Bergenbio ASA

OSE:BGBIO

Earnings Call Transcript 2022-Q3

[Martin Olin, executive]

Good morning, and welcome to the third quarter 2022 update from BerGenBio. I'm Martin Olin, the CEO of the company. I just remind everyone about the formalities, forward-looking statements. BerGenBio, in summary, we are entirely focused on the development of selective AXL inhibitors for the treatment of aggressive diseases. Our lead compound, bemcentinib has already been studied in more than 600 patients as of today and is currently being advanced into significant opportunities.

First one, first-line non-small cell lung cancer in a particular subset of patients that carry a mutation in the STK11 gene. And we are moving forward with a Phase Ib/IIa study. I'll come back to that. We are also advancing bemcentinib in -- within hospitalized COVID-19 patients through a Phase IIb study.

We are laser focused to deliver clear value drivers in the next 12 to 18 months. This is the recent highlights. So we announced in the third quarter that we had dosed the first patient in the Phase IIb study under the EU-SolidAct platform enrolling up to 500 patients across Europe. We also initiated our Phase Ib/IIa study in evaluating bemcentinib in combination with standard of care, which is checkpoint inhibition and chemotherapy in first-line non-small cell lung cancer patients that harbor the STK11 mutation. And we know that STK11 mutations occur in up to about 20% of this population and result in inferior survival outcomes on current standard of care.

We ended the period with NOK 225 million in cash, and we announced post period the closing of a NOK 100 million loan facility from our largest shareholder, Meteva, enabling the execution of the focused strategy that we announced earlier this year and made particular focusing on the 2 opportunities that I just mentioned.

We're also pleased to report that we had the last patient last visit in the 003 study, so that's the relapsed/refractory AML, second-line patients. And we also recently had the last patient last visit in our 008 study, which will allow us to lock the data base and analyze the data, and we will report both studies in the beginning of next year.

In line with the focused strategy, we've also announced that tilvestamab is not within the focused strategy, and we have therefore initiated partnering outreach for the tilvestamab, which is our monoclonal antibody that has completed a Phase I study in ovarian cancer, not specifically for ovarian cancer, but we believe that the ovarian cancer setting was the right setting for us to acquire the tissue biopsies under which we could evaluate the fibrotic impact of tilvestamab.

The whole rationale behind BerGenBio is focused on why AXL inhibition. Well, it's known that actual activation results in several deleterious effects in cancer and severe respiratory infections, potentially others, but we are focusing on these 2 indications. In cancer, we know that AXL activation leads to innovation migration, drug resistant, proliferation, survival -- increased survival of cancer cells, but also immunosuppression. And in respiratory diseases, we see that it's involved in viral entry, migration, immune suppression, ECM production based on cell proliferation, but also reduced cytokine signaling.

This is a snapshot of our clinical pipeline that shows bemcentinib has or is being studied across a number of oncology indications. The first-line is one -- first-line non-small cell lung cancer, STK11 patients, which we are initiating or have initiated. The 2 studies that I just mentioned have now been completed. That's the second-line non-small cell lung cancer study, where we have combined bemcentinib with pembrolizumab and also docetaxel.

We also completed the 003 study, relapsed and refractory in all second-line patients and in MSD and solid tumors as well, which is an out-license program with ADC, so we don't have any control over that. And finally, with bemcentinib, the COVID-19 Phase IIb study. And as I mentioned, tilvestamab is we have initiated the partnering effort for that.

The focus of today's presentation will be the priorities of the focus for the company, which is first-line non-small cell lung cancer STK11 mutated patients and COVID-19 hospitalized patients. So I'll walk you through the first indication, which we believe represents a unique opportunity for bemcentinib to address a significant unmet medical need.

And why do we believe that? Well, our data from our completed second-line studies in non-small cell lung cancer support in our mind why it makes sense to inhibit AXL with bemcentinib. First of all, in the 005 study, to remind everyone that's bemcentinib in combination with docetaxel in second-line plus patients demonstrated improved efficacy, and therefore, also demonstrated the potential for the delay of chemo resistance that we see patients are acquiring. And in the 008 study, which is a study where we combined bemcentinib with pembrolizumab, we have seen a very interesting and encouraging efficacy in patients that has over expressed or activated AXL showing median PFS and median overall survival outcomes that are actually pretty similar to what you see in first line, which we believe is demonstrating the importance of AXL as a driver of disease progression.

And in addition, we have supporting data that identified this a significant opportunity. First of all, we know that these patients have inferior outcomes on standard of care therapy today. We also have seen with our own data, but also data that we have collaborated with Inserm that these STK11 patients almost universally over expressed or have activated action. We know that the STK11 patients are characterized by a severely immunosuppressed tumor environment with high levels of ROS, EMT, oxidative stress that is actually, in our opinion, the result in poor prognosis.

And the early retrospective data that we have mentioned before, it's a small data set, but they also support that there is benefit for these patients of inhibiting AXL with bemcentinib. So the 2 clinical -- the studies that I'm mentioning, the 005, in essence, we believe that, that data justify that there is an opportunity to delay the chemo resistance by reversal of the cancer cell survival and escape mechanism. And the 008 data justifies the combination with pembrolizumab. So the 2 elements that are standard of care today, we believe fits very well with bemcentinib.

This is the 005 data that we have shown before with an overall response rate in second line and beyond of 35%, and one should recon that what you normally see with docetaxel here is 6% to 9%. So almost a fourfold increase in the response and 47% of the patients had stable disease at the best response. And the most common side effects, we believe, are not detrimental and are manageable in this setting. And there are very few non-hematological grade 3 events. So they were rare.

In the 008 study when we specifically look at those patients who are AXL positive or the determination they are -- have an activated AXL, that's about 50% of the patients, and they actually show benefit that are pretty close to what you see in first-line non-small cell lung cancer patients as also referenced here on the 2 tables. So both on the median progression-free survival and on the overall survival, these are very, very meaningful benefits in second-line cancer patients.

So AXL when is activated, actually reduces the apoptosis, so the ability to kill the cells, but also promotes the immune response macro environment. So on the left-hand side, we know that AXL activation leads to an improved cancer cell survival and escape mechanism for the treatment. And on the right-hand side, we also know that in the macro environment around the tumor, the AXL activation leads to immune suppressed environment, causing the tumors not to respond to today's therapies.

And when we look at the STK11 patients, we can see that it causes high oxidative stress, hypoxia, inflammation, which result in an almost universal AXL expression in this population, which is quite interesting. The cancer cells are using the AXL pathway to sense the stress and therefore, they are to trigger a molecular mechanism to actually enable the cancer cell to survive the toxic environment that they are being exposed to. And they have a phenotypic characteristics that are known to drive the AXL expression and the activation. So what we see is a pretty significant increase in the AXL expression in these STK11 mutated patients, why we believe it's particularly relevant to consider that population.

We know this is just a summary to remind you about the size of this opportunity. So on the pie chart on the left-hand side, it's about 20% of first-line non-small cell lung cancer patients in U.S. and the 4 big European countries is actually more than 30,000 patients on an annual basis. We know that they have low response rate. We know that they have shorter survival and median progression-free survival. And we also know that they have a reduced response to both chemo, but also immunotherapy and there is no targeted therapies available for these patients today. So indeed, this is a significant unmet medical need, which we believe can actually be targeted by bemcentinib to potentiate the current standard of care.

So in combination with today's standard of care, which is a checkpoint inhibition and chemotherapy. On the left-hand side, we are showing the cellular impact of bemcentinib inhibition of AXL by reducing -- or it causes reducing of EMT-driven immune evasion and drug resistant. It enhances the antigen presentation, and it also reduces the DNA damage repair and enhance cell death. And on the tumor microenvironment, also very important. It reactivates or re-sensitizes the tumor to checkpoint inhibition therapy through the proliferation of the TCF1 and CD8+ T cells.

From a safety perspective, the educated listeners will know that we have dosed bemcentinib previously in the oncology trials with a loading dose of 400-milligram and a daily doses of 200 or maintenance dose of 200. And this is a snapshot of the safety data that we have seen when we combine bemcentinib with pembrolizumab at that dose level, which in reality tells you or shows you that there are no significant safety issues of that combination compared to other relevant therapies.

And the important thing is here that we are moving forward with the Phase Ib/IIa study at a significant lower dose, so no loading dose and a daily dose of less than, potentially less than 50% of the previous dose. So we do expect that we're not going to see any additional safety issue even in the triplet combination.

From a competitive perspective, we consider the opportunity to be a significant white space in the broader STK11 mutated population. Yes, there are competition in the KRASG12C area, but that is only 12% of the STK11 mutated population. So indeed, we believe that bemcentinib is well positioned from a competitive point of view. Indeed, we are, to our knowledge, the only one that is moving forward with a broad approach for the first-line STK11 patient population.

With that, we are moving forward and have initiated the Phase Ib study, which is the dose escalation part in the U.S. and the doses that we will test is 75, 100 and 150-milligram in all comers patients, Why all comers? Well, we want to get the safety done as quickly as possible. And the IIa part, which will be the dose expansion part potentially involving 2 doses will be in STK11 mutated population, particular. So we believe that we will be able to report the data from the Ib in the second half of next year and be able to initiate the Phase II expansion study also in the second half of next year.

Now move on to the hospitalized COVID-19 opportunity. We believe and we have said that many times that we believe bemcentinib offers a novel approach to an effective treatment for hospitalized COVID-19 patients. We have a strong package of preclinical but also clinical evidence that supports the unique mechanism of action, which is the prevention of the viral entry, the increased immune response to the virus, but also importantly, the ability to repair the lung tissue damage that is important for the recovery phase. Our preclinical data points to an almost universal efficacy regardless of the variant but also in other diseases, respiratory diseases, I should say.

And the 2 prior COVID-19 studies that we have conducted shows clear trend to improve survival and a delay of disease progression. We also believe that the recent events, including the very ADCOM meeting, shows that our approach of doing a significant and robust study, a Phase IIb started with up to 500 patients is the right approach to seek an approval in this indication.

This is just a little bit of repetition, but to remind everyone that this is the unique and also the competitive advantage in our opinion of bemcentinib by the mechanism of action or the modalities by impacting the wild entry, increase the immune response, but also repair the lung tissue damage. And we don't see any change. This is the current guidelines from the NIH in treatment of hospitalized COVID-19 patients. There is, in our mind, no change in that landscape. So there is still a significant medical need for those patients who are hospitalized and require oxygen.

The ACCORD2 data in our mind justifies why bemcentinib in combination with standard of care is a relevant treatment modality. Already at day 29, we saw a survival benefit, which is retained throughout at day 60, but also very importantly, the clinical benefit that the patients are seeing is at 90% in the active arm versus 69% in the control arm or standard of care alone. And these are some of the recent data that we have generated, which clearly points to the fact that on the relevant markers that are relevant for this particular setting, potentially also other respiratory diseases clearly points to the fact that the mechanism of action that we are talking to is reflected in the outcome of the relevant clinical biomarkers.

So with that, we are moving forward. We are enrolling patients through the EU-SolidAct study. We are still activating sites. And hopefully, very soon, most of the sites will be up and running. And we are really looking forward to report the data as we have guided previously in the second half of next year.

Our third quarter 2022 financials show a decrease in the operating expenses, which is actually also what we implicitly guided on when we did the -- announced the focused strategy. So we are seeing a reduction in our burn, rightsizing the organization and focusing on the 2 indications, and we expect to see a lower burn going forward compared to the historical burn.

If we look at our cash burn and specifically the third quarter, NOK 65.8 million or $6.6 million, which is somewhat lower than the quarterly average from the last year. We ended the period, as I said, with NOK 225.1 million and which is about USD 20.7 million. But importantly, we also secured the shareholder facility from Meteva of $9.5 million, providing cash resources of more than USD 30 million. And then again, at a projected lower cash burden going forward than previously.

If we look at the key catalysts relevant for the 2 indications, we are going to report the 008 final data in the first part of next year, which is certainly relevant in terms of the argument and the clinical efficacy of bem in this indication. We hope to be able to report the Phase Ib data in the second half of next year. We will initiate as planned, hopefully, the Phase IIa study also in the second half, and we'll have additional preclinical data in the STK11-mutated population also in the first half of next year. For the hospitalized COVID-19 patients, we expect to report the data in the second half of next year. And we're also going to provide additional preclinical data on other respiratory infections.

With that, I would like to say thank you for the attendance, and we will open up for questions.

[Unknown Executive]

Thank you. First of all, are there any question in the audience here? If not, we can go to the online questions. So the first one is about the STK11 Ib study. When will the data from STK11 Ib include -- no, sorry, will the data from the STK11 Ib include focus on efficiency? And if yes, do you expect that it could trigger interest from large players in the business?

[Martin Olin, executive]

Do you want to answer that question, Cristina?

[Cristina Oliva, executive]

Yes. Yes. So the primary endpoint of the Phase Ib study is going to be safety and tolerability. We will have a secondary endpoint of preliminary antitumor activity. And the reason of these 2 endpoints is actually to give us enough confidence from a feasibility and safety perspective to move into a biomarker-driven patient population. So we will have only very preliminary antitumor activity, keeping in mind that the sample size is going to be pretty limited.

[Unknown Executive]

The next one is about the EU-SolidAct study. Could you say something about how the recruitment for the EU-SolidAct is progressing? And do you have some guidance on when we can have the first data from that study?

[Martin Olin, executive]

So I think we have already provided the guidance, which is the second half of next year. That's what we expect the outcome of the data of the study. It's really too early to provide any guidance as to the enrollment. And I don't think that we would provide any specific guidance on the enrollment as such. But we will, of course, update the market when relevant in terms of the finalization of the enrollment. But it's really too early at this point actually to say anything other than what we have already guided.

[Unknown Executive]

Then it's a question about respiratory infection collaboration. You guided in the second quarter presentation on additional data from respiratory infection throughout collaboration that you would soon announce. What is the status of that matter?

[Martin Olin, executive]

We will soon announce the collaboration.

[Unknown Executive]

And then it's a question about the loans facility. It's more related to why we haven't offered that to old shareholders. I think maybe the answer to this question is to remind about the tops for -- for the loan, this is a nonsecured loan from the largest shareholder, it's an intention to rule out the equity. It's no fixed term on the version to equity. So it's just an intention. So I think that addressed the question why we haven't offered it. It's favorable terms for the loan. It's given from the larger shareholders. So it's nothing else to disclose on the announcement we did when it was completed, included all the terms. I think that conclude the Q&A.

[Martin Olin, executive]

Okay. Any questions in relation to what has been said here? No? Okay, thank you.