Nucleic acid polymers (NAPs): targeting subviral particles to acheive HBV functional cure

NAPs do not need pegIFN to clear HBsAg or HDV RNA.

However, pegIFN is required to stimulate the T-cell function needed to eliminate integrated HBV DNA from the liver. This is not required for “cure” of HDV but is required for high rates of functional cure of HBV.

Becuase HBsAg normally interferes with the action of pegIFN, using pegIFN with NAPs gives a greatly improved immune stimulation with pegIFN.


dear availlant,

I am already on pegINF, send me NAPs so i can combine :slight_smile:


@availlant I keep on the reading this trail with intrest and hope. At times hope keeps us going. Allow me to ask, are you the only guys working on NAPs for HBV?

Also, are there other drugs already approved that use a NAP type of technology?..even if for different diseases?

Last, is TherVacB based on a NAP technology? If not, would you know the significant difference btn NAPs and the technology being applied by ThervacB? Based on what is publicly available or at your disposal?. Have tried digging in vain. Not sure if they have even started the human trials. Would you or any other person in this community of ours know?

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Yes NAPs are wholly owned by Replicor Inc. We are the only company developing this technology.

Yes NAPs do have activity against other diseases but the current focus on development is HBV and HDV.

TherVacB is a therapeutic vaccine based approach that will attempt to stimulate an antiviral T-cell response to help in the treatment of HBV infection. The difference between NAPs and therapeutic vaccines is that NAPs target the bulk of HBsAg (> 99.99%) whereas trials with previous therapeutic vaccines have had little or no effect on HBsAg.

I look forward to seeing how the TherVacB approach will work. It might be useful to have a different form of immunotherapy to add to NAP-based combination approaches.


Availlant, I am very impressed with your clear explanation of such a confused topic about CHB in today’s world.
Truly your knowledge and understanding of the subject is outstanding. I certainly will read more about the latest science, and I will follow you on this network very closely. Thanks again for your help and great contribution to this Community of people in needs.

Thanks for the feedback and sharing the real facts;
We all agreed that the future looks good by 2030 for the majority of us:

However; I though there will be some medicine that will cure 40%~60% of patients in 3-4 yrs…Like Replicor Rep2139 and others that are now in phase 2 trails…

By the way, I wonder if Replicor phase 3 trail started and when their data is expected??
I am very interested in participating their phase 3 clinical trials… not much info available on their website.



@Nass I think maybe @availlant could comment on this…I have read a number of useful updates from him about Replicor. Not sure if phase three you refer is REP 2139-Mg or weather they have more up their sleeves…

Hi Nass and CNN,

REP 2139-Mg is the final version of NAPs which will be taken through to commercialization.

Mature phase II trials for combination therapy with NUCs, RNAi and CAMs have proven that combination approaches with these agents cannot establish functional cure.

Current phase II data with REP 2139-Mg based combination therapy shows this approach delivers 78% immune control (no further therapy required) with 39% functional cure. These are in the most difficult to treat HBV genotype (D) where pegIFN very rarely achieves functional cure.

There is an ongoing compassionate use program with REP 2139-Mg in patients with HBV/HDV co-infection with compensated and decompensated cirrhosis who have either failed on bulevirtide or are not eligible for it. See here

This approach is allowing us to confirm the safety and efficacy of a once weekly SC injection of REP 2139-Mg in patients with the most advanced liver disease. This will allow us to open enrollment of our next clinical trials to a much wider population of patients with a very convenient dosing strategy.

Hope this helps.


Thanks Availlant
And thanks for your tireless research and dedication for a cure!
This is a very promising and probably will be one of the best treatment to come in few years. Please keep us updated when the clinical trials enrollment begin.
I guess next clinical trails are phase 2b or 3?


The best way to keep abreast of clinical development details is to ask to join our mailing list for press releases at

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Will do! Thanks

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Was reading another post about FDA rejection of bulevirtide and have seen your response. Is Bulevirtide or the drug rejected by FDA similar to REP 2139-Mg? Or what similar or different?

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Bulivertide is a peptide drug derived from a portion of the HBsAg protein involved in the entry of HBV (and HDV) via a specific receptor on liver cells (called the NTCP receptor). This drug provides a very efficient barrier to this entry mechanism in all hepatocytes but must be taken every day by subcutaneous injection. Unfortunately, in most patients there still remains a portion of HDV which is not impacted by this drug.

REP 2139-Mg is a drug polymer built from the building blocks of found in DNA (so very well tolerated and easily manged by patients). This drug has multiple actions:

  1. Binds to the host protein involved in the formation of HBV subviral particles (which is also used to envelop HDV virions during their formation).
  2. Binds to the hepatitis delta antigen protein involved in the replication of HDV prior to envelopment.

REP 2139-based combination therapy achieves universal HDV RNA loss during therapy and high rates of functional cure of HBV and HDV infections (no viral rebound when therapy is removed). The ease and convenience of a once weekly subcutaneous therapy of REP 2139-Mg for 48 weeks is now being confirmed in an ongoing international compassionate use access program.


When do you think Replicor start a trial in USA

Moving all Replicor/NAP talk to this thread.


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Welcome to the forum Kenya1961.

The best way to stay up to date on clinical developments is to subscribe to our mailing list at

Best regards,

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I will definitely Thank you!

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Hi all,

We are waiting for replicors NAP since it is only one therapy which has shown to reduce HBsAg and induce ALT flares.
My question is does it take into consideration highly mutating nature of Hep B or just targeted towards HbeAg + CHB?
Also eagerly waiting for replicors progress on NAP trials any update on timeline when is next trials starting and would there be one in US?. The results published are really promising and can work wonders as mono or combination therapy.
I really appreciate for all people working towards cure.


Hi Ash_Malhorta,

Nucleic acid polymers target a host protein in liver cells which is critical for the assembly of HBV subviral particles. These subviral particles are a critically important target since they represent > 99.99% of circulating HBsAg.

Because NAPs target a host protein, their antiviral effect will be the same regardless of HBsAg baseline (even > 125,000 IU/mL), HBeAg status, HBV genotype, the presence of HBV mutants or the presence of co-infections like HDV, HIV or HCV. This universal response has already been demonstrated in the 5 clinical trials that have performed to date with NAPs. Aside from the unique ability of NAPs to target subviral particles, one of reasons why NAPs are still the only agents to achieve high rates of HBsAg loss is that they act independently of any viral protein.

You are correct that the highly mutable nature of HBV is a considerable problem with many agents in development. It is one of the reasons why technologies which are critically dependent on the absence of mutations (like ASO and siRNA and CRISPR and others) have not succeed in clinical trials to achieve functional cure.

Some of the clinical data to date suggests that NAPs can eliminate HDV infection in monotherapy but this question has not yet been properly addressed and we need more data to understand this issue.

In the case of HBV infection, it is important to realize that functional cure is a two step process:

  1. Clear subviral particles so that immune responsiveness can be restored.
  2. Reawaken the immune system with therapies like pegIFN to restore immune control.

It is important to understand that while NAPs are very effective in achieving HBsAg loss, the currently available clinical data indicate that high rates of functional cure of HBV require combining NAPs with immunotherapy. Of course more clinical data is required to address this question.

There are two ways to keep apprised of developments at Replicor:

  1. Contact Replicor at and ask to be part of our mailing list when we issue formal press releases.
  2. Follow Replicor on Linked In here where periodic interim updates are posted.

Best regards,

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Thanks for the explanation Andrew! Really appreciate it. I know you are also up to date with TherVacB approach. Are they using siRNA as well for priming and reducing HBsAg or is that something else?
I know the vaccine will only work in absence of HBsAg so the critical question would be would the vaccine even work in Hbe negative CHB where usually HbsAg is high and not sure if mutants produce siRNA?