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Recent popular reports from Yimike ★ Invitation Letter2021 CSGCT Gene and Cell Therapy Medical Summit will be held in Shanghai ★ Over US$1 billion! Next-generation ADC platform technology supports the development of 5 ADC therapiesMedClub broke the news November 26, 2021/eMedClub News/--Recently, Arrowhead Pharmaceuticals, a biopharmaceutical company that aims to develop new drugs for the treatment of intractable diseases, announced Signed an exclusive license agreement with GlaxoSmithKline (GSK)
.
According to the agreement, GSK and Arrowhead will jointly develop and promote Arrowhead's research RNAi therapy ARO-HSD for the treatment of non-alcoholic steatohepatitis (NASH)
.
Currently, it is still in phase 1/2 clinical trials
.
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of excessive fat in the liver, which can cause liver damage similar to the damage caused by alcohol abuse.
7% to 30% of NAFLD patients will develop non-alcoholic steatohepatitis (NASH).
Cause liver damage
.
At present, there are more than 100 million NASH patients in the world, and at least one third of NASH patients will eventually develop cirrhosis, and their risk of liver cancer is significantly increased
.
As of now, there is no approved NASH therapy
.
ARO-HSD is an investigative RNAi therapeutic drug targeting HSD17B13, which aims to achieve protective loss of function by down-regulating the expression of HSD17B13 in liver cells
.
HSD17B13 is a member of the hydroxysteroid dehydrogenase family, involved in the metabolism of hormones, fatty acids and bile acids
.
Published human genetic data indicate that the loss-of-function mutation of HSD17B13 can provide strong protection for patients with alcoholic hepatitis, cirrhosis and NASH
.
ARO-HSD can inhibit the production of proteins expressed by the HSD17B13 gene
.
At the 72nd American Association for the Study of Liver Diseases (AASLD) Annual Meeting held this year, Arrowhead announced the preliminary results of the Phase 1/2 clinical trial of ARO-HSD
.
The results of the test showed that ARO-HSD dose-dependently reduced HSD17B13 mRNA levels were observed in all patients.
At a dose of 200 mg, the mRNA level was reduced by more than 90%
.
In addition, in patients treated with ARO-HSD at doses greater than 100 mg, a decrease in liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was observed
.
Among the 18 patients receiving treatment, 9 patients observed a decrease in liver fat levels, which was 4%-41%
.
The liver stiffness (kPa) of 6 patients decreased by 4-37%
.
Under the terms of the agreement, Arrowhead will receive an upfront payment of US$120 million and is eligible for development and commercialization milestone payments of more than US$1 billion
.
Arrowhead is also eligible for tiered royalties on product net sales
.
GSK will obtain the development and commercialization rights of ARO-HSD in all regions except Greater China
.
"Due to inflammatory damage and fibrosis caused by excessive accumulation of liver fat, NASH may become a life-threatening disease
.
The convincing genetic evidence that the HSD17B13 gene mutation protects the liver from inflammatory damage means that we have the opportunity to develop a potential'first-in-class' therapy to improve the clinical outcome of NASH
.
Dr.
John Lepore, research director of GlaxoSmithKline (GSK), said, "We are very pleased to promote this innovative treatment into Phase 2 clinical studies
.
It may become an important potential new drug for the treatment of patients with NASH
.
“It’s worth mentioning that Arrowhead has deployed multiple pipelines in the liver, lung, tumor and muscle fields based on its RNAi technology platform (TRiMTM)
.
▲Arrowhead’s pipeline (photo source: Arrowhead official website) TRiM™ platform TRiM™ platform Using ligand-mediated delivery methods, a simple structured tissue-specific targeting system is formed
.
Based on its more than ten years of mature targeted drug delivery tool foundation, Arrowhead uses the TRiM™ platform to gradually remove drug-independent properties and chemical components , To maintain the best pharmacological activity
.
The
TRiM™ platform optimizes the following components for each candidate drug as needed: high-affinity targeting ligands, diverse linkers and chemical properties, structures with strong pharmacokinetics, and A high-affinity RNAi trigger with sequence-specific and stable chemical properties
.
▲Arrowhead technology platform (picture source: Arrowhead official website) RNAi therapy RNAi is a gene silencing phenomenon in which small interfering RNAs induce silencing complexes through RNA (RNA-induced silencing) complex, RISC) and mediate the degradation of target mRNA and inhibit its translation
.
Using this mechanism, RNAi can be used to silence specific genes related to disease
.
As far as complement-related diseases are concerned, RNAi therapy can block the production of complement pathway factors and is expected to inhibit the uncontrolled complement activation that can lead to many diseases
.
▲RNAi therapy mechanism (picture source: Arrowhead's official website) RNAi therapy belongs to gene editing technology therapy, and it is also a therapy technology based on modifying specific RNA sequences to produce targeted therapeutic effects
.
In 1998, Andrew Fire and Craig Mello published a groundbreaking paper that determined that double-stranded RNA (dsRNA) is the causative agent of Caenorhabditis elegans post-transcriptional gene silencing (PTGS).
They called this phenomenon RNA interference (RNA interference, RNAi)
.
In 2006, two pioneers of RNAi, Andrew Fire and Craig Mello, won the Nobel Prize in Physiology or Medicine for this discovery
.
After the RNAi mechanism was discovered, its potential in the development of new drugs was quickly appreciated
.
Since Fire and Mello won the Nobel Prize for RNAi, funds from large pharmaceutical companies have also flooded in, giving the RNAi technology a period of vigorous development
.
However, the development of RNAi therapy is not smooth.
Some serious problems with RNAi drugs discovered in clinical trials have made pharmaceutical companies confused about where to go
.
Until recent years, a number of RNAi drugs have been approved by the FDA for listing, which has enabled RNAi therapy to open the door to the capital market and gradually move towards the mainstream medical market stage, becoming one of the most promising new therapies
.
At present, RNAi therapy has shown great potential in the treatment of various diseases, and RNAi drugs have become one of the most promising new therapies
.
Reference materials: 1.
https:// .
com/biotech/gsk-takes-a-1b-dive-into-nash-penning-rnai-pact-target-arrowhead-pharmaceuticals3.
https://ir.
arrowheadpharma.
com/news-releases/news-release-details /arrowhead-presents-additional-clinical-data-investigational-1
.
According to the agreement, GSK and Arrowhead will jointly develop and promote Arrowhead's research RNAi therapy ARO-HSD for the treatment of non-alcoholic steatohepatitis (NASH)
.
Currently, it is still in phase 1/2 clinical trials
.
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of excessive fat in the liver, which can cause liver damage similar to the damage caused by alcohol abuse.
7% to 30% of NAFLD patients will develop non-alcoholic steatohepatitis (NASH).
Cause liver damage
.
At present, there are more than 100 million NASH patients in the world, and at least one third of NASH patients will eventually develop cirrhosis, and their risk of liver cancer is significantly increased
.
As of now, there is no approved NASH therapy
.
ARO-HSD is an investigative RNAi therapeutic drug targeting HSD17B13, which aims to achieve protective loss of function by down-regulating the expression of HSD17B13 in liver cells
.
HSD17B13 is a member of the hydroxysteroid dehydrogenase family, involved in the metabolism of hormones, fatty acids and bile acids
.
Published human genetic data indicate that the loss-of-function mutation of HSD17B13 can provide strong protection for patients with alcoholic hepatitis, cirrhosis and NASH
.
ARO-HSD can inhibit the production of proteins expressed by the HSD17B13 gene
.
At the 72nd American Association for the Study of Liver Diseases (AASLD) Annual Meeting held this year, Arrowhead announced the preliminary results of the Phase 1/2 clinical trial of ARO-HSD
.
The results of the test showed that ARO-HSD dose-dependently reduced HSD17B13 mRNA levels were observed in all patients.
At a dose of 200 mg, the mRNA level was reduced by more than 90%
.
In addition, in patients treated with ARO-HSD at doses greater than 100 mg, a decrease in liver alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was observed
.
Among the 18 patients receiving treatment, 9 patients observed a decrease in liver fat levels, which was 4%-41%
.
The liver stiffness (kPa) of 6 patients decreased by 4-37%
.
Under the terms of the agreement, Arrowhead will receive an upfront payment of US$120 million and is eligible for development and commercialization milestone payments of more than US$1 billion
.
Arrowhead is also eligible for tiered royalties on product net sales
.
GSK will obtain the development and commercialization rights of ARO-HSD in all regions except Greater China
.
"Due to inflammatory damage and fibrosis caused by excessive accumulation of liver fat, NASH may become a life-threatening disease
.
The convincing genetic evidence that the HSD17B13 gene mutation protects the liver from inflammatory damage means that we have the opportunity to develop a potential'first-in-class' therapy to improve the clinical outcome of NASH
.
Dr.
John Lepore, research director of GlaxoSmithKline (GSK), said, "We are very pleased to promote this innovative treatment into Phase 2 clinical studies
.
It may become an important potential new drug for the treatment of patients with NASH
.
“It’s worth mentioning that Arrowhead has deployed multiple pipelines in the liver, lung, tumor and muscle fields based on its RNAi technology platform (TRiMTM)
.
▲Arrowhead’s pipeline (photo source: Arrowhead official website) TRiM™ platform TRiM™ platform Using ligand-mediated delivery methods, a simple structured tissue-specific targeting system is formed
.
Based on its more than ten years of mature targeted drug delivery tool foundation, Arrowhead uses the TRiM™ platform to gradually remove drug-independent properties and chemical components , To maintain the best pharmacological activity
.
The
TRiM™ platform optimizes the following components for each candidate drug as needed: high-affinity targeting ligands, diverse linkers and chemical properties, structures with strong pharmacokinetics, and A high-affinity RNAi trigger with sequence-specific and stable chemical properties
.
▲Arrowhead technology platform (picture source: Arrowhead official website) RNAi therapy RNAi is a gene silencing phenomenon in which small interfering RNAs induce silencing complexes through RNA (RNA-induced silencing) complex, RISC) and mediate the degradation of target mRNA and inhibit its translation
.
Using this mechanism, RNAi can be used to silence specific genes related to disease
.
As far as complement-related diseases are concerned, RNAi therapy can block the production of complement pathway factors and is expected to inhibit the uncontrolled complement activation that can lead to many diseases
.
▲RNAi therapy mechanism (picture source: Arrowhead's official website) RNAi therapy belongs to gene editing technology therapy, and it is also a therapy technology based on modifying specific RNA sequences to produce targeted therapeutic effects
.
In 1998, Andrew Fire and Craig Mello published a groundbreaking paper that determined that double-stranded RNA (dsRNA) is the causative agent of Caenorhabditis elegans post-transcriptional gene silencing (PTGS).
They called this phenomenon RNA interference (RNA interference, RNAi)
.
In 2006, two pioneers of RNAi, Andrew Fire and Craig Mello, won the Nobel Prize in Physiology or Medicine for this discovery
.
After the RNAi mechanism was discovered, its potential in the development of new drugs was quickly appreciated
.
Since Fire and Mello won the Nobel Prize for RNAi, funds from large pharmaceutical companies have also flooded in, giving the RNAi technology a period of vigorous development
.
However, the development of RNAi therapy is not smooth.
Some serious problems with RNAi drugs discovered in clinical trials have made pharmaceutical companies confused about where to go
.
Until recent years, a number of RNAi drugs have been approved by the FDA for listing, which has enabled RNAi therapy to open the door to the capital market and gradually move towards the mainstream medical market stage, becoming one of the most promising new therapies
.
At present, RNAi therapy has shown great potential in the treatment of various diseases, and RNAi drugs have become one of the most promising new therapies
.
Reference materials: 1.
https:// .
com/biotech/gsk-takes-a-1b-dive-into-nash-penning-rnai-pact-target-arrowhead-pharmaceuticals3.
https://ir.
arrowheadpharma.
com/news-releases/news-release-details /arrowhead-presents-additional-clinical-data-investigational-1