Good day, and welcome to the Hansa Biopharma conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on a touch-tone phone. To withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to Hansa Biopharma CEO, Renée Aguiar-Lucander. Please go ahead.
Thank you very much. Good afternoon or good morning. Welcome to this Hansa Biopharma conference call to present the top-line results of the PAES study. This is a very exciting day for all of us at the company, but also, I believe, for many highly sensitized patients who have limited options apart from dialysis today. We're very proud to be able to bring you the positive results of our post-authorization efficacy study. I'm Renée Aguiar-Lucander, CEO of Hansa Biopharma, and joining me today is Richard Philipson, Chief Medical Officer. Next slide, please. Please allow me to draw your attention to the fact that we'll be making forward-looking statements during the presentation. You should therefore apply appropriate caution. Next slide, please. This is today's very brief agenda. I will initially provide a very brief introduction, and our CMO will then present the top-line results.
We'll have a brief overview of the next steps and the Q&A session. Next slide, please. For those of you who may not be familiar with Hansa Biopharma, we have a novel first-in-class IgG cleaving platform. This really is focused on enzymes who very rapidly and efficiently cleave IgG in about two to six hours and reduce it by over 95% from baseline. This involves all classes of IgG, both intra and extravascularly. Next slide, please. Highly sensitized patients, that means patients with a CPRA score in excess of 80, represent about 15% of the approximate 170,000 patients on the kidney transplant wait list in Europe and the U.S. today. Annually, around 10% of these patients are removed from the list due to death or because they become too compromised or sick to transplant.
Out of these patients, approximately 25% are highly sensitized, reflecting the high unmet medical need amongst this patient group. We believe that imlifidase represents a pioneering breakthrough for these patients, who often wait for extended periods of time for an organ offer or may never receive one. We're therefore very excited to share the top-line data the PAES trial. Next slide. With no further ado, I want to hand over to our CMO, Richard Philipson, who will take you through the data. Richard.
Thanks, Renée. I’d like to present the top-line data from the Post-Approval Efficacy and Safety Study 20-HMedIdeS-19. This was a controlled open-label study in imlifidase desensitized kidney transplant patients who had a positive cross-match against a deceased donor prior to treatment, and which included non-comparative registry and concurrent reference cohorts. Next slide. The primary objective of the study was to determine the one-year graft failure-free survival in highly sensitized kidney transplant patients pre-treated with imlifidase to turn a positive cross-match against a deceased donor into a negative cross-match. Secondary objectives include the evaluation of renal function, patient survival, and graft survival up to one year after transplantation. Of course, safety was also an objective of the study. Next slide. Here I provide an overview of the design of the study.
Starting at the top of the schematic, patients enrolled in the imlifidase treatment group were highly sensitized with the highest unmet medical need based on the local kidney allocation system. Patients underwent a delisting step at pre-screening to increase the likelihood of receiving a donor organ offer. When an organ offer was received, if the patient was cross-match positive to the organ, the patient proceeded to treatment with imlifidase and transplantation, subject to meeting required eligibility criteria and converting from cross-match positive to cross-match negative. It was planned to enroll 50 patients into this treatment group. Moving down the schematic, there are two non-comparative reference groups. It is important to note that patients were not randomized to these reference groups, and there are no statistical comparisons made between the imlifidase treatment group and the reference groups.
Furthermore, patients in these two reference cohorts have different baseline characteristics when compared with the imlifidase treatment group. The non-comparative concurrent reference group comprises 50 to 100 contemporaneous kidney transplant patients enrolled at the same study sites at the approximately same time as patients enrolled in the imlifidase treatment group. These patients were not sensitized and had a negative cross-match to the deceased donor organ offer. The rationale for inclusion of this reference group is to understand outcomes at the same sites when undertaking matched kidney transplants. Finally, the non-comparative historical reference group comprises 100 kidney transplant patients randomly selected from a patient registry from 2010 onwards.
Selection of patients was performed by the registry administrators and was completed prior to the start of enrollment of the main study. Patients in this cohort were sensitized up to a lesser degree than patients in the imlifidase treatment group and were cross-match negative to the donor organ offer. Again, to emphasize, the primary objective to determine the one-year graft failure-free survival in highly sensitized kidney transplant patients applies to the imlifidase treatment group only. Next slide. In this slide, I summarize the key eligibility requirements for the three cohorts included in the study. All patients enrolled in the study were male or female, aged 18 to 75 years, with an ABO compatible deceased donor aged 10 to 70 years.
Patients included in the imlifidase cohort were highly sensitized, whereas patients in the non-comparative concurrent reference cohort were not sensitized, and patients in the non-comparative historical reference cohort were sensitized, but to a lesser degree than the imlifidase cohort. Patients in the imlifidase cohort were cross-match positive to the donor organ offer, whereas patients in the other two cohorts were cross-match negative. Patients in the historical cohort were transplanted in the period 2010 to 2017. Next slide, please. I'll now present the baseline characteristics of the study population. Because we have limited information on the historical reference cohort when compared with the information available for the other two cohorts, I'll present only data relating to imlifidase and concurrent reference cohort. Next slide, please. In the imlifidase cohort, 51 patients were enrolled and treated with imlifidase.
One patient did not complete transplantation for technical surgical reasons and was excluded from the intention to treat, or ITT, population. A further two patients were excluded from the ITT population as they were later found to have met one of the exclusion criteria for the study. The imlifidase ITT analysis population therefore comprises 48 patients, and the safety population comprises 51 patients. In the concurrent reference cohort, two patients were excluded from both the safety and ITT populations as they received donor organs from individuals outside the specified age range of 10 to 70 years. Retention in the study was excellent, with greater than 90% of patients in the imlifidase and concurrent reference cohorts completing the study. Next slide, please. Patients in the imlifidase cohort had a mean age of 49.8 years and approximately 60% were male.
77% of patients in this cohort were White and a further 12.5% were Black. In the concurrent reference cohort, patients were less old, with a mean age of 55.4 years. The proportion of males was again approximately 60%, and there was a similar race distribution. Next slide, please. Looking at the baseline characteristics, all patients in the imlifidase cohort were on dialysis, whereas in the concurrent reference cohort, a small proportion of patients, 11.5%, were not receiving dialysis prior to transplantation. When looking at the number of previous transplants, it's interesting to note that approximately 90% of patients in the concurrent reference cohort had not had a previous transplant, whereas in the imlifidase cohort, the majority of patients had had at least one previous transplant, with approximately one-third of patients having had two or more previous transplants. Next slide, please.
In terms of exposure, in the imlifidase cohort, four patients or 8.3% required second dose of treatment to achieve cross-match conversion. Next slide, please. I'll now move on to describe the top-line outcomes from the study. As previously mentioned, the primary objective was to determine the one-year graft failure-free survival in highly sensitized kidney transplant patients pre-treated with imlifidase. In the imlifidase cohort, using a Kaplan-Meier survival estimate, graft failure-free survival at one year was 89.6%. In the concurrent reference cohort using the same analysis, graft failure-free survival at one year was 91.7%. Next slide. Turning to patient survival, there was one death in the imlifidase cohort and two deaths in the concurrent reference cohort. The Kaplan-Meier estimate of patient survival at one year in the imlifidase cohort was therefore 97.9%, and the corresponding estimate in the concurrent reference cohort was 96.7%.
When looking at graft survival, four patients in the imlifidase cohort and three patients in the concurrent reference cohort experienced graft loss. The Kaplan-Meier estimate of graft survival at one year in the imlifidase cohort was therefore 91.6%, and the corresponding estimate in the concurrent reference cohort was 95%. Kidney function at one year was evaluated using estimated glomerular filtration rate, or eGFR. In the imlifidase cohort, eGFR at one year was 52.4 mils per minute. The corresponding outcome in the concurrent reference cohort was 56.5 mils per minute. With respect to safety, imlifidase was generally well-tolerated with a safety profile consistent with previous clinical trial experience. There were no new safety findings.
In conclusion, the study was well conducted with more than 90% of patients completing the trial. Demographics and baseline characteristics were in keeping with the kidney transplant population, and it is noteworthy that the overwhelming majority of patients in the imlifidase cohort had had at least one previous transplant, with approximately one-third having had two or more transplants. Efficacy outcomes at 12 months in the imlifidase treated patients were excellent. Graft failure-free survival was 89.6%. Patient survival was 97.9%. Graft survival was 91.6%, and eGFR was 52.4 mils per minute. Imlifidase was generally well-tolerated, with a safety profile consistent with previous clinical trial experience, and there were no new safety findings. A full description of the efficacy and safety outcomes will be presented at a future congress. Now I would like to hand back to Renée.
Thank you, Richard. Next slide, please. In summary, this data, we believe, is consistent with prior data sets from imlifidase, highly clinically meaningful, and supports a submission to EMA for the conversion from conditional to full approval. We'll continue our work and preparations on this and we target filing in Q4 this year. It's exciting times for highly sensitized patients, we in turn are very excited to be part of this journey and importantly, to be able to observe that the outcomes are substantially similar between the highly sensitized cohort and the non-highly sensitized cohort as per the data just presented. Next slide, please. Finally, I just want to remind you of the upcoming Capital Markets Day, where you will have the opportunity to listen to how the transplant community interprets the data generated and how this might impact standard of care going forward.
I invite you all to either appear in person in New York or via link. With that, next slide, please. I think we are ready to take any questions.
We will now begin the question and answer session. To ask a question, you may press star, then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question today comes from Thomas Smith with Leerink Partners. Please go ahead.
Hey, guys. Good morning. This is Brian Conley on for Thomas Smith. Congrats on the data, thanks for taking our question. Could you comment on whether you saw cases of antibody-mediated rejection and how those patients' eGFR readings at one year compared to those who didn't experience AMR rejection? Second, will you be sharing this full data set with the FDA to support your ongoing BLA review, and if so, when do you plan to do so? Thank you.
In terms of your first question about AMR, I want to emphasize that what's being presented today is the top-line data. We don't have the analyses on other outcomes in the study, including AMR and CMR. Those will be available to us in several weeks from now. It's simply the top-line data that we're presenting today. Renée, would you like to
Yeah. With regards to the FDA, I think that we would expect to share this data with the FDA. In terms of exactly when and in what format, I think we still need to kind of clarify.
Thanks so much.
The next question comes from Matt Phipps with William Blair. Please go ahead.
Hi. Thanks, and congrats on the data. It looks very consistent with ConfIdeS. I guess, as you look at some of this data, I wonder how homogeneous were some of the post-transplant protocols, and do you think presenting this data helps these different sites kind of align on, I guess, best practices that can be carried forward commercially? Thank you.
I certainly think this is a very substantial body of data. I think from that point of view, I think, once the data are taken through to the regulatory authority in Europe, are disseminated at a future congress, and find their way into prescribing information and scientific information, I think that's going to provide prescribers with a really useful body of information to help support the use of the product. Of course, as Renée has said, although there were no statistical comparisons between the cohorts, obviously we do have the information from the concurrent reference cohort and the outcomes in the imlifidase-treated patients certainly look similar to the outcomes in the concurrent reference cohort, which contain patients who are receiving matched organ transplants.
I think obviously this type of structured approach in any of these more kind of clinical trial settings, I would say, is always helpful to inform the best way of doing this in a real-world setting. Obviously, a lot of times in these type of settings, you do a lot more tests, you have a lot more visits. You're focusing on things that are more from a clinical trial perspective. Yes, I do think that the actual structured approach to both pre and post-transplant care will be helpful to bring into the commercial setting as well.
If I could ask a quick follow-up. Only 8% of patients needed a second dose of imlifidase. Is that consistent with some of the real world data you guys have seen? Is there anything that drives maybe that second dose from a baseline perspective? Is it the highest CPRA levels or just total levels of IgG? Thanks.
Yeah. I think that level of requirement for a second dose is broadly similar to what is seen in real world practice. In terms of commenting on this specific trial, I think we still need to get all the data to understand more about the patients who need a second dose. I think it would be premature for me to comment on those patients and the characteristics of those patients.
Yeah, I think we've seen anywhere from 10%-15% broadly, a use of a second dose. Yes, I think it's fairly consistent.
Great. Thanks for taking my questions and congrats on the data.
Yeah.
As a reminder, if you would like to ask a question, please press star then one. The next question comes from Suzanne van Voorthuizen with Kempen. Please go ahead.
Hi team, this is Suzanne from Kempen. Thanks for taking my question. Just one. Assuming the study continues to follow patients, will there be an opportunity to report longer follow-up data in the coming years as well? Is that something that you can also somehow leverage for the U.S. commercialization strategy? Thank you.
From the point of view of follow-up, yes indeed. There is a long-term follow-up component to this. All patients who are enrolled into this study and entered into a long-term follow-up, so that will report data out to up to five years.
This is obviously consistent with the already published five year data from the phase II trials. I think obviously that data is, I would say, already available to the community in that published and presented form. Obviously, yes, we would expect to continue to follow and report that data with regards to this long-term outcome as well.
As there are no further questions, I'd like to turn the call back over for any closing remarks.
Thank you very much to listening to this call regarding the PAES top line data. We look forward to welcoming you again to future calls. Thank you.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.