BioLineRx Ltd. (BLRX) Earnings Call Transcript & Summary

Good morning, and welcome to the BioLine event. [Operator Instructions] Please note, Dr. DiPersio will not be able to join us for the Q&A session today. [Operator Instructions] I would now like to turn the call over to your host, Phil Serlin, Chief Executive Officer of BioLineRx. Please go ahead.

Good morning, and thank you for joining our investor update and KOL webinar today. I'd like to start out the morning with some brief opening remarks. As you've seen over the past few weeks, the company has taken several important steps to support its long-term growth with a focus on achieving the near-term potential of becoming a revenue stage company with a best-in-class therapeutic product. Let me recap these achievements. On Friday, September 9th, we submitted our new drug application to the FDA for motixafortide in stem cell mobilization for patients with multiple myeloma. This is our first NDA submission and a significant accomplishment for the company. We anticipate the FDA's decision on acceptance of the NDA by November. And if accepted, we expect a PDUFA date in Q2 2023 under a priority review process of applicable or Q3 2023 under a standard review process. On Thursday, September 15th, we secured a $40 million debt financing agreement with Kreos Capital. Kreos has been a supportive partner since 2018 when we sought to increase our ownership stake in motixafortide. We are pleased to have the opportunity to work again with a lender that is very familiar with our company and continues to support the development and commercialization of our lead product. Pursuant to the terms, we can draw down the initial tranche of $10 million immediately. 2 additional tranches totaling $30 million can be drawn down upon the achievement of prespecified milestones. This agreement strengthens our balance sheet and more importantly, gives us access to capital on a nondilutive basis. On Monday of last week, we announced the pricing of a $15 million equity offering. The Kreos facility together with a $15 million equity raise and our cash on hand, enabled us to fully finance a robust U.S. commercial launch of motixafortide while maximizing the value of the asset for our company. And yesterday, we introduced motixafortide trade name, APHEXDA and announced our plans to commercialize it independently in the United States, assuming FDA approval. As we have noted previously, the target market here is quite concentrated. We have been advancing key prelaunch activities for the past several months. And with these recent financings, we believe we are very well positioned to build out the relatively modest infrastructure that would be required for stem cell mobilization as compared to a new product launch in a broader oncology indication. We believe the compelling financial model is scalable over a lower expense burden with a quicker path to breakeven and profitability versus the traditional pharma model. So as you can see, we have made a significant amount of progress toward our strategic goals, and we will use today's webinar to review our planned commercialization approach and the benefits that it brings to patients and the value it will contribute to the company. Let's go to the forward-looking information slide for a few moments. And now let me talk about today's agenda. We will begin this morning with a presentation by Dr. John DiPersio, Chief of the Division of Oncology, Washington University School of Medicine in St. Louis. Dr. DiPersio served as the lead investigator for our very successful Genesis Phase III clinical trial that formed the basis of our new drug application in stem cell mobilization. His presentation will focus on the unmet clinical need that exists in stem cell mobilization and where a superior mobilization agent such as APHEXDA can fit into the evolving treatment landscape. Following Dr. DiPersio, Lissa Gray BioLine's patient advocacy lead will moderate a panel discussion between a multiple myeloma patient, her caretaker and an apheresis nurse. This presentation will highlight the challenges of apheresis from a patient and institutional perspective and further highlight the need for more effective mobilization agents. Our last presentation will be done by BioLineRx USA President, Holly May, who will provide a detailed overview of the alternatives that we considered when developing our effects to U.S. commercialization strategy, our rationale for commercializing independently and a high-level review of our plan and preparations to date. I will then come back with brief closing comments before we open the call up for your questions. At this point, I'd like to introduce Dr. DiPersio, please go ahead.

It's great to be with you this morning. And what I'm going to do in the next 30 minutes is give you a little lowdown and description of stem cell mobilization and why motixafortide may fit into the general scheme of how we treat patients in the future undergoing stem cell transplantation and gene therapy. While transplantation is an interesting process, and most of the transplants done in the United States and throughout the world, in fact, are done using peripheral blood stem cells. And so these stem cells sit in the bone marrow, and they rarely move from the bone marrow into the blood and into the bone marrow. Again, the static process is very low level. But in order to get sufficient numbers of stem cells to do a transplant, you have to mobilize and that's this process called egress or mobilization. And for that, we can collect those stem cells, purify them, if necessary, for gene therapy or just let them be used for stem cell transplantation. So these are collected by an apheresis procedure quantified and then infused back into the patient where they home to the bone marrow niche and start growing and differentiate into mature stem cells, mature hematopoietic cells, including myeloid cells, erythroid cells and platelets. This results in multilineage reconstitution of patients, which is lifesaving. This is just a cartoon showing how this is done. Stem cells are move from the donor after mobilization through a process called apheresis, and that usually takes 5 to 8 days with GCSF, which is a standard of care. I will tell you in a minute how that happens biologically. And then those stem cells are collected, cryopreserved and then after the patient has received ablative chemotherapy destroyed to destroy their underlying stem cell population. Those new stem cells, which were collected before the ablation procedure are then infused into the patient. And then those stem cells home to the bone marrow and mature into normal myeloid cells, erythroid cells and platelets, which again is life-saving to the patient. The clinical needs for optimal mobilization are really twofold today. Number one, we need optimal stem cells for transplantation. Currently, approximately 95,000 transplants are done annually in the world, approximately 35,000 to 37,000 are done in the United States and 55,000 are done in Europe and other areas of the world. This process of mobilization is utilizes GCSF, which requires, again, 5 to 8 days of individual injections results in unpredictable yields is associated sometimes with adverse events such as severe bone pain and even at times, splenic rupture. And it is not used in all diseases, for instance, in sickle cell disease, GCSF is contraindicated because of the increased risk of inducing vaso-occlusive crises and debt actually. So it's completely contraindicated. And that means that there is really a need for novel mobilization regimens to mobilize more stem cells, shorten the time for mobilization and to do this with fewer adverse events. So the goal of any optimal mobilizing regimen is to develop a predictable and reliable approach to stem cell mobilization with minimal apheresis sessions. The second major reason for optimal mobilization has to do with the collection of stem cells for genetic manipulation. This is the beginning of the age of gene therapy. And there was a period of time that gene therapy has waxed and had disappeared from our armamentarium, but now it's back in full force, not only for the treatment of malignancies with things like CAR T, but also for genetic manipulation of stem cells to cure inherited diseases of the bone marrow such as thalassemia and sickle cell anemia. In order to perform these procedures, one needs to collect not only stem cells, but a lot of stem cells, and we need to collect stem cells are a better of high-quality so that various approaches to modifying these stem cells can be done with the expected losses, which occurred every step during genetic manipulation. These losses occur at the time of lentiviral, transduction, gene editing, base editing and all of the treatments that are used now for the genetic reversal of diseases such as sickle cell anemia require lots of stem cells, and they need to be obtained safely and without the use of GCSF. So these stem cells not only can treat diseases such as thalassemia and sickle cell anemia, but there are a number of other diseases now that stem cells are going to be genetically manipulated to reconstitute local microenvironment to cure diseases. This is a report showing that the intra 3-roll ventricular delivery of hematopoietic progenitive resulted in robust engraftment of microglial cells in the central nervous system. This can be used to actually reverse some of the storage diseases that occur resulting in CNS defects and death in patients. And so stem cells are going to be used in many other diseases in addition to some of these inherited diseases like sickle cell anemia and thalassemia. Well, the optimal use of this approach was a proof-of-principle experiment was just published a month or 2 ago by my friend and colleague, Luigi Naldini from Milan. And he showed in a very important paper published in cell that if you optimize stem cell mobilization and you couple that with figuring out how to condition patients for stem cell transplantation for nonmalignant diseases using non-radiation and non-chemotherapy regimens, then you can safely reverse these genetic diseases. Now he did this in a mouse model. But this is ultimately the goal of gene therapy to use genetically manipulated stem cells in patients that have been conditioned with non-radiation, non-chemotherapy regimen so that they're safe and don't have any long-term consequences. The bottom line for all of these genetic manipulations is you need a lot of stem cells to do these procedures safely, efficiently and stably over time. We think of gene therapy as an ex vivo, you take the stem cells out that you mobilize and then genetically manipulate them. This group and an André Liber group at the University of Washington, have been pioneering in effort to actually do this in vivo in patients. But for instance, using adenovirus to genetically correct diseases such as thalassemia or sickle cell anemia by actually just injecting adenovirus in the peripheral blood. And what they find, just like with all the other approaches to genetic manipulation is that stem cells have to be mobilized efficiently into the peripheral blood for this to work. So even in this setting where there's no conditioning that's necessary in that you do in vivo transduction, which is going to be something that everyone is going to look for in the future that, that will require lots of good mobilized stem cells in the peripheral blood to do this effectively. So this is here to stay, and I think that optimizing mobilization quickly and safely is optimal. So this is just the numbers of autologous and allogeneic stem cell transplants done in the United States today. This shows you the kinds of diseases that most patients are being transplanted for. And you can see that most of the allogeneic transplants in the dark blue are being done for malignant diseases such as AML and ALL. While most of the autologous transplants, which are a dominant transplantation procedure done in the world today are done for multiple myeloma and, to a lesser extent, in non-Hodgkin's lymphoma. This is the transplant activity report of the United States showing over the past 3 years. This is a little bit dated between 2013 and 2017. Approximately 106,000 procedures have been done. So this translates in today's world to about 36,000 transplant procedures done in the United States today. And as I mentioned, there's approximately 55,000 to 60,000 done in Europe and other areas of the world. So 95,000 altogether. Well, to mobilize stem cells, you've got to get these stem cells out of the bone marrow into the peripheral blood and knee. This is an all scanning electron micrograph that I took purified stem cells that are bound to the bone marrow microenvironment. And those little pieces of threads that attach the stem cell to the microenvironment. Those are the things that need to be disrupted for those stem cells to leave the bone marrow and circulate in the peripheral blood. So the goal of a mobilizing agent is either to modulate the microenvironment so that these tethers are broken or to just immediately and competitively block those interactions, so the stem cells flowed away into the peripheral blood. So think of it this way as a boat at a dock and the dock has multiple boring lines. And there are redundant processes such as CXCR4, VLA-4 are the major ones that are expressed on stem cells and their ligands which are expressed in the microenvironment. And those ligand receptor interactions hold those stem cells into the bone marrow and you must break those to actually get those stem cells to release into the blood. Now GCSF does it by decreasing the expression of SDF-1 in the bone marrow. That takes 5 to 7 days to work. And so you have to give shots of GCSF for 5 to 7 days for this to actually work. And so that's a very slow process. Alternatively, you can use competitive inhibitors of these interactions and directly block those interactions, and that results in the cutting of these more lines in, for instance, motixafortide and plerixafor 2 examples of drugs that block the CXCR4, STF1 ligand receptor interaction and there are other compounds in the VLA-4 side that are being developed preclinically that may help in the mobilization as well. This is the first trial that we did, and I was the PI of this study. This is the registration studies for non-Hodgkin's lymphoma, but more importantly, for multiple myeloma, in which plerixafor plus GCSF was compared to GCSF alone for mobilizing stem cells in multiple myeloma patients going on to autologous stem cell transplant. And you can see from this graph that there's a dramatic improvement in the mobilization of stem cells when patients were given plerixafor plus GCSF versus GCSF alone. And the interesting thing here is that the non-Hodgkin's lymphoma patients or even a worse group of patients that had a higher rate of failure to both GCSF and Clorox plus GCSF because they're more heavily pretreated. But you can see that a number of patients that get GCSF in fact, almost 85% of them fail to mobilize sufficient numbers of stem cells in a single day with GCSF and even 50% with plerixafor and GCSF. So there's lots of unmet medical need here. So let's fast forward a number of years of the development of BL-8040 or Motixafortide. Motixafortide is a novel 14 amino acid cyclic synthetic peptide inhibitor of CXCR4. It's present CXCR4 is present, as I showed you on all hematopoietic stem cells. And it's the principal regulator of stem cell homing and egress from the bone marrow into the peripheral blood. BL-8040 or motixafortide binds to CXCR4 with high affinity, higher than plerixafor and has a very long occupancy rate due to a very slow off rate. And this has implications for both quantitative and qualitative mobilization of stem cells compared to other CXCR4 inhibitors in GCSF. This is what I mean in that this is a little tough to follow, but this is a time 0 after giving plerixafor or BL-8040, this is a tool compound for BL-8040 call T1 40. This is the same as plerixafor or time. And you can see that at time 0, both plerixafor and Motixafortide block the binding of this antibody called 12G5, which actually binds to CXCR4. So at time 0, both plerixafor, which is also called AMD3100, and Motixafortide, which is called T140, block that interaction. However, it's 60 minutes after the -- adding these 2 compounds, only motixafortide continues to block that receptor while the effect of AMD3100, or 4x4 is completely gone in just 30 minutes. So a much tighter binding very much slower off rate and continued blocking of the receptor, as you can see in the lower graph on the right here. This has clinical implications as well and that these drugs, specifically Motixafortide, needs to be given only once every 2 days, while plerixafor needs to be given at least once a day. So this is the stem cells that are mobilized. This is from our lab. And you can see that all the stem cells are very primitive stem cells, the more differentiated progenitors are mobilized in response to motixafortide. And that is related to a certain extent on the expression of CXCR4 on the surface of these cells, which you might expect to be the case. And you can see, comparing the mobilization of CD34 cells, I was pre and post. There's a nice mobilization with plerixafor which has even improved with Motixafortide. So what is the competitive landscape for mobilization today the standard of care is just GCSF alone. Some transplant centers use a combination of cytoxan and GCSF. But Cytoxan is a toxic chemotherapy. It does have life-threatening complications in both short term and long term because it's an alkylating agent. People can die after stem cell mobilization with cytoxan because it causes profound neutropenia but it is a way of mobilizing stem cells with GCSF, but it even actually ironically takes longer than GCSF. So GCSF, you can mobilize stem cells in 5 to 8 days. But with chemotherapy, it takes 10 to 14 days, and there are lots of complications associated with it. So it's really not considered really in the competitive landscape. The competitors, in addition to BL-8040, which is motixafortide, includes MGTA-145 from Magenta, which is a Growbeta, our CXCR2 agonist, which is now in development, and it had been initiated in trials for allogeneic transplant patients and in multiple myeloma patients. Those trials are currently on hold as Magenta focuses on their approach to sickle cell anemia. And there are studies looking at mobilization of sickle cell anemia patients for gene therapy are now just moving forward, but not open yet. So that is the major competitor. And there's one other competitor out there called AVA-4746 from AVERA, which is an alpha 4 inhibitor. This is a VLA-4 inhibitor. It's an oral medication. And it really has been tested very minimally in preclinical models only, and they're not close to the clinic. This is just a little bit more information about the AVERA drug. And the MGTA-145 from Magenta, as I mentioned, it's a CXCR2 agonist. It's a truncated grow beta. It induces neutrophil activation, which may be a problem in sickle cell anemia as well. It induces the release of metalloproteinases, which cleaves some of those tethers, which I showed you previously on the slides that are responsible for holding those stem cells into the microenvironment. And they're combining MGTA with plerixafor as a rapid mobilizing approach for sickle cell anemia patients so they can avoid GCSF. Now when they tested this in normal volunteers as they found that MGTA was a very weak mobilizing agent, as you can see in the left panel here. And even when added to plerixafor, there was only a slight increase in mobilization. And I think this is probably why they're really reconsidering their approach and focusing more on sickle cell anemia because that increase is not dramatic compared to just plerixafor alone, which is known to be a very weak mobilizing agent by itself. So getting back to the issue at hand here, and that's motixafortide, as I said, it's a novel cyclic peptide. It has high affinity for CXCR4 and long receptor occupancy. Based on this biology, by line has initiated and completed a Phase III 2-part multicenter, randomized, double-blind, placebo-controlled study, testing motixafortide plus GCSF versus placebo plus GCSF in multiple myeloma patients undergoing auto transplant. The dose of motixafortide was established at 1.25 milligrams per kilogram, and the FDA asked for a lead-in part of the study, which was to do a number of patients, 12, in fact, with this current dosing, just to determine that this was the correct dose and that there were no obvious safety issues, which was performed. And then the second part of the study was a randomized double-blind placebo-controlled study with 122 patients, which was ended early at the interim analysis, which ended up being the final analysis because of superiority of the motixafortide plus GCSF arm versus GCSF. The key inclusion criteria shown here and the exclusion criteria are shown here. And this will be hopefully published soon in a good journal so that we can all see it together and evaluate the results. This is the design of the Genesis study was exactly modeled after the Plerixafor study, except Motixafortide was given on the evening on the fourth day of GCSF and then it was not given again until 2 days later. While in the plerixafor study, it was given in the evening before the collection and then daily after that, if the collection goals were not meant. The primary goal was to collect greater than 6x 10^6 CD34 per kilogram in 2 collections with secondary endpoints looking at the number of stem cells collected after a single apheresis procedure. This is the results of the study, showing a dramatic and highly statistically significant difference between the placebo plus GCSF mobilization shown in the blue line versus the motixafortide plus GCSF shown in the green line where the primary endpoint was highly statistically significant. We're 92.5% of the patients with motixafortide and GCSF reached the goal and only 26% of the control group. And the secondary endpoint was 88%, almost 90% of the patients reached the goal after a single apheresis procedure while only 9.5% in the GCSFs plus control group reached that benchmark. So the interesting aspect of this study is that 70% of the patients in this trial had received multiple cycles of lenalidomide as standard induction therapy for their myeloma. That's very important since we know that lenalidomide is a stem cell poison and it's been shown by a number of groups to dramatically reduce the chance of effective and successful mobilization. So these patients compared to the previous registration study with plerixafor really was studying a much worse population of patients since in this study, where the results do not on the surface appear to be comparable, and they seem to be better with motixafortide randomized studies between the 2 have been done. Only 4.6% of these patients actually had any lenalidomide as part of their induction therapy for their before stem cell mobilization, which is -- this is an important point. This also can explain the reduction not only in the success rate, but also in the success rate of the GCSF control group, which in this arm 17.3% got there in 1 day and in our study, only 9.5%. So this could easily be explained by the difference in utilization of lenalidomide between the 2 trials. Well, this slide shows it all, I think, and this is the control group on the right that receive GCSF plus control. And you can see that their mobilization was very modest. And here are the patients that received motixafortide on day 4. And you can see that there's a dramatic and monumental increase in the CD34 in the peripheral blood in these patients. Some of them got up into the 100, 200 and 300 numbers, which is pretty remarkable. And most importantly, the median number of CD34 cells per kilogram collected in 1 apheresis with ametixafordide and GCSF was 10.8 x 10^6 versus 2.25 x 10^6 in the control group. Well, what about the quality of the stem cells? We did multiparameter flow cytometry, 40 color flow cytometry and single-cell RNA seek to determine the quality of the stem cells mobilized with motixafortide in GCSF versus GCSF alone. And these are some of the phenotypic markers that we use to define these populations. And I think these are standard and accepted around the world for people who are experts in stem cell biology. And we found interestingly enough, when we did tSNE plots and looked at all of these subpopulations that patients mobilized with motixafortide in GSCF had not only more stem cells but had a significantly higher percentage of stem cells that were considered the most primitive and had the greatest potential for a multi-lineage differentiation compared to GCSF and control. And when we looked at an exactly parallel group of patients, a contemporaneous control group that during the same period of time were mobilized in the exact same way with plerixafor plus GCSF as standard of care, same ages, same previous treatments, et cetera. We found that in every setting, not only were the primitive stem cell numbers better in the motixafortide plus GCSF, but the total number of stem cells and all of these more differentiated progenitors exceeded the plerixafor group almost in every case. So we were happy to see that, number one, the number of these primitive multipotential stem cells was enhanced, but also not only compared to GCS control, but to our temporaneous control group that received plerixafor and GCS stuff. So this is what's called a fake mapping pseudo time analysis for stem cells. And the most primitive stem cells are these green cells in the HFC-1 population, and we could track these stem cells using single-cell RNA-seq data. And we were able to show that there are significant differences between GCSF plus plerixafor and GCSF plus motixafortide in the proportion of these different subpopulations them cells. And you can see these green population right here from the motixafortide only. This was done in a normal allo donors is almost efficient in patients receiving plerixafor or GCSF. And these are really the most primitive and most durable and long-lasting multipotential stem cells. Well, what does lenalidomide have? I'm just getting back to my point that I was trying to make previously. This is -- just to show you 3 studies. This is a study from the Mayo Clinic looking at patients who had received standard GCSF mobilization or GCSFs chemotherapy mobilization. And they looked at total collection of stem cells and the daily average in the collection on day 1. And you can see that if you were exposed to lenalidomide prior to stem cell collection, it reduced the total number of CD34 cells you could collect significantly. And also, the daily average was reduced and the day 1 collection was reduced. And this also occurred in patients mobilized with GCSF plus chemotherapy. So the effect of lenalidomide had a significant negative impact on G-mobilization and G+ chemotherapy mobilization. These are 2 other studies which show the same thing, one from the Mayo Clinic, one from Memorial Sloan Kettering, which showed if you had received standard non-lenalidomide therapy, your chance of CD34 collection was significantly higher, and the number of days and percentage that required for collection and the percentage of patients who failed collection was significantly lower if you had not been exposed to lenalidomide. So this is the same in the Memorial Sloan Kettering study shown on the right. And we just finished a study showing that daratumumab when added to lenalidomide had a significant negative impact on mobilization in patients receiving plerixafor and GCSF. And in the future, all patients in the United States at least, will be receiving 4 drug induction therapy for their myeloma. So all of these patients will not only be exposed to lenalidomide, but another stem cell poison daratumumab bringing forth the need for even a more improved stem cell mobilization approach. And this is just an abstract showing there was no data here, but I just thought I'd show you this. This showed a significant difference in mobilization. This is the only other report besides our group showing that there's a significant negative impact on daratumumab on collection of stem cells as well. This, again, shows the comparison of motixafortide with 2 other CXCR4 inhibitors in normal allo donor, so significantly improved and the actual mobilization showed that in a retrospective analysis that our center published in Blood Advances recently showed that patients receiving motixafortide as the only mobilizing agent and allo donors was superior to plerixafor on. There are other drugs that are being developed for the mobilization and this is -- I'm only showing you this to show you how plerixafor in motixafortide compared with one another when other drugs are added as well. So here is an example of a drug that we've been developing, which is a very weak mobilizing agent. It's a VLA-4 inhibitor. But you can see compare the let's see the orange line here. This is plerixafor plus our drug with motixafortide in our drug. So this results in a dramatic only almost a doubling of the mobilization, also a much longer period of mobilization. So this is extended mobilization and a higher mobilization when combined with another drug, just showing you that again, in these comparisons in these models suggest that motixafortide is superior to plerixafor. So this could be pursued in the autologous gene therapy approach. And one approach would be to combine a VLA-4 inhibitor with motixafortide. And so that's what we're planning to do. As a proof of principle that motixafortide not only by itself or with GCSF is an effective and superior mobilizing agent, but we're really interested to see if it can be combined with VLA-4 inhibitors, which would actually allow it to be potentially used in the future as a single active mobilizing approach for gene therapy for patients with sickle cell anemia and thalassemia and other inherited diseases of the bone marrow. So in conclusion, I hope I've convinced you that there continues to be a significant unmet medical need for optimal safe and rapid stem cell mobilization. We need this for optimal multi-lineage stable engraftment after stem cell transplant and for successful gene therapy using transduction gene editing and base editing. The Genesis trial, which I reviewed with you today confirms the superiority of motixafortide plus GCSF over GCSF alone for mobilization of multiple myeloma patients. The Genesis trial interestingly, had 70% of all the patients were exposed to significant doses of lenalidomide, while only 4.6% in the plerixafor registration study, making those differences even more dramatic. Daratumumab will be also an additional agent added to all induction regimens for myeloma and will have a negative impact on mobilization requiring even better mobilization approaches if we're going to move forward. So not only are the stem cell numbers dramatically increased after motixafortide and GCSF, but also the quality was increased with increased numbers of primitive stem cells and progenitors. The expectation is that similar results would be seen in other indications, such as non-Hodgkin's lymphoma and allogeneic donor mobilization. And although no randomized study is comparing motixafortide to 4 plus or minus GCSF, have been performed, retrospective analyses of both human and mouse studies suggest that motixafortide compares very favorably to plerixafor in of these models. And I want to thank you for your attention, and I'll hand it over.

Thank you very much, Dr. DiPersio, for your interesting and comprehensive presentation. I'd now like to introduce Lissa Gray, BioLine's patient advocacy lead, who will moderate a panel discussion between Mary Cortiment, who is a multiple myeloma patient, her husband and caretaker Albert Cortiment as well as Sharyn Boissevain Chen, Lissa's nurse. Lissa, please go ahead.

Thank you, Phil. As Phil mentioned, we are so fortunate today to have a myeloma patient, her caretaker, a transplant coordinator, join us to share their experiences so that we can better understand what it's like to undergo the critical process of stem cell mobilization and collection. The 3 panelists will highlight some of the aspects that you heard brought up by Dr. DiPersio, and bring to life some of the current challenges with the process, which underscore the need for novel mobilization agents. We're first going to talk to Sharyn, who works at a large academic center, a multi myeloma center that performs over 200 transplants a year. And she'll give us an overview of the current stem cell mobilization and collection routine. So Sharyn, if you wouldn't mind, in to introduce yourself, including your background and then your current role.

Yes. Happy to be here. I've been a nurse for almost 20 years and have always been in hematology stem cell transplant, worked inpatient for almost 10 years as the bedside nurse, charge nurse and assistant manager. And then in the last 10 years, I've been a transplant coordinator, so meeting patients and their families who are going to undergo a stem cell transplant for their next step in their care.

Great. Thank you. And if you wouldn't mind, Dr. DiPersio has already outlined it somewhat, but from a nursing perspective, because you gave an overview of stem cell mobilization and collection that process for multiple myeloma patients.

Yes. So I make patients who are along their journey for their multiple myeloma treatment and get them through their stem cell collection and their transplant. We get them set up for their days of apheresis and it's -- as you can kind of imagine from what Dr. DiPersio said to, it is a very complicated procedure. Our patients will receive multiple days of growth factor to stimulate those stem cells to come out of the bone marrow and into the peripheral blood and we can collect them. Patients do experience side effects with these injections. The at times experience bone pain. And this is the bone marrow swelling with these stem cells that we want to collect. At the center, I work at the day before patients have their stem cells collected, they will have a very large rigid IV catheter placed here in the neck. We called a Quintin catheter. It's one of the more challenging aspects of this part of the apheresis procedure for the patients because it's pretty uncomfortable and cumbersome. There's not a lot of head movement allowed, and it can be painful. We try to keep in as little days as possible, but it will really depend on how many days of apheresis the patient needs. The catheter has 2 lumens from one lumen the blood is extracted and goes through the apheresis machine where all the blood components are separated. We take those stem cells from the blood, and that's what saved for the future transplant, and then the rest of the blood is returned through that second lumen. And our patient is line in the bed for about 5 to 6 hours, very long day. They can't get up for a walk break or to go to the backroom. We can't interrupt the flow with the apheresis machine. And that takes another couple of hours to get results of that collection. So we get our patients at TooraCenter at 7:45 in the morning, and they're with us until about 6:00 or later depending on how the collection went and how long it takes to get those results. So if we do need to get another day of collection, they come back for a second day that, sometimes third or fourth or even fifth day if we need to. So it's a pretty rigorous process, really hard on the patients and the family in terms of going through that type of procedure.

Great. Given what you've described, can you highlight some of the stressors that a patient may face when they go through, in particular, multiple apheresis days?

Yes. It is a stressful procedure for the patients. It's also very logistically challenging to a lot of times, our patients have to travel many miles to get to our center for their treatment. So their caregivers taking time off work. they're staying in a hotel, working on how to figure out meal planning, things like that. So it is a long day. And they're worried because they're not sure how it's going to go because we do say, "Okay, it's going to take either 1 or 4 days to collect enough stem cells for your transplant." And they know that the transplant is such an important aspect of their care to get into that deep remission that we're looking for. So it is a lot of pressure on the patients that like perform well during that collection. So it's very emotionally exhausting for the patients and also just physically exhausting as well. The other thing that I should point out, too, is that patients have to be off their therapy, and that's what Dr. DiPersio was talking about being off the lenalidomide or whatever else they're on. Here they are on their myeloma treatment, and it's going really well, they're responding. And then we have to say, "Okay, take a break from that medication because we need your bone marrow to take the rest before we collect stem cells." So that can be really anxiety-provoking too because they're off their treatment that's working so well. They might have pain associated with their diagnosis, so even just coming to us daily like that and being in the bed day, lots of pieces that can be challenging for our patients. So we do it every day so we give them a lot of reassurance, but it's still really hard and can be scary in exhausting too.

Great. And then what benefits do you see with the possibility of fewer apheresis sessions or even a single apheresis session.

I mean if we could really predict and say, okay, we have all these patients who need to collect, for example, in a given month or a given week, we would be able to just so much more efficiently collect patients and not push them out many weeks because we don't have a slot per se to collect them. We're a pretty busy center, and it's just really difficult to predict who is going to collect in 1 day or 4 days. And so if we could anticipate knowing that they could just collect them one day, we could be a lot more efficient in our practice. I mean even just yesterday, it was a busy Monday at my workplace, and we were juggling all these different people that we're going to be collecting that week and having to decide how to balance the whole staffing and how many shares we have. So if we knew that we could reliably collect somebody in one day, it would help our center to just anticipate how to plan. And again, going back to the patient, just saying, "Okay, most likely you'll collect them one day." It would just be a huge a huge milestone for that kind of procedure.

Great. And then finally, is there anything else you'd like to add that I didn't ask about?

No. I mean I think we covered it -- in general, I mean having that predictability to know that we can collect our patients in just 1 day would just be a huge just a huge gift for the patients and then also for our center 2, just to know that we can plan accordingly and get our patients through this process as easily and quickly as possible.

Great. Well, thank you so much, Sharyn, and we're thankful for your time and also the opportunity to learn from your expertise. And Mary? Thank you again for joining us today. And if you wouldn't mind, just reintroducing yourself and then giving us a description of your experience with multiple myeloma from your diagnosis through to your stem cell collection in preparation for your transplant.

Well, first of all, my name is Mary Cortiment and I am 66 years old We have 3 daughters and 7 grandchildren. I have multiple myeloma since 2017 and just to put a human face to it, it is a noncurable peer. It's a lifetime diagnosis. up to the point where I was suggested that I have stem cell, I have multiple treatments every week, and they all failed. So they got my oncology team to do a stem cell transplant. Starting that process is a little different than Sharyn talked about at their center. At our center, 2 weeks before, I was scheduled for the transplant. I went in to have a port pediment and it was like a 3 lumen core. It was a little lower basis a high in my neck. We for a surgical procedure and had to go to the hospital and have my caretaker drive me, that port was put in, and he had to learn how to flush it because it was in so long. So it was in approximately 2 weeks before I had my stem cell, and then it stayed in the entire time until the day I left the hospital. So that's a little different the way our center does their process. I then had to go to the hospital with my caretaker and he had to learn how to give the injections of a medication that would boost my stem cells. So we did that. He gave me the medication, and I had that for 8 days. So I went in on a Wednesday for my apresis process, and I was scheduled to go in the hospital for the stem cell transplant on Monty. So on Wednesday, I went to the hospital, we had -- we lived 60 miles from the hospital, and we had to be there at 7:30 every morning. And just like Sharyn said, it is a long 5- or 6-hour process. I did have a bone pain and discomfort from the other medications, the boosting medications. So I just didn't feel that great. When we got there, we were putting a little room that is very similar -- it's not like a chemotherapy room. It's very similar to a surgical recovery room, the curtains drawn. There's huge machines, there's a bed for me, and then there's a little plastic care for my husband to sit in, all hump up all day long. So as after the first -- we were told we needed 2 million cells. After the first day, we had to wait. And again, it was beginning to get late, we were told that I only collected 400,000 cells. And that was a little shocking to me, considering I needed $2 million. So I was worried, and we went home, turned right around, came back at 7:30 the next morning, had the apheresis process. My husband sat there and waited for me. We waited afterwards, and we were told that I wasn't anywhere close to collecting enough cells. So they had me go back up to the hospital and they gave me up to the treatment, and they gave me another dose of some type of cell boosting. At that point, I was physically and emotionally exhaustive. And I just couldn't at 6:00 at night go drive 60 miles and make that turnaround the next day. So I opted to stay in a hotel close to the hospital and use their shuttle service. My husband had to go home because we have dogs and we need someone to be here and care for our dog night. So he went home, I went to the whole hotel room. I went the next morning at 7:30 by shuttle over to the hospital by myself. I had another day of apheresis. I waited there and that was horrible fear that I was not going to have enough cells and fear that I wasn't going to be able to have my stem cell transplant. And ultimately, at that point, that was the therapy that was suggested to me, and I was afraid I was going to die if I couldn't get it. So they said that I had enough sells, and I could go home. So I'd call my husband 60 miles to come and get me, we had the expense of a hotel. We had the expense of Valle parking, gas, a hotel room. I mean it was just an expensive process that we had not planned on. I had Saturday and Sunday and Monday, I had to be taken to the hospital. Now I want to add, during this time, it was COVID and the restrictions were terrible. I originally was going to go into the hospital in March of 2020, and the transplant center was shut down and not reopen until May of 2020. So I had all of that inside the COVID anxiety, my husband couldn't go with me. It was just a horrible process and that's apheresis segment of it really made it very difficult when I went into the hospital. I was already very stressed and very anxious and had a lot of anxiety. So that's pretty much my story with the apheresis and the start of the stem cell journey.

Well, thank you for sharing it with us. I heard a lot of the various challenges. I think you did -- the challenges of the process came through very, very clearly. So I'll just ask finally then, if you would -- was a medication that would allow you to only need potentially on apheresis session. What would the benefits of that be to you as a patient? And how would that -- how could you foresee that improving your stem cell mobilization and collection experience?

Well, it would improve it in the fact that I wouldn't have the 3 days, I wouldn't have the expense. I'm not just one person that it happens to. I am on social media myeloma pages. And this is the routine, if not even patients having more trouble than that. I only know if one person ever got theirselves in one day. So it would help emotionally, financially, it would help with the anxiety. It would let the amount of time I had to have the floor there would just be a lot of things that it could come because that 3 days caused so much insight in our life.

All right. Well, thank you again, Mary, and we wish you the very best in your upcoming treatments. And we'll now hear from Albert. Albert, so would you please start by introducing yourself and then your connection to Mary and your role in her care.

My name is Albert Cortiment, and I'm a caretaker to my wife Mary Cortiment who has been diagnosed this disease since 2017. Backing up some of what you said, we had to -- we had you'll see a doctor, a special factor for this SIMs transplant. And you told us that there was a risk factor in this that could die from this. And I wasn't about to make the decision on her doing it or not doing it. It was totally in her ballpark. She had to make up the system herself, and she did make this a decision. So making that decision then go ahead to go back to the hospital again a couple of days or whatever it was, and we learn how to give our injections and everything and learn how to flush out to the line, I think I never done nothing like that before my wait. But it was all new to me. I've got to keep it together for sure. When we started collecting the cells, the first day went up there, it wasn't a long day. It was really a long day. And sitting there and watching her thinking in my mind, I could possibly lose my wife looked out during this process. I was terrified. And then having to go back up again, the second day, like goodness, it's just like, "Okay, are we very good enough at this time or we going to be able to do this. They're going to have to come up with something else. We didn't know what. So the emotion is just running and running and running my head is just running around of consent. We're just trying to figure it all out. So having liver at the hospital on a second day at the hotel that second day, and go home, and I think about it all the way home and all that low. Just anxiety, the physical part of it, everything you just it was a war. I love my wife to death. And if I had to drive from Ohio to New York every day, I would take it. There's just nothing I wouldn't do for her so there on the third day we got everything, we had to weaken to think about this. And still the part of everything they have to possibly go long within my mind. What could I do to make this better for her? And you know what, the hardest thing was is there wasn't a darn thing I could do. But just try to give her some moral support. And I'm hoping I did a good job with that. And they had some time for him to go in for the STEMCO transplant. So COVID everything. I have to go up there and drop her off at the hospital, was a bag and kiss her goodbye and that was it. So was that my last kiss? Was that my last hug? Didn't know. I didn't know. I couldn't go in. And so we text back and forth. And we call and it was really hard for her being in for 15 days and it was hard on me as well. I had to cook for her myself. I have just you're thinking about what's going on, how we're going to do, how we're going to do that. I never even took care of the bills, she takes care of the bills. I didn't know what I was going to do. And it's just a roll of coast arrive is what it is. And I would wish on anybody.

I hear, Albert, the description you're giving of the roller coaster, the logistical, the physical, the emotional pieces and I appreciate you highlighting everything in your experience. And thank you to all 3. I just want to take this opportunity to say that it is so important that we hear directly from the people that go through the mobilization and apheresis process, the people that it impacts most. And so thanks for joining us today.

Thank you for having us.

Thank you very much, everyone, for the very important and compelling panel discussion I'd now like to introduce Holly May, our newly appointed President of BioLineRx USA, who has 13 product launches under her belt, and we are looking forward to her successfully completing her 14th launch with APHEXDA. Holly, the floor is yours.

Thank you, Phil. I'm so excited to be here today. And the first thing is we do have a brand name. And so BL-8040, motixafortide will now be referred to as APHEXDA. So in my early days with BioLine, we dove into a deep analysis of our commercial options. And we really consider 2 main pathway, to partner or to go it on our own. And so looking at the partnering, there were a couple of different optionalities there where we thought we could out-license or even bring in a co-commercialization turnkey-type partner. And while there were many considerations, the option here really was leading to a lower profit percentage. And also, BioLine would have to give up some of that market development control as we fit into the portfolio of another company. And so the self-commercialization route was given good consideration because here, the thinking is that we wouldn't be having to do a profit split. We wouldn't lose up that very important market development control and quite frankly, it was a much more attractive option from an overall cost perspective. But I would like to give a little bit of thinking about the key considerations that we had behind that optionality of going in ourselves versus using a partner. So the first thing I think that's been very clear today is that we have a highly differentiated clinical candidate. And that makes the ability and the story and the value proposition of going into the marketplace very strong. And we also, as you're going to hear in a moment, and I know that Dr. DiPersio touched on this. It's a well-defined marketplace, especially for a smaller company that wants to launch into the U.S. market. With a lot of the experience that I have, we knew -- I've gone through this playbook before of recruiting a knowledgeable commercial and U.S. teams. So that was a knowable thing. And also BioLine has very strong manufacturing already in place from being a clinical company that it is. And bringing on the right thinking from a distribution perspective, it was something that I thought was very doable. And then, of course, both models, we look at what the revenue would be, but also most importantly, the profitability picture. So with that, with the deep analysis that we did, we made the determination that we would go on our own. So let's just look at the decision of doing this ourselves to see exactly how and what we've been doing thus far. So first of all, we've made the decision to put the U.S. headquarters in Massachusetts in the Greater Boston area. And so what that affords us is a very deep talent pool since we know that there's strong talent is in the biotech hub of the Greater Boston area. Thus far, I've been very happy to be able to bring on some experts, some subject matter experts with very deep multiproduct launch experience and backgrounds. And then as I said previously, I myself have gone through this playbook before with career experience on successful launches and very on-time launches. And then we -- it's very important to say that all of this planning is focused on not just an on-time launch, but the potential of having a priority review. So that's the timeline that we're anchoring against because it is the ultimate goal to be able to launch within a week or 2 of PDUFA approval. So what's been happening? We've already worked extensively on the things that would be defined as long lead time items, things such as manufacturing, distribution for those who know about this whole U.S. commercialization process. Serialization does take a long time, and we're well on our way there as well as getting the appropriate state licensing. We have done foundational market research, which is going to feed into both marketing and market access plans very nicely so that we really understand the market that we're going into, the customers and stakeholders and the needs there. We've already launched some work on our thinking around pricing and then early activation of medical affairs and building relationships is key and critically important. And I'll talk a little bit more about that in just a moment. So I think before we talk about more activities, it's really important to think about what the opportunity is as we define commercially the value of APHEXDA And so based on the Phase III GENESIS data, we do know that APHEXDA achieves optimal cell -- stem cell collection for nearly all multiple myeloma, autologous transplant procedures with just 1 dose of administration on top of GCSF. So looking at those transplant patients with multiple myeloma really starts to define what that market potential is. And this graph here speaks to that opportunity in the U.S. And with thinking about multiple myeloma with the potential to possibly expand into other indications approximately 80% to 90% of all autologous hemopoietic stem cell transplants are in the multiple myeloma and lymphoma space. And the multiple, it's important to know that this is not a longitudinal slide. However, the number of multiple myeloma auto transplants has been growing and has more than doubled since 2010. So just looking at the autologous cell transplants on the left gives a good perception and idea of the market that we are targeting in the United States. So I think the other thing in really thinking about going to market is what has already been discussed from an unmet need perspective. But this is really the anchor to the value proposition. We've heard that currently, there is still great unmet need, even with the therapies that are in the market right now. We know that there's still unmet need, and we've heard from both the clinical -- the physician perspective as well as the patient caregiver perspective on this, that still today, the potential for extended mobilization days as patients could possibly be collecting as we've seen upwards anywhere from as many as 4 to 8 days. and with the goal being to limit the number of days from a quality of life perspective and also from just a logistical perspective in the institutions, the apheresis centers. Also with increased mobilization days comes the increase of costs to the health care system to the patient, et cetera. And as I said, the scheduling piece is another logistical issue that needs to be thought here. And despite the advances that have already occurred in stem cell mobilization, some patients are really unable to mobilize enough in their mobilization sessions. Historically, there's anywhere from 15% to 35% of the patients really aren't able to mobilize enough, and that's what our market research has been showing. And then this just results in higher procedure costs to both the systems and to the payers. And then I think that this -- Dr. DiPersio really did a good job of talking about how the mobilization and induction has changed over the years. There's more and more elderly patients who are currently able to go to transplant. And with this, as many as for the quad induction for drugs regimen for induction. That is also, as we've heard, starting to reduce those overall yields. And so there's a good opportunity and space for a product like APHEXDA to potentially fulfill the unmet need and become the standard of care. So now let's talk a little bit more about why -- I mean that's a good background, I think, but let's really talk about what this means from going to the market. From my experience, I can say that this is really an ideal product and market for a small company with the goal of establishing themselves as a commercial entity in the U.S. And if you think about this, BioLine has the balance sheet has the management experience, building the management experience with deep subject letter expertise. We've got a great clinical product. But let's take a little bit of a deeper dive into some of these elements. So first of all, right product. Why do we say right product? We just heard from an apheresis nurse and from a multiple myeloma patient and her caregiver about the difficult patient journey, which really sets up that unmet need that I just described in my previous slide. There's definitely room in this market for improved treatment. And it should not be too difficult to get the word out because autologous transplants and hence, stem cell apheresis is highly concentrated with an unknown number of centers, making a targeted approach with a fairly small team of MSLs, account managers and sales professionals. It makes it fairly easy. So in other words, I guess what I'm trying to say is a small field footprint minimizes the costs and can also facilitate a large impact. So that's the right product, right market. Let's talk now about the right people. As I've described, we have had great success in thus far in our recruiting efforts, and we've developed a plan to phase in talent systems and resources according to both the premarketing, relationship building and scientific exchange needs. In addition, we are rightsizing the hiring process to not overbuild, but to hire the necessary U.S. entity support functions that will be required for BioLine to be able to do business in the U.S. So right product, plus right market, plus right people equals successful launch. We believe this focused and targeted approach will allow us to launch successfully into the marketplace, fulfilling the needs of the stakeholders while not unduly giving up too much shareholder value. Additionally, I think it's important to know that we are planning for a launch as close to our PDUFA date as possible. So let's now look at a very important prelaunch pre-marketing activity, a real important part of market preparedness is relationship building and understanding individual medical center practices. And this paves the way for stakeholder perceptions of both who BioLine is as well as what that stem cell mobilization landscape looks like. And the best way to accomplish this is the scientific exchange through medical science liaisons. Additionally, creating awareness of the company, our product and its data can be achieved through real solid scientific communication plans. Therefore, the early deployment of medical affairs activities is just foundational to physician and nurse education and something that I would put on that list of that long lead time item category. So BioLine U.S. has already begun this deployment. We started with a solid strategy, which encompass data generation through thinking about what the publication plan would be and the hiring and training of MSLs. We have used and will be using our U.S. medical affairs team to gather important insights on medical center practices and the protocols. And that will then -- and also to assist in putting in place an advisory board to make sure that we have the most informed launch as possible -- so I think that -- you want to move forward? Great. Thank you. So I just want to summarize the U.S. commercialization plan to say that we are targeting that $360-plus million U.S. stem cell mobilization marketplace. So that's the space that we're looking at from an overall sales perspective. And right now, BioLine is at a real crucial point in the U.S. launch readiness because we have, in fact, very excited to say that we filed our NDA. And so we have this differentiated clinical profile around efficacy, safety and dosing from our randomized Genesis Phase III data. We have the early market research, which shows pharmaco -- a very strong pharmacoeconomic outcomes. We've got limited and manageable requirements for our footprint in the U.S. with very successful uptake. Also, we have significant activities that have been initiated to meet the potential for a priority review. We've -- and this is all built around the thinking of what those real key success drivers or value drivers would be. So these include a belief in APHEXDA value proposition by the decision-makers, prescribers and payers, the rapid uptake in major transplant centers via increased awareness of BioLine and APHEXDA the publications and the continuing medical education activities to broaden the understanding in the stem cell transplant marketplace with differentiated outcomes and also coverage and reimbursement to secure good formulary status in the treatment centers and our key accounts. And probably lastly, it's important to say that we're really leveraging our U.S. infrastructure that we're building for APHEXDA for the potential for growth of BioLine in the U.S. for future commercial candidates. And with that, I would like to turn it back over to Phil.

Thanks, Holly. And thank you, Dr. DiPersio for your enlightening talk, and thanks also to the patient and caregiver for sharing the treatment journey with us is truly inspiring. This concludes our formal presentation. In summary, we believe that if approved, effect plus GCSF can quickly become the standard of care for all multiple myeloma patients by offering compelling value to both patients and to Transat facilities, recapping the overwhelmingly positive results for our Genesis Phase III study, which compared effects plus GCSF versus placebo plus GCSF, the study met all primary and secondary endpoints with an exceptionally high level of statistical significance. Of particular note, almost 90% of patients receiving effects of plus GCSF underwent transplantation after only one administration and 1 apheresis session. In addition, patients in the effects GCSF arm collected a median of approximately 11 million stem cells per kilogram in only one apheresis session versus $2 million in the GCSF arm. This confers significant benefits to Transcat facilities by allowing them to more efficiently schedule the apheresis sessions at the apheresis centers since apheresis machines tend to be in short supply at many of these sectors, also reducing the number of sessions required to mobilize the optimal number of stem cells or transplantation, lessens the burden on patients. This is particularly important as the advancement of new induction treatment regimens for multiple myeloma patients, which generally include multiple therapeutic compounds within the combination has been shown to substantially decrease the ability of patients to mobilize the target number of cells with existing products. It is for these reasons, in addition to the very positive pharmacoeconomic data that we reported previously that we believe affects the plus GCSF can quickly become the standard of care for all multiple myeloma patients. And while our initial focus will be on autologous central transplantation in multiple myeloma, longer term, we see opportunities to expand into peripheral indications in additional therapeutic areas. Autologous stem cell-based gene therapy is just one example of an area where improved mobilization agents are highly needed. In closing, we are proud to have the opportunity to introduce APHEXDA as a significant advancement in stem cell mobilization. We plan to work closely with the FDA during its review process, while in parallel, prepare for a robust commercial launch that ensures rapid and broad access for patients. And at this point, we'll open up the call for questions.

Thank you, Phil. [Operator Instructions]. But with that, we'll open it up with our first question from Mark Breidenbach at Oppenheimer.

Can you hear me?

We can.

Just maybe I was hoping to get Holly's thoughts on how motixafortide could compete with generic plerixafor given that this drug is going to be going off patent likely in 2023?

Thanks for the question. We are well aware of the market dynamics in the market that we're entering. I will say that we expect to distinguish APHEXDA based on its compelling clinical efficacy and pharmacoeconomic benefit. And when I speak about the clinical efficacy piece, I mean both from a quantity and a quality of a sales perspective. And I think it's important to reflect back on what we just heard from Dr. DiPersio, that there is a very strong clinical need for better mobilization agents, particularly with the treatment regimens that we see today, including Revlimid and DARZALEX. And he speaks about what that's actually doing from an overall treatment perspective. So we really think that there's a very compelling benefit to both the patients and the transplant centers for just more reliable transplant procedures. And we've also heard today from the nurse practicing at a major transplant center as well as from a multiple myeloma patient caregiver that there really is an opportunity to secure more stem cells from transplant and that, that would really relieve a lot of the burden to the patient and to the transplant facility. So all of this together wraps into the broader perspective on value proposition. And so based on those factors, we really believe that APHEXDA has the potential to be the preferred and optimal agent. That said, we are also doing market research around price and price sensitivity, and that will all be wrapped into the final decision on go-to-market.

Okay. And just in terms of -- with the approval of Abema and CaRVICTI in multiple myeloma, these products are being run in earlier settings. What are your expectations for the trend for autogas stem cell transplant in multiple myeloma over the next 5, 10 years? Are you expecting continued growth? Or are you expecting CAR-T to start eating into this market?

Abi, would you like to take that one?

Yes, sure. Mark, thank you for the question. Actually, every time there are things that are in development and more and more drugs are in development. But at the end of the day, tetransplantation is still the standard of care for treatment in multiple myeloma. And in any case, for example, if in the future, and I don't think in the near future, maybe in the far future, it will be not the first treatment. It will be the second one. Then autologous transplantation will be still there. This is the standard of care right now. Even with the approval of the Arzalex, there are still -- these patients need to underwent still transplantation. Furthermore, I must just say that in the last years, more and more patients are undergoing transplantation, even if they are over the age of 67. 67 was the cut of age a few years ago, and now we are going up and up. We have seen this. If you take studies from a few years ago, the median age was lower and in our study, which was much higher than in the past. Then even -- again, even with the new advances of therapies, I still believe that -- and not just believe we have seen that it's an increase in autologous transplantation for multiple myeloma.

And can I add on to that?

Yes, you can.

Thank you. So that's exactly what is being -- I think we've mentioned a few like eyes in the perspective of BioLine. But our perspectives are being rooted in very deep market research. So we know that with our first launch, we can't miss. We can't afford to miss. So we are looking at the marketplace from multiple angles. And this question that you ask is a good one because it is exactly what we are explaining right now with physicians who are practicing and with multiple myeloma hematology experts. And the feedback that we are getting from all of our deep analytics is that, that's not necessarily a near-term horizon competitive concerns. The future, as may look a little bit different, but in our near-term projections, we are not hearing from the marketplace that there's anything that's going to imminently change the need for stem cell transplant.

So the next question comes from John Vandermosten at Zacks.

Great. So we've got the $360 million market size. How much of that do you expect to take and will affect to replace or build on the sales in the existing market?

Holly, would you like to take that?

Sure. So at this point in time, we aren't talking deeply about our revenue forecast, but we -- again, from the insights that we're generating in the market right now, we are projecting to be very much focused on that multiple myeloma. That's our label indication. And so we are looking at that totality and we have projections over where we think we can be with peak sales, which should be occurring within the first few years. We could give you more from the deeper perspective. But right now, we're not necessarily able to share all of our perspectives on where we're landing from a revenue perspective.

Okay. And what you just mentioned brought up another question that I had. -- on when you feel that profitability may be reached. You said you're going to probably achieve peak sales relatively quickly. How long do you think that will take to get to that point?

Yes, John. So I mean I'm going to take this instead of Holly. I mean, we're really not able to give any guidance on breakeven or profitability at this point. I will just say, as Holly mentioned, this is a small footprint. This is a very manageable launch from a cost perspective because it's a limited number of transplantation centers throughout the United States. And therefore, we do believe that this could be quite a nicely profitable product, but I can't give you any more guidance than that at this point.

No, I got lots of unknown there. One of the trends in HSCT is that the addressable populations increased pretty dramatically. I think we heard that it doubled on the call today, and I've seen other information to support that improvements in the space has enabled older and sicker patients to put transplant. So APHEXDA affect to continue this trend and kind of expand that even greater just because, I mean, it was a great story from the patient on the burdens of the apheresis. What are the thoughts on that?

Holly, do you want to take that?

So yes, so we are seeing an increased trend over the last decade. And I think that if we -- some of the information that Dr. DiPersio shared with us is showing that, that market is expanding due to age due to better treatment for multiple myeloma. So it's allowing more patients, older patients, the opportunity for treatment and for longevity. Yes, I'm not sure if I'm answering your question, but we are looking at trends over time in autologous stem cell transplant, specifically autologous and using that for our future projections. And that is the trend that we are definitely seeing.

Okay. Great. Yes. I mean we're always learning technology is improving. Last one for me is just the opportunity for combination therapies. We had in the initial part of the presentation, just some of the mechanism of action of the drugs and how they release the mooring line, so to speak. And there are several different types of mooring lines. So I'm wondering if a combination approach might be appropriate maybe with the Magenta drug or something else. What are the thoughts on that?

Abi, do you want to take that?

Yes, sure. For sure, we will think for the life cycle management for further indications and combinations. We are already working on that. They are on top of the unmet need in the autologous transplantation in multiple myeloma. There are other unmet needs, for example, sickle cell anemia in which patients cannot -- are not able to receive GCSF and need very good mobilizers because they need a lot of sales to do the gene therapy. And we are already working on that, again, as a single agent and in combination for several indications. The Magenta drug, I don't know it's the fit for us, but we have several things in mind.

Okay. Great. Actually, I do have one more, and maybe you can follow up with me on this. But I'm just wondering what the capacity utilization is of the apheresis unit that was referenced in the panel discussion or even just overall if we have that information because it seems like -- that would be an important driver of uptake of the product.

Holly, go ahead.

Trying to answer. So I think I can answer the question. So again, this is one of the things that we are approaching from 2 different directions. We have -- we've been doing blinded market research. And so that is giving us a very fair assessment of the burden to the apheresis centers. We're hearing about how many days that are automatically booked for a patient right now, up to 4 days just automatically. So those chairs are held for patients. We believe that we can shift that dynamic knowing that most patients will only require 1 apheresis session. So that's important. We're also approaching this from a different direction, and I spoke about that in my section as well, where we have deployed medical science liaisons to do very early discussions and work around scientific exchange, not making any claims about APHEXDA, but really trying to understand center by center, how those -- how decisions are made and how scheduling occurs because that is a key critical part of the overall economic story. So we are on understanding the way that this is working right now in the U.S. marketplace. There's a good story. I mean it's a good story is what we're learning.

The last analyst question will come from Joe Pantginis at H.C. Wainright.

Thanks for all the details and visibility around the program. So I think my questions are mostly logistical. So first, I guess, Holly, you really gave a lot of details about the plan. Can you give maybe some numbers with regard to the size of the field force? Obviously, it's very targeted, very niche and how we're looking at potential how that number might change as you look towards additional indications.

Yes. So small is what I'm going to say, small and targeted -- so I mean I clearly have ideas right now, but some of this also has to do with how we finish looking at some of the data. We know that it's that 80-20 or 80-30 rule about where most of the autologous stem cell transplants are done in the United States. So it's very concentrated into less than 100 centers. Even though there's more centers doing transplants, that's where the majority, we can really make a big impact in that type of footprint. And we know that being able to get rapid uptake in market share is critically important. So we will be doing some traditional things like not only thinking about promotional sales, but also what we need to deploy as far as payer and account type folks. Again, not a lot. We feel like we can do this with a small footprint, and we already have begun to deploy and have MSLs working in the field as well. And we do believe that, that 3-pronged deployment will afford us the best possibility for a quick uptake. All that said, it's really small. And I've actually led this type of deployment before in transplant centers, and it doesn't really require a lot of people. And that's -- I think I said this, but I want to say this again, if there -- this is an ideal product for a company like BioLine to step into the commercial world in the United States. It just doesn't take extensive resource and OpEx in order to gain a really high impact. And I think that was a primary driving force for us making the decision to go this alone and be able to retain profits.

Got it. And if you look at the last end of my question about how the size thoughts might change as you go into additional indications, I would sort of ask that question again, but also more specifically, because Phil mentioned it, Dr. DiPersio mentioned all the different aspects that you guys would be considering potentially, do you have any early thoughts or plans beyond multiple myeloma that are at the protocol stage at this point and when we might see potential visibility on those programs.

I don't know who to give it to, Holly, do you want -- I mean maybe Abi, do you want to talk a little bit about that?

I'm wondering whether I can talk about this problem.

I don't know how much you can say. I mean all I can say. I mean, listen, we're looking at -- we're always looking at life cycle management possibility. We're also -- we're speaking with multiple potential collaborators all the time. We have a lot of ideas. I will say that our #1 priority is to have a successful launch of APHEXDA in multiple myeloma at this point. That's our #1 priority. We want to get there. We want to successfully launch it. We want to get to profitability as soon as possible. Everything else will come afterwards at some point, whether it's in the short term or the medium term. But I think that we want to be clear that right now, we're focusing the company completely on the successful launch.

Got it. And it totally makes sense with that focus. So just really 2 more questions, one a little maybe nonanswerable at this point, but you know I have to ask it anyway. It's always about what's next. So it's great visibility today on the commercial plans initially. And what are your current thoughts? And where does the process stand with regard to the ex U.S. opportunity? Because you -- obviously, you've had a lot of visibility with regard to regulatory authorities over there recently. And anything to share?

Yes, sure. So I mean I'll say that we're actively evaluating the European market in substantial detail both from a pharmacoeconomic perspective or regulatory and a commercial perspective. And when based on this analysis, we are going to decide on the best pathway forward regarding submission in Europe. In any event, I think that we've made it very clear, we are not going to commercialize in Europe on our own. We are going to look for a partner. I also want to mention that there are also other markets in the Asia Pacific, of course, and we're not ruling those markets at all, some of which rely somewhat on FDA approval in order to be able to launch into those markets from a regulatory perspective, again, with a partner, not on our own. And so we have future plans, and we think that there is potential upside to this program, significant upside to this program, both in Europe and in other places in the world. But I will say again, we're focusing right now on the U.S. and on a successful launch in the U.S.

Got it. And then just the last logistical question. I apologize if I missed this in any of your filings, I just wanted to make sure. With regard to the $40 million debt that you just announced recently, the additional 30, have you identified what those milestones are to trigger those tranches? Obviously, one is probably obviously approval or something like that, but are they disclosed?

Yes. So we have not disclosed them from a business competitive perspective. We're just not able to disclose what the milestones are, but they are contingent, of course. And so when we reach those milestones, of course, they will be available to us.

I'll now hand it over to Tim McCarthy of LifeSci Advisors to answer or read off any questions that came in over the webcast. Tim?

Thanks, Sarah. Several of the questions were asked and answered by the analysts. So there's one remaining question, which is regarding the location and manufacturing of the product.

Yes. So we are using high-quality, well-known manufacturers to manufacture both the drug substance and the drug product. The drug substance is being manufactured in the U.S. and the drug product is being manufactured in Western Europe. And so again, they're high-quality, well-known previously FDA-inspected facilities.

Okay. Great. There is actually one more. one moment. Can you please advise if there are any issues meeting the CMC requirements? Is the company well prepared for the FDA inspection of the manufacturing facility.

Okay. For that, I'll turn it over to Ella. Go ahead.

Okay. So with regards -- the FX is a peptide, and we have developed it according to all regulatory requirements. And therefore, we do not anticipate any particular challenges with this regard with regard to the regulatory requirements. And regarding the second part of the question of the FDA inspections of the manufacturing facilities, we are working with them. And what I can say is this, we are as prepared as can be.

Okay. So that's the end of the question-and-answer period. Phil, would you like to wrap up the call?

Yes, sure. So I'd like to thank the participants as well as all those who have joined us on the webinar today. A recording of the entire webinar will be available on the company's website starting in about 2 hours from now, and it will be available through October 31st, 2022. That's it for now. Thanks for joining us, and have a great day.