Hansa Biopharma AB (publ) ($HNSA)

Good day, and welcome to the Hansa Biopharma Conference Call. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Hansa Biopharma's CEO, Renee 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 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. And I'm Renee 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 a very brief agenda. I will initially provide a very brief introduction, and our CMO will then present the top line results, and we'll have a brief overview of the next steps in 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. And this really is focused on enzymes who very rapidly and efficiently cleave IgG in about 2 to 6 hours and bring that down to more than -- reduce it by over 95% from baseline. This involves all classes of IgG, both intra and extravascularly. Next slide, please. So highly sensitized patients, that is 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've 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 the 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 through the PAES trial. Next slide. And with no further ado, I want to hand over to our CMO, Richard Philipson, who will take you through the data. Richard?

Thanks, Renee. I'd like to present the top line data from a 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 crossmatch against the deceased donor prior to treatment and which included noncomparative registry and concurrent reference cohorts. Next slide. The primary objective of the study was to determine the 1-year graft failure-free survival in highly sensitized kidney transplant patients pretreated with imlifidase to turn a positive crossmatch against the deceased donor into a negative crossmatch. Secondary objectives include the evaluation of renal function, patient survival and graft survival up to 1 year after transplantation. And 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 prescreening to increase the likelihood of receiving a donor organ offer. When an organ offer was received, if the patient was crossmatch positive to the organ, then 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 2 noncomparative reference groups. It's 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 2 reference cohorts have different baseline characteristics when compared with the imlifidase treatment group. The noncomparative 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 crossmatch 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 noncomparative 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 but 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 1-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 3 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 noncomparative concurrent reference cohort were not sensitized and patients in the noncomparative 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 2 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 a limited -- we have limited information on the historical reference cohort when compared with the information available for the other 2 cohorts, I'll present only data relating to imlifidase and concurrent reference cohorts. Next slide, please. In imlifidase cohort, 51 patients were enrolled and treated with imlifidase. One patient did not complete transplantation for technical surgical reasons and was included -- excluded from the intention to treat or ITT population. A further 2 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, 2 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 a little older 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 at least 1 previous transplant with approximately 1/3 of patients having had 2 or more previous transplants. Next slide, please. In terms of exposure, in the imlifidase cohort, 4 patients or 8.3% required second dose of treatment to achieve crossmatch 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 1-year graft failure-free survival in highly sensitized kidney transplant patients pretreated with imlifidase. In the imlifidase cohort, using a Kaplan-Meier survival estimate, graft failure-free survival at 1 year was 89.6%. In the concurrent reference cohort, using the same analysis, graft failure-free survival at 1 year was 91.7%. Next slide. Turning to patient survival. There was 1 death in the imlifidase cohort and 2 deaths in the concurrent reference cohort. The Kaplan-Meier estimate of patient survival at 1 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, 4 patients in the imlifidase cohort and 3 patients in the concurrent reference cohort experienced graft loss. The Kaplan-Meier estimate of graft survival at 1 year in the imlifidase cohort was therefore 91.6% and the corresponding estimate in the concurrent reference cohort was 95%. Kidney function at 1 year was evaluated using estimated glomerular filtration rate or eGFR. In the imlifidase cohort, eGFR at 1 year was 52.4 mL/min. The corresponding outcome in the concurrent reference cohort was 56.5 mL/min. And then 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. So 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's noteworthy that the overwhelming majority of patients in the imlifidase cohort had at least 1 previous transplant with approximately 1/3 having had 2 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 mL/min. 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. And now I'd like to hand back to Renee.

Thank you, Richard. Next slide, please. So in summary, this data, we believe, is consistent with prior data sets from imlifidase, is highly clinically meaningful, and supports a submission to EMA for the conversion from conditional to full approval. We'll continue our work in preparation for this, and we target a filing in Q4 this year. It's exciting times for highly sensitized patients, and 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. And 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. And with that, next slide, please. I think we're ready to take any questions.

[Operator Instructions] The first question today comes from Thomas Smith with Leerink Partners.

This is Brian Conley on for Tom Smith. Congrats on the data. So could you comment on whether you saw cases of antibody-mediated rejection and how those patients' eGFR readings at 1 year compared to those who didn't experience AMR rejection? And 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?

So in terms of your first question about AMR, I want to emphasize that what's been presented today is the top line data. So we don't have the analysis on other outcomes in the study, including AMR and CMR. So those will be available to us in several weeks from now. So it's simply the top line data that we're presenting today. Renee, would you like to?

So 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.

The next question comes from Matt Phipps with William Blair.

Congrats on -- the data 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?

Well, I mean, I certainly think this is a very substantial body of data. So I think from that point of view, I think once the data 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. And of course, as Renee 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.

And I think, obviously, this type of structured approach in any of these, kind of, more, kind of, clinical trial settings, I would say, is always helpful to inform, kind of, the best way of doing this in, kind of, a real-world setting. Obviously, a lot of times in these type of settings, you have a lot more -- you do a lot more tests, you have a lot more visits, you're focusing on, kind of, things that are more from a, kind of, clinical trial perspective. But yes, I do think that the actual structured approach to both, kind of, pre- and post-transplant care will be helpful to bring into the commercial setting as well.

If I can 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? And is it -- 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?

Yes. So I think that level of requirement for second dose is broadly similar to what is seen in real-world practice. And I think 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. So I think it would be premature for me to comment on those patients and the characteristics of those patients.

Yes. I think we've seen, kind of, anywhere from 10% to 15% broadly, kind of, a use of a second dose. So yes, I think it's fairly consistent.

Great. Thanks for taking my questions and congrats on the data.

[Operator Instructions] The next question comes from Suzanne van Voorthuizen with Kempen.

This is Suzanne from Kempen. 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? And is that something that you can also somehow leverage for the U.S. commercialization strategy?

So from a point of view of follow-up, yes, indeed, there is a long-term follow-up component to this. So all patients who are enrolled into this study then entered into a long-term follow-up. So that will report data out up to 5 years.

And this is obviously consistent with the already published, kind of, 5-year data from the Phase II trials. So I think, obviously, that data is already, I would say, already, kind of, available to the community in that, kind of, published and presented form. But obviously, yes, we would expect to, kind of, 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 for listening to this call regarding the PAES top line data, and 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.