Vir Biotechnology, Inc. (NASDAQ:VIR) today announced initial topline data from its ongoing trial of VIR-3434 in patients with chronic hepatitis B virus (HBV) infection. Data from the first blinded cohort of eight patients, two of whom received placebo and six of whom received a single dose of 6 mg of VIR-3434, showed that six of eight patients achieved a mean reduction of 1.3 log10 IU/mL in serum hepatitis B virus surface antigen (HBsAg) by day eight, the day when nadir was achieved in most patients.
VIR-3434 is an HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and reduce the level of virions and subviral particles in the blood. It has also been Fc engineered to include the XX2 'vaccinal mutation,' allowing it to potentially function as a T cell vaccine, in this case, against HBV. The XX2 vaccinal mutation, which has the potential to transform standard antibodies into T cell vaccines, has also been incorporated into one of Vir's investigational COVID-19 monoclonal antibodies, VIR-7832, which is currently planned to enter a Phase 1b/2a trial this quarter. Vir has licensed exclusive rights to the XX2 mutation for use in infectious diseases.
'The need for a functional cure for the nearly 300 million people living with chronic HBV is paramount. Lowering HBsAg may help unlock a patient's immune system, allowing it to provide the immune control necessary to achieve a functional cure,' said Kosh Agarwal, M.D., lead study investigator and consultant hepatologist and transplant physician at the Institute of Liver Studies, King's College Hospital NHS Foundation Trust in London. 'These early, first-in-patient results are exciting because they demonstrate that even at a very low dose, VIR-3434 is able to markedly lower HBsAg.'
'Extrapolating from our preclinical data, we expected it might require much higher doses of VIR-3434 to achieve this level of HBsAg knockdown. To have achieved it with a dose of 6 mg is unexpected,' said Phillip Pang, M.D., Ph.D., Chief Medical Officer of Vir. 'Coupled with initial data that shows VIR-3434 was well tolerated at up to 3,000 mg in healthy volunteers, I am hopeful that we are seeing just the beginning of VIR-3434's capabilities.'
The Phase 1 clinical trial of VIR-3434 is a randomized, placebo-controlled trial designed to assess the safety, tolerability, pharmacokinetics, antiviral and immunomodulatory activity of VIR-3434 in healthy volunteers and patients with chronic HBV infection with HBsAg levels less than 1,000 IU/ml. The trial is designed to progress from healthy volunteers to chronic HBV patients in a staggered, parallel fashion with the goal of rapidly generating early proof-of-concept data in patients. Additional data will be submitted for presentation at an upcoming medical conference. A Phase 2 trial combining VIR-3434 with Vir's HBV-targeting siRNA, VIR-2218, is expected to commence in the second half of this year
o
VIR data promising, but small sample size (8) with much to be proven. 1.3log KD pretty much inline with what everyone else pursuing HepB has been able to do so far. However, does seem like they have us beat on lower dosage (6mg) assuming that’s what they ultimately stick with.
Also to keep in mind....HBV very complicated and just KD alone isn’t enough to beat this virus. Consensus that a combo therapy is required to turn off HBV replication, eliminate current HBV, and boost immune system to where it can regain control of the body. Dosages, combos, and much larger and longer trials are going to be required (along with a BP to help foot the bill).
JNJ is way ahead of them already by at least 2-3 years.
B
Regarding JNJ's three outstanding targets, we're probably coming close to getting some news. With a little help from Tad, we've been able to potentially identify a couple possible targets. It'll be interesting to see what the actual targets end up being, but my guess is that Alzheimer's and Tuberculosis will be in the mix.
Here are a couple interesting links showing JNJ's current interests:
Vir just downgraded by JPM to Underweight, target 30 now trading at 78. Guess they aren't impressed
b
If Alny is down today on the VIR news, this tells me that ARWR isn't down on the VIR news either. Just more daily price fluctuations noise. Just because VIR reported some positive numbers on a very small and early study does not mean that anything is any different than yesterday.
I want news out of JNJ as well, but the sheer amount of money they are pouring into the many JNJ-3989 trials already tells me a lot.
R
So we now know when Chris and Javier mentioned starting Phase 2 trials for ANG3 and several for APOC3 in first half of 2021 that we are looking closer to April than June.
Next on Phase 2 launching pad is HSD or additional APOC3 trials. Announcements maybe coming fast and furious this week as a prelude to next week’s conference call. Buckle up as the G forces are rising!
V
VIR results were in healthy volunteers and patients with chronic HBV infection with HBsAg levels less than 1,000 IU/ml. As I recall, some of the patients in ARWR trials had levels in 200,000-300,000.
I
Yesterday I was wrong. JNJ cam targets 8 HBV genotypes A-H. Can't seem to get the link posted.
M
A lot of Call volume in $110 & $100 Feb Calls. This volume came late in the day. Some Big bet out of the money Calls.
M
Arrowhead Pharmaceuticals Files IND for Phase 2b Study of ARO-ANG3 for Treatment of Mixed Dyslipidemia Jan 25, 2021 at 7:30 AM EST PASADENA, Calif. --(BUSINESS WIRE)--Jan. 25, 2021-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for a Phase 2b dose-finding clinical study of ARO-ANG3, the company’s
PASADENA, Calif.--(BUSINESS WIRE)--Jan. 25, 2021-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for a Phase 2b dose-finding clinical study of ARO-ANG3, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with mixed dyslipidemia.
Javier San Martin, M.D., chief medical officer at Arrowhead, said: “Cardiovascular disease remains the major cause of death, even after advances in therapies that reduce LDL cholesterol. This highlights the need for new therapies that can help patients at risk for cardiovascular disease to optimize their lipid profiles and protect them from atherosclerosis progression and cardiovascular events. By inhibiting ANGPTL3, Arrowhead’s investigational ARO-ANG3 is designed to reduce triglycerides and decrease LDL cholesterol in patients with mixed dyslipidemia. We have been very encouraged by the clinical data from this program to date and look forward to further assessing the safety and efficacy of ARO-ANG3 in the upcoming Phase 2b study.”
Following FDA’s review of the IND, the company intends to initiate AROANG3-2001, a Phase 2b dose-finding clinical study in patients with elevated triglycerides and low-density lipoprotein cholesterol (LDL-C). The primary objective of the study is to evaluate the safety and efficacy of ARO-ANG3 in adults with mixed dyslipidemia and to select a dosing regimen for later stage clinical studies in this patient population. The study is designed to include a total of 180 participants in three cohorts. All dose cohorts will enroll in parallel, with 60 participants per cohort randomly assigned in a 3:1 ratio to receive ARO-ANG3 or placebo.
D
Will Jnj/Janssen be presenting on Hep B at EASL 2021? If so, the abstract deadline is 1 week away.
f
ARO APOC ARO-APOC3
Primary Purpose: Treatment Official Title: A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome Actual Study Start Date : March 8, 2019 Estimated Primary Completion Date : January 21, 2021 Estimated Study Completion Date : January 21, 2021
j
When you have super-clean safety coming in, you can do this: All dose cohorts will enroll in parallel, with 60 participants per cohort randomly assigned in a 3:1 ratio to receive ARO-ANG3 or placebo.
t
My take and my question about the VIR HBV data compared to ARO-HBV (JNJ-3989):
- VIR is definetely cherry picking by just showing a small piece of the data cake. This piece is good but what with the other pieces? We'll see if they can beat us with duration and other components (beside HBsAg level).
I am really no scientist so my question could sound quite stupid: is it possible to compare this data anyhow with a clinical trial conducted bij Arrowhead in the past? I'm curious for that. I've been looking in the presentations and PR's on the ARWR website but couldn't find simular data (eight days after dosing) for ARO-HBV. I was able to find some pieces from ARC-520. I know this is the old platform but am I correct to state that ARO-HBV is quite "simular" to ARC-520? I found this:
"In a cohort of NUC-naïve, HBeAg-positive patients, best peak HBsAg reduction has been 99% (1.9 log) and the mean maximum HBsAg reduction has been 1.05 log through 15 days post ARC-520 treatment."
(Link: PR - September 24, 2015: Arrowhead Reports Peak Reduction in HBsAg of Up to 99% (1.9 log) After a Single Dose with Hepatitis B Candidate ARC-520 in Treatment Naïve Cohort of Phase 2a Study)
I also found this in the AASLD The Liver Meeting 2013:
"HBeAg levels declined by more than one log by day 4 and returned to baseline by day 43."
This is in chimps however, but it shows that a single dose of ARC-520 also reduces HBsAg within eight days to these levels.
I could be a moron and it's possible I don't understand the science. I'm sorry if that's the case! Will try to post links below.
C
Interesting action on 1 month chart. Shake out and then a tight range, all on low volume. Short decrease. Sensing the next move into higher ground
P
Market is booming and someone tries to take arwr down daily. Wild intraday swings which I’ve not seen before. Thought on the pressure of late?
o
Another “generic” PR from team ARWR on Twitter and LinkedIn....what are these folks up to??
“Arrowhead’s Targeted #RNAi Molecule, or TRiM™, platform utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting while being structurally simple. Learn more about the $ARWR technology here”
o
Another interesting “like” on LinkedIn regarding the PR today for Ph2 on ANG3.... Oncology Area Business Manager @ Sanofi Genzyme
The purpose of these “like” posts is to demonstrate that there are a number of upper level folks amongst BP who are following this “little” RNAi company.... all who could be potential partners in the future.
Vir Biotechnology, Inc. (NASDAQ:VIR) today announced initial topline data from its ongoing trial of VIR-3434 in patients with chronic hepatitis B virus (HBV) infection. Data from the first blinded cohort of eight patients, two of whom received placebo and six of whom received a single dose of 6 mg of VIR-3434, showed that six of eight patients achieved a mean reduction of 1.3 log10 IU/mL in serum hepatitis B virus surface antigen (HBsAg) by day eight, the day when nadir was achieved in most patients.
VIR-3434 is an HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and reduce the level of virions and subviral particles in the blood. It has also been Fc engineered to include the XX2 'vaccinal mutation,' allowing it to potentially function as a T cell vaccine, in this case, against HBV. The XX2 vaccinal mutation, which has the potential to transform standard antibodies into T cell vaccines, has also been incorporated into one of Vir's investigational COVID-19 monoclonal antibodies, VIR-7832, which is currently planned to enter a Phase 1b/2a trial this quarter. Vir has licensed exclusive rights to the XX2 mutation for use in infectious diseases.
'The need for a functional cure for the nearly 300 million people living with chronic HBV is paramount. Lowering HBsAg may help unlock a patient's immune system, allowing it to provide the immune control necessary to achieve a functional cure,' said Kosh Agarwal, M.D., lead study investigator and consultant hepatologist and transplant physician at the Institute of Liver Studies, King's College Hospital NHS Foundation Trust in London. 'These early, first-in-patient results are exciting because they demonstrate that even at a very low dose, VIR-3434 is able to markedly lower HBsAg.'
'Extrapolating from our preclinical data, we expected it might require much higher doses of VIR-3434 to achieve this level of HBsAg knockdown. To have achieved it with a dose of 6 mg is unexpected,' said Phillip Pang, M.D., Ph.D., Chief Medical Officer of Vir. 'Coupled with initial data that shows VIR-3434 was well tolerated at up to 3,000 mg in healthy volunteers, I am hopeful that we are seeing just the beginning of VIR-3434's capabilities.'
The Phase 1 clinical trial of VIR-3434 is a randomized, placebo-controlled trial designed to assess the safety, tolerability, pharmacokinetics, antiviral and immunomodulatory activity of VIR-3434 in healthy volunteers and patients with chronic HBV infection with HBsAg levels less than 1,000 IU/ml. The trial is designed to progress from healthy volunteers to chronic HBV patients in a staggered, parallel fashion with the goal of rapidly generating early proof-of-concept data in patients. Additional data will be submitted for presentation at an upcoming medical conference. A Phase 2 trial combining VIR-3434 with Vir's HBV-targeting siRNA, VIR-2218, is expected to commence in the second half of this year
Also to keep in mind....HBV very complicated and just KD alone isn’t enough to beat this virus. Consensus that a combo therapy is required to turn off HBV replication, eliminate current HBV, and boost immune system to where it can regain control of the body. Dosages, combos, and much larger and longer trials are going to be required (along with a BP to help foot the bill).
JNJ is way ahead of them already by at least 2-3 years.
Here are a couple interesting links showing JNJ's current interests:
https://www.jnj.com/innovation/quest-for-alzheimers-cure-treatment-why-one-company-refuses-to-give-up
https://www.jnj.com/innovation/innovating-global-tuberculosis-medication-treatment
Thoughts??
I want news out of JNJ as well, but the sheer amount of money they are pouring into the many JNJ-3989 trials already tells me a lot.
Next on Phase 2 launching pad is HSD or additional APOC3 trials.
Announcements maybe coming fast and furious this week as a prelude to next week’s conference call. Buckle up as the G forces are rising!
Jan 25, 2021 at 7:30 AM EST
PASADENA, Calif. --(BUSINESS WIRE)--Jan. 25, 2021-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for a Phase 2b dose-finding clinical study of ARO-ANG3, the company’s
PASADENA, Calif.--(BUSINESS WIRE)--Jan. 25, 2021-- Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for a Phase 2b dose-finding clinical study of ARO-ANG3, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with mixed dyslipidemia.
Javier San Martin, M.D., chief medical officer at Arrowhead, said: “Cardiovascular disease remains the major cause of death, even after advances in therapies that reduce LDL cholesterol. This highlights the need for new therapies that can help patients at risk for cardiovascular disease to optimize their lipid profiles and protect them from atherosclerosis progression and cardiovascular events. By inhibiting ANGPTL3, Arrowhead’s investigational ARO-ANG3 is designed to reduce triglycerides and decrease LDL cholesterol in patients with mixed dyslipidemia. We have been very encouraged by the clinical data from this program to date and look forward to further assessing the safety and efficacy of ARO-ANG3 in the upcoming Phase 2b study.”
Following FDA’s review of the IND, the company intends to initiate AROANG3-2001, a Phase 2b dose-finding clinical study in patients with elevated triglycerides and low-density lipoprotein cholesterol (LDL-C). The primary objective of the study is to evaluate the safety and efficacy of ARO-ANG3 in adults with mixed dyslipidemia and to select a dosing regimen for later stage clinical studies in this patient population. The study is designed to include a total of 180 participants in three cohorts. All dose cohorts will enroll in parallel, with 60 participants per cohort randomly assigned in a 3:1 ratio to receive ARO-ANG3 or placebo.
ARO-APOC3
Primary Purpose:
Treatment
Official Title:
A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome
Actual Study Start Date :
March 8, 2019
Estimated Primary Completion Date :
January 21, 2021
Estimated Study Completion Date :
January 21, 2021
All dose cohorts will enroll in parallel, with 60 participants per cohort randomly assigned in a 3:1 ratio to receive ARO-ANG3 or placebo.
- VIR is definetely cherry picking by just showing a small piece of the data cake. This piece is good but what with the other pieces? We'll see if they can beat us with duration and other components (beside HBsAg level).
I am really no scientist so my question could sound quite stupid: is it possible to compare this data anyhow with a clinical trial conducted bij Arrowhead in the past? I'm curious for that. I've been looking in the presentations and PR's on the ARWR website but couldn't find simular data (eight days after dosing) for ARO-HBV. I was able to find some pieces from ARC-520. I know this is the old platform but am I correct to state that ARO-HBV is quite "simular" to ARC-520? I found this:
"In a cohort of NUC-naïve, HBeAg-positive patients, best peak HBsAg reduction has been 99% (1.9 log) and the mean maximum HBsAg reduction has been 1.05 log through 15 days post ARC-520 treatment."
(Link: PR - September 24, 2015: Arrowhead Reports Peak Reduction in HBsAg of Up to 99% (1.9 log) After a Single Dose with Hepatitis B Candidate ARC-520 in Treatment Naïve Cohort of Phase 2a Study)
I also found this in the AASLD The Liver Meeting 2013:
"HBeAg levels declined by more than one log by day 4 and returned to baseline by day 43."
This is in chimps however, but it shows that a single dose of ARC-520 also reduces HBsAg within eight days to these levels.
I could be a moron and it's possible I don't understand the science. I'm sorry if that's the case! Will try to post links below.
“Arrowhead’s Targeted #RNAi Molecule, or TRiM™, platform utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting while being structurally simple. Learn more about the $ARWR technology here”
The purpose of these “like” posts is to demonstrate that there are a number of upper level folks amongst BP who are following this “little” RNAi company.... all who could be potential partners in the future.