Myricx scientists and founding collaborators were the first to identify that inhibition of NMT is highly effective in the treatment of MYC-driven cancer models acting through the unfolded protein response (UPR). UPR stress is a known vulnerability of cancer and Myricx is now using its discoveries to build a proprietary pipeline of targeted cancer therapies. The company is developing NMTi as small molecule drugs as well as novel selective cytotoxic payloads for ADCs.
In addition to the poster on its lead ADC programme, scientists from Myricx’s collaborators presented two posters on Myricx’s small molecule programmes and NMT biology, including in vivo reprogramming of tumour-associated macrophages to an anticancer phenotype by modulating NMT activity1 and how deregulation of MYC-family proteins sensitizes cancers to NMT inhibition, resulting in the identification of NMTi sensitivity and mechanism.3
Professor Ed Tate, Myricx co-founder and lead author of the posters presented by the Imperial College London/Francis Crick Institute teams, said, “NMT is a hot emerging drug target in cancer and Myricx has developed high-quality proprietary chemical inhibitors of NMT that have led to breakthrough discoveries and unlocked an unexpected and unique mechanism of cancer cell killing, specific to cancers with vulnerabilities associated with the unfolded protein response. Furthermore, we have recently shown that NMTi has the potential to drive anti-tumour innate immune responses, including the reprogramming of tumour-associated macrophages in the tumour microenvironment.
“These discoveries alongside the massive potential of NMTi as a selective ADC payload pave the way for novel and highly efficacious treatments for patients.”
- Poster number: 439: From foe to friend: In vivo reprogramming of tumour-associated macrophages to an anti-cancer phenotype by modulating N-myristoyltransferase activity – presented by @Wouter Kallemeijn, Francis Crick Institute/Imperial College London
New Drug Targets 16 April 1:30 PM Section 16 board 3
- Poster number: 2635: N-Myristoyltransferase (NMT) inhibitors as novel potent payloads for antibody drug conjugates – presented by our CEO @Robin Carr
Antibody Technologies session 17 April, 1:30 PM Section 13 board 3
- Poster number: 4871: Dysregulation of MYC-family proteins sensitizes cancers to NMT inhibition: identification of NMTi sensitivity and mechanism – presented by @James Zhang, ICR/Imperial College London
Anticancer Approaches Targeting Signal Transduction Pathways 18 April 1:30 PM Section 13 board 14
Copies of these posters will be available on our website after they have been presented – HERE
Notes to Editors:
About Myricx Pharma – www.myricxpharma.com
Myricx Pharma Ltd (“Myricx”) is a small molecule drug discovery company engaged in developing novel proprietary inhibitors of human N-myristoyltransferases (NMT) for the treatment of cancer, both directly and as selective cytotoxic payloads for antibody drug conjugate (ADC) drugs.
Operating as a mainly virtual company based in London, UK, Myricx was founded in 2019 based on discoveries made at Imperial College London and the Francis Crick Institute by its co-founders Prof Ed Tate, Dr Andrew Bell and Dr Roberto Solari. The Company has raised an initial £4.5million in seed investment from Sofinnova Partners and Brandon Capital Partners. Myricx has the rights to key NMT discoveries, and composition-of-matter and use patents of its scientific co-founders through exclusive license agreements with Imperial College London.
Follow us on LinkedIn.
About Myristoylation
Myristoylation is a lipid modification to a specific group of target proteins in a cell. It involves the attachment of myristic acid, a 14-carbon fatty acid, to a protein’s N-terminal glycine residue. This process is catalyzed by the ubiquitous eukaryotic enzyme, N-myristoyltransferase (NMT), which uses myristoyl-coenzyme A (CoA) as a substrate.
Myristoylation is an irreversible change to proteins and plays a vital role in protein–protein interactions, targeting proteins to cytoplasmic and plasma membranes, and regulating cellular signaling pathways in several biological processes. It is also known to be involved in a range of diseases including cancer.
SOURCE: Myricx Pharma
Post Views: 330
