Hello, everyone. Welcome to PagSeg's Half Year twenty twenty one Results Presentation. Before giving the floor to Thomas, I remind you that you have the opportunity to ask your questions already by raising your hands or by writing them down in the Q and A tab during the Q and A session. Thomas, I leave you the floor.
Thank you very much. Thank you for joining us today. I'm Thomas Kuhn. I'm the CEO of the company. After my introductory comments, I will hand the call to Anne Renevo, our CFO, to review the first half twenty twenty one financial results.
And then David Morter, Chief Scientific Officer, will provide an update on our financial pipeline. Before we begin, this is our forward looking statements. 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. So as some of you know, POCEL 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 Ineglinine, now launched and marketed as Twinig 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 represents the intersection of high unmet medical needs, preclinical and clinical data, opinionally there on tourism, significant commercial opportunity and attractive time horizon. We are now very focused on NASH and rare metabolic indications starting with adrenalochodystrophy with the aim to advance into pivotal trials, one program in NASH and one program in ELs. 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 Popsell to drive shareholder value.
With additional funding from Twinig, we are investing these funds to accelerate and expand our clinical pipeline of rare metabolic disease programs By developing products in rare metabolic diseases, in addition to NASH, we can be more efficient with our resources and more experimentally deliver novel medicines to patients with even stronger potential to create significant value for the benefit of our shareholder. 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 PXL-sixty five S2 STD-one trial with 123 biopsy proven patients on hold. We look forward to the results in roughly a 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 Twin Lead approval and launch in Japan represents a major milestone for Copseil and the culmination of several years of clinical development work.
This is a strong validation of our R and D capabilities and the international footprint that we have established. The approval in Japan allowed Proxela to receive €13,500,000 of the 3rd and final tranche of the IPO loan in June and €13,200,000 milestone payment from our partner Sumitomo in July. Sumitomo, who is the market leader in Japan for type 2 diabetes, launched streaming last week on September 16. Based on our current forecast, Hocktail is entitled to future potential sales bank payments of up to approximately €200,000,000 as well as escalating double digit royalties. We believe that €3,000,000 is an important addition to Sumitomo's existing number 1 diabetes franchise through its differentiated mechanism of actions targeting the 2 defects of diabetes, including favorable efficacy and safety profile.
Based on the clinical data obtained in Phase II and Phase III, we believe that TRIMIG has the potential to be used as a monotherapy alone as well as in combination with other products, specifically complementing well suited to our existing infrastructure in type 2 diabetes. This approval of 3 megabytes provide patients with type 2 diabetes the opportunity for greater flexibility in their treatment. 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 on tourism, 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 PoXell has the ability to commercialize on our own, which would allow us to capture greater economies.
We believe that Boxel 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, and good evening, everyone. So I will now review our financials for the first half of twenty twenty one. So let's start with revenue on Slide 9. So, for example, we reported revenues of €13,300,000 for the 1st months ended June 30, 2021, as compared to €6,400,000 during the corresponding period in 2020. This revenue mostly reflects the CHF 1,750,000,000 milestone payment from SumitomoDaimip Pharma triggered by the June marketing approval for Imiglinin in Japan.
The payment was received in July. So turning to Slide 10, which is a statement of comprehensive income. So as a preliminary remark, as a biotech company, the majority of Oxyrasulces are allocated to research and development activities. Net R and D expenses amounted to €14,700,000 for the first half of twenty twenty one as compared to €12,600,000 for the corresponding period in 2020. R and D expenses for the first half of the year primarily reflected the clinical study costs incurred for Phase 2 Destiny 1 study evaluating PDCL65 in March.
To a lesser extent, they also reflected some Phase 2a clinical program residual costs for PACE77O, the treatment of NASH and also the regulatory costs incurred over the period for imeglinin for which the company obtained the marketing approval in June. As a reminder, R and D expenses are net of the R and D tax credit that resulted in an income of €1,500,000 for the first half of the year, which is the same level as for the first half of twenty twenty. General and administrative expenses amounted to €5,400,000 for the first half of twenty twenty one, as compared to €6,000,000 for the first half of twenty twenty. The financial loss amounted to €1,200,000 for the first half of twenty twenty one as compared to an income of €2,000,000 for the first half of twenty twenty. This loss primarily reflected the interest attached to the company's headwinds.
The net result for the financial period ending June 30, 2021, was a net loss of €8,000,000 as compared to a net loss of €12,100,000 for the corresponding period in 2020. So moving along to Slide 11 with DSS. Two comments. First one is the trade receivables that amounted to €13,300,000 at the end of June 30, 2021, compared to €0,300,000 at December 31, 2020. This reflects the marketing approval milestone for IMAGENIN in Japan that was accounted for at June 30, 2021 and paid in July.
Cash and cash equivalents amounted to €36,900,000 at June 30, 2021, compared to €40,200,000 at December 31, 2020. The change in cash for the 1st semester amounted to minus €3,000,000 reflecting €13,000,000 coming from financing activities and minus €16,000,000 coming from operations. So moving along to Slide 12 with the shareholders' equity and liabilities. So the shareholders' equity amounted to €21,600,000 for the first half of the year compared to €26,900,000 at December 31, 2020, which mostly reflects the half year 2021 net loss. Total financial liabilities amounted to €37,000,000 compared to €24,000,000 at December 31, 2020, mostly reflecting a €30,000,000 loan with IPF and a €6,000,000 loan with PG.
Last comment, the litigation with Merck has been settled and the current provision has been fully reversed accordingly. So turning to Slide 13 with the statement of cash flows. So as previously explained, the cash flow from operations activities amounted to minus €16,100,000 for the first half of twenty twenty one compared to EUR 14,500,000 for the first half of twenty twenty. This included the half year 2021 net loss, but also a €10,000,000 change in working capital, which mostly reflected the €13,200,000 milestone payment that was received as part of the marketing approval of hemiglin in Japan and recorded at the end of 2021, paid in July. The cash flow from financing activities amounted to €12,800,000 for the first half of twenty twenty one compared to €23,200,000 for the first half of twenty twenty.
This mostly represents the drawdown of the full tranche to the IPL loan for the amount of €13,500,000 So moving to Slide 4 team, thank you. We have listed the relevant shareholder information as well as our research coverage in both Europe and the U. S, which includes 5 Mainz, ODDO, Van Garnier and Peter Group, the group Petercam in Europe, Jefferies in the UK and GMP in the U. S. So, I will now hand over to David 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 and D activities. Starting with our advance into rare metabolic disease with our existing platforms, the deuterium modified TZD and AMPK activator small molecules. So let me first summarize some of the key features of our 2 lead molecules. PXL-sixty five is the deuterium stabilized R stereo isomer of p aglitazone, a widely prescribed medicine for type 2 diabetes.
But unlike PO, 65 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 PVR gamma side effects like weight gain and fluid retention. And given its relationship to PO, the employed leveraging a large safety database for the parent compound. More than 130 humans have been exposed to 65 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 isomer translates into humans. PXL-seven 70 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. Now, 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, BLCFA, 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. Thus, 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 BLCFA 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. And we have developed evidence to show that both of our platforms, AMPK activators and DTCDs can be leveraged to address this pathophysiology to correct the primary defect by suppressing BLCFA 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 neurobehavior with both 65 and 770. And 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 65 and piaglitazone, 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 65. Based on all the preclinical and clinical data we have for both platform leads, we now plan to initiate 2 parallel and identical Phase 2a biomarker driven POC studies, 1 with 65 and 1 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, the LCFA 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. And 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 3 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, a 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 770 and 65 enable poxell to have a significant role in this area.
In addition to strong preclinical data in ALD, both PXL-seven seventy and PXL-sixty five have evidence to support their development for NASH. Clinical validation exists for both. For 65, a wealth of clinical data in NASH with the parent molecule, piaglitazone, has demonstrated substantial efficacy at this point in 6 independent trials. For 770, our recent Phase 1b and Phase 2a results have also yielded prominent efficacy signals. Both are 1st in class and both are daily oral approaches.
And an innovative development approach can also be pursued for both molecules as well. As we announced last week, our PXL-sixty five Phase 2 study, DESTINY-1, is now fully enrolled and will yield results approximately 1 year from now. By leveraging the 505(2) regulatory path, we designed a streamlined single Phase 2 study with 3 closely separated dose levels. Based on Phase 1 data and PKPD modeling, 15 milligram dose is predicted to achieve the efficacy equivalent of 45 milligrams of pioglitazone without significant weight gain or edema. Results from this trial will enable the selection of 1 or potentially 2 doses for advancement into Phase 3.
With PXL-seven seventy, we demonstrated good safety and tolerability in humans as well as having established target engagement. In the most recent trial, the STAMP NAPL D Phase 2a 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 PXL-sixty five in NASH and the assessment of both 65 and 770 in ALD before considering the further pursuit of PXL-seven 70 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 the growth, including the readout from the 65 SCE1 Phase 2 trial in NASH, for which David gave you an update as well as the 2 proof of concept biomarker studies for the treatment of adrenal agronomycologist. So to summarize, the launch of TwinIG in Japan opens a new chapter for PoXella and provides a future funding stream to PoXella 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 CAS 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 and A session. Thank you very much.
Thank you very much all for your presentations. We can now proceed to the Q and A session. So 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 and A tab below their screen. So we have Lucy Codrington, who would like to have the floor.
Hello, Lucy.
Lucy, you have the floor.
Hi. Thanks for taking my questions. Just a couple for me. So I was wondering if it'd be possible to provide a little more detail on your commercial expectations for Twineague, particularly in light of the MHLW sales prediction. I understand that MHLW is traditionally very conservative, but even if I were to double it, it still seems quite light compared to my forecast.
And if we were to use Equisales for context, how do you view TWIMEIG 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 65 data look better for ALD, but 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 865 than 770. How would you potentially manage that situation? I know it would be a good situation to be in, but kind of how would you view that then? And then finally, if it's possible, could you give a rough guide to the cost of the ALV 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, Lucie, for your question. So let's start maybe with Ymir Limine. So in terms of forecast, so I mean Sumitomo has not given any official forecast there. And so it would be difficult for you to answer these questions. But there is, however, a number of elements that basically we can share with you.
Just to recall that the consensus of analysts, I mean not only you, Lucie, most of the analysts or all of our analysts really have in mind that the product really could deliver between $400,000,000 $450,000,000 sales for enabling ad 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 3,000,000 in Japan. And 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 8,000,000 to 9,000,000 patients overall.
So I think what you have in your model, we believe it still will be something that we believe we could target because again demonstrated very strong profile for Amelgine. 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 exiting the market and really setting up really the flow really for the launch of the products there. To come back to another piece of your questions, and it's so interesting vis a vis this what I just mentioned. As you said, so Sumitomo, they have 5 products on the portfolio for diabetes, including Equa.
You might have seen that for the last year, they disclosed that basically they nearly generated close to €900,000,000 really for the old franchise. Equa is a major contribution to it now, so between 3 to basically around, let's say, dollars 350,000,000 overall. We believe this is very interesting vis a vis IMAGLIMIN. Given the profile of IMAGLIMIN, as we've said, given what we've shown in the Phase III, Sumitomo has in mind, of course, to combine imidlinine to any product available in Japan, starting with DPP4 inhibitor. So including Equa, of course, as you can imagine, We know that DPP4 inhibitor is the largest prescribed treatment in Japan.
And of course, that will help to really ramp up the uptake of Imaglin on the market. But 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 monotherapy indication and even the first line indication. And we believe that this could occur really in the near future. As a reminder, we showed very robust efficacy of imeminin during our Phase III trial with close to a minus 1% towards the reduction, very good safety. So that's why on all this basis, we remain very excited about the potential of the product.
We believe that what Sumitomo Sumitomo is doing with Decora could reflect well what they could do as well on Inelgulin. And so that's why we remain really bullish on what really inhibulin could deliver as a sales agent. So that's really related to your question on Trini. Going back to your question in really on the strategy more and on the platform. So you are right.
I think we have in mind that our platform, whether this is the MPC and S expression platform or the deteriorated CD platform, have a strong potential in various indication. And the example that you took, I would say, could be definitely the right one where basically 65 could deliver very good results in both ALD in the upcoming Phase II as well as in NASH in the DESTINY trial there. Just to mention things now, these 2 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. And so the goal will be, as we mentioned earlier, to really continue and push forward 1 program into the pivotal program for ALD and 1 really for NASH. And what we have in mind clearly is that the same product cannot be really progressed in these 2 very different pathologies.
For obvious reason, we all have in mind, of course, the price difference between rare disease and NASH, but there are much more reason to do this. So that's why if that's okay and as you said, it would be a good program to have, we have the same products really having really positive and robust results really for 2 patients' indication. That's where developing our next generation compound could be very important. We have ongoing efforts on this and 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 2 different indication, we'll have the ability to select the lead assets 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 770 also has strong potential in ALD and we could be in a situation where we might have 65 going forward for NASH and choose to focus the ALD indication on with 770, that's another scenario. That would be the best case scenario perhaps.
So I hope that's answered your question. So your last question on the cash runway. And so before leaving the floor to Anna, just to put you some figure there. I think one of the interest answers your question of these rare diseases strategies that, of course, in contrast to NASH and diabetes, which require 100 and 100 of patients in the studies. In rare disease, of course, there would be a much more limited number of patients there.
So as you see now, the 2 proof of concept studies that we plan to do will be of 12 patients each. So that's a very limited number of patients. And so that's a few $1,000,000 investment for each study. So not a lot of really investments compared to other disease. And then going forward, of course, we are working on the confirmatory program.
But again, we have in mind that for ALD, and we have already an interesting discussion in that, 100 or maybe 150. And of course, this amount, this year is to be confirmed of patients we will inquire. So that's again, that's not a big number. And that's why with our proven capabilities, definitely the goal will be to move forward and deep these opportunities because we could have everything in hand to do that by ourselves. There.
And that would also be true, by the way, for the commercialization there. So that's really one of the key interest moving there. Maybe, Anna, you want to give some numbers on all this?
Yes, with pleasure. Hi, Lucie. So yes, let me please share with you some maybe more precise view on our cash runway. So, as you know, as of June, the cash and cash equivalent was €36,900,000 And in addition, we received in July a milestone comfortable cash position today and this cash position fully covers our plan on NASH and it totally covers the full completion of the ongoing Phase 2 Destiny trial for PIXELO 65 in March until the readouts which are expected in Q3 2022. So coming to the IV program.
So our funding capacity depends on a number of factors, starting with the level of priority and steady base payment that we will receive from Inigliemon in Japan. So 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 would be used to further accelerate our development plan in IMN I and D. And maybe last comment, as Thomas mentioned, the 2 IMN proof of concept studies are only a few million. We believe that it will be less than €10,000,000 to fully implement this study.
So we are very committed to funding these trials.
Okay. So would you say you would reiterate your prior guidance, which was kind of cash through 2022? Absolutely, yes. Okay. Very helpful.
Thank you so much.
Thank you, Lucy.
Thank you very much for your answers. We have a question about the Imaglumine product, TwinAg now that it has been commercially launched. Have you collected feedbacks from Japanese professionals? And what are the nature of these feedbacks, Thomas?
Yes, absolutely. Well, I mean, Sumitomo has done this. That's, of course, part of the work to really they've been educating the market. And so of course, they wanted to know what could be really the main attribute of the products there. So the key attributes that really have been emphasized by the market and by the subscribers really to Sumitomo on Inelaming are the following.
Firstly, the novelty and the mechanism of actions there. It's a dual mechanism of actions targeting really the 2 key effects of diabetes, so improving the beta cell function as well as improving insulin resistance, which is unique. And of course, the prescribers are very bullish on that because in contrast to other products currently in the market, I mean, in the beginning, we'll be able to really target the root of the disease. And so they believe that it's going to be very important. They also emphasize that given that mechanism have the potential to slow down really the progression of the disease and to also prevent the occurrence of the diabetes complications because by targeting the mitochondria, you can basically protect the beta cell function as well as preventing the micro and macro vascular complications there.
3rd, I think the safety of the product has been re 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 old. And so I think a safe product really is important really for this population because they are basically more sensitive than the younger population. And of course, the efficacy that has been showed in the Phase III has been really interesting a monotherapy as well as in combination with all existing agents there. As a reminder, we showed very robust efficacy on top of all other products currently standard of care available in Japan.
So I think all this really is really the foundation for great success in Japan. And so we are confident that this could basically translate into a significant impact on the market.
Thank you very much, Thomas, for your answer. So I remind our participants that they have the opportunity to ask questions either orally or by writing them down. So we have a new question regarding Hoexcel's increasing focus on rare metabolic indication in NASH. So maybe, Thomas, you can explain and develop why POCEL has increased its focus.
Yes. Okay. I can get back to this. So what I mean with the approval for and the commercialization of Trini, Proteller 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. And definitely, as a biotech company, we want to reinvest really this cash into new development opportunities to deliver new products to the patient and to grow further the company and to deliver, of course, shareholder value to our shareholders.
And 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 enabled us to that and I think that's really the basis targeting the kinase activation, targeting really the non genomic pathways of the diodes in the unit. That could be interesting in all these indications. And so that's why we believe that it's important to fully leverage that. So that's the first point. The second point is that in terms of time horizon, that could be so very interesting.
Of course, NASH will take more time. So that's why having this rare disease really could provide short term, near term catalyst there. And we can basically with our plan move forward into a particular program for both NASH and rare disease in 2023. So that's really near term catalyst that could be very interesting there. And so 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 and deep into the development and even maybe into commercialization there because we'll have everything in hand basically to do that. In NASH, at some point of time, is it going to be for Phase 3 or later? Having a partner or board that could be, we believe, importance there. But if 65 really confirmed, the potential it has linked to Biovlitazone, as David reminded us, I think that could open up a lot of doors there. And of course, the partner will be needed there, but that could really balance and what we're doing in the rare disease field there.
So that's why we feel that really running on our 2 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 Twin Media in Japan. David, do you want to add something?
Maybe just a couple of other points. So from a purely scientific and clinical perspective, it's clear that there are a lot of rare diseases. It's also clear that the majority of them don't have approved therapies. And so we feel compelled to really look into that. And secondly, about a third or so of all of these rare diseases have a metabolic pathophysiology.
And then 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. But 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 very much, David and Thomas. We have Jason Butler, who asked for the floor. Jason, you have the floor.
Can you guys hear me now?
We can hear you well.
Great. So first of all, congrats on the progress and completing completing enrollment in the 65 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? And just how are you handling potential missed patient visits?
Yes. No, good question, Jonathan. And of course, we've been very pleased by the preparation of the enrollment. So basically, if you recall, and for those who are not familiar with the story, first, we delayed the initiation of the trial because we are supposed to initiate the trial in Q2 2020, so right really during the first wave of the pandemic. And we decided basically to wait a little bit to make sure that the clinic, the hospital, the caregiver that could handle the product will be in a system.
So that's why we initiated the trial in September. And so when we did that, of course, it gave us more time to 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. So I think we prepared that well. The study you know, RASRAN in the U. S.
Only and we notified really, I think, good sites there. We had a lot of the team, our clinical team has done a really, really good job there together with the CROs we work 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. So 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 Paluritasone has been a plus because of course the investigator, they had Pioglitazone in mine and they know Pioglitazone.
And so in contrast maybe to other drug, we could continue really enrolling and screening a lot of patients, really motivated to join our study. So that has absolutely not been the issue there. In terms of screen failure, I think we had what we expected there, maybe slightly higher, maybe slightly due to COVID-nineteen there, but not too dramatically basically. So it's been, I think overall, pretty good and with according to plan. And maybe this sparenter has helped really to give confidence on all these there.
And then of course, the goal now will be to make sure that we keep all these patients in our trial there. So again, we have already worked on a planner to make sure that we need the patients to continue going through the different visits there. We have, as you may imagine, very regular monitoring visit to make sure that basically the patients are assessed. We're still going to have really the maximum number at the end of the trial. And to be clear, we had in mind that really a 20% dropout really could be the right number.
So all these really have helped us to basically so far I mean conclude the enrollment and look forward really for the results in 1 year under the condition that we have in mind. David, anything else?
Yes, maybe just a couple of points. So, 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. So we're sort of benefiting from the best practices that have been adopted across the field.
So those are the only things to add. And then the dropout rate to date has been very low and within the range that we would predict for normal times. So hopefully, it will remain the case and we'll be on schedule to complete on time.
That's great. That's really helpful. And then could you just talk to us about dose selection for 65 and 770 in ALD versus NASH and what you're thinking about the potential need for future dose optimization as you move forward in the indication?
Yes, good questions. Bill, do you want to
add? Well, yes. So for let's there's slightly different paradigms. But for 65, we are trying to adhere to the 505(2) regulatory pathway for either indication. And that means by definition that total exposure to pioglitazone related molecules should not exceed the 45 milligram, the highest approved dose of pioglitazone.
So we're keeping that in mind as we select the dose for the ALD study that there's a limit to we can't go above and we're within a fairly narrow dose range. We know what p aglitazone exposure in humans is associated with good efficacy. So that's sort of the intent there. And we can leverage a lot of the data that we have from the Phase 1 and from the preclinical models. With 7 70, 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. And we will use the highest sort of the highest efficacious and tolerated dose there, which we think is we're pretty confident we'll achieve good drug exposure that is consistent with what we see for efficacy in animal models of both ALD and other diseases as well. So that's our plan currently. And 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 and congrats again on the progress.
Thank you, Jayden.
Thank you very much, Jason, Thomas, David. We have David Senav who would like to take the floor.
Hello, Thomas,
Catherine and David. Thanks a lot for the update and the explanations. Two questions from my side. First of all, I was wondering if you can give a quick update on the partnering discussions that you're still pursuing for the Phase 3 that you would conduct with the diabetes patients with the chronic kidney disease for approval potentially in the U. S.
And the EU? And then secondly, so you explained that in case the same oxal compounds would perform the best in ALD and NASH that you would select a 3rd compound to advance in one of the 2 indications. So as I understand it, you would prioritize the pivotal study in ALD. And 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?
Yes. Thank you for those questions, David. So I can start answering, and I'm sure David will weigh in there. To answer the first question, so on the status for hemolyneux in outside really the Asia for which Sumitomo has the rights. Well, as you know, the product is basically Phase 3 ready in this target population of diabetes with chronic kidney disease, Stage 3b and 4, which is the indication that basically our former partner on Metavent has worked out over the years years.
We continue to see really an opportunity there. And so that's why we've engaged into partnering discussion, really targeting the usual suspect in diabetes, but also in the kidney area because I mean that could be really as the in the intersection really of both diseases. So that's ongoing. As you can imagine, maybe it's difficult to give you an update at this stage. But definitely, as soon as we can, we'll update you.
But the goal is, of course, to explore really any options to make sure that basically we can fully leverage the enabling potential there. To come back to your question, 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 2 indications and actually would be the best for both NASH and ALD. Well, it's we still need we will look at the data of course to compare which indication to pursue with the 65 and which indication to pursue with a follow-up component, with the next generation component there.
Because there could be multiple implication, as you have in mind, and you are right, we can move forward quickly with the lead asset. So of course, the timing will be very important there. But also, depending on the profile of the product and on the backup component and the stage of development, I mean, 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, 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 L and D, as I said, we really have in mind we're in order 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. And so really having as well feedback from a potential partner could be also very important.
So
that's why all these elements should be basically analyzed and assessed to determine how we want to move forward with the lean molecule, whether this is a 65 and 70, and then the next generation products there. And then to answer your question and then I will let David give you more information about that. That's why we've been working since now months months and years to really identify really next generation companies for both platforms. And having in mind that, of course, the profile should be really adjusted to target either NASH OLD if that's the case there. It could also be interesting for other indication because this platform have other potentials there.
But we are in line to really bring forward into new development candidates that will be particularly well suited for either of these two indications. And so we still need really some activities to bring a candidate in development. But I think we are progressing well. And maybe, David, you want to highlight a few things there.
Yes. 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. And then we would have to go through a a position to look at proof of concept studies in either indication.
So I want to clarify. So I think more than 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 a loan, then perhaps we would pursue NASH and then select a backup compound or next gen compound for ALD in the case of 65 and EZB related 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. So we await the data end of next year. And then, yes, decisions will be made on the next steps.
Thank you for the explanation.
Thank you very much for your question and answer. Thomas, I think we have addressed all questions from our participants. I propose to give you back the floor and this will be now.
Well, thank you. Thank you, everyone, for attending the call. Thank you for your support. So it was really good to answer these different questions. As you understood, we have a number of things ongoing in the company, and we look forward really to keeping you all updated about our progress.
And I wish you in the meantime really a good day and a good evening. And we'll talk soon. Thank you very much. Bye bye.