Well noted @availlant , we as patient as very suspicious for every news because we believe highly respected and smart researcher do anything with reason , unfortunately that is not case in reality.
Thank you very much
Dear @lemlem ,
Patient frustration is certainly understandable as there have been a lot of technologies that were promised to achieve functional cure of HBV that have not done so. However, the fault lies with the early positioning of these technologies by industry before their true potential was investigated properly in the clinic. This is an unfortunate byproduct of companies who are public, where hype is always a part of the salesmanship involved in managing market perception of companies.
On other hand, basic scientists (some of whom are on this forum) are dedicated in their research for HBV cure and are more reserved in making statements about achieving functional cure with their research. Please be careful to not group these individuals in the former group.
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This is regards to the Precision trial in Hong Kong. The patient dosed in March is the same one as Precision released on the safety slide of their presentation at ASGCT Conference.
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Promising results at the lowest dose level. I hope virus eliminating results at the next ascending dose levels. Feeling quite relieved, excited and optimistic by seeing such a rapid pace of Precision Biosciences.
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Did you post the link to what youâre talking about?
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Any thoughts from the experts? @availlant @ThomasTu
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Dear @Mike2 ,
Very mild HBsAg reductions as expected. These approaches exert moderate stimulation of innate immunity in the liver like all mRNA vaccines (which is what is driving the bulk of HBsAg reduction here) which persists for many months after the administered dose. The persistence of these mild HBsAg declines âafter treatmentâ is still occurring under the influence of this stimulation (just like Gal-NAc siRNA) and will ultimately rebound in most patients.
Patients with < 1000 IU/mL HBsAg should never be allowed into a trial like this as it really gives false postive results not applicable to the HBV patient population in general.
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Hi @Mike2,
Thanks for raising this press release. Essentially, itâs all consistent with my previous comments on this technology, though itâs good that they have shown it to be relatively safe in the short term.
As @availlant, the reductions in HBsAg are relatively minor when compared to what we need to achieve to induce a functional cure. Presumably they will be working on ways to improve the effect size.
Thomas
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Dear @availlant,
These are the resutls from the lowest dose of PGENE-HBV. They are moving to an escalating dose. Do you think that the escalating dose will make a lasting difference?
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Dear @Nawab ,
Dose escalation of PGENE-HBV has already been shown to have no important effect on HBsAg decline. They may try to do further dose escalation but I expect no real improvement in HBsAG response and an increased risk of side effects from TLR 7 stimulation (which is the primary mode of action of PGENE-HBV).
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Dear @availlant,
Isnât surprising that all the drug candidates show very promising results in preclinical development but dismal outcomes in clinical trials? Precision biosciences reported 99% antiviral resutls in preclinical development but as they moved to trials, there was no such response. And it is almost the same case with all drugs. Why?
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Dear @Nawab ,
This disconnect between animal data and clinical data is easily explained:
In the mouse models used we have three confounding issues:
- Mice respond differently to the immunostimulatory effects of antisense, siRNA and mRNA vaccines (PGENE-HBV, TUNE and nChroma compounds in development). Effects in mice are stronger than in humans.
- Dosing of these agents in mice is different than in humans (much higher in mice) to get the sequence specific effects.
- Mouse models used do not have any HBV genetic diversity. This is present in humans and defeats any sequence specific approach.
So when compounds from these animal models are uses in humans, we are only left with the residual immunostimulatory effects of these oligonucleotide-based approaches - which have only mild to moderate effects on reducing HBsAg. Hope this helps.
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Hi @Nawab,
Great question. Such is a clinical trial. The majority of ideas die at the preclinical level. Those that make it further sometimes fail to yield great results. That is why it takes a longer time and a lot of money to go from development to public consumption of such products. Some companies donât want to invest, knowing they might fail and lose their money. It is a complex and expensive process. I wish it were a simple, easy, and straightforward one.
This is just my opinion on the subject. Best, Bansah1
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Dear @availlant
PBGENE-HBV liver biopsy results showed inactivation with indels of viral DNA. Does it not confirm some element of gene editing? Do you think this gives some hope?
Thank you for your opinion.
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Dear @SR123,
In the patient from cohort 2 (patient 5) described in the press release, there is no dobut that some of the integrated HBV DNA has become edited. Whether this really leads to inactivation of integrated HBV DNA in the patient is not possible to prove by this kind of analysis.
However, is also certain that a the majority of integrated HBV DNA will escape the editing process, both because of the inefficiency of the editing process and also because some of the integrated HBV DNA will contain escape mutations preventing CRISPR targeting. Also, selection pressure from the CRISPR effect (which lasts several months) will ensure that any new integration events are with HBV DNA with escape mutations.
The most important issues to be mindful of are :
- Baseline HBsAg in the patients enrolled - many have very low levels of HBsAg (which is not a good reflection of the global average).
- The effect on HBsAg. A 50-60%reduction in HBsAg is no better then what is seen with NUCs or pegIFN in monotherapy. This is most likely coming from inactivation of cccDNA from the immunostimulatory effects from this mRNA vaccine like drug.
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Thank you for always responding. We really appreciate you in this community. Looking at the small data set they have though, IF the HBSAG doesnât rise in the long run and stays well below baseline (not functional cure) would that not be something to build upon? For example patient 1 at the smallest dose 0.2, is about 50% less hbsag 5 months after their 3rd and final dose. The reason im saying this is because other clinical trials using different investigational drugs (sirna, aso) , the hbsag rose quickly after stopping therapy, nowhere near 5 months and thats at the lowest dose. So if at higher doses it drops hbsag to under 100 and stays there without coming back up wouldnât that be something that can be further investigated with other latter treatments that may produce FC?
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Dear Thomas,
Thanks for holding the Forte.
Is it true that Beijing has developed a functional cure for hep B? Is so, can we discuss the veracity without medical bias?
Thank you always
@Pat Iâm assuming youâre referring to this? https://firstwordpharma.com/story/6321087
I donât know anything about that drug, but it seems like itâs a type of interferon. The existing interferons sometimes achieve hep B functional cure, but the cure rate is not high. Do any @ScienceExperts know how this one compares to Pegasys?
It is a âlook-alikeâ to Peg-alfa 2a
China approves worldâs 1st domestic drug for hepatitis B cure
Published : October 14, 2025
Ref: China Daily
- China has approved Pegbing, the worldâs first domestically developed drug aimed at a functional cure for hepatitis B, according to China Daily.
- Pegbing, developed by Amoytop Biotech in Xiamen, is an injectable treatment intended for use with antiviral medication to achieve sustained clearance of hepatitis B surface antigen in adults with chronic hepatitis B.
- The Chinese Foundation for Hepatitis Prevention and Control called it the first global market authorisation for a drug targeting functional cure, marking a new stage in the fight against the disease
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