Bergenbio ASA

OSE:BGBIO

Earnings Call Transcript 2021-Q1

[Operator]

Ladies and gentlemen, welcome to the BerGenBio Q1 2021 Conference Call. [Operator Instructions] This conference call is being recorded. I'll now hand the word back to the speakers. Please begin your meeting.

[Richard Godfrey, Chief Executive Officer]

Thank you, and good morning. My name is Richard Godfrey. I'm the CEO of BerGenBio. Welcome to our Q1 2021 report, highlights and financials. This morning, I'm joined by Rune Skeie, our CFO. Next slide, please. Let's just draw your attention to our forward-looking statement and safe harbor comments as we are a listed company on the Oslo Stock Exchange. Next slide, please. In this morning's update and presentation, I'd like to introduce our AXL inhibitors and our Q1 and recent highlights. I'd like to talk a little bit about bemcentinib and our clinical trials, specifically in COVID-19, where we released some top line data yesterday. And I will briefly update on our program in acute myeloid leukemia and in non-small cell lung cancer. We'll then talk about tilvestamab, our anti-AXL antibody. And then I'll hand over to Rune for a financial report. And then we'll close with 2021 highlights and also an outlook before we take questions. Next slide, please. So just by way of a reminder, we've been pioneering research on AXL, a receptor tyrosine kinase that mediates aggressive diseases. These are aggressive diseases in cancer, viral infection and fibrosis, and we know that AXL is upregulated in these disease states. We've developed 2 first-in-class selective AXL inhibitors: bemcentinib, which works on the intracellular domain of the receptor kinase AXL; and tilvestamab that works on the extracellular domain. Both are in clinical development. Next slide, please. More specifically, bemcentinib on the left here is just a simple oral pill. It's manufactured at scale now such that we are able to supply for a Phase III study. It has an enviable safety profile, having been studied in more than 400 patients. It's a simple one-a-day administration, and it combines well with all other treatments we've tested it with. Tilvestamab is a fully humanized monoclonal antibody. It's administered in a biweekly infusion. We've developed a robust and stable formulation. It has a high affinity. It's currently in Phase I testing, having completed Phase I single ascending dose testing without any adverse event and good PK. We're now in a Phase Ib/II study, which I'll talk about a little bit later. Next slide, please. This is a summary of our development pipeline for bemcentinib and tilvestamab. You can see that we are developing bemcentinib as a monotherapy in COVID-19 and have just completed recruitment and reported top line data from our Phase II study. We're evaluating bemcentinib in acute myeloid leukemia and MDS, myelodysplastic syndrome, as a monotherapy and also in combination with LDAC in second-line AML. I'll talk some more about that later. In collaboration with Merck, we're testing bemcentinib in combination with pembrolizumab in non-small cell lung cancer in 3 patient settings: chemo refractory, checkpoint refractory and checkpoint-chemo refractory. And as I just mentioned, tilvestamab is in a Phase Ib/II study right now, which we'll talk about a little later. Next slide, please. So as -- in spite of the challenges of the global pandemic and COVID-19, we continue to have a very busy quarter starting this year. In January, we were able to update on our clinical study in lung cancer in combination with KEYTRUDA at the world congress on lung cancer. In February, we announced that we -- that the independent data monitoring committee recommended continuation of our study in COVID-19, and that study, as I've mentioned, has now completed recruitment and top line data reported. March was a busy month where we initiated the first patient in our Phase Ib study with tilvestamab, and we also presented some COVID data at a new conference for us, the Conference on Retroviruses and Opportunistic Infections. We also completed the recruitment in the first part of our last study in combination with KEYTRUDA. April, we announced that we have completed recruitment in the COVID study and some initial interim safety data. And also, we were able to report that there seemed to be a survival benefit from patients receiving bemcentinib as opposed to those taking standard of care. And just yesterday, we announced the top line data from our Phase II study of bemcentinib in hospitalized COVID-19 patients. So a busy quarter and a lot to look forward to for the rest of the year. Next slide, please. I'd just like to introduce you to our executive leadership team and in particular, welcome Nigel McCracken, who joined us earlier this quarter as the Chief Scientific Officer. Nigel joined us with a wealth of industry experience and knowledge acquired from large pharma and also biotech companies. So welcome, Nigel. Looking forward to working with you as time unfolds. Next slide, please. I'd straight away like to jump into giving an update on the synopsis of the presentation that we made yesterday of our Phase II trial assessing bemcentinib in hospitalized COVID-19 patients. The upshot of this top line data is that we believe that bemcentinib has the potential to increase the rate of ventilator-free survival in more than 50% of hospitalized COVID-19 patients. And indeed, in doing so, we're addressing the greatest challenge faced by hospitals worldwide fighting the pandemic. And that specifically is avoiding the patients progressing into intensive care units and requiring ventilation. Next slide, please. We presented several times now the unique mechanism that AXL facilitates viral infection and the unique mechanism by which bemcentinib is able to prevent viral infection and promote our immune system in fighting viral infection. On the left-hand side here, we can see how bemcentinib stops viral entry into host cells by blocking the endosomal path via which the virus can get into the host cells. And we can also see on the right how bemcentinib is able to stop actual signaling that, in turn, stops the suppression of our immune system. We should also stress that this mechanism of action is independent of the spike protein or mutations of that, and as we know, that is a big fear with the mutant viruses that have started to emerge in the population. Next slide, please. Because of the unique mechanism of action of bemcentinib in potentially treating COVID-19 patients and also its general ability to prevent this EMT and aggressive diseases, we can see that bemcentinib has the potential to be effective across the wide range of the clinical development of COVID-19, from the initial mild stages where we anticipated to be able to reduce viral infection and increase -- and stop the infection from progressing through to the more severe cases to stop the disease from becoming hyperinflammatory and requiring the need to progress into intensive care units and even potentially, in the long term, where its anti-fibrotic effects could be a benefit for the so-called long COVID. Next slide, please. So bemcentinib has been studied in COVID-19 patients across 3 countries, in South Africa, India and the United Kingdom. In the United Kingdom, it was part of an ACCORD program that we previously presented on. And that data is still maturing, and we're unable to present too much of an update on that at the moment. But we are able to report top line data from our studies in India and South Africa. I think it's noteworthy that this is a real-world exploratory study, where we're evaluating bemcentinib in patients presented in hospitals with quite a broad inclusion criteria. Next slide, please. This is a different way of viewing the World Health Organization 9-point scale of the disease progression and the increased pulmonary support that patients may require. So you can see at the top there grade 0 in green, where the patient is in good health and has no infection. And then you can see the grades 1 and 2 are patients that are outside of the hospital, many of whom, in actual fact, do not display any symptoms. Patients that are grade 3, 4 and 5 were ones that were recruited into our study. Grade 3 patients were admitted to hospital but do not require oxygen. Grade 4 require oxygen, and grade 5 required what they call the high-pressure noninvasive ventilation. It's Grade 6 and 7 which is the real bottleneck and the real challenge for hospitals, when patients require high-pressure intertubular mechanical ventilators and intensive care units. The non-progression to that is of critical importance both for patients but also for the health care systems and the hospitals. Next slide, please. In the post-hoc exploratory analysis of our data -- and we have an awful lot of data from many patients in different geographies, ethnicities and health care systems. In this post-hoc exploratory analysis, we identified a substantial subset of patients that are affected by a more severe disease that seemed to benefit more from bemcentinib. In other words, those with the less severe disease, they naturally cleared the virus and recovered quite quickly on their own accord, maybe without any benefit from the standard-of-care drugs or bemcentinib. But it was the grade 4 and 5 patients that really saw a benefit. Indeed, as we analyze the data, we saw, in actual fact, there were very few grade 3 patients enrolled in our study, just 11, in fact. And as the time has unfolded, rarely are these grade 3 patients admitted to hospital, and they really do not require oxygen and generally have a much shorter stay in hospital. The second element that we observed was the patients who had a higher inflammatory status seemed to benefit more from bemcentinib. And this is determined by a protein called CRP, C-reactive protein. It's a standard marketer that's conducted on admission to hospital, and it's a marker of inflammation. It appeared that bemcentinib benefit is greater in patients with a higher baseline of inflammation, and we've set the threshold of 30 milligrams per milliliter. This, in actual fact, is quite a low threshold when we compare to other drugs that are being developed in COVID and are also using this to select patients. There's notably 1 or 2 drugs that have identified patients with a very, very high threshold and indeed, in turn, a much smaller patient population. So just a few words about ventilator-free survival. It's an endpoint derived from many studies in acute respiratory distress syndrome, and it's defined as being alive at day 29 and not deteriorating to require ventilation. Of course, the most important objective in treating COVID-19 patients is the prevention of death and then the prevention of more serious condition requiring ventilation and intensive care units. This is a great benefit to the patients, of course, and also great benefit to the health care systems and limited the resource requirements in order to care for them. Next slide, please. When we studied ventilator-free survival in our subset of patients, remember this was more than 50% of the patients on our study, in a very broad global study, what we can actually see is that patients treated with bemcentinib appear to be protected from early deterioration in day 2 or 3 as compared to the standard-of-care patients. And what I'm really referring to here is the blue line and the red line on the right-hand side here. You can see the blue line is the bemcentinib patients who seem to have a very constant, non-detectable probability of progressing to ICU and ventilation as opposed to the red line, which is the patients just on standard of care. And you can see here that there was quite a sudden drop in the early stages of this disease for those patients without bemcentinib. And indeed, this effect was maintained through 29 days, which, of course, is the important point by which we conclude that the disease has been cleared. When we looked at these subgroups of patients, we could see that ventilator-free survival in the bemcentinib group was at 90% as opposed to those on standard of care alone, which was just 72%. This is a significant and meaningful endpoint indeed. We haven't applied a lot of statistics here as this is a hypothesis testing rather than a predefined endpoint. We have put a p-value here of 0.06, which, for the statisticians that are tuning in too, tells you this is very close to statistical significance, which is a very, very encouraging result from such a small study population and also guides us as to what we may be required to do in terms of a confirmatory study. Next slide, please. Of course, ventilator-free survival is a very good predictor of overall survival. And although our study is quite small, by combining the numbers of patients on our study and also the survival data from the ACCORD study, we have a larger and more representative patient population and research group. What we can see here in blue is that the survival rate of patients taking bemcentinib is 96.5%, and those just taking the standard of care was 91%. Of course, the good news is that the vast majority of patients who enter hospital with COVID-19 actually do survive. But nonetheless, seeing this addition of 5.5% survival benefit from bemcentinib, from simply taking a one-a-day pill, we believe, is of great value. Next slide, please. So in summary, bemcentinib has the potential to be a treatment option for COVID-19 patients. Lest we forget, it's a simple, convenient one-a-day pill that combines well with other treatment. And indeed, the data that we are presenting is in addition and on top of standard of care that patients would have received on the study, including steroids and antivirals such as remdesivir. It has a favorable and enviable safety profile, and no safety signals or concerns were noted in the study. Of great importance, we think, is the fact that this novel mechanism of action is independent of the spike protein on the virus, and therefore, we would expect this effect to be retained even in the event of mutations in that spike protein, which may render the patients sort of resistance to the vaccine that's being rolled out worldwide. I just mentioned ventilator-free survival of the bemcentinib-treated patients of 90% versus 72% on the standard-of-care patients is a meaningful and valuable endpoint, particularly in such a large subset of patients. And of course, the survival benefit is also of great value. So with this data, we will continue our dialogue with regulatory agencies, government agencies and industry partners to determine the optimal way to further develop bemcentinib in COVID-19. Next slide, please. Our main focus, of course, has been and continues to be developing bemcentinib as an oncology agent. And our lead program in this indication is in acute myeloid leukemia, where we have been granted by the FDA orphan status and Fast Track designation. Work that we've conducted in the last year or so has allowed us to define a new and significant patient population, the relapsed AML patient populations, patients that have failed first-line treatment for which there is no effective standard of care. And we anticipate updating this data at the EHA conference on the 9th of June. Next slide, please. So we know that acute myeloid leukemia is a rare and aggressive cancer of the blood. It's a minority disease but still quite substantial with more than 20,000 cases in the United States each year, and it's about 1/3 of all leukemias. It occurs predominantly in the elderly and frail patient population over 60 years of age. The first-line treatment has evolved over the recent years such that more than 2/3 of these patients actually see a complete remission from this first-line treatment. However -- and this is the really important part. However, all of those patients relapse. Indeed, the median overall survival of these patients even with these advances in the first line is a little over 1 year, indeed 14.7 months. Having relapsed, the median overall survival for the patients is just 4.7 months, and the 5-year survival rate remains quite dismal at low single digits. As such, this AML market is poised for substantial growth over the next few years, really underpinned by development of novel agents such as venetoclax and potentially bemcentinib. Next slide, please. Identifying the correct position for a new therapeutic requires that we understand the treatment algorithm that these AML patients follow. Approximately 1/3 of the patients are fit enough and robust enough to withstand intensive chemotherapy, which allows their disease to be controlled before they are taken for bone marrow transplant and stem cell transplant. But more than 2/3 of the patients are unable to withstand intensive chemotherapy. Traditionally, the only treatment options for these patients has been low-dose chemo and palliative care. More recently, that's been supplemented with a new drug called venetoclax, which has resulted in this improvement in terms of complete response rate. As we can see on the right here, the complete response rate is 14.7 months. And in the little graph on the right there, you can see how that looks on the blue line and the green line, where there's an improvement of approximately 4 or 5 months. But as I mentioned before -- previously, all patients relapse, and having relapsed, there's no treatment option for these patients. We see great opportunity for bemcentinib to be used in combination with another low-dose chemo agent called LDAC to provide survival benefits for these relapsed patients. Next slide, please. So in our research to explore the potential of bemcentinib to treat patients with acute myeloid leukemia, we first of all did a Phase I study as a monotherapy, and on completing that, we established the safe and effective recommended Phase II dose. We also saw intriguing efficacy particularly in patients that we can identify with a biomarker, which we've called soluble AXL, sAXL. We're also able to confirm through some translational research that in actual fact, there's an immune-oncology effect going on here, and the immune system is promoted following the administration of bemcentinib to these patients. We then progressed to Phase II, where we continued the monotherapy study in both AML and myelodysplastic syndrome patients, and we tested bemcentinib in combination with the 2 low-dose chemo agents that are often used. One of them is a hypomethylating agent called decitabine, and the other one is a more traditional chemo agent called LDAC or low-dose Ara-C. We saw no great activity in combination with decitabine, but we saw significant activity in combination with LDAC. And a great intrigue was in the relapsed patients that we've identified have an unmet medical need. And indeed, cohort B2 and B5, which is an expansion of B2, is in the relapsed patient population. Next slide, please. So some preliminary data that we've presented is shown here, where we can see the 2 patient populations, the refractory and the relapsed patients, and these patients have received bemcentinib and LDAC. We can really see very little activity, in fact, no activity whatsoever in the refractory patient population, but there is quite intriguing activity in the relapsed patient population. Indeed, 4 of the 11 patients in the top there show complete response. You really would not expect to see that. That represents 36%. Although the numbers are small, but you really would not expect to see a complete response here. Moreover, these complete responses are seen quite late in onset, around month 3 and 4. Again, very unusual to see that from a chemo agent in this disease setting, but of course, to be quite expected with an immune-oncology agent. In other words, when bemcentinib is able to stop the actual signaling and we allow the immune system to start functioning properly, after 8 weeks or so, we start to see some effect from the chemo agent and we're starting to see complete responses. The swimmer plot that we're looking at now represents the time on treatment. This is a very good surrogate for survival. Clearly, if patients stay on treatment, it means that the patients are benefiting in some respect, and the doctors think that they should continue on the clinical trial. And that's a surrogate for overall survival, which would be the regulatory endpoint for this second-line relapsed patient population, which is still maturing, and we hope to update the markets with this -- and the scientific community with this data at the EHA conference in June. Next slide, please. I'd like to briefly talk about our ongoing work in non-small cell lung cancer in combination with pembrolizumab. Next slide, please. I think we all know that lung cancer remains the #1 cancer killer and a substantial unmet medical need, particularly in the relapsed setting, and it's a significant market, approaching $40 billion. Next slide, please. Similar to acute myeloid leukemia, understanding the treatment algorithm is really important for us in developing a therapeutic for non-small cell lung cancer. Whilst the first-line treatment option is now predominantly a checkpoint inhibitor such as pembrolizumab in combination with chemo, across the board of all disease or non-small cell lung cancer, that is not mutation driven. In the second-line setting, there really is a vacuum, and no effective treatment has been approved. We see great opportunities in the second-line setting but potentially also in the first-line setting, and we continue to do some considerations there. Next slide, please. So the study in second line that we're pursuing in combination with KEYTRUDA is in cohort A, chemo refractory patients; cohort B, checkpoint refractory patients; and cohort C, checkpoint-chemo refractory patients. Cohort A has completed recruitment and final analysis. Cohort B has finished stage 1, and we presented an update on that earlier this year. Stage 2 is recruiting now. And Cohort C has now completed recruitment, and we are pending the analysis of that first cohort of patients. Next slide, please. Just by way of brief summary and remind you of data we presented previously from cohort A, this is in patients that are checkpoint-naive, chemo refractory. We can see clearly when we differentiate the patients according to our biomarker, cAXL in this case, composite AXL, that it's the cAXL-positive patients that see the greatest tumor shrinkage. And indeed, cAXL negative really doesn't predict for any benefit whatsoever. Again, looking at duration of response, we can see it's the cAXL patient -- positive patients that have a very durable outcome, several partial responses and quite durable responses which, in turn, look to manifest itself in survival benefit. On the right there, we can see a fourfold improvement in progression-free survival in the AXL-positive patients over the AXL-negative patients. And at the bottom right, we can see this overall survival data, where AXL-positive patients have a median overall survival of 17.3 months as opposed to the AXL-negative patients, which is just 12 months. And indeed, the AXL-negative patients is consistent with the historic controls. So this is very intriguing data in chemo-refractory patients, checkpoint-naive patients. And whilst this may be a smaller patient population today, we think this information is quite informative for a potential first-line study. Next slide, please. We presented this data earlier this year at the world congress on lung cancer. This is in patients that are checkpoint refractory, again, in combination with pembrolizumab, similar pattern of result. It's the patients that are AXL positive in red that see the greatest tumor shrinkage. It's the AXL-positive patients that see the longest duration of benefit in the bottom figure here on the bottom left, where you see quite durable responses heading out quite a long way. And indeed, the presence or the absence of cAXL seems to predict for no benefit at all, if you look at that on the bottom left. This in turn has manifested itself in a 2.5-fold improvement in median overall survival with the AXL-positive patients, as seen in the top right. And what was very, very encouraging is the translational research conducted in parallel with this study elucidated that there were the presence of specific immunosuppressive immune cells, macrophages and dendritic cells that are AXL positive and the hypothesis there being, by inhibiting AXL, we prevent this immunosuppression by these unique immunosuppressive cells. And by blocking the activity of those cells, we allow the immune system to work more effectively. So we look forward to presenting more data from B2 and from cohort C later this year. Next slide, please. Turning our attention to tilvestamab, which is our anti-AXL monoclonal antibody. Next slide, please. So this is a functionally blocking, fully humanized monoclonal antibody. It binds to AXL and displaces GAS6, the ligand for AXL with high affinity. We have good preclinical data that demonstrates efficacy and developed a robust manufacturing process and a stable formula. Phase I study is complete and Phase II -- Phase Ib/II study is ongoing.Next slide, please. So the first study that we completed was in healthy volunteers. It's a single ascending dose study to confirm safety and pharmacokinetics. We evaluated 4 dose levels. We can see here 0.1 milligram per kilo through to 3 milligrams per kilo, and we also had a matched placebo to act as a control. The progression and -- the confirmation of safety and the progression between each of the dose levels was confirmed by a protocol steering committee. The outcome was that tilvestamab appeared to be well tolerated at all doses, including the top dose. The adverse events were mild, transient and comparable to the placebo, and there was no observed immunogenicity. There's also no observed stimulation of cytokine such as C-reactive protein. We mentioned that earlier, which is also a good sign, that the antibody will not cause an inflammatory response in the patients. The pharmacokinetics really showed that there was an above-dose proportional increase in plasma concentration in the ascending dose, and we saw detectable antibodies at biological relevant concentrations after day 18. That's important because it suggests that it may be possible to go to a 3 weekly dosing interval, which has significant impact on the cost effectiveness of treatment with bemcentinib -- sorry, tilvestamab. Next slide, please. So our development program is quite straightforward. Having completed the Phase I safety study, we're now toggling into a Phase Ib ascending dose study in patients, and that will confirm a recommended Phase II to take into -- Phase II dose to take into a Phase II study. Next slide, please. The trial that we initiated earlier this year, we're calling it trial 149-102, is a multiple ascending dose-finding and safety study that would also determine pharmacokinetics. The study is being conducted in platinum-resistant ovarian cancer patients, and that's really because we know that these patients have a high level of AXL expression. We're able to biopsy these patients upfront to confirm their AXL expression and therefore, help us with success in this study. We also have a good experienced global centers which are able to conduct mandatory sequential biopsies. And that means that we're going to be able to see -- however the plasma concentration increases, the pharmacodynamic or the impact of AXL on the tumor is able to be measured and monitored in real time. The upshot of that is that we should have a high confidence in our recommended Phase II dose as we progress from the safety studies into the efficacy studies. And we also should have a strong probability of proof of mechanism, which is very important for pursuing a regulatory strategy. So this study is ongoing now. And you can see on the right there, it's a fairly standard dose-ascending study. We're starting at 1 milligram, go to 3 milligrams. And then, in actual fact, we're going to 5 milligrams per kilo. And we have the option within this study to expand, to look for additional safety signals or indeed, efficacy signals. Next slide, please. At this point, may I hand over to Rune Skeie, our CFO, to talk you through our financials.

[Rune Skeie, Chief Financial Officer]

Thank you, Richard. I will give you an update on the key financials for the first quarter 2021. Next slide, please. We are reporting an operating loss of NOK 83 million for the first quarter. This is significantly higher than the first quarter 2020 and is due to costs of new clinical trials started up in the last few quarters. Particularly, in the first quarter, we had our COVID study running with a significant number of patients enrolled and also the start-up of the Phase Ib study in tilvestamab Richard just mentioned. In addition, we have continued developing the organization in preparation for late-stage development. Overhead cost is well managed with more than 85% of operating expenses spent on research and development activities. Next slide, please. The cash flow in the quarter was negative by NOK 63 million. The cash burn on operating activities in the quarter ended at NOK 71 million. And the average for the last few quarters was NOK 57 million, so significantly higher due to the cost in the first quarter of 2021. We closed the quarter with NOK 659 million in cash at the end of the quarter. Next slide, please. You probably are familiar with our analyst coverage, with -- both in the Nordic by Arctic, DNB and Carnegie but also in the U.S. by Wainwright and Jones Trading. The report from sponsored research, Edison Group, is available on BerGenBio website. And now pay your attention to the next event in the financial calendar this year. That's the half year report in August, the 17th of August. I'll then hand it back to you, Richard, to summarize the presentation.

[Richard Godfrey, Chief Executive Officer]

Thank you, Rune. Thank you. Next slide, please. So just a summary, a helicopter view of the value-driving milestones over the last year, where we initiated 2 COVID studies, we were able to report our interim data from our non-small cell lung cancer study, we've defined a significant and meaningful patient population of acute myeloid leukemia and highlighted some preliminary data that looks very encouraging and we progressed tilvestamab from Phase I into a Phase Ib study. And this year, as of yesterday, we announced and confirmed top line data targeting bemcentinib as a potential treatment for hospitalized COVID-19 patients. Looking forward, you can see that we still have a lot of work to do. We need to confirm how we will develop bemcentinib as a treatment for COVID-19 and hopefully secure a regulatory approval there. Similarly in acute myeloid leukemia. We need to confirm the endpoint of median overall survival and confirm that, that is significant. And we hope to have an update on that data in June. And with tilvestamab, we need to complete the safety studies and prepare ourselves for some Phase II studies. So a busy year ahead of us, but very good track record leading to this point. Next slide, please. And in terms of expected news flow and scientific content that we'll be presenting at conferences, you can see that there's a sequence of conferences ahead of us now with ASCO in early June. We're also presenting an update on tilvestamab in June as well. We'll present the AML data at EHA on the 9th of June. We've introduced 2 additional conferences in July, ECCMID and ASV. These are antiviral, anti-infective conferences. And more details of bemcentinib clinical data will be presented at the ECCMID conference in -- on the 9th of July. Then towards the end of the year, we hope to update with lung cancer data at the SITC, the immuno-oncology conference, in November and some more data on AML and potentially MDS at the ASH conference at the end of the year. So a busy conference schedule, lots of scientific data and clinical data to present. Next slide, please. So in summary, by way -- looking at the investment highlights for BerGenBio, I think we have a few points of great significance to reference here. First of all, of course, COVID-19. In the last 24 hours, we've spoken a lot about this, our top line data confirms safety, fewer deaths and increase in ventilator-free survival in a very significant patient population. We think this is of great value. We are developing, of course, 2 AXL inhibitors, bemcentinib and tilvestamab, in quite a diverse clinical program, although we are focusing now quite acutely on relapsed AML, the COVID indication and in second-line lung cancer. Near-term clinical milestones are linked to that focus that we have and also on defining a registration path going forward. Of course, we are underpinned by pioneering biology, and BerGenBio scientists and collaborators remain world leaders in understanding the role and function of AXL in mediating aggressive disease. And as an organization, we remain well-resourced with an experienced drug development team based in Oxford in the U.K. and also a network of industry and academic collaborators that we continue to work with. So with that summary, I'd like to close the presentation and take any questions that may arise. Thank you very much.

[Rune Skeie, Chief Financial Officer]

Yes, there are some questions. The first one is about the COVID study. When do you expect to release more data from the COVID study?

[Richard Godfrey, Chief Executive Officer]

Thank you, Rune. Well, I think I just illustrated on the previous slide, if we could show that, that our conference schedule suggests that early July, we'll be able to present more detailed clinical data at a conference. I've also referenced several times in presentations that the clinical data from our study and also combined with the clinical data from the ACCORD study will be collected -- will be analyzed separately and also together in a meta-analysis and draft for publication in a high-impact medical journal, and that work is ongoing right now. So more data, I think, is -- will be in that keeping. The determination of this very significant and meaningful endpoint, I think, was really the objective of our study and is the upshot of what we've learned. And I think we now need to be talking to regulators and government agencies about how we can take that forward and secure some sort of route to approval and used in patients.

[Rune Skeie, Chief Financial Officer]

Next question is if confirmative study in COVID-19, could grade 4 and 5 patients with CRP equal or higher than 30 be an inclusion criteria for the study?

[Richard Godfrey, Chief Executive Officer]

Most definitely, yes. That is the great learning that we've secured from this very, very broad real-world investigation that 020 was. I mean remember, no one's ever investigated bemcentinib as a treatment for viral infection. Bemcentinib is not an anti-inflammatory. It's not targeting the virus itself. It's actually blocking the mechanisms by which the virus functions. And confirming where that sees greatest effect with clinical meaning in a randomized study, which is what we've done now. So this was really quite a powerful exploration that we've conducted. Diverse geographies, variable health care systems, various ethnicities have all combined so that we have a compelling and significant learning here. So grade 4 or 5 patients, those that are at greatest risk in hospital, those with an elevated inflammatory state, also a great risk, they are the patients that see the greatest benefit and probably would not clear the disease themselves without treatment intervention. And I'd say our treatment intervention is on top of the standard of care that they received in the hospital where we saw this real great meaningful benefit, 90% avoiding ventilators and surviving out to 29 days. Those are real benefits. So most definitely, we would use CRP in grade 4 or 5 patients to recruit for going forward.

[Rune Skeie, Chief Financial Officer]

Did you see any difference in the patients that progressed to ventilator care in the high-risk group, if it was grade 4 or grade 5 patients that progressed? Also, given that the change in the curves show -- came very early at day 2, is there a risk that the patient might have been misclassified as they were admitted to hospital and that could explain some of the difference in progression rates?

[Richard Godfrey, Chief Executive Officer]

I see. So let me just read the question. I can see it on the screen now. Did you see any difference in the patients that progressed to ventilator care in the high-risk group? I haven't got that data at hand, so I can't comment on that, I'm afraid, at the moment. And that may be part of the fuller analysis. I think really, the question is -- oh, yes, sorry, sorry. Yes, of course. That's the survival data. That's the whole point of the survival data. I see the question now. Did you see any difference between patients that progressed to ventilator? Most definitely. The patients that took bemcentinib had a greater survival chance than those that did not, and that's the outcome. This is why it's so significant. But by not progressing to a ventilator, you're more likely to survive. And indeed, patients that did progress to ventilators are -- which almost certainly would have been the case before death. We know that bemcentinib actually did protect from death. The survival rate was 96.5% versus the 91% in the standard of care. So the answer is most definitely, we see a difference between those patients who progressed to ventilator. And that's the whole point of this chain of data, you don't progress to a ventilator and you live longer. And the second question was to do with the early benefit. And again, we see -- we flagged that because we think that's of great importance. Remember, the duality of mechanism that we're talking about here with bemcentinib. It prevents the virus from entering the host cells, and it stops the inflammatory suppression. So of course, by the time the patients have gotten to hospital, they already have a rampant viral infection within their tissues. They start bemcentinib with our loading dose on day 1, 2 and 3, and immediately, what we can see is that they no longer -- they see the non-progression. They don't get worse quickly. Whereas the patients that don't take bemcentinib, they seem to progress along a normal trajectory towards ventilator-free. And then -- having then stopped the viruses from entering the host cells, the second part of the mechanism, which is preventing the immunosuppression, kicks in, and then the immune system starts to work because the type 1 interferon is not suppressed. And then you start to see a clearance of the disease. So that's exactly in keeping with what we would have anticipated from the mechanism. Indeed, this result is complete confirmation that in the clinic, we seem to stop the virus from infecting the cells and which -- and we allow the immune system to start working and clear the disease. So we're very encouraged by this observation, which is why we mentioned on that slide that we have this early protection in day 2 and 3 in the patients that take bemcentinib.

[Rune Skeie, Chief Financial Officer]

And there's a question about patient recruitment. How difficult is it to get new patients into the cancer studies?

[Richard Godfrey, Chief Executive Officer]

Well, recruitment in the cancer studies is challenging for many reasons and possibly even more so in the last year, in the COVID pandemic. Patients are tending not to visit hospitals unless they have to, which makes recruitment and enrollment into studies more complicated. They -- the biotech sector has been a winner in the last 12 months in terms of resources, and lots of trials and lots of agents have been funded. So there's more competition for patients. So yes, recruitment is a challenge, and it's a challenge that we face as indeed does every biopharma company. But nonetheless, I think nothing speaks louder than compelling data and strong and good safety, and we see that. So our investigators that we speak to on a regular basis are very encouraged by our data. They are actually seeing that their patients are living longer by taking bemcentinib. And this is a chemo-free regime. They're not experiencing adverse events. So I think we're faring well. But I sense the frustration. Of course, I live it every day, that we wish that we could recruit patients faster and get results quicker. But we're -- I think actually, we're doing quite well, considering the landscape that we're operating in at the moment.

[Rune Skeie, Chief Financial Officer]

Then there's a question about AML. As seen with relapsed AML, bemcentinib also showed promising monotherapy responses in relapsed high-risk MDS. It seems like a low-hanging fruit given the monotherapy dosing and high medical need. Will the company seek to increase clinical development efforts in this patient group?

[Richard Godfrey, Chief Executive Officer]

Yes, we are still -- I can answer that, Rune. We're still evaluating monotherapy, but I think the effect from the combination with LDAC is greater, not just in response rate. It's part of understanding the role of AXL in the -- by inhibiting AXL, you stop the cells from surviving and you make them more sensitive to the chemo agents. So response rate will not be the regulatory endpoint for AML going forward. It will be survival benefit. And we're seeing very, very encouraging survival benefit in the combination with LDAC in this relapsed setting. So -- and that seems to be more substantial than what we've seen as a monotherapy, both in AML and in MDS.

[Rune Skeie, Chief Financial Officer]

And there's a follow-up question on the same topic. Is it possible to have a late-stage study setup given the data already produced? It's in MDS.

[Richard Godfrey, Chief Executive Officer]

Sorry, I didn't...

[Rune Skeie, Chief Financial Officer]

No, this is a question about if it's possible with a late-stage trial for the MDS patient population.

[Richard Godfrey, Chief Executive Officer]

For sure. I mean, I think we need to focus. The MDS study, I think, is very intriguing. It's particularly encouraging when we look at the data in combination with the biomarkers that have been identified. I think we just need to be focused. So I think the opportunity in AML is possibly one that we should land first. But we're certainly not closing the door to an MDS study where we see equally encouraging data there. So I think we just need to prioritize our activities and move forward.

[Rune Skeie, Chief Financial Officer]

There is a question on AML as well. How many patients are you aiming to enroll in cohort B5 of the AML study? And how many have been enrolled up to today?

[Richard Godfrey, Chief Executive Officer]

Okay. Well, we don't comment on enrollment status, but I think the cohort was slated to be 20 patients. So we should update on that in the not-too-distant future.

[Rune Skeie, Chief Financial Officer]

Next question, do you see any potential opportunity for the AML-targeting antibody tilvestamab in chronic COVID-19-related lung fibrosis?

[Richard Godfrey, Chief Executive Officer]

Maybe so, absolutely. I mean there's a lot of opportunities. I think once we understand the mechanism of AXL and how it mediates aggressive diseases and how potentially tilvestamab could play a role here, I think there's certainly an opportunity there. So again, it's about focus. I think our priority needs to be to get into a late-stage confirmatory study and on a track for registration as well as going broad in terms of exploring lots of different options. But most definitely, I think I alluded to it earlier in the presentation, that inhibiting AXL, I think, has great potential for the so-called sort of long COVID, pulmonary fibrosis type of lingering condition that we're hearing about so often now in the media from patients that have had COVID. And indeed, we're considering and discussing options for COVID study to include longer durations of treatment.

[Rune Skeie, Chief Financial Officer]

Can you discuss the expression of AXL on the epithelial lung cells of COVID-19 patient and potential disease-related overexpression?

[Richard Godfrey, Chief Executive Officer]

Well, it's -- well, we know -- let me read the question, if I can see it on the screen. Can I? Sorry, I need to read the question. It's a little bit confusing. I can't read it. Could you help me read it again, please?

[Rune Skeie, Chief Financial Officer]

Yes. Can you discuss the expression of AXL on the epithelial lung cells of COVID-19 patient and potential disease-related overexpression?

[Richard Godfrey, Chief Executive Officer]

Okay. Great. I don't -- just thinking for a moment. I don't know that we have patient data to confirm -- to discuss on AXL expression of the lung epithelial cells from COVID patients. It's not easy to get these samples from patients. Preclinical models, definitely, we know that AXL is significantly upregulated in the epithelial cells of animals that are affected with COVID viruses. And then with regards to AXL expression in treatment, we are in parallel looking at our biomarkers, particularly soluble AXL, sAXL, it's a blood-based marker, as a potential indicator of benefit in COVID patients, either as one that would predict benefit or one that could show pharmacodynamic that patients are benefiting. So we're looking at that in parallel. To be -- at this moment in time, I think we have sufficient definition of a patient population without introducing a new biomarker. C-reactive protein is a very well-established blood-based marker that every hospital uses and tests patients on admission as a guide to see the inflammatory status of patients and understand how severely ill they are. We could certainly do a longitudinal study in the future, but I don't think we need to consider that at the moment. We have a very clearly defined patient population right now.

[Rune Skeie, Chief Financial Officer]

Then there's a question about tilvestamab on the ongoing study. So how long a time will the review process between dosing be to increase the stake?

[Richard Godfrey, Chief Executive Officer]

Oh, it's a standard -- that's a good question, very technical question. I believe it's 2 cycles, 28 days, I believe, if I remember correctly. I don't know if it says on the slide. I believe it's 2 cycles. So you dose the patient. You wait 28 days so they receive multiple doses. Then the protocol safety review committee then confirms safety and pharmacokinetics because, remember, that's critically important as well and then confirms progression to the next dose level.

[Rune Skeie, Chief Financial Officer]

Then there's a follow-up question on the COVID study. So on the patient that progressed, was it grade 4 or grade 5 patients that progressed?

[Richard Godfrey, Chief Executive Officer]

Grade 4 or grade 5 that progressed to -- I don't quite know. So obviously, grade 4 patients will progress to grade 5, and grade 5 patients will progress to grade 6. So the majority of the patients enrolled in this study were grade 4, so I presume the majority of the patients would be grade 4. I don't know that I've got a breakdown by grade. In actual fact, in the study, as I recall, that we recruited, there were just 11 grade 3 patients and 11 grade 5 patients. The vast majority of the patients were grade 4 that came on the study, which again is exactly in keeping with the patients that are enrolled in hospitals worldwide. They are the patients that have a real need for oxygen, and what you desperately do not want is for them to progress onto forced oxygen or ventilation. So I think this is why this is such a powerful observation that we've made now, that by administering bemcentinib to these patients, you actually prevent or reduce the need to progress onto high-flow oxygen or ventilators.

[Rune Skeie, Chief Financial Officer]

I believe this question is not specific into indication. But if you enter a Phase III study, are you at this time financially -- able to finance this alone? Or will you be required to involve a partner?

[Richard Godfrey, Chief Executive Officer]

That's a very big open-ended question. I think it depends on the study, the study dynamics, how large the study is and what else we want to do in parallel. I think you confirmed earlier, Rune, what our cash position was at the end of quarter 3 and what our typical burn rate is. So it really depends on the scope of the Phase III study. Partners are very welcome because not only do they provide capital, but one would hope they also provide some operational and regulatory support as well. So we continue to support -- to communicate with potential partners on a regular basis.

[Rune Skeie, Chief Financial Officer]

Okay. I think that's end of the Q&A session.

[Richard Godfrey, Chief Executive Officer]

Very good. Thank you, Rune. I want to say thank you to all that tuned in, and I look forward to updating the market with news as we progress during the coming weeks and months.