BerGenBio ASA

Good morning. My name is Martin Ohlin and I would like to welcome you to the third quarter 2024 update from BergenVaya. I would like to remind everyone about the forward looking statement. The Q3 highlights and post-period highlights, i.e. the period after the third quarter, importantly consists of significant updates from the BGB16 study, our study of benzantamib in the frontline therapy in non-small cell lung cancer for STK11 mutated patients. the enrollment in the Phase 1b study, and we saw an encouraging safety profile, but also, importantly, we saw that the plasma levels of benzantamib were in the therapeutic relevant window, which is also encouraging, and it confers very well to what we saw in the BGB008 study, which was in the second line, non-small cell lung cancer study, We are advancing the collaboration with Tempus, such that the contextual benchmark arm will be available when we are announcing the Phase 2a results, and even with the interim data. The recruitment activities are now fully up to speed, with all sites being activated. I'll come back to that a little bit later. And we now expect the first interim analysis of the Phase 2a study to occur in the first part of 2025. I think we can say that it's really encouraging that SDK-level mutated patients in frontline therapy consists or represents a significant unmet medical need, and the publication of data that supports this continues to evolve. It is that 20% of the population in frontline therapy that actually have SDK11 mutations. So that's reassuring from a market potential. But we also believe that given the mechanism of action of benzenzimib, we might be able to show a difference by stimulating the immune response from the current standard of care, which is checkpoint inhibition combined with platinum doublet chemotherapy. On a financial basis, year-to-date operating expenses was 117.9 million. Year-to-date versus 148.3 million in 2023, representing a 20% decrease over last year. The operating expenses in the third quarter in particular were quite close to the operating expenses in the third quarter of last year. But there are some quarterly variations primarily linked to the sourcing of standard of care, which is supported for the 16 study. The cash position at the end of the third quarter was almost 175 million compared to 200 million at the end of the second quarter this year. So a relatively lower burn and somewhat below the guidance that we have provided of 40 million a quarter. But we still expect it to be around that 40 million quarter on a forward-going basis. We have two updates. On other programs in the pipeline, one to Vestamap, which we back in 2022 announced that we would no longer pursue the development of that compound ourselves, but we would seek a partner. Unfortunately, it has not been possible to identify an attractive opportunity with the partnering arrangement, and therefore we've decided to discontinue all the activities. ADC Therapeutics have been licensed an Axla antibody from Bergen Bio and has an ongoing phase 1B program, ADC T601, which they have informed us that they have discontinued due to a too narrow therapeutic window, and I will come back to both of these events. If we hone back on the main focus of Berk and Bayer, which is the 16th study in frontline therapy for STK11 mutated patients in non-scramus, non-small cell lung cancer, we believe it represents a significant opportunity from a couple of viewpoints. The first one being, although checkpoint inhibition is very effective if you have a high PD-L1 expression, It is not that effective if you have a low or a negative PDL expression, and I'll come back to that a little bit later. But also, additionally, it's known that there are a number of mutational drivers, so-called oncogenic drivers, that actually will indicate the relevance of standard-of-care therapy towards these mutations. And STK11 mutations is clearly a non-actionable mutation. There's no targeted therapy available for the mutation. And we are seeing a significant number of the patients suffering from an effective treatment in today's situation. Another new publication that sort of supports the bold move we made in 2022 is that STK11 mutation is really characterized by having a high incidence of a negative PD-L1 expression, meaning that they are not likely to benefit from checkpoint inhibition. And this graph shows that STK11 actually has the highest number of a negative PD-L1 expression. Also, newly announced data confirms that the significant unmet medical need is actually relevant from a number of medical viewpoints. One is the overall response rate, which is significantly lower than the wild-type situation. but also, which is very meaningful for the patients, is that even if you would respond, the median overall or progression-free survival and overall survival is significantly lower than the wild-type with statistical significance. So this all points to what I said before, a significant unmet medical need and no targeted therapies available. This translates into a significant market opportunity. In the Western world, we believe this is around 30,000 patients on an annual basis that will be eligible for the treatment combination of Benzentamib plus standard of care. And this translates at the current market price for such a treatment of around $4 billion on an annual basis. If we home in on further on why we believe benzensamib could make a difference here, just to remind everyone, benzensamib is a TKI inhibitor, a small molecule. We believe that it's highly selective for Axel, and therefore they will be associated with fewer side effects. We have seen monotherapy in a number of indications. We have an extensive safety database. We have studied the molecule in more than 600 patients today. We've also proven that it actually improves the outcome for the patients in combination with chemotherapy on the one hand, which was the 005 study, but also with checkpoint inhibition, which was the 008 study, which we reported earlier. It concentrates, interestingly, in the lung by a 40-fold over normal tissue, which is, of course, relevant. for the disease we're treating, but it also importantly crosses the blood-brain barrier, which is also relevant because unfortunately a number of the, even the frontline patients with metastatic disease have brain metastasis. We have received the fast track designation from the FDA in this particular indication, and our IP should protect us until 2042. If we look at the scientific rationale for why we are doing this quadruplet combination is that if we look at an immune-responsive tumor, it's really characterized with the presence of CD8 plus T cells, a PD-1 relevant expression, and also supportive dendritic cells. In an immune-suppressed tumor environment, we see that there is no CD8 plus cells, or at least lack of them. There is a low or a negative PD-L1 expression, and there is suppressive dendritic cells that And we believe by stimulating the immune system through the axial pathway, by inhibiting the axial cell surface protein, we can restore checkpoint inhibition response, but also delay the resistance to chemotherapy. If we then hone in on the ongoing study, the 16th study, this is a schematic overview of the study. So we completed the phase 1B study, three doses studied, 75, 100, and 150 milligram. We have gotten the approval from the data monitoring safety boards. We were hit with two doses, 100 and 150, into the 2A study. If we then look at the Phase 1b patient characteristics, it was all comers, meaning that there are any PD-L1 status and no actionable mutation, so it was not particularly designed to include STK11 patients. As we have reported, we have completed the enrollment, and we are following up the patients that are still on treatment. The Phase IIa study, which is a global study, meaning that we are conducted in the U.S. and in Europe, in selected countries, in 32 active sites, is designed to involve 40 patients, and those patients are patients that have a confirmed mutation in the STK11 gene. The recruitment is ongoing and we remain positive about being able to enroll the 40 patients within the guidance we have provided. We've seen a couple of administrative delays in some sites, but they are being addressed as we speak. So I don't expect that this will significantly impact the enrollment. This slide is going back to the question with the new doses, and some of the audience will remember that in the previous studies, benzantamib was administrated as a loading dose of 400 mg followed by a daily dose of 200 mg. and it was given with no particular restriction as to with food or without food. Our modeling data clearly shows that it should be given with food, but the modeling data also shows that it is Probably not necessary to give such a high dose, particularly in a setting where we have two other or three other therapies, checkpoint inhibition, which has its own side effects, but also platinum-adopted chemotherapy, which also has its own safety issues. So we decided, based on that model, to bring the dose down and have no loading dose. And this slide on the left-hand side is actually what we have seen in the 008 study, so in about 100 patients when we combine it with checkpoint inhibition. And it clearly shows that the lower quartile of exposure, i.e. not the highest one, are actually within the therapeutic window. conferring to durable and long responses to the therapy. And the plasma tests that we have done in the 16 study on the right-hand side really confirms that the 100 milligram is exactly in the sweet spot of the therapeutic window. So this is really assuring from a safety but also efficacy point of view. If we look at the competitive situation, nothing has really changed other than we are seeing a number of companies addressing the STK11 mutated population in frontline therapy by different immunotherapy approaches. But Bergen-Barr remains the only one who have an excellent inhibitor. in the frontline setting. So one could say that we are leading the effort and we're probably the first one to recognize from a clinical point of view this unmet medical need back in 2022. So to summarize it all, STK11 is a significant unmet medical need. It's recognized that it's underserved, and it requires different immuno-oncology approaches. We know that axillary expression is a key driver of resistance to chemotherapy in STK11 mutated patients, but also to checkpoint inhibition. As I showed earlier, we can also see that STK11 patients have a high incidence of low PD-L1 expression, meaning that they would not at least be viewed to respond to checkpoint inhibition. We have validated the efficacy of benzensamib in two second-line non-small cell lung cancer studies, as I said before, in combination with chemotherapy, but also in combination with checkpoint inhibition, in this case, K-tutor. We have shown monotherapy of benzantamib, which is an important notion to keep in mind, because this is most likely a success criteria for a new immunotherapy in a different setting, though. The ongoing study, the 16th study, is progressing, and we now expect the first interim data to be released in the first part of 2025. And as I said, we are the only excellent inhibitor in frontline therapy for this population. On a pipeline update, Tilvestimab, we specifically announced in 22 that we would not continue the development internally of Tilvestimab. Back then, Tilvestimab was in development for fibrotic diseases. We have been in an extensive partnering outreach process in the last almost two years and unfortunately we have concluded there is not an attractive partnering or partnership to be identified at attractive terms and therefore we have decided or the board has decided yesterday evening that all Sylvester Map activities are to be discontinued which means that we are dropping the program completely. The ADC601, which is the antibody conjugate program, which contains an Axel antibody from Birkenbauer, has been in a phase 1A, is now in a phase 1B study. And unfortunately, ADC Therapeutics has informed us that the therapeutic window for the program is too narrow, most likely due to toxicities. And they have reassured us that there is no correlation between the toxicity that they have seen with the conjugate and the fact that they are using an excellent antibody. So this is, of course, reassuring for us, unfortunate for ADC therapeutics. But none of these events will have any financial impact in the outlook or the guidance as we have not included any of these in our future outlook. So Berg and Bayer today is probably just reiterating the focus of who we are. We're focused on developing benzenzimib in lung cancer. We have our own program, which is benzenzimib combined with standard of care and frontline therapy for non-small cell lung cancer for patients with a mutation in the STK11 gene. And that's currently in a phase 2A study. As I said, we expect the readout early next year on the first part. But we also have another interesting program. It's not fully under our control, but it's an interesting program from the fact that Dr. Taverna from the University of Texas in Antonio has published some quite groundbreaking studies preclinical data on the combination of a STAT3 inhibitor in combination with an Axel inhibitor. So we are in a three-way partnership. I think I can say in a clinical study phase one, A, B study. In second line, lung endosomal carcinoma, where Bergen-Barr is providing pentazimib, and Sobi, the Swedish pharmaceutical company, is providing pacritinib. And the study is fully funded by the NIH in the United States. And we expect the first patient in that study to be late this year or very early next year. If we then move into the financial overview, It's actually pretty much as we have guided. So around 40 million on a quarterly basis. This third quarter in particular was somewhat lower, primarily linked to less sourcing of standard of care. So we buy them in bulks to have them at the sites. So there will be some variations on a quarter-to-quarter basis. But I think it's reassuring that the guidance we have provided remains intact and our cash possession of 175 million Norwegian kroner almost is still projected to finance our operations under a going concerns principle until into the third quarter of 2025, at which point we are planning to complete the enrollment of all the patients in the phase 2A study. If we look at if we are delivering what we are saying, I think we can say pretty much so. In the second half of 2024, we have guided on a number of items to be delivered. So in the 16th study, the completion of the Phase 1b study, the report of the safety data, we have identified the second dose from the Phase 1b study to be initiated in the 2a part. And we've also established a synthetic control arm. Other news flow, the study that I just alluded to, led by Dr. Taverna, has been initiated, but there's still no patients enrolled. It's not under our control, but we are very hopeful, given the very interesting scientific hypothesis, that patients will be identified and treated as soon as possible. We have updated on the outcome of our tilvestamat partnering efforts. That brings the program to a full closure. And I also updated you previously on the ADC program that unfortunately means that they are discontinuing the program. We are still in the making of providing additional data on the mechanism of action, which will be from PBMC blood samples from the patients in the 16 study. So we believe we might still be able to deliver that this year. If we're looking into next year, now we are really a focused company. We believe that we are targeting an update from the phase 2a in the first part of 2025. There will probably be numerous interim analysis. This is an unblinded study. So at meaningful time points, we will be able to look at the data and communicate that to the market. But of course, we're also looking forward to complete the enrollment of the patients themselves. So, in a nutshell, Bergen Bayer is a very focused company, focused on benzenzimib in lung cancer in two studies. One is our own control, which is the 16th study, where we in the phase 1b have shown acceptable safety, but also that we are within the therapeutic window from a plasma point of view. The 2A study is ongoing. All the sites are activated. And the collaboration with Tempus is expected to deliver a contextual benchmark as we analyze the data on an ongoing basis. And as I said, we expect to provide the first interim analysis in 2025. From a financial point of view, we are in the position we have guided on, around 175 million Norwegian kroner, which will fund the company's operations, the planned operations, into the third quarter of 2025. With that, I would actually like to hand over to our chairman, Anders Stuhlgren, who will provide an update on the situation of the leadership in the company.

Thank you very much, Martin, and good morning. So the company is very committed to deliver on the strategy and also the board of directors. We have a very experienced and competent organization in place to execute on it, and all activities will continue as planned. I'm also very pleased to say that David Coleman has been a new member of the board of directors He has a very strong international background in licensing, marketing and M&A and will bring a very good experience to the board. As you know, Martin has decided to leave the company and we are in an active search for a new CEO and I hope to come back to you on that in due course. What has been agreed with Martin is also that he will stay in place until we have the new CEO and for a transition period. So from the board of directors, it's very clear message. We will stay with our strategy that Martin outlined. We will continue all and we have a very competent and experienced team to execute on this during the transition period when we have a new CEO in place. So with that, I think we conclude our presentation and we will go over to the Q&A. So perhaps, Rune, you want to ask a question?

Yes, we have a few questions. So you expect to present the interim data from the BGBC in the first part of 2025. Can you give more specific guidance on that?

part of 2025 is going to be in the earlier part of 2025 we cannot provide an exact date because we do not control the data readout and therefore we cannot identify a specific date or month but it's going to be in the first part of 2025.

And when do you expect to present the complete data set from the phase two part?

So hopefully the patients will live as long as we can hope for. And that will tell you that the final readout of the study could actually be late 26, if you think about it this way. But you know, it's data driven. So in the protocol of the study, We have committed to follow the patients for two years or treating the patients for two years so that that's ultimately the final end or the time at which point we would analyze the data. And it cannot be more specific than that because we don't know until we have the data.

And why was the work until Vastama discontinued?

So as I said, in 2022, as part of focusing the strategy on benzenzimib, we discontinued all internal efforts on tibestamab. We believed at that time that there was potentially someone who would partner the asset and further develop it, not necessarily in fibrotic diseases in which we were developing it, but in potentially other indications. But unfortunately, we also have to accept that that is not the case. At least I'm very glad that we retained Benzentamib, because Benzentamib, in our opinion, performs at least as good or even better compared to Tilvestamib. So that's reassuring for ourselves.

And a question about the new board member, David Koltman. So why was he taken into the board?

Yeah, so David has a very long experience from several companies, both pharmaceutical and biotech companies in the business development and licensing. And that was a competence that we want to add to the board. And he's also a very recognized international leader. So we are very pleased to have David to the board. And I think we have a very competent board now that's actively working together with the management team to ensure that we execute on our very focused strategy. So very pleased to add David to the board.

And then a question about why the CEO Martin Olin is leaving or any specific reason and will his departure impact the BGB activities?

Perhaps you take the first part. I can take the first part.

So I can reassure the audience that my decision to leave the company is not connected to Bergen Power, but simply the fact that I have been presented with an opportunity that I simply had to pursue. And maybe I'm wrong.

Maybe I'm wrong.

I don't think it has anything to do with Bergen Bauer. I'm sure it doesn't have anything to do with Bergen Bauer, actually. So it's a personal decision. And of course, I'm sorry that it has to be the same time.

Yeah, so, I mean, we're sorry to see Martin leaving, but I'm very confident, as I said before, in the team, we have a good experience, a committed team, which I've seen myself during the last couple of days, and I'm actually, also, as we said, it's the first priority for me is to find a new CEO and coming back on that, so we will come back on that shortly, and that, of course, is key priority for me is to ensure that we get a new CEO in as soon as possible and I'm also very pleased we're having Martin staying until that's happening and for a transition period so there is no nothing that would slow down our activities that it's nothing that will change our strategy we are fully focused on delivering this opportunity for patients where there is a very high unmet medical need as well for these SDK 11 patients. So nothing has really changed there.

I think it's important for me to make sure that everyone understands that there is no disagreement between me, the management or the board. heart or the reason once I made my decision to resign.

There's a question about the disappointment about the limited news flow between quarterly updates. Can you explain why?

It's like that when you are in a clinical study and that's kind of the only program we are running ourselves. But no news is not necessarily bad news. The reality here is that it's data-driven, and we just need to have enough patients being exposed to the drug for a long enough time before it's relevant to make our own analysis, which is the basis for communicating to the market. So I realize, and I get it, it's maybe not... what you want but this is the reality of running a clinical study where the readouts are quite long in oncology compared to some other indications. So the waiting time is a little unwanted but necessary.

Any plans to change the communication strategy?

I think our communication strategy is hopefully received as being very transparent, open and direct. We always want to inform the market on relevant and important information. We are not providing... what I call smokescreen information, just to provide information. We are providing information that is relevant for the shareholders, hopefully at an appropriate time. But I get it. I wish we could announce the data much sooner, but the reality is that we have to wait for the data to mature.

Thank you, Martin. Thank you, Anders. I think that completes the questions. Thank you.

Thank you very much.