Study Result

Jun 28, 2021

Press Release

Thank you very much. Welcome all of you listening in. We are hosting this web cast since we yesterday evening published positive results from the interim readout from our ongoing Phase III trial with our biosimilar candidate ex LUKAIM. I have with me today our Head of Clinical Affairs, Dina Jormann. And for those of you who do not know me, my name is Martin, CEO of XBain Biopharma. Okay. So if we can go to Page number 3 to start off. Just to remind you all, exlucaine is a biosimilar candidate to Lucentis. And Lucentis is a drug used in treatment of several severe eye diseases, mainly age related macular degeneration and also diabetes related macular ADMN. And these are diseases which leads to a deteriorating vision for the affected individuals. These are big diseases. We estimate it to be some 18,000,000 eyes affected globally, 5,000,000 or so across Europe and the U. S, 13,000,000 or so in the rest of the world. And important to note here, high fraction of affecturize those untreated due to the high pharmaceutical costs of the on label drugs for these indications. So we believe due to this, it's a great prospect to bring more cost efficient treatment alternative to this market in the form of biosimilar to Lucentis. So we can shift to Page number 4. And here, I want to have Dina Juhlman, our Head of Clinical Affairs, describe a little bit more in detail the setup of EXPLORER our Phase III trial for XENUKA. Thanks, Martin. Hello, everyone. So EXPLORER is an ongoing study, During which we are evaluating efficacy and safety of our product, exlucaine, compared to Lucentis. We do this in patients with newly diagnosed neovascular AMD. About 580 patients We're allocated equally to receive monthly injections of exlucaine or Lucentis for a duration of about 1 year, a total of 13 doses. At the time of this teleconference, 76% of patients Have finished their participation in the study. The primary objective of the study is to show that exlucaine is equivalent to Lucentis. And to assess the equivalence hypothesis, the primary endpoint in the study is the change in visual acuity at week 8 compared to time point before treatment commenced, also known as baseline. And when we speak about visual acuity, we talk about a BCVA, which is a standardized way of assessing how well patients can read letters on a certain chart from a certain distance. The visual acuity assessors, so staff at the clinics, they are They're trained and they're certified centrally to conduct this very important assessment in a standardized manner, which Ensure that we have a consistency in the way the results are gathered and then analyzed. Approximately 140 clinics in 15 countries contributed to successful completion of patient recruitment in November last year despite the challenges due to COVID-nineteen pandemic. And to date, the treatment schedule and Testaments in the study have been in large maintained and the majority of the deviations that we are Seeing due to the pandemic are minor and not expected to have an impact on the interpretation of the data that we have collected so far. Now I understand that you're all very curious about the top line data readout from the interim analysis that was done last week. And this analysis includes data up to and including month 6 visit for all patients on the study. And Martin is going to tell you a bit more about this later. Important to note is that the study is still ongoing. And the last patient last visit is expected to occur end of this year, followed by complete study analysis shortly thereafter in January 2022. The trial is conducted in collaboration with Syneos Health. This is a multinational CRO with extensive experience in conducting trials in the field of ophthalmology. The trial is This is supported by a team of ophthalmologists at Syneos Health that are specialized in eye and vision care. So in other words, very experienced and well versed partner on this pivotal clinical trial. Maarten, will you presented results. Thank you very much, Georgina. So if we move on to Page 5. So this is now top line data from the interim readout, which then includes data from all patients up to treatment month number 6. And we selected 5 endpoints for this top line data. We're still awaiting data on remaining secondary endpoints in this trial and some of them are listed in the bottom of this page. And also, it's important to note that the 12 month data, which then is due in beginning of next year, is crucial for concluding the full study and for the authorities in terms of assessing biosimilarity. But if we look at these 5 first endpoints, which forms part of the top line results and we selected these ones because we deemed them to be the most important ones. Okay. So the primary endpoint was change in visual acuity measured in BCVA, best corrected visual acuity from baseline to week 8 as the primary endpoint. And that was selected week 8 since that's the point in time where the change in Visual Acuity is the largest and therefore, it's the point in time where you most likely are going to identify any potential differences with a biosimilar candidate and the originated product. And the statistical criteria set forward here was that the 95% confidence interval, if we speak about EMA, European Regulator Outorte, around the difference between the means of extra gain and the centers, respectively, needs to forward in a predefined equalized margin, which in this case was plusminus3.5 letters as agreed with both EMEA and FDA. Now FDA worked with a 90% confidence interval, but we imagine 95% confidence interval. And here, we were this is the most important of course, and we're very happy to announce that the trial met the primary endpoint, and that is to say conference interval around the difference was contained within this defined equivalence margin. So that's very good, of course, and that demonstrates an equivalent efficacy with regards to improvement in visual acuity compared to Lucentis. Then we looked at a very important secondary endpoint, which is reduction in the retina thickness. And this is important since it's a crucial part with regards to the mode of action of these products. As you know, these are called VGF alpha inhibitors. They're injected into the eye and they're binds into a growth factor called VGF alpha, which then inhibits the growth of abnormal blood vessels in the eye. And the subtraction of these blood vessels can be measured. We are measuring the thickness of the retina. And that then leads to improvement in vision. So this is a very important endpoint, which is on the causal pathway towards improvement in Visual Activity. And some regulatory authorities, At least EMA also accepts this endpoint as a primary endpoint with regards to biosimilar trials in this field. So this is an important endpoint. And here, we're working with the descriptive statistics. And Bottom line is that we cannot identify any clinically meaningful differences between extra gain and placentis. So this is very good. Next one here, as many of you know, typically in clinical development of biosimilar. You first have to do a Phase I trial where you compare pharmacokinetics of your biosimilar candidate to the originator in healthy volunteers. And then you go on in a Phase III trial where you compare efficacy and safety in well selected indication. Now when it comes to biosimilars 2 Lucentis, it's not meaningful to conduct a Phase I trial in that manner because, again, it's a drug injected into the eye and a very small portion of the active ingredient finds its way out of the eye into the systemic circulation. And you cannot really measure the concentration of the API in the blood circulation in a manner so that you can compare it strictly statistically speaking. It's very low concentrations and the variability is very high. But what we agreed with the regulatory authorities to do in this case was to go straight into Phase III, but in a subset of the patients, 60 patients in this case, look at pharmacokinetics. And here also, we work with descriptive statistics. We're looking at the maximum concentration at day 1 and at week 20. And also here, we cannot observe any clinical and meaningful differences between actually gained in the centers. So that's very good as well. Then we look at immunogenicity. So this is essentially the body's own potential response to the drug itself. And here, you measure antidrug antibodies or neutralizing antibodies via blood samples across all the patients at all time points and compare the cases in which you find either antidrug antibodies or nephylizing antibodies. And here as well, we cannot see any clinically meaningful differences between exelucane or Lucentis. And then, of course, it comes to safety profile where we look at adverse events of different severity and different kinds. And this is, of course, crucial aspect of, well, any Phase III trial, but particularly in ophthalmology and and intravitreal injected drugs because it's very sensitive towards and virtual events. And here, we cannot see any clinically meaningful differences either between extra clinical and Lucentis. So overall, looking at these five endpoints, We come out positive. We met the primary endpoint and across the 4 secondary endpoints here list that we see no clinically meaningful differences. So we're very happy with this interim readout. It's encouraging. But again, we need to be clear on that there are multiple additional secondary endpoints for which we yet have not seen the data. So we're going to receive the data and analyze the data in due time ahead of submission of the marketing authorization application. And then also it's crucial, of course, that what we show here, we also see with regards to all these different secondary endpoints by the time of month 12 when all the patients have concluded 12 month treatment. So that's really the key outcome of this interim readout. So we can move on to Page number 6 here. And to look ahead a bit, we now confirm our previously communicated plans to proceed towards submission of the marketing authorization application to EMA in Q3 this year and to FDA Q4 this year. And in accordance to an agreement with both authorities. We make the submission on the basis of these interim results and then we complement the regulatory filed with the 12 month data during the Q1 of 2022. And counting on the 12 month regulatory process, which I think we need to count on in a case like this, We expect to have approval in place in the second half of twenty twenty two and then allow for launch of the product by our 2 partners, Starland, Bausch and Lomb. And that is shortly after the patent expire of the originated product in Europe, which is July 2020. So exciting times for us, of course, now. We expect for it to be on market in 18 months or so. So it's very short time now ahead up until we can actually see the product on the market. It's very exciting, of course. And we're very excited about the prospects for the product, both with regards to what we can do for the patients in this area and also the commercial prospects of the product. So that was all from the formal presentation. So here, we can open up for any potential questions. We can start with questions that come over phone potentially. Thank you. And we have a question from the line of Matthias Hegblad from Handelsbanken. Please go ahead. Matthias, if your line is on mute, can you please unmute yourself? Matthias, can you hear us? I don't believe Matthias is on the line. So just as a reminder, if you do wish So we only have Matthias, but I don't think we can get through. So I'll hand it back, and then we can try again if Matthias registers. Sure. Thank you. And I actually see no questions coming in over e mail either. So I don't know if we should give it a couple of more minutes or maybe it was so clear that it doesn't result. Any questions here? Yes, no questions coming in really. So I think then that was really all from us, and we can probably then conclude this call. And Thank you all who listened in. And we are, of course, as always available. You can Send any questions you might have after this call over e mail or give me a call, and we shall be discussing any potential questions here. But with that, thanks a lot, and we can then close the call.