Abivax, a clinical-stage biotechnology company developing novel therapies that modulate the immune system to treat chronic inflammatory diseases, viral infections, and cancer, recently announced promising results from its phase 2an maintenance trial in rheumatoid arthritis (RA) after one year of continued daily treatments with 50mg of its asset ABX464.

Out of 40 patients who enrolled into the ABX464 maintenance study, 23 patients have now reached the first year of treatment and all achieved at least a ACR20 score, with 19 and 12 patients achieving ACR50 and ACR70, respectively. The ACR20/50/70 measures a 20/50/70% improvement in the tenderness and swelling in designated joints and a 20/50/70% improvement in at least three important measures.

DocWire News spoke with Hartmut Ehrlich, Chief Executive Officer of Abivax and Philippe Pouletty, Chairman of the Board of Directors of Abivax, about these important and exciting findings.

DocWire News: Provide us with some background on yourselves.

Philippe Pouletty: So Philippe Pouletty, MD. Immunology by training. Biotech cellular entrepreneur. I spent 30 years in Stanford and Silicon Valley, and then the last 20 years in France to start and try to grow a successful biotech tech companies.

Hartmut Ehrlich: My name is Hartmut Ehrlich. Like Philippe I am also an MD. CEO of Abivax after several substantial positions in the industry. Started my career actually doing R and D in the Lilly Research Labs, after I’d been graduating from medical school. Then worked in clinical at Sandos in immunology, oncology, at the time when there still was a Sandos; so before Novatis. Then joined Baxter healthcare, initially as a medical director for Europe, but over time then grew into the role of the vice president for global R and D for the bioscience division. And after almost 20 years with Baxter, I got a call from Paris, from Philippe, basically asking me whether I would be interested in joining a new, to be founded, company in Paris. And the rest is I guess, history.

Talk to us about Abivax, and its mission.

Philippe Pouletty: So the history of Abivax is we started two biotech companies. One called PCOS, focusing on the science of mRNA, but not for vaccines, for moderation of mRNA and therapeutics. And another company, which was [inaudible 00:02:17] to develop a technology coming from strict research and University of Chicago, which was modulation of NKT cells. Then once these two young companies made some progress, we decided to merge them. Which became Abivax in 2013, which is when I gave a call to Hartmut to lead this newly formed company, which had the two interesting product candidates. And with Hartmut, we took the company public on the European stock market, Euronext, and have been growing the company together since then.

How prevalent is rheumatoid arthritis (RA), and what is its impact?

Hartmut Ehrlich: It is clear that rheumatoid arthritis is a very debilitating disease. It affects primarily the joints, but not only the joints, and from the prevalence, numbers are that it is really the largest chronic inflammatory disease that we are dealing with. So there are many more patients in rheumatoid arthritis, if you compare it to the other usual chronic inflammatory diseases like ulcerative colitis, Crohn’s disease, et cetera. Rheumatoid arthritis is about three times more prevalent than any of these diseases and there’s a high likelihood that anyone knows someone who has actually this disease.

Talk to us about the phase 2a maintenance trial which assessed the use of one of your assets on RA patients.

Hartmut Ehrlich: Yes. And I’m actually not going to start with the maintenance part. In chronic inflammatory diseases you are typically having a period of two to four month, which is called induction, where you are looking, does your product work in the patients. And if you see that it works, then you continue into the maintenance study. Because the goal, as these are chronic diseases, is not to provide a treatment, the effect of which lasts only a very short period of time, but for chronic diseases, you need chronic treatments that help patients over years and years.

And therefore, indirect development in these diseases, you typically do an induction study first. See, is there some response from the patients? And then you go into the maintenance part, which of course then looks at, are we going to see the efficacy even becoming better over time? With many products, you actually see, unfortunately, the reverse. That patients respond initially, but then are losing their responsiveness and therefore the maintenance studies are a crucial part of the development and the assessment of the capability of your drug candidate to actually help the patients in the long run, which is so critical.

And so we started our Phase 2A, which was a proof of concept study. We just wanted to see, is the product working? And so we had three study groups with 20 patient each. Hundred-milligram treatment once daily, a hundred-milligram of a AB464, then 50 milligram, 464 once daily, and of course the placebo. And after the end of induction phase, which in this study was a period of three months, the patients that responded and the patients that felt the treatment effect, they then actually wanted to move on into the maintenance study to see whether the positive data, that we had seen after three month, would actually even become better the longer the treatment lasted.

This is something that we have clearly seen in our primary indication. In our priority indication of ulcerative colitis, where we could clearly establish that ABX464, compared with all the other products in this space, offers the best one-year maintenance data. So in the long run, this is really the product of choice for patients. And that was the goal; to see whether we would see a similar effect in rheumatoid arthritis as well.

What are the clinical implications of these findings?

Hartmut Ehrlich: Well, the clinical implications around rheumatoid arthritis, of course, are typical problems that you have with your joints. It’s a disease that can actually cripple the joints in the absence of treatment. So the measurements that you have are: are joints swollen, are joints warm, which all would indicate ongoing inflammation, and most importantly, are the joints painful for the patients. And there are scales that have been established. Because of course, you’re not only dealing in rheumatoid arthritis with patients that have one or two joints affected. As always a number of joints that are infected by the disease and then you look overall, how does your product work from the period of reducing the circumference of the joints, which is due to the inflammation, and especially also pain, how movable are the joints for patients, et cetera.

And as I mentioned, this is via certain algorithms then going into scales, which tell you to what extent the patient improved from before. And what we were seeing already very encouraging activity after the three month of treatment, from the point of view of patients getting better. And we saw this even further improved, in the maintenance study where after one year we really saw outstanding results, from the point of view, as to how many patients saw this particular relief of their symptoms, the increase in the mobility of the joints, et cetera.

And the key opinion leaders that we are working with are clearly interpreting these results as not only interesting or warranted to follow up but as something that really might indicate that the treatment outcome, with a ABX464, could be really a benchmark going forward.

Philippe Pouletty: And that’s very much related to the novel, unique, mechanism of action of ABX464, which up regulates a physiological micro RNA, which you and I Rob, do have, and which in inflammation will play a natural break-role of inflammation. Whenever we have useful inflammatory reaction, after this inflammation that’s played its role, to eliminate bacteria for instance, then inflammation has to be slowed down and that’s what [inaudible 00:11:33] 13P4 does. And very importantly, it attacks on several key cytokine pathway in inflammation. And that’s a big differentiator from other drug candidates, or drugs on the market, which target a single pathway, for example, PNF has a cytokine.

And with these drugs, you have to push very hard on a single pathway to impact the overall inflammation. And that means they can be resistant to treatment, escape from treatment, and also side effects. Whereas with ABX464, it’s nicely, down-regulate several key cytokines, so that we have a very good safety profile established now on over 1000 patients. And patients will see the efficacy and remission long-lasting in contrast with other drugs.

That’s what we saw in ulcerative colitis; that’s what we’re seeing, although the results are not as extensive yet in RA, that’s what we see in RA.

What are some exciting developments coming from Abivax in the coming years?

Hartmut Ehrlich: Well, in 2022, there are a number of exciting events coming up for the company. Very soon, meaning in the next week or two, we will be able to provide the full analysis of the one-year maintenance data in ulcerative colitis. And I mentioned this for rheumatoid arthritis as well. And what we are seeing in rheumatoid arthritis actually seems to duplicate what we are seeing in ulcerative colitis. Because ABX464, in the induction, the onset of therapeutic efficacy is very rapid. And after the two month of induction treatment, we really have results that are on par with certainly the best molecules that are currently in this area.

But if we then continue to treat for the whole year, then we are seeing that, certainly in ulcerative colitis, the rate of clinical remission, which is the end-point that everyone is looking at, because that means essentially complete absence of symptoms and the clean endoscopy, that means that patients are having no longer major symptoms from the disease and also a clean endoscopy. And the percentage of patients that actually end up in clinical remission with ABX464, at this point in time, is higher than for any other product that is either on the market or in late-stage development.

These are not comparative trials, but these are trials that conducted according to very similar procedures and therefore this is a very, very, meaningful outcome. And the long-term efficacy of ABX464 is undisputed.

And this is what we are now going to establish for rheumatoid arthritis as well. The advantage that we have in ulcerative colitis is we have the face to be data in. And so we have a total database of patients treated in the disease, of roughly; let me calculate, around 200 and 285 patients. Whereas in rheumatoid arthritis, we are at an earlier stage. We have only been treating 60 patients at this point in time. So we don’t want to make too farfetched conclusions, but what we can say is that the efficacy that we are seeing in rheumatoid arthritis, and the pattern of additional activity during the whole first year of treatment, that is what we are also observing now with rheumatoid arthritis. And that makes us very encouraged about moving forward in these patients, and being able to provide therapeutic options that are not available for them at the time. And especially therapeutic management options or drugs that have a different mechanism of action. Because what very often happens, as Philippe mentioned, patients get resistant to treatment, and then you need to change to another treatment.

And we have seen, for example in ulcerative colitis, that patients that had failed on three or sometimes even four active drugs, biologics, antibodies, in these patients, that once they were put on ABX464…

You never heal this disease; you just provide symptomatic care. And in rheumatoid arthritis, we believe that we have the same opportunity to position the product accordingly, which would really be a good message for the many patients with this disease.

Philippe Pouletty: Now, of course, what these results also mean is that we have a drug candidate which can address multiple chronic inflammatory disease. You know, of course, the IBD disease with Crohn’s and ulcerative colitis and in rheumatology, won’t be probably only RA, but it could be Ocular spondylitis. Then there are a number of other chronic inflammatory disease in dermatology, which can be addressed. So that’s very exciting for us, that it’s a drug candidate which can broadly work on chronic inflammation for multiple diseases.