Welcome to the BioInvent's Audiocast with Teleconference Q4 2021. For the first part of this call, all participants will be in a listen-only mode, and afterwards there will be a question and answer session. Today, I am pleased to present Martin Welschof, CEO, and Stefan Ericsson, CFO. Please begin your meeting.
Thank you very much and welcome everybody to our quarterly call. I would like to start with a brief summary of the events that happened during the last quarter. We had positive interim data from our lead program, BI-1206 in non-Hodgkin lymphoma, where we could see increased and sustained responses in relapsed patients. That was particularly very impressive in follicular lymphoma. At the same time also we released positive early clinical data from BI-1206 in combination with pembrolizumab for solid tumors. We also made good progress in our collaboration with CASI Pharmaceuticals. We received the IND for China for clinical studies in China at the end of last year.
We also were very proud that we advanced to the Nasdaq Stockholm's mid-cap segment. Last but not least, we also got an Orphan Drug Designation granted for BI-1206, which was very important also from a strategic clinical development perspective, and we got that for follicular lymphoma. We published a very nice publication in Journal for ImmunoTherapy of Cancer together with Transgene, and that was about our preclinical data here with BT-001, where we could show a very convincing proof of concept for our 50/50 collaboration with Transgene, and I will come back to that later also a little bit more in detail.
As you know, we are currently running four active clinical programs, and we also got the CTA approved for our fifth program at the end of last year, which is BI-1607. There we should also start clinical development then during the first half of this year. We also then further built the organization. We extended quite a bit, especially in clinical, but also in the other two departments, which means manufacturing and research and discovery. We appointed a key position with Marie Moores, and she was appointed Chief Operating Officer, and we're very happy to have her on board. On the next slide here, you will get a little bit of background again, just as a reminder on BI-1206 in combination with rituximab.
This is our lead program. This is a Phase 1/2a study that you see here outlined on this slide. Just want to mention here that we're focusing on patients who have relapsed or are refractory indolent non-Hodgkin lymphoma, specifically marginal zone lymphoma, follicular lymphoma, and mantle cell lymphoma. We're now at the end of the dose escalation, which is part A, and we are about to move into part B, which is the dose expansion. Just to summarize the data that we basically presented at the end of last quarter. For BI-1206 in combination with rituximab, we could show a strong objective response rate of 54%. We had 3 complete responses and 4 partial responses in 13 patients that could be evaluated at that time point.
The treatment stabilized disease in one additional patient, actually giving a disease control rate of 62%, 8 patients out of 30. The important thing here really is to emphasize that the complete responses that we have seen are high-quality complete responses. That means they're long-lasting, beyond 12 months, 24 months, and 36 months in 3 patients. Just to give you an idea, the 36 months patient that was in treatment for 1 year and is now 2 years in complete response without any additional treatment, which is, I think, very exciting. The safety profile of BI-1206 as outlined here is good. We had some infusion-related reaction that we could manage very well with a novel steroid regimen.
BI-1206 shows actually a highly promising response rate in patients with a high medical need. On the next slide, you will see that we're focusing on follicular lymphoma, where we had especially impressive response rates. There we are looking at nine patients at that time when we released the data. In those nine patients, we had an overall response rate of 67%, a disease control rate of 78%. Three complete responses with the long durations that I already mentioned on the previous slide. As already said, the longest complete response is still lasting 24 months after the end of treatment, in addition to the three complete responses, three partial responses, and one stable disease. Very impressive data.
On this slide, you see the next key milestones that are up and coming. We're about to select the dose for part two and then move into the expansion phase, part B, as I already explained. We have a date for the end-of-phase 1 meeting with the FDA. During that, we'll discuss the dose for part two and then the Phase 2 study design, which potentially could be a pivotal study. As you already have learned, we have successfully filed, in collaboration with CASI, an IND for China. We are now about to include China in our global clinical development strategy, and that will be implemented during part B.
We actually also have developed a subcutaneous formulation, and that will be ready to be tested in the clinic during the second half of this year. Actually, quite a number of interesting key milestones. Going to the next slide, so you will see the outline of the other study that we're running with BI-1206, in this case in combination with pembrolizumab, targeting solid tumors. On the left-hand side, you see that we're focusing on patients with solid tumors who have relapsed or are refractory to anti-PD-1 or anti-PD-L1 treatment. It's a similar design, so it's basically part A, which is dose escalation, and then after that we go into part B, into dose expansion. It's worth to mention that we run this study in collaboration with Merck.
This is a clinical supply and collaboration agreement, and we're still in early phases of the dose escalation phase. Nevertheless, we could show already some interesting data also at the end of last year. At that time point, Q4, we had 11 patients and three dose cohorts that have been treated. Out of those 11 patients, we already saw two positive responses observed in two patients, which is quite interesting because first of all, you have to keep in mind this is not liquid tumor, this is solid tumors. Then normally you would expect that you need a little bit more time in order to develop responses. We were actually quite positively surprised to see that early. Then on the bottom of the slide, you see what is next.
Obviously we'll continue with dose escalation. The next cohort, as written here, is the 2 mg/kg cohort. Hopefully, towards the end of this year, we will determine the recommended Phase 2 dose and then move into dose expansion. Also, this, I think, is obviously early days in this study, but I think we're quite happy about the positive responses that we have seen. On BI-1808, which is the third one in line, so to speak, or on the block. As you remember, there we had very strong preclinical validation as a single agent, but also in combination with pembrolizumab. Based on that, we kicked off a clinical trial in early last year.
We're currently running the single agent arm of the study, which is BI-1808 as a single agent. We're well into the dose escalation phase. We hope to provide updates on the study by mid this year. Once we move into dose expansion, then we move into non-small cell lung cancer, ovarian cancer, and CTCL, which is a rare T- cell lymphoma. We'll also start dose escalation for the combination part with pembrolizumab as soon as during the first half of this year. That will be a little bit smaller dose escalation since you already have the single agent dose escalation. Once that is done, we move then also in the combination arm into non-small cell lung cancer and ovarian cancer.
This is also done under a clinical supply and collaboration agreement with Merck. We had also very strong data, preclinical data. I mentioned at the beginning that we had a very nice scientific publication about BT-001 proof of concept publication preclinically. Since we have a very strong preclinical validation, we also started clinical development early last year for this program, obviously, under the 50/50 joint venture with Transgene. We're currently in part A, where we test single agent BT-001 intratumorally, and we're also planning to give an update during the first half of this year on that part. Once we have done part A, we move into part B, where we combine BT-001 with pembrolizumab.
Phase 2a would be then focusing on several cohorts with a different tumor types. This study is running very well, as is BI-1808. That leads me to the financial overview, and I hand over to Stefan.
Thank you, Martin. I will present the financial overview for Q4 and the twelve-month period, January to December. All amounts are in SEK million, unless I say something else. The net sales were SEK 4.9 million in Q4 2021, compared to SEK 98.7 million in Q4 2020. That's SEK 94 million lower. The decrease is mainly related to that we, in Q4 2020, received an upfront payment of $5 million from CASI Pharmaceuticals and a $3 million milestone from Pfizer and a EUR 2 million milestone from Daiichi Sankyo. These three payments corresponded to, in total, SEK 91 million. Net sales for January, December 2021 was SEK 19.4 million. For the same period in 2020, net sales were SEK 147.4 million. That's a decrease of SEK 128 million.
The decrease is related to the just mentioned upfront payments received in Q4 2020, but also that the revenues from production of antibodies for customers was roughly SEK 31 million lower than in 2020. There was no research funding in 2021, which was SEK 7 million in 2020. On cost side, in Q4 operating cost increased from SEK 69.3 million in Q4 2020 to SEK 83.8 million in Q4 2021. That's an increase of SEK 15 million. We had mainly higher costs in BI-1206 and BI-1607. There was mainly lower cost in BI-1808. We also had higher personnel costs. For January to December, the increase of operating costs was SEK 75 million from SEK 222.8 million in 2020 to SEK 297.10 million in 2021.
which include a one-time payment of GBP 2.5 million or SEK 28 million to CRUK in exchange for reducing our agreement obligation to them regarding BI-1206. During the period we had significantly higher costs in BI-1206 due to the just mentioned payment to CRUK, but also to increased cost for the smaller-scale study in 2022. We had also higher costs in mainly BI-1607 and BI-1910. We had quite lower cost for production of antibodies for customers. Finally, personnel cost was quite higher compared to 2020. The loss for Q4 2021 was -SEK 78.8 million, and the loss for January to December 2021 was SEK 278.4 million. The share issue completed in March 2021 amounted to SEK 962 million before issue expenses.
Liquid funds, current and long-term investments end of December amount to SEK 1,365 million. Yeah, that was my summary of the day. Over to you, Martin.
Thank you, Stefan. That would lead me probably to, not my last slide yet, but almost. On this slide, you will see a summary of the upcoming key catalysts. I'll just summarize them once more. I think I mentioned it already during the presentation. For BI-1206 OD program in combination with rituximab. As I said, we are about to select the dose for part two in non-Hodgkin lymphoma and then initiate the Phase 2 part of the study. As I also already mentioned, we'll start to include Chinese patients into the worldwide clinical development of BI-1206 for non-Hodgkin lymphoma. That should happen during the first half of this year. BI-1808 our anti-TNF receptor 2 program.
There we will present initial Phase 1 clinical data by mid this year. Just to remind you, BI-1808 is really one of the very interesting programs in that sense that TNF receptor 2 might be one of the new and upcoming immuno-oncology targets. We're clearly leading the pack and would be the first company bringing out clinical data on that very exciting target. BT-001, this is our 50-50 joint venture with Transgene, during which we combined our anti-CTLA-4 antibody, our proprietary anti-CTLA-4 antibody with the oncolytic virus platform of Transgene. There we also will present initial Phase 1 clinical data during the first half of this year.
Then last but not least, BI-1607, which is our second anti-FcγRIIB, and our fifth clinical program that we will start during the first half of this year. In addition, we might see potential additional milestones from collaborations and maybe potentially also additional partnerships. Thank you very much for your attention, and then we would be happy to receive questions. Thank you very much.
Thank you. Ladies and gentlemen, if you do wish to ask a question, please press 01 on your telephone keypad now. If you wish to withdraw your question, you may do so by pressing 02 to cancel. Our first question comes from the line of Richard Ramanius from Redeye. Please go ahead. Your line is now open.
Hello. Thanks for taking my questions. First scientific questions concerning BI-1206. Have you seen any correlation between dose and response in lymphoma?
Yes. Thank you, Richard. Absolutely. I think we could clearly demonstrate we did that also during our KOL event, that we see, of course, more responses in the higher doses, as we have shown actually during the KOL event.
Okay. Perhaps this is a speculative question, but one of your complete responses is nearing three years, so that's close to remission or in popular words, a cure. How common is that in this indication? And do you see any potential of BI-1206 leading to complete responses?
Yes, I think that's a very good question. Thank you, Richard. Obviously, this is a very high-quality complete response, something that you probably would see not so often. Basically, that means that patient since two years not receiving any treatment and is having complete response, and you could even call that remission or cure, but obviously you never know, there might be a relapse at a later time point nevertheless. I think whatever it is, it's a very high quality, long-lasting complete response, something that you see very, very rarely. I think what I didn't explain during the presentation, so with BI-1206 currently, we're focusing on second and third line of patients who do not respond anymore to anti-CD20 based treatment, in this case, rituximab.
I think what is quite interesting, and it became very obvious when we had our KOL event, we were joined by Professor Michael Wang from the MD Anderson Cancer Center, one of the leading experts for mantle cell lymphoma, but also for Richter lymphoma. In his view, anti-CD20 based treatment remains central, even, you know, giving the new approaches with, for instance, CAR-T or bispecific antibodies. In his view, if you have something that could reinitiate or reinvigorate, whatever you want to call it, the response to anti-CD20 based treatment, that would be very preferred. If you can do that in a safe and tolerable manner, that would be even perfect.
I think what I'm trying to say is that even though we are currently developing BI-1206 for second and third line, I think there's also good potential for first line, especially when you see these high-quality responses.
I thought about your new subcutaneous formulation. How does the path to approval look for that project? Will you have to develop it through Phase 1 and onwards? How does the patent situation look like?
Yeah. First of all, I think this is very, very good news because, as you know, we are controlling the infusion-related reaction that we're seeing with a steroid treatment, which works very well. We might be able to do it even better with subcutaneous. We would not need steroid treatments anymore. The other thing is, of course, it's a very convenient application because infusions, you have to go to a center for this. If you do sub-q application, it's much, much easier. You don't have to go to an infusion center.
You know, the thing that we have everything under one roof, that means that we have the capability to do our own subcutaneous formulation, I think was also quite helpful because we made the decision early last year, and now we already have a product ready to be tested in the clinics by second half of this year, which is very, very quick. Basically, that's what we're going to do. We'll treat it in parallel as we move ahead with the infusion-based application of BI-1206. We'll also discuss it already, maybe not at this stage, but a little bit later with the FDA. Our idea currently is that we move it in parallel.
Based on the preclinical experiments that we have done so far, we believe it will work very well. Then once we have shown that it works, then it can be basically joined with the other development stream. We have to run it at the beginning in parallel, and then it will join later the main development stream.
Okay, how does the patent situation look like for this compared to the infusion version?
Absolutely. Obviously, since it's a new formulation, we also have the chance to put additional IP around this product as well.
Okay, thanks. I had two financial questions. I saw costs increase slightly in 2022. Will we see any increases in costs during full year 2023 compared to 2022? Can you comment anything about cost in 2022, if you can comment on that and potential size of milestones in 2022.
Stefan, do you want to address that?
Yeah, sure. First question around guidance for our R&D cost in 2022. We don't give that. We can see that we are having more programs in the clinic, so that would increase of course. We don't give exact figures. What we can say is that based on current plans, we foresee to have financing until end of 2024. That cash runway could be extended somewhat if we get upfronts from new collaborations or if we get milestones. Regarding milestones, we don't give guidance for that.
Okay, thank you. Those were my questions.
Our next question comes from the line of Sebastiaan Van der Schoot from Kempen. Please go ahead. Your line is now open.
Hi, Martin and Stefan. Thank you for the update. Appreciate it. I just have three questions from my side. The first one is on 1206 in non-Hodgkin lymphoma. Can you clarify whether during the dose expansion part of the study that CASI can also be leveraged for patient recruitment?
Obviously we don't give any further updates on the second part because we want to wait for the end of Phase 1 meeting with the FDA. Once that is in place and we have response of the FDA, we will you know update the market with the specific details on the part 2 of the study.
Okay, great. Thank you. Then the second question is on announcing the complete dose escalation data. Will that also be happening after the end of Phase 1 meeting? Will you give a complete update on the total data sets and what the next plans are, or a go or no-go for a potential pivotal trial in follicular lymphoma, or what is your current thinking on that?
Yeah, our current thinking is in any case to provide, you know, an update from the feedback of the FDA, which of course will also include the data of the first part because that will then obviously the view of the FDA of the data of the first part will influence what we hopefully can do in the second part. As I said, our hope is obviously that we kick off with a pivotal study. We'll provide a comprehensive overview once we have the feedback of the FDA.
Okay, great. Then, on BI-1808, you already mentioned that you're pretty far in or pretty far that those escalation is going well. Can you maybe comment on what type of data can we expect? Do we already expect single agent activity with this drug, or is that more something that we should wait for with the combination with pembrolizumab? Is there maybe other data that we can look forward to, maybe biomarker data or something similar?
I think it will be a mix of everything. Obviously, again, data-driven, and I cannot mention anything here yet at the moment. What we are thinking is that at the time where we get out, yes, we'll give obviously a summary on safety. We'll talk about certain markers, hopefully, and then hopefully also about clinical science. As I said, that will be data-driven, but our view is that we will give a comprehensive overview during the first half, or roughly, about the first half of this year.
Okay, great. Just one question on the, your collaboration with SkylineDx. Is that only on the non-Hodgkin lymphoma program, or is it much more, and does it also go beyond FcγRIIB?
Currently it's focused on FcγRIIB, which is the non-Hodgkin lymphoma as well as the solid cancer.
Okay.
Okay.
Great. Thank you, Martin, and thank you, Stefan, for the update.
Thank you.
Thank you very much for your questions.
Thank you. Our next question comes from the line of Joseph Hedden from Rx Securities. Please go ahead. Your line is now open.
Good evening. Thanks for taking my question. Just wondering if we can get an update on the Pfizer collaboration.
Apologies, Joseph. If you could please, speak up. I don't think you're audible for the speakers currently.
Can you hear me now?
Yeah. That's much better, Joseph.
Oh, sorry about that. Thanks for taking the questions. I just wondered, Martin, if we could get an update on what's happening under the Pfizer collaboration, and perhaps thoughts for this year, or near-term expectations.
Yeah. Just to remind everybody, with Pfizer, you know, we moved into a different part of the collaboration during last year. The program was focused on generating interesting targets and antibodies for tumor-associated myeloid cells. Tumor-associated myeloid cells are probably one of the most important cell types in the tumor microenvironment. We have discovered quite a number of targets and antibodies. Pfizer made their picks regarding targets and antibodies and moved it into their internal development. There's no active contribution at the moment from our side. We do not disclose, you know, how the whole collaboration is structured. Obviously, as you might remember, there was an upfront, and there were certain.
an FTE coverage and certain milestones during the discovery phase, and we have the same obviously during the development phase. We didn't disclose anything, and that is also based on agreements and discussions that we have with Pfizer. It's what I can say it's in development with Pfizer. As Stefan already said, obviously we have also antibodies in development with other companies such as Daiichi, Mitsubishi, Takeda, Bayer, and so forth. We don't give any outlook when we hit certain milestones. When they happen, we'll disclose it to the public. What I can say is that Pfizer was very keen to move ahead with those programs or the targets and the antibodies that they have picked.
You know, as they hit milestones, then we will announce that to the market. What I can say in addition, obviously, we did a very broad screening on tumor-associated myeloid cells. As I said, we actually discovered a high number of interesting targets and antibodies. There's quite a number with us that we could consider for further partnering or for our own development, basically.
Okay. That's great. Thanks very much.
Thank you. You're welcome.
Thank you. Our final question comes from the line of Sebastiaan Van der Schoot from Kempen. Please go ahead. Your line is open again.
Hi, Martin and Stefan. Yeah, just wanna put one more question in regarding 1607. When are you gonna update the markets on the indication that you're gonna apply the new FcγRIIB antibody in, and in which combination?
Yeah. That will be. Stefan, please help me there. We will have abstracts at AACR, at least one-
Okay.
Covering BI-1607, that will basically then give you a little bit more of granularity. That will be probably the next time when we talk more about BI-1607. As I explained already earlier, we have been quite secretive about it because we're still filing IP, which we have done by that time point, and then, of course, we can disclose more details.
Okay, great. Looking forward to it. Thank you.
Thank you, Sebastiaan.
Thank you. At this stage, we have no further questions. I'll hand back to the speakers for any final remarks.
Thank you very much, everybody for attending. I think that was actually a quite exciting Q4. We delivered all the milestones that we promised and I think even a little bit in addition. Yeah, stay tuned. I think this year will be quite exciting and interesting as well, probably even a little bit more than last year since we now have four active programs that will deliver milestones, as I already described during the presentation. I think me and the team remain very excited what is lying ahead of us, and hopefully, it will be very successful. Thank you very much.
This now concludes the presentation. Thank you all for attending. You may now disconnect your lines.