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

Ladies and gentlemen, thank you for standing by, and welcome to Inventiva's H1 2020 Financial Results Presentation.

Thank you, Joanna. Welcome, everybody. I'm very happy to open this session for -- while we were preparing this webcast, we actually realize this has been a fantastic and a quite exceptional first half for Inventiva and I would say, on all fronts. As you know, we make some forward-looking statements. So please do not hesitate to go on our website and download all the regulatory document that are available. Today, you will not be surprised. So I'll share the floor with Pierre, the Co-Founder and CSO; and with Jean, our CFO. And also in terms of agenda, no particular surprise. We spend, I would say, most of the time going over the lanifibranor result in NASH and also putting some perspective on this result, how they've been viewed by physicians and also what's next and what can you expect from this program. So let me very briefly go over who we are and what are -- in a nutshell so -- and our highlights. So in terms of who we are, we specialize in small molecule. We're developing lanifibranor in NASH with what we believe are probably the best result ever shown by an oral drug in a long-term Phase IIb biopsy-driven study. In parallel, we're also advancing odiparcil, small molecule that could really prove beneficial to patients with MPS VI. Investors are, of course, focus on lanifibranor, but we should not forget also the very promising collaboration we have with AbbVie with ABBV-157, which -- where we expect prove -- clinical proof-of-concept in patients with psoriasis in Q4 of this year. The team is also working on YAP-TEAD but this is a earlier, but also we are excited by the progress we have made there. And we are excited, of course, by the several successes that we have had in reinforcing our cash position with the highlights in July of the NASDAQ. And now we have a runway through Q4 2022. So let's focus on the highlights. So Pierre will come back on the NATIVE results. So I will be very -- I won't dwell a lot on it. Instead maybe I point out that you'll see new data, which we just generated on circulating biomarkers. And I would say that they are confirming that we are working with the drug lanifibranor that is really dealing with NASH and treating the disease on all fronts because there, again, we see that fibrosis biomarkers are moving on the right direction with statistical significant reduction in apoptosis biomarker, in inflammatory biomarker on top of the fibrosis biomarker. So all of this is extremely exciting, as well, very excited by the decision by Professor Cusi that, as you know, is a lead investigator of Phase IIb in patient with NAFLD and type 2 diabetes. And following the result of the NATIVE study, results that were higher than what he expected, has decided to reduce the sample size from 64 to 34, a considerable decrease. So once again, showing that we really have an active drug. And then also very excited by how the results have been perceived in the field, and this has, I would say, concrete consequences and one of it is the constitution of our Scientific Advisory Board and the NASH. Scientific Advisory Board were really pleased to welcome Dr. Arun Sanyal, who has joined the team that was already in place with Dr. Manal Abdelmalek from the U.S., Sven Francque, Kenneth, of course, and all of the group is joined by Jean-Louis Junien, our scientific advisor. So that's lani in a nutshell. On odiparcil over the summer, the team has progressed with the interaction with the FDA. And with -- we have opened the IND in the U.S. So we are now able to start clinical trials in the United States. We have decided following the request by patients that were in the Phase IIa study to extend this study. And so the patient that finish this study will be included in a new extension study. And also, we are making progress in setting up the Phase I/II in children called SAFE-KIDDS. For those of you that are interested on the mechanism of action, we published a review of the mechanism of action in the PLOS ONE care review journal. In terms of ABBV-157, as I said in my introduction, look for updates in Q4 when AbbVie will finish the Phase I in patients with psoriasis. According to ClinicalTrial.gov, this trial is on time and results are due by mid-October. Financially, Jean will come back to the various success. But if you make a sum, you see that we raised close to EUR 125 million in the first 6 months. And now we have a cash runway through Q4 2022. And for us, this is important because this gives us sufficient, of course, cash to launch as planned, the pivotal trial with lanifibranor in NASH. So let me turn now the floor to Pierre, who will go through a review of lani and especially the result in NASH.

So yes, thank you, Frédéric. Hello, everybody. Very pleased to be here today. I'm sharing with you some slides on lanifibranor, odiparcil and the ROR gamma program. So of course, you are all very familiar with the profile of lanifibranor, but as a recap, it's a pan-PPAR agonist of unprecedented chemical structure, so it's not a [indiscernible]. It's not a fibrate. As a pan-PPAR agonist, it has moderate and well-balanced activity on this PPAR isoforms, PAR alpha, delta and gamma. And as you know, there is a strong static rationale supporting the concept that this unique mechanism of action would be very well suited for the treatment of NASH with the potential to address most, if not all features of NASH and particularly steatohepatitis and fibrosis. And as shown in our long-term non-clinical tox studies as well as recent clinical studies, lanifibranor is so well tolerated and safe. So the NATIVE trial investigated the efficacy and the safety of 2 doses of lanifibranor in patients with biopsy-proven NASH. And a combined score of inflammation and ballooning of at least 2 points out of a maximum of 4 as determined using the SAF score. The study randomized a total of 247 patients, with 72% of the patients having a NAS score equal or superior to 6 and 76% having fibrosis F2 or F3 scores, which means a very -- quite severe population. And the study was certified on type 2 diabetes. So next slide, you all very well informed, of course, of the results of this study. But as a recap, you know that the primary endpoint was met with steatosis achieved with a high dose of 1,200 milligrams per day and more than 40% of responders at the low dose of 800 milligrams per day, and this in the ITT population. Both regulatory endpoints, resolution of NASH with no worsening of fibrosis and improvement of fibrosis with no worsening of NASH were also met with the static effect at the high dose in the ITT population. And interesting to note is the effect of lanifibranor on the compositing end points, measuring the percentage of patients showing both resolution of NASH and improvement of fibrosis under treatment. And it can be seen here that in the ITT population, there were 3 and 4x more patients meeting this endpoint in the lanifibranor low and high doses versus placebo. And this effect was start seeing at both the low dose and the high dose. Next slide. So regarding liver enzymes, ALT, AST and GGT, all work quickly, meaning within a month, brought back to normal levels. And was maintained to such levels all along the study time course. So biomarkers of fibrosis, apoptosis and inflammation were also measured during the NATIVE trial. And on the fibrosis side, as you know, Pro-C3 detect the synthesis of type 3 collagen, which is anticipated to reflect the formation of new fibrotic tissue. And relatively to placebo, lanifibranor produced significantly greater reductions from baseline to week 24 of Pro-C3 in the overall study cohort. And among those with baseline Pro-C3 levels above 14 micrograms per liter at baseline and this cutoff being indicative of advanced fibrosis according to papers from Brill published in Diabetes Care 2019. Lanifibranor also produced a significantly greater reduction of TIMP-1 -- of the ratio TIMP-1 to MMP 2 ratio, which depicts the inhibition of matrix remodeling process. Relatively to placebo, lanifibranor treatment also significantly decreased plasma levels of CK18, which is an apoptotic marker. As well as ferritin and CRP, both being inflammatory markers. So in conclusion, these findings are consistent with the histological data from the NATIVE study, and confirm the anti-inflammatory, anti-apoptotic and anti-fibrotic mechanism of action of lanifibranor in NASH patients. Now regarding the lipid profile, as previously observed in our Phase IIa trial, both doses of lanifibranor rapidly increased HDL cholesterol and decreased plasma triglycerides. And there was no change in LDL-cholesterol. In NASH patients with type 2 diabetes, both doses produced a quick and highly significant decrease in fasting glucose as well as a decrease in insulin levels, indicating improvement of insulin sensitivity. And HbA1c was reduced by more than 0.5%. In the overall diabetic population, that was a well-controlled population, baseline levels of HbA1c was a mean of 6.5% in each treatment point. So in terms of safety, lanifibranor continues to show a favorable safety and tolerability profile, which is consistent with observations from previous clinical trials. The adverse events were generally mild to moderate in severity. There were 5 drug-related AEs leading to drug withdrawal, 2 in the placebo group, 1 in the 800-milligram group, which was moderate diarrhea and 2 in the 1,200 milligram group with 1 mild cardiac failure and 1 mild diarrhea. Relatively to serious adverse events, they were a total of 13 and after excluding biopsy related SAEs, there were 3 SAEs in the placebo group, 1 restructure, 1 cardiac failure, 1 urticaria. And 2 SAEs in the 800-milligram group with 1 pancreatitis, 1 undifferentiated connective tissue disease and 4 in the 1,200 milligram per day dose group with 1 angina unstable, 1 gastroenteritis, 1 pyelonephritis and 1 foot operation. So regarding body weight, and consistent with known insulin sensitizing pharmacology. We observed a modest weight increase with a mean of 2.4 kilos in the 800-milligram group and 2.7 kilo in the 1200-milligram group. And here, a couple of clarifying points regarding weight gain. Firstly, based on the paper from Professor Cusi and Professor [ Harrison ]. 6 months of prior treatment in patients with NASH. So actually, the study looked at the reason why these patients increase in weight and they demonstrated that this weight gain was not due to water retention. And the second thing is that in the same paper, you can read that weight gain most frequently develops within the first few months of treatment and appears to plateau thereafter. And this is actually what we observed in the 52-week system experience systemic sclerosis trial where patients on the high dose achieved a maximum of weight gain at week 24. And then the way it plateau over to the end of the study. Regarding edema, there was a total of 14 patients who reported peripheral edema, 2 in the placebo group, 5 in the 800-milligram per day dose group and 7 in the 1,200 million per day dose group. And all of them, except one, were of mild intensity and all were transient. What is interesting to note is that 8 out of 14 disappeared spontaneously; and 2, after treatment with diuretics of flavonoids. In other words, no treatment discontinuation due to edema. Next slide. So we feel like what we wanted to share with you is also the results from a physician survey that was performed in the U.S. and EU 3, meaning in Germany, U.K. and France. And in brief, these physicians positively value the fact that lanifibranor can address both improvement in fibrosis and NASH resolution and considered attractive lanifibranor positive effects on insulin resistance and glycemic control given the overlap of NASH with type 2 diabetes. There were different perspectives on the importance of weight gain. The majority of physicians believe that given lanifibranor efficacy profile, the cost benefit ratio was acceptable. And with proper patient counseling around weight loss, some of the weight gain could be offset. Some of the physicians suggested combination therapy could be used to manage or reduce weight gain, for example, with GLP-1 and physicians globally expressed less concern about edema, noting that the majority of them are mild. Frédéric?

Yes. Maybe I'd also point out another study independent from us. So this is internal research, but there was another very interesting study that was commissioned by Guggenheim Research published last week. In 45 U.S. physicians that treated, I think, 9,500 patients. I really invite you to go through that paper. It really carries some very positive messages for lanifibranor. First of all, very pleased to see that 80% of the physicians were aware of lanifibranor results and 88 had a favorable view on the risk benefit profile. And ultimately, and this is great because what we want to do at the end of the day is to commercialize our product. 82% of them were likely to prescribe. And on the weight gain, similarly to what we are seeing in our research, they viewed lani weight gain profile as acceptable and as well edema was generally viewed as tolerable. So globally, now we have 2 research -- 2 physician research that really confirmed the positive risk-benefit ratio of lanifibranor.

Yes. Thank you, Fredrik. And then also other evidence that lanifibranor tolerability profile is favorable is on this slide compared to other trials. You can see that for the NATIVE trial, the discontinuation due to AEs is in the low range, relatively to other trials in NASH. The SAEs were also in the low range. There were no cardiac disorders SAEs in NATIVE trial with lanifibranor. And of course, as you know, no pruritus and a positive lipid profile. So the next slide is, again, to put things in perspective, relatively to the current competition in the field. So lanifibranor, as you know, is the only NASH drug candidate. The produced NASH solution with no worsening of fibrosis and fibrosis improvement with no worsening of NASH, with -- in each case, more than 40% of responders. So next slide, just to mention the fact that, as you know, there is an investigator-initiated study with lanifibranor in type 2 diabetic patients with NAFLD, which is ongoing at the University of Florida. And this, under the leadership of Professor Cusi. And the objective of this study is to investigate the effect of the low dose, the 800-milligram dose of lanifibranor on hepatic insulin resistance, de-novo lipogenesis and intrahepatic triglycerides content. Based on the efficacy data on steatosis that we read in a NATIVE trial using a histological assessment, Professor Cusi took the decision to reduce the sample size from 64 to 34 patients in this trial and -- which is a very good news. So on the next slide, to recap on the next key milestone for lanifibranor in NASH. Finalization of Phase III synopsis and protocol is currently ongoing. We have end of Phase II meeting with FDA at the end of this year in Q4. Feedback from scientific advice will come also later this year in Q4. The finalization of this study with University of Florida and Professor Cusi is expected to take place in 2021 and as well as the launch of our pivotal Phase III trial with lanifibranor in NASH. Finally, an important meeting this year, as you know, of course, is the NAFLD. We have submitted, with our team and our investigators, several abstracts regarding the native trial results. So hopefully, there will be a lot of additional data presented with lanifibranor at NAFLD in November. So regarding odiparcil. So as you know, odiparcil is a small orally available molecule. It's potent substrate of galactosyl transferase I. The first enzyme responsible for the synthesis of GAGs that are of the DS and the CS form. And in sales, odiparcil will figure the synthesis of small soluble GAGs that will be excluded out of the cells, reducing the amount of GAG entering the glycosaminoglycans degradation pathway. And in studies performed with cells from MPS VI patients, we were able to demonstrate that odiparcil can reduce intracellular GAG accumulation. And all these data have been recently published in PLOS ONE. Also published on the in vivo data in mice model of MPS VI showing that daily oral administration of odiparcil can increase in the urinary GAG, reduce GAG accumulation in several organs and restore impaired mobility as well as corneal clouding, supporting the concept that this GAG clearance mechanism of action may have therapeutic potential for the treatment of MPS VI. So to assess that, to address this point, we have completed a Phase IIa study in MPS VI patients. The objective of this study was to assess the safety, pharmacodynamics and pharmacokinetics and efficacy of 2 doses of odiparcil in MPS VI patients. The study was conducted in 2 cohorts, a double-blind, placebo-controlled cohort of 15 MPS VI patients, who were receiving ERT plus low dose or a high dose of odiparcil or placebo twice daily during 6 months, and we had an open-label noncompetitive growth of 5 MPS VI patients naive for ERT who received 500-milligram of odiparcil daily during 6 months. The main efficacy parameters were related to clinical manifestations that are partially addressed by ERT such as mobility or respiratory function. And another category of efficacy endpoints were those absolutely not addressed by ERT. Basically, ophthalmology, cardiac function, audition and pain. So in a nutshell, the outcome from the study is that the safety, which was the primary objective, further supports the good overall safety profile of odiparcil. We had positive results regarding the efficacy after 6 months of treatment. We saw improvement in patients treated with odiparcil in addition to ERT with regards to corneal clouding as well as cardiac and respiratory function. For example, when looking for patients, we improved for more than 1 clinical manifestations, there were 3 out of 6 patients in the odiparcil plus ERT group versus none in the ERT alone group. And in the odiparcil treated group, 3 patients improved on respiratory function, 2 on corneal clouding and 4 on echocardiography with a decrease of left ventricular mass index or severity of mitral valve regurgitation. So considering the short study duration, 6 months, the fact that patients were under long ERT treatment duration and have an advanced status in the disease, and they were mostly severe patients and adults, we believe that the improved study showed positive signal regarding the efficacy of odiparcil in MPS VI patients. So the next steps on this program is the preparation of the improved expansion study, which is open-label safety and efficacy study in all completers of the improved trial. And preparing to launch a Phase II study in MPS VI children, the duration of which will be extended from 6 to 12 months following a scientific advice meeting with the EMA in order to give a better opportunity for demonstration of clinical benefit. Finally, regarding our collaboration with AbbVie, as you know, ABBV-157 is ROR gamma inverse agonist that was discovered through the AbbVie-Inventiva collaboration, which has moved forward in the clinic for the treatment of moderate to severe psoriasis. The single ascending dose and multiple ascending dose trial has been completed. And there is a second trial that has been initiated that will include patients with chronic plaque psoriasis. And the trial completion is expected by Q4 this year. So with this, I will leave the floor to Jean for the financials. Thank you.

Good morning. Good afternoon, everyone. So let's go quickly through the numbers. They are quite straightforward. So on a shareholder basis, we have consolidated the situation, which was quite already balanced between European and U.S. shareholders, especially with the NASDAQ IPO with an increase of 20% roughly of the outstanding shares. And we have been comforted by the existing shareholders as for any rate since the beginning of being public, plus new comers in the picture with a reputed shareholder. The key thing is, as mentioned by Frédéric, is obviously the level of cash as of today. The situation has dramatically in the good direction since last December, since we have close to EUR 134 million at mid-July. The situation of the June accounts were at 52.3%. And as mentioned, we have succeeded raising the $107 million with our recent IPO. And when you make the math comparing to the market value at EUR 385 million, I'll let you make the calculation. And we have a quite low-value in terms of market and a great move for improvement at the moment, considering the dynamic of our portfolio. And at the same time, we have also extended broadly the coverage. If you compare with the last semester, obviously, together with the IPO operations and extending the coverage in the U.S. Let's go quickly through the P&L figures. In terms of sales, we were not -- we had not planned some revenues this year. So nothing which was not unexpected. The other income, as usual, it's a specific R&D tax credit in France increased in Q2. The fact that our R&D expenses have decreased. This is the key information of this semester. I may say we have decreased by 36%, the R&D effort. And basically, due to the fact that first semester '19 we were full boost on all the expenses, including the SSc program, which was still ongoing at the time. And we also record in the first semester 2020 the savings effect of the restructuring plan that we had implemented Q1 '19 after the discontinuation of the SSc program. So it explains definitely, the decrease in R&D. Obviously, as you can imagine, with the very nice program we have ahead, other expenses will increase for developing the Phase III plan [indiscernible] in particular. G&A slightly increased, but also in line with the preparation of the IPO operations and upgrading the organization. And we incurred also nonrecurrent loss, same level as last year. Last year, we got the provision for the restructuring plan. And this year, we incurred, as you know, with the IPO in the U.S., some expense together with accounting treatment of each operation. So all in all, the net loss reached EUR 15.6 million compared to EUR 19.5 million last year, so an improvement. In terms of cash, again, we have raised EUR 125 million in 12 months. So it's specified here the EUR 10 million French State loan is related to the COVID. The EUR 15 million private placement in February this year, and the IPO proceeds that everybody knows about. So we are in a rapid position to face '21, '22 and '23 years in the future. So if you have no question, we can go the conclusion with Frédéric.

Yes, very quickly -- [Foreign Language], Jean. So the next step for us and what you can expect to see from market, of course, news on lanifibranor. Pierre mentioned the ASLD communication, we plan to be active there. And also, we have this very important meeting with FDA and EMA to decide the design of the Phase III. So this will be -- it's really important. Odiparcil, after the positive improved study will continue, and there are 2 studies that will be launched first half of next year. And new results are expected from AbbVie with ABBV-157 with the achievement of the clinical book in psoriatic patient, which is due for Q4 2020. So as you see, a lot of events and news that you can expect from us. So that was the last slide. And therefore, I would turn back to the operator, who will explain how to ask your question.

[Operator Instructions] Your first question comes from the line of Lucy Codrington from Jefferies.

Just a few from me. So now that you've got the U.S. IND for odiparcil, will U.S. patients be included in the SAFE-KIDDS study? Or will you be conducting separate studies in the U.S., at least initially? Secondly, in terms of formulation, both for odiparcil and lanifibranor, just has the pediatric formulation work been finalized ahead of the peak study? And secondly, could you provide an update on the formulation work for lanifibranor ahead of the Phase III. I believe you have been aiming to try and reduce the number of tablets. And I'll stop there.

Thank you, Lucy. So I'll take the early part of the question, and then Pierre can go over the CMC on lani. So the Phase I/II safety for odiparcil will be carried out in Europe, 4 centers, if I remember correctly that are considered for this Phase I/II. The IND was opened in the U.S. for supportive Phase I. And concerning the pediatric formulation for odiparcil, yes, it's readily available, and it's not on the -- it's not a limiting factor for the odiparcil safety trial. On lani you had a question on the Phase III formulation.

Yes. So the Phase III formulation will be -- we have -- for the 800-milligram dose, we have 2 tablets of 400 and for the 1200-milligram dose, 2 tablets of 600 and the formulation is the same than the one that we have used for the NATIVE trial.

Well we move from capsule to tablet for the phase tablets.

With the phase tablets.

Yes. Tablets, yes.

Your next question comes from the line of Derek Archila from Stifel.

Just a couple from us. Maybe first on any color you can provide on specific subgroup analysis that you might present at ASLD specifically around weight gain and maybe diabetic and nondiabetic patients? That would be my first question. Second, in terms of the data you showed today around the patients with edema, do you have a sense of what percentage of those patients had diabetes? And then the last question, in terms of MPS and odiparcil. So you talked about when you're going to be starting these trials, I guess, when would we see the next data set from those newly initiated trials? Is that something that's going to be a late 2021 event? Or are we talking 2022 and beyond?

Sorry, Derek, we were cut off. So you had a question about the communication at ASLD and clarification question about the edema. So maybe, Pierre, can you?

Yes. So on the ASLD, yes, we have submitted an abstract, which provides an analysis of the data according to diabetic status. And regarding your question on edema, if those were more frequent in diabetic patients versus nondiabetic. I cannot answer. I don't have the figures. I just mentioned the fact that according to investigators, there were only 2 drug-related edema at the low dose and 2 drug-related edema at the high dose. But I don't know if they were diabetic or nondiabetic patients.

Yes. I think my last question might have got cut off, but I just wanted to ask around odiparcil and MPS in terms of you talked a lot about starting these new studies. I just wanted to kind of get a sense of when we could expect additional data from odiparcil in that indication.

So we have not given any forecast, these are also -- it's also due to the COVID-19. It's very, as you know, fragile population. What we can say is that it -- as you've seen, we have decided to extend following the scientific advice with EMA, the Phase I/II increased by from 6 months to 1 year. So if we start in 2021, there's no data to be expected soon, we have at least to treat by -- for 1 year.

Your next question comes from the line of Etzer Darout from Guggenheim Partners.

This is Paul on for Etzer. Just a few quick ones from us. So first, regarding the biomarker data, can you provide a little bit more color about the significance of these fibrosis signal changes in the context to the NASH patients? And maybe anything we've seen from other late-stage NASH programs? And secondly, are there any additional incremental biomarker data we might expect at the later meeting in November?

Yes. Okay. Yes. So I think the important -- a few important message with the biomarker data we've just presented to you is that we have clearly -- clear evidence that, as expected, I would say, lanifibranor behaves and have anti-inflammatory antiapoptotic and antifibrotic mechanism of action in NASH patients. So we look that by 2 different angles. So for the fibrosis, for example, Pro-C3 is a marker of ongoing fibrogenesis. And you can see that we have a significant effect in NASH patients with -- at 6 months, a significant reduction of circulating Pro-C3 relatively to placebo. And then we looked also at steat population having a Pro-C3 level above 14, and those are the ones for which there is even a more active fibrogenesis. And there, we see it's still a quite significant effect of lanifibranor on this fibrogenic marker. Then on the other angle, we looked at more on the fibrolysis and ratio of TIMP-1 on MMP-2. And here, we served a very clear and significant reduction of this TIMP-1 and MMP-2 ratio, which indicates that together with Pro-C3 data that lanifibranor is indeed inhibiting the metrics remodeling process. So that is very encouraging. And I think it's totally in line with the histological observation of an improvement of fibrosis in NASH patients after 6 months. And then the rest goes also in the good direction, I would say the CK18 is a well-recognized marker of apoptosis, and we can see very strong reduction, minus 41%, highly significant versus placebo. And inflammation, obviously, CRP ferritin is also very well decreased by our lanifibranor treatment. So I think these are very strong data, quite compelling and supporting the -- again, the overall anti-inflammatory, anti-fibrotic and anti-apoptotic effect of lanifibranor in NASH patients.

Great. And can we -- yes, so I just -- any additional data we might expect at the later meeting in November in terms of biomarkers.

Yes, absolutely, we will have more color on these different biomarkers and still work is ongoing. And then, of course, this will be completed by the ASLD meeting, yes.

Your next question comes from the line of Ed Arce from H.C. Wainwright.

Congrats on the wonderful data there with NATIVE. The data that you shared this morning, the new biomarker data, I just wanted to ask about the Pro-C3 above the 14-microgram per milliliter threshold. I think you mentioned that there was some work done around that as significance and a paper that you might have cited, if you could review that again, that would be helpful.

Yes. The paper is from Brill, Brill is from the team of Professor Cusi. It's Diabetes Care 2019. And he basically described this cutoff as being indicative of advanced fibrosis.

Okay. All right. Great. And then just wanted to ask about the 2 patients that withdrew from the study, 1 mild, 1 moderate case of diarrhea. Maybe just in a broader context, how does this fit within the overall profile with regards to GI events on lani?

So the area has been observed in a few patients, right?

Yes.

So I don't have any...

Yes, we don't have a lot of insight. So we do not have any specific worries about GI. It's clearly not related to the mechanism of action. I would say we have not yet received any particular feedback or a script on those 2 patients. And GI did not appear as something significant in the trial, I would say.

Yes. Yes, we had -- this is part of the AE. So we had 1 moderate diarrhea, the low dose and 1 mild diarrhea at the high dose.

Right. Okay. Fair enough.