Inventiva S.A. (IVA) Earnings Call Transcript & Summary

Thank you, Judith, and thanks to everybody for attending, and welcome to this live webcast for our full year 2019 results. As usual, we will be making forward-looking statement. And for you who have been attending these last events, know that I'll be sharing the floor with Pierre Broqua, the Co-Founder, Inventiva and our CSO, who will cover all the pipeline updates; and with Jean Volatier, our CFO, will go through the financial highlights. And so without losing too much time, let's move to the highlights of 2019. And I will focus on our 3 clinical programs starting with lanifibranor. The key, I would say, highlight has been, of course, the completion of the patient recruitment. And Pierre will go through the patient characteristic and we're extremely pleased with the profile of the patient we have recruited because we think really that they bode well for the results that are upcoming in the next few months. Also, we are pleased with the safety of the trial so far, confirmed by 4 positive DSMBs. The last one took place in September and they confirm that the profile and the safety so far of the trial, it is really very good. This good safety of lanifibranor has been also confirmed by the external validation with FDA lifting the clinical hold applicable to the PPAR that was in April. And we are, of course, extremely pleased by the result of FDA decision and also by FDA decision to warrant and to grant to lanifibranor Fast Track designation. We also communicated on the reinforcement of our patent protection. We're already at the composition of matter patent, but also the fact that we extended the protection in key countries, in Europe and in the U.S. with the protection covering the use of lani in fibrotic indication, including NASH, well, that's also very positive. Moving to odiparcil. If you follow-up, you know we were very pleased with the positive publication of the iMProveS study after 26 weeks of treatment in patients which had a severe form of the disease and with the disease being established. Because these were adult patients, we were able to show significant improvement in key clinical parameters. So that was extremely very positive. And also, the good news we are complemented, I would say, by the Rare Pediatric Disease designation and also by the launch of a new biomarker study. I'll be very pleased -- we were not surprised, but really pleased to see that we received the milestone ahead of time. And also, if you follow-up the communication, if you participated to their pipeline update, you know that they've communicated on ABBV-157 as being one of their key early products. And we're, of course, looking ahead and looking to the publication of their Pio results later this year. Financially, 3 successful capital increases with the participation of our key investors on both sides of the Atlantic resulting in a cash runway that is now secured until the end of Q2 2021. So these are the key highlights, and now I hand the floor to Pierre who will go through lanifibranor, odiparcil and ABBV-157 highlights.

Thank you, Frederic. So hello, everybody. I will start with lanifibranor, and I'm on the slide with the delivery on the different PPAR pathways. So as you know, of course, the 3 PPAR isoforms are involved in the pathophysiology of NASH. All of them can impact the systemic and hepatic manifestations of the disease. For example, in the liver, PPAR alpha regulates fatty acid oxidation in hepatocytes, that has also a key role on endothelial function which regulates intrahepatic vascular resistance and portal pressure. PPAR delta as you know regulates skeletal muscle insulin positivity. And in the liver regulates Kupffer cells and macrophages inflammatory responses. And finally, PPAR gamma is a key regulator of hepatic cell activation with anti-fibrotic activity. And in addition, PPAR gamma can also regulate intrahepatic vascular resistance. And systemically, PPAR gamma as you know is a very strong regulator of whole body insulin sensitivity. So because of this wide range of regulatory functions, we believe that concomitant activation of the 3 PPAR isoforms will lead to an optimal therapeutic efficacy in NASH. Next slide. So in this context, lanifibranor as a well-balanced PPAR agonist can address all the key features of NASH. Phase II study in type 2 diabetic patients has shown improvement in insulin sensitivity as well as dyslipidemia, and we have now a large number of preclinical investigations all published or communicated at different conferences demonstrating that lanifibranor could rapidly and sustainably reduce the steatosis, inflammation and ballooning as well as fibrosis and reducing portal pressure in models of NASH but also of advanced fibrosis. So next slide. So the NATIVE trial. As you know, the efficacy and safety of lanifibranor in NASH patients is currently being investigated in this study, which is the Phase III NATIVE study. The NATIVE study is a double-blind, randomized placebo-controlled trial investigating 2 doses of lanifibranor, 800 and 1,200 milligrams daily, administered during 24 weeks in patients that were included in the trial based on the combined score of ballooning and inflammation, and those patients have to show a combined score of 3 or 4 out of maximum of 4. Next slide. So if we look at the main objective of this study is to demonstrate that these patients, lanifibranor can decrease the combined score of inflammation and ballooning by 2 points. And this, without worsening of fibrosis. And this is the primary endpoint. We will analyze the effect of each dose versus placebo as well as each dose within one another. And because the study is stratified for diabetes status, the primary endpoint as well as the other endpoints will be analyzed in the diabetic and nondiabetic population. Next slide. So here is the list of the secondary endpoints. The key secondary endpoints are, firstly, the percentage of patients with NASH resolution and no worsening of fibrosis. We will have also data on the improvement of fibrosis by at least 1 stage without no worsening of NASH. Have information about the number of NASH improvers, meaning the patients that would have 2 points of NAS CRN score decrease from baseline, this with no worsening of fibrosis. And a long list of secondary endpoints that will include the change in glucose metabolism, in liver function, in main plasma lipids, inflammatory markers, fibrosis markers as well as the usual clinical chemistry markers. And the analysis will be performed in the whole population, and as mentioned already as well as in diabetic and nondiabetic subjects. Next slide. So today, we have randomized 247 patients. Those patients have been randomized in more than 70 sites across U.S., Canada, Europe, Australia and Mauritius, and 74% of the patients are in Europe and 15% in the U.S. Next slide. So the randomized population includes 40% of type 2 diabetic patients. As you can see on the table, the demographic criteria such as gender, age, weight, BMI are well balanced between both diabetics and nondiabetics. The activity score is similar and the fibrosis F score is slightly more severe in type 2 diabetic patients as expected. In the overall population, the main activity score is around 3.3 out of a maximum of 4, and 76% of the patients have a fibrosis score of 2 or 3. And as mentioned by Frederic, we are very happy that this NATIVE population is therefore constituted of mostly severe patients, which is good, as it is the population to treat and the ones that are most likely to respond to pharmacotherapy. Next slide. And here, you see it's another way to express data to show that the screening strategy has indeed led to the recruitment of severe patients because when you look at the NAS score, you see that actually 72% of the population from the NATIVE trial have a NAS score equal or above 6. Next slide. So along the way, we had 4 DSMBs. The last DSMB took place in September '19. There were 227 patients reviewed, meaning 92% of the randomized population. 139 patients had completed 6 months duration of the trial, meaning that 57% of patients were analyzed in this DSMB. And you see that the conclusion for the late one or from the yellow one was that there was no issue. And the DSMB recommended to continue the study as planned, confirming the good safety profile of lanifibranor. Next slide. So key milestones ahead of us. Last patient first visit, September '19. Last patient last visit in the coming weeks. Database hard lock is, of course, planned Q2 as well as the headline results publication, Q2 as planned. The last information we wanted to share with you. We plan to host a KOL breakfast at the EASL this year. The meeting will feature presentations by Pierre Bedossa as well as Sven Francque who will discuss the NATIVE clinical study and its patient selection strategy. Next slide. So that was for lanifibranor, and I will now go through the recent information about odiparcil, so next slide. So as you know, odiparcil is a small molecule, overly available with GAG-driven mechanism of action and this is applicable for the treatment of, MPS, mucopolysaccharidoses, where chondroitin sulfate, CS, and/or dermatan sulfate, DS, accumulates. So we know that odiparcil is able to decrease lysosomal accumulation by promoting the formation of soluble CS and DS which can be excreted in the urine. It is an orally available drug that distributes very well in tissues that are poorly penetrated by enzyme replacement therapy. And we believe that odiparcil has the potential to treat clinical manifestations that are not treated by ERT. I has, of course, the potential to be prescribed in combination with ERT, but all the in vivo data we have generated in preclinical models support also the concept that -- as well as iMProveS, can be -- that odiparcil can be also given as a monotherapy. So the odiparcil-mediated reduction of intracellular GAG accumulation has been demonstrated in vitro and in vivo, a recap on this -- from main data in the coming slides. Of course, I will focus this presentation on the positive Phase IIa clinical study that was performed in MPS VI adult patients at the iMProveS trial where we demonstrated good safety and first signal of efficacy. And I will remind you that odiparcil has been previously in another development program where the drug was given to more than 1,800 subjects. So we have a long set of data confirming the good safety and tolerability of odiparcil overall. And finally, in terms of method of use, we have a use patent claiming the use of odiparcil for the treatment of MPS. This patent is granted in the U.S. and in Europe, and we have limited exclusivity up to 2039, which includes a 5-year extension. And we have obtained also recently orphan drug designation in MPS VI as well as Rare Pediatric Disease designation in MPS VI also. So next slide. So odiparcil is a small, readily available molecule. It's a potent substrate of galactosyl transferase I, which is the first enzyme synthesizing CS and DS. What happens in the cell is that odiparcil will stimulate, displaces CS or DS on top of odiparcil, and this will trigger the diversion of endogenous protein GAGs synthesis to soluble odiparcil-bound CS and DS that would be released out of the cell. We can also measure them in circulation in vivo as well as in urine. And I'll show you data obtaining preclinical studies as well as iMProveS. So when you put odiparcil in presence of cells from MPS VI patients, such as what you see on the bottom of this slide. What will happen is that odiparcil will decrease the accumulation of GAG in those cells. And you will see, in parallel, an increase of the release of this odiparcil-bound GAG. So this is what we call a GAG clearance mechanism of action. Next slide. So odiparcil is able to clear CS and DS. So it has, of course, the opportunity to treat patients that accumulate CS and DS such as MPS VI and MPS VII patients. But it has also the potential to treat patients that accumulate either CS or DS such as MPS I or MPS II or MPS IVA patients, and I will show you a slide preliminary findings in MPS I mice supporting this concept. Next slide. So the other very interesting thing about odiparcil is that a small, overly available molecule. It is well distributed and can penetrate hard to reach tissues such as poorly vascularized tissues or tissues that are protected by a barrier such as the eye. And we have evidence that, indeed, odiparcil can reach the tissue and considerations that are active. And this gives the potential of odiparcil for treating clinical manifestations that are not treated by our key -- full distribution of ERT into these hard-to-reach tissues. Next slide. So we have generated in vivo data that are supporting the GAG clearance therapy concept and the concept that, indeed, odiparcil is active in tissues that are poorly treated by ERT. So you can see in this slide which recaps data obtained in MPS VI mice, that if these mice are treated clinically with odiparcil, we can see a decrease of GAG accumulation. On the left top of this slide, this is GAG accumulation in the liver, which has decreased after odiparcil treatment. And on bottom of the slide, we see also a decrease of GAG accumulation in the cornea, in the eye, which actually leads to the restoration of a healthy corneal structure in those MPS VI mice. And parallel to that, we see that odiparcil can restore mobility in these mice. And of course, we measured soluble GaG clearance and increase in urinary GAG in those MPS VI mice. Next slide, please. So this slide actually summarizes some preliminary data that we have obtained in MPS I mice and showing that odiparcil can reduce GAG accumulation in vivo as seen by a reduction of GAG content in the liver. And odiparcil can also potentially address clinical manifestations not addressed by ERT in MPS I as shown by a reduction of GAG content in the eye as well as a normalization of the growth plate thickness. Next slide. So odiparcil was recently investigated in MPS VI adult patients with the objective to assess the safety, the pharmacokinetics, the pharmacodynamics and the efficacy of 2 doses of odiparcil. After a period of screening and preliminary safety assessment of 2 weeks into patients, there was a wash-out period and further screening. And the study was then conducted in 2 main cohorts, a double-blind placebo-controlled cohort of 15 MPS VI patients who continued receiving their ERT and were randomized to receive 250 milligram or 500 milligram of odiparcil or placebo twice daily during 26 weeks; and an open-label noncomparative cohort of 5 MPS VI patients naive for ERT who received 500-milligram of odiparcil twice daily during 26 weeks. And patients were followed up for 1 month after the end of the treatment. We had a total of 20 patients enrolled, received at least 1 dose of study treatment, and population constitutes the safety analysis set. And the treatment period was completed in 13 patients. Therefore, this constitutes the set available for efficacy. Next slide. So the clinical study met its safety primary objective, further supporting the good overall safety profile of odiparcil already observed in the previous Phase I and Phase II clinical studies. All 4 European investigators of the iMProveS study reported positive experience with odiparcil in terms of safety. The majority of adverse events were mild or moderate. One death occurred, unfortunately, in the placebo group. There were 3 serious adverse events that were assessed as treatment-related in patients in the odiparcil groups. Two serious adverse events were biological findings qualified as laboratory false positive and 1 SAE was a skin reaction. So compared to previous Phase I and Phase II clinical studies conducted with odiparcil for the prevention of thrombosis, there were no new safety findings observed. Next slide. So in terms of odiparcil pharmacodynamics. On the left-hand side, this is the graph of total urinary GAGs measured over time. So in blue, we have the placebo. In red and green, the odiparcil low and high dose, respectively, in ERT patients. In brown, the odiparcil high dose in non ERT patients. The uGAGs are increased, as you can see, with odiparcil treatment as early as 1 week of treatment and reach a steady state. At high dose, the clearance of urinary GAGs is comparable between ERT and non-ERT cohorts. And on the right-hand side, you see the PK/PD correlation graph showing that urinary GAGs are correlated with odiparcil exposure in plasma. Next slide. So efficacy wise, the main efficacy parameters were related to mobility, respiratory function, pain, ophthalmology, cardiovascular function and audition. The mobility was assessed during -- using the 6-minute walk test, the 9 hole peg test, the shoulder range of motion of both shoulders. Respiratory function was assessed by forced vital capacity, FVC, as well as forced expiratory volume. Cardiac function was assessed by ECG. The vascular function -- and echocardiogram, sorry. The vascular function was assessed by carotid intima media thickness, CIMT. Ophthalmology, by visual acuity, slit lamp examination and corneal opacification measurement. The pain assessment, from the brief inventory questionnaire. Audiology, this was assessed in, as mentioned in above, evaluable patients of 13. The parameters were set at baseline and end of treatment. And 2 kinds of analysis were performed, the usual statistical approach using descriptive analysis based on treatment groups and the interpretation of individual results performed by experts and from the trial steering committee. Next slide. So we observed a trend for improvement on 6-minute walk test in the 250 b.i.d. group and the non-ERT 500 b.i.d. compared to placebo. FVC was improved so respiratory function was improved in all odiparcil groups, and this was also observed by the second measure we used, the FVC 1. And there were no changes in the 9 hole peg test or no changes in the shoulder range of motion. Next slide. So now when looking across several clinical manifestations such as respiratory, ophthalmology and cardiology, we observed that the majority of odiparcil-treated patients improved in more than 1 efficacy endpoint. In the placebo group, 2 patients slightly improved in the single function, which is -- which was ophthalmology in patient A and cardiovascular in patient B. In the odiparcil-treated groups, 5 patients slightly improved or improved, including 3 patients, C, D and F, in 2 or 3 efficacy parameters. If we look by function. Respiratory, we had 3 patients, C, E and F, have slightly improved their efficacy by 4% to 9% compared to none in the placebo group. For ophthalmo, we had 2 patients, D and F, who improved on their corneal opacification measure. And for cardiovascular, we had 4 patients, C, D, F and G, slightly improved or improved for their cardiovascular function such as no longer mitral regurgitation, decreased severity of mitral or aortic regurgitation and decrease in left ventricular mass index or decreased CIMT of both carotids. And across functions, you can see that this is really balancing. We had 3 patients, C, E and F that improved -- slightly improved 2 or 3 of these functions. Patient C improved on ophthalmology and cardiac functions. Patient D improved on respiratory and cardiac functions. And patient F on all 3 functions. So clearly, there were signals of efficacy with odiparcil that were observed in the iMProveS study and this -- in this category of patients treated by ERT. In naïve patients, we had also signals of efficacy. We -- in the 3 ERT-naive patients receiving odiparcil 1,000 milligrams daily, we had improvements in 1 to 3 functions. So for example, we had 1 patient that improved FVC by 18% as well as range of motion on both shoulders as well as on pain. And we had 1 patient improving on range of motion of both shoulders and pain also. And finally, the last patient who had been hospitalized for 1 month and had, therefore, been poorly odiparcil-compliant during this period had also, nevertheless, pain improved. So the next steps regarding odiparcil clinical development. So we are preparing and plan to start by the end of this year a safety study. So it's going to be a randomized placebo-controlled study evaluating the efficacy and safety of odiparcil compared with placebo during 6 months in patients that are treated by ERT. And the patient inclusion criteria in terms of age will be children having between 5 and 15 years of age. This study will include a preliminary open-label PK/PD assessment and will be followed by an open-label noncomparative long-term safety and efficacy extension evaluation. The plan, of course, is to do a pivotal Phase III study, will be randomized, placebo-controlled with the objective of evaluating the efficacy and safety of odiparcil in a mixed population of ERT-treated and naïve children and adults. So the last thing I wanted to share with you regarding odiparcil is the fact that we are going to present and host a satellite session at the 16 -- sorry, next slide, Jean -- at the 16th International Symposium on MPS and Related Disease. And this will be in Barcelona on July 31 to August 2. And the presentation of the iMProveS results will be given by Professor Nathalie Guffon. And that will be closing the odiparcil set of slides. So Jean, can you move to the next slide, directly to Slide 37. Thank you. So the last point I wanted to share with you is the update about ABBV-157. As you know, this is a ROR gamma inverse agonist clinical compound co-discovered by Inventiva, which actually has a blockbuster potential in several autoimmune diseases. As you know, ROR gamma is a master regulator of Th17. So in charge of Th17 differentiation as well as IL-17 expression and secretion. The concept is already clinically proven with a standard of care in moderate to severe psoriasis being in the field of IL-17 or IL-23 monoclonal antibodies. And ABBV-157 program, so far, as you know, there has been a single ascending dose and multiple ascending dose studies completed in healthy volunteers. A second clinical study has been initiated, a randomized, double-blind, placebo-controlled multiple dose study to evaluate the PK, safety and tolerability of ABBV-157 in 60 healthy volunteers and patients with chronic plaque psoriasis. The study has started in 2019 and will be completed later this year in October. And as you know, Inventiva in this context is eligible to milestone payments and sales royalties. And with this, we'd like to thank you and to give the floor to Jean. Thank you so much.

Okay, let's go quickly through the key financials. I am on the slide with the shareholder base. As you know, we have consolidated this year this base with close to EUR 24 million capital increase, in Q3 last year, with EUR 8.9 million; and more recently in February 2020, with EUR 15 million. So the existing shareholder, U.S. and European-based, have renewed their trust into the company and, therefore, allowed Inventiva, and it's a very important information, to operate until the end of Q2 2021. And what is very important is after the NATIVE headline results, as you know, and like all the market these recent days who are suffering on the market value due to the COVID-19 epidemic and we are close to now to USD 110 million, but in U.S. dollars. Next slide. Let's go to the key information. First of all, the profit and loss account. So we reached EUR 7 million in revenues, so more than doubled compared to last year. This is due to, as mentioned by Pierre and Frederic, the milestones we received from AbbVie for EUR 3.5 million. It's also due to the reversal of deferred revenues related to the Boehringer Ingelheim contract which terminated this year. And the other income or other operational income are deriving from the, as you know, the R&D tax credit, slightly decreasing due to last year, some amendments relating to prior year. Obviously, the most important information is the level of research and development expense, which reached EUR 33.8 million. It's a moderate increase of 7%, which is a mix of strong savings. Following the redundancy plan, we had to decide after the discontinuation of the sclerosis systemic program early last year. And a focused continued effort on clinical development activities on the key programs, odiparcil and NASH, especially with the Phase II completion which is very consuming in terms of cash. And in a lesser extent, the preclinical development for YAP/TEAD. G&A, as you can see, stable. It's our second full year consecutive of a dual-listed company, but we are controlling those expenses. And the other nonrecurring income at EUR 1.5 million negative is essentially due to the redundancy plan I was talking about for EUR 1.2 million for, as I remember last year, we had recorded some tax provisions related to the tax audit and change at the end of '19 and we had also to record some advisory fees related to the fundraising activities. And we finished up the year at minus EUR 30 million improvement compared to last year at minus EUR 33.6 million. In terms of cash, which is the most important information as of today, we reached EUR 35.8 million at the end of December last year compared to EUR 56.7 million. And the level I mentioned of cash does not obviously consider the EUR 15 million gross proceed we raised last February. And again, as I said, it allows us to operate until the end of Q2 2021 after NASH results. The operating cash flow is much better than last year at EUR 28.4 million. And it's due also to very good news in terms of cash inflows. I mentioned AbbVie. We received lately the EUR 3.6 million of R&D tax credit for 2017, which was late from the administration. And we also, to be noted, received in January 2020, which is also very positive for our cash horizon, EUR 4.2 million of 2018 R&D tax credit, which represents 100% of what was due from the administration. And this leads to a pretty good position now to operate for this year and for the first semester of 2021. And if you have any questions, more detailed questions about the financials, I will be glad to answer at the end of the presentation. Frederic?

Thank you, Jean. So last slide, before we move to the question, it's the catalyst. So as you have understood, we have a very important catalyst coming up very shortly which are the NATIVE headline results. And that will be very key in this -- in the coming period. Concerning odiparcil, the team now is working in fully understanding the results from iMProveS and preparing for the end of the year the trial in children. And of course, we are looking forward to AbbVie communication on the progress of ABBV-157. And if you go on ClinicalTrials.gov, you'll see that the trial is scheduled to end in October this year. So this is what we wanted to share with Jean and Pierre on lanifibranor. And I think we have some questions and lot of time to answer those, so I'll let the operator introduce how to do that.

[Operator Instructions] And our first is from the line of Lenny Van Steenhuyse from KBC Securities.

First question from my end is considering the MPS clinical development plan, whether or not you already can give some guidance on potential initiation of the pediatric trial? And whether or not there is any possibility of overlapping following Phase III trials before the pediatric trial has fully been completed, is that a possibility or not? Second question from my end would be on next to the NATIVE trial. Of course, we have the NAFLD readouts for lanifibranor. I can remember that previously, the readout could be quite close to the NATIVE study, is that still the case? Or perhaps some general guidance on timing on the timing on this one?

Lenny, so let me take those questions. So for MPS, the pediatric study, the design, the finality of the protocol is currently under discussion. But we plan to stick to the guidance that we gave to start this trial towards the end of the year. Concerning on an overlap, so to run this trial in parallel to a Phase III, this is something that is possible but we need to discuss with regulatory authorities. It's not the policy that we are taking currently. So currently, our plan is a sequential approach where we would do the safety, the trial in children, and then move into a pivotal trial. Then your question concerning the study run by Professor Cusi. So this is an investigational grievance study. The objective is to measure intrahepatic triglyceride in patients with NAFLD and type 2 diabetes. The trial is currently ongoing. We have not changed the date for headline results, so we anticipate this result in 2021. We do not view these results as key in the end of Phase IIb meeting in NASH, which we plan to have following the NATIVE trial somewhere in Q3 of this year.

Okay. Perhaps a last question from my end. Of course, we had a lot of clinical activity in the course of 2019. Could you perhaps give us some indications of your R&D cost expectations as, of course, the MPS trial has wound down, and the NASH trial is coming wound down quite shortly. So what's your feeling on R&D costs for 2020?

Okay. For 2020, yes. Okay. Yes. We plan to have stable expense this year compared to last year. Obviously, if the NASH results will be positive, we will definitely revise the budget to accelerate on the preparation of the Phase III. But as of today, and what I said about cash runway is based on a stable, which is quite reasonable stable level of OpEx for this year.

Our next question is from the line of Lucy Codrington from Jefferies.

I've got a couple. So just thinking about the NATIVE readout. I guess there's limited information you could give us. But in terms of what constitutes success in this study, should we be using the lanifibranor Phase II post-hoc analysis as a reasonable bar in terms of the threshold of efficacy? I do understand that they were slightly different endpoints. And then secondly, will the regulatory defined endpoints for the NASH resolution and fibrosis be disclosed with the headline data? Or do we expect those to be disclosed later on with the more detailed data? And then thirdly, if you could give us an update on the YAP/TEAD program, that would be great.

Okay. Lucy, maybe I'll try to give my take on the NATIVE, and let Pierre correct me if he did agree with me on NATIVE and then complement your answer on YAP/TEAD. So what would be a good result? Comparison with elanifibranor, no, we do not take that as a benchmark. We view our drug different from elanifibranor. I think the PPAR gamma component brings really differentiator towards the change in compound. PPAR gamma, as explained by Pierre, is it's really important in bringing antifibrotic activity, antisteatotic activity and also the insulin sensitivity, which we believe is very differentiated from others. And therefore, in terms of benchmark, I would rather look at the result developed by -- or produced and presented by Professor Cusi with Pio in NASH patient. That would be, I think, a good benchmark. On your question about regulatory, yes, we will present the data at the secondary end point on NASH resolution. And we plan to have those data when we present the headline result. Please, please correct if this was not your question. And then I would like Pierre complement my answer and then also cover the YAP/TEAD part.

Thank you, Frederic. No, I agree with what you answered. On the YAP/TEAD, well, the program is advancing well. We are aiming for having a preclinical development candidate by September this year. We have extended, I would say, the chemistry scope with working on additional chemical series and other approaches to, say, enlarge the chemistry opportunities in this program.

So just back on the readout. Is that -- given that the Pio studies tended to be longer and you talked about the fibrotic effect that you get through the PPAR gamma. But obviously, we've seen in past trials that you need longer durations to see that. Are you expecting that you will still be able to see the same degree of efficacy on the NASH resolution side of things that you're seeing with Pio even though this is a shorter study?

Regarding the Pio over 6 months, they had efficacy and inflammation and ballooning. So we expect and we hope to see efficacy in inflammation and ballooning. And therefore, a NASH resolution because, as you know, inflammation and ballooning is included in that resolution. You're perfectly correct that Pio was able to show efficacy on fibrosis over a longer period of time. We hope, nevertheless, to be able to show a trend on fibrosis over a 6 months' period. Also given the fact that, as Pierre showed, we were able to include in the trial patient with an advanced stage of fibrosis and we hope that we'll be able to show that we are able to stabilize or reduce fibrosis and have a trend on that.

[Operator Instructions] Our next is -- our next has disappeared. There are no further questions coming from the phone lines.

He's back. Fred Gomez. Yes, we have.

I have 3 questions on NATIVE. Regarding the statistical analysis plan, can you confirm that the testing you're asking, you will test the highest dose versus the placebo? And if it's positive, you will have a look at the 800 milligrams versus the placebo? You mentioned comorbidities and the fact that you will conduct a subgroup analysis in diabetes patients. We know that some of them, like the GLP-1, they can have an effect on NASH. Can we expect an impact of other medication in this specific group of patients? And the last one, the primary efficacy endpoint is a decrease of at least 2 points on the SAF-activity score. Given the score at baseline, which is above 3.2 for the 2 halves, do you plan to conduct a post-hoc analysis or something maybe that has been prespecified and discussed with the agencies looking specifically at a decrease of 3 points to see if there is an effect?

Okay. So on the -- let me answer the sub-question in the inflammation 3 points. On the comorbidities, you're right, you have a patient with type 2 diabetes but a treatment that can potentially have an impact on NASH are excluded. So for example, GLP-1, the treatment or patients treated with GLP-1 are not included in our trial so to avoid any mix of confounding factors. Pierre, do you want to take over about the SAF and the possibility to measure the 3-point decrease?

Yes. So, indeed, so we would conduct the analysis as mentioned with the first dose versus placebo evaluation. The 3 points was not included so far when we think about it. The SAF is not totally finalized so we are going to consider this question. Thank you.

We have another question. It comes from the line of Thomas Yip from H.C. Wainwright.

Congratulations on a great 2019. I'm asking a couple of questions from Ed. So first question we have for lanifibranor, top line NASH data readout that we're expecting in the first half of 2020, are we just expecting the response on the SAF only? Or should we expect a full list of data, including the secondary efficacy endpoints like liver enzymes and insulin sensitivity as well?

Pierre, maybe give an update with the...

Yes, yes, sure, sure. So yes, we are going to have headline results. We will have the NASH resolution, certainly, along with the primary endpoint. And we have -- we wish that we have also the main glycemic control information available. This was your question. And then the rest will come soon, I think.

Okay, okay. Thanks for that clarification. And then obviously, you've made progress on odiparcil with MPS. Can you tell us preliminary? Have you given any thoughts regarding the Phase III design? What size, term and duration, and how many dosing arms?

On the Phase III pivotal trial, we have not given any clarification. We have, of course, ideas based on the duration of the approval trial of, especially Naglazyme. But really, what we need now is to sit down with regulatory agencies, this is planned for this year, and discuss the duration. And also one of the key advantage of our product is while the ERT was approved on the 6-minute walk test and an increase in urinary GAG, we have seen with our compound, efficacy in the corneal opacification for vital capacity. On several organs, where really ERT is not effective and we are effective. So we need to sit down with the regulatory agency and really work with them on the fact that our drug has a different mechanism of action, efficacy on different organs and really have a primary endpoint that takes into consideration the efficacy on all of these issues where ERT is not efficacious. And that needs a discussion with regulatory agencies.

Okay, understood. And then moving on to 157. Are there any plans to report data collected so far in healthy volunteers?

So on this, we are fully dependent on AbbVie communication. We are entitled to royalties. We're entitled to milestone, but the clinical development is conducted by AbbVie. It's a competitive space. Even if competition has been reduced because Pfizer has announced that they have stopped their program. The GSK has announced that they have stopped their program. Takeda has announced that they stopped their program. So we are there on the leading pack, and I'm confident AbbVie is moving ahead very quickly, but also wants to manage their communication optimally so that they can keep their advantage. So we know the trial will end in October. That's what they have written in ClinicalTrials.gov. But on the communication of what the drug is doing in healthy volunteers, what the drug is doing in patients with psoriasis, we are fully dependent on their communication.

Okay, understood. And then one final very quick financial question. How many shares outstanding do you have as of December 31?

In the slide, I think it's 30 million-something -- million shares.

Yes, 30.6 million.

Okay. Okay. Congratulations again, and I apologize on Ed's behalf for the technical difficulties.

Thank you, Thomas. Okay. We do not have a question online. So I guess this concludes our webcast. Thank you everybody for attending. And I'm looking forward to see you soon at EASL [ next quarter ] or other events in the coming months. Thank you very much.