Dear @Nawab,
The current compassionate access program has ended, however we have plans to re-initiate compassionate access with an improved formulation. The data from the compassionate program is being published but can be found here. Please consult the Replicor website here to keep informed of clinical development plans.
I saw that the planned trials moved from Europe/USA to just France. Will it remain only France or US locations as well? I was really looking to sign up when the trials were open.
Dear @Albasil808,
We know many patients are waiting to enroll in the next clinical trials for NAPs. While the next phase IIA trials are planned to take place in France, follow-on trials required for marketing approval will expand the number of countries involved significantly.
Dear @availlant for phase 2 including the compassionate program there are already 3 test or trail done like proof of concepts, why still replicor is in phase 2A ? Is not the test done before also part of phase 2 ? And also dose it mean still left phase 2B and phase 3 ? in EU do we will have many place or country phase2A or B clinical trail other than France ? Like germents or Spain ?
Thank you
any plans to include Poland ?
Dear @lemlem,
Its a good question.
Actually we have performed 5 clinical trials and one compassionate use program.
Unfortunately, one of the unique challenges with NAPs have been their breakthrough nature, since we started generating clinical data in 2009 - these include 1st to target subviral particles, first to achieve HBsAg loss, first to stimulate high rates of ALT flares (and first to treat through these flares) and the first to achieve high rates of HBV functional cure and HDV cure. These results were initially viewed by skepticism by many in the expert community.
This is complicated by the complex nature of NAP biochemistry which is more difficult to grasp (even for experts in the field) than other approaches which we have seen fail.
Finally, we have had to work to improve and better understand how to use NAPs in the clinic against the back drop of a lot of other competing technologies (CAMs, therapeutic vaccines siRNA and antisense) which had the backing of the industry (and venture funding) but which have all failed to date.
So we have had to prioritize our clinical development to prove out the critical aspects of NAP technology (dosing, safety, efficacy with other agents and optimization of the clinical formulation) without having the resources flesh out the design of these trials to satisfy less important requirements for the approval process.
With the completion of the compassionate program, most (but not all) of the skeptics have been silenced and we are now planning the conduct of phase IIA trials specifically designed for approval.
The main aspect of this trial design includes control groups where NAPs are used alone and also using a dose of NAPs which we know does not work. This is a formal requirement to justify the single NAP dose to be used in larger phase IIB studies.
Dear @availlant
Thank you for taking time to answer our doubt as usually.so till date now replicor works to convince scientific community of hbv and now working for for FDA(phase 2 and Phase 3).hope things go well and with accelerated program hope to approve fast at end of phase 2 or first of phase 3.
Thank you very much
I accidentally came off way too aggressively before when I was talking about AI based first approaches but here is a thought that hopefully puts it a lot more succinctly
What about a team that uses a tool like this: https://www.klyne.ai/
To rapidly screen libraries of compounds for binding affinity to various HBV targetsāHBsAg, HBx, cccDNA-associated proteins, etc.āand then ran through high-throughput in vitro ā in vivo ā clinical prioritization based on those hits?
Iām wondering how much time could be saved by modeling stuff in AI services like that before moving to physical experiments. And it seems like there would need to be at least one person on the team thatās a machine learning expert to keep track of the various solutions that keep appearing. I keep seeing new stuff every week that looks like itās worth following through with
Hi @bob,
Great find and I think this could be a fruitful approach of filtering some components for specific activities.
However, this depends on the information we have so far. For example, as I understand, there isnāt a great model for HBx and it is probably got a fairly extensive unstructured region which is likely important for interacting with all sorts of molecules in the cell. Because of this pleotropic and pleomorphic nature, it becomes really hard to predict given the limitations in what we can supply the algorithm.
Not trying to poo-poo people from using new approaches, but there may be tricky barriers, which is why you might not hear about results from the community (not for lack of trying, but lack of progress).
Cheers,
Thomas
Hereās a new open source and totally free implementation that outperforms AlphaFold3: GitHub - jwohlwend/boltz: Official repository for the Boltz biomolecular interaction models
I see quite a lot of this, and although itās great that itās free and open source, it also means that anyone that wanted to use it would have to install it and host it until thereās third party providers, which is technical. So thereās no website you can just log in to like with the commercial software