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Discussion about Mycludex, Replicor and others
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Discussion about Mycludex, Replicor and others

Hi,

    I wanted to keep a separate post regarding the latest discussions about the the following drugs.

GI 13020
Myrcludex B
Rep9AC'
ARC520
GS9620.

Could anyone post latest updates about above especially Myrcludex ?


23 Comments Post a Comment
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Avatar_m_tn
stef could you please tell me updates abput MYR
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Avatar_m_tn
http://hepatera.ru/?ln=en
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Avatar_m_tn
Myrcludex Development:

Maxwell Biotech Venture Fund’s Portfolio Company Hepatera Recruits First Patients in Phase 1b/2a Clinical Trial of Myrcludex B for HBV


http://www.rusventure.ru/en/press-service/news/detail.php?ID=11903

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Avatar_f_tn
Hello, everyone, some info about Myrcludex B trial:
Two patients, dose - 0,5 mg:
First patient: before trial Alt-300, in 2,5 month after beginning of trial Alt- 50
Second patient: before trial Alt-180, in 1,5 month after beginning of trial Alt- 73
This is all what I know for now.
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Avatar_m_tn
That's very good info. Do you know if they are on a combo, I remember someone was saying that they only took patients who were on antivirals already.
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Avatar_f_tn
Оnly naive patients are taking part in trial.
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Avatar_m_tn
Good news, but ALT fluctuates, so cannot be a reliable marker for success unless ALT is persistently normal. Mycrludex is supposed to prevent re-infection, so how to test that?
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Avatar_m_tn
Yes your right. But still it's a good sign considering studyforhope mentioned dosing was suboptimal.
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Avatar_f_tn
Unfortunately this is like this. We have to wait, reliable results will be in summer.
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Avatar_m_tn
Do you have data re the quantitative surface antigen levels in these two patients?
Also were they simultaneously with Myrcludex .5mg started on antivirals?

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Avatar_f_tn
Do you have data re the quantitative surface antigen levels in these two patients?
No, other information is available yet.

Also were they simultaneously with Myrcludex .5mg started on antivirals?
No, they don't. Only Myrcludex.
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Avatar_f_tn
Good news as expected.
Wont say much for now.
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Avatar_m_tn
The only place for such a vaccine would be in the setting of the Teplicor patient after his artificial surface antigen suppression ends, to stabilize and reenergize the vaning immune response against the surface antigen once the VL is very low and tne natural immune stimulation against this antigen becomes also low, leading to a slow recovery of the virus after month or a few years. If you look carefully at the replicor poster inset from the aasld2012 you will notice that only 25% of the patients of the first trial were able to hold their svr, hence no cure for most, back to square one. Now in the second trial they added immunostimulation with ifn or thymosin alpha towards the end. It remains to be seen if this will long term stabilize the svrs once all therapy has stopped for a longer  This is one of the most fascinating questions right now in HBV therapy, but we will have to wait for the answer for quite a while.

This is your post in other thread. But they save 90% of people cured hbv because of replicor. ? Why is this contrast ?
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Avatar_m_tn
It is the looseness of the term "cured" that is applied at a time when the final sustained response percentage is not yet known. The fact that the surface antigen is suppressed in over 90% percent of patients treated is fantastic, but by itself is only an expression of the fact that the release of the antigen particles from the infected cells is blocked, not that the cells lost their cccDNA.

This is not to be compared to the loss of surface antigen as it occurs spontaneously or under IFN treatment, which reflects loss of infected cells or cccDNA.

However, this highly efficient surface antigen suppression leads as a secondary effect indeed to an incredible effective loss of DNA later on by immune action due to the diminshment of the immune suppressive action of the surface antigen, this effect takes about 6 month to fair completion and needed an additional immunostimulatory treatment towards the end to truly lead to DNA UNd status of most patients.

But the critical question after this has been achieved is the STABILITY of this status once the treatment has stopped. The fist trial with the Rep9AC has shown, that an additional stimulation of the immune system is certainly required, since as reported at the AASLd 2012, only 25% of the patients in the first trial were able to sustain their respopnse over time, thus they were , sadly, not cured.

These were furthermore young, e antigen positive patients, that can be expected to have a dual Tcell response to core and surface antigen.

But the new combo with immunostimulatory agents looks more promising in this regard, we will eagerly look forward to the SVR rates under these new conditions, hopefully much better.

There is no doubt huge power in the Replicor approach, and their drugs work amazingly efficient in achieving almost perfect suppression of surface antigen release while in the body. But in the end it is the secondary effect of immuneclearance that will have to be sustained and the removal of infected cells has to be almost complete and coupled with such a  high efficiency remaining resident memory response both on the T and B cell level, that a respreading of the remaining HBV can be permanently blocked by internal forces without continued treatment.


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Avatar_m_tn
How about trying to vaccinate people after Replicor treatment to see if that can teach the immune system?

In any case what Replicor is offering is the best case scenario. And  it should be used now. Details can be worked out later. 25% holding svr is still a positive outcome. Those that loose antibodies they need to look more closely at peoples immune systems. But it can be done  only on a mass scale. 10-20 people control groups is nothing, not many scientists  can participate in such narrow trials to offer their ideas.
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Avatar_m_tn
Myrcludex B  trial 1b/IIa  results expected end of this year.....hope it will works..but after that how many phases more if these trail successful ?????
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Avatar_m_tn
Just have got a feedback from Myrcludex in Moscow. Not much news but at least something. I asked how current trial is going and when to expect the drug in the market. The answer is as follows:

"Current trial is going well, the drug is well tolerated, in case of successful trials and registration  we should expect the drug on Russian market in 2016."
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4652753_tn?1364585546
Hi,

I won't be able to give a lot of information so that may be a problem but this is what I have.  My workmate is bringing his father to the U.S. from Nepal to live with him as a dependent.  His father has long-term HEP B which he doesn't pay attention to.  Our insurance will not cover his father as a dependent so not sure what options there are given that he will need testing first before it is determined what the next step is.

I don't know anything about HEP B and am currently being treated myself for HEP C so not sure I have the energy to look into this but really want to help as much as I can since this is his elderly father.

Where should I instruct my workmate to begin?  What are the current drugs to treat HEP B and does it depend on genotype or is there such a thing with HEP B.

We are looking into medicaid for his dad since he cannot afford insurance.

Sorry this is so scattered, a little brain fog on my part.  Thank you for any information at least getting me started to help him.

Thanks!
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Avatar_m_tn
[This should make djxpress happy]
press release

Feb. 26, 2013, 9:00 a.m. EST
Arrowhead Data Demonstrates RNAi Candidate ARC-520 Silences Hepatitis B Virus
Single injection induces multi-log repression of viral RNA, proteins, and viral DNA

PASADENA, Calif., Feb 26, 2013 (BUSINESS WIRE) -- --Long duration of effect lasting over 30 days

--Regulatory submissions planned for Q2 2013

Arrowhead Research Corporation ARWR +10.05% , a targeted therapeutics company, today announced the publication of data demonstrating multi-log reductions in hepatitis B viral DNA and proteins lasting over 30 days after a single injection in animal models. This suggests that Arrowhead's RNAi-based candidate ARC-520 has the potential to treat chronic hepatitis B virus infection in a fundamentally different manner, with the goal of achieving a functional cure. The paper, entitled "Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection," by Wooddell et al, was published online ahead of print in the journal Molecular Therapy (doi:10.1038/mt.2013.31).

In the publication, Arrowhead scientists describe the use of a novel Dynamic PolyConjugate (DPC) technology to deliver small interfering RNAs (siRNAs) designed against the hepatitis B virus (HBV). This DPC technology incorporates a biodegradable peptide composed of naturally occurring amino acids and a liver-targeted molecule that is co-injected with a cholesterol-conjugated siRNA (chol-siRNA). In proof-of-concept studies, utilization of this DPC to deliver chol-siRNA targeting Factor 7 to non-human primates results in >99% knockdown of target gene expression and >80% knockdown for over one month after a single injection. Multi-dose studies in mice showed no diminution of knockdown activity or toxicity upon repeated injection at therapeutic doses. In transient and transgenic mouse models of HBV infection, a single co-injection of DPC with chol-siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect.

"This publication is important because it speaks to a specific product and a broader platform," said Dr. Christopher Anzalone, President and Chief Executive Officer. "These data suggest that ARC-520 could be a powerful therapy for chronic HBV infection, a disease with 350 million infected people worldwide and no cure. We are on schedule to file with regulatory authorities next quarter to begin first-in-human studies. During phase 1 we will be able to measure the drug's ability to knock down production of new infectious virus as well as viral proteins, including s-antigen, e-antigen, and the core protein that forms the capsid. The ability to substantially knock down these viral proteins is what is unique about ARC-520 and what many in the field believe will be necessary to revive the host immune response and potentially provide a functional cure, which no other current therapy can reliably do. More broadly, this paper reports on a delivery system capable of extremely efficient gene silencing that can be used for a variety disease targets."

About Arrowhead Research Corporation

Arrowhead Research Corporation is a clinical stage targeted therapeutics company with development programs in oncology, obesity, and chronic hepatitis B virus infection. The company is leveraging its platform technologies to design and develop peptide-drug conjugates (PDCs) that specifically home to cell types of interest while sparing off-target tissues, create targeted drugs based on the gene silencing RNA interference (RNAi) mechanism, and work with partners to create improved versions of traditional small molecule drugs.
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Avatar_m_tn
looks good.  I have an appointment with Gish next month.  I read that he is on the Board of this company - maybe I can ask him if he can get me included in the trial - fingers crossed!
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Avatar_m_tn
You can expect a phase I healthy human volunteers toxicity study to be required and completed, before a phase II proof of concept study with HBV patients will be started.

This press release was on the heels of the paper that was mentioned in the press statement. Everybody has full access to the full text. I would recommend reading the paper and then whoever has done that could participate in a detailled discussion about this approach, its promises, strength and pitfalls inherent to this therapeutic concept. Maybe a small discussion group can be formed from informed readers.
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Avatar_m_tn
The companys presidents remark seem to point to the possibility to start a phase I right away with HBV to see how capable the drug will be in reducing antigen and DNA levels. I wonder if the FDA would allow that considering the potential of liver damaging side effects due to the targeting to liver cells. But one can hope that that hurdle might be skipped, cutting out a year of development time.
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Avatar_m_tn
Looking forward to the discussion. I will certainly find and read the paper.

I've been reading tons of papers on precore mutants ( g1896a + c1858t ) it's somewhat draining me mentally. Hopefully reading about a potential cure would be a switch to the positive side.
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