Alligator Bioscience AB (publ) (ATORX) Earnings Call Transcript & Summary

Thank you very much. So welcome to this conference call, which will focus on today's interim report and the associated press release. Slide 2. So as usual, the presentation does include some forward-looking statements. Let's go to Slide 3. We announced today that Alligator will focus clinical activities to our lead programs ATOR-1017 and mitazalimab. In short, the decision is based on the strong positioning and positive data for these 2 programs, while there is a need for further evaluation of data in the ATOR-1015 program. So our focus will be on ATOR-1017 and mita, while further clinical development for ATOR-1015 is to be conducted with a partner. These are the key messages, and I will now go into this in more detail. First, a slide summarizing the most recent news flow, Slide 4. So during the third quarter, we had presented data from all 3 clinical programs; as well as a novel bispecific drug concept, Neo-X-Prime; and the recruitment of Gayle Mills as Chief Business Officer at Alligator. Let's now start with ATOR-1015, slide 5. Slide 5: The ongoing dose escalation study, it's currently evaluating repeated intravenous dosing at 750 milligram or approximately 12 mg per kg. And this is a really high dose; for reference, about 4x higher than the highest dose used for Yervoy. As communicated earlier, we have observed infusion-related reactions that are believed to be related to the development of antidrug antibodies. The reactions seem to be manageable, and we still expect completion of the ongoing study before end of the year. It does, however, call for changes to the clinical dosing and dosing regimen for future studies; and for thorough evaluation of clinical data, including biomarker analysis. In parallel, we have initiated discussions for conducting further clinical development with the partner. So this allows us to focus our resources to ATOR-1017 and mitazalimab and to make sure that their clinical development programs reflect their great potential. So let's move to ATOR-1017, Slide 6. ATOR-1017, it's at the front of the second-generation 4-1BB antibodies. Now why is that important? The first-generation antibodies had design flows. The BMS product urelumab, the left-hand side, that induced a strong activation of all 4-1BB receptors, leading to toxicity and a maximum tolerated dose of 8 mg which is very low, whereas the Pfizer compound utomilumab, it's overcompensated with an antibody with too low activity even at very high doses. ATOR-1017 is designed for high efficacy but with more selective activation of the -- in the tumor area, and this is to reduce systemic toxicity. So this profile is now supported also by emerging clinical data. Next slide, slide 7. So Slide 7: Data from the ongoing dose escalation study was reported in August, a flat dose of 40 milligrams. This is 5x higher than that of urelumab. That was cleared with few adverse events. Dose evaluation now continues at 100 milligram, and we expect to be able to report the full study within 6 months. The individual patients are shown in the swimmers plot below, where the colors represent different doses. So the study allows intra-patient dose escalation. This is to give every patient best chance of benefiting from the treatment. This is allowed to start at low doses and fast dose escalation in single-patient cohorts while still having all patients escalate in the clinically relevant dose levels. We find the data very encouraging and are now planning for bringing ATOR-1017 into Phase II efficacy studies in 2021. 4-1BB has potential in several important solid and liquid tumor indications, including head and neck, gastric, ovarian, lymphoma. And there is a large number. And our goal is to be able to start more than one such efficacy study with this product. With that, I will move on to mita. This is Slide 8. We are finalizing our preparations for a clinical efficacy study in pancreatic cancer. The background is, of course, the emerging clinical validation for CD40 in this disease, where current treatment options are very limited. We plan to combine with chemotherapy, which is mitazalimab on top of modified FOLFIRINOX; and to add on PD-1 once an efficacy signal has been demonstrated with mita on top of FOLFIRINOX. CTA for this study will be submitted before end of the year, and we plan to report first interim efficacy data in Q4 2021. We also recently presented data confirming a clinical proof of mechanism for mitazalimab as a single agent. So there is no active clinical trial ongoing. This may sound confusing, so let me briefly explain, Slide 9. This is based on data collected in the Phase I study run by Janssen and that was reported last year. They included a lot of advanced biomarker assessments, including RNA sequencing. And when we compile this data, a distinct pattern emerge confirming the proof of mechanism. A large number of immune genes were upregulated in the patients up on treatment with mitazalimab. And this included key signals such as PD-L1, shown to the right. Overall, we got strong confirmation that we activate both dendritic cells and macrophages in these patients, which are the key targets of -- for mitazalimab. So Slide 10. We've also reported on our progress within Discovery by launching a novel concept for more specific cancer immunotherapy called Neo-X-Prime. Neo-X-Prime, this is our bispecific -- builds on our bispecific platform Ruby, and I will try to explain why it's a -- novel and why it has such great potential. The Neo-X-Prime antibodies. We bring tumor parts to the antigen-presenting cells, which allows them to selectively guide the immune system towards the tumors. If you look in the lower left corner, I will try to explain. The Neo-X-Prime antibody catches tumor exosomes in the circulation or otherwise in the body and brings them to antigen-presenting cells. Now move to the cell in the middle. This is where the Neo-X-Prime activates the antigen-presenting cells and promotes uptake of these exosomes and the tumor neoantigens that are inside the exosomes. And finally, on the right-hand side, this allows the antigen-presenting cells to selectively initiate a tumor-specific immune response through cross-presentation and priming of T cells and hence the cool name Neo-X-Prime. One particular beauty of the Neo-X-Prime concept is that, the tumor exosomes, they carry all the mutated material of the tumor, which is specific for each patient, in other words the neoantigens of the tumor. So instead of guessing what the immune system should be attacking, like you do with this, for example, a cancer vaccine. Our Neo-X-Prime antibody solves this problem by picking up the patient's own tumor exosomes; very promising from a theoretical perspective, but the reason we are so very enthusiastic about this is that there seems to be that this is what makes all the difference. Let's look at Slide 11. Neo-X-Prime, in short, outperforms every immunotherapy antibody we have tested previously in our model. And this is illustrated in one example in this slide. Our plan is to move forward and build a platform of several drug compounds by initiating co-development with a partner on the Neo-X-Prime concept. And this is one of the key objectives of our BD efforts, which are now led by our new CBO, Chief Business Officer, Gayle Mills. Next slide, Slide 12. Gayle joined Alligator a month ago and is now part of the executive management team. She has a very long experience within oncology, within antibodies and immuno-oncology and with several major deals on her CV. Gayle is based in California and she has a very strong network in the U.S. And she will lead our partnering activities going forward for Discovery but, of course, most importantly for our clinical programs. So finally, let's move to Slide 13, the financials. And the important number in this slide is money in the bank, SEK 137 million. This will take us another 12 months and allow us to progress ATOR-1017 and mitazalimab into efficacy studies. So next slide, Slide 14, and with this slide illustrating our focus for 2021 and our potential to have 2 major assets starting up clinical efficacy studies in 2021. I would be happy to open up for questions. Thank you so much.

[Operator Instructions] And we have a couple of questions coming through, so far. The first is from the line of Samir Devani of Rx Securities.

It's just on 1015. I'm -- I guess I'm a little bit surprised on the back of last month's announcement where you guided that the 600 mg was -- you hadn't seen any significant adverse events. And that's obviously a clinically relevant dose, so I'm just wondering perhaps if you can elaborate on what further data you've seen that have meant that you are sort of deprioritizing the asset.

Yes. Thank you, Samir, for the question. And you're quite right. 600 milligram was a manageable dose. And we still did see infusion-related reactions at this dose. We have seen it at lower doses and we've seen it at 750. We did have one grade 3 event with 750, but in essence we are convinced that we could manage the toxicity, for example, by premedication. One complicating factor here is that it's associated with development of antidrug antibodies, and that makes it more difficult for dose -- further dose escalation and also for more longer-term repeated dosing. So we are now looking into the data. We are starting to analyze biomarkers. And then what we are looking for now is to form a sound basis for a study with a modified design. And the first, of course, impact of this is that, once you modify the design, we need to redesign the protocol and we need to start all over with the regulatory submission. So that will lead to major delay in the program plans. And that is also why one -- as we have very promising data for 1017 and for mitazalimab and especially since they are extremely well positioned in their respective fields, we think it's wise now to focus our investments on these 2 programs. So at the same time, we are looking for a partner for clinical development of 1015, but it's not our priority right now because of these challenges.

That's very helpful. And can I -- just maybe just one follow-up just on the antidrug antibodies. Is the rate that you're seeing there significantly higher than, say, for Yervoy?

I have not made that comparison. We will present the data, and that will be part of that presentation, at I believe SITC, coming up here in a few weeks. And there will be a full data presentation from the study there. So there seems to have been associating with these infusion reactions, and that is part of what's complicating the picture for us.

And we currently have one more question in the queue. [Operator Instructions] The next question is from the line of Ingrid Gafanhão of Kempen.

I have a couple of questions, if I may. So maybe I wanted to start asking about the antidrug antibodies that you observe. I'll be waiting to see the data at SITC, but I was hoping maybe you can let us know if it was something dose dependent or something that you only started observing at higher doses.

I -- from -- as far as I understand now, there seems to be the stronger reactions at higher doses, but it is far from clear. And we do have infusion reactions also at lower doses, so there seems to be a connection there, but it's not -- as usually in biology, it's nothing that is 100%. And we are looking at these data right now to understand it better, but it's quite clear that -- the induction of antidrug antibodies over time in -- and it's -- depends -- how fast and how much might depend on the dose, but I don't quite have that picture right now. But that complicates the initial ambition to run high doses with repeating doses over a long time. So now that is the design we have to rethink. And we think there are interesting ways forward, but that has to be a modified design to the program.

Okay. No, that's clear. And just a follow-up on 1015: We saw the [ title in this ] coming up for SITC in a couple of weeks, but [indiscernible], so I was hoping you can give us a high-level idea of what we can expect for the presentation.

Yes. So for SITC, we will present full data. We haven't started looking at some of the important biomarkers like tumor histology and so on. That will be extremely interesting, but I do not think that will be ready in time. I don't think that has started yet, but otherwise, there will be a full presentation of the data we have, so far. And that means all the patients, all the safety and the biomarkers that are analyzed to date, so essentially a Phase I presentation.

[Operator Instructions] No, there doesn't seem to be anyone else coming through, so I'll reopen your line, Ingrid.

I also [ am pretty much worried if you cannot ] comment a lot on your partnering efforts at this stage, but can you just share some high-level information about incoming interest both for ATOR-1015 but also for your Neo-X-Prime? What kind of interest do you see coming in? Which kind of companies? And yes, I'm just curious a little bit to understand how we should be looking at it.

I think, I mean, when it comes to 1015, given that we have some challenges right now and are redesigning, what we are expecting is more co-development partnerships. So we do not look for a major out-licensing deal at this moment. We think it's up to us to demonstrate with a partner, to demonstrate an efficacy signal, and that is the plan. When it comes to Neo-X-Prime, again it's early concept. We do have drug candidates generated and -- but again with our focus on 1017 and mita, we really need partners to join in, in the development of Neo-X-Prime to make it a very strong and efficient development. We are looking forward to bring several compounds forward. And that, in our current capacity, we cannot do ourselves, so we're talking about joint ventures here for Neo-X-Prime.

Okay, all right. So that's very clear. And if I may: There was one last question on the 1015, more about antidrug antibodies. Maybe from your data or from other data from other oncology antibodies as well, what is actually do you think that drives the antidrug antibody towards a candidate?

And so I'm -- so if I understood the question right, it's you ask, "What you think is a driver for the antidrug antibodies."

Yes.

Yes. I -- well, I can only speculate. I mean, if you go start with an endogenous antibody, that is sort of a perfect format that has been refined over millions of years of evolution. And then we add an entity to the antibody, which we do with an -- a bispecific like 1015. And that always runs risk of annoying the immune system with sort of surprising it with a new formats, but apart from that, we can only speculate. It's -- that is it's quite common with bispecific antibodies, so as such, it doesn't have to be a major issue, but it complicates the plans forward. So it leads to rethinking and redesign.

[Operator Instructions] Okay, there are no further questions coming through at this time, so I'll hand back to our speakers for their closing comments.

Okay, thank you so much. And thank you for joining this webcast.