Ladies and gentlemen, welcome to the Aspaveli Call Event, ERA Congress Conference Call and Live Webcast. I am Sandra, the course co-operator. I would like to remind you that all participants have been listened to only mode, and the conference is being recorded. The presentation will be followed by a Q and A session. You can register for questions at any time by pressing star and one on your telephone. For operator assistance, please press star and zero. The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to Guido Oelkers, CEO. Please go ahead, sir.
Yeah, thank you, Sandra. Hello everyone, this is Guido Oelkers, CEO of Sobi. We are delighted to welcome you to this call and discuss the update of Aspaveli phase III VALIANT data presented at the ERA Congress last weekend. Please turn to slide number two. As per usual, you know, this is a forward-looking statement, please take note of it. With this said, please turn to slide number three. I am very pleased to have Professor Fadi Fakhouri from the Nephrology Clinic at the University of Lausanne joining us today, and he will take you through the 52-week data and other highlights of the ERA Congress for Aspaveli. We are also joined by Nicholas Webb, the Head of Clinical Strategy Immunology at Sobi, who will give you a short introduction to the topic.
Also joining us for the call is Lydia Abad-Franch, our Head of R&D and Chief Medical Officer. With this, I said, you know, I would like to hand over to Nick.
Thank you very much, Guido, and good morning, good afternoon to everybody. I'd like to introduce you to C3 glomerulopathy and immune complex membranoproliferative glomerulonephritis. We'll refer to these as C3G and ICMPGN. These are two closely related rare, chronic, and heterogeneous kidney diseases. They present most commonly in children and young adults, typically with hematuria and proteinuria, so blood and protein in the urine. It is overactivity of the complement system, a key component of the human immune system that is central to the underlying pathogenesis of both diseases. This overactivity of the complement system leads to deposition of a key complement component called C3. Its breakdown products get deposited in the glomerulus, the important filter within the kidney. This deposition triggers the development of inflammation, which, left untreated, goes on to cause chronic damage, so sclerosis of the glomerulus and fibrosis of the surrounding interstitial tissue.
The diagnosis of these disorders is made by kidney biopsy. Under a light microscope, both diseases look very similar, and one distinguishes between the two using the results of immunofluorescence staining. Here in C3 glomerulopathy, the staining is predominantly positive for C3. There is an abundance of staining for C3, whereas in ICMPGN, there is staining for both C3 and also immunoglobulins without dominance of C3. That is the major distinguishing feature between these two disorders. On the next slide, please. Current treatment algorithm recommends that one starts with RAAS inhibition, the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors as supportive therapy, as is the case in all glomerular diseases associated with proteinuria.
In the majority of cases, this does not produce resolution of proteinuria, and in this situation, the guidelines recommend the use of nonspecific immunosuppression with either prednisolone, mycophenolate mofetil, or a combination of the two. Now, unfortunately, these compounds have poor efficacy and are associated with significant adverse effects. Even with optimal use of these agents, around 50% of patients will progress to kidney failure over a 10-year period, necessitating treatment with either dialysis or kidney transplantation. Because the underlying complement dysregulation continues unchecked, even when transplantation occurs, the disease can come back and damage the transplanted kidney. This occurs in up to 80% of patients, and where this occurs, approximately one half of them will end up losing their transplanted kidney as a result of this recurrent disease. A real shortage of therapies for this disorder.
On the next slide, pegcetacoplan, the subject of today's discussion. This is a novel therapy which targets the underlying disease pathogenesis in both C3G and ICMPGN. The drug selectively binds to C3 and C3b, and in doing this, this blocks C3 cleavage by all of the convertases and the downstream effects of complement activation. The net effect is control of this overactivated complement system, which is causing the underlying damage in these disorders. Now, the use of pegcetacoplan has already been assessed in two phase two studies in both C3G and ICMPGN. In just one slide's time, Professor Fadi Fakhouri is going to present to you the 52-week results of the VALIANT study.
This is a pivotal phase three study investigating the use of pegcetacoplan in patients with both C3G and primary immune complex MPGN, both in adolescents over 12 years of age and adults, and incorporating patients with both native kidney disease as well as recurrent disease after kidney transplantation. With further ado, I'd like to hand over to Professor Fakhouri. He's been introduced already by Guido as the Professor of Nephrology, University of Lausanne in Switzerland. He is a true leader in the field of complement renal disease, complement-driven renal disease. Fadi, thank you very much.
Thank you so much for the invitation and introduction. We're going to focus on the VALIANT study results, mostly on the 52 weeks. Next slide, please. I'm going to start with a brief summary of the design. It was a randomized controlled trial, not very frequently seen in the nephrology field, comparing pegcetacoplan twice weekly to placebo. It was not simple placebo. It was placebo on top of maximal standard of care, which included maximal tolerated doses of ACE inhibitors and a significant proportion of patients of SGLT2 inhibitors, and more than 80% of patients had, on top of the immunosuppressive drugs, mainly MMF and corticosteroids. It's not just plain placebo.
Six months randomized control period, pegcetacoplan versus placebo, and at the end of six months, you had a kidney biopsy, repeat kidney biopsy, and then all patients were switched to pegcetacoplan for an additional six months, and at one year, they went into an open label extension trial called VALE. Next, please. The inclusion criteria, as Nicholas Webb already alluded, it was an elegant design that combined adolescents and adults, C3G, early immune complex MPGN, native kidney, and kidney transplant recurrence. Inclusion criteria was the usual one, more than 1 g per gr proteinuria and eGFR above 30 mL per minute, which goes with the exclusion of patients who had more than 50% fibrosis in the glomerulus or in the interstitial aspect. Next, please.
The primary endpoint was the same at six months and 52 weeks, mainly the log transform ratio of UPCR, and as you are probably aware, UPCR is currently widely accepted by clinicians and more and more by health authorities as the optimal available surrogate marker for long-term outcome in glomerular disease. We have for C3G specific data from the RAIDO series in the U.K. and from the Spain study group on C3G, very nice data showing a close correlation between reduction in UPCR and long-term evolution of eGFR. There were also key secondary endpoints, including proportion of patients achieving composite renal endpoint that combined more than 50% reduction in proteinuria and stable or improved eGFR, more than 50% reduction in UPCR, and, and this is very important, pathological features of transplant, including mainly decreased C3c staining in renal biopsy repeated at six months.
Kidney biopsy was not mandatory at one year. There was an analysis of change of eGFR over the period of inclusion in the study, and safety also was monitored. Next, please. There were 134 patients included, a very significant number for a rather rare kidney disease. Distribution was more or less balanced between the two groups. They represented patients that needed treatment and had unmet needs for their C3G and immune complex MPGN. As you see, they have high proteinuria, around 3 g per g. Standards of these patients also had maximal RAAS inhibitors and MMF and corticosteroids. They had mildly decreased eGFR, and there was a distribution that reflects clinical practice with 80% C3G, 20% immune complex MPGN, and around nine patients between the two groups that were kidney transplant receivers. There were 3.5-year evolution of disease between diagnosis and inclusion in the trial.
As I already said, patients representative of the population of C3G that have high unmet needs. Next, please. These are the results at 26 weeks, which were already very impressive. 68% reduction in proteinuria versus placebo, a figure rarely, if ever, seen in trials with glomerular disease. Most importantly, 71% of patients clearing all their C3 deposits in the kidney biopsy. I think C3 glomerulopathy and pegcetacoplan are going even to change our approach to how we define the remission of glomerular disease, and we have to take into account not only proteinuria, but also improvement in pathological features. Interestingly, even at six months, you have a beneficial effect on the slowing of progression of CKD because you have plus 6 mL per minute in the pegcetacoplan group compared to placebo.
There was a slowing of the destabilization of eGFR slope in the pegcetacoplan group compared to placebo. Next slide, please. This is what we saw in 71% of patients, something we have never seen in such massive and impressive ways before pegcetacoplan, the complete clearance of C3 deposits from the kidney after three months of treatment. Next, please.
Most importantly, this improvement in proteinuria occurred regardless of the subgroup of patients, whether they were adolescents, adults, C3G, immune complex, native kidney, transplanted, proteinuria more than 3 g per g or lower than 3 g per g, and even in patients on immunosuppression, already on immunosuppression, mostly by MMF and corticosteroids, they had a similar response compared to patients without immunosuppression, which means that you have a massive additional positive effect of this drug on top of, of course, nonspecific antiprotein drugs, but also immunosuppressive drugs that were used, and in my opinion, will no more be used in this indication. Next slide, please.
If we focus on the most significant subgroup in terms of relevance and severity of the disease, nephrotic-range proteinuria patients, those who were resistant to immunosuppression, pegcetacoplan immunosuppression, and adolescents, as you see, reduction in proteinuria is still very impressive, around 70%, and the clearance, or at least more than 2+ , decreases in C3c staining, which is already a very good improvement in pathological feature seen in roughly 70%-80% of patients. Next, please. What happened after six months when all patients in the placebo were switched to the pegcetacoplan? Let's start with the pegcetacoplan group. The decrease in proteinuria started as early as one month, continued over six months, and was stable over the six additional months. At one year, you had almost 77%-67% reduction in proteinuria.
Once the placebo group is switched to pegcetacoplan, you have the same rapid, dramatic decrease in proteinuria, starting as early as one month, and at the end, you have similar magnitude of reduction in proteinuria in the placebo compared to the patient treated from the beginning with pegcetacoplan. Next, please. If you go into more patients, more secondary endpoints, for example, more than 50% proteinuria reduction at week 52, 53% in the peg to peg group, and a very impressive figure of 40% in patients who were switched in the second time from placebo to pegcetacoplan. Next, please.
If you go to the composite renal endpoint, which combined more than 50% reduction in proteinuria and stable or improved eGFR, this was achieved in both groups in 41% and 36% of patients, very impressive results, especially in regard of the relative severity of the patient included in the study. Next, please. If we have a look to the eGFR, eGFR more or less stabilized in the peg to peg group, and in the placebo group, it tended to decline in the placebo period and then tended to increase during the pegcetacoplan group with somehow a reversal.
At the end, both groups have a similar eGFR and very convincing stabilization and slowing of the progression of CKD seen as early as one year, something we do not see very frequently in glomerular disease, where we have to wait at least three, four, five years to see an effect on eGFR. Next, please. What about safety? Nothing of concern. Very mild adverse events, some reaction to injection at the site of injection, very transient. One death, absolutely not related to treatment, was related to COVID. Next, please. During the whole period, there were only four infections in patients who, in more than 80% of cases, already had immunosuppressive drugs on top of complement inhibition. As you see, there was one pneumococcal pneumonia that was deemed serious. The rest was rather mild, if any, infections, including one streptococcal pharyngitis and one urinary tract infection. Next, please.
This is my last slide. This is the same slide seen at 26 weeks. Now it is updated for 52 weeks. As you see, 67% reduction in proteinuria in all patients, the peg to peg group and placebo to peg group, 71% of clearance of C3 deposits. It is 26 because, as I said already, biopsy at one year was not mandatory, and a very impressive slowing of progression of CKD with stabilization of eGFR at one year. P egcetacoplan was well tolerated. With such impressive data, I do not feel that I have much to add to this very nice data. Thank you. I would be more than happy to answer your questions if I may.
Yeah, thank you, Professor Fakhouri. Please now turn to slide 25, and let me start sharing some exciting updates on our regulatory process.
First of all, after our regulatory filing in February, we expect to receive the CHMP opinion by end of this year. This opinion is the critical step towards obtaining market authorization, as you know, in Europe, and we look forward to receiving positive outcome and putting on track for a launch in early 2026. For Japan, we are on track to submit to PMDA the 52-week data and provide a complete regulatory package. The enFuse injector is a cutting-edge delivery device designed for subcutaneous administration. It represents a significant advancement in patient care, offering greater convenience and potentially improving adherence. We are on track to make the enFuse device or injector available in Europe for key indications, including PNH, C3G, and ICMPGN. This aligns with our commitment to delivering innovative solutions to patients. In parallel, we are making great strides in preparing for the product launch.
Our teams are fully engaged in building commercial and medical capability to ensure a successful rollout. This includes training of our sales teams, but also medical teams, engaging with clinical opinion leaders, and ensuring supply chain readiness. Please turn to slide number 26. P egcetacoplan represents a transformative opportunity in nephrology, as you've just seen, and we are confident in its blockbuster potential. This confidence is grounded in the significant unmet medical need, the sizable patient population that could benefit from this therapy. In Europe alone, as we stated previously, there are around 8,000 diagnosed patients with C3G and primary ICMPGN. Beyond Europe, there's an additional potential in selected international markets across Sobi territories. The total diagnosed population is approximately 16,000 patients.
I think one should highlight also, when you look at the slide, that these numbers will be with the flux we expected, an increase of diagnosed patients and also the eligible patient pool over time, given the advantages of our product. This highlights the global opportunity we have to expand, access, and deliver meaningful outcomes for patients with these rare kidney diseases. However, unlocking the full potential of pegcetacoplan requires more than just addressing the numbers. It demands a deep understanding, obviously, of the complete patient journey. This means identifying, addressing barriers to diagnosis, ensuring that every patient with kidney diseases receives an accurate and timely diagnosis, providing support they need throughout the treatment journey. Our recent market research shows high enthusiasm from HCPs, as indicated by the quotes from HCPs across various countries based on the VALIANT data.
We look forward to making pegcetacoplan available to doctors and patients in the near future for potential treatment in both indications. Please turn to slide number 27. We have a lot of exciting opportunities at Sobi. It is clear that Aspaveli is a cornerstone of our corporate strategy. Our corporate strategy, as we outlined previously in the Q1 report, has two main launches ongoing with Altuvoct and Vonjo. We have three key regulatory filings in process, obviously Aspaveli being the most important one, but still, Gamifant and secondary HLH, also very important for the group. The NASP submission is on track to complete the rolling submission by end of this quarter. We have four important innovative development programs underway: Altuvoct in synovitis, Gamifant in interferon gamma-driven sepsis, Vonjo in VEXAS and CMML.
In 2025, we will invest in building for a successful launch of Aspaveli and NASP in 2026. We will continue rolling out Altuvoct in hemophilia and prepare the organization for launch of Gamifant in secondary HLH and H2. These, combined with our longer-term potential for Vonjo and Gamifant in sepsis, amount to very significant opportunities for Sobi and continued significant growth potential. Please turn to slide number 28. As you can sense, we are excited about our opportunities here, the impact that we can make considering significant unmet medical need. We are addressing C3G and primary ICMPGN, which are devastating diseases, and there are currently limited treatment options. These conditions profoundly impact patients' lives, and the lack of effective therapies leaves a significant gap in care. This unmet medical need represents a large market opportunity, as quoted in Europe alone, 8,000 diagnosed patients with these conditions.
This is a sizable population that could benefit from a targeted therapy like pegcetacoplan. What sets pegcetacoplan apart as a best-in-class therapy is really that we were able to demonstrate in both C3G and ICMPGN these impressive data. The data we have seen so far remain very strong, also in the 52-week data, reinforcing our confidence in the potential to transform standards of care for these patients. As a company, we are fully committed to bringing the therapy to market as quickly as possible, and launch in Europe remains on track for early 2026. This timeline reflects our dedication to ensuring that pegcetacoplan is available to patients who need it most as soon as possible. With that, I would like to open Q and A and like to refer back to the operator.
We will now begin the question and answer session.
Anyone who wishes to ask a question may press star and one on the telephone. You will hear a tone to confirm that you have entered a queue. If you wish to remove yourself from the question queue, you may press star and two. Questioners on the phone are requested to disable the loudspeaker mode and eventually turn off the volume of the webcast while asking a question. Anyone with a question may press star and one at this time. Our first question comes from Gonzalo Artiach from Danske Bank. Please go ahead.
Hi, and thank you for taking my questions. A couple of them for Dr. Fakhouri, if I may.
We see that in the group of patients that switch from placebo to treatment after 26 weeks, the benefit seems to be numerically lower compared to what was seen in patients treated with pegcetacoplan in the double-blind phase at 26 weeks. For example, in proteinuria reduction, it's 16 percentage points lower benefit versus the first dataset. Would you think that this is because patients that switch from placebo to pegcetacoplan receive the drug later compared with patients in the double-blind phase six months later, actually? Patient baseline characteristics at the time of pegcetacoplan treatment were somewhat clinically worse versus baseline levels at the beginning of the randomized phase. Just wanted to hear your view on that. A second question, if I can.
At the ERA Congress last weekend, the Iptacopan Peer C3G team pointed out that C3c staining in kidney biopsies is potentially underestimating actual C3 presence in biopsies compared with polyvalent antibodies that bind to several complement breakdown products. I would like to hear your view on that also. Thank you very much.
Thank you for this specific question. First question, I agree with you. Six months is a long period for such rapidly progressing patients with C3G, and probably they lost a little bit of time under placebo. That's why again, the reduction is still very, very significant, but I agree with you. It may seem a little bit smaller than the back-to-back, but six months in such highly rapidly progressing disease makes a big difference. Second, I think C3c staining is done worldwide. It's one of the most used staining in immunofluorescence for kidney disease.
If I may remind you, the diagnosis of C3G in the consensus document was based on immunofluorescence. It is rather basic staining done everywhere worldwide, and it is reliable. I think decreasing C3c staining alone does not speak much. When you have decreasing C3c staining plus 70% reduction in proteinuria, it gives more value one to another. When you have one clinical feature and one pathological feature going in the same direction, it is more reassuring regarding the efficacy of the treatment. I do not have big concerns about C3c staining. In real life, because I have started using pegcetacoplan in real life and also clinical trials, we have the same tendency in terms of reduction of proteinuria and in terms of reduction of clinical C3c staining.
Thank you very much.
As a reminder, if you wish to register for a question, please press star followed by one.
The next question comes from Alistair Campbell from Bank of Canada. Please go ahead.
Thanks very much for taking my question. Really, it's just a question on the competitive landscape now that iptacopan has also gained its first approval for C3G as well. I'd be intrigued to know from Dr. Fakhouri how you see both of these products lining up against each other, which one you broadly have a preference for. Maybe if you ask the second question for the current labels for the PNH area, again, just what are you seeing in terms of dynamics in PNH in terms of subaltern rolling out there? Thanks.
I'm going to start with the first question that is more directed to nephrology. As you have seen, pegcetacoplan, I have to get the data on pegcetacoplan, but you are aware of the data on pegcetacoplan. We have two drugs.
Patient and clinician would compare. One is older, others subacute. In my point of view, the reduction of C3c staining is a good marker of efficacy of a complement inhibitor, particularly in C3G. If I may, we did a survey with another disease complement inhibitor, which is atypical HUS, about patient preference, about drugs, the route of administration, and everything. What drives the choice of a patient for a drug in a complement-related disease? What came first? It was 120 patients, 120 patients worldwide. What came first is efficacy, tolerance, and then what went behind is route of administration, fixed drug administration. Clinicians and patients will have to look at the data. They will be published soon, probably in very high-ranking journals. They will see the effect.
What I can tell you is that what I see of pegcetacoplan is going to be hard to beat because 70% reduction in proteinuria and clearance of deposit makes it a very powerful drug for a specific and very efficient drug for C3G and immune-complex entities. Question, probably others would be more qualified to answer.
Maybe I can give you a quick hint on where we are with PNH. I mean, you have seen our Q1 results. I think they speak for themselves. Very powerful growth. Yes, the market is getting more crowded, obviously, with oral treatments. The therapeutic benefit, I mean, on the delta versus oral is obviously more pronounced in C3G and ICMPGN than it is in PNH. Still, the product is making good progress. We are rolling it out also in new markets.
As a consequence, we think that this is going to be a continued growth product for us as we speak, despite, obviously, heavier competition and the more crowded environment. Maybe go to the next question if this is okay.
For any further question, please press star followed by one. Gentlemen, it seems that there are no further questions at this time. Back over to you for any closing remarks.
Yeah, I mean, first of all, I'd like to thank Professor Fakhouri for his contribution and for his explanation, and also Nick. I mean, this is for us, obviously, a meeting just to shed some additional light. I think many of you may have seen data or were present at ERA. We just wanted to make sure that you do not miss and you get a sense of our excitement. We are fully behind this product. This is together with Altuvoct.
These are two top priorities for the group. We believe in this product, and we give it our best shot. We understand that we are up against formidable competitors, but this is not the first time that we are in this David and Goliath situation. We like it. We're thriving on it. This time, we have a spectacular product in our armament. I would like to thank you for your interest in Sobi and look forward to staying tuned. If you have questions, please refer to our AR, Gerard, or Jennifer, and we would be very happy to connect you with the relevant experts. Thanks a lot, and wish everybody a great afternoon or morning wherever you are. Thank you.
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