Bergenbio ASA

OSE:BGBIO

Earnings Call Transcript 2020-Q4

[Richard Godfrey, Chief Executive Officer]

Good morning, and welcome to BerGenBio's 2020 Quarter 4 and Year-End Report, Highlights and Financial Summary. My name is Richard Godfrey, and I'm the CEO of BerGenBio. I'm joined this morning by Rune Skeie, our CFO; and Hani Gabra, our Chief Medical Officer. Our presentation and our quarterly report can be found on our website. Next slide, please. I should draw your attention to our forward-looking statements and safe harbor comments on Slide 2.Next slide, please. We have quite a broad agenda today. To introduce you to our recent highlights, a summary of our biotechnology around AXL tyrosine kinase and our lead candidate bemcentinib, an update on our clinical trials, a comment on tilvestamab, our anti-AXL monoclonal antibody, a report on our financial status and an outlook for 2021. Next slide, please. As a way of a reminder and introduction to BerGenBio, we are world leaders in understanding the role and function of AXL tyrosine kinase, specifically as it mediates aggressive diseases, including immune-evasive therapy resistant and metastatic cancers, fibrosis and viral infections. We are developing 2 selective AXL inhibitors, bemcentinib, our oral once-a-day hydro selective inhibitor of AXL. And tilvestamab, our anti-AXL antibody. Bemcentinib is in a broad Phase II development program. And in parallel, we're developing biomarkers and companion diagnostics. As an organization, we are listed on the Oslo Exchange under the ticker BGBIO. We have multiple clinical collaborations in the United States, the U.K. and other parts of the world. We're an organization of 49 staff, predominantly located in Oxford in the U.K., although in Bergen, Norway is our head office and our research facilities. We closed quarter 4 2020 with NOK 722 million on our account. Next slide, please. So quarter 4 and recent highlights. Well, as for all of 2020, it was an unprecedented year and had not least of all challenged by the pandemic that's affected so many people and so many businesses. And I'm pleased to be able to report that we continued in spite of that, making strong progress with our business and our development objectives. In October, we announced that we enrolled the first patient in our sponsored study in COVID-19 patients in South Africa and India. And we also presented some early data on our anti-AXL antibody, tilvestamab. Also in October, a further clinical trial initiated. This is in the so-called MiST study in meso -- malignant pleural mesothelioma. This is a collaboration with Merck, combining bemcentinib with pembrolizumab. In November, we hosted a virtual R&D Day, and details of the presentations can be found on our website.We also announced that we were selected to make an oral presentation at the prestigious SITC immuno-oncology Congress. In December, we continued to update the world with data from our studies in leukemia and myelodysplastic syndrome at the American Society of Hematology Congress, and we also presented at the DNB Nordic conference. Also in December, the ACCORD 2 study also in hospitalized COVID 2 patients restarted having paused for a funding hiatus earlier in the year. And more recently, in January, we were selected to make an oral presentation of our lung cancer study at the World Congress of Lung Cancer, again, a virtual conference this year where we also presented clinical and translational updates from our second line study in non-small cell lung cancer. So a busy quarter, and we continue to make strong progress with our development programs.Next slide, please. Just a reminder on the target of our therapeutics, which is a protein called AXL. Next slide, please, Slide 7. We've known and continue to be assured that AXL is an independent negative-prognostic factor in a broad variety of cancers. If you're unlucky enough to have cancer and AXL is upregulated and mediating that disease, your survival outlook is significantly worse, as indicated by the red lines on these survival curves. And this pattern seems to be consistent across most cancers.Next slide, please. Our drugs, bemcentinib and tilvestamab selectively inhibit the actual signal. On the right here, we can see a graphic of the receptor tyrosine kinase AXL as it crosses the cell membrane. And you can see bemcentinib works at the intracellular part of the receptor and tilvestamab at the extracellular part of the receptor. We know that AXL mediates fibrosis, viral infection and cancer.Next slide, please. In the counter setting, AXL is a key survival mechanism where it's hijacked upon cancers when their environment becomes hostile. AXL expression is low under normal healthy physiological conditions. But when that environment where the cancer cell is living becomes hostile, whether it's hypoxic, inflamed, stressed by chemo agents or inflammation, AXL is upregulated as a way to survive the cancer cells. So on the right, in the center here, we can see a graphic that depicts the tumor with all the different cells that constitute the tumor, and the various stress factors that lead to AXL steadily being upregulated. On the right, we can see the cancer cell breaks away, becomes stellite in appearance, acquires resistance to drugs and indeed, hypoxia and other agents in the microenvironment, evades immune cell death and can also metastasize. On the left, we graphically represent that AXL is upregulated on cells of the immune system that are also present in the tumor. And in doing so, they suppress and stop the immune response that otherwise would clear the cancer cells.Next slide, please, Slide 10. With this knowledge, we've developed a composite AXL diagnostic assay so that we can simultaneously measure AXL expression on tumor cells and immune cells within the cancer. And by doing so, we're able to identify the patients who are most likely to benefit and respond from AXL inhibition. In other words, we can find the patients whose tumor is using AXL to survive. And by inhibiting AXL, we can prevent that survival and tumor clearance.Next slide, please, Slide 11. Over recent months, we've announced and presented several times that recent discoveries and learnings, in particular, made by Professor Wendy Maury of the University of Iowa, have told us that AXL is targeted by envelope viruses to enter the host cells and to dampen the viral immune response that we otherwise would not. This is particularly important in today's pandemic where the SARS-CoV-2 virus is able to bind to AXL and get taken into the cell and the vesicle, as depicted on the left here of the graphic. And once inside the host cell, is able to hijack the host cell. But at the same time, it leads to an upregulation of AXL, which, in turn, leads to a dampening of the immune response that otherwise would be mounted by the host cell and environment. This mechanism and a clear understanding of how AXL mediates viral entry and immune supression underpins our clinical trials in COVID-19 patients.Next slide, please, Slide 12. This is a summary of the independent key opinion leaders that presented at our virtual R&D Day in November, and I direct you to use these presentations at our website.Next slide please, Slide 13. An introduction to bemcentinib, our first-in-class selected and potent orally available AXL inhibitor.Slide 14. Here it is, it is produced as a capsule all the biotechnology is in the engineering of a selected molecule. It's potent. And that we today, we manufacture it at scale, ready for late-stage Phase III studies and potentially even early commercialization. It's a robust molecule, and we simply manufacture as a capsule to package it in a pot at the moment. It's administered once a day. And its mechanism of action is synergistic with other therapies. We now have extensive experience of administering this medicine to patients and growing confident in its safety, and also its tolerability by patients has been taken over long periods of time and indeed in combination with other drugs.Our development program. Next slide, Slide 15. Our development program that we're sponsoring focuses on leukemia, acute myeloid leukemia, and myelodysplastic syndrome. Non-small cell lung cancer in combination with KEYTRUDA or pembrolizumab in various settings. We are sponsoring a study in COVID-19, as you possibly are aware, and also developing tilvestamab.But in order to explore -- next slide, please. In order to explore the full potential of our AXL inhibitors, we're also supporting a number of investigator-sponsored studies, where we're testing bemcentinib as a monotherapy in combination with checkpoint inhibitors, targeted agents and chemo agents with a variety of partners at different locations around the world. Next slide, please, Slide 17. When evaluating the competitive landscape, it's worthy to note that selective actually inhibitors are the ones that we need to pay attention to. By selectively inhibiting AXL, we are able to identify the patients using our diagnostics and are most likely to benefit from our drug. We're able to combine successfully with other drugs as there are no overlapping toxicities and the drugs are very well tolerated. BerGenBio's assets, bemcentinib and tilvestamab, are clearly, and remain the most advanced and the most broadly developed selective AXL inhibitors in the world today. Although there are other assets being developed at earlier stages.Next slide, please, Slide 18. I'd like to give a clinical trial update now, particularly following data that we presented at the ASH Conference in December. Firstly, let's talk about our data in acute myeloid leukemia in patients that have relapsed from their first-line treatment where they are administered bemcentinib, in combination with low-dose Ara-C, which is a chemo agent. Again, I'll remind you that bemcentinib has been granted orphan status in AML and fast-track designation in AML by the FDA. We know that acute myeloid leukemia is a rare and aggressive blood cancer. It is a natural fact, the largest of the leukemias. It's generally a disease of the elderly, more than 2/3 of the patients are over 60 years old. Recent developments in treating acute myeloid leukemia have led to significant increase in the market size, and we're pleased to be part of that market development.Next slide, please, Slide 20. We have a thorough understanding of the role that bemcentinib plays in modulating acute myeloid leukemia and myelodysplastic syndrome. We know that AXL is associated with core survival in patients, we know that AXL mediates an immunosuppressive niche in the bone marrow where the disease originates from. And we also know that AXL promotes the release of the undifferentiated graph cells, which is the root cause of the disease. So by inhibiting AXL, we would hope that we can provide increased survival for these patients.Next slide, please, Slide 21. We have conducted, indeed, coming to the end, quite a broad Phase I/II study, evaluating bemcentinib in acute myeloid leukemia and MDS. This initially started as a Phase I study where we confirmed dosing and sourced an early signals of efficacy. We then expanded into a Phase II study, where we continued to test bemcentinib as a monotherapy. We're also in combination with drugs that are routinely used in these patients. Of particular interest and an attractive signal, was seen in combination with LDAC in Cohort B2 that was subsequently expanded to Cohort B5.Next slide, please, Slide 22. When we look at the data from Cohort B5, this is a combination of bemcentinib and LDAC in patients that are relapsed, i.e., that fail their first line of treatment. We can see quite a significant difference between the relapse and the refractory patients. Indeed, the relapsed patients saw -- 8 out of 11 patients or 73% of the patients showing clinical benefit, meaning that their disease was being controlled and not progressing. Furthermore than that, nearly half for the patients, 45% of the patients, saw a overall complete response meaning that their blast count was falling to less than 5%. It's also noteworthy that responses were seen late also indicating this was an immune-mediated response. And the duration of the treatment was quite substantial, in excess of 6 months and still counting. We see this data as very encouraging and identifying this as a potential route to registration. And we will update the markets with that in the coming months.Clinical trial update for relapsed high-risk MDS. This time we're treating these patients with bemcentinib monotherapy.Slide 24, please. Again, it's a leukemia. It's a cancer of the blood. 84% of these patients are with high-risk MDS. And again, it's a market that's seen substantial growth over recent years, clearly underpinned by innovation. What's noteworthy is that the median overall survival of patients that have failed their first-line treatment is just 5.4 months, quite a dismal outlook for these patients. And this is where we see a great unmet medical need that we believe we can offer benefit.Next slide, please, 25. We know that AXL mediates proliferation survival of the leukemic cells within the bone marrow, which is what's driving the disease. And also resistance to the chemotherapeutic agents that they otherwise would take in the first line.Next slide, please, Slide 26. Ex vivo models have indicated that by inhibiting these MDS stem cells with bemcentinib, we can actually see a reduction in their proliferation, supporting the rationale for treating these patients with bemcentinib monotherapy. Slide 27, please. Here, we can see the clinical data from the BERGAMO study where 22 high-risk MDS patients were treated with bemcentinib monotherapy. We can see that the overall response rate was 36%. The CR rate, the complete response rate was 18%, and the duration of response was 9 months and counting, offering a very, very attractive option for these patients who otherwise would be facing a survival outlook of 5 months or less. What was of particular interest here was that by looking at our soluble biomarkers, in other words, biomarkers in blood, we were able to identify the patients that saw benefit, as indicated by the orange marks on the left of the graph here. And on the right, we can see clear difference between the orange signals and the blue signals indicating that we can clearly distinguish the patients that are seeing benefits, and therefore, showing survival benefit as opposed to the patients on the -- in blue that show no benefit. And therefore, we do not think to benefit from an AXL inhibitor. This data is also very encouraging and still subject to some more resets but again, a possible route for registration. Next slide, please, Slide 28. This is a clinical update of our trial in refractory non-small cell lung cancer. This is a clinical trial where bemcentinib is combined with pembrolizumab, and it's completed in collaboration with Merck. Next slide, please, Slide 29. By way of a reminder, we're conducting this study in 3 cohorts: Cohort A is chemo refractory patients, Cohort B is checkpoint inhibitor refractory patients and Cohort C is patients that are refractory and having taken chemo and checkpoint inhibitors. And you can see that B2 and C1 continue to recruit patients now. It's possibly fair to mention that in actual that recruitment has somewhat slowed here as a result of the pandemic, but continues. And we're quite optimistic that we will be able to report out some data later this year as patients are being recruited, and we're able to monitor their compression. Slide 30. As summary of the clinical outcomes from Cohort A, whilst this cohort may not be so relevant in today's standard of care, we think it's very important as it informs potential first-line treatment options. Quite clearly in this data, we can see that patients that are actual positive, in red, see actual positive are the patients that see the greatest benefit with the greatest amount of time. Indeed, the survival benefit for these patients is 17 months as opposed to just 12 months to be AXL negative. And the progressing free survival, the PFS, was fourfold greater than the AXL positive patients. Slide 31, please. In developing bemcentinib plus KEYTRUDA in checkpoint refractory patients, it's appropriate that we have a very clearly defined, precise and specific definition of patients that are in the checkpoint refractory. And these are patients that have previously seen the benefits, have subsequently relapsed. That relapse is being confirmed and then come onto our trial without taking any other medicines intravenously.Slide 32, please. This data was presented in the middle of last year. And again, we're differentiating the patients according to their cAXL score. I think we can see clearly here that the cAXL positive patients in the top part of the graph, are those that see the greatest benefit and response and the cAXL negative are really not seeing any benefit at all. They came on the study with a progressive disease, meaning that their tumor was growing. And in the vast majority of these patients, the tumor continued to grow. By inhibiting -- by giving an AXL inhibitor to those patients, they saw no benefit. As opposed to the AXL positive patients where the vast majority of patients saw meaningful benefit and for quite a long duration of time. In actual fact that data is stilly mature to the survival benefit for these patients that the progressing free survival was 2.5x longer in the AXL positive patients.Of great interest was the transformational findings when we analyzed these patient's tumor samples. By doing a deep sequence analysis, we saw that patients that benefited had gene upregulation associated with AXL, epithelial-to-mesenchymal transition and also a species of immune cells called macrophages and dendritic cells that are known to be immunosuppressive.Next slide, Slide 34, please. We know that these AXL-positive immune cells drive T-cell dysfunction. And as you know, T-cells are the warhead, and the foot soldiers of the immune system that aptly seek and destroy cancer cells. When AXL is upregulated in the dendritic cells and the macrophages, it exhausts and caused the T-cells to be dysfunctional, which is a very, very interesting observation in keeping with other publications in high-profile journals during the year. And also confirms that bemcentinib may reverse a quite resistance to checkpoint inhibitors by targeting these immunosuppressive immune cells. And as we know, we continue to recruit our study in checkpoint refractory and checkpoint chemo refractory patient populations.Next slide, please, Slide 35. So we clearly know that AXL defines poor prognosis in patients and the non-small cell lung cancer patients. And the cAXL positive patients have significant enhanced survival when combined with bemcentinib and KEYTRUDA in checkpoint naive and checkpoint refractory patients. Indeed, in these 3 Kaplan-Meier plots here, we can see that the survival trajectory of patients that are AXL positive. On the left-hand side would otherwise be worse than the AXL negative is actually reversed when we are in the -- when we're combining checkpoint inhibitors and bemcentinib in these 2 cohorts. Next slide, please, Slide 36. Clinical update on COVID-19 studies. We are conducting 2 studies, ACCORD-2 trial, which is an investigator-sponsored study in the United Kingdom. And BGB-20 (sic) [ BGBC020 ], which is a BerGenBio-sponsored study in India and South Africa. Slide 37, please. We know that AXL facilitates SARS-CoV-2 viral entry through this endosome or vesicle formation, as you can see on the left here. And in turn, we see an upregulation of AXL that dampens and suppresses the type 1 interferon immune response that otherwise would help our warriors clear viral infection. So the rationale is strong and solid and continues to be validated not only by Wendy Maury but also by others. Next slide, please, Slide 38. You're aware that we are conducting these 2 studies, the ACCORD study is a multicenter Phase II adaptive design randomized study across the United Kingdom. Bemcentinib is 1 of 3 drugs that have been evaluated simultaneously in this study, and recruitment is ongoing at the moment. Study 20 in South Africa and India is showing strong recruitment. The medicine is reported to be well tolerated by the patients, which is being confirmed by 2 independent data monitoring committee meetings in recent months. And we anticipate being able to release top line clinical data towards the end of quarter 1 this year.Slide 39, please. Just a reminder of the objectives of this study. So the primary objective of this study was to evaluate the efficacy of bemcentinib, and add it to the standard of care treatment for COVID-19 patients. And as you are aware the standard of care treatment has evolved during 2020 and new drugs have been added in. Bemcentinib is a selective inhibitor of AXL, and it seems to be well tolerated and combinable with these standard of care drugs. So the standard of care has evolved. And the idea was to see that patients will be released from hospital quicker or indeed not progress by taking bemcentinib.The key secondary endpoints that are also very, very important are also being monitored. These include being able to monitor and evaluate the ability to prevent deterioration of the patients, to evaluate the number of oxygen-free days and also to evaluate acute respiratory syndrome with patients that are in hospital and include -- also including the viral mode. So there are multiple key secondary endpoints that are physiological and allow doctors to make assessments as to whether or not the patients are doing better when taking bemcentinib.And then beyond that, we have exploratory endpoints that help us understand how bemcentinib is able to modulate the disease and also modulate the way in which our bodies are able to handle the disease, by analyzing a whole range of different parameters, cytokines, viral load, et cetera. So we would hope to have a collection of these data points and information to report by the end of quarter 1.Slide 41, please. So we can see that bemcentinib is being executed in a broad development program. As of monotherapy, in combination with checkpoint inhibitors, chemo agents, targeted agents and also the epigenetic agents, the hypomethylating agents. We certainly see that bemcentinib has the potential for being a foundation for cancer therapy in the future.Slide 42, please. Tilvestamab. Tilvestamab is the anti-AXL monoclonal antibody. Slide 43, please. It's a functional blocking, fully humanized monoclonal antibody. It binds to AXL in the extracellular domain and has demonstrated strong antitumor efficacy in vivo models. It has a high affinity and indeed displaces GAS6. We've developed a robust manufacturing process and formulation, and we have a stable product formula. We've now completed Phase I studies, and are now progressing to a Phase Ib/IIa study, which is a multiple ascending dose in patients, and we'll be announcing that very soon. Slide 44, the finance report. Thank you. And I hand over to Rune.

[Rune Skeie, Chief Financial Officer]

Thank you, Richard. My name is Rune Skeie. I'm CFO in BerGenBio. And I will give you an update on the key financial for the fourth quarter and the full year 2020. Next slide, please, Slide 45. We are reporting an operating loss of NOK 72 million for the quarter and NOK 261 million for the full year 2020. This is significantly higher than the fourth quarter and the full year 2019 due to start-up costs of new clinical trials, higher drug manufacturing expenses and organization development in preparation for late-stage clinical trials. Overhead cost is well managed with over 80% of the operating expenses spent on research and development. Next slide, please, Slide 46. Net cash flow in the quarter was negative by NOK 53 million. Cash burn on operating activities in the quarter ended at NOK 56 million, slightly above the average for the last few quarters. And we closed the year with NOK 721 million in cash.Next slide, please. I will ask you to pay attention to the financial calendar for 2021. Our annual report will be released on the 25th of February, and the Annual General Meeting is scheduled for the 19th of March. And next financial reporting and presentation for the first quarter 2021 will be given on the 19th of May. Next slide, please. At last, I would like you to remind you about the broad analyst coverage we have with Wainwright and Jones Trading covering from the U.S. Arctic, DNB and Carnegie is covering the Nordic area. And we also have Edison in the U.K. and reports from Edison is available on BerGenBio website.The takeaway from this financial section should be that we have a strong cash position at year-end and good cost control. And I will then hand it back to you, Richard, to summarize the presentation.

[Richard Godfrey, Chief Executive Officer]

Thank you, Rune. Slide 49, 2020 highlights and outlook. So in spite of the challenges that everybody faced in 2020, mediated by the pandemic of COVID-19, we saw a very, very busy and successful year. We started the year in January, confirming that we met the efficacy endpoint to progress our lung cancer study from stage 1 to stage 2 in paces that were refractory to lung -to checkpoint inhibitor. Early in the year, we announced that bemcentinib was selected by the U.K. ACCORD platform to be tested in COVID-19 patients. And during the first half of the year, we were successful in raising NOK 740 million from the continuing operations of our business. We announced an encouraging interim translational data from our lung cancer study during the year at various conferences, and we also were pleased to have announced that we initiated a monotherapy study in glioblastoma, a tumor of the brain, in the United States. In October, I think, we announced the initiation of our sponsored study in COVID-19 patients in South Africa and India. And as I mentioned earlier, this study is recruiting strongly. We announced December, the efficacy endpoints were met in the BERGAMO study, in particular, interest with the treatment of high-risk MDS patients with bemcentinib monotherapy. And we also announced very encouraging interim clinical data in our Phase II study in bemcentinib plus LDAC in relapsed AML patients. So a busy year, lots of ongoing activity and lots of data being presented. As we turn our attention to 2021, you can see that we are well positioned for continued success. Our pipeline is promising with the 2 first-in-class AXL inhibitors in broad clinical development, and we have encouraging clinical proof of concept, safety and translational data in bemcentinib in multiple indications.The science underpinning the COVID-19 studies is robust. We look forward to updating the market with the efficacy data. It would appear as though bemcentinib is well-tolerated thus far in these patients as confirmed by our independent data monitoring committee. Upcoming data to look out for would be: survival data in our leukemia patient population received in bemcentinib and LDAC. Top line clinical data for our ongoing study with bemcentinib in combination with the checkpoint inhibitor, KEYTRUDA, and refractory non-small cell lung cancer data, and as previously mentioned, their clinical data. And also the translational data from our COVID-19 studies.From a strategic point of view, we see AML and MDS indications as offering significant patient benefit in an area of unmet medical need. And these are under serious consideration for late-stage registration directing studies, and we will brief the markets when we have a clear plan forward there. And of course, tilvestamab, a monoclonal antibody against AXL, which has been lagging behind somewhat in its development trajectory will progress into Phase Ib/IIa studies very soon. And as a business, of course, we remain well-funded closing 2020 with NOK 722 million on our account. So in addition to the business announcements that we'll make during the year, we always have a busy schedule. Slide 52, a busy schedule of anticipated news flow at various conferences. You can see in addition to the usual cancer conferences where we have presented data, such as the ASCO Conference, for solid tumors, the EHA Conference, the European Hematology Association, World Lung and SITC and ASH. You also anticipate being able to present later and the information at virology and anti-infectious conferences during the year. In particular, we have targeted some conferences in July.So with that, I thank you for your attention and open for any questions.

[Rune Skeie, Chief Financial Officer]

So we have some questions from -- according to the COVID trials. So the first one is, if results from stage 1 ACCORD and BerGenBio study 020 shows significant effect and benefit. Do you expect that to be enough for bemcentinib to be set in a treatment against COVID-19 or would additional studies be needed?

[Richard Godfrey, Chief Executive Officer]

Well, of course, it's a very good question. Thank you. Of course, the answer relies in the data. I think to be fair, the studies are still rather small. And the inclusion criteria for patients is rather broad. This is very much evaluating a spectrum of patients from the stage 3 who are serious enough to go into a hospital, but not necessarily requiring oxygen through to patients that are very, very ill and about to be put onto a ventilator, and also being conducted in multiple countries where standard of care is different and pressures on health care systems are also different. So I think in answer, in summary. I think probably we'd need to do additional studies. But we've seen some quite brave moves taken by regulators offering conditional uses. So I think we need to wait for the data. But my expectation would be that an additional trial will be required in identifying patients more specifically.

[Rune Skeie, Chief Financial Officer]

And a question about if we will inform the market when the 2 studies is fully recruited?

[Richard Godfrey, Chief Executive Officer]

Yes, we will. Yes.

[Rune Skeie, Chief Financial Officer]

Sorry. Yes. It's one question about the data monitoring committees. So the question is if there are 2 different monitoring committees? Or if the same committee have actually met twice into releases in late June.

[Richard Godfrey, Chief Executive Officer]

Yes. No. We've reported on the data monitoring activities for the committee that is associated with our sponsored study. The ACCORD study is a study that's been sponsored by the University of Southampton. They also have an independent data monitoring committee. As I say, we're not necessarily at liberty to communicate their findings, but they've been quite transparent. And I would anticipate that they will convene a data monitoring committee, and we'll announce continued recruitment or anything else once that's been convened. But the data managing committees that we've announced about are specifically related to the studies that BerGenBio is sponsoring, and that's the steady number 20 in South Africa and India.

[Rune Skeie, Chief Financial Officer]

And then we have some questions about the potential Phase III studies. When that could be announced? And which indication will be the first?

[Richard Godfrey, Chief Executive Officer]

Yes. Well, as alluded to on Slide 51 of the strategic outlook, I think we have a growing confidence in the data that we're seeing in the leukemia settings in combination with LDAC in AML, monotherapy and high-risk MDS. We are still -- that data is still maturing. We are consulting with regulators as to a registration path. And I think when all of this becomes apparent, which I believe will be during this year, we will then be able to announce our clear plans and time lines for initiating registration studies.

[Rune Skeie, Chief Financial Officer]

And then it's a question about probably to the financials. So that the production has increased. If you can give more details about the manufacturing of the drug.

[Richard Godfrey, Chief Executive Officer]

Yes. Has the production increased? Could you elaborate?Yes. Well, we've -- I think we announced last year that we've moved from a small-scale manufacturer to a global manufacturer that has the capabilities and capacity to produce material suitable for Phase III studies and early commercialization. That production and transfer is ongoing. Larger scale. Lots are being manufactured in India, Canada, and also in the United States. So it's a global supply chain. And it's a big project. No red flags. And we're confident that we'll have sufficient growth for our development needs. The potential requirements should we have early commercialization, will obviously put strains on the manufacturing supply chain. And we have been working with Paramount and others to have a contingency there.

[Rune Skeie, Chief Financial Officer]

It's a question about COVID again. Given bemcentinib unique dual mechanism of action in COVID-19, how do you see it faring against emerging variants?

[Richard Godfrey, Chief Executive Officer]

Well, that's a really nice question. Thank you for that question. So yes, it's interesting because there's not -- as we know, these variants that we're hearing so much about in the news are all variants in the spike protein. And the spike protein attaches to the ACE receptor, and the ACE receptor is responsible for bringing the virus into the host cell. What Wendy Maury has said nicely so is that there's a massive increase in infection when the ACE receptor is facilitated by AXL, that also is a cell ACCORD co-receptor. We have no knowledge and no data to suggest that AXL will -- the binding of the COVID to the PS receptor, which in turn connects to the ACE receptor is affected by these mutations. So we absolutely think that there will be no change in the role and function of AXL with these new barriers. Not to say that there are variants that we haven't identified, that won't escape the PS receptor and the AXL, and they will be, but we have no knowledge of them. And there's no reason why we think that there will be that selection pressure at the moment. We are continuing to work to investigate this, but we have no results to report, yet.

[Rune Skeie, Chief Financial Officer]

Also a follow-up question on the COVID. So with top line data from the COVID-19 study expected in Q1 this year, can you discuss the plan of action following a potential successful readout? And how have you been preparing for it in terms of additional Phase III trial, approval and large scale manufacturing?

[Richard Godfrey, Chief Executive Officer]

Yes. So again, as we discussed earlier, it really depends on the data. The ACCORD study and our study is rather broad in its inclusion criteria. So it's a -- we must wait for the data and understand what it's teaching us before we can have any specific plans. As mentioned earlier, my anticipation is that an additional trial would be required to confirm the role and function of AXL benefit of AXL inhibition with bemcentinib in a more precise patient population with more clearly defined endpoints. But we need to wait for the data to guide us as to what to do next. I mentioned earlier that we have had and continue to have conversations with our supply chain in the event of sudden increase in demand and say that, that certainly will be challenging. But nothing is impossible, particularly in these COVID days.

[Rune Skeie, Chief Financial Officer]

Also a COVID-19 question, do you believe you can get an emergency use approval if Phase II result is good enough?

[Richard Godfrey, Chief Executive Officer]

Again, similar to the answer to the last one, I think emergency authorization is certainly an ambition. I would anticipate and I don't want this to be misinterpreted. I would anticipate that we would still need a little bit more precise data in order to confirm emergency use. But it all depends on the data. The data is starting to roll in now with a substantial number of patients recruited, that we can start to interpret it. But it is a randomized trial and it is statistically powered. So we do need to wait for the data in order for us to interpret what is evident.

[Rune Skeie, Chief Financial Officer]

Next question is, can you -- individuals buy bemcentinib on own risk without doctor approval?

[Richard Godfrey, Chief Executive Officer]

No. And that's really not a good idea. This is an experimental medicine, and only available in very tightly controlled clinical studies, and it's not available for purchase. And doctors and individuals shouldn't be seeking it for patients.

[Rune Skeie, Chief Financial Officer]

And last question, can you give any guidance on how we should think about the future R&D expenses given the potential for registration studies in both AML and on small cell lung cancer, to start in 2021?

[Richard Godfrey, Chief Executive Officer]

Well, we don't guide on specific cost base, but I can say it's not unreasonable to anticipate that the cost base would increase as the scale of clinical trials increases. And I think it will become more apparent in those that are studying and analyzing our business when we are able to disclose the exact scope and state and form of the studies that we're proposing. But it's not unreasonable to anticipate there would be an increase in costs should such studies be undertaken.

[Rune Skeie, Chief Financial Officer]

That was the last question.

[Richard Godfrey, Chief Executive Officer]

Thank you, Rune. Well, thank you to the organizers, and thank you for those that tuned in. And please stay safe, and look forward to updating you with news in the coming weeks and months.