Point out that you have the possibility to ask your questions by writing them in the question tab at the bottom right of your screen. These questions will be addressed to the management during the Q&A session at the end of this webinar. I now hand over to Thomas.
Thank you, Nicolas. Hey, everyone. Good morning. Thank you for joining us today. I'm Thomas Kuhn, the CEO of Poxel. After my introductory comments highlighting our key achievements of 2022 and early 2023, I will go into the details of today's announcement with our debt restructuring and a new equity-linked financing, and I will give an update on the recent trend of TWYMEEG sales, our lead product. I will review the full year 2022 financial results before leaving the floor to David, our Chief Scientific Officer. David will provide an update on our clinical pipeline, and will then conclude and open the call for questions. Before we begin, this is our forward-looking statement.
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 filing. Let me start with the key financing updates. Given the momentum of TWYMEEG sales and the potential of our development pipeline, we are pleased that we have significantly extended our cash runway for two years through Q2 2025 based upon a successful restructuring of our debt concurrently with the new equity-linked financing, assuming a full drawdown. This debt restructuring agreement postpones initiation of repayments until Q1 2025 at the latest, to be repaid with positive net royalty flow to Poxel, anticipated to start in Sumitomo Pharma fiscal year 2024, based on the strong growth trajectory of TWYMEEG sales.
Concurrently, we also announced today that we finalized an equity-linked financing with IRIS, with initial drawdown of EUR 3.5 million. We are really satisfied that we have finalized this important step for the company's progress. We now have more financial flexibility that we can build on to secure additional financing options, including our ongoing active partnership discussions to our programs, with the objective to pursue our strategic plan in rare disease. This past September marked the anniversary of the first year of consolidation of TWYMEEG, our first approved drug for type 2 diabetes patients in Japan. We have observed a strong growth trajectory in sales in the past few months, 90% over the last quarter. That led our partner to increase its full year 2022 forecast by 20%.
This strong growth trend also give us better visibility on our future royalties and royalty rate, which we expect will increase to 10% during Sumitomo Pharma's fiscal year 2024. Regarding our clinical development program in rare disease of adrenoleukodystrophy, our first indication, our phase 2 proof of concept studies for PXL770 and PXL065 are prepared to initiate subject to additional financing. During the year, we substantially added to the regulatory designations for our rare disease indications. For ALD in the U.S., but also in Europe, orphan drug designations were granted to both PXL770 and PXL065. The fast track designation also granted to both in the U.S. For autosomal dominant polycystic kidney disease, that, you know, we call ADPKD, the FDA granted orphan drug designation to PXL770. Additionally, our preclinical results in ADPKD were published in a prestigious journal, Kidney International.
These results support the development of PXL770 as a phase 2 clinical program in ADPKD. In NASH, 2022 was a very important year as we reported positive results from our phase 2 DESTINY-1 study. In that trial, PXL065 met its primary efficacy endpoint, with a liver fat reduction for all those statistically significant. We demonstrated a strong improvement in fibrosis without worsening of NASH, which as you may know, is an FDA approval endpoint and represents the key unmet medical need for this disease. We presented this phase 2 result at the Annual American Association for the Study of Liver Diseases, AASLD, in November. Our live breaking abstract was selected by AASLD as one of the best of the liver meeting for 2022. These results were also recently published in another prestigious journal, the Journal of Hepatology.
A review by Nature concluded that a safer pioglitazone alternative is of great interest. We continue to believe that the NASH field represents a large and underserved opportunity. We recognize that the landscape in NASH remains a changing environment due to large investment required to run the phase 3 trials. However, there have been several positive developments in NASH over the past few months, including with the recent news as of yesterday, along with our positive readouts. It is very encouraging for the field that there is no approved medicine for patients. Organizationally, we continue to execute upon the saving plan we initiated in 2022, which include a significant workforce reduction. This saving plan aims to adapt the company's resources to the current clinical development plan while preserving critical resources and competencies.
As part of this saving plan, we have also decided to resize the board to four current members from eight as of today. The board members are stepping down with transition to a new board advisory committee that will continue to assist Poxel. Today, we issue that you all know a separate press release to announce the detail of finalized agreements with our lender and with IRIS. We are very pleased to have finalized that important step for the company's progress. Indeed, thanks to the successful restructuring of our existing debt and the new increased equity-linked financing facility, our cash runway is now extended two years through Q2 2025. This debt restructuring has been facilitated by TWYMEEG strong growth trajectory, providing increased confidence that TWYMEEG royalties will generate substantial future cash flows.
In both agreements with our lenders, IPF and the banks with whom we contracted French government guaranteed loan that we call PGE loan here in France, amortization payments under the existing debt facility are postponed to reinitiate when the company expects to start receiving positive net royalty flow from TWYMEEG sales in Japan, expected Q1 2025 at the latest under the contract. Before the end of Sumitomo fiscal year 2024, ending March 31, 2025, Poxel expects TWYMEEG net sales in Japan to reach JPY 5 billion, enticing Poxel to receive 10% royalties on all TWYMEEG net sales and a sales-based payment of JPY 500 million. Positive net royalties and sales-based payments will be directed to the debt reimbursement until the loan is fully repaid.
The company expects the PGE loan to be fully repaid in Q2 2028 and IPF to be fully repaid in Q2 2029 at the latest. After this time, subsequent net royalties and sales-based payments will revert back to the company. Concurrently, we enter into a new equity link financing arrangement with IRIS. An initial amount of EUR 3.5 million has been drawn down. At our sole discretion, we have the option to draw additional tranche for up to a total of EUR 15 million over two years. The total outstanding amount held by IRIS will not exceed EUR 7 million at any time. We now have more financial flexibility that we can build on to secure additional financing options, including ongoing active partnership discussions related to our program with the objective to pursue our plan in rare disease.
Let's move now to some commercial update on TWYMEEG. As you can see on the next slide, yeah, on this one, we have observed a strong growth trajectory in sales in the past few months, 90% over the last quarter. That's on the left panel. That led our partner to increase its full year 2022 forecast by 20% on the right panel. Based on the latest results, it's very likely TWYMEEG results will exceed the new forecast raised by Sumitomo of JPY 1.8 billion. In this slide, I'd like to remind that TWYMEEG is an important addition to Sumitomo existing number one diabetes franchise through its differentiated dual mechanism of action and favorable efficacy and safety profile.
As I mentioned earlier, this past September marked the anniversary of the first year of commercialization of TWYMEEG, our first approved drug for type 2 diabetes patients in Japan, marketed by Sumitomo Pharma, the leading diabetes company, sorry, in Japan. TWYMEEG is 18 months into launch now, and Sumitomo is recording sales significantly above their forecast for the following reasons. The number one, the one-year prescription restriction now lifted as well as easing COVID restrictions. Second reason, the key positioning in Japan market given TWYMEEG dual mechanism of actions. Indeed, by highlighting the potential for co-benefit linked to this dual mechanism action, TWYMEEG can be prescribed as add-on to any type 2 diabetes therapy and as a monotherapy. There has been increasing combination used with DPP-4 inhibitors, but also more recently with SGLT-2 inhibitors.
DPP-4 inhibitors are the most widely prescribed therapeutic class for type 2 diabetes patients in Japan. SGLT-2 inhibitors are more and more prescribed in Japan given the additional benefits, specifically on kidney protection. Third reason, the strong sales and marketing infrastructure from our partner, Sumitomo. Fourth reason, Sumitomo continues to be very actively promoting the product at conferences and through additional publication. All this contributing to adoption and raising awareness about TWYMEEG with physicians. Last but not least reason, Sumitomo is running extensive medical affairs and phase 4 clinical activities to support the product commercializations. Specifically to strengthen the product positioning in patients with limited treatment options, such as the elderly and renally impaired ones. Sumitomo's phase 4 study targeting type 2 diabetic patients with chronic kidney disease, CKD 3B, 4, and 5, from moderate to severe, is nearly fully enrolled.
The strong growth trend also give us better visibility on our future royalties and royalty rate. For Sumitomo fiscal year 2023, so ending March 2024, Poxel expects to receive 8% royalties on net sales. Before the end of Sumitomo fiscal year 2024, ending March 2025, Poxel expects TWYMEEG net sales in Japan to reach JPY 5 billion, entitling Poxel to receive 10% royalties on all TWYMEEG's net sales and a sales-based payment of JPY 500 million. Beyond 2024, Poxel expects to receive escalating double-digit royalties as well as additional sales-based payments upon achievement of contractually based sales threshold.
As a reminder, in accordance with the Sumitomo license agreement, Poxel is entitled to receive escalating royalties of 8%-18% on net sales of TWYMEEG and sales-based payment of up to JPY 26.5 billion, or approximately EUR 200 million. As a reminder also, as part of the Merck Serono licensing agreement, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of imeglimin, independent of the level of sales. Going to the next slide. As part of our refocusing of our activities, we reviewed the organization of the board and decided to resize the board as of March 31st to four current member. Khoso Baluch as the new Chairman of the Board, Pascale Boissel, and Richard Kender as independent members, and myself.
Existing board member, Pierre Legault, Janice Bourque, and Kumi Sato will transition to new board advisory committee, along with the former director, John Kozarich, and will continue to provide their expertise to assist the company in all its activities. Let's now review the financials for 2022. Let me start with the revenue. Revenue for 2022 reflects JPY 95 million, so roughly EUR 0.67 million of royalty revenue from Sumitomo Pharma, which represents 8% of TWYMEEG, sorry, net sales in Japan. Poxel reported revenues of EUR 13.4 million for the year ending 2021, which mostly reflects the JPY 1.75 billion milestone payment from Sumitomo Dainippon Pharma, triggered by the June marketing approval of TWYMEEG in Japan. Going to the income.
As we have seen, our revenues in 2022 mostly reflect royalty revenue from Sumitomo Pharma, which represents 8% of TWYMEEG net sales in Japan. As we record the cost of sales, Poxel will pay Merck Serono a fixed 8% royalty based on the net sales of imeglimin in accordance with the Merck Serono licensing agreement. As a biotech company, the majority of our resources are allocated to research and development activities. In 2022, R&D ex-expenses amounted EUR 13.9 million as compared to EUR 27.5 million in 2021. R&D expenses in 2022 and 2021 primarily reflect the clinical study costs incurred for the phase 2 DESTINY study evaluating PXL065 in NASH. To a much lesser extent, they also reflect some preparing costs for the proof of concept studies for both PXL770 and PXL065 in ALD.
After R&D tax credit has resulted in an income of EUR 1.5 million in 2022, as compared to EUR 2.3 million in 2021. Net R&D expenses totaled EUR 12.5 million in 2022, as compared to EUR 25.2 million in 2021. General administrative expenses amounted to EUR 9.4 million, sorry, in 2022, as compared to EUR 10.6 million in 2021. The financial loss, excluding foreign exchange revaluation, amounted to EUR 9.7 million in 2022, as compared to EUR 2.1 million in 2021, sorry. It mainly reflected the interest attached to the company's indebtedness, including interest on IPF, as well as the exit fees fully recognized in the P&L in 2022, but only due at maturity.
The net result for the financial period ending December 31st, 2022, was a net loss of EUR 13.4 million, as compared to a net loss of EUR 23.8 million in twenty . Moving to the assets. Total assets amounted to EUR 60.6 million at year-end 2022. A similar event to year-end 2021, mostly reflecting the debt obligation in 2028. Cash and cash equivalents amounted EUR 13.1 million at December 31st, 2022, compared to EUR 32.3 million in 2021. The change in cash, EUR 19 million, reflect EUR 2,022 million cash burn from operations partially offset by EUR 3 million cash in from financing activities. This EUR 3 million reflect the EUR 6 million from IRIS financing, partially offset by debt and interest payments. Moving to shareholders equity and liabilities.
Total shareholders equity amounted to EUR 18.2 million for the year end of 2022, compared to EUR 8.2 million at the end of 2021, which mostly reflects the 2022 difference. Total financial liabilities amounted to EUR 44 million compared to EUR 35 million at the end of 2021. Most affecting EUR 32 million of the IPF's debt, EUR 6 million of the PGE loan, and EUR 4.6 million of IRIS financing related to its non-converted amounts at December 31st. The cash flow from operating activities amounted to EUR 21.8 million in 2022 compared to EUR 16.9 million in 2021. The cash flow from financing activities amounted to EUR 3 million in 2022 compared to EUR 9 million in 2021, mostly representing the IRIS equity-linked financing.
As we just released in our press release, based on the debt restructuring announced today, on our cash position at the end of 2022, the full amount available under the new equity financing with IRIS, the current R&D plan, excluding the initiation of the phase 2A clinical proof concept studies for both PXL065 and 770 in ALD, and a strict control of our operating expenses, we expect that our resources will be sufficient to fund our operation and capital expenditure requirements through Q2 2025. In parallel, we are actively pursuing additional financing options, including ongoing active partnership discussions related to our programs that will fund, sorry, the launch of phase 2A clinical proof concept studies for both PXL770 and 065 in adrenol. This chart summarize our pipeline.
David will come back in all details on this. Just to summarize, last September, we announced the positive top line results from PXL065 phase 2 DESTINY-1 trial. In U.S. and Europe, PXL770 and PXL065 were granted orphan drug designation. In the U.S., fast track designation was granted to both PXL770 and 065 for the treatment of ALD, designed to expedite development of pharmaceutical products, which demonstrate the potential to address unmet medical needs in serious or life-threatening conditions. Drug with fast track designation are eligible to apply for accelerated approval and priority review at the time of a new drug application submission, which may result in a faster product approval. PXL770 was also granted orphan drug designation for an orphan kidney disease called autosomal dominant polycystic kidney disease, ADPKD.
David will now summarize our development effort in a rare disease and NASH. David?
Thank you, Thomas. I'll now update everybody on our R&D activities, starting with our rare disease programs. Let me start with AMP kinase activation. PXL770 is our novel AMPK activator, the first such molecule to be studied in any human disease. As this slide depicts, AMPK has the potential to improve many disease processes, and PXL770 has produced substantial efficacy in multiple disease models, including those for NASH, diabetes, diabetic nephropathy, and ALD. Most recently, we've seen compelling benefits in polycystic kidney disease models, which I'll share with you shortly. The clinical development to date has demonstrated target engagement and translation of several disease-related efficacy parameters to humans, suggesting the likelihood of broader translation for this mechanism. Preclinical and clinical safety have also been very favorable, with more than 200 humans exposed for 12 weeks.
Let's review again adrenoleukodystrophy or ALD. ALD is a neurometabolic disease caused by mutations in the ABCD1 gene encoding a key fatty acid transporter that results in accumulation of very long-chain fatty acids, or VLCFA, which leads to damage of neurons. As an X-linked disease, males are more severely affected. ALD is also now frequently diagnosed based on recent and broad-based adoption of newborn screening. The prevalence of ALD is similar to hemophilia, about 20,000 in the U.S. alone. Patients with ALD typically have progressive and debilitating spinal cord degeneration or adrenomyeloneuropathy, AMN, and also frequently develop severe brain lesions. We are committed to targeting ALD, which is a very serious disease without any approved pharmaceutical therapy.
Based on the strong rationale for AMPK in ALD, we developed preclinical data for PXL770, which demonstrates substantial efficacy potential both in patient-derived cells and in the classical animal model, the Abcd1-null mouse. These data were also published last year, and a similar set of robust preclinical data for PXL065 have also been generated and also published in 2022. Based on all the preclinical and clinical data we have for both platform leads, we are planning to initiate two parallel and identical phase 2A biomarker driven POC studies. One with 770 and one with 065. We have open U.S. INDs, orphan drug and fast track designation for both molecules. The team is now fully prepared to initiate both trials, which will enroll adult male patients with adrenomyeloneuropathy, the most common form of ALD.
Each trial will enroll up to 12 or 24 adult male patients with AMN. Following a run-in period, patients will be treated for 12 weeks with one or two oral daily doses of either molecule. Readouts will include PK, safety and measurements at several time points of key disease-related biomarkers, the LCFA and neurofilament light chain, both of which are validated as disease-associated. Additional exploratory biomarkers will also be assessed. Following analysis of these results, we should be able to choose the preferred molecule for further advancement into a pivotal trial to begin as soon as possible. We remain excited to pursue treatments for ALD as this represents an area of extremely high unmet medical need. It also provides substantial commercial opportunity given premium pricing for orphan drugs with similar prevalence.
The ALD community remains very engaged, and we have established relationships with key opinion leaders and collaborations with important patient advocacy groups. Let's now turn to ADPKD. ADPKD is an orphan inherited form of chronic kidney disease, and its prevalence is about 140,000 in the U.S. ADPKD also has very high unmet medical need. More than 50% of patients develop end-stage renal disease, and only one drug is approved, tolvaptan, which is associated with modest efficacy and substantial safety and tolerability challenges. The pathophysiology of ADPKD involves altered kidney metabolism, and several publications cited here provide strong rationale for AMPK activation as a therapeutic approach. With the recently completed preclinical assessment of PXL770 in ADPKD, we've seen compelling benefits, and this phase 2 ready asset has also garnered significant interest from potential partners.
PXL770 produced strong suppression of cyst formation in 3D in vitro assays on the left panel, and in an established in vivo rodent model, we saw normalization of kidney function and robust reductions in kidney size and cyst area in the middle and right panels, along with other improvements in kidney histology, as well as target engagement. These results were published last month, as Thomas mentioned in Kidney International. Validation of AMPK in ADPKD also adds value and creates optionality for PXL770. Preparations for phase 2 and regulatory interactions are now ongoing. Let's now turn to a clinical update of our NASH program. Starting with a recap of recent results of our phase 2 DESTINY-1 trial in NASH with PXL065, which is as I'll remind you, our NCE deuterium-stabilized R-stereoisomer of pioglitazone.
Please also recall that PXL065 lacks significant PPARγ activity, but retains NASH efficacy in animals via its actions on non-genomic pathways. The rationale for studying 065 in NASH is largely based on a large body of literature with the parent molecule, pioglitazone, which has shown robust efficacy in biopsy trials noted here. I'll also call your attention to Pio's benefit on fibrosis, the greatest driver to progression of more severe liver disease. Despite the strong degree of efficacy and recommendations to prescribe Pio off-label, side effects like weight gain and edema preclude its widespread use in NASH. The DESTINY-1 phase 2 trial was designed as a streamlined phase 3 enabling approach as part of our 505(b)(2) pathway for overall development. 117 NASH patients randomized into the four groups noted here and treated for 36 weeks.
The primary endpoint was relative change in liver fat content, and biopsies and non-invasive tests were also evaluated with the aim of generating data that could inform the potential to later achieve established NASH regulatory requirements for initial approval. In this study, all PXL065 groups met the primary endpoint, and up to 40% achieved a relative reduction of greater than or equal to 30% in liver fat content. We also observed improvements in ALT, biomarkers of fibrogenesis and fibrosis risk scores, which included PRO-C3, PIIINP, ELF, FIB-4, and NFS, which are not shown on this slide. Although the phase 2 study was not powered for histology benefits, improvements in several parameters derived from the biopsy results were noted.
In particular, 35%-50% of PXL065 treated subjects achieved greater than or equal to one stage fibrosis improvement versus 17% with placebo. This is a substantial effect on fibrosis. Pooled results are shown on this slide, where PXL065 improved fibrosis in 39% of treated patients versus 17% with placebo. In comparison to reported data with other contemporary NASH development candidates, the efficacy of PXL065, in other words, the delta above placebo, appears to be potentially superior. Importantly, the DESTINY-1 trial results also successfully address the hypothesis that PXL065 would have substantially reduced PPARγ-driven side effects. No dose dependent weight gain or increases in edema were observed, nor were there any other potential PPARγ-related adverse effects like anemia.
Overall, PXL065 was very well tolerated with a safety profile that supports late-stage development. As Thomas mentioned, results from the DESTINY-1 trial were presented at AASLD in November, and the complete data were also published earlier this month in the Journal of Hepatology. We're also very happy to see that this has engendered positive reviews, including public statements from KOLs and in a recent comment published in Nature shown here. In summary, the DESTINY-1 trial met its primary endpoint and achieved other objectives, including the demonstration of histologic effects that included a strong reduction in fibrosis. Other metabolic benefits were also evident, HbA1c and insulin sensitivity improvements. Moreover, we achieved our goal of showing that PXL065 has reduced potential for PPARγ-driven side effects and a good safety profile overall.
Therefore, PXL065 is a differentiated NASH development candidate with a competitive profile that could also be complementary and well suited for use in combinations with other agents such as Madrigal's Resmetirom or others. We're actively working towards further regulatory interactions for a potential pivotal phase 3 program, subject to ongoing partnership discussions. I'll now turn it back the presentation back to Thomas to wrap it up. Thank you.
Thanks very much, David, for the clear presentation of our programs. To summarize, 18 months of commercialization in Japan has confirmed TWYMEEG's strong growth trajectory, as demonstrated by the 90% revenue increase over the prior quarter, leading to Sumitomo to increase its full year 2022 forecast by 20%. The debt restructuring that we announced earlier today has been facilitated by TWYMEEG's strong growth trajectory, providing increased confidence that TWYMEEG royalties will generate substantial future cash flows. This debt restructuring, along with the new equity-linked financing facility, significantly extends our cash runway by two years through Q2 2025. We are actively working to finalize other additional financing, including ongoing partnership discussions, to be able to advance our rare disease strategy, starting with our ALD system.
This year has also been important for product development as we continue to build the value of our assets focused on rare diseases and NASH. In rare diseases, we are prepared to launch the ALD proof of concept studies subject to additional funding, which is our priority. In ALD, for both assets, 770 and 65, we added valuable regulatory designations, orphan drug in Europe and U.S., and Fast Track designation in the U.S. The completion of clinical studies in ALD PK/PD makes PXL770 a phase 2-ready program with orphan drug designation. For PXL065, IP portfolio has been augmented with a new U.S. patent, which provides additional protection through 2041. In NASH, the year has also been important for product development as we completed our phase 2 study for PXL065 and reported positive results that open the way to further development with potential partners.
While the landscape is challenging, there have been several positive developments in NASH over the past few months. It is very encouraging for the field as there is still no approved medicines for patients. As a conclusion, I'd like to remind that Poxel missions and vision remain to discover, develop, and commercialize innovative therapies for patients suffering from serious chronic and rare diseases with underlying metabolic pathophysiology. To fulfill our mission, our objective is to apply our strong R&D capabilities to build and strengthen the value of our assets focused on rare metabolic disorders and NASH. I want to thank our talented employees for their incredible energy and dedication during very challenging times. I'm also grateful to the patients and physicians who participate in our clinical trials. Lastly, of course, I would like to thank all of you for your continuous support as a shareholder.
We look forward, of course, to updating you on our progress. This close the session today. Thank you for being with us. We will now open up the Q&A session. The moderator will provide instruction for participants. Thank you very much.
Thank you very much, Thomas. Before starting the Q&A session, I just would like to remind to the participants that you can ask your question by writing them in the questions tab at the bottom right of your screen. First, we have a question from Degroof Petercam. David, you have the floor now. Now you can speak.
Yeah. Hello, David.
Perfect. Okay. Good afternoon, Thomas, David. Thank you very much for the presentation. I have two questions. First of all, on NASH. You've probably seen the phase 2 study results from 89bio yesterday announcing pretty strong statistically significant fibrosis improvement and NASH resolution data. About half year ago, there was also Akero with a positive phase 3 study. I was wondering how you look at this in light of your own data, and how do you see this impact your own ongoing partnership discussions? Secondly, on the AMN program, your preclinical data looks pretty strong and also the funding amounts needed for these initial proof of concept studies are rather limited.
I was wondering if you can share some feedback from discussions you had or you're having with potential partners, and to what extent the approval of SKYSONA in the second half of last year for CALD makes companies and investors perhaps hesitant to step in for these programs. Thank you.
Thank you very much, David, for your question. First, going to NASH. Yes, we've seen indeed the results from 89bio yesterday, for the person attending the call, 89bio and Akero are developing a similar class of product, the FGF21. As you said, David, this is really nice data, showing really confirming the efficacy of this class of product, on both endpoints, NASH resolution and fibrosis improvement. Overall, I think, you know, this is really positive for the field, and that's why, you know, we mention that as you know, there were in the past sort of setback in NASH, and now we are seeing much more, you know, favorable trends.
All this is contributing to a more favorable environment for NASH, so which is of course, positive for us. It also give, you know, confidence, I think, you know, to companies willing to enter NASH, that really, you know, this indication could be successful. The opportunity remain intact, because as we all know, there is no approved product, you know, as of today.
To answer your question, I don't think, you know, I think, you know, it's a positive for our partnership discussion because as I said, it can really strengthen, you know, potential partners, we targeting NASH, that you know, if anyone you know can be positive, you know, in the field there. We have a very differentiated product compared to 89bio and Akero. New mechanism actions, different mechanism action. Unique properties compared to these two products is that we have an oral product, whereas, you know, they have injectable products. We all know that for NASH, as for diabetes, benefiting from an oral product, you know, is much more interesting.
They have, you know, very good results, injection, you know, require for the patients with, you know, the safety liabilities associated with that. We've seen basically, you know, the same tolerability and safety profile between the two products. Compared to 65, showing a very clean profile. We believe that, you know, this is really interesting for 65. The last piece I'd like really to mention on why, you know, we remain really confident for 65, is that being fully differentiated from others, our product, you know, could be combined with any other product. Starting with Resmetirom from Madrigal, because our product showed, as David mentioned, very strong improvement in fibrosis, whereas Resmetirom really showed a very good result in NASH resolution.
Combining the two could be really effective to target the two key endpoint for NASH, plus additional benefits, glucose-lowering effect and insulin sensitizing effect for six-five and liquid effect for Resmetirom. The combination potential, you know, is there. Overall, I think, you know, it's positive for the field to have more solution to come there. There is a desperate need really to have, you know, solution for patients, you know, suffering from NASH. I think, we view this, you know, as another positive milestone with regard to our NASH development program. David, do you want to add anything on this?
Yeah. The only other thing I was gonna say about 89bio, I think they have very good results. Their quantitative effect on fibrosis is pretty much exactly the same as Akero reported. And coincidentally is pretty much the same as what we achieved as well. Now, our P value was 0.06 in the DESTINY-1 trial for the dose that had the greatest efficacy on fibrosis. That's because we intentionally designed a study with a smaller sample size that was not fully powered for histology benefits. We're able to rely on the six previous biopsy studies done with the parent molecule, pioglitazone, where there was evidence from those studies of very robust effects on fibrosis as well.
We feel very confident that our effect on fibrosis that we've seen with PXL065 is real and will translate in phase 3 to a robust effect. That's the only other thing I wanted to add on NASH. Maybe your other question, David, was regarding ALD and the approval of SKYSONA from bluebird bio. I could take that, Thomas, if you'd like.
Please do.
We think that, you know, there is increasing interest in ALD from potential partners and investors.
Skyzona really doesn't hurt us in any way. It actually helps. That product is approved as an ex vivo gene therapy exclusively for patients who are younger patients, adolescents and children with new onset, very early-stage onset of cerebral adrenoleukodystrophy, which is a subtype of ALD that we're not specifically targeting right now. We're targeting the more common form, which is adrenomyeloneuropathy, the more adult onset form of spinal cord degeneration. There's completely independent indications here, and we also have the potential, we think, in the future to potentially target cerebral disease in patients who would not be eligible for a product like Skyzona or for the older version of that, which is hematopoietic stem cell transplants. Does that address your question, David?
Yes, thanks. Thanks a lot.
Maybe to add on this, last answer from David, I think, well, of course, it's very important really for the patients, and the, and the kids are suffering from this, very severe disease. Also, you know, as David mentioned, it raise awareness on ALD. I think, you know, we've been very active, you know, discussing with the, with the patient association, and we know that there is really, a big, big unmet medical need there and, and we'd like to contribute to this. Of course, you know, our key objective, as I mentioned, during my speech, is really, you know, to, continue our financing options.
Now that our debt overhang, you know, is behind us, we believe, you know, we could, you know, successfully, you know, close other financing options that could, of course, you know, lead to really resuming our activities and our clinical studies in the end. Yeah. More to come.
Okay. Thank you, everyone. We received also several questions from GMP Securities. The first one: Do you expect to receive a sales milestone in the fiscal year ending in March 2025? Do the milestone also go to pay off the loans?
We, in our assumption, and of course, you know, we base our restructuring agreement with our lenders based on the conservative case. I did mention the 20% increase of the sales guidance that Sumitomo has communicated, and we believe there could be more upside. To the other sales side, we base our assumptions on the conservative case there. The first sales-based payment, we believe we should get it in Sumitomo fiscal year 2024. This is really the first answer to the question.
To answer the second question, until, you know, full redemption of the debt, all the royalties and, the sales-based milestone, and it could be, you know, several, will go indeed, will contribute to the redemption of the debt.
Thank you, Thomas. The second questions from GMP Securities is: What happens to the debt obligation if TWYMEEG sales don't hit the target to go to the 10% royalty rate?
Again, as I said, you know, we've defined, you know, a way forward, you know, based on the conservative case, assumptions. We believe given, you know, the trajectory of TWYMEEG, you know, that, you know, we could fulfill the, this, obligation. Actually we really believe that, you know, TWYMEEG sales, you know, will surpass, actually this low conservative case there. If that's not the case, of course, you know, we need really to rediscuss, you know, with our lenders, because, this could be, you know, a default.
Okay. Thank you very much. The last question was about the NASH. This question has been largely answered, but if you can give any additional color on partnering discussion, that would be great.
Yeah, absolutely. I think, you know, as we mentioned, we believe we have a very differentiated product with a new mechanism of action. Strong clinical data that David really emphasized, specifically on the key unmet need in NASH, which is really the fibrosis improvement. A very key attribute is the fact that the product is originated from pioglitazone, we believe, you know, it benefit from a lower, you know, lower risk profile compared to other product because... The data we generated in our phase 2 really fully, you know, confirm our expectation based on pioglitazone experience that David mentioned earlier there. I think, you know.
Of course, going forward, we could, you know, leverage the 505(b)(2) pathway , this is really, you know, we believe a strong package for data. That being said, we know that NASH is a challenging environment, and specifically, you know, the cost of the phase three and the timing to run phase three, you know, is indeed, you know, a concern. However, the opportunity is there. We believe, as we said earlier, that the recent, you know, good development in NASH, Madrigal at the end of last year, 89bio yesterday, and Akero and the other, will contribute really to really eliminate the concern on NASH.
That everyone will really realize, you know, the opportunity down the road, because it remains a very, very significant opportunity, and we are really committed to it. You have millions of patients really requiring a product. I think, you know, there could be really good solutions, of course, including PXL065, alone, but also in combination with other products. As soon as once one product, yeah, for instance, Resmetirom, you know, could grow the market, we believe that this could really, you know, accelerate, you know, discussions in the field there. Remaining, you know, positive on our ability really to partner your the product. We know the environment remains, you know, somewhat challenging, but we are really committed to that.
Again, the opportunity is there, and we have a good product to do this.
Thank you very much. We received another question about the situation in India. As of today, there are at least two companies that started selling the drug. Poxel claims no partnership has been concluded yet. How is this possible?
Just maybe just to step back a little bit. I'd like to highlight a few things on India. It's well known in the pharma industry that really India, you know, is a really, you know, a specific country. In terms of, you know, value, we recognize there is, you know, really millions and millions, you know, patients there. We need to keep in mind that, you know, the pricing in India, you know, are very low and are really with a big, big, you know, pricing pressure with new generics, you know, coming at a very regular pace there.
The opportunity, the business opportunity, you know, in India is, we need to keep that in mind, is limited compared to, you know, what we have in other countries and specifically, you know, nothing to compare, you know, with Japan. That's one. The second specificity is, you know, that India, you know, partially recognize, you know, the patents regulation there. That's why, you know, some Indian companies, you know, believe that specifically, you know, they could market, you know, our product as a monotherapy. Currently, the product is only approved as a monotherapy. We are in ongoing discussion with these companies and with other companies.
The goal would be for us, you know, to really have a partnership for India, so that, you know, the products can be really delivered out to the patients. The bigger opportunity in India, as everywhere in the world, is in combination. Of course, for combination, we have a lot of very robust patents that of course, we will enforce in case, you know, we cannot find a partnership. We've not closed any transaction. Otherwise, you know, we would have communicated on this. We have, you know, ongoing discussion. We want to find, you know, the best partnership, you know, possible in this country. If we cannot do this, of course, we will enforce our patents. We'll keep you know the market posted on this.
Thank you, Thomas. Another question we received. When do you plan to recruit, sorry, a new financial director?
I think, you know, this is our plan. You know, with Anne leaving the company earlier this year, as I mentioned, we have Anne built a very, you know, strong finance team. We have currently, you know, a lot of expertise and capabilities, you know, within this team there. We have been extremely focused, as you can imagine, working with, you know, the finance team and our legal team and everyone in the company on this restructuring there that we could successfully close and that we've announced, you know, yesterday. Going forward, we will of course, you know, strengthen the company, you know, where needed.
Thank you. Another question, focused on the imeglimin. Did you know that, when you signed the partnership with Sumitomo Pharma, that a 1-year restriction would apply?
Absolutely. I think you know it's well known, because, you know, that applies basically, you know, to any product, nothing specific to imeglimin. What, however, you know, back in 2017, we didn't have in mind, is that this one-year restriction period would be at the same time of the COVID-19 pandemic. You know, it's really, you know, the combination of the two, that really, you know, made things difficult. Because as you can imagine, when launching a product, and specifically under this restriction, you are very limited in terms of, you know, promoting your product, you know, to and detailing your product to prescribers. Also, you know, preventing our patients to go to the hospital.
Because please recall that for a new class of product like imeglimin, TWYMEEG, it's usually, you know, managed by, you know, specialists, and so endocrinologists, diabetologists, requiring really some time to go to the hospital. Really the combination of the two, you know, made it, as you can imagine, difficult. That being said, we have always had that in mind, Sumitomo, you know, is extremely well-positioned, you know, in the field there. They are the number one company in Japan. They have a very good infrastructure. Despite, you know, this challenging period, they continue to really, you know, to intensively promote the product. They continue to invest very significantly in the product.
I mentioned, you know, the very extensive phase 4 and medical affair plan. There are, you know, several studies ongoing, including, you know, this phase 4 study in the CKD population underway, you know, in Japan. All these, you know, have been initiated right after, you know, the launch of the product. Despite, you know, the challenging environment, Sumitomo really continued executing extremely well the plan. We are now, you know, seeing the benefit of it now with this very significant growth that we believe, you know, will continue over the next years.
Thank you very much. Maybe the final question from this session. Can we know the name of the American shareholder who wished to remain anonymous during the AK at EUR 7.5? Do you have a word for your longtime shareholders who are all at a very high loss on the stock, and who were hoping for a return on investment for imeglimin?
I think as we mentioned, I mean, we have not, you know, and we'll not, you know, disclose, you know, the this investor name. That was, you know, part of our agreements there. I can tell you that, you know, we had, you know, following this, you know, regular contact there. I think, you know, we know that we wish really a better trajectory for, you know, the stock price. I think everyone can see that really we are doing, you know, all our best to support that. I think, you know, we need to think about also, you know, the macroeconomic context, which is difficult, you know, specifically, you know, for biotech company.
Now, you know, following, you know, this last announcement, where we could, you know, successfully restructure our debt. We now, you know, benefit from a very solid foundation for the future. The goal is now really to, as I mentioned, move forward, you know, with additional financing options to get back on track really for development. As a biotech company, as I mentioned, I mean, this is, you know, what we've done and successfully done in the past. The goal will be, of course, you know, to execute our plan in a rare disease. We believe that, you know, with this fresh situation, we are now well equipped for this.
I believe that if we can do this, you know, we generate values because there is tremendous values, you know, in the assets and in programs that we are developing. We hope that, you know, there should be impact actually. Of course, with that, I also want really to thank really all our shareholder really for their continuous support during this challenging context.
Thank you, Thomas. I think we covered all the questions we received. maybe if you have, a final word to close this webinar.
Yeah. Thank you, Nicolas. Well, thank you very much all for attending this conference call. It was good really to hear all the questions, not only related, you know, to our yesterday's announcement, which is of course very important to our financing, which as I said, you know, is a big priority for the company. Also really to our business development activities and of course, which is the most important for us, you know, R&D developments there. We will keep you posted on all these topics in the coming weeks and months there. We believe, you know, we could have a, you know, significant progress on all those, starting of course, you know, with financing.
We are really, you know, looking forward to update you as soon as we can on all this. With that, I'd like to thank everyone for your attention, and I wish you all a good rest of the day. We'll talk soon. Thank you very much. Bye-bye.
Thank you, everyone. Thank you, everyone.