Genfit SA (GNFT) 2022 Q4 法說會逐字稿

Good day, and welcome to the GENFIT Full Year 2022 Financial Results Corporate Update.

At this time, I would like to turn the conference over to Stefanie Magner. Please go ahead.

Hello, everyone. Thank you for joining us on this conference call organized to follow up on the press release we published yesterday with our 2022 annual results and an update on our R&D pipeline. It can be accessed via our website at ir.genfit.com.

Joining me on the call today are Pascal Prigent, CEO; Tom Baetz, CFO; Dean Hum, CSO; Carol Addy, CMO; Meriam Kabbaj, [CTO]; and Pascal Caisey, COO, who will also join for the Q&A session.

Before we begin, I'd like to remind everyone that statements made during this conference call, including the Q&A session, relating to the group's expected future performance, market potential, business prospects, events or plans, including clinical plans, regulatory approvals, anticipated timelines for clinical development and study enrollment whether developed a loan or in partnership and expected cash used in our operational activities are forward-looking statements as defined under the U.S. Private Securities Litigation Reform Act of 1995. They're based on management's current assumptions and estimates, which although believe to be reasonable, are subject to numerous known and unknown risks and uncertainties which could cause actual results to differ materially from those expressed in or implied or projected by the forward-looking statements.

For a further discussion of material risks and other important factors that could affect our business operations and financial results, please refer to those statements contained in our most recent filings with the SEC and AMF. These forward-looking statements speak only as of the date of this webcast and other than as required by applicable law, we don't undertake any obligation to update or revise forward-looking information or statements, whether as a result of new information, future events or otherwise.

Following the prepared remarks, we'll open up the call for questions that will be addressed by GENFIT Management. Please limit yourself to one initial question to allow time for others.

I now turn the call over to our CEO, Pascal Prigent.

Thank you, Stefanie. In this call, I will highlight the progress we've made across GENFIT in 2022, and I will discuss our perspectives for 2023 as we are now nearing an inflection point with the upcoming release of ELATIVE's top line results.

2022 as an important year in so far as we continue to execute the strategy we outlined for you at the end of 2020 and reaffirmed in 2021. The 3 components of our strategy remains the same; one, maintain good financial visibility; two, accelerate our late-stage PBC program; and three, build a richer and more diversified pipeline. We obviously have been working on those 3 components over the past 3 years, but [what] could see 2020 as a year where we focused on improving our financial situation, in 2021, it was the acceleration and strengthening of our PBC program with Ipsen deal. And in 2022, it was a reinforcement of our pipeline.

As outlined last year, our R&D strategy is to develop assets in rare and severe liver diseases for which there is a high unmet medical need. We have chosen to focus more specifically on ACLF because we believe that the lack of available therapies, the number of affected patients and existing public health trends make it a medical priority. The acquisition of a clinical stage biopharmaceutical company, Versantis in 2022, consolidated GENFIT's position as a leader in acute and chronic liver failure and other severe liver diseases.

Our pipeline now includes 6 programs, 4 clinical stage and 2 preclinical stage programs. We believe that this rich pipeline, combined with an important near-term catalyst and robust cash position provides us with a unique opportunity to drive significant value creation in 2023 and beyond.

So let's first talk about financial visibility. And I will let Thomas give you more details about our financials in a few minutes. But we are in a good place. We have a robust cash position at the end of '22. And in fact, the EUR 140 million of cash and cash equivalents that we had at the end of 2021 -- 2022, sorry, concern all of our existing programs and take us to Q3 2024. In addition, if the results from our Phase III PBC trials are positive, we should receive several regulatory milestone payments in this period as part of the agreement with Ipsen. And obviously, this will significantly further expand our cash runway.

About the PBC program. So in 2022, we made good progress. We announced the enrollment of our last patient in ELATIVE (inaudible) and we confirm that we expect to report top line data from a pivotal Phase III study in PBC towards the end of this quarter. We continue to believe that elafibranor could offer another treatment option for patients who suffer from this devastating disease and that, based on its Phase II result, its profile could be very attractive for patients with PBC who do not respond well to UDCA.

Beyond ELATIVE, GENFIT and Ipsen also stepped up their collaboration throughout 2022 in order to maximize the potential of a program. And in particular, there were significant investments and efforts to be [ready] to file as quickly as possible as well as prepare for a potential commercial launch next year. And I believe it's worth remembering a few facts. So first of all, by 2024, if approved, elafibranor could potentially become a new therapeutic option for patients with PBC not responding to UDCA and become the first alternative to currently approved second-line treatment.

Second, in this market, elafibranor has a differentiated profile. Phase II results with elafibranor in PBC, showed in just 12 weeks of treatment, a statistically significant improvement on both the primary endpoint as well as on the composite evaluation criteria, which is the same as the primary endpoint of a pivotal Phase III trial to support accelerated approval. We believe that a larger trial and longer treatment duration should confirm that finding. In addition, the results showed a positive trend on the improvement of pruritus, while preserving a favorable safety and tolerability profile. All of those positive conclusions have been published in the Journal of Hepatology in 2021. And also, obviously, we expect the active trial to confirm the favorable safety and tolerability profile of elafibranor and add to the safety data for more than 1,000 patients in our biopsy-based RESOLVE-IT trial in NASH.

Third, this is a market that's estimated to be at EUR 1.5 billion in the coming years and up to EUR 3 billion in the U.S. and EU (inaudible) by 2030. We think that by combining a desirable profile, first-in-class status with Ipsen's proven capabilities and footprint in both the U.S. and Europe could lead to commercial success. And that in a fairly sizable and fast-growing market with relatively low competitive intensity with only one approved product and one additional Phase III program underway. If the trial is positive, the commercial perspective is therefore promising. And under the agreement with Ipsen, GENFIT is eligible for double-digit royalties of up to 20% of total elafibranor sale. In addition, GENFIT is also eligible for regulatory, commercial and sales-based milestones up to EUR 360 million with a potential first significant milestone payment as early as 2023 and an additional potential milestone payments next year. So therefore, we really look forward to providing top line efficacy and safety data in the next couple of months as this will hopefully make this potential more tangible.

Let's talk now about the pipeline. While these near-term results of our PBC trial will obviously be transformative for GENFIT, we also see beyond this outcome. And indeed, we have people working to expand and diversify our pipeline beyond PBC. GENFIT is determined to capitalize on its strength and knowledge in rare liver diseases to bring innovation into several therapeutic areas where patients have critical needs.

I will now provide a brief update on the rest of our pipeline. The areas we have chosen to concentrate our efforts on share a few characteristics. They are rare liver diseases. There are serious condition for which no or few therapeutic options are available. And given the magnitude of the unmet needs related to this disease, it is expected that most of these programs will qualify for some of the expedited regulatory pathways provided by (inaudible).

Finally, let me point out that although rare, these different conditions taken together represent a total market potential of EUR 11 billion in the U.S. in the largest European countries by 2030.

So let's start with the preclinical stage programs that we have that is in addition to PBC, of course. The first one is VS-01 and ACLF. ACLF is an underserved medical condition that's associated with high short-term mortality, 23% to 74% mortality at 28 days depending on severity grade. Currently, no drugs have been approved in ACLF. In the U.S. only, there are over 600,000 hospitalization per year for decompensated cirrhosis with 10% to 30% of ACLF prevalence in this population. The number of patients is expected to grow due to the aging population, the increasing prevalence of nonalcoholic fatty liver disease, NAFLD, NASH, diabetes, obesity as well as alcohol consumption and drug-induced liver injuries.

10 years ago, the total inpatient cost for cirrhosis with and without the ACLF was already estimated to be more than EUR 10 billion with a cost of [hospitalization] that was 3x higher when patients had ACLF (inaudible) just sclerosis. So very high burden on the health care system.

VS-01 is an innovative [first-in-class] therapeutic drug candidate based on proprietary scavenging liposomal technology. It's administered directly into the abdominal cavity following drainage of ascites, one of the most common complication in patients with ACLF. The Phase I trial highlighted the favorable safety and tolerability profile of VS-01 and provided encouraging preliminary efficacy results with about 80% of treated patients improving or stabilizing their disease. The Phase II will be an international, open-label, randomized, controlled, multicenter proof-of-concept study but we'll assess the efficacy, safety and tolerability of VS-01 with about 60 adult patients with ACLF grades 1 to 2 and ascites. It is anticipated that the first patient will be screened in the trial this quarter.

The second clinical stage program we have is evaluating NTZ in the same indication, ACLF. Two Phase I studies were completed in the fourth quarter of 2022 and the first quarter of 2023. They provide preliminary insights into NTZ pharmacokinetics and safety in the setting of hepatic impairment or renal impairment. The studies support moving into the next phase of a program, which will be a Phase IIa proof-of-concept study in patients with ACLF grade 1 and 2 but will be further discussed with FDA. The study initiation is targeted for the second half of 2023.

Our last clinical program is evaluating GNS561, the novel clinical stage autophagy PPT1 inhibitor for the treatment of cholangiocarcinoma. CCA is the second most common primary liver malignancy diagnosed globally and represent about 15% of all primary liver tumors. The incidence is increasing, and there are limited therapeutic options for this aggressive disease. The 5-year survival rates are 5% to 15% in the advanced and [unresectable] cases. Even after curative intent surgery, the clinical outcomes are disappointing with 5-year survival rate of 7% to 20%. As a reminder, in December 2021, we licensed the rights from General Science to develop and commercialize it in CCA in the U.S., Canada and Europe, including the U.K. and Switzerland. GNS561 mechanism of action showed promising results and preclinical and clinical evidence provided the scientific rationale to develop this asset.

The Phase Ib/IIa trial will evaluate GNS561 in patients with advanced KRAS-mutated CCA. In the Phase Ib will evaluate the safety and tolerability of GNS561 in combination with a MEK inhibitor. We also identify a recommended doses for Phase IIa in which the safety and efficacy of the combination will be assessed in patients who have otherwise failed standard of care for first-line therapy and who do not have an actionable mutation. GENFIT targets to screen the first patient towards the end of the second quarter of 2023.

Now a word about our 2 preclinical programs. The first one, VS-01-HAC is a potential first-line life-saving treatment for acute hyperammonemic crisis associated with inborn errors of metabolism in urea cycle disorder or UCD, an organic acidemia or OA. IND-enabling nonclinical studies are targeted to be completed in 2024. The second program, VS-02-HE is developed in Hepatic Encephalopathy, which is one of the major complication of advanced liver disease and portal hypertension. It is closely linked with ACLF. As many of -- as 45% of patients with cirrhosis will experience at least one episode of HE. VS-02 is a urease inhibitor and hydroxamic acid derivative that is designed to inhibit ureases in the [gut]. IND-enabling nonclinical studies are targeted to be completed by 2025.

Although these are early stage programs, they represent a significant potential with a market size of severe Hepatic Encephalopathy alone estimated to be around $3 billion in the U.S., in the largest European countries by 2030. For UCD and OA estimation for 2030 is about $1 billion for the U.S. and the EU (inaudible).

Before handing it over to Thomas, let me conclude with a word about NIS2+, the next generation of our NIS4 technology for identifying at-risk NASH patients. Several presentations were made during the last AASLD highlighting the potential of NIS2+ to be an effective screening tool for the enrollment of patients with at-risk NASH in clinical trials and as a potentially valuable [politic] tool for early detection of fibrosis progression in at-risk NASH patients. The future of NIS2+ is for an in vitro diagnostic test or IVD as a stand-alone diagnostic and we continue to explore the possibility of obtaining regulatory approvals along with the development and commercial partner.

The recent development in the NASH field means that this market could soon see the launch or one or more therapeutic option. When that occurs, it will be essential for physicians to identify appropriate patients and will be essential for payers to ensure good use of the approved drugs. I think we all know that biopsies are not scalable and cannot be the solution and that the noninvasive test is a much needed alternative. We believe we have the best solution to identify this at-risk patients.

I'm now handing over to Thomas, who will highlight key financial amounts from today's press release.

Thank you, Pascal. Hi, everyone. Thank you for joining us.

So firstly, I would like to refer to the press release issued yesterday evening for a summary of our financial results for 2022. Our revenue and other operating income for 2022 amounted to EUR 26.6 million compared to EUR 85.6 million for 2021. Our operating expenses amounted to EUR 53.9 million in 2022 compared to EUR 53.8 million in 2021. As a result, in 2022, GENFIT generated consolidated operating loss of EUR 27.3 million compared to an operating gain of EUR 31.8 million for the previous year.

Our financial results for 2022 was a financial income of EUR 3.5 million compared to a financial income of EUR 37.7 million for 2021. As a result, GENFIT generated a net loss of EUR 23.7 million in 2022 after adding a corporate income gain benefit -- tax benefit of EUR 0.1 million compared with a net gain of EUR 67.3 million in 2021 after deducting corporate income tax expense of EUR 2.2 million.

As of December 21, 2022 -- 31, 2022, our total financial debt amounted to EUR 75.3 million compared to EUR 74.2 million at the end of 2021. As of December 31, 2022, GENFIT had EUR 140.2 million in cash and cash equivalents and current financial assets compared to EUR 258.8 million at the end of 2021.

Now that you have the numbers in mind, let me give you some color and explain where these figures come from. Briefly touching upon revenue and other operating income, our revenue essentially came from 3 streams related to Ipsen. For context, in December 2021, we received EUR 120 million nonrefundable upfront payment from Ipsen as part of our licensing and collaboration agreements. EUR 80 million was recognized as revenue in 2021 and EUR 40 million was booked as deferred revenue and is gradually recognized as revenue in subsequent periods following the completion of the ELATIVE double-blind study. As such, of that initial EUR 40 million in the deferred revenue balance, EUR 15.9 million was recognized as revenue in 2022.

EUR 3.3 million was recognized as revenue in 2022 in accordance with the inventory purchase agreement signed with Ipsen pursuant to which Ipsen purchased inventory of elafibranor active pharmaceutical ingredient and drug product during the second half of 2022, with the prospect of transferring the conduct of the ELATIVE study to Ipsen.

EUR 1 million in revenue was generated from the services rendered by GENFIT to Ipsen in accordance with the transition services agreement signed in 2022, which essentially outlines the scope of services to facilitate the transition of some activities related to the Phase III clinical trial evaluating elafibranor in PBC.

Other operating income included mainly the research tax credit granted by the French tax authorities, which amounted to EUR 6 million for 2022.

Now a word on our acquisition of Versantis. On September 29, 2022. We closed the acquisition of Versantis, a private Swiss-based clinical stage biotechnology company focused on addressing the growing unmet medical needs in liver disease. This acquisition aims at consolidating GENFIT's position as a leader in ACLF, significantly expanding GENFIT's pipeline and combining Versantis expertise with GENFIT's know-how in conducting complex development programs in liver disease, to strengthen and accelerate research and development.

The total purchase price includes an initial payment of CHF 40 million or EUR 41.9 million paid at closing. The net cash adjustment of CHF 2.8 million or EUR 2.9 million paid in December 2022. Acquisition costs totaling EUR 1.8 million paid in 2022 and additional milestone payments of up to CHF 65 million, contingent on certain outcomes in the future. The impact of this acquisition, net of the cash acquired totaled EUR 41.5 million.

A word on our debt balances. For context, at the beginning of 2021, we were able to renegotiate the partial buyback of our convertible bonds. In addition, in the latter half of 2021, we were also able to secure 3 non-dilutive loans totaling EUR 15.3 million granted in the context of the COVID pandemic. The nominal amount of our convertible loans as of December 31, 2022 stands at EUR 56.9 million, the same balance as at the end of 2021. There has been no conversions of this debt in 2022. The outstanding amount of our non-dilutive loans as of December 31, 2022 stands at EUR 15.2 million compared to EUR 15.3 million as of December 31, 2021. There was no new issuance of debt in 2022. As a reminder, during the first half of 2022, as we were already planning to do in late 2021, GENFIT requested an extension of both the bank, [PGE] and the (inaudible) France, PGE, post extensions were granted by the respective counterparties.

About our cash position as at the end of 2022, GENFIT had EUR 140.2 million in cash, cash equivalents and current financial assets. Net of cash in transit earmarked for payments in early January of EUR 0.3 million, and that is compared to EUR 258.8 million at the end of 2021. The decrease in cash, cash equivalents and current financial instruments between the end of '21 and the end of '22 includes the payment of EUR 24 million in January 2022, representing the VAT collected on the initial upfront payment received from Ipsen in December 2021. The disbursement of employee participation in the profit of GENFIT SR in May 2022 for a total of EUR 0.6 million for the fiscal year 2021 and the acquisition of Versantis [AG] totaling EUR 41.5 million, net of the cash acquired.

Finally, in our projections, as we continue to advance our current product candidates from the preclinical studies and conduct clinical trials, we expect that our cash used in operational activities will amount to EUR 60 million in 2023. This amount does not include potential expenses we may incur in the future -- in future business development activities, such as in-licensing.

I now turn the call over to Pascal.

Thank you, Thomas. So before moving to Q&A, I would like to thank all the patients and the physicians who are collaborating with us to advance treatment options in all the disease we target.

And now I'd like to open the call for questions. So operator, if you can begin the Q&A session, please.

(Operator Instructions) We'll go first to Thomas Smith with SVB Securities.

First on the ELATIVE study. Can you just remind us of your latest expectations and what you expect to show on the primary composite endpoint as well as the secondary endpoints of [outfast] normalization and pruritus improvement?

Tom, thank you for your question. I guess our expectations will obviously be to replicate what we've seen in the Phase II.

So I don't know, Carol, do you want to comment on this?

That's exactly right, Pascal. And Tom, thank you for your question, and good morning to you as well.

Yes, indeed, we anticipate with ELATIVE, which as you know, this will be a 52-week data readout as opposed to the 12-week data readout for the Phase II study. We do anticipate seeing a similar improvement in biochemical indices of cholestasis. And similarly, the same favorable trend that we observed in improvement in pruritus. Of course, this will be a more robust data readout given the increased duration of exposure to elafibranor and as well the increase in sample size in the ELATIVE trial relative to the Phase II trial.

Understood. That's helpful. And just to follow up on that. We saw on (inaudible) that you made some changes to the secondary endpoints in the way that you're measuring changes in pruritus. Can you just walk us through the changes that you made, the rationale there and how you expect that to impact the signal for elafibranor on pruritus?

Sure. So just to refresh memories, as we understand, pruritus is one of the major symptoms that are impacting patients with pruritus. And if I'm a patient with PBC, this is really impacting my overall quality of life, and I want relief as quickly as possible. So certainly, when we think about how we translate that to clinical trial conduct, and as we saw in our Phase II trial after 12 weeks of exposure where we saw favorable trends in improvement, this is suggestive that elafibranor has the potential to provide short-term relief of symptoms. And so with that in mind, we did include some near-term time points in the ELATIVE trial to better understand elafibranor's potential to provide near-term relief of symptoms of pruritus, but as well sustained relief, which is also important for patients experiencing this symptom.

Okay. Understood. And just maybe lastly on the VS-01. It sounds like you're on track to dose the first patient in the Phase II ACLF study this quarter. Is it still your expectation that you'll be able to report interim data from the study in the first half of '24? And just remind us what we can expect to see from that interim analysis.

Sure. So you're right. We are imminently on track get our first patient enrolled. We have regulatory approvals in 4 countries in the EU, an IND submitted in the U.S., and so patient screening is imminent. We are on track based upon what we understand to have interim analysis readout in first half of 2024 but also with the understanding this is the first time we've enrolled a study with -- in patients with ACLF and we understand this is a rare condition. And so we will be learning a lot as we get the study underway.

In terms of interim analysis, this will really be aimed to understand whether we will -- after 40 patients having been enrolled be on target in terms of the effect size that we are anticipating, and this will be helping to guide our further enrollment of the study and whether or not we would need to adjust the sample size accordingly. So really aimed for internal decision-making.

Okay. Got it. And for internal decision-making, so I guess, how are you anticipating, I guess, communicating the results from that interim analysis? It sounds like we shouldn't expect to see data, but maybe more qualitative color around what you're seeing and I guess, any changes to the study design? Is that fair?

Yes, I think that would be a fair assessment, Tom.

And looking forward to the ELATIVE data later this quarter.

We'll go next to [Sue Sheila Hernandez] with Kempen.

This is Suzanne on for Sue Sheila. Just a few questions, if I may. We were wondering on ACLF for the NTZ and VS-01. Are you planning to target the same patients in the NTZ Phase II as in the ongoing Phase II with VS-01? And could you once again elaborate for us how both products fit in the treatment paradigm? And then I have a follow-up.

Sorry, you cut-off a little bit at the end of your question. So I got the first part and I'm going to let Carol answer about the different population. But the second part of your question, we didn't get it here. Unless Carol, you got it?

No, I was going to say the same. Suzanne, you did break up at the end.

Right. So it was -- if you could elaborate once again how both products fit in the treatment paradigm?

So let me address your first question. And if I'm understanding how are we distinguishing the patient populations that we will be enrolling in our VS-01 trial relative to the NTZ trial, if I understood your question correctly.

Certainly, both studies will be enrolling patients with ACLF 1 or 2, 1 or 2 being indicative of the number of organ failures experienced by these patients. Now the distinction here is that our VS-01 trial will be inclusive of patients with ACLF grade 1 or 2 and who also have ascites, though ascites is the fluid that accumulates in the abdominal cavity and patients having ascites typically undergo a procedure called paracentesis, where this fluid is removed by a catheter that's inserted into the abdominal wall. So -- and so VS-01, of course, is administered through the same catheter.

And so in contrast, the NTZ study will not require that patients have ascites, although many patients will. We do anticipate some overlap, but we're also being mindful of how this will impact our site selection so that we're not going to be in a competitive enrollment situation.

And so in terms of treatment paradigm, there are a number of guidelines, clinical guidelines that are available in the EU and in the U.S. that provides recommendations for standard-of-care for these patients, for example, treatment of ascites, treatment of infections of the ascitic fluid that we refer to as spontaneous bacterial peritonitis, as an example. What we anticipate is the use of VS-01 and NTZ on top of a background of standard-of-care for short-term treatment of ACLF and we know that these patients progress very rapidly in their clinical course, our anticipation based upon what we've observed to date, both in preclinical and clinical studies, as is the case with VS-01 that we would expect to see short-term impact that could help in further progression to additional organ failures and what we're hoping to see, of course, is regression and improvement in those 4 organs that have failed.

The one thing that I would add, [Suzanne], is, I mean, obviously, we are a little bit breaking new ground in ACLF but the expectation is that because this is such a serious disease, multifactorial, very complex with high mortality, it's very unlikely that one drug is going to be a silver bullet. So it's probable that you could use multiple drugs to manage those patients. And one thing that for us is important, is the fact that NTZ and VS-01 would at least theoretically act on this disease for a very different mechanism of action. And therefore, they are not competing. They are more like complementary therapeutic options.

Got it. That's very helpful. And then lastly, if I may, if I understand correctly regarding your cash runway into Q4 next year, that this includes the potential milestones from Ipsen. Can you provide more color on the size and what events those milestones from Ipsen are related to? Just wondering if there's a more significant chunk residing in one trigger or if it's more fairly spread.

So yes. So it does not include the milestone from Ipsen. So our guidance is Q3 '24 with the current cash or cash equivalent and that does not include the milestone. If we do include the milestone or cash runway, it goes significantly further. We have not guided on the size of the different milestones. The only numbers we've provided and that's part of the agreement with Ipsen, it is the [total] amount of milestone, which is EUR 360 million. But we are not guiding on the respective milestones.

We will go next to Martial Descoutures with ODDO.

Another quick question on your guidance. You highlighted that you have financial visibility until Q3 2024, so I would be really interested to know what do you include in this guidance in terms of development, not in terms of milestone for Ipsen, but specifically in terms of your development? So in your business plan, where will you be in your pipeline calendar, specifically for VS and NTZ at this horizon?

Martial, yes, we do include everything. So the finalization of the program in PBC with elafibranor, all 3 Phase II studies. So as we've said, we are (inaudible) that are starting or starting to screen patients right now and one that's forecasted to do it in the second half of the year. So mainly -- mostly those are VS-01 in ACLF. NTZ in ACLF as well as GNS561 in cholangiocarcinoma and all the preclinical work that's currently ongoing with VS-02 and VS-01 in UCD. So all of that is included in the guidance. We've, of course, all the additional work that's being done by R&D in terms of the different activities that we have. So when we say we funded until Q3 '24, it's like everything we've discussed is in scope.

We'll go next to [Alex Cogut] with [Bryan Garnier].

So just on ELATIVE. I was just wondering if the trial is powered specifically to draw statistical significance on pruritus? And how would you expect the impact on liver enzymes to materialize considering the results in Phase II? And then I have a few other questions.

Carol, do you want to take that?

Yes. Sure, Pascal. Alex, thank you for the questions.

So indeed, in ELATIVE, we have framed our pruritus endpoints as key secondary endpoints. As such, the study is, in fact, designed to ensure that we are able to demonstrate statistical significance in terms of change from baseline in pruritus as we are assessing by means of daily assessment of NRS scores.

And so the other question that you had was pertaining to changes in transaminases. Could you maybe help me to better understand, are you referring to change in transaminases from an efficacy perspective or from a safety perspective because we can consider both.

I guess from an efficacy perspective first, right, because if you -- I think in a Phase II, it was a bit of a less clear trend. I mean granted there was a smaller trial. So I was just wondering how would you expect that to pan out in the Phase III?

Yes. Again, in keeping with the earlier response, we do anticipate that we will be replicating the results of our Phase II trial in that study. As you're aware, we saw it demonstrated significant improvement in cholestatic indices whereas stability was demonstrated in transaminases. So stability, which we interpret in a favorable sense in terms of not having any adverse effect in terms of safety profile.

Got it. And then on the -- once you have the Phase III top line results, how long does Ipsen have contractually time-wise to decide on the next step?

Yes. We can't really speak on behalf of Ipsen, suffice it to say, we're working very closely now with Ipsen in close partnership so that we may enable the data readout by the end of this quarter. And then certainly, we'll be working to support them in terms of next steps, in terms of ultimately NDA submission. So that will really be their responsibility. We're playing a very supportive role here.

And I would say, I mean, it's not contractual, but if the results are supportive of a filing, obviously, it's in both companies' best interest to grow as quickly as possible.

Yes, I was just wondering there, are there any other considerations they would have on the results to be supportive of filing? I mean, apart obviously from the -- let's say, the primary and the key secondary end point?

No. I mean if the efficacy is what we hope it will be then -- and if we have a [salable] product, then we'll go ahead.

Okay. And then just a last question on NTZ. Could you elaborate on the significance of the sort of the upcoming data in May in light of the sort of the Phase IIa you're planning?

Sure. So Alex, the data that we have acquired thus far with NTZ is the basis of -- from 2 Phase I studies that were conducted and these studies are enabling and supportive of our proceeding with a proof-of-concept study in patients with ACLF. So remember that patients with ACLF have varying degrees of liver and many times renal impairment or failure. So it was very important for us to do some initial studies, the Phase I studies, one in individuals with hepatic impairment, the other in individuals with renal impairment so that we would better understand the pharmacokinetic profile of NTZ in these conditions and more importantly, safety.

Safety, of course, is top priority because our ultimate patient population patients having ACLF our acutely ill and so we really wanted to have a very good understanding of safety prior to going into the evaluation of NTZ in a proof-of-concept study in patients.

Great. Thank you for all of these questions. I think that, that concludes our call.

I would just say in closing that 2022 was very important and transformative year for GENFIT. It was marked by both the progression of our lead program and the expansion of our pipeline in rare and severe liver disease, notably with the acquisition of the Versantis. We are now approaching an inflection point. This quarter, we expect to report data from our pivotal Phase III study in PBC. There is still an important unmet medical need in this market, and we are very encouraged by the previous Phase II data reported as part of this program. We believe elafibranor has significant potential, and we hope it will be demonstrated soon.

Beyond this exciting milestone, we have built a rich pipeline that now includes 3 additional Phase II stage programs in 2 preclinical stage programs. This pipeline, combined with a robust cash position, and potential near-term commercial perspective for elafibranor provide us with a unique opportunity to drive significant value creation in 2023.

So we look forward to providing future updates soon and forward the year. Thank you very much for your attention.

This does conclude today's conference call. Thank you for your participation. You may now disconnect.