BerGenBio ASA

Good morning. My name is Martin Ohlin and welcome to the quarterly report for the first quarter of 2024 for Bergen Bayer. I'll just remind the audience about the formalities. So the highlights of the first quarter, I would characterize it as continuing on the plan with our focused strategy within frontline non-small cell lung cancer for STK11 mutated patients. And we are very encouraged to have received the recommendation or the decision by the Data Safety Monitoring Board from the Phase 1b study to continue in the expansion in the additional cohorts, but also the opening of the Phase 2a part of the study, which is specifically for STK11 mutated non-small cell lung cancer patients in frontline therapy. I'm also very pleased to follow up on the announcement we had yesterday, which is that given the fact that benzenzumab in our mind is one of the leading selective axil inhibitors in the clinic, has been selected to be part of a study run by the University Hospital at San Antonio by Dr. Taverna in combination with Dr. Good morning. My name is Martin Ohlin and welcome to the quarterly report for the first quarter of 2024 for Bergen Bayer. I'll just remind the audience about the formattages. So the highlights of the first quarter, I would characterize it as being continuing on the plan with our first focus strategy within frontline non-small cell lung cancer for STK11 mutated patients. And we are very encouraged to have received the recommendation or the decision by the Data Safety Monitoring Board from the phase 1b study to continue in the expansion in the additional cohorts, but also the opening of the phase 2a part of the study, which is specifically for STK11 mutated non-small cell lung cancer patients in front-line therapy. I'm also very pleased to follow up on the announcement we had yesterday, which is that given the fact that benzenzumab, in our mind, is one of the leading selective axil inhibitors in the clinic, has been selected to be part of a study run by the University Hospital at San Antonio by Dr. Taverna in combination with Dr. pacritinib, a stat-3 inhibitor, and it's a fully funded study. So the contribution from Birkenau will be benzenzimib itself. The financial position at the end of the first quarter ended fully in line with our guidance, and we further strengthened our cash position by the warrant exercise, which was conducted in April and contributed with 139 million in Norwegian kroner. We continue to operate the company at a significant reduced burn rate compared to previous years. And we are now operating the company at around 40 million NOC a quarter, which means that we are funded with the warrant exercise proceeds until the third quarter in 2025. Today's presentation is focusing on the frontline non-small cell lung cancer opportunity, which we believe is a very significant opportunity. Just to remind everyone that the unmet medical need in frontline therapy is primarily related to PD-L1 negative and low patients. So these are the patients that doesn't respond very well to the standard of care immunotherapy plus chemotherapy. But also there is a significant population of patients who harbor a mutation in the gene called STK11. It constitutes up to 20% of frontline non-small cell lung cancer patients, and today there are no available good therapies for this patient population. and the support for the unmet medical need continues to evolve. There's recently a published meta data set from BMC, Biomed Cancer, that includes more than 4,000 patients, of which more than 600 patients, had a mutation in STK11 patient, and the data basically replicates what has been published previously, but this is a meta-analysis, so it's a pretty interesting evolution and additional evidence in the fact that most of the STK11 patients have a low PD-L1 expression, and that leads to a lower overall response rate to checkpoint inhibition, and certainly their PFS and overall survival were worse than the wild-type population. If we look at the market opportunity, we believe that it's around 30,000 patients in the U.S. and the big five EU, which constitute a potential of roughly 4 billion U.S. dollars a year. And I will now hand over to Christina to take you through the case of benzantamib in non-small cell lung cancer.

Thank you, Martin, and good morning, everyone. Over the next few slides, actually I would like to walk you through the case of Axol inhibition with Bamsentinib in first line non-small cell lung cancer. I want to remind everyone some major characteristics of Bamsentinib. Bamsentinib is a highly differentiated Axol inhibitor that actually is able to provide an improved inhibition with fewer side effects is also able to concentrate significantly in lung tissues and able also to cross the blood-brain barrier, which are both very important characteristics for the patient population affected by lung cancer. We have studied bemsantinib in over 600 patients, hence we have an extensive knowledge of the safety profile and extensive safety database. We have observed also activity with Bamsentinib in monotherapy in a multitude of indications. And we have completed several studies specifically relevant for the lung cancer indication, two Phase II studies completed with the combination of Bamsentinib and chemotherapy and also with the checkpoint inhibitors. actually providing us the rationale for moving into the first line indication. Bamsentinib has also been granted the fast track designation by the FDA in the first line in STK11 mutated non-small cell lung cancer and in second line non-small cell lung cancer. It has also an extensive IP through 2042. So, several studies have already established what is the role of Axol on tumour and immune cells and it appears evident that actually it's critical for the neoplastic survival and for the disease spread. Axol expression is associated with poor prognosis, worse clinical outcome and therapeutic resistance. is expressed in a multitude of tumours and specifically on tumour cells its signalling actually triggers some activities that you see depicted here on the left hand side like increased survival, proliferation, angiogenesis, therapeutic resistance but also immune evasion. Axol is also expressed in a variety of host cells and specifically on a variety of immune cells that you see represented here on the right panel, specifically dendritic cells, monocytes, macrophages and natural killer cells. The interactions between actually the neoplastic cells and the immune cells in the tumor microenvironment can potentiate the axial expression and lead to what we call a pro-tumorigenic environment. We therefore expect that the inhibition of Axel through the use of Bamsentinib could play a role on this dual compartment, both the tumour cells but also the very important tumour macroenvironment. As I said previously, Bamsentinib has demonstrated added benefit when combined with both chemotherapy and checkpoint inhibitors. Therefore, we believe that actually treating patients earlier on, so in first line before they develop resistance, might significantly delay the disease progression and also extend their overall survival. So the STK level mutated patients, which is the patient population that we have selected for our first line indication, is actually characterized by a so-called cold tumor macroenvironment, which is characterized by being refractory to immunotherapy. And what happens in this immunosuppressive environment? As you see here at the bottom of these slides to the left-hand side, there is a striking infiltration of immunosuppressive cells, just to name a few of the blue ones that you see here, the TAN, the tumor-associated neutrophils, but also the Treg. At the same time, There is a significant exclusion of inflamed immune cells that are here represented at the bottom in red, like the CD8 and CD40 cells for instance. And this all in all actually represents a cold system which is very poorly responsive to immunotherapy. Another observation that is important is that actually in over 80% of these STK11 mutated patient population, Axol is expressed and this actually reflects again the role of Axol in what we called immune deserts. Therefore, the inhibition of Axol in this immunosuppressive environment can lead to a a restored response to anti-PD-L1, at the same time a reduction in the resistance to chemotherapy. So where are we with our ongoing study? We have selected, as I said, a patient population which is currently underserved by the available therapy. And that's the first-line STK11-mutated non-small cell lung cancer. The study, actually, I want to remind, is composed of two parts, Part 1b and Part 2a. The Part 1b is a classic dose escalation study where increased dose levels of bamsentinib will be combined with the standard chemotherapy and immunotherapy treatment regimen. The phase 2a is going to be with a specific patient population, the STK level mutated non-small cell lung cancer, and the patients will be exposed to those levels as became feasible from the 1b. I'm very happy to report that actually the study is on plan and is moving according to our timelines. The review of the safety data that has been conducted by the Independent Data Safety Monitoring Board has allowed us to proceed through the planned dose cohort, but also to initiate already the Phase 2a part. There will be an interim analysis expected late this year or early next year that will be based on the preliminary data on overall response rate and progression-free survival. And as I mentioned, we are very pleased to announce that the 2A part has been open to enrolment and has been initiated across a multitude of European and US sites, according to plan, with a very active investigators' engagement. Bemcentinib remains within the context of the STK11 mutated non-small cell lung cancer, remains actually the only one that targets only an STK11 mutated patient, but also remains the only one with a very early entry into the clinic in the first line setting. So all in all, what's the case of Bamsentine before this first line, STK11 non-small cell lung cancer? In the medical community, there is a growing awareness of the need for new and better treatment in STK11 mutated non-small cell lung cancer. The axol expression leads actually to resistance to checkpoint inhibitors and chemotherapy in this patient population. At the same time, STK11 mutated patients present a high expression of axol on both, as I said, the immunocomponent, but also the tumor cells. We have reported efficacy of benzantinib in two Phase II studies that have been completed, one in combination with chemotherapy and the other one in combination with checkpoint inhibitor, both in pre-treated non-small cell lung cancer. Bamsentinib has demonstrated monotherapy activity in a multitude of difficult-to-treat oncology diseases. We therefore believe that actually using Bamsentinib as an early intervention in the first line in the first line setting could improve the clinical outcome of this underserved patient population by actually potentiating and delaying the resistance to the current treatment available. The BGB016 phase 1b2 study is progressing in accordance to the guidance and what we've been reported earlier on. And BEMSENTIV at the current stage remains the most advanced axon inhibitor that is developed and in clinical studies in STK11 non-small cell lung cancer. Let me now switch gear and report to you what Martin has just announced. We are very pleased to report actually this collaboration that focuses on the new NIH-funded studies in pre-treated non-small cell lung cancer. These clinical studies originate from a groundbreaking research conducted by Dr. Taverna and her team that actually has identified that Axol and STAT3 are upregulated in advanced lung cancer and together actually they produce an increased environment that is pro-tumorogenic. With the basis of this preclinical evidence, the NIH has granted an NIH fund that will cover over a five-year period. that would enable Dr. Taverna and her team to develop a Phase 1b2 investigator-led study. This study will combine an axon inhibitor, specifically bamsentinib, with a STAT3 or JAK2 inhibitor, pacritinib, in patients previously treated with at least one line of therapy affected by advanced lung adenocarcinoma. The study will be conducted at the University of Texas in collaboration with us and SOBI and will be complementary to the currently ongoing study. We also believe that this experience will provide us additional knowledge on the mechanism of Axol inhibition in patients with lung cancer. And I would now hand it back to Martin for an update on key financial and news flow. Martin.

Thank you, Christina. So Christina's update, with that I would move into the key financial and news flow. So as I previously said, we are really tracking on our guidelines that we have previously announced. So we are spending roughly 40 million Norwegian kroner on a quarterly basis. We have significantly reduced almost by 50% compared to historical numbers, the burn rate of the company. And we expect the burn of around 40 million Norwegian kroner a quarter to continue in the foreseeable future. We are very pleased with the capital raise we secured in the warrant exercise window in April. This provides a cash position at the end of this quarter, the coming quarter, of roughly 200 million kroner. So we are well funded and we will be able to complete the enrollment of the patients in the 2A study that Christina spoke about. We also believe that this cash position will take us into the second half of 2025. An important information to the shareholders in connection with the AGM on the 23rd of May this month, it was decided to do a so-called reverse share split. And what does that mean? It means that... For each 100 shares that you own today, you will own one share after the reverse share split. This will reduce the number of shares from roughly 3.9 billion to 39 million. It will not affect the corporate value. So at least from a theoretical point of view, this will not be dilutive to the existing shareholders from a valuation point of view. It's important to keep in mind that This share split, 100 to 1, will have the consequence that fractional shares will not be issued. So if you own a number of shares that cannot be divided by 100, this will be fractional shares, that component that can be not divided by 100. and shareholders who have that position will not be compensated for the rounding down. You may remedy the situation and make sure that you have a number of shares that can be divided by 100, but of course that's up to each and every single shareholder. But this is the last day to remedy that situation, and we expect that the consolidation will be completed on May 31st this month. Also important to know that there will be a new ISI number, which will change as of tomorrow. If we look at the new flow, this we have guided on previously. And I'm very pleased to say that we have actually been able to deliver on the guidance. We have initiated the 2A, a very important milestone in the company's progression and pursuit of the strategy. Now we have a global study. which will encompass 33 sites when all the sites are active, which is, we're getting there, very close. We are also very actively in discussion with the establishment of a synthetic control arm, so remind the audience that the phase 2a is a non-randomized study. but the synthetic control arm will, in our mind, in a very innovative way, provide a contextual data set that could strengthen the relevance of the data that we will generate from the Phase 2A study. Later this year, we expect to provide an overview of the safety from the 1B, the totality of the three cohorts, and hopefully we'll also be able to... announce some interim analysis on a limited number of patients from the Phase IIa study. The more comprehensive interim analysis for the IIa will of course be announced in 2025 when we have all the patients enrolled and they have been in the study long enough for them to be relevant in the interim analysis. Other news flow, I've already spoken about the one exercise period, which we are very pleased and thankful to the shareholders for their contribution. We have announced previously also the SRA data, which continues to suggest that benthamin actually could play an important role in severe respiratory infections. As we have said previously, we are not... advancing benzensamib in severe respiratory indications from a clinical point of view, but we continue to do it from a preclinical point of view, simply because we believe the hypothesis is very strong for benzensamib in that indication. And as we have announced yesterday, we now have a clinical study funded by the NIH, which we believe will allow us to provide additional information about the role of benzensamib in lung cancer. In the second half of this year, we expect to provide an update on the Telesta map outlicensing process. We will continue to publish manuscripts from studies that have been completed. And we also expect an update from our partner, ADCT, on the program ADCT 601 in two indications. So that's the new flow. And in summary, Bergen-Barr continues to focus on the advancement of benzenzimib in frontline therapy for STK11 mutated patients in non-small cell lung cancer. The data safety monitoring review, when it's over, it's really relieving, but it's also a very... Comforting to know that as we had projected, we have not seen any new safety issues in the combination, the triplet combination of betansamib checkpoint inhibition and chemotherapy, and we now have a global phase 2A study up and running, and most of the sites are actually open for enrollment. The interim analysis in our mind for the specific STK11 mutated patients will potentially unlock significant value and define the development going forward for benzenzimib in this significant unmet medical need. The cash position with the addition of the warrant exercise in April will fund the company and our operations into the second half of 2025. And we believe we are progressing very well towards the goal of hopefully showing that benzenzimib can make a clinical difference to patients that otherwise don't have many good options for a treatment. Thank you very much for listening. And I think we will now move to the Q&A session.

Yes, we have a few questions. So the first one is, what are the key milestones and challenges you foresee in the development and commercialization of benzentamine for non-small cell lung cancer patients with STK11 mutations? And how do you plan to address these challenges to ensure a successful outcome?

Very good question. So first of all and foremost, it is to have the readout from the ongoing Phase IIa study. which will, in our mind, define the next development states in frontline therapy for STK11 mutated patients population. The signal that we are going to identify will also define the size and therefore the timeline and the cost for a patient. development in the next day, most likely a phase 2B, potentially a phase 3 study or a registration study. It all depends on the strength of the signal. So let's have the data, and then I think we can define what the development plan will look like. From a commercial point of view, I think we've been very adamant that we would be looking for a partner to commercialize benzensamib in this indication when we hopefully get there.

There is a question about the new trial you announced yesterday. So what do you expect as an outcome from the new trial in lung cancer? And is there any overlap with the current 016 trial?

So the study is a phase 1b2, as Christina alluded to. And so we will certainly get a... and hopefully confirm that the combination is safe. There might be some early signs of efficacy from the combination, but it's not a randomized study, so we have to be cautious about what the data will generate. But it's going to be very informative in the sense that this is pre-treated patients, so second-line lung cancer patients. So we believe that, first of all, it's not at all competitive to the strategy we are pursuing, but it will potentially add a new potential indication or line of therapy in lung cancer.

A follow-up question here on the same trial. Will you report the first patient is enrolled in the new study, and can we expect that in the near future?

So the study is an investigator-led study, which means that it's under the control of Dr. Taverna and her group, and we don't per se have any control or access to information other than when it's provided by the Dr. Taverna group.

Thank you. That completes the Q&A. Thank you.