Abivax SA (AAVXF) CEO Hartmut Ehrlich on Q4 2018 Results - Earnings Call Transcript

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Earning Call Audio

Abivax SA (OTCPK:AAVXF) Q4 2018 Earnings Conference Call March 15, 2019 9:00 AM ET

Company Participants

Hartmut Ehrlich - Chief Executive Officer

Didier Blondel - Chief Financial Officer

Jean-Marc Steens - Chief Medical Officer

Conference Call Participants

Dylan van Haaften - NIBC

Thomas Guillot - Kepler Cheuvreux

Hartmut Ehrlich

Yes. Thank you, operator, and good morning, good afternoon, ladies and gentlemen. So my name is Hartmut Ehrlich. I'm the CEO of Abivax. And with me are Didier Blondel, our Chief Financial Officer; and Dr. Jean-Marc Steens, our Chief Medical Officer. So we are glad that you took the time out of your busy schedules to get an update on the latest news on Abivax focusing on, first, the six months results, the six months interim results of the 12 months maintenance study, which represented as an all planner during the 2019, ETO conference in Copenhagen last Friday. And secondly the 2018 full year results of Abivax, including a portfolio update. And with this, operator, could we please move to Slide No 3?

So I just wanted to give you a brief background on ABX464, especially around the potential in inflammatory diseases. The molecule is coming from the proprietary Abivax library of compounds, which was put together with the buyers to modulate RNA biogenesis and the library by now contains more than 2,000 molecules. ABX464 is a small molecule. It’s a quinoline that is administered once a day as an oral capsule. It is a first-in-class molecule with a novel mechanism of action, which is based on the selective upregulation of an anti-inflammatory microRNA specifically miR-124.

In more than 200 healthy volunteers and patients, ABX464 has shown a very good safety profile after the administration, and the anti-inflammatory effect was confirmed in the Phase 2a proof-of-concept study. It was an induction study in patients with ulcerative colitis the top-line results of which we reported in September of last year. And of course, we are going into more detail, especially around the results -- the encouraging results of the maintenance study.

But before we go there -- just to reinforce that this is a disease area, inflammatory diseases with a very high level of medical need and also very large market sizes, so just a first indication ulcerative colitis alone is around US$5.7 billion. But if you look at the total market size and inflammatory diseases, and this includes neuro-inflammation, neuro-inflammatory diseases like multiple sclerosis and Parkinson’s, if you consider that. Then the total market at this point in time is greater than US$70 billion.

And so with this short introduction, Dr. Jean-Marc Steens, our Chief Medical Officer, will walk you through this specific data.

Jean-Marc Steens

Thank you very much Hartmut, and good morning, good afternoon, everybody. So I will start on Slide 4, reminding you how the breakthrough in the mechanism of action actually was leading us to test this molecule ABX464 in a preclinical model, which lends itself to IBD both Crohn and colitis in the Dextran Sodium Sulphate preclinical model.

And you see on this slide, on the left, how the mice only received the [indiscernible] irritants, how the black squares gone down very rapidly because during the severe colitis, which is induced. And actually these mice are dying at day ten. And that's very well understood when you look on the right hand side the intestinal damage, which is caused the left part of the histology, you see that is a flat structure with an influx of immune cells in the submucosa. And of course that explains why there is no absorption of any liquids, fluids nutrients at all, and that explains why these mice are [indiscernible]

In contrast, when ABX464 was as much administered together with these potent irritants, we see a normal intestinal structure explaining why these mice are doing well over the 65 days experiment. We shared this data with ECCO leadership -- European Crohn's and Colitis Organisation leadership, who will recommend this to take 464 in patients with ulcerative colitis in a clinical trial.

On Slide 5, you have the study design of this first proof-of-concept study in patients with moderate to severe ulcerative colitis. And these are patients who are failing or intolerant to their drugs and they were initially randomized to receive either 464 as an oral capsule 50 milligram, oral capsule once a day or placebo for an induction phase of eight weeks with endoscopy performs a day zero and day 56, at the beginning and at the end of the induction phase. The study included central reading of the endoscopies. So the endoscopy was applied have no idea whether it was a day zero, a day 56, and no idea weather, of course, patients had received [indiscernible] and placebo.

And you can see on the slide the study endpoints, which are commonly used in this type of study. And patients were then, after this induction phase of eight weeks, patients were subsequently enrolled in 52 weeks open label maintenance study where they could receive the drug in an open-label fashion and an active drug, of course, ABX464 as a single dose 50 milligrams in open-label. Today we're going to look at again at the eight weeks induction phase data, but also, as I presented last Friday, the interim analysis of the first six months of the maintenance phase.

Let me move to Slide 6. And of course the primary endpoint for this first time that this drug was being given in ulcerative colitis patients with safety. And we can conclude as an adverse event profile was very similar to the one observed in our HIV program, which totals more than 180 patients.

AEs in this study as well designs for grade 1 to 2 consisting of some nausea abdominal cramps and headaches, which were transients of nature [indiscernible] for a few days and did not leave patients withdrawing from the study. Of note is that there were four inspections of grade 1 or 2, and I'll detail them there was one case of rhinitis, one case of sinusitis, one case of [indiscernible] and one case of laryngitis that again is with grade 1 or 2s, so no serious [indiscernible] and no severe infections, which is, of course, an important consideration in the therapeutic area here. And we have also -- on top of that, we have to also report that nor in this study, nor in the previous studies, which again accounted for more than 180 patients, have we seen any case of lymphopenia, neutropenia nor any severe infections so far.

On Slide 7, you see the efficacy endpoints, which all, first of all, showed in a very consistent way, the very favorable outcome for ABX464. And we show here now the data from both the [indiscernible] analysis and intense to treat analysis. And you can see that in terms of clinical remission, which is the most important endpoint for life insurer and by regulators, you can see that the delta between 464 and placebo is in excess of 20%, which is really a very high percentage, of course, we have to be careful, it's a first study, it's a Phase 2a study, but still to reach that 20% -- more than 20% delta between active and placebo makes the thing that it did confirm the future studies. This would be extremely promising for this confront.

We also see that some endpoints such as endoscopic improvements and that's what was called previously because of healing, but in the new terminology is now endoscopic improvement. That's also total and part of Mayo score, we'll reach statistical significance. And to reach statistical significance in the Phase 2a proof-of-concept study is quite rare because of the small percentage, sorry, the small sample size, of course, of these studies. Obviously, you'll also see Faecal calprotectin going down and miR-124 going being overexposed. And we're going to go into more detail in the next slides around a number of these endpoints.

So if you go on Slide 8, on Slide 8, you see in terms of Total and Partial Mayo Scores. And we look, especially in the Partial Mayo Score, where you have multiple endpoints compared to the total Mayo Scores. The Total Mayo Score comprised endoscopy plus the frequency of these tools, the presence of blood in this tools and position assessments, whereas the partial, so you have only two time points there at day zero and day 56, where the partial Mayo Score has weekly assessment, because it does not include endoscopy.

And the feature which we see here and especially, when moving into the sub-population of biopsies refractory is that you can see the curves really diverging from both all patients, but especially even more for those who are bounced refractory from in the Partial Mayo Score from two weeks onward, which leads us to make the hypothesis that definitely based on these data and hopefully being confirmed in largest studies, we could see a false onset of action of these drugs in these patients.

If we move to Slide 9, miR-124 which, of course, we're going to come back later on from our mechanism of action how miR-124 is a cornerstone and has been the major breakthrough in understanding how this molecule works. Well, you see that the patients in -- when you take blood from the patients in this study at day 28, you see, the patient who have received 464 in red and at day 56 you see them in red again. You see how they have a full induction of expression of miR-124, which is much higher than those were under placebo. Similarly and that’s quite also again reassurances that you don't see that only in the blood, but, of course, the disease happening in guts the just when you take retrobiopsy you see again at day 56 and over expression of miR-124 in at the rectrobiopsies.

So we can move now. And so this was for the induction phase. And this data has been already communicated a number of times. But now, let's move on to the maintenance phase. Why is it important to have maintenance phase data? Because -- this is chronic disease and chronic disease deserves a chronic solution. And so despite the fact that, of course, there are many drugs available that we see, unfortunately, that's for a number of these drugs are patients lose their response after six to 12 months. And so showing that, our drug indeed has the durability of a sec is of paramount importance for patients in this disease.

We have cumulative exposure of ABX464 for 19 patients with a minimum of eight months and the maximum now over 15 months. And today we still have 19 out of the 22 patients who initially were enrolled in this maintenance study, 19 patients are still in this study and we present you the data for the first six months open label 50 milligram 464. Of course, we cannot talk about Total Mayo Score here at six months because the next endoscopy is planned at month 12. So we report here on safety on Partial Mayo Score and of calprotectin levels.

On safety, we can conclude there was no additional safety concerns during the course of the maintenance study. This has been obviously reviewed by the DSMB at frequent occasions and it is in line which was observed during the induction phase.

On Slide 11, you're going to see the -- both the Partial Mayo Score and Faecal calprotectin. Let's concentrate first on the left, the Partial Mayo Score, where you see the six months time points on Partial Mayo Score. The top bars are the ones for patients who initially were on placebo during the induction phase. So that enters the maintenance phase after having received two months of placebo. And of course, no surprise that their Partial Mayo Score is higher as day zero of the maintenance phase. But you see that it's doing down in a very significant way when you have a 68% decrease of the total -- of the partial Mayo Score over six months for patients who started initially on placebo. The lower bars are for the patients who were originally in the active had received already 464 for two months during the induction phase. And there you see not only that the affects is maintained, but that it's still improving with the further 36% decrease of the Partial Mayo Score resulting in 76% from day zero of the induction phase. So in terms of Partial Mayo Score, we definitely can conclude that there is not only a maintaining of durability of the effect --effects, these improves overtime along with the patients are on the drug.

When it comes to Faecal Calprotectin -- the Faecal Calprotectin data, they're even more interesting is to see that, again, you see patients either -- are the patients who started journey two months with placebo only received active drug at day zero of the maintenance phase and lower dose who are already on active drug during the induction phase. And what you see is that actually these patients reach levels of Calprotectin, which are very close to normal levels. They are between 50 and 80 microgram per milligram, which is really with -- very close from the range from normal ranges. So starting from very high levels going down to this one, which definitively is an expression of why these patients indeed are improving.

So this is for the six months. The nine months data we're going to present during our presentation. As I told you we've presented six months data last week at Copenhagen, at ECCO. We've had received the nine months approval for an oral presentation at DDW in San Diego next May. And we have also resubmitted and received regulatory and ethics approval of -- for an extension of the maintenance study allowing patients to receive 464 for a second year at the end of their first 52 weeks. And the first patients started this first -- this one year extension last January.

So we move to Slide 12, in summary, I hope you will agree with me that the data from this new candidate drug with the new mechanism of actions may benefit patients with ulcerative colitis. The safety and efficacy, both, during induction and six months open label interim analysis of the maintenance phase are promising and warranted further clinical evaluation.

On Slide 13, what are the current activities now? Well, of course, based on the Phase 2a, we have been submitting in a number of countries including the European countries and Canada, the protocol for our Phase 2b, which will be run in the same patient population with moderate to severe ulcerative colitis in a much larger number, 232 patients, we're going to evaluate different doses as well. And so that study is rolling, has been submitted to a number of regulatory agencies.

In terms of next indications, we are submitting Phase 2a protocols in Crohn’s disease and rheumatoid arthritis. And for Crohn’s disease, of course, they had the same preclinical model is valid to go into that. And we have very attracting preclinical data from rheumatoid arthritis, which have been welcomes by clinical investigators. And therefore, we are in the process of submitting of Phase 2a to [indiscernible] in that indication.

So I'll close here on the clinical part. I hand over to Hartmut to discuss mechanism of action, which was of course the major breakthrough of last year.

Hartmut Ehrlich

Yes. And as all of you know these data that published about two months ago in the Scientific Reports of Nature, we have summarized for you what is going to happen. So on the left side, the graph shows what is happening in the absence of ABX464 sort of in -- under normal physiological conditions, the Cap Binding Complex, the CBC, which basically ensures the quality control and splicing of a number of mRNA's is really not able to slice one specific RNA and this is a long non-coding RNA, which contains miR-124, the sequence of miR-124. And as a consequence, this long non-coding RNA essentially stays in the cytoplasm is being, sorry, stays in the nucleus, is being degraded, and the miR-124 molecule the sequence is not being released.

By contrast, as shown on the right part of this slide, when ABX 464 binds to the Cap Binding Complex, and with this binding induces a conformational change the slicing of this long non-coding RNA is promoted. And as a consequence, miR-124 becomes available in the inflamed tissues to actually exert it's anti-inflammatory actions through the reduction of pro-inflammatory cytokines like TNFα, like IL-6 and it's receptor like MCP-1 the monocyte chemoattractant protein that's also called CCL2. And as a consequence, the break on the inflammatory responses is applied, and the system turns to an anti-inflammatory stage.

I would like to leave it here, and answer any questions related to the mechanism that you may have during the Q&A session. And with this, if we move on to Slide #15, we are shifting gears and talk for a short while about ABX196 in Hepatocellular Cancer.

ABX196 is a glycolipid that we licensed in from The Scripps Research Institute a few years ago. And we are now preparing the first clinical trial with this molecule, with this immune enhancer in Hepatocellular Cancer. Why Hepatocellular Cancer? Hepatocellular Cancer recently became a target for immune biological treatments and especially for checkpoint inhibitors. The first molecule that was licensed there was Nivolumab. And what I've summarized here on this slide, the outcomes of a clinical trial with Nivolumab, which in the meantime, has been confirmed not only another Nivolumab studies, but also with additional checkpoint inhibitors like pembrolizumab. And what you're seeing, if you're taking sort of your average HCC population, if you treat these patients with Nivolumab, there is overall about a 20% response rate.

Now that may not sound like a lot. It means that you have to treat for patients to find the response in one, but the median durations of these responses are much, much higher than they’ve seen in the past. And this actually is the reason that the FDA accelerated the approval for Nivolumab based on the -- based on the duration of these responses. But you still see that there is a lot of room upwards from the point of view of treatment outcomes that can be envisaged. And if you think what checkpoint inhibitors do, they basically block a signal on cancer cells that tells the immune system do not eat me. And so, with the checkpoint inhibitors you're basically making tumor cells more susceptible to the attack of the immune system, but there is no intrinsic enhancer for the immune response in this kind of a treatment regimen that is relying solely on checkpoint inhibitors.

So if we move on to Slide #16 that is the rationale why we are going into this indication. As I've shown you , the disease is devastating rapid mortality, which you just see, if you look at the prevalence of HCC, for example, in Europe with 77,000 cases, 65,000 new of them. You see that the average survival time is clearly less than 10 a year. And this is currently represented in sales that are in the range of $200 million, sorry $400 million, but that was clearly before the checkpoint inhibitors were introduced. Now with our molecule, which is a potent immune response activator, we have seen in a number of preclinical models that there is a survival benefit and a benefit, if you look at the infiltration of the liver et cetera. And the liver -- and that's an additional rationale for using ABX464, which is in a liposomal formulation that specifically targets the deliver. And so after a successful pre-IND, with the FDA, we are planning to file the IND in the next 4 to 6 weeks so that we are able to start this clinical trial in the U.S., the principal investigators from The Scripps Clinic, so also from La Jolla. But plus three additional sites in the southwestern part of the U.S. in the first study and patients with Hepatocellular Cancer. So that's a very important milestone for us going forward.

And with these few comments, I would like to introduce again, Didier Blondel, who will walk you through the key company facts and specifically the financials for Abivax.

Didier Blondel

Thank you, Hartmut. Good morning, good afternoon everyone. So I'm Didier Blondel, the Chief Financial Officer at Abivax. And I will first drive you through a kind of included, general reminder of what is Abivax today. Abivax is five years old. It’s a listed company since the 2015, on Euronext Paris. I’ll show the structure for around 10 million shares for the company as on the two major components, Truffle Capital, which is holding 47% of our shares by the end of 2018, and float for 45%.

We’re a small sized company, 25 people, and that’s since almost the inception of the company. Half of the team is in Montpellier, where we have a cooperative lab with CNRS. For those who don't know, the CNRS will take kind of equivalent of NIH for the French organization, and half of the team is located in the head office of the company in Paris. We are obviously R&D driven. So you see that most of our team, obviously, is in R&D, but we see ID that with small and minimal team, we’ll be able to leverage external resources and expenses for the company. And we think that with the highly skilled and seasonal leadership team of the company, we can do that. We know how to do that.

In terms of cash, but I will come back to that more details in next slide. We are ending up 2018 with certain million euros cash in hand.

So going to the next slide, which is reflecting the key figures of the company, which is again of the key financial indicators of Abivax in 2018. So first, let's say on the P&L side, so we're ending up 2018 with the loss of EUR15.8 million. No surprise we are biotech and we are -- we have high R&D expenses, which, I explaining, why we have this plus is increasing, which is explained by the fact that our R&D costs are increasing between 2017 and 2018. And this is coming both from the majority of the portfolio, and also from the fact that we have also decided to invest in a very disciplined way in ABX464, the truly inflammation as well as in our research lab and research activities. And ABX464 is representing almost 70%, 69% of our R&D investments in 2018, and our research costs are 23%. So it's giving you this -- let’s say overall figure on the where we are investing at Abivax. We also pay attention to keep our G&A at a level that is through our [indiscernible]. So we’re a little company so obviously G&A relating to that. But as you can see, we are trending towards 20% in 2018 and probably even lower in the future.

And maybe one comment on the line of revenues. In France, and I will come back to that later when I'm talking about the cash of the company. We're benefiting from -- through, let's say possibilities options, which are the research tax credit, and the Bpifrance funding.

So research that credit is reimbursement of costs by the value French state based on the level we're doing -- of investment we’re doing in R&D. So this is, obviously, increasing between 2017 and 2018 because our R&D costs are increasing. And Bpi funding is a program that we are in place since the beginning of 2017 for five years, where we get support from the Bpifrance Public Bank to scale up our R&D and our research activities, especially in the RNA biogenesis in [indiscernible] So this is also explaining why we have EUR5 million over used in 2018.

As Jean already mentioned what headcount was, it doesn't move between 2017 and 2018 almost. And cash, our cash situation is moving from EUR17 million by the end of 2017 to EUR13 million end of 2018. So the explanation is obviously coming from what we're spending, especially in R&D, and this is reflected in the net loss. But also important to mention that in 2018, we were able to sign an agreement with Kreos Capital. That's [indiscernible] loan, which is 80% head bond and 20% convertible bonds. This agreement was signed for EUR20 million. We had the first growing -- the first tranche exercise during summer time 2018 for EUR10 million. So that's been why our cash is only reduced by EUR4 million in 2018. But also important to mention, and even I think it was in the press release we have issue this morning that we have well been able to signed an amendment to the Tranche B so that this fund be now is becoming available to Abivax. So there is EUR12 million more to come. That would have to come before mid-July 2019 and that can be triggered by a device once we have completed the first regulatory and its approval in the country for Phase 2b study in ulcerative colitis.

So it’s the available funding up to EUR35 billion is enabling us to sustain operations for 12 months until Q1, 2020 and EUR35 million. And I think you already saw that in our press release already upfront by the current cash by the quantity of the Kreos agreements that I just underlined a few minutes ago. By the equity line, the real impact of the equity line that we have been restricted our shareholders, with different shops size would be around EUR7 million, and obviously, the recurring [indiscernible] funding that we are doing every year that is counting for EUR5 million. We say that our cash spending level was EUR1.5 million per month in 2018. Obviously, this will be more in 2019 because as you heard, we are starting Phase 2b in ulcerative colitis to Phase 2a is [indiscernible] and incrementally that prizes and an oncology study on ABX196. And obviously, the cash spending will be accelerating in 2019 onwards.

So without further due, I'm going to hand it over to Hartmut.

Hartmut Ehrlich

Yes. Thank you. Thank you, Didier. So I think we're going to go into the Q&A. And I wanted to ask Lupa to please open the lines for questions.

Question-and-Answer Session


Thank you. [Operator Instructions] And your first question is coming from Dylan van Haaften from NIBC. Please go ahead.

Dylan van Haaften

Just have three short questions. Obviously, we spoke about the data before. I was just wondering how you're going to power the Phase 2b? And would that be sort of aim for significance at 8-week clinical mission? And the second question is on if you had any patients in this trial that were refractory to tofacitinib? Or you're going to include these patients in the Phase 2b? And the third question is could you maybe frame the rate of inflammation against normal grade 1, grade 2 rate of inflammation for TNF and JAKs? Thank you.

Hartmut Ehrlich

Okay. So it’s -- your first two questions, but you may want to repeat your third question because I didn't catch it. So this -- the Phase 2b study will be a study, which will have a primary aim to look at optimal dose for going into Phase 3. And we're going to look at 25 6,100 milligram versus placebo. And so that it will be powered, of course, to determine which dose we're going to move forward. So that's the primary, and of course, that will be done at eight weeks based on the various endpoints, including clinical remission, of course. In terms of patients' refractory to JAK inhibitors, yes, we did not include them in our Phase 2a that is because during that time, the JAK inhibitors were not licensed yet, but we're going to include them those who were refractory or intolerance to position it in our Phase 2b study. Of course, it will always try to size to have an equal distribution of the refractory to drug a, drug b, drug c [indiscernible] an overwhelming participation of one group versus the other. And so, Dylan, if you don't mind repeating your third question?

Dylan van Haaften

Thanks for the answers first of all, Hartmut. Just the third question was on the rates of inflammation. I think you mentioned some, herpes simplex and rhinitis. Just wondering what kind of levels of inflammation of the patients participating in the trial you would see in a typical TNF or JAK trial?

Hartmut Ehrlich

Well, we know that there's a number of these other compounds have black boxes based on their adverse event profile. And of course, these are adverse events don't happen in a high frequency, but still it was deemed serious enough and these are serious infections where so far what we have seen a grade one, grade two minor infections. So that's the differentiator. Second, we have not seen any serious infections. Yes, fortunately. But again, of course, you need large sample sizes to determine that potential level of a serious infection. But I would also want to stress that we are basing our first assessment here, not only on the Phase 2a study, but also on our day-to-day of patients, which now including the Phase 2a have more than 110 patients who have received ABX464. For now some of them, sorry, more than 200, 210, I'm sorry -- more than 210 patients. ABX464, with some of them having received the drug now for more than 15 months. So that's why we based on our conclusion at this stage, but of course, as we know, in the clinical development, we have to go for a large numbers and that's why we go into the Phase 2b as well.


[Operator Instructions] And your next question is coming from Thomas Guillot from Kepler Cheuvreux. Please go ahead.

Thomas Guillot

Two, if I may. First, on your rheumatoid program, what that the super -- your development into this seed whether than another inflammatory disease and it'll be neuro-inflammatory disease such as multiple sclerosis. What has driven the decision? That was my first question. My second question, regarding the level of financial expense, you expect in 2019, with the first tranche of your loan with Kreos, what should we expect on that side? Thank you.

Hartmut Ehrlich

So let me go into your first question, and Didier will answer the second one. So what triggered our decision to go right away into rheumatoid arthritis, I think there are three reasons for me to mention. First of all, it's the general anti-inflammatory effect that we have seen with the molecule, and are any reason inflammatory disease, which -- and this is the second point -- which is actually treated, as you know, by a number of molecules, for example TNF alpha. That are also used for treating ulcerative colitis. And here clearly the sort of the final tranche of the mechanism, when it comes to inflammation, is very similar between RA and ulcerative colitis. But if other beyond that, and I think it's important to stress that why RA now and why not neuro now? We have exciting preclinical data around the effect of all molecule in rheumatoid arthritis, which we do not yet have in the neurological inflammatory indications. The reason that we are stressing them as well and it's actually coming from two reasons. Number one, our molecule in contrast, for example to the biologics, is able to penetrate the blood brain barrier. And for that reason we are having the molecule now in two preclinical models, one for Parkinson's, one for multiple sclerosis. And I think we can also easily imagine a couple of additional indications that we are tackling pre-clinically. And if we see the desired effect in these models, we would also, of course, think about bringing the molecule into these particular diseases. I hope that that clarifies the reason for decision making. And Didier will address the second question.

Didier Blondel

Okay. So on the second question, so Kreos agreement was made of two tranches, Tranche A, which has been exercised in July 2018, and Tranche B. So obviously for those who are pulling us since some time, the Tranche B had conditions. The Tranche B at two conditions originally when we signed the Kreos agreement that number one would do get a raise of at least EUR15 million, and number two that this will happen before the end of 2018. None of the two conditions were met. And that's why we discussed with Kreos and we reached an agreement early 2019, in January 2019, to have access to Tranche B with another condition. And this condition is to start of the Phase 2b study in ulcerative colitis. And start means that we would get for one country, so for the first country regulatory and ethics approval. Based on that, Abivax can trigger the growing at any time. We just add the time limit to do that, which is the 16th of – sorry, 15th of July. So in our plans, we obviously daunt of this EUR10 million, the second Tranche B EUR10 million, because obviously, we are confident that we will meet this condition in due time.

Thomas Guillot

Okay. Just, and -- so for the first tranche, what is the level of financial expense you wait for 2019, for the first tranche. You added $500,000 expense for your first tranche mostly in the -- for the last year. And what level of do you expect for 2019?

Didier Blondel

So just -- I will just share with you the accounting methods, sorry to be a little bit boring with that. But the way that has been accounted and this is, obviously, with the full agreement of our [indiscernible] is that we have taken all the expenses relating to each tranche, so whatever those fees interests are, we're putting them together and we're spreading them over the duration of the loan. In other words, so the end size is what open size in 2018 for us. So here, given you what is the impact for 2019 for the full year.

Thomas Guillot

Okay. And my last question is on the Phase 2b and UC. The primary end point you mentioned on clinical [indiscernible] was a modified Mayo Score, a reduction from baseline in modified Mayo Score. Is it the clinical response that is corresponds to clinical report or s it slightly different?

Hartmut Ehrlich

The modified Mayo score compared to the regular Mayo score does not include the physician assessment anymore. And that's what make change and that's what guided by both AVA and European agencies to stay well. We should not take that into account anymore when calculating Mayo scores.

Didier Blondel

You brought something up that I believe is very important to clarify. You were talking about clinical response. And we talked about the primary endpoint, this is not clinical response, this is clinical remission. And the clinical remission basically, if you if you just put it in one sentence is to have the patient symptom-free, so that's clinical remission. And the clinical response is actually an amelioration of about one third of the gravity of the symptoms that the patient is having. So to reach a clinical response is of much lower hurdle than reaching clinical remission, which was exactly what we were sort of so delighted with in the Phase 2a rate of 35% of achieving clinical remission in the patients, which is not observed with all drugs that are currently on the market.

Thomas Guillot

Okay. Just because I was a bit surprised that you didn't get -- you didn't include that they can get response into the Phase 2b?

Didier Blondel

No. It's part of it because, of course, I mean, all these elements contribute to Mayo score, so obviously, part of it.


Thank you. Your next question coming from Vincent [indiscernible] Please go ahead.

Unidentified Analyst

I'd like to have a quick update on the adverse events profile. I think one patient drop filed at one fold due to headache. And I think after eight weeks in your induction path, you reported CNS adverse events have around 20% in the treatment, others zero percent in the placebo. So I wonder if you could provide us an update on those types of adverse events at six months. And my second question would be, do you have any other market or inflammation that you can follow this on six months or nine months such as [indiscernible]

Didier Blondel

Yes. So in terms of headache, again, as I said, it is something which where we’ve seen in our HIV program, as part of the adverse event profile. These headaches are usually, I mean, are mild to moderate. They are grade one, grade two. They’re transients. They are usually happening within the first two weeks at the [indiscernible]. That is not preclude them that they could eventually also have an adolescent stage. And, of course, the patients all time, so far we've had -- out of our 200 patients, we’ve have only four patients dropping out for adverse events or wanting to leave the study, which relates to adverse event. So it's really very, very small. And remember, we have been dosing patients, not only on 50 milligrams within our HIV program, at 150 milligram, which may lead to some slight -- some increased adverse events profile. Here, in the six months, interim from analysis in date we have one patient who have agreed to as much as four months after the first dosing because the patient was on placebo initially, and four months within the maintenance phase [indiscernible] only grade two, the patient elect to withdraw from the study, which is arriving to patient anytime during the state. So we were quite confident that this should not -- this is not of major concern. Of course, the drug is penetrating, as Hartmut said it's crossing the blood brain barrier. So this could be one of the explanations why we could see some of these type of adverse events. In terms of other modular information, yes, we've been looking at a number of them, and we're still -- the traditional one as you mentioned by CFD, we did not see major changes or major alternations in CFD. We did -- we are still looking, of course, as a home battery other inflammation markers, which, as you know, are triggered by the over expression of miR-124. And -- but these data are not available yet.

Hartmut Ehrlich

And I think to the CFD we should also add that at the start of the treatments the median mean CFD levels we're actually for this study population were within the normal range. So CFD is a very poor marker for ulcerative colitis. I think that's the conclusion. But this has been known for some time now.

Unidentified Analyst

If I may just add one more quick question with regards to your cash balance and your intention has to grow through capital wide in the short-term. If I wonder whether this might be opportunity for you to provide solid base on your annual strategy going forward. Thanks so much.

Hartmut Ehrlich

Okay. So this is not the first time we're mentioning what is our strategy. Obviously, we know that we have to find new money in the future to continue to fund the development of the [indiscernible] and you have that -- we have the foundation behind ABX464 and ABX196. So we have 12 months right of this. So we'll, let's say quietly looking at the two options that are ahead of us. The first option is partnering. So obviously, I will -- we will, and I will not comment further on this partnering with naturally an option that we could consider for financial reasons, but also in order to be able to amplify and expand the developmental of [indiscernible] in an accelerated manner. That's number one. And number two, capital race. But what is very clear for us is that capital rise. We have to take care of our shoulders, the large need or small. This is important to us, and as I've already occasion to explain a couple of times. We think that the current market capitalization and share price of Abivax is highly undervalued. If we're comparing with the value of the assets, starting with ABX464 and even if we are reducing ABX464 in UC and Phase 2a. So under the position, it's clear that we don't want, and I don't think our board would agree that we would go for capital rise in the short-term. So that's why today we are quietly, let’s say, investigating these two options. And we'll go back to the market whenever we have made our decision and there will be ready to move forward.


Thank you. [Operator Instructions] We seem to have no questions at this time. Please continue.

Hartmut Ehrlich

Okay. Then thank you very much, ladies and gentlemen, for your interest and specifically for the questions at the end. I hope we have convinced you about the path forward for ABIVAX, which we consider as very exciting. And with this, I would like to finish the webcast. Thank you very much.