Is Cure coming in future?

Dear @void,

We are working to make REP 2139-Mg available as soon as possible. Unfortunately, I cannot comment on timelines.

@availlant

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I recently came accross Tune Therapeutics and their approach towards curing Hep B. It says :“Tune Therapeutic’s lead candidate TUNE-401 can epigenetically silence all forms of hep B”.

Preclinical data looks promising and they plan commence with clinical trials by end of 2024.

What are the thoughts on this approach?

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Hi Eddy,

In my opinion, this could be a great addition to our existing approaches. Indeed, a couple of other groups are also pursuing this (Chroma, and Epigenix). It uses a process that is already used by the body during clearance of acute HBV infection (cccDNA silencing) and ramps it up. I am hoping that it shows some activity in patients too.

Cheers,
Thomas

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After achieving a low viral load or undetectable hbv dna state Has anyone tried the approach of removing the infected liver and putting them on liver assisted devices and the person in injected with high doses of immunoglobulin , vaccine and antiviral therapy after a period a new and healthy liver is transplanted will this lead to complete cure

Hi @anonymous70,

Good question and I’ll assume we are putting aside the general shortage of donor organs needed by people all over the world.

My understanding is that people with Hep B who get (HBV-negative) liver transplants are given lifelong antiviral treatment because of the risk of reinfection and reactivation. This is especially important because of the immunosuppression that liver recipients need to be under to make sure that they don’t reject the organ. Metanalyses seem to suggest that immunoglobulins don’t change this (High-potency nucleos(t)ide analogues alone or plus immunoglobulin for HBV prophylaxis after liver transplantation: a meta-analysis | Hepatology International).

Together, this would suggest that this approach would not be an ideal way of inducing a complete cure.

@simone.strasser would love your input and/or corrections

Thomas

@Availlant I greet you. Wondering if there is any recent update about progressing to seek approval. And cure rate for NAPs currently. Like also, do we have any drug on the blink of breaking through? In 2025?

Dear @CNN ,

We are currently working to optimize the subcutaneous formulation of REP 2139-Mg so that it will work efficiently in all patients. When this is complete, we expect to continue registration trials.

The latest flavor of antiviral approach in HBV is the attempt at epigenetic modification (silencing) of cccDNA and intergrated HBV by three closely related approached by Tune, Precision Biosciences and nChroma. Unfortunately, like all siRNA and antisense before them, they are highly sequence dependent approaches. Thus, as has already been shown for siRNA and antisense in HBV, escape mutations for all these approaches will be present even before these therapies are given. More problematic is that these approaches do not efficiently target highly condensed latent cccDNA.

The patient community should be careful when looking at the clinical data coming from these new approaches becuase, like siRNA and antisense, the lack of specific effects of these agents will be hidden by their immunostimulatory properties (they are all essentially mRNA vaccines driving the expression of epigenetic modifying proteins in the liver with the ensuing transient inactivation of cccDNA). Evidence of this has already been shown in pre-clinical studies (ALT elevations in healthy animals).

@availlant

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