BerGenBio ASA

So I'll do this in English.

I'm Martin Olin, the CEO of Birkenau. Welcome to the second quarter 2024 presentation. And for those who have not heard about Birkenbauer before, we're all about Axel inhibition. And why are we doing that? We're doing that because it's known that Axel, which is a cell surface receptor or protein, is involved and critical in a number of serious diseases. I'm happy to report that on our very focused strategy, we progressed very well in the second quarter. particularly on the clinical and on the financial aspects. In our main study, which is called BGBC16, which is a study in frontline therapy in non-small cell lung cancer for patients who have a mutation in a gene called STK11, a significant unmet medical need. I'm happy to report that we have completed all the three cohorts in the phase 1B. So the 1B is a safety study. We tested three doses, 75, 100, and 150 milligrams. And we received a positive recommendation for the Data Safety Monitoring Board, allowing us to include the second dose of two doses in the 2A part, which is specifically for patients who have the STK11 mutation. So that's ongoing, and that's a great achievement for the company. The study is designed to involve up to 40 patients in the Phase 2A part. Of course, a Phase 2A study is not a randomized study, so there is per se no control arm. That's quite usual for a Phase IIa study, but we have addressed The need, I would say, for having a reference instead of a control arm. So we have teamed up with Tempus, one of the leaders within artificial intelligence for what is called tumor ctDNA profiling, which means gene profiling of the patients, a US company listed on NASDAQ that has a unique network to a number of hospitals in the US. And I'll come back to what this means for the study, but that's a very important and encouraging advancement. We are the leading Axle inhibitor and development for this indication. There is a significant unmet medical need, about 20 patients 20% of non-small cell lung cancer patients, even in frontline, have a mutation in the STK11 gene, causing them to respond very poorly to standard of care therapy. And we have shown that by inhibiting Axel with benzenzimib, our molecule, we can actually improve both the innate and the adaptive immune system to respond better to standard of care, which consists of chemotherapy plus immunotherapy. We raised very successfully 138.9 million from the warned exercise. So in combination of what I call the two-state financing, we've raised almost 400 million Norwegian kroner since June of last year. And we ended the quarter with 200 million Norwegian kroner in cash. And our average spend is around 40 million a quarter. So this will take us into the second half of 2025, at which point we have completed the study. and we'll have several readouts from the study as we go along. We also completed a reverse share split, 100 for 1, so we have dealt with the penny stock issue, as pointed out by the financial authorization here in Norway. But let's go back to the opportunity. So what are we talking about? We're talking about addressing probably the most significant issue market opportunity within medical care, which is cancer treatment. It's projected to grow by almost 10% and adding $150 billion, getting to a staggering number of $400 billion by 2028 in cancer treatments. And we're only talking about the pharmaceutical part, not the cost for cancer. the additional and surrounding costs for the treatment. Non-small cell lung cancer is one of the largest indications. Unfortunately, it's also the deadliest one. So more than 2 million people die every year from non-small cell lung cancer. And Bergen Bio is addressing what is at least believed by a number of analysts and experts to be The critical areas to change the outcome for the patients, i.e. improve the treatment and Bergen Bio with our compounds, are actually addressing three of the cornerstone approaches. One is precision medicine, which is you identify an issue and you can actually target that issue very specifically. We're doing that with the STK11 patients, mutated patients. We also have a partner program, with a company called ADC Therapeutics, where they're using one of our antibodies in a conjugated fashion so they can get the toxin into the cells. And we have also seen, both in preclinical but also in some clinical data, that we are able to stimulate the immune response, the innate immune response, which is our own immune response, to actually respond better to both immunotherapy but also chemotherapy. And if we look at non-small cell lung cancer, 20 years ago, it was just one group of patients. Today, it's actually a very heterogeneous group. So first of all, you are tested for your PD-L1 expression because that will highly predict the outcome. So if you have a high expression on PD-L1, you're very likely to respond well to immunotherapy. But if you have a low or a negative PD-L1 expression, it's not likely that you're going to have any benefit from immunotherapy. But yet it's still applied because there's no alternatives for the doctors today. To add to the complexity, this slide can be sliced even further down into what is called mutational status. And there are a number of mutations that are known to be oncogenic drivers, which means that these are the primary reason for why the cancer grows. and there's no therapy if it's non-actionable. But there are some actionable mutations, which means that there are targeted therapies that can address the EGFR receptor mutation, and those treatments have turned out to be extremely successful, i.e. it prolongs the life significantly for those patients. But the majority of the mutations that are known today and are involved in the growth of cancer are not actionable, which means that there is no therapy available for them. STK11 is probably the largest group in these non-actionable mutations, and there is currently no therapies available for the patients. And the outcome for these patients are pretty devastating. So from you are diagnosed until you no longer respond to therapy, less than six months, and you can expect to live less than 10 months. And this is from the first diagnosis. This is a pretty devastating diagnosis. If we look at the market opportunity, doing the numbers, so we're talking about first-line non-small cell lung cancer, STK11 patients. It's about 31,000 patients in the Western world. If we take out those mutations, if you record it, EGFR, BRAF, and ELK, We're down to around 30,000 patients. The average monthly price for a treatment in the U.S. today is around 14,300 U.S. dollars. And we expect at least to be able to treat the patients for 10 months. So we extend the time on treatment. from around 6 to 10 months, and hopefully will extend the life even more for these patients. And this comes down to a market opportunity of around $4 billion on an annual basis, so a very significant opportunity. Why is it that we believe that we have a go at it? Well, first of all, we have some very unique features about benthamin. It's a small molecule, so you can take it as a pill. It's all available. It's very potent and highly selective for axon, so it doesn't inhibit any other cell surface proteins. It concentrates very interestingly in the lung compared to other tissue, which is, of course, neat because that's the disease we are addressing, but it also crosses the blood-brain barrier, which is very important because, unfortunately, a lot of these lung cancer patients have metastasis in the brain, and we can address that because our molecule actually can cross the blood-brain barrier. We have a very extensive safety database. More than 600 patients have been treated with the drug. We have seen activity from the drug by itself, so not combining it with other drugs. We've seen activity in multiple indications. We know that it combines very well with chemotherapy and immunotherapy. We've done two studies in second-line non-small cell lung cancer in more than 100 patients. where in both of the studies we extended the time people were on treatment, but we also extended their life compared to the reference. We have a fast-track designation issued by the FDA, which means that the regulatory agency in the United States have acknowledged the medical need, and they are encouraging people like us to move forward fast, as fast as possible in this indication. The fast-track designation means that we'll be at the same side of the table with the FDA instead of on the other side of the table as we progress in the study. And we have patent protection until 42. So this is actually the core of why we believe we have a drug that potentially could change the outcome for patients. So if we look on the left-hand side, this is the characteristics of a tumor that respond well to treatment. So chemotherapy and immunotherapy. And why do they respond well? It's because they have presence Of CD8 plus T cells, these are the T cells that can kill the cancer cells. They also have a very high expression of PD-L1, which is needed for immunotherapy to work. So K-truda, for example, does not work if you don't have a PD-L1 expression because then there's nothing to bind to. But they also are characterized by having stimulatory dendritic cells. So this is the innate immune system. If we then look at an STK11 mutated tumor, what we can see is that the CDA plus T cells are excluded, so they're not present. There is no or low PD-L1 expression, and there is suppressive dendritic cells. So this is actually what we call an immune desert where everything works against the immunotherapy to work. What we can see when we Inhibitaxel is actually that we restore the immune system to get the CDL details presented and we have stimulatory dendritic cells and we can also see that we can activate the response to PD-L1 expression even if there is a low PD-L1 expression. Why is that? You could argue that if you don't have the expression, you cannot get the activity. But the reality is that it's not only the tumor cells that are important, it's also the microenvironment around the tumor cells. So that's why we can activate the result. This is a schematic of our Phase 1b-2a study. So the Phase 1b study is a safety study to make sure that the drug, when combined with Keytruda and chemotherapy, is safe in this patient population. You can say, why are you doing that when you have tested your drug in 600 patients? Well, we've never tested it in a triplet combination, which is Keytruda, chemotherapy, and Benzenzimib, our drug. I'm very happy to report that all the three doses were cleared by the Data Safety Monitoring Board, meaning that they are safe and tolerable. And we have, earlier this year, taken the first dose, which is 100 mg daily, into the Phase 2a part. And recently we announced that the... Third and final dose of 150 mg per day were cleared by the Data Safety Monitoring Board, so we're also moving that forward. So these two doses, 100 mg and 150 mg, will be dosed in 20 patients each, so in total 40 patients. And this will be done in what we call a global study. So both in the US and in Europe. And recruitment is ongoing. And I would say that we are very much on plan. What's really groundbreaking and interesting is that we've been in dialogue with Tempus for a while. And we have agreed to sign up with Tempus for them to basically, for each of the patients that we enroll in our study, they will have the genetic profile and the characteristic of that patient, and then they will enroll a patient through their network in the U.S., so we get what I call a digital twin who will receive standard of care. So by doing it this way, we will prospectively, and not looking backwards but looking forward, we'll actually be able to identify 40 patients who will be on standard of care who have the same genetic profile as the patients in our study, and therefore this provides a very meaningful contextual benchmark to the data that we generate, which is standard of care plus pentantamib. So this is kind of, in my opinion, one of the ways we will see clinical studies in serious diseases like cancer being conducted going forward, because doing it the traditional way would probably double the expense and double the timelines to do the study. So we're doing this in a very cost-effective way, and timely fashion, but yet we are getting a very meaningful data to compare with. This is an overview of the competitive situation, and I can say that we are still the leading axel inhibitor in frontline therapy in non-small cell lung cancer. There's no one else who's competing exactly for our population, but there's also no one who is competing with an axel inhibitor in this patient population. There are, of course, a number of other approaches and I would not say that any of them would not work, but at least we are the only one who is specific to frontline and are including all STK11-mutated patients, regardless of whether they have a commutation or not. There are some of them who are doing it with the KEEP1 and KRAS. That's a minor portion. So although they might be successful, we are still addressing the lion's share of the market opportunity with our approach. So if we... Summarize it, it's well established these days that STK11 represent a major unmet medical need in lung cancer. And we believe that our approach is one of the interesting ones. We know that axillary expression is a key driver of resistance to chemotherapy and checkpoint inhibition in STK11 patients. We also know that they have a high expression, which is interesting. So it actually works well together in a normal population. you probably see an actual expression of around 60%. We're talking about lung cancer patients. In STK11 patients, it's probably above or around 90%. So this may be the reason for why these patients are resistant to chemotherapy and immune checkpoint inhibition. We know that our drug have activity. We are progressing the study very well. And we are going to, because it's not a closed or randomized study, we have access to the data. So we'll give... an update to the market later this year and in the beginning of 2025. And again, we are the leading excellent inhibitor. Most recently, we announced a very interesting and very promising approach, which has been published by Josephine Tavernier from the University Hospital at San Antonio. And the science is pretty groundbreaking. It shows that the STAT3 pathway It's very tightly linked to the actual pathway and maybe the reason for why lung cancer patients does not respond well to therapy. This is not non-small cell lung cancer, but lung cancer generally speaking. And based on that publication, Dr. Taverna has actually received a sponsorship from the NIH in the US. So this is a fully sponsored study. And we are participating in this study, so we're combining benzenzimib with pacritinib, or Vanjo, which is owned and marketed by Sobi, a Swedish pharmaceutical company, but not approved in lung cancer. So there's a significant interest, both from Sobi and, of course, Bergen Bayer, but certainly also to test whether the groundbreaking scientific publication that Taverna has published actually translates into cancer. efficacy in patients. This is a new opportunity, and it's fully sponsored, so there's no additional cost for BirkenBio, other than the fact that we are sponsoring Benzenzimib, which we have on the shelf anyway. On the financials, I would say overall we are tracking completely in line with the guidance we have provided previously. So we have significantly reduced the spending in the company after we did the strategy change in 2022 in the beginning, and then in 2023 fully implemented. So our burn rate is around 40 million a quarter on average, and 75% of that is related to the clinical study. So there may be small variations between the quarter. We also saw one in the second quarter. Probably around 8 million of that variation from the 40 is explained by the fact that we are purchasing standard of care to be given to the patients, and we're buying the drug up front, the standard of care, and then using it in the quarter after. So if we adjust for that, the quarter was kind of dead on 40 million. We ended the quarter with 200 million. and we expect the burn rate to be the same as we go forward, 40 million a quarter. So we have another four quarters of runway, and we expect to complete the study in the summer 2025, and we will have ongoing readouts. So we're pretty sure that we're going to be able to provide the market with updates from the study, meaningful data points that can guide on what should be the next step for the development of benzantamib with a non-small cell lung cancer. This is an overview of the new slow. We have completed the 1B, and we have also announced that we have initiated the second dose. We have established a synthetic control arm, which we have also guided on that we would do. And then for the remainder of this year, we'll have the first patient hopefully included in the NIH-funded study, the one conducted by Dr. Taverna, We'll have an update on tilvestamab, our antibody, also addressing Axel on the out-licensing process, an update from the partner program with ADC Therapeutics. We'll also provide some additional benzenzimib data from the 008 study, which was in the Phase IIb study, where we combined benzenzimib with prempolizumab. And what we are looking for is actually to see the argument, if we can validate that in the clinic, as I just showed you before, on these cells can we actually see that we are improving the ability of the immune system to respond. We'll have safety overview in this second half as well, and we'll also have the first interim analysis from the phase two part. On the regulatory side, we're going into next year, we will meet with the regulatory agency to have some guidance on what should be the next development or the next study. and hopefully a pivotal study in this significant indication with an unmet medical need. We will complete the enrollment on the plan and we will provide interim analysis on the Phase 2a data, which will be, in our mind, very meaningful and probably the opportunity to potentially provide some very valuable data to the shareholders. So, all in all, a very clear focus in frontline therapy, where there is a significant medical need, no treatments that are effective, available to the therapy. We have shown that our combination is safe. Sounds easy, but very important. Safety first. The phase 2a is on plan, and we now have the two doses in. The collaboration with Tempus provides a very relevant and innovative approach to getting a control set data because everyone will ask you okay so how are patients doing if they are on standard of care and most companies have been looking backwards on historical data but there's always some caveat that it's not the same patient population or so you know you're data mining this approach provide us with a match of the patients so we can be sure that these patients have the similar profile as the one in our study very important The interim analysis that we will provide will be the first kind of look at what's the efficacy of this treatment. Is it as good as we can hope for? Hopefully. And this will unlock significant value in our mind. And we have the money to complete the study. We don't have the money, if you ask me, to have the final readout of the study, because I hope that these patients will live much longer than they do on standard of care. That's the presentation. And I think we will open for questions.

Anyone from the audience? First of all, any live questions in the audience?

Yes. Hans Hekland from Salsia. I just wonder, you mentioned the pivotal study that you are supposed to discuss with FDA.

Yeah.

Do you have any idea of the size, the number of patients that that will be, and then the timing for such a study?

As you know, it always depends on the strength of your data. If we can bring back the STK11 mutations as if they did not have the mutation, which will be a very strong signal, I would say that 250 patients is probably what you would be thinking about under a fast track designation. So 250 patients in a randomized study, two for one randomization probably, the enrollment always depends on how much you are prepared to invest in it, how many sites, and it's at a global study, etc. But it's not unreasonable to believe that you can enroll this kind of study in two years with the right partner, I would say. Thank you.

Any other questions here? If not, we have some online questions. So the first one is, what is the status on patient recruitment for the Phase IIa?

So as I said, we have included the second dose, and the first dose 100 milligram were initiated in May this year. We're not providing specific guidance on numbers per se. We are rather focused on the fact that we will enroll the study by the summer next year, but we will provide data as we go along. And the first data point will be late this year in the beginning of 2025.

Thank you. And what are the major milestones remaining on the Phase 2 and when do you expect to present these interim data from the Phase 2a?

Kind of the same question, but first interim data late this year, beginning of 2025. For me, the really important milestone is the final data set from the 2a study in comparison to the Tempest data.

Why was the dose for the phase 2 decided just recently? This is the second dose done. Are you lagging behind?

No, so the 2A study consists of two doses, and that's to address a requirement from the regulatory agency in the US, which is a fair requirement, is that don't show us your highest dose, show us your best dose, which is the balance between safety and efficacy. And that's why we have two doses in the 2A study. That's to address that issue up front and not to have to address it later on in a study, because if we would have to have two doses in a phase 2B or pivotal study, that will probably expand the study to be 275 or even 500 patients. So we're addressing that issue up front. That's why we're doing it.

Can you say anything about what, in your view, would make a positive readout in the phase 2 part? Which study provides the best reference, and what magnitude of improvement are you aiming for?

So there are no comparative studies, but we're trying to generate one with this synthetic approach. In my opinion, if we can increase the response time for patients, how long will they be able to positively respond on treatment? by hopefully more than three months, the longer the better, but more than three months, improvement of PFS from around five months to eight months, and overall survival from around 10 months to all the way up to 14 or 15. That will be extremely good data, in my opinion.

So why do you plan to burn cache on an external data set, the synthetic control arm, when you still need randomized data?

So this is actually to try to address the issue of what's the reference of your data when we are in the front of the FDA, the agency with our data set. If we have no data to compare it to and would use historical data, I'm very sure that the FDA would say the same thing as I saw them the last time. Well, these data are not comparative to the data you have generated. By doing it this way, we are at least generating a comparative and relevant data set Yes, it's not randomization, but it will provide very valuable insight into the strengths of our data and hopefully convince the FDA that we have enough to go into a phase 2B slash pivotal study.

And can you say anything about the financial terms on the terms agreement?

I cannot say anything about the financial terms, but I can assure you that doing it this way comes at less than half the cost. and less than half the time that it would otherwise be if we had to generate it by ourselves.

Any updates on the ADCT 601 study, the phase 1 trial?

No, we are in dialogue with ADCT therapeutics on an ongoing basis, and I think we can expect an update in the remainder of this year.

And the same questions for the Sobe UT Health Sant'Antonio study, the Tervana study.

So we know that the protocol has been approved by the FDA, and we are basically waiting for the patients to be enrolled. So that's probably coming very soon.

And one question. Given the ongoing clinical success on the steady cash flow, what specific strategic are in place to transition Bergen-Bio towards profitability? and ensure long-term financial sustainability?

That's a very good question. I think the strategy that we have applied since two years almost now is to conduct a study in... a significant unmet medical need, a patient population that really is underserved today. We feel that we have a very good shot at it. If we can generate attractive data in our BGB16 study, so the Phase 1b2a study, we feel confident that we can either continue to raise money to conduct the next study ourselves, or partner with a significant player to conduct the study and therefore also get access to sales and marketing capabilities, which we don't arguably have ourselves. So these are the two very, in my opinion, obvious options. And it's going to be data-driven, so the data will tell us and dictate which direction we'll go for.

Thank you, Martin. That completes the Q&A section.

Thank you for attending.