BioInvent International AB (publ) (BINV) Earnings Call Transcript & Summary

Hi, good morning, everyone. Thank you for joining us here at Day 2 of the B. Riley Virtual Oncology Conference. I will have a number of fireside chat and company presentations today. And it is my pleasure to welcome our first issuer, Andres McAllister, Chief Medical Officer of BioInvent. Andres, please take it away.

Thank you very much. Thank you. So I will just -- in the interest of time, I will move quickly. So BioInvent is a company located in Lund. Here are our forward-looking statements. Just a very short introduction. We're a company totally focused in immunotherapy of cancer. And obviously, while it's important to note that immunotherapy has really changed the way patients are treated today, there is a number of -- a huge number of efforts still being made. While there are some interesting targets, most of the patients still fail to respond at least in the long term. So the majority of targets and treatments are still to be developed. So we're not there yet. Basically, that's the main message. I think where we want to -- what we are doing at BioInvent is we took the problem backwards. So basically, we developed this function-first discovery approach. Basically, what we do is we take tumor tissue from patients and without any further manipulation, we take the -- that tumor. It is disrupted. We look at antibody binders that bind to the immune system present in that tumor and look for those binders that actually have the best antitumor activity when tested in animal models before knowing the target. And once we have found those interesting targets and antibodies that have strong antitumor activity, just at that time, we go and try to find the target. So it's actually the convolution of a target that has already activity in animals. So that's why we call it function-first. By using that approach, we have put into the clinic a number of different compounds, basically listed here on the left-hand side, BI-1206, which basically recognizes Fc gamma receptor IIB, and that is the target, of course, that came out through the approach that I described that Fc gamma receptor IIB is also being shown to be important in modulating the activity of anti -- of immune-modulating antibodies, such as anti-CTLA-4 and anti-PD-1. So that's why we are also developing it in combination with pembrolizumab. We have another version of the antibody, which basically enhances the activity of tumor-directed antibodies, such as trastuzumab, which is what we did here. It could also be used with other antibodies, so it's a bit of a platform system. Another target that has come out of our platform is TNF receptor 2. This is a very interesting, new, upcoming target in the area of immuno-oncology. TNF receptor 2 is present in the tumor micro environment and in particular, in regulatory T cells and macrophages. We are developing that, as I will tell you in a minute, in combination with pembrolizumab. And last but not least, BT-001, we came up with this, again, using that platform. We came up with a particularly powerful antibody, anti-CTLA-4. That antibody because it is much more efficient at deleting regulatory T cells. We clone that antibody into a viral vector. This is being done in combination with Transgene in France, and that antibody is expressed by the virus, and we are treating patients intratumorally. So basically, that is the pipeline that we are developing. We have one -- another anti-TNF receptor 2 compound that we'll move into the clinic during the second half of this year. So to go to the first part of our pipeline, Fc gamma receptor IIb, as I mentioned, we're developing in 2 indications, in non-Hodgkin's lymphoma and in solid tumors. In non-Hodgkin lymphoma, the study is a 3+3 dose escalation design, where we have completed the dose escalation. Now we are moving into -- we have moved into the expansion cohort doing the IV, using IV infusions. During the course of that escalation process, we have seen very interesting responses. In particular, 3 complete responses that have lasted for over 2 years after the end of treatment. That is, of course, of high interest and other series of partial responses that are -- one of them is actually still ongoing. And so very interesting results during that escalation phase. In addition to that, we developed a subcutaneous formulation. We are actually starting that arm of the study, as we speak. That escalation -- that subcutaneous formulation should allow us to improve the exposure, make it easier for patients and the treating physicians, so that a more flexible approach can be used. That is actually beginning. As I mentioned, we enrolled our first patient at the end of last year. And the escalation there is moving forward. We're basically using 1 patient dose escalation with a BLRM adaptive design so that we can move quickly through the escalation process. And we hope to be able to be at higher exposures very soon. And of course, the dose that we started with is very much comparable to the higher doses in the IV format, in the IV infusion that we used during the IV escalation period. So we feel this is, of course, very interesting. Basically, the idea here is to enhance the activity of anti-CD20 targeting agents, so recover or enhance the activity of rituximab. It is -- this antibody is a first in class. There is no other competitor. It's very interesting in the sense that it would allow for the generations of chemo preregimen for second and third lines. So that's, of course, something very interesting. And as I mentioned, very interesting complete responses that we have already observed during the escalation phase. In the same -- for the same antibody, it's also being developed in patients with solid tumors. This study started after the first study. This year, we're combining it with pembrolizumab, and we have a supply agreement that we have signed with Merck, who is providing pembrolizumab for this study. We have also escalated this here. We are using an adaptive design for the escalation part of this study, and we are still in that phase. But we -- here, again, we will be using the subcutaneous formulation for the expansion cohorts and for the first -- for the upcoming part of the study. So I think that will also be allowed a great deal of flexibility, and we're hoping that, that subcutaneous formulation will really open a very nice way forward for the antibody. In this study, we've had a couple of very interesting responses as well. One in particular is a very important partial response with disease in a patient with hard to treat uveal melanoma. This patient, of course, had been exposed to previous lines of pembrolizumab and nivolumab, so anti-PD-1 targeting agents. And yet we see a partial response of 50 -- greater than 50% reduction in lesions, and the patient has now been on study for over 17 weeks. And we also had another case, which was a very typical case of suitable progression. That patient had a sarcoma, metastatic sarcoma to lungs and bones and who was in a very difficult condition. After entering the study, the patient started responding clinically very much. Unfortunately, the lesions grew and the patient had to be taken off study. But after several -- after a couple of scans later, we saw a complete disappearance of the metastatic lesions and very much radiological improvement. The patient has not received anything else since, entered a compassionate patient protocol and has been, ever since, in -- without any -- so this is still under control and no further treatment, no different treatment in this patient. So we will move forward, again, here with the subcutaneous formulation. And one point perhaps that I have not mentioned is that during the escalation in both these studies, we observed infusion-related reactions, which were managed clinically without too much difficulty. But still, we thought that the subcutaneous formulation will be the answer to better -- to have a better tolerated drug during that first part of the infusion. And thus, this is one more reason why we are -- we decided to move to the subcutaneous approach. BI-1607, that is the other antibody that targets Fc gamma receptor IIB. BI-1607 is being developed in combination with trastuzumab. There, the study that we are performing is a dose escalation. Again, we're here using an adaptive design in combination with trastuzumab in patients who have failed previous trastuzumab or, yes, HER2 targeting agents. The study is in the escalation part. It's being developed in sites in Spain, the U.K., Germany and the U.S. And this study is ongoing quite well. We're going through the escalation period, and there's not very much to report right now, but the study is moving along really well. And it's -- as I mentioned before, it's a different version than in the previous one. BI-1808, this is TNF receptor 2. Again, this is another one of the targets that came out of our first screen. It's clinical. We're doing, again, a clinical study where we have escalated with using an adaptive design again. We have completed the escalation and the drug has been extremely well tolerated. We have full receptor occupancy during the full treatment period. The study, we -- it was so well tolerated that we decided to go one dose higher than it was originally thought we would do. We have already gone at that dose, and we have, in addition, opened another arm in combination with Keytruda. Here again, we have a -- the same type of agreement with Merck, who's providing Keytruda for the study. That cohort has already begun. And we are in the process of completing that Phase I part of the study and will soon move to the Phase II part of the study to explore activity of the drug in different indications, in particular, lung cancer, ovarian cancer and CTCL depicted here in your -- right-hand side of the study -- of the slide. As you can see, it's important to note that CTCL is a rare type of T-cell lymphoma. If we see activity in this indication, that would allow us to go for accelerated path to registration in those patients. We have already included some patients in the first part of the study, and we're hopeful that there will be something of high interest. In the case of CTCL, TNF receptor 2 is highly expressed by the tumoral T cells, which are the tumoral cells in this case. So in addition to the immunomodulatory activity, we may have a direct targeting agent for the T cell lymphoma. In combination with pembro, depicted here on the right-hand side to the bottom of the slide, we will also test lung cancer and ovarian cancer. Both these indications are indications that were carefully chosen. And in particular, the synergistic activity that we have observed in animal models would be ideal because we could probably -- particularly in the case of ovarian cancer, we could have a very good positioning of the immunotherapeutic approach, which, of course, has now been approved in that indication. Yes. So I think I -- this is -- where the study's being run, it's being run in Europe, in the U.K. and the U.S.A. We have seen some interesting already responses. We have had 3 stable diseases in -- that, unfortunately, subsequently progressed. And we had one interesting stable disease with tumor reduction in lung cancer patient during the course of the escalation period. And as I mentioned, there's been no safety or tolerability concerns for that during the course of the study. So here, again, very interesting data and very interesting upcoming results and progression during the next year and 1.5 years. BT-001, that's our drug, our virus drug in combination with Transgene. This is a 50-50 partnership with Transgene. As I mentioned, this is an anti-CTLA-4 antibody that was cloned into the virus. The virus we are conducting this study in solid tumors and basically, doing intratumoral administration at ascending doses. We have gone through the -- all the doses, and we were at the final dose and completing the last cohort. And as soon as we do that, we should be able to begin their combination with pembrolizumab, which, of course, should be of particular interest since these will be 3 mechanisms of action at -- with antitumoral activity, all simultaneously. The -- this should begin during this -- first half of this year. So that should be very interesting. I think it's important to note also that during the first cohorts, we're able to see expression of the antibody locally in the tumor. We were able to see viral replication in the tumor. So really, where it's supposed to be working is at work. And so we -- and importantly, we did not see any systemic exposure to the anti-CTLA-4 antibody. So the antibody is expressed in the tumor, but due to the toxicity, the potential toxicity of anti-CTLA-4, we -- it was important to monitor the exposure, the systemic exposure to the antibody, and we have not been able to see any toxicity or any concerns with respect to the systemic exposure. So really showing that this is a profile -- an interesting way of delivering the antibody to where it needs to go. So the next step is completion of this Part A, finalizing the dose escalation and starting the combination with pembrolizumab. So in addition to that, we, BioInvent, has several agreements with a number of different companies. All of these are listed here. These are basically important validators of our approaches of generating antibodies. And these are in the hands of external partners, but these are agreements that have been done in the past with BioInvent's technology. And in terms of expected catalyst for 2023, I mentioned the preliminary results of subcutaneous. Since we are going to have a very quick escalation, we should be able to get interesting results during -- by -- sometime during the first half of this year. We will begin the part -- the subcutaneous administration in the solid tumor study. That is also coming during the first part of this year with -- we will also report on preliminary results of 1808 single agent. And all of those patients that we're treating during the escalation process, we should be able to compile the data and report it to the -- report it during the first half of this year. As I mentioned, we will start combination with Keytruda in the BT-001, the oncolytic virus trial. We will -- by the end of the year, we should have a -- preliminary results of the Phase I of 1808. That is the anti-TNF receptor 2 in combination with pembro and 1607. That's the second Fc gamma receptor IIB antibody in combination with trastuzumab. And last but not least, TNF receptor 2 biology is intriguing, interesting, and different formats of antibodies can have different activities. And that is the reason why, despite the fact that we have -- we are moving forward our first candidate 1808. This is a different format of antibody. It binds -- so 1910, I'm talking about. It's a different antibody. It binds to a different epitope, and it's a different IgG isotype. And so we are moving forward with that antibody as well. It is very much differentiated for -- from 1808, and we will move that forward during the second half of this year. So, yes -- so I think I have told you most of it where we stand from the clinical development standpoint. As I mentioned, those are the 5 and soon to be 6 clinical programs. We have that integrated research engine that has functional screening and in-house GMP manufacturing. That research engine that we called F.I.R.S.T has been validated by 2 very interesting deals during the past few years. The most recent, we did a deal with Exelixis and prior to that, with Pfizer, who have selected targets and antibodies to be developed in the future. So they're actually developing them right now. It's important to note that we have a very strong international shareholder base. And the -- with the investors, the key investors depicted here. And we're very happy with our investor base, and we have a very solid cash position currently thought to be toward the beginning of 2026 with -- based on the global -- on the current plans that we have. So basically, that is our story in a nutshell. So happy to answer any questions in case you may have, and I'd be happy to try to answer them. Thank you.

Excellent. Andres, this was a very helpful overview. And obviously, a lot going on at BioInvent, with a pretty compelling catalyst setup over the next couple of years here. So just a couple of questions that came in throughout the presentation. Maybe you can start by providing a bit more color on the manufacturing facility? And sort of what's the competitive advantage of having that in-house?

Yes. That's -- thank you for the question. I think it's a very interesting question. BioInvent has obviously been around for some time. And it's basically part of the history of the company that it developed a manufacturing facility a very long time ago. Of course, that's probably something you wouldn't do today if you were starting with a new company. But the fact of having it under the same roof allow -- actually gives you a great competitive advantage. And I will give you a quick example, it's the subcutaneous formulation, quickly in the development of Fc -- enter Fc gamma receptor IIB, BI-1206, we realized that it would be ideal to have a subcutaneous formulation. So because we have that in-house facility, we basically turned around, generated a new GMP batch very quickly, and it -- and we were able to implement this in record time. I don't think if you had to go through external partners, that is not something that you would be able to do and -- or at least in the time that we did it. So when we first made the decision of doing it, I don't think there was 1 year that elapsed until the time we were already making the submissions to be able to treat patients. And actually, we are -- we were already treating patients. So that is the kind of competitive advantage that it gives us. We're super happy with what we can do, having it as a tool. And I think it's -- actually, it's a great competitive value.