Poxel S.A. (POXEL) Earnings Call Transcript & Summary

[Audio Gap] David Moller, Chief Scientist Officer; Pascale Fouqueray, Clinical Development and Regulatory Affairs, Sébastien, Chief Operating Officer; Noah Beerman, Business Development and President U.S. operation will be available for Q&A session after our call is complete. [Emanuel] will be moderator of the will be the moderator -- sorry, for this webcast. [Operator Instructions] Yesterday evening, we issued a press release, which included our full year 2020 financial results and a corporate update. For those of you who do not have a copy, you can access one on the Investor Relations section on our website at poxelpharma.com. We will be using slides as part of the presentation to guide this discussion. You can access the slide on our website in the investor company Information section under the name of full year 2020 financial and corporate presentation. Before we begin, I would like to read our forward-looking statement. Some of the statements of this presentation constitute forward-looking statements, which are statements that are not historical facts. These statements are based on the company's current strategy, plans, objectives, assumptions, estimates and projections. Investors should therefore not place undue reliance on those statements. The company makes no representation, warranty or prediction to that the results anticipated by such forward-looking statements will be achieved. And such forward-looking statements represent, in each case, only one of many possible scenarios and should not be reviewed at the most likely or standard scenario. Forward-looking statements speak only as of the date that they are made, and the company does not undertake to update any forward-looking statements in light of new information or future on -- or future events. Further information can be found in most recent regulatory filings. However, the company anticipate that the COVID pandemic could have further material negative impact on its business operations. The worldwide impact of COVID-19 may notably affect the company's internal organization and efficiency, particularly in countries where it operates and where confinement measures are implemented by the authorities. In addition, COVID-19 may impact market conditions and the company's ability to seek additional fundings or enter into partnerships, particularly delays in the supply of drug substance or drug products in the initiation or the timing of results of preclinical and/or clinical trials as well as delays linked to the responsiveness of regulatory authorities could occur, which could potentially have an impact on the company's development programs and partnered programs. The company will continue to actively monitor the situation. For today's call, Thomas will begin with a brief introduction recapping our key achievement in 2020 in context with the COVID-19 pandemics. Next, Anne Renevot, our CFO, will provide a summary of the 2020 year financial results. Thomas will followed with Imeglimin. David Moller will cover NASH program and our third emerging pillar of pipeline extension. We will close our presentation with Thomas providing a review of the full year 2020 and upcoming milestones for 2021. we will then move to the question-and-answer portion of the call. I will now hand the call over to Thomas.

Thank you very much, Catherine. And thank you all of you for joining us today, and welcome, everyone. When I opened this call a year ago, following up on what Catherine shared, we were in the uncertain beginning stages of the COVID-19 pandemic. As in 2020, I feel very fortunate to confirm that Poxel remains strong and well equipped to face the future. In the context of the COVID-19 outbreak, which was declared pandemic by the World Health Organization on March 12, 2020. The company is regularly reviewing the impact of the outbreak on it's business. As of the date of this conference call and based on publicly available information, the company has not jointly identified the occurrence of a material negative effect on its business due to the COVID-19 pandemic that remains unresolved. We indeed implemented proactive corporate initiative, such as home office with an appropriate IT infrastructure. Our processes in Japan progress smoothly as planned for Imeglimin, our clinical activities for both PXL065 and PXL770 also progressing well according to plan. We took the decision to delay the initiation of the Phase 1 trial for PXL065 in December -- in September, sorry, to make sure to benefit from a safe environment for patients and [indiscernible], which was a wise decision, and the trial is now running smoothly as well. We rely on multiple vendors from manufacturing activities, which helped to mitigate potential delays. And finally, as far as financing is concerned, Poxel benefited from a French government guarantee loan of EUR 6 million in the fall. Related to this line, our mission we remain extremely, as you know, committed to our mission to deliver novel therapies to patients with serious chronic metabolic disorder. Throughout the course of the last year, we overcome the challenges to progress our pipeline and reach key milestones while keeping the best interest and health of our employees as our primary concern. Based on this, I'm confident in our ability to advance our program and achieve our business development goals as we continue pushing through the [indiscernible]. I would like here to thank all of Poxel employees for their dedication throughout the past year and extend thanks to you as well for joining us today. I'm very pleased to have the opportunity to update you on where Poxel currently stands and the productive future, it is headed toward as a global company with strong leadership and a proven track record of R&D capability. As you can see in this chart, our strategy has evolved to now on compass 3 major pillars. Each of which is aimed to deliver first-in-class medicines and key value inflection points. Our first pillar is Imeglimin, our lead candidate for the treatment of type 2 diabetes. We can see here that we have accomplished a major achievement in 2020. Submitting the Japanese new drug application in July 2020 was a critical step towards bringing our first product to the market, which is what we set out to do when we founded Poxel more than 10 years ago. Product approval and the first launch in Japan is on track to occur mid of this fiscal year with our partner, Sumitomo Dainippon Pharma. Imeglimin has a very unique product profile and a novel mechanism of actions, and we remain confident that we can provide a significant benefit to type 2 diabetes patients globally, both alone and in combination with other drugs. That's why we are currently exploring various options to progress Imeglimin in Europe and the U.S., following regaining the rights from Metavant earlier this year. Including all data and materials generated as part of this collaboration. We'll provide you a status update as soon as possible. The second pillar of our strategy encompasses our 2 mid-stage molecules PXL770 and PXL065, which are derived from the [AMPK] and Thiazolidinediones platforms, respectively. With PXL770, we reached a critical milestone in 2020 with positive Phase IIa results to support a NASH. We were thrilled to see the translation of preclinical data to efficacy result in human, and we predict that the effects on inflammation and fibrosis, which we are not captured in early development, could be revealed by biopsy results from a pending Phase II results. For our second mid-stage NASH development program, PXL065, a new chemical entity derived from pioglitazone, we successfully initiated the best in line Phase II studies I mentioned earlier, and we anticipate results to be available in mid-2020. In our emerging third, we are leveraging both platforms to deliver and develop new molecules that target other indications, in particular, rare metabolic disorder. We also aim to establish new partnerships that will further expand our pipeline in this area. As you can see in our pipeline chart, this pipeline illustrates, sorry, well, our diversified strategy. It includes our most advanced run candidate Imeglimin for the treatment of type 2 diabetes. For which we followed 2 different strategies: one, targeting the broad diabetic population in Japan that led us to our partnership with Sumitomo Pharma and a different 1 in the U.S. and Europe, focusing on diabetic patients with renal impairment, chronic kidney disease, moderate and severe, with the aim to repartner in region in order to advance it through this. On NASH, PXL770 and PXL065 are both in place to -- to come back to PXL770 Phase IIa data and our Phase II B plan. David will cover it. For PXL065, we initiated the DESTINY 1 Phase II study in early September last year. We'll also provide an update on this program today. Last, David will also give you an update on our 2 platforms progress with the aim to advance another product in development by the end of the year. So as you can see, we continue to make significant progress with our 3 clinical stage candidates. Imeglimin, PXL770 and PXL065. We are well positioned to continue on our path forward, bringing this novel therapeutic for entire patients living with metabolic disease. I will now turn the call over to Anne, who will provide an update on our 2020 financial.

Thank you, Thomas. Hi, everyone, and thank you for joining us today. So I will now review our financials for the full year 2020. So starting with our revenue on Slide 8. Poxel reported revenue for EUR 6.8 million in 2020. This revenue includes the JPY 500 million milestone payment approximately EUR 4 million, Poxel received from Sumitomo Dainippon Pharma for the submission of the Imeglimin J-NDA. IN a less extent also includes an allocated portion of the EUR 36 million upfront prepayment received from Sumitomo in 2017 as well as the residual medium in Phase III program cost secured in 2020 that were reinvoiced to Sumitomo. For the recall, mostly allocated portion of the payment and the reinvoiced cost of the Phase III trials have been recognized in revenue based on the completion rate of these program, which has been fully completed in 2020, and therefore, led to this decrease in revenue in 2020. Moving along to the income statement on Slide 9. So as a preliminary comment, as a biotech company, the majority of our sources are located to research and development activities. R&D expenses amounted to EUR 26.7 million in 2020 as compared to EUR 14.2 million in 2019. The R&D expenses in 2020 mainly reflected the ongoing Phase II programs of PXL770 and PXL065, the 2 NASH candidates of Poxel. The decrease in R&D cost was mostly driven by the completion of the TIMES program in plan. For which expenses of only EUR 1 million were incurred in 2020 as compared to EUR 20 million in 2019. R&D costs are net of the R&D tax credit that amounted to EUR 4.5 million in 2020 as compared to EUR 4.4 million in 2019. General and administrative expenses amounted to EUR 9.9 million in 2020 as compared to EUR 11.1 million in 2019. The decrease in G&A costs reflects nonrecurring costs incurred in 2019, partially offset by increasing percent costs in 2020, reflecting equipment to support the continued development of the company. Financial loss amounted to EUR 2 million in 2020 as compared to a loss of EUR 1.1 million incurred 2019. The financial loss mostly includes 1.1 million interest paid in relation to our loan [indiscernible]. It also includes EUR 1.3 million noncash income, reflecting the change in IPF warrant fair value and also a EUR 1.7 million exchange rate loans, which was mostly noncash as well as mainly reflecting year-end revaluation of our deposits in dollars. The net result for the financial period ending December 31, 2020, was a net loss of EUR 31.9 million, compared to a net loss of EUR 25.7 million in 2019. So turning on Slide 10. As of December 31, 2020, total cash and cash equivalents were EUR 40.2 million or USD 49.4 million as compared to EUR 37.2 million as of December 31, 2019. Moving to Slide 11. The most significant trend in shareholders' equity and liabilities is the financial liabilities that amounted to EUR 24 million as of December 31, 2020 as compared to EUR 10 million as of December 31, 2019. The financial liabilities mostly include our loan with IPF for a total amount of EUR 16.5 million as well as the PGE loan for EUR 6 million. These absolute trade payables amounted to EUR 8 million as of December 31, 2020, as compared to EUR 16 million as of December 31, 2019. And this decrease mostly reflecting the completion of the TIMES program in 2020. Moving along on Slide 12. The change in the ending cash in 2020 was a EUR 3 million increase. Which reflected the net loss of 2020 as well as positive cash flow of EUR 29 million from financing activities. That include nile a EUR 17.7 million fundraising in May, but also the drawdown of the third -- the second tranche of our loan for EUR 10 million as well as a EUR 6 million PGE loan as well as obtain in Q4 2020. On Slide 13, we have listed relevant shareholder information as well as our research coverage in both Europe and U.S. I will now hand the call back over to Thomas and David.

Thank you very much Anne. So I see to start really introducing you and going into detail on -- for Imeglimin and specifically starting for Imeglimin in Japan. I've already highlighted our achievements for Imeglimin in Japan at the beginning of this presentation, but I'd like to provide a more in-depth of depth on -- at this stage. As some of you know, we've built an extremely successful partnership with Sumitomo in Japan and Asia on large scale. In 2020, Sumitomo was expected to have the #1 diabetes franchise in Japan, and has given financial guidance of approximately USD 900 million in sales just for this franchise. Given that Sumitomo does not have any other late-stage product in development for type 2 diabetes. We believe that Imeglimin is a crucial component to its pipeline given its potential as an overall treatment for diabatic patients. Following our successful Phase III program in which Imeglimin demonstrated a robust efficacy with a favorable safety profile in monotherapy, as you can see here, and in combination with standard of care available in Japan, as you can see here on TIMES 2 and TIMES 3. And based on these very favorable conditions, Sumitomo has developed an attractive launch strategy, which should lead to a rapid and significant market uptake for several reasons: Namely, Imeglimin will be positioned as an adult treatment for DPP4, the leading treatment prescribed to roughly 80% of diabetic patients in Japan. Sumitomo currently has DPP4 therapeutic on the market, named Equa, which it aims to combine with Imeglimin, given its attractive efficacy safety and tolerability profile. Imeglimin is now undergoing review by the PMDA in Japan, the regulatory agency in Japan to receive approval for manufacturing and marketing in Japan mid this year. We anticipate market approval and product launch this year. This is a huge fit, as you can imagine, for any biotech company, particularly 1 of our size. And we are immensely proud to align with Sumitomo and steps away from providing a new treatment option for a sizable patient population. The approval, as you can see here, will trigger a payment from Sumitomo of roughly EUR 14 million with a royalty payment, which we follow post lunch. The Imeglimin launch in Japan also triggers the option to broaden on the third tranche of the IPF loan that Anne discussed about for an additional EUR 13.5 million. As previously mentioned, Imeglimin in the U.S. and Europe. We recently regained Imeglimin rights from our previous partner, Metavant. Metavant decided to stop Imeglimin development for strategic reasons, including a -- or even decision to exit the diabetic space. Last year, Metavant had a constructive meeting with the FDA to align on the Imeglimin Phase III plan. The FDA has provided Metavant with a path forward for a Phase III program in diabetic patients with chronic in disease Stage 3b/4. Taken together, we believe we have a strong data package in hand to repartner Imeglimin in order to advance it through Phase III in the U.S. and Europe. We believe that our success within Imeglimin Japan highlights the significant benefit it can provide in treatment regimens and put us in a strategic position to expand its reach to the U.S. and Europe markets moving forward. I will now ask David to jump in the discussion to present you our NASH programs. David?

Thanks, Thomas. Going to the next slide, I just want to remind you that both of our NASH programs are first-in-class oral agents. And for both, we have evidence of clinical efficacy and are leveraging innovative development approaches. After I update you on NASH, I'll then conclude with a brief overview of additional opportunities we are exploring from our AMPK and deuterated TZD platforms. Let's begin with an update on PXL770, and our first-in-class direct AMPK activator. Importantly, we know that endogenous AMPK activity is suppressed in the context of over nutrition or diabetes. PXL770's mechanism is therefore aimed at restoring AMPK activity in tissues, including in the liver and NASH. In addition to modulating several metabolic pathways that are drivers of liver fat accumulation, we've shown that AMPK activation independently inhibits inflammation and stellate cell activation, which is a key step in the development of liver fibrosis. At last year's AASLD conference in November, we presented further preclinical data to describe PXL770's effects to directly affect components of NASH, including anti-inflammatory effects in rodent and human immune cells as well as its effect related to improvements in mitochondrial function. In September last year, we also presented preclinical and cardiorenal results at the European Association for the Study of Diabetes annual meeting. And here, we highlighted observed improvements in kidney and cardiac disease in another preclinical model. Taken together, our preclinical results supported the utility of this novel target in NASH as well as expanding the potential use of PXL770 and AMPK for more important co morbid conditions or other indications. Back in June 2020, we also announced important results from the positive Phase Ib PK/PD study for PXL770. This was a 1-month study in non diabetic subjects with elevated liver fat content and insulin resistance. In this trial, we demonstrated significant evidence of target engagement and early efficacy signals. In 2020, we also announced positive top line results from our Phase IIa trial with PXL770 and the full data set later in December. As described on this slide, this was a 12-week treatment duration in subjects with presumed NASH based on increased liver fat content. As expected, roughly half the subjects in each cohort also had type 2 diabetes. 2 doses and 2 regimens were tested to better characterize the profile of activity of this compound and target. This trial confirmed the effects of PXL770 to reduce liver fat content. This effect was greatest at the top dose of 500 milligrams per day, and we also demonstrated an improvement in liver enzymes ALT, although this parameter was in the normal range or only slightly increased at baseline. Effects on liver fat content and liver enzymes, including both ALT and AST or greater in diabetic patients, which represent close to 50% of the overall NASH population Overall, these results support our plans to further develop the molecule in NASH. Despite having very well controlled fasting glucose and hemoglobin A1C at baseline, patients with diabetes also exhibit clinically meaningful reductions in both key glycemic parameters, which was consistent with the preliminary results observed in the small cohort of insulin resistant subjects from the PK/PD study. In comparison with other oral agents in development for NASH, where comparable Phase IIa data are available with roughly the same patient population and similar durations of treatment, we believe that we have a promising clinical profile for NASH, along with a potential glycemic benefit for patients with coexisting diabetes. Looking at all the results we have obtained with PXL770 to date, one can see that many of the effects that were demonstrated preclinically have translated into significant clinical efficacy signals. What remains to be confirmed in Phase IIb are improvements in key histologic endpoints, including inflammation and fibrosis. Based on the encouraging results from last year, we are now planning to initiate a Phase IIb study for PXL770 later this year. Our focus will be to show that PXL770 has the ability to promote NASH resolution as the primary endpoint and also to examine its potential to attenuate fibrosis. Given that greater responses occurred in patients with diabetes, along with glycemic benefits from our previous studies, we will focus on patients who also have diabetes or pre diabetes, and who are -- we are also considering a second Phase II study designed to evaluate specific metabolic benefits. Therefore, based on the characteristics of this compound activating the AMP Kinase enzyme, we have a promising opportunity to target a large subgroup of patients with NASH and coexisting type 2 diabetes. As shown here, there's a large overlap in pathophysiology and epidemiology of these disorders. This is a very large population estimated to be 40% to 50% of NASH. And these are also patients who have more severe liver disease and are a greater risk of progression to cirrhosis and generally have poorly controlled hyperglycemia. To summarize the status of PXL770, it's important to also note that the compound was generally safe and well tolerated throughout Phase I and Phase IIa. Of note, it is the first direct AMP Kinase activator to be studied in patients with NASH or any disease, and we are all excited to finalize the planning and start the enrollment later this year with the potential data readout in 2023. I'll now move on to our second mid-stage NASH development program, PXL065, a novel deuterium stabilized single stereoisomer and NCE derived from pioglitazone, a widely used drug approved for type 2 diabetes and already used off-label in the treatment of NASH. This compound is expected to provide the benefits of pioglitazone without triggering the increase in body weight observed with this class of drugs and linked to the mechanism of PPAR gamma activation. Specific clinical data reported for pioglitazone in NASH provide the primary scientific rationale for PXL065. Along with preclinical results showing that PXL065, the pioglitazone are antimere, retains the full efficacy profile in NASH without PPAR gama mediated side effects, such as weight gain or fluid retention. In November 2020, we presented the Phase Ib results for PXL065 at AASLD, the liver meeting, and analysis of the pharmacokinetics results based on concentration in R and S and antimere predicted that the efficacy of a 15-milligram once-daily dose would be equivalent to 45 milligrams of ACTOS, the branded version of pioglitazone with little or no PPR gamma related side effects. The opportunity to provide an improved treatment option to capture the benefits of pioglitazone without the burden of side effects would be groundbreaking for patients afflicted with NASH. Building on the promising data from last year, we successfully initiated DESTINY 1, a Phase II trial, evaluating several doses of PXL065 in biopsy-proven NASH patients. The goal of this trial was to identify the optimal dose or doses for Phase III with PXL065. The primary endpoint of the study is the reduction in liver fat content and effects on liver histology will also be examined. We've received supportive feedback from the FDA to advance PXL065 using the 505(b)(2) regulatory pathway. This provides the potential to bridge to vast amounts of safety and efficacy data from previous pioglitazone studies. We're confident in our ability to move the development of PXL065 forward efficiently and anticipate DESTINY 1 results in mid-2022. Our 2 NASH programs represent first-in-class approaches with distinct and novel mechanisms, but we're pursuing -- pursuing innovative development paths. Both molecules also have combination use potential and favorable safety profiles to date. I'll conclude the review of 2020 by summarizing new pipeline expansion efforts that leverage each of our key platforms. Throughout last year, we continued the expression -- the expansion of our pipeline with an emphasis on orphan and specialty indications with next-generation AMPK activators and deuterium stabilized thiazolidinediones, which modulate non genomic or non PPAR pathways. To date, we have generated robust preclinical data with models of adrenoleukodystrophy and several kidney diseases. We intend to advance at least 1 of our next-generation molecules into IND-enabling development studies around the end of this year and we'll continue working on this build-out in 2021 and 2022. We will share further details with you as soon as we progress new candidates for it's clinical evaluation. Back to you, Thomas.

Thank you very much, David. So I'd like to conclude this call with the milestone that we've achieved in 2020 and giving you some perspective for 2021. As we -- as you've heard on the milestone achieving 2020, are immense for Poxel, Imeglimin is on track to become a commercial product in Japan this year and has the potential to trigger substantial payments for the company. Further, we continue making promising progress in the development of PXL065 and PXL770, as you've heard, and we are well equipped to successfully advance them through. Our ability to navigate the uncertainties of the year marked by a pandemic that shook the foundation of global health care and the economy, speaks volume to our strengths and capabilities in the metabolic therapeutic area. As we've clearly outlined today, 2021 will be a very important year for Poxel. We've continued to demonstrate our ability to bring novel treatments to patients with severe metabolic disorder and this vision is likely to become a reality this year. We are committed to advancing our programs alone and together with partners in an effort to move our products through clinical development and ultimately through regulatory approval and then to patients. Thank you for taking the time to revisit the past year and look forward to the future of Poxel together with us today. We are, as always, grateful for your support in our mission to ameliorate the lives of the affected bi metabolic diseases. I now suggest to open the line to move for question and answers. Thank you very much.

Thank you, Thomas. Well, you have the opportunity to click on the button, raise your hand, and you will have the floor. Maybe Jason Butler, who will ask your first question. Maybe, Thomas, we could begin with his first question about the design of the PXL770 Phase II if you have anything new about it?

Well, yes, I think we did present it, and maybe I can show that again on the -- I guess, general and maybe some specific questions there. So we are really finalizing the design of the trial. As David really illustrated on DM will be really to really focused on diabetic and prenetics patients there in biopsy-proven NASH patients. So with a biopsy at the beginning and a biopsy at the end with the primary endpoints really being the NASH resolution without worsening of fibrosis. 1 year treatments, so which we believe is sufficient to really show not only the efficacy of the product on this primary end point, but on all other endpoints, but also really confirm the set profile of that other part. Pascale, I don't know whether you want to add anything from this...

No, no. I think you covered the design of the study nice. It's a very classical Phase II b for the 770.

Maybe one last point -- yes. Go ahead.

I was just looking at Jason's question online, I can see it now. It's obviously different from the 065 trial, which is the one that's shown on this slide, maybe, Thomas, you can go back to the prior slide with the 770 design. The main difference is that in the case of 065, we're using the 505(b)(2) pathway. So the trial is somewhat shorter and a little bit smaller, and it's not necessarily powered to see a statistically significant effect on histology. We're going to leverage a lot of the data, as you know, for pioglitazone from other trials. However, with the 770 trial, it's a larger trial, it's longer duration. So as Pascale said, it's much more of a kind of classic Phase IIb design for NASH. I hope that answers your question, Jason.

Okay. We have a question from Lucy Codrington.

Just a couple. For the -- for Imeglimin, I was wondering if you could remind us of the payway that erode to Merck for the income on that. And then secondly, just whether Sumitomo has guided on any potential peak sales for Imeglimin specifically or any guidance on what they think the launch dynamics might be.

For Imeglimin, so as a reminder, although we cannot provide due to confidentiality in the exact number, but as we've guided you on the market, so Merck will be eligible to high single-digit royalties basically on the net sales. And Poxel will be eligible on escalating double-digit royalties also based on the revenues in the Sumitomo territory. So that's you need to answer your first questions. To answer your second question, well, DSP has not given any guidance at this stage on really on -- as I am sure you know forecast for Imeglimin, but maybe I can share with you a few elements that can help you. To be clear, they will issue the guidance later this year. In Japan, it's really common for pharmaceutical company to issue guidance when they are closer to the launch. So just a few elements here. As we mentioned earlier, Japan is a very dynamic market. Second market after the U.S., $4 billion to $5 billion market. Then the Sumitomo is extremely well positioned in this market. As we've mentioned during our speech, they have the #1 franchise there. They have 5 products on the market with different classes, DPP-4 inhibitors, Equa, as I mentioned earlier, a GLP-1 agonist liraglutide. And then they have metformin as well and SUREPOST and [indiscernible]. So they are really, really extremely well positioned in this market. And what's interesting is that Imeglimin will nicely complement all their franchise. Again, they have no other as such products. And as I mentioned earlier, the goal that they believe will trigger the most rapid uptake on the market and will be to combine Imeglimin to DPP-4 inhibitors and specifically to Equa. And so to give you a feel for that, I think and as you know, we see the consensus analyst, because we can refer to that. I really have in mind that the product could deliver big sales around $400 million to $500 million at peak, the peak we get there between 4 to 7 years after launch. And we believe this is a good forecast, relevant basically to ours, but of course, we're looking forward to getting the Sumitomo guidance.

We have a question from Tsan.

So I have a couple. First 1 for Anne. As you think about Imeglimin revenues -- sorry, royalties coming in, just curious about your capital allocation priorities. Are most of the cash flow coming in, going to fund R&D, pay down debt, things like that. So just curious if you can share with us your thoughts on that. Second, I believe, David, you kind of talked about 770 could have data in 2023. Just curious about the turnaround time between getting the Phase II B data and how fast you can start-up the Phase III trial? And also, third question, maybe from a drug development perspective, as you think about 770 and 065 and the second-generation compounds targeting mostly metabolic, rare metabolic conditions, are there any PK/PD considerations or pharmacological properties are you looking for to kind of separate out NASH, diabetes indications versus rare metabolic disease indication.

Thank you very much, Andy. And so while maybe Anne on the first question on capital allocation, just to mention that, as you can imagine, Andy, our goal is really to develop the company, strengthening our pipeline. So of course, our resources are mainly dedicated to R&D activities. And of course, as you said, I think we are really close to this -- really key virtuous cycle where basically we will generate some revenues from Imeglimin. That, of course, we want to reinvest in our 2 other pillars of our strategy NASH, and of course, the development of new product for indication. So that's clearly where we stand and our vision is to continue really investing in the discovery, the development and consolidation of the product. Anne, however, do you want to give more insight on this up to Andy?