Swedish Orphan Biovitrum AB (publ) (SOBI) Earnings Call Transcript & Summary

Hello, everybody, and welcome to the Sobi IR call on the VALIANT top line Phase III data, which we published last Friday -- or last Thursday. We're very excited about the results of this data set and what it eventually means for patients with these diseases. So let's jump right into Slide 2. So this is just a normal forward-looking statements. Can quickly go on to Slide 3, and I'll just introduce the agenda for today. We're very, very happy today to have Professor Fakhouri from the University Hospital, Lausanne in Switzerland, join us on the call. He's going to help us put the data into context and give his insights from his extensive chemical experience in treating patients with C3G and IC-MPGN. So I'm very much looking forward to hearing his thoughts and appreciate the time he has taken to join us today. We're also joined today by Lydia Abad-Franch, the Head of Research and Development and the Chief Medical Officer for Sobi, and along with Michael Lai, Medical Development Leader of Pegcetacoplan for Sobi. To kick us off, we have 45 minutes. We'll dedicate most of the call for Q&A. But to start with Michael will take us through the top line results just to refresh everyone from the actual study, should not take too long, but then we'll dedicate most of the time for discussion with Dr. Fakhouri and the Sobi team. So I'll hand over to Michael and if we go to Slide 4.

Thanks, Gerard. So good afternoon, everyone. I'm pleased to share these really exciting top line results from the VALIANT trial with you today. Next slide, please. So I'll first start off with a brief reminder of the study design. This Phase III trial enrolled 124 patients with either C3 glomerulopathy, C3G or primary immune complex mediated membranoproliferative glomerulonephritis, IC-MPGN. The primary endpoint of this trial is the amount of proteinuria as measured by a log transformed ratio of the urine protein to creatinine ratio or uPCR, at week 26 compared to baseline. Study participants received either pegcetacoplan or placebo during this 26-week period in a randomized, double-blinded manner. Of note, this study enrolled both adolescent and adult participants as well as those with disease in their native kidney and those with disease recurrence after kidney transplant. Next slide, please. Now for the results. The study met the primary endpoint with a 68.3% relative reduction in proteinuria at week 26 in the pegcetacoplan group compared to the placebo group. This was -- this difference was highly statistically significant. From this slide, you can see that this was driven by a 67.3% reduction from baseline in the pegcetacoplan group compared to a 3.2% increase from baseline in the placebo group. In the next 3 slides, you will see how this positive result is consistent when you go into subgroups by disease type, age group, and in native kidney disease versus recurrent disease post-kidney transplant. Next slide, please. So for C3G versus IC-MPGN disease subgroups, there were similar improvements in proteinuria with 65.9% and 74.7% relative reductions compared to placebo, respectively. Next slide. For adolescents versus adults. Again, there was similar improvements with 74.6% and 62.7% relative reductions compared to placebo, respectively. Next slide, please. For native kidney disease versus recurrent disease post-transplant, a consistent improvement was seen even in the more number of participants in the post-transplant group. The relative reductions compared to placebo was 67.7% and 65.2%, respectively. Next slide, please. We now move briefly to cover the -- an overview of the key secondary endpoints. Overall, these endpoints support the positive efficacy of pegcetacoplan over placebo. Statistical significance was demonstrated for the proportion of participants who achieved a composite renal endpoint, which was defined as achieving stable or improved eGFR compared to baseline and at least 50%reduction in uPCR compared to baseline. Pegcetacoplan treatment also achieved statistical significance in the proportion of participants with proteinuria reduction of at least 50% from baseline. Regarding the activity score of the histologic index score, pegcetacoplan treatment was associated with a numerical improvement from baseline, but this was not statistically significant when compared to the placebo group. The remaining 2 secondary endpoints, although not formally tested statistically in the analysis did show a benefit of pegcetacoplan over placebo. The proportion of participants with a reduction in C3c staining under kidney biopsy was greater in the pegcetacoplan group than the placebo group. Furthermore, the eGFR in the pegcetacoplan group was stabilized compared to a decline in the placebo group. These two endpoints had nominal p-values of less than 0.0001 and 0.0322, respectively. Next slide, please. Regarding safety, pegcetacoplan showed favorable safety and tolerability consistent with this established profile. Rates of adverse events, serious adverse events and adverse events leading to study drug discontinuation was similar between the groups. There were no cases of meningitis or serious infections attributed to encapsulated bacteria. Next slide, please. So in summary, the VALIANT top line data show that treatment with pegcetacoplan led to a 68% reduction in proteinuria compared to placebo as well as improvements across multiple measures of disease activity. This benefit was consistent across a broad patient population. Pegcetacoplan was well tolerated with a safety profile consistent with known data. So we will be sharing the full results from this study in upcoming medical meetings later this year. Both Sobi and our partner, Apellis will work closely with regulatory authorities to make this treatment available to patients as quickly as possible. Now I'll hand back over to Gerard.

We cannot hear you Gerard, sorry. You're on mute.

Sorry, classic mistake. So yes, I just said thank you very much, Mike, for going through the overall results. We'll jump straight into the Q&A. So operator, if you can just remind people how to ask a question, and you can open the lines for Q&A.

We now begin the question-and-answer session. [Operator Instructions] The first question is from Mattias Häggblom with Handelsbanken.

I have two, please for Dr. Fakhouri. So perhaps, firstly, if you could help me put into context, the 68% reduction of proteinuria versus the 35% generated by iptacopan in the study presented earlier this year at ERA. Despite the cross-drive comparison, can you maybe help me think about what this difference may translate into long-term kidney function given your experience and in light of this only being a 6-month trial. And then secondly, this is a fairly young patient population, average age 26 years, if I understand correctly. So can you talk about the oral option with, again, iptacopan versus twice-weekly subcutaneous pegcetacoplan for such patient population from your physician point of view but also from a patient preference and how to think about route of administration and importance here?

Thank you for these two excellent questions. First, clearly, 70% reduction is quite impressive. And it's much, much more convincing from the clinical point of view compared to 30% with iptacopan. To be honest the 30% was seen by some clinicians as a rather small disappointment. But here when we are talking about 68%, it's an impressive result. Especially taking into consideration the fact that this patients had ACE inhibitor, SGLT2 inhibitors for a significant number of them. And this reduction was seen on top of MMF and corticosteroids in a very significant proportion of patients. So clearly, this is the first time I see such a very significant reduction in proteinuria in any complement inhibitor trial. Usually, we are around 30%, 35%. Here, we are approximately around 70% across all the subtypes of patients. And what gives more significance to the reduction is that, as you saw in the subanalysis, you have also a reduction in C3 deposition. And this makes a big difference especially in terms of the long-term outcome of these patients because the aim of the treatment is to remove C3 deposits on top of proteinuria. So clearly, when you take 70% reduction in proteinuria and the reduction in C3 staining, this is the most impressive result in C3G patients treated with any complement inhibitors that I'm aware of. And as you know, so most widely accepted prognostic factor in C3G as in other glomeruli disease is proteinuria. So yes, I think 70% reduction will translate in long-term protection of kidney function, no doubt about it because in all glomeruli disease, we are aiming to reduction of proteinuria but here, we have also the proof that we are also removing the primary driver of disease which is C3 deposition that has not been seen with iptacopan, as you know. So in my point of view, when you had 70% proteinuria reduction to a significant reduction in C3 deposition, it's clearly a very impressive result. Going back to your second question about oral versus subcut, I think the preference the patient will go firstly to the most potent and the most efficacious drug. While I agree with you that subcut may be a problem in some situation, but when you have such impressive difference in results in terms proteinuria and in terms of C3 deposition reduction, I think subcut will be more easy to sell or to convince patient to go to subcut because the difference in terms of efficacy are very, very different if you compare to iptacopan in terms of proteinuria, but also in terms of reduction in C3 deposition. And as you are aware, in PNH, Sobi is working and Apellis are working on another way to deliver the drug more easily to patients that will ease also the subcut infusion procedure. I hope I answered your question. Otherwise, don't hesitate and I can go back to any point you wish.

Maybe two follow-ups before I jump back into the queue, maybe for the company then. I understand this is not a commercial call given the people who is on it. But you still perhaps help me, this is an undeveloped market where patients are diagnosed, but there are no targeted therapy available. So help me think about how you think this market will build once we have approved therapies rapidly helped by total medicines and reimbursement in place or slowly and gradually as you and others would have to build and educate this market? And then a second follow-up and then I'll stop. Any comment yet if you think you will need 12-month follow-up for the European submission. I know this has been discussed for the U.S. perspective on the previous call, but any insight to the -- and in fact whether it's not in the 12-month follow-up.

I will answer the first question and leave Sobi's expert to answer the second. I think as an orphan disease with no available treatment, efficacious treatment and to use by default, meaning MMF and corticosteroids in my -- of my experience, almost 70, 80 patients are still managed on corticosteroids. So I think it would be rather quick to get the approval because you have an orphan disease with no efficacious treatment and high burden to patients, but I leave the answer to the Sobi expert.

Lydia, maybe if you want to comment on the filing status?

Absolutely. So and it's a little bit following up on Dr. Fakhouri's comment. So we have already started our discussions with regulators. And obviously, what we expect is that based on the huge unmet medical need and the highly significant results. And we expect to have a rather straightforward conversation with the regulators, but we will be updating all of you once we have advanced these discussions. But we are really positive and looking forward to bringing this product to the finish line as soon as possible because the patients really are in desperate need.

What we hope also, if I may, is that I'm not aware, maybe I am wrong, I'm not aware of any trial prospective control trial in glomeruli disease where we have seen such a huge decrease in proteinuria. Usually around 40%, 50% were very happy, now we're reaching 70%. In rather mostly severe case because they have resisted to MMF and corticosteroids before going into the trial. They had SGLT2 inhibitors and probably they had rather old disease because they were waiting for the drug and the trials to be open. So I'm not very -- I'm very confident that the regulatory authorities will go very quickly because 70% is a figure not seen very frequently in glomeruli disease.

And maybe if Lydia might want to comment just on the status of the device, where we are with that?

Well, again, we are trying to bring this as soon as possible to the patients, and we are quite advanced as well. So these are things that again, I agree with Dr. Fakhouri very much point and convenience for patients might be important. But when you are talking about a severe disease with very severe long-term consequences, I think efficacy always. It's most important for patients and clinicians rather than convenience. So despite that we are also working on having easier devices to handle this subcutaneous infusion so that patients can also have an easier experience on the top of the high efficacy.

[Operator Instructions] We have a question from Harry Gillis with Berenberg.

Thank you for taking the questions and I am hosting the call. So I have a few, if I may. First of all, just for Dr. Fakhouri. Of your -- of the patients you treat, I'm presuming mainly in the moderate-to-severe category. I was just wondering what proportion of patients you ultimately think are good candidates for targeted therapy and how many overall would be good candidates and are likely to be either treated with pegcetacoplan or iptacopan. And then just thinking about the size of the prescriber base, this is perhaps more for the company. Just trying to wonder, just trying to understand how patients today are treated across different settings and whether it requires quite a lot of the commercial effort to start to ramp those sales or due to the high unmet need, you think you can ramp those sales pretty quickly? That's it for now, thank you.

May I start? Am I allowed to start?

Yes, please.

I would say at least 2/3 of patients, 2/3 of patients will require treatment. And don't forget that this disease is very peculiar because it has flare ups and remission phase. So 2/3 at least. And the other option, other issue to have in mind is that those who have lost kidneys and are going to renal transplantation with such efficacious drug they probably will get it prophylactically which will increase the number of patients. So I would say 2/3 because some of them are rather stable. Some of them are very rapidly progressive and presently are minority to be honest. But we are left with at least 2/3 who will require some form of complement inhibition with the most efficacious treatment available. And even because you refer to a very severe case, also rapidly progressive probably they will need some anti-inflammatory drug in the acute phase, but they will need also some form of complement inhibition in the long term. So 2/3 at least would be my answer.

And just on the -- from the commercial side, I mean, we do have sort of synergies with in terms of marketing and regulatory on the PNH side. We need to see -- we'll have to build up the commercial infrastructure from a sales force perspective. We need to see where we go and that's something we'll be working on very diligently in the next several months. But we expect this to be, I would say, a pretty rapid update considering the strength of the data. I mean, this data is very, very strong. So we think that would stand for itself.

Sorry, if I may just I'll go with follow-up, sorry -- if there's is no other questions. Just wondering of the 8,000 patients in Europe. Just trying to get a sense of how many of those today, is it basically all of these are on some form of treatment and regularly see a physician? And then a second question for Dr. Fakhouri, if I may. I know you touched on this with the first question, but with the strength of the data being more important than the routes of administration. But if you had to guess, ultimately, what proportion of your patients who receive a targeted therapy, would you expect to receive pegcetacoplan versus iptacopan provided you had equal access to both.

So I'm going to start answering you. I would say to 2/3 of patients because as you said, some patients do not require treatment at some phase of their disease because they are rather an adjacent disease and [ calm ] come period of the day, I agree with you. But sooner or later, this patient had some sort of activation of that disease, and I'll stick to the 2/3 of patients. Of what I see -- as already said, efficacy will be -- will play a major role in the choice of the drug that can be offered to the patient. And when you have 70% reduction in proteinuria compared to 30%, I think the 70% will win the day and most of the patients, despite subcut and especially if the subcut infusion are made more easy with new devices, they will go for the subcut because the result is impressive, not only in terms of proteinuria, as I said, but also in terms of reversal of the disease by reversing the C3 deposition in their kidneys. So I believe that all the patients included in the trials no one complained about subcut. It was rather a device that is -- they are working on it to make it more easy for patients. If they were, let's say, if the both drug had 30% reduction in proteinuria, I think oral would have been an advantage. But now when you have 70% compared to 30% plus the recovery or reversal of C3 deposition is going to be tough to beat the 70% in my opinion.

Yes. We have a follow-up question from Mattias Häggblom with Handelsbanken.

Thanks so much. Seem to be a bit of slow here on questions. I thought I'd give it another shot, two more, please. So your partner described the opportunity as a blockbuster potential for what I assume was their region. So orphan drug markets is also entirely similar within the U.S. and Europe. So at least with strong data as a consequence. So we think this represents a lot faster potential in your regions as well? And then secondly, sort of linked to this, do you think you will need to change the current pricing for PNH given the upcoming likely label expansion? Or how should we think about pricing?

I think from the market size, I mean, we do see this as a very significant product now moving forward. I mean this -- especially with this data set, it's going to be very significant. I think we won't comment right now on sales -- peak sales potential. But it is -- yes, with this data set has definitely changed even our view internally on the asset. I would say on pricing, it's still a bit early. I think as a base right now, you probably should assume we will try and keep this similar PNH pricing, which this is -- these are the negotiations and discussions we will have now over the next 12 months as we go through the regulatory process and get ready for launch. So from right now, it's just a little bit too early to comment anything on pricing.

If I may add it's not commercial comment, it's a clinical comment. These are costly drugs and clinicians will pay more easily when you have 70% reduction compared to 30%. And we said that, for example, in [ anti-platelet ] the effect was tremendous in terms of kidney survival, so health authorities and hospitals and clinicians were ready to pay. And now every percentage reduction in proteinuria will cost a lot. So when you have 70%, it's better than 30%. It will make the price more easy to support from the clinical point of view. The other marketing and commercial aspects I'm not -- I don't want to go into these details...

The next question is from Yifeng Liu with HSBC.

And I think one for Dr. Fakhouri, on the sort of kidney transplant, non-transplant patients, as you see the numbers in the kidney transplant patients trial seems to be relatively few or small. I just wonder to what extent does that reflect what you see in a daily practice. And secondly, I think just on the endpoint, so I think my question being the primary endpoint the uPCR using this trial and also some -- and also in terms of improvement or stable for eGFR reduction in proteinuria. So going ahead, do you see how that's going to evolve? So in terms of whether there's a chance that future data might be needed on sort of improved eGFR data on this sort of indication?

Okay. I'm going to start with the transplant patient. We had, if I remember, were 20 or 25 patients with kidney transplant, which is a significant number of patients. And don't forget that you had the NOBLE study, small number of patients, but as a concept of proof with the clearance of C3 deposits. But I think as in atypical HUS the recurrence of the disease will be almost disappearing in the coming years when you have an efficacious treatment, meaning in native atypical HUS, we have a lot of patients that were waiting for renal transplantation. And when eculizumab arrived, it changed everything. And now the percentage of patients reaching end stage kidney disease has so decreased that the issue of kidney transplantation has not become as important as it used to be. But still, here, what I see is that as for atypical HUS, probably pegcetacoplan going to use prophylactically, in patients at high risk for recurrence after transplantation for C3G patients and also for immune complex MPGN. So I think with 2022 a patient in this trial plus the NOBLE trial, we have already enough data to see an effect and to see very valid results and conclusions drawn for the post renal transplant recurrence patient. And for eGFR, yes, I agree with you. We'll need more long-term data on eGFR. But still, you have already seen a difference with the placebo in a very short period of time of follow-up. And if you use proteinuria as a surrogate marker because clinicians and health authorities know that you will need 3, 4 years to get at least idea about eGFR. But still, you have a massive reduction in proteinuria, a very significant reduction in C3 deposition and already a difference in terms of eGFR evolution between placebo and pegcetacoplan. And it's going to be a good start to discuss with health authorities regarding the long-term protection of kidneys.

We have a follow-up question from Harry Gillis with Berenberg.

We don't hear you Harry. Maybe we'll come back to him. I think Mattias has another follow-up question.

Yes. Mr. Mattias Häggblom with Handelsbanken has another follow-up. Please go ahead.

Yes. Thanks so much. And sorry for being so exhaustive here. I was curious to hear Dr. Fakhouri to the extent you also see patients with IgA in your practice? And then I had a follow-up.

Yes. Your question is if I see IgA nephropathy in my practice? Yes.

Excellent. So the follow-up then is, given the effect this drug seems to have on the kidney and the glomeruli, how would you think about exploring this drug in that patient population?

As you know you have a lot of complement inhibitors going into IgA nephropathy. I think the big difference between C3G and IgA nephropathy is that in C3G complement is the main drug. In IgA nephropathy complement is the secondary drug of the disease, which means I don't think we can expect such tremendous decrease in proteinuria with complement inhibitors in IgA compared to C3G. But it's a good option to explore but the prototypic complement renal disease where you can prove easily the efficacy of your drug is C3 glomerulopathy. But IgA nephropathy has become a very overcrowded field, and you have a lot of complement inhibitors going into IgA nephropathy. I'm afraid that just a personal opinion, the results would not be as impressive as the 70%. It's going to be around 30%, 40% reduction in proteinuria, which will already be good, but it doesn't reflect the fact that complement is the main driver. In IgA in my opinion, it is secondary driver of the disease. But we'll have to see if Sobi and Apellis would like to go into IgA nephropathy once they have shown very, very massive reduction in C3G.

[Operator Instructions]

Okay. I think there seems to be all the questions we had. So thanks very much for all the questions that were asked on the interest and really, really big thanks to Dr. Fakhouri for joining us and giving his expert opinion and insight. It was really useful for the call. And thanks, everyone. Thanks to the Sobi team for joining. And thanks, everyone, for joining and your interest in Sobi.

Thank you. Bye-bye.