Hello, everyone. Welcome to Poxel's half year 2021 results presentation. Before giving the floor to Thomas, I remind you that you have the opportunity to ask your questions orally by raising your hands or by writing them down in the Q&A tab during the Q&A session. Thomas, I give you the floor.
Thank you very much. Thank you for joining us today. I am Thomas Kuhn. I am the CEO of the company. After my introductory comments, I will hand the call to Anne Renevot, our CFO, to review the first half 2021 financial results, and then David Moller, Chief Scientific Officer, will provide an update on our clinical pipeline. Before we begin, this is our forward-looking statement.
Just to remind that forward-looking statements are subject to inherent risks and uncertainties beyond the company's control that could cause the company's actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements. Further information can be found in our most recent regulatory filings.
As some of you know, Poxel's missions and vision remain to discover, develop, and commercialize innovative therapies for patients suffering from serious chronic diseases, and rare diseases with underlying metabolic pathophysiology.
Congratulations to our highly experienced team in the metabolic disease field, which achieved our first product approval in June for imeglimin, now launched and marketed as TWYMEEG in Japan. Following this success, we announced a new strategic direction, which align our vision and mission with a faster to market strategy in rare diseases. We increased our focus on rare metabolic indications that represent the intersection of high unmet medical needs, preclinical and clinical data, opinion leader enthusiasm, significant commercial opportunity, and attractive time horizon.
We are now very focused on NASH and rare metabolic indications, starting with adrenoleukodystrophy, with the aim to advance into pivotal trials, one program in NASH and one program in ALD. The approval of our first product in Japan, followed by the product launch by our partner last week on September 16, opens a new chapter for Poxel to drive shareholder value.
With additional funding from TWYMEEG, we are investing these funds to accelerate and expand our clinical pipeline of rare metabolic disease programs. By developing products in rare metabolic disease, in addition to NASH, we can be more efficient with our resources and more expediently deliver novel medicines to patients with even stronger potential to create significant value for the benefit of our shareholders.
As you can see in this chart, this is our pipeline. It is a well-diversified pipeline in terms of indications, clinical stage, and risk profile. David will walk you through our development plans for NASH and ALD and how this can position us to be potentially initiating pivotal trials in ALD in 2023. Our clinical pipeline continues to advance. Earlier this week, we announced the completion of the enrollment in the PXL065 phase II DESTINY-1 trial with 123 biopsy-proven patients enrolled.
We look forward to the result in roughly 1 year from now in Q3 2022. We also intend to further strengthen our existing metabolic pipeline with additional internal and/or external opportunities. We specifically have next generation compounds from our existing platform technologies that could reach clinical stage in a near-term horizon. The TWYMEEG approval and launch in Japan represents a major milestone for Poxel and the accumulation of several years of clinical development work.
This is a strong validation of our R&D capabilities and the international footprint that we have established. The approval in Japan allowed Poxel to receive EUR 13.5 million of the third and final tranche of the IPF loan in June, and EUR 13.2 million milestone payment from our partner, Sumitomo, in July. Sumitomo, who is the market leader in Japan for type 2 diabetes, launched TWYMEEG last week on September 16th.
Based on our current forecast, Poxel is entitled to future potential sales-based payments of up to approximately EUR 200 million, as well as escalating double-digit royalties. We believe that TWYMEEG is an important addition to Sumitomo existing number one diabetes franchise through its differentiated mechanism of actions targeting the two defects of diabetes, including favorable efficacy and safety profile.
Based on the clinical data obtained in phase II and phase III, we believe that TWYMEEG has the potential to be used as a monotherapy alone, as well as in combination with other products, specifically complementing well Sumitomo existing infrastructure in type 2 diabetes. This approval of TWYMEEG provides patients with type 2 diabetes the opportunity for greater flexibility in their treatments.
As mentioned earlier, we really want to expand and further strengthen our clinical pipeline of rare metabolic disease programs as it represents the intersection of high unmet medical need, preclinical data and clinical data, opinion leader enthusiasm, significant commercial opportunity, and attractive time horizons.
Particularly, this market opportunity for rare disease is highly attractive due to premium pricing supported by prior orphan drug approval, and Poxel has the ability to commercialize on our own, which would allow us to capture greater economics. We believe that Poxel is well-equipped to be a leader in this field given our exciting programs and our capabilities. I will now hand over to Anne, our CFO, to go through the 2021 H1 financial statement. Anne.
Thank you, Thomas. Good evening, everyone. I will now review our financials for the first half of 2021. Let's start with revenue on slide nine. Poxel reported revenues of EUR 13.3 million for the first months ended June 30, 2021, as compared to EUR 6.4 million during the corresponding period in 2020. This revenue mostly reflects the JYP 1,750,000,000 milestone payment from Sumitomo Dainippon Pharma, triggered by the June marketing approval of imeglimin in Japan.
The payment was received in July. Turning to slide 10, which is a statement of comprehensive income. As a preliminary remark, as a biotech company, the majority of Poxel resources are allocated to research and development activities. Net R&D expenses amounted to EUR 14.7 million for the first half of 2021, as compared to EUR 12.6 million for the corresponding period in 2020.
R&D expenses for the first half of the year primarily reflected the clinical study costs incurred for phase II DESTINY-1 study evaluating PXL065 in NASH. To a lesser extent, they also reflected some phase IIa clinical program residual costs for PXL770, the treatment of NASH, and also the regulatory costs incurred over the period for imeglimin, for which the company obtained marketing approval in June.
As a reminder, R&D expenses are net of the R&D tax credit that resulted in an income of EUR 1.5 million for the first half of the year, which is the same level as for the first half of 2020. General and administrative expenses amounted to EUR 5.4 million for the first half of 2021, as compared to EUR 6 million for the first half of 2020.
The financial loss amounted to EUR 1.2 million for the first half of 2021, as compared to an income of EUR 2 million for the first half of 2020. This loss primarily reflected the interest attached to the company debt issuance. The net result for the financial period ending June 30, 2021, was a net loss of EUR 8 million, as compared to a net loss of EUR 12.1 million the corresponding period in 2020. Moving along to slide 11 with the assets.
Two comments. First one is the trade receivables that amounted to EUR 13.3 million at June 30, 2021, compared to EUR 0.3 million at December 31st, 2020. This reflects the marketing approval milestone for imeglimin in Japan that was accounted for at June 30, 2021, and paid in July. Cash and cash equivalents amounted to EUR 36.9 million at June 30, 2021, compared to EUR 40.2 million at December 31st, 2020.
The change in cash for the first semester amounted to EUR -3 million, reflecting EUR 13 million coming from financing activities and EUR -16 million coming from operations. Moving along to slide 12 with the shareholders' equity and liabilities. The shareholders' equity amounted to EUR 21.6 million for the first half of the year, compared to EUR 26.9 million at December 31st, 2020, which mostly reflects the half year 2021 net loss.
Total financial liabilities amounted to EUR 37 million compared to EUR 24 million at December 31st, 2020, mostly reflecting a EUR 30 million loan with IPF and a EUR 6 million loan with PGE loan. Last comment, the litigation with Merck has been settled, and the current provision has been fully reversed accordingly. Turning to slide 13 with the statement of cash flows.
As previously explained, the cash flow from operations activities amounted to minus EUR 16.1 million for the first half of 2021 compared to EUR 14.5 million for the first half of 2020. This included the half year 2021 net loss, but also a EUR 10 million change in working capital, which mostly reflected the EUR 13.2 million milestone payment that was received as part of the marketing approval of TWYMEEG in Japan and recorded at the end of June 2021, paid in July.
The cash flow from financing activities amounted to EUR 12.8 million for the first half of 2021, compared to EUR 23.2 million for the first half of 2020. This mostly represents the drawdown of third tranche of the IPF loan for the amount of EUR 13.5 million. Moving to slide 14. Thank you.
We have listed the relevant shareholder information as well as our research coverage in both Europe and the U.S., which includes five names, Oddo, Bryan Garnier & Co., and Degroof Petercam in Europe, Jefferies in the U.K., and JMP in the U.S. I will now hand over to David Moller to provide an update on our clinical programs.
Thank you, Anne. It's my pleasure to now provide you with an update on our R&D activities. Starting with our advance into rare metabolic disease with our existing platforms, the deuterium-modified TZD and AMPK activator small molecules. Let me first summarize some of the key features of our two lead molecules. PXL065 is the deuterium-stabilized R-stereoisomer of pioglitazone, a widely prescribed medicine for type 2 diabetes.
Unlike pio, 065 lacks significant PPAR gamma activity and mediates its efficacy via non-genomic TZD-related pathways, such as modulating the mitochondrial pyruvate carrier, and inhibition of acyl-CoA synthetase 4. Strong efficacy has been documented in several preclinical disease contexts, including NASH and ALD, but without PPAR gamma side effects like weight gain and fluid retention. Given its relationship to pio, the 505(b)(2) regulatory pathway in the U.S. can be employed, leveraging a large safety database for the parent compound.
More than 130 humans have been exposed to PXL065 per se, and the expected clinical safety has been validated, and we've also shown that selective dose proportional exposure to the preferred isomer, the R stereoisomer, translates into humans. PXL770 is our novel direct AMPK activator, the first such molecule to be studied in any human disease.
In preclinical models of several diseases, it exerts substantial efficacy. Clinical development to date has demonstrated target engagement and translation of several diabetes and NASH-related efficacy parameters to humans, suggesting the likelihood of broader translation for this mechanism. Preclinical and clinical safety have also been established with favorable safety profiles in more than 200 humans exposed for up to 12 weeks. Let's move on and talk a bit about adrenoleukodystrophy.
X-linked adrenoleukodystrophy, or ALD, is a monogenic inborn error of metabolism due to mutations in the ABCD1 gene, which encodes a key cellular fatty acid transporter. This defect results in accumulation of very long chain fatty acids, VLCFA, with damage to several tissues, in particular neurons. As an X-linked disease, males are more severely affected, but many females are as well.
ALD is increasingly being diagnosed based on the recent and broad-based adoption of newborn screening. The prevalence of ALD is similar to that of hemophilia or spinal muscular atrophy. About 20,000 patients in the U.S. alone. This slide provides a high-level view of ALD pathophysiology. As I mentioned, increases in VLCFA, specifically saturated C26 fatty acid, are the primary driver of disease, with downstream pathologies leading to axonal degeneration for both cerebral and spinal cord forms of disease.
Importantly, multiple recent publications support the utility of both AMPK activation and TZD-related pathways for the treatment of ALD. We have developed evidence to show that both of our platforms, AMPK activators and dTZDs, can be leveraged to address this pathophysiology to correct the primary defect by suppressing VLCFA levels and by potentially ameliorating downstream consequences that include mitochondrial dysfunction, inflammation, and cell death.
Over the course of the last year, we've carefully studied both of our lead molecules in classical ALD preclinical models. These include patient-derived cells and the ABCD1 null mouse. In data that are not shown on this slide, we observed that both compounds produce substantial reductions in VLCFA, both in vitro and in vivo, including in brain and spinal cord.
In more recent experiments shown on this slide that were also conducted using the ABCD1 mouse, we observed evidence of improved neural histology and neural behavior with both 065 and 770. Some examples of these data are shown here. In the images on your left and accompanying graph, you can see that distorted axonal morphology is improved, in this case by 065 and pioglitazone, but we've also seen similar effects with 770.
On the right are quantitative results of balance and coordination using a balance beam test, and here we see that the diseased mice exhibit impaired performance versus wild-type mice, and the treatment with 770 was able to reverse this defect. A similar profile also seen with 065.
Based on all the preclinical and clinical data we have for both platform leads, we now plan to initiate two parallel and identical phase IIa biomarker-driven POC studies, one with 065 and one with 770. The study design was developed with substantial input from several disease experts in the U.S. and Europe. Each trial will enroll approximately 12 adult male patients with the most common subtype of ALD, AMN.
Following a run-in period, patients will be treated for 12 weeks with a single oral daily dose of either molecule. Readouts will include PK safety and measurements at several time points of key disease biomarkers, VLCFA and neurofilament light chain, both of which are validated as disease-associated. Additional exploratory biomarkers will also be assessed. These trials are expected to begin in early 2022, with data available later that year.
Following analyses of these results, we should be able to choose the preferred molecule for further advancement into a pivotal trial to begin in 2023. We intend to finalize our phase III plan with regulatory agencies and further discussions with experts and also with patients. Depending on treatment duration and the final selection of endpoints, our pivotal trial could lead to an NDA filing in 2025.
In summary, we're very excited to pursue treatments for ALD as this represents an area of very high unmet medical need due to a lack of current therapies. It also provides a substantial commercial opportunity given premium pricing for orphan drugs with similar prevalence, and we can expedite clinical development. The ALD community is very engaged with us, and we've established relationships with key opinion leaders and collaborations with important patient advocacy groups. Now let me briefly summarize our progress in NASH.
Given the unmet medical need, and given that there are still no treatments available for patients, we believe that our innovative approaches with both PXL770 and PXL065 enable Poxel to have a significant role in this area. In addition to strong preclinical data in ALD, both PXL770 and PXL065 have evidence to support their development for NASH. Clinical validation exists for both.
For PXL065, a wealth of clinical data in NASH with the parent molecule, pioglitazone, has demonstrated substantial efficacy, at this point in 6 independent trials. For PXL770, our recent phase I-B and phase IIa results have also yielded prominent efficacy signals. Both are first in class and both are daily oral approaches. An innovative development approach can also be pursued for both molecules as well.
As we announced last week, our PXL065 phase II study, DESTINY-1, is now fully enrolled and will yield results approximately one year from now. By leveraging the 505(b)(2) regulatory path, we designed a streamlined single phase II study with three closely separated dose levels.
Based on phase I data and PK/PD modeling, the 15 mg dose is predicted to achieve the efficacy equivalent of 45 mg of pioglitazone without significant weight gain or edema. Results from this trial will enable the selection of one or potentially two doses for advancement into phase III. With PXL770, we demonstrated good safety and tolerability in humans, as well as having established target engagement.
In the most recent trial, the STAMP-NAFLD Phase IIa study, we showed evidence of efficacy with respect to both NASH and diabetes-related parameters, and a substantially greater response for all parameters in patients with fatty liver disease who had coexisting type 2 diabetes.
This finding may relate to literature showing that endogenous AMPK activity is suppressed in the context of hyperglycemia or other aspects of metabolic dysfunction. As Thomas mentioned, our newer strategy includes first evaluating the potential of PXL065 in NASH and the assessment of both 065 and 770 in ALD before considering the further pursuit of PXL770 for NASH. I'll now turn the presentation back over to you, Thomas, to conclude.
Thank you very much, David. Over the next 12 to 18 months, as you have understood, we have a number of near-term milestones to drive, sorry, the growth, including the readout from the PXL065 DESTINY-1 phase II trial in NASH, for which David gave you an update, as well as the two proof-of-concept biomarker studies for the treatment of adrenoleukodystrophy. To summarize on the launch of TWYMEEG in Japan opens a new chapter for Poxel and provides a future funding stream to Poxel that we are willing to invest to accelerate and expand our clinical pipeline in rare metabolic diseases, first leveraging our internal platforms.
We are very excited that our new strategic direction with an increasing focus on rare metabolic disease, in addition to NASH, has the potential to deliver significant value to shareholders. As we turn over cards on multiple phase II studies in 2022, that may allow us to initiate pivotal trials in 2023. With that, we look forward to updating you on our progress. I'd like now to thank everyone for your attention, and we can now open the Q&A session. Thank you very much.
Thank you very much all for your presentations. We can now proceed to the Q&A session. I remind our participants that they have the opportunity to ask questions either orally by raising their hands or by writing them down in the Q&A tab below their screen. We have Lucy Codrington, who would like to have the floor. Hello, Lucy. Lucy, you have the floor.
Hiya. Thanks for taking my questions. Just a couple from me. I was wondering if it'd be possible to provide a little more detail on your commercial expectations for TWYMEEG, particularly in light of the MHLW sales prediction. I understand that MHLW is traditionally very conservative, even if I were to double it still seems quite light compared to my forecast.
If we were to use Equa sales for context, how do you view TWYMEEG compared to Equa's commercial performance so far? Excuse me. Secondly, it seems to me you could end up in a conundrum in which the PXL065 data looked better for ALD, you end up also having very strong NASH data, whereby the path to market and the potential addressable population in NASH are arguably bigger for PXL065 than PXL770. How would you potentially manage that situation?
I know it'd be a good situation to be in, kind of how would you view that then? Then finally, if it's possible, could you give a rough guide to the cost of the ALD studies or, and or your projected cash runway now that you are going to be conducting the ALD trials? Thank you.
Thank you very much, Lucy, for your question. Let's start maybe with imeglimin. In terms of forecast, Sumitomo has not given any official forecast there. It will be difficult for me to answer these questions. There is, however, a number of elements that basically we can share with you on.
Just to recall that the consensus of analysts, not only you, Lucy, most of the analysts or all of our analysts really have in mind that the product really could deliver between $400 million-$450 million sales really for imeglimin at peak in Japan, which we believe is the right number. To come back to your questions, the MHLW report that you've seen has basically been generated in the context of the pricing discussion for TWYMEEG in Japan.
Of course, as you can imagine, it's a very conservative approach there. One element that you need to keep in mind is specifically, the low patient base that has been included in this report. As we all know, there is a significant higher number of patients in Japan between basically 8 million-9 million patients overall.
I think what you have in your model, we believe is still really something that we believe we could target because again, we demonstrated very strong profile for imeglimin. Sumitomo is the number one really player in diabetes in Japan with the largest sales force, 800 sales force. They have been very active lately, educating the market and really setting up the floor really for the launch of the products there. To come back to another piece of your questions.
As you said, Sumitomo, they have five products on the portfolio for diabetes, including Equa. You might have seen that for the last year on, they've disclosed that basically, they've nearly generated close to $900 million really for the whole franchise. Equa is a major contribution to it now. Between $350 million to basically, well, around let's say $350 million overall.
We believe this is very interesting vis-a-vis imeglimin. Given the profile of imeglimin, as we've said, given what we've shown in the phase III, Sumitomo has in mind, of course, to combine imeglimin to any product available in Japan, starting with DPP-4 inhibitor, so including Equa, of course, as you can imagine. We know that DPP-4 inhibitor is the largest prescribed treatment in Japan.
Of course, that will help to really ramp up the uptake of imeglimin on the market. Also what's interesting is that very early on, and that's unique in Japan, Sumitomo will have the opportunity to basically broaden the patient base and target really a monotherapy indication and even a first-line indication. We believe that this could occur within the near future.
As a reminder, we showed very robust efficacy of imeglimin during our phase III trial, with close to a minus 1% reduction. Very good safety. That's why on all these bases, we remain very excited about the potential of the product. We believe that what Sumitomo is doing with Equa could reflect well, what they could do as well on imeglimin. That's why we remain really bullish on what really imeglimin could deliver as a sales engine.
That's really related to your question on TWYMEEG. Going back to your question really on the strategy more and our platform. You are right. I think, we have in mind that our platform, whether this is the AMPK activation platform or the deuterated TZD platform, have a strong potential in various indication.
The example that you took, Lucy, could be definitely the right one, where basically PXL065 could deliver very good results in both ALD in the upcoming phase II, as well as in NASH in the DESTINY-1 trial there. Just to mention things, these two readouts will be available pretty much at the same time, with the readout for NASH in Q3, and the readout really for ALD, it's better in Q4.
The goal will be, as we mentioned earlier, to really continue and push forward one program into the pivotal program for ALD and one really for NASH. What we have in mind to be clear is that the same product cannot be really progressed in these two very different pathologies. For obvious reason, we all have in mind, of course, the price difference between a rare disease and NASH, but there are much more reason to this.
That's why if that's true, and as you said, it would be a good program to have, to have the same product really having really positive and robust results really for two very different indication. That's where developing our next generation compound could be very important. We have ongoing efforts on this.
The goal will be to bring a new candidate for development in the near future, so that if really one platform deliver the best result for these two different indication, we'll have the ability to select the lead asset for one indication and then to push the next generation compound for the other indications there. I don't know, David, whether you want to elaborate on this.
No, I think that's a good point. Of course, the PXL770 also has strong potential in ALD, and we could be in a situation where we might have PXL065 going forward for NASH and choose to focus the ALD indication on with PXL770. That's another scenario. That would be the best case scenario, perhaps.
I hope that answer your question. Your last question on the cash runway. Before leaving the floor to Anne, just to put really some figure there. I think one of the interests towards your question of this rare diseases strategy is that, of course, in contrast to NASH and diabetes, which require hundreds and hundreds of patients in the studies. In rare disease, of course, there will be a much more limited number of patients there.
As you see now, the two proof of concept studies that we plan to do will be of 12 patients each. That's a very limited number of patients, that's a few million investment for each study. Not a lot of investment compared to other disease. Going forward, of course, we are working on the confirmatory program.
Again, we have in mind that for ALD, and we have already interesting discussion in that, hundreds or maybe 150, and of course, this amount, this figure is to be confirmed, of patients will be required. That's, again, that's not a big number. That's why, with our proven capabilities, definitely, the goal will be to move forward and deep these opportunities, because we could have really everything in hands to do that by ourselves there. That could also be true, by the way, for the commercialization there. That's really one of the key interests moving there. Maybe Anne, you want to give some numbers on all this?
Yes, with pleasure. Hi, Lucy. Yes, let me please share with you some maybe more precise view on our cash runway. As you know, as of June, the cash and cash equivalent was at EUR 36.9 million. In addition, we received in July a milestone payment for EUR 13.2 million. We have quite a comfortable cash position today. This cash position fully covers our plan on NASH.
I t totally covers the full completion of the ongoing phase II DESTINY-1 trial for PXL065 in NASH until the readouts, which are expected in Q3 2022. Coming to the IPF program. Our funding capacity depends on a number of factors, starting with the level of royalties and sales-based payment that we will receive from imeglimin in Japan.
Since we are extremely confident about our plan, we believe that we should not wait, and we aim to strengthen our balance sheet, and are currently considering additional funding by equity or non-dilutive, which will be used to further accelerate our development plan in ALD. Maybe last comment, as Thomas mentioned, the two ILN proof of concept studies are only EUR few million. We believe that it will be less than EUR 10 million to fully implement these studies. We are very committed to funding these trials.
Okay. Would you say you would reiterate your prior guidance, which was kind of cash through 2022?
Absolutely. Yeah.
Okay. Very helpful. Thank you so much.
Thank you, Lucie.
Thank you very much for your answers. We have a question about the imeglimin product, TWYMEEG, now that it has been commercially launched. Have you collected feedbacks from Japanese professionals, and what are the nature of these feedbacks, Thomas?
Yeah. Absolutely. Sumitomo has done this. That's of course, part of the work. They've been educating the market. Of course, they wanted to know what could be really the main attribute of the products there. The key attributes that really have been emphasized by the market and by the prescribers really to Sumitomo on imeglimin are the following.
First, really, the novelty and the mechanism of actions there. It's a dual mechanism of actions targeting really the two key effect of diabetes. Improving the beta cell function as well as improving insulin resistance, which is unique. Of course, the prescribers are very bullish on that because in contrast to other products currently on the market, imeglimin will be able to really target the root of the disease. They believe that it's going to be very important.
They also emphasize, given that mechanism, the potential to slow down really the progression of the disease and to also prevent the occurrence of the diabetes complications. By targeting the mitochondria, you can basically protect the beta cell function as well as preventing really micro and macrovascular complications there.
Third, I think the safety of the product has been greatly emphasized. Just to remind everyone, in Japan, it's a fairly aged population with more than 60% of the population, diabetes population, older than 65 years or older. Having a safe product really is important really for this population because they are basically more sensitive than the younger population. Of course, the efficacy that has been shown in the phase III has been really interesting as a monotherapy as well as in combination with all existing agents really there.
As a reminder, we showed very robust efficacy on top of all other products currently standard of care available in Japan. I think all this really is the foundation for great success in Japan. We are confident that this could basically translate into a significant impact on the market.
Thank you very much, Thomas, for your answer. I remind our participants that they have the opportunity to ask questions either orally or by writing them down. We have a new question regarding Poxel's increasing focus on rare metabolic indication in NASH. Maybe, Thomas, you can explain and develop why Poxel has increased its focus.
Yeah. Okay. I can get back to this. What I mean, with the approval for and the commercialization of TWYMEEG, Poxel will be entitled to receive a significant cash infusion from the sales of the product with the milestone, with the sales-based payment, as well as with the royalties we should get from Sumitomo. Definitely, as a biotech company, we want to invest really this cash into new development opportunities to deliver new product to the patient and to grow further the company and to deliver, of course, shareholder value to our shareholder.
We believe that really, having a balanced approach with diseases like NASH as well as rare disease could be very interesting, because one, our platform enable us to that, and I think that's really the basis. Targeting the kinase activation, targeting really the non-genomic pathways of the TZDs.
That could be interesting in all these indications. That's why we believe that it's important to fully leverage that. That's the first point. The second point is that, in terms of time horizon, that could be also very interesting. Of course, NASH will take more time. That's why having these rare disease really could provide short-term, near-term catalyst there.
We can basically, with our plan, move forward into a pivotal program for both NASH and rare disease in 2023. That's really near-term catalyst that could be very interesting there. That's why really these two approaches, we continue to be extremely, really motivated to go there, because that could offer significant opportunities.
As I mentioned, for rare disease, we will have the ability and the capabilities to move by ourselves deep into the development and even maybe into commercialization there, because we will have everything in hand basically to do that. In NASH, at some point of time, is it going to be for phase III or later, having a partner on board could be really important there. If PXL065 really confirm the potential it has linked to TZDs, as David reminded us, I think that could open up a lot of doors there. Of course, a partner will be needed there, but that could really balance what we are doing in the rare disease field there.
That's why we feel that really running on two different legs, such as rare disease and NASH, is really a good strategy for us going forward with, of course, the very solid foundation that we have with TWYMEEG. David, do you want to add something there?
Maybe just a couple of other points. From a purely scientific and clinical perspective, it's clear that there are a lot of rare diseases. We feel compelled to really look into that. Secondly, about a third or so of all of these rare diseases have a metabolic pathophysiology. Based on a lot of some newer literature that pertains to both of the platforms that we're now working with, it's becoming more and more evident that there are a number of rare diseases that we could potentially be targeting.
Traditionally, these targets and these pathways have been represented as key targets for NASH, and that's why we got into that initially and really focused there for up until very recently. Now it's clear from the literature and some of our own experiments that there's a lot of other indications in the rare disease space as well.
Thank you, David.
Thank you very much, David and Thomas. We have Jason Butler who asked for the floor. Jason, you have the floor.
Hello, Jason.
I'm afraid you're on mute, Jason. You should unmute.
Can you guys hear me now?
We can hear you well.
Great. First of all, congrats on the progress, including completing enrollment in the PXL065 phase IIb trial. Can you speak a little bit about the work that you've done to minimize the impact of the COVID pandemic on that trial? How is the dropout rate or completion rate looking in the trial compared to your expectations before it started? J ust how are you handling potential missed patient visits?
Yeah. No, good question, Jason. Of course, we've been very pleased by the completion of the enrollment. Basically, if you recall, and for those who are not familiar with the story, first, we delayed the initiation of the trial, because we were supposed to initiate the trial in Q2 2020, so right really during the first wave of the pandemic. We decided basically to wait a little bit to make sure that the clinic, the hospital, the caregiver that could handle the product would be in a safer mode there. That's why we initiated the trial in September.
When we did that, of course, it give us a bit more time to really elaborate the processes on how to manage the patients, how to manage really all the logistics to make sure that whatever could happen in the future, and we've seen that, unfortunately, as with new waves, new variants coming in, we could mitigate that and basically make sure to ensure the good safety of the patients, and make sure to continue progressing really the trial. I think we prepared that well. The study was run in the U.S. only, and we identified really, I think, good sites there.
I think our clinical team has done a really, really good job there together with the CROs we worked with, really being in very regular contact, almost daily contact, really, with the caregiver, with the person dealing with the trial to make sure that we could provide them with any answer should this be. Really very close interactions there and I think that has proven to be very successful there.
To answer and to give you some more color on this and to answer as well your question, I think as well, and maybe that's just really my perception, but dealing with the product coming from pioglitazone has been a plus because, of course, the investigator they have pioglitazone in mind now, and they know pioglitazone.
In contrast maybe to other drug, we could continue really enrolling and screening a lot of patients are really motivated to join our study now. That has absolutely not been really the issue there. In terms of screen failure, I think we had what we expected there. Maybe slightly higher, maybe slightly due to COVID-19 there, but not too dramatically, basically.
Yeah, it's been, I think overall pretty good and really according to plan and maybe this parent drug has helped really to give confidence on all this there. Then, of course, the goal now will be to make sure that we keep all these patients in our trial there. Again, we have already worked on a plan to make sure that really the patients will continue going through the different visits there.
We have, as you can imagine, very regular monitoring visit to make sure that basically the patients are safe, with the goal to have really the maximum number at the end of the trial. To be clear, we had in mind that really a 20% dropout really could be the right number there. All this really have helped us to basically so far conclude the enrollments and look forward really for the results in one year under the condition that we have in mind. David, anything else?
Yeah, maybe just a couple points. Jason, there is some flexibility built into the protocol in terms of allowing for patients if they have to delay their final visit for imaging and for biopsy. Secondly, we're working, as you know, with Stephen Harrison and his Summit organization. They're very experienced, and they've been running a number of trials under the same circumstances in parallel.
We're sort of benefiting from the best practices that have been adopted across the field. Those are the only things to add. The dropout rate to date has been very low and within the range that we would predict for normal times. Hopefully it will remain the case, and we'll be on schedule to complete on time.
No, that's great. That's really helpful. Could you just talk to us about dose selection for PXL065 and PXL770 in ALD versus NASH and what you're thinking about the potential need for future dose optimization as you move forward in the indication?
Yeah. Good questions. David, do you want?
Yeah. They're slightly different paradigms. For PXL065, we're trying to adhere to the 505(b)(2) regulatory pathway for either indication. That means, by definition, the total exposure to pioglitazone-related molecules should not exceed the 45 mg, the highest approved dose of pioglitazone. We are keeping that in mind as we select the dose for the ALD study that there's a limit we can't go above, and we're within a fairly narrow dose range.
We know what pioglitazone exposure in humans is associated with good efficacy. That is sort of the intent there, and we can leverage a lot of the data that we have from the phase I and from the preclinical models. With PXL770, we have a range of different doses that have been studied in healthy subjects and in patients with fatty liver disease so far.
There's a limit that's an upper limit that's defined on the basis of tox margins and what's been previously tested in humans. We will use the highest efficacious and tolerated dose there, which we think we're pretty confident will achieve a good drug exposure that is consistent with what we see for efficacy in animal models of both ALD and other diseases as well. That's our plan currently, then we would potentially have the option to add additional dosing groups or dose down or to have additional sorts of adaptive designs in later-stage development as needed.
Okay, that's great. Thanks for taking the questions. Congrats again on the progress.
Thank you, Jason.
Thank you very much, Jason, Thomas, David. We have David pio who would like to take the floor.
Hello, David.
Hello, Thomas, Catherine, and David. Thanks a lot for the update and the explanations. Two questions from my side. I was wondering if you can give a quick update on the partnering discussions that you're still pursuing for the phase III that you would conduct with the diabetes patients with the chronic kidney disease for approval, potentially in the U.S. and the E.U.
Secondly, you explained that in case the same Poxel compound would perform the best in ALD and NASH, that you would select a third compound to advance in one of the two indications. As I understand it, you would prioritize the pivotal study in ALD. I was wondering what extra data you need to show, what extra clinical testing you need to do to advance that other compound that you would select to advance that compound in a pivotal study in NASH?
Thank you for those questions, David. Maybe I can start answering, and I am sure David will weigh in there. To answer the first question, on the status for imeglimin outside really the Asia for which Sumitomo has the rights. As you know, the product is basically phase III-ready in this target population of diabetes with chronic kidney disease, stage 3B and 4, which is the indication that basically our former partner, Metavant, has worked out over the years there.
We continue to see really an opportunity there, that is why we have engaged into partnering discussion. Targeting the usual suspect in diabetes, but also in the kidney area, because that could be really as in the intersection, really of both diseases. That is ongoing. As you can imagine, maybe it is difficult to give you an update at this stage.
Definitely as soon as we can, we'll update you. The goal is, of course, to explore really any options to make sure that basically we can fully leverage the imeglimin potential there. To come back to your second question, maybe just one point to make sure. If we are in this really positive scenario, where basically the product could be one product, it could be really interesting in two indications and actually would be the best for both NASH and ALD.
We will look at the data, of course, to confirm which indication to pursue with the 65 and which indication to pursue with a follow-up component, with a next generation component there. There could be multiple indication, as you have in mind, and you are right, we could move forward quickly, with the lead asset. Of course, the timing will be very important there.
Also, depending on the profile of the product and on the backup component, and the stage of development, this timing could be revisited really for the second indication there. There will be as well a number of other components. What about the competition? We know that there will be some interesting progress in NASH and in ALD, and of course, that could help us as well assessing whether we need to prioritize NASH or ALD, depending on the results there.
Another element, and of course there could be much more, would be in ALD, as I said, we really have in mind to progress really the assets by ourselves. In NASH, of course, down the road, and we haven't fixed really when is the best timing for this, but having a partner on board could be important.
Really having as well feedback from a potential partner could be also very important there. That's why all these elements will be basically analyzed and assessed to determine how we want to move forward with the lead molecule, whether this is PXL065 and PXL770, the next generation products there. To answer your question, I will let David give you more information about that.
That's why we've been working since now months and years to really identify really a next generation compounds for both platform. Having in mind that, of course, the profile should be really adjusted to target either NASH or ALD, if that's the case there. It could also be interesting for other indication because this platform have other potentials there.
We have in mind to really bring forward into new development candidates that would be particularly well suited for either of these two indications. We still need really some activities to bring a candidate in development. I think we are progressing well. Maybe David, you want to highlight a few things there.
Yeah. The only thing I would add, Thomas, is just to be clear, David, our next generation molecules are looking good, but we won't be in the clinic for some period of time. We would be seeking to identify a specific molecule from each platform around the end of this year. Then we would have to go through tox studies and phase I studies before we could be in a position to look at proof of concept studies in either indication. I want to clarify.
I think if we have this luxury of having really good data in both indications, and the financing to pursue either as we see fit, whether it's with a partner or alone, then perhaps we would pursue NASH and then select a backup compound or next-gen compound for ALD in the case of PXL065 and dTZD related molecule, because we could move a lot faster to have a next generation molecule in development and through development for ALD than we could for NASH, given where we are today.
Okay. No, that's clear. Perfect. We await the data end of next year. Yeah. Decisions will be made on the next steps.
Absolutely.
Thank you. Thank you for the explanation.
Thank you, David.
Thank you very much for your question and answer. Thomas, I think we have addressed all the questions from our participants. I propose to give you back the floor and end this webinar.
Well, thank you. Thank you everyone for attending the call. Thank you for your support. It was really good to answer these different questions. As you have understood, we have a number of things ongoing in the company, and we look forward really to keeping you all updated about our progress. I wish you, in the meantime, really a good day and a good evening. We'll talk soon, I'm sure. Thank you very much. Bye-bye.