Good morning, and welcome to the BioLineRx APHEXDA FDA approval conference call. My name is Yoni Schottenstein, and I will be your operator for today's call. All lines have been placed on mute to prevent any background noise. After the conclusion of the speaker's prepared remarks, there will be a question-and-answer session. It is my pleasure to introduce John Lacey, Head of Investor Relations and Corporate Communications at BioLineRx. John, you may begin the call.
Thank you, Yoni. Welcome everyone to this morning's call, where we are very pleased to discuss the U.S. Food and Drug Administration's approval of APHEXDA, the trade name for motixafortide. Joining me today are Phil Serlin, our Chief Executive Officer, Holly May, President of BioLineRx USA, and Beth Giblin, U.S. Head of Medical Affairs. In addition, Ella Sorani, our Chief Development Officer, will be joining the call for Q&A. I'd like to remind you that certain statements we make during the call will be forward-looking. Because such statements deal with future events and are subject to many risks and uncertainties, actual results may differ materially from those in the forward-looking statements.
For a full discussion of these risks and uncertainties, please review our annual report on Form 20-F and our quarterly reports on Form 6-K that are filed with the U.S. Securities and Exchange Commission.
With that, I'll turn the call over to our CEO, Phil Serlin.
Thank you, John, and welcome to our call, everyone. With the FDA approval of motixafortide, which will be known commercially as APHEXDA, we have achieved an important milestone for patients, caregivers, prescribers, and the company. In the U.S., APHEXDA is now indicated in combination with filgrastim, commonly known as G-CSF, to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. As many of you are aware, multiple myeloma is the second most common hematologic malignancy, and autologous stem cell transplantation is part of the standard of care treatment paradigm for multiple myeloma and delivers prolonged survival for patients with this cancer type. Historically, depending on induction regimens and mobilization strategies, up to 47% of patients have had challenges collecting target numbers of hematopoietic stem cells for autologous transplant after one session.
Today, greater numbers of multiple myeloma patients are receiving more powerful induction therapies, and stem cell yields may be negatively impacted as a result. Aphexda is the first innovation in stem cell mobilization for multiple myeloma to be approved in the U.S. in over a decade, and we believe that it has the potential to address today's challenges by delivering more reliability in stem cell mobilization with fewer days of apheresis sessions and fewer doses of G-CSF for people living with this cancer. There are many people to thank for bringing this new innovation to approval. First, I want to thank the patients who had the courage to enroll in our trial and help advance the field. I want to thank the clinicians, transplant center care teams, caregivers, and advocates who supported these patients throughout their transplant journey.
I also want to thank our BioLineRx team, past and present employees, our advisors, and board members for their contributions to this milestone. This approval would never have happened without you. Finally, I'd like to acknowledge the key role the FDA has played in supporting the development of APHEXDA and other innovative therapies for patients with cancer. We are grateful for their meaningful and supportive interactions throughout this process. With regard to launch, we are ready from an organizational perspective and plan to get APHEXDA to transplant centers and patients within the next few weeks. We are encouraged by our discussions with payers regarding coverage and reimbursement for APHEXDA, and we look forward to partnering with transplant centers to deliver APHEXDA to patients in need.
Now, let me turn the call over to our U.S. Head of Medical Affairs, Beth Giblin, who can walk us through what the approval means from a clinical standpoint. Beth, over to you.
Thank you, Phil, and good morning to those on the call. I want to reinforce our appreciation of the FDA on this first approval indication for motixafortide. As we've said for many months, we've had great dialogue with our FDA reviewers and want to thank them for their diligence throughout this review process. Today, as Phil mentioned, APHEXDA is indicated in combination with filgrastim, more commonly known as G-CSF, to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma. APHEXDA is a CXCR4 antagonist with long receptor occupancy, greater than 72 hours, and is the first innovation in stem cell mobilization for multiple myeloma to be approved in the U.S. in a decade.
Based on the strong efficacy data from the GENESIS Phase 3 trial used to support our indication, we believe APHEXDA will play a critical role in addressing unmet needs and will introduce a new treatment paradigm for those with multiple myeloma who require an autologous stem cell transplant. Multiple myeloma is the second most common hematologic malignancy, and autologous stem cell transplantation is part of the standard of care treatment paradigm for multiple myeloma and helps deliver prolonged survival for patients with this cancer type. The American Society for Transplantation and Cellular Therapy guidelines recommend a collection target of three to five million CD34+ cells per kilogram. Additionally, collection of sufficient number of cells to perform two transplantations is recommended.
The International Myeloma Working Group consensus recommends four to six million CD34+ cells per kilogram, with a target of eight to 10 CD34+ cells per kilogram to allow for two transplants if needed. The success of autologous stem cell transplant does depend on adequate mobilization of stem cells during the treatment process. While increasing number of patients with multiple myeloma are candidates for autologous transplantation, some patients are experiencing mobilization challenges and resulting consequences. Poor stem cell mobilization can be attributed to a variety of risk factors. As age increases, there is a reduction in the population of available stem cells that can be used for transplantation. The proportion of older patients receiving autologous transplantation has increased over the last decade, with around 38% of patients being aged 65 years or older in 2021.
Evolving induction regimens in multiple myeloma can further impair mobilization, with fewer cells mobilized and additional days of apheresis required. Other risk factors include prior mobilization failure, previous treatment failure, previous radiation therapy, and low CD34 cell counts pre-apheresis. Studies indicate that many patients require multiple apheresis sessions and/or may never progress to transplant. As age and use of more potent triple and quadruple induction therapies increase, most patients will require CXCR4 antagonist mobilization, either upfront or as rescue therapy. The GENESIS study included patients considered representative of a typical multiple myeloma population undergoing autologous transplantation, with a median age of 63 years and with approximately 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
As mentioned, increased age as well as exposure to three and four induction regimens, including drugs such as lenalidomide, have been associated with impaired stem cell mobilization.
In this contemporary population, patients in the APHEXDA plus filgrastim arm were able to mobilize more than four times the amount of stem cells with a single dose over a 24-hour period compared to placebo plus filgrastim. If you put it another way, after only one dose of APHEXDA plus G-CSF, a majority of patients successfully collected 6 million cells per kilogram in one to two apheresis sessions. In this study, central lab data was used for efficacy, which found that 67.5% of patients in the APHEXDA plus filgrastim arm were able to achieve the stem cell collection goal of at least 6 million CD34 cells per kilogram within two apheresis sessions, versus 9.5% for the placebo plus filgrastim regimen.
Local laboratory data, which was used for clinical decisions, found that 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the APHEXDA arm versus 21.4% in the placebo arm. The overall safety profile was found to be favorable in the GENESIS study, and APHEXDA was generally well tolerated. Serious adverse reactions occurred in 5.4% of patients receiving APHEXDA plus filgrastim. These reactions included vomiting, injection site reaction, hypersensitivity reaction, injection site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions occurring in GENESIS, incidence greater than 20%, were injection site reactions, including pain, erythema, and pruritus, pruritus, flushing, and back pain. We believe that APHEXDA provides a strong and meaningful clinical benefit to patients and prescribers and addresses the demand for new therapy that can meet today's challenges.
Now, let me turn the call over to our BioLineRx US President, Holly May, who will provide an update on our plans to launch APHEXDA.
Thank you, Beth, and good morning, everyone. As Phil and Beth both indicated, we are very excited for APHEXDA's approval. Beth did a great job laying out the tremendous clinical benefits that APHEXDA can have on patients. It's important to remember that an apheresis procedure can be challenging for patients and their caregivers. Currently, patients undergo four daily doses of G-CSF before their first apheresis session. On the morning of the day of apheresis, the patient is given another dose of G-CSF. A central venous catheter is implanted in the upper chest, and apheresis is then performed in the chair for up to six hours. After that, the cell count is determined, and if the patient has not mobilized to the targeted count, the catheter remains in place so the process can be repeated the next morning.
In some patients, there is the potential for this to continue for up to four days. For patients who must travel to the apheresis center, this can be a significant logistical burden, and it can also be a considerable psychological burden, not knowing if there will be enough mobilized cells to continue on the treatment journey to transplantation. The patients alone don't feel the burden of uncertainty. Our insight generation showed that many transplant centers can find it challenging to efficiently manage their apheresis chairs. There are challenges with scheduling and optimizing chair time based on the patient-to-patient variability in individual stem cell yields. We believe that APHEXDA can change this paradigm by providing improved treatment journeys for patients and more certainty for transplant centers. Accordingly, we have set the price for APHEXDA at $5,900 per vial.
This price is based on extensive research and reflects the value proposition of APHEXDA while appropriately considering the new generic landscape. Our expert commercial operations and medical affairs leadership teams have extensive experience in stem cell transplantation as well as multiple myeloma. Through these leaders and their field teams, we are executing our launch strategy and engaging with top centers and physician leaders around the country. As Beth described earlier, our first strategic launch imperative is to educate physicians and other healthcare providers on the unmet needs of roughly 8,000 patients who proceed to autologous stem cell transplantation each year in the United States. Our second strategic imperative is to establish APHEXDA as the mobilization agent of choice. We are focusing at launch on the top 80 centers that perform more than 85% of autologous transplants for multiple myeloma.
Our early post-launch focus is on the centers with the greatest unmet need due to their inability to collect an optimal number of stem cells and/or to manage patient apheresis chair demands. We aim to achieve unrestricted and affordable patient access across government and commercial payers for APHEXDA. Our commercial team of account directors have met with payers covering more than 90% of commercially covered lives, which includes both commercial payers and CMS. Payers have viewed the APHEXDA clinical data favorably and supported the positive benefits to the patient and the healthcare system. Based on early feedback, we have confidence that payers recognize the significance of APHEXDA, and so we are committed to working with them to help ensure patient access by generating broad coverage within the first few months of launch.
It's important to know that our supply and distribution team has been working diligently to ensure that there will be product in the pipeline as soon as possible. Since we have now received the approved FDA label, we have a tight and precise plan for final packaging and QA release, shipment, customs clearance, and delivery to the third-party logistics vendor. Additionally, we have established strong business relationships with both the transplant community and the large specialty distributors to ensure we can efficiently deliver APHEXDA to the patients who need it, regardless of their location in the United States. This plan allows for product in the hands of customers within weeks of launch. Finally, we are establishing a dedicated patient-centered support program called BioLineRxConnect, which is designed to assist with insurance coverage, financial support, the payer process, and additional resources.
A fundamental component of our mission is a dedication to improving access and outcomes for all eligible patients. Once the doctor and the multiple myeloma patient have decided that APHEXDA is the right choice for mobilization, BioLineRx can help find the resources patients need to get started. We are excited to be bringing APHEXDA to the marketplace as the first new therapeutic in stem cell mobilization in over a decade, and our U.S. team will be working hard to establish it as the new treatment paradigm for autologous transplant patients and multiple myeloma patients, their physicians, and the transplant centers that care for them. Now I'll turn the call back over to Phil.
Thank you, Holly. Let me reiterate our belief that the FDA approval of APHEXDA is an important advancement for patients with multiple myeloma who will undergo autologous stem cell transplant. This approval also marks a major step in BioLineRx's mission of building a legacy of changing lives around the world. I'd now like to open the call up to questions.
Thank you. Ladies and gentlemen, at this time, we will begin the question-and-answer session. If you would like to ask a question, please press star one. To withdraw your question, please press star two. If you're using speaker equipment, kindly lift the handset before pressing the numbers. The questions will be polled in the order they are received. Please stand by while we poll for your questions.
The first question is from Joe Pantginis of H.C. Wainwright. Please go ahead.
Hi, everybody. Good morning and an absolute congratulations. This truly is a momentous occasion for the company, and I'm so happy I was with it for the whole story. And I'll tell you, Phil, we're missing you, missing you in New York right now, but I think a drug approval is a good excuse, so we'll cut you some slack there. So a couple questions, if you don't mind. So first, so thanks for providing the cost per vial, $5,900. I wanted to get a sense maybe of some projections regarding obviously, patients might have one or two apheresis and how you're thinking of the average number of vials for each patient.
All right. First of all, Joe, thanks very much for your kind words. I really appreciate it. Yes, this is truly a momentous occasion for the company, and we're looking forward to executing. Let me turn the call over right now to Holly. She can answer your question, so hold on for one second.
Hey, Joe, this is Holly. Yes, we're all just so incredibly excited for the approval of APHEXDA by the FDA. So to answer your question, APHEXDA is a weight-based dosing. It's 1.25 mg/ kg, and based on our research of the average weight of a multiple myeloma patient, this averages out to two vials per patient.
Got it. No, that's extremely helpful. Yep. Sorry. Yep. So and then I guess the next question is, now that you have the approval in hand, we're very excited, even on your earnings call, that you said, you know, you're basically ready to go now. You'll have it in patients and centers by the end of the month. How can we view anything that the approval triggers with regard to any need to now, you know, increase capacity that you might have been waiting on based on the approval, or you just basically have everything you need?
Yeah. So are you talking specifically about increasing capacity in manufacturing? Is that your question, Joe?
Yeah. Yes.
Cool.
... Okay, so on manufacturing.
Manufacturing, yeah. Sorry.
Yeah, so we're well set on the manufacturing side. We have everything in place. We've had it in place for a while now, and we're just ready to go.
Mm-hmm. Got it. Got it. And then, I guess the last part here, you know, obviously, you're gonna be partnering with more transplant centers. What is the low-hanging fruit right now with regard to the launch, you know, with regard to centers? I guess, I mean, is it obvious that you'll be targeting the centers that were part of Genesis? You know, the physicians are already engaged, and then where are you looking to go from there?
Go ahead, Holly.
Yep. Yes. So yes and yes. So we, yeah, so yes, and yes. So in the pre-launch period, we had our medical teams out for over a year now, just making sure that they've got good relationships with the Genesis clinical trial sites and all of the stakeholders within those sites. But we have a very, very tight plan. I think we've been talking for quite some time about the fact that this is a fairly small footprint and able to make a large impact in the marketplace. We are focused on the top 80 centers, which actually perform 85% of the transplant, allogeneic stem cell transplants for multiple myeloma patients per year.
We've also hired a very experienced field team that have relationships from past employers with the stakeholders. So we believe that we are going to be able to make an immediate impact. But even within those top 80 centers, we even have those prioritized around those that have the greatest unmet need in regards to clinical care, logistics, et cetera. And so we've got a really, really tight plan on how we want to approach the market. We also are at 100% right-sized in our field team. We have three field teams. We've got the sales team, we have the medical team, and we also have the national account payer team.
Again, extensive research in the number of accounts that need to be covered by those field individuals in order to make the most significant impact.
No, that's fantastic. Thank you. And do you mind if I ask one more question, and thank you for indulging me? I guess this is a little bit more of a hand-waving question or, you know, speculation. As APHEXDA is, you know, being used in the real world, do you anticipate any sort of adjustments or, you know, how physicians or nurses would give it that might increase the number of cells, say, in one versus two apheresis, you know, how real-world use might impact the potential increase in the number of cells quicker?
Let's see if I understand that question.
Based on experience and things you've learned and a bit of speculation.
Yes. So we have learned from our market research that there is a desire for being able to mobilize a high number of stem cells for each patient. Now, the saying that we have is, if you've seen one transplant center, you've seen one transplant center. So the reason for the need for increased numbers of cells kinda varies, whether it is institutions that want to have the cells in reserve for a second transplant, or if it's just a transplant center that wants to infuse a higher number, or you have a higher number of stem cells for their first transplant. I'm sorry. So this is insight that we have absolutely been generating through our pre-launch activities to really understand institution by institution, you know, what their desired practice is.
You know, following guidelines is important, but each institution then has their own kind of protocols in place as to what they want. So because we know that, we have been able to really kind of forecast where we think there could be increases in utilization of a stem cell booster like motixafortide, especially one that has such strong clinical results. So I do want to make sure that I've answered your question fully, because I'm not sure if that is enough.
You, no, you really have. You, you totally have, Holly. Thank you so much for that. And, guys, thank you so much for the color on the answers. Congratulations again, and on to the next.
All right. Thank you so much.
Thanks, Joe. Really appreciate it. Thank you.
The next question is from John Vandermosten of Zacks. Please go ahead.
Thank you. And I also wanted to send all my congratulations. It's a lot harder now than it used to be to get an FDA approval, so they're definitely in order. I wanted to build on Joe's question, just on the number of vials that may be required. So I think the two vials and also some clarity from Holly on that. So two vials for apheresis session, and then with a potential for maybe, on average, a second apheresis session. Is that correct?
I, yeah, I think I can try to, I can try to answer that, because we're having trouble hearing you a little bit, John. But, you're saying, what, you know, for each administration, let me just, clarify. For each administration or treatment, each administration of APHEXDA, there would be, on average, two vials given. And as you know, we don't need to administer it for each and every apheresis session, which is an advantage of ours. We can, one dose, the two initial vials are enough for two days of apheresis sessions. And so therefore, we don't anticipate, in most cases, having to administer more than the first two vials. Does that answer your question?
Yes, it does. Exactly. All right, thank you.
Okay, great.
As we know, there are more conditions beyond multiple myeloma where stem cell mobilization can benefit, such as lymphomas and leukemias. I'm wondering what needs to happen for those to be added on, practically, I suppose, to you know, to the patients who can take advantage of it? Thanks.
Well, John, I'm just having a lot of trouble hearing you. Is it possible for you to repeat your question?
Yes, I apologize for that. So there are a number of other conditions beyond multiple myeloma where stem cell mobilization can benefit, such as the lymphomas and leukemias. And I'm wondering what needs to happen for APHEXDA to expand into those broader indications.
Oh, I understand. Okay, so you wanna talk about how, what would—what we would need to do to expand? Do you wanna take that maybe a little bit, Ella?
Yeah, sure. Hi, I can address this. So we are looking into a life cycle management, trying to assess APHEXDA to maximize the potential wherever we can in order to make it possible to use it. We are assessing currently what would be the best way to do it, but we're definitely looking into the possibilities to extend the use of APHEXDA.
Okay.
Yeah. I mean, we have both plans through our own clinical trials that we've announced on, you know, label expansion areas, such as the clinical trial in sickle cell. That said, we do understand there's other areas where mobilization agents are used, and we do have a pretty solid investigator-sponsored study program for those investigators or for those sites that are interested in additional areas. We are taking all of those things under consideration, in addition to having our own plans around the label expansion needs for motixafortide.
Okay. And then, you know, kind of expanding on that, even more. You know, there are a lot of other indications that you mentioned in terms of gene therapy and other and the oncology, the cancer indications as well. How does this approval help with those efforts?
Yeah, well, I mean, first of all, I think just having, you know, an approved drug is just, you know, provides a lot of validation, for, you know, for discussions with potential collaborators, et cetera, et cetera. I think we also mentioned when we spoke about our out-licensing agreement in China, that there are a number of territories and regions and countries around the world that will accept U.S., you know, FDA approval as the basis for their own local approval. So this will, potentially open up rather quickly for us, the, you know, these markets and for our, especially for our, Asian partner, there are a number of areas in Asia where FDA approval is sort of a, you know, an easy pathway forward to, you know, to, approval in those countries.
And so we could ostensibly, hopefully see revenues from, you know, from that area, you know, earlier than you know, we would typically expect if we had to run a Phase 3 or some kind of a study there as well. Similarly, even in you know, in places like China and Japan, which do require a study, they would you know, generally require only a small bridging study and not you know, not an additional Phase 3, and so that would also be very helpful for us as well. There are other areas, not just China, we're looking at. You know, we have a rest of world strategy that we've you know, we're starting to build already and we're starting to execute on.
So, you know, we also are looking at other countries as well around the world that, you know, that we could use this approval as, you know, as a launching point to enter those markets as well, with a partner, of course.
Great. Great. And then last question for me is, just on manufacturing and looking ahead, because, you know, hopefully in a few months, this will be a global product. Do you anticipate having multiple manufacturing facilities around the globe, or do you think that one will be sufficient?
I think it's something that we are obviously considering. But you know, I don't have any news on that right now, but it is something that we are considering. At the moment, our manufacturing sites are sufficient for, you know, our foreseeable, you know, supply needs in the future, but it's certainly something that we would consider as time goes on.
Great. Thank you, Phil. Thank you everyone else. Appreciate it.
All right. Thank you.
This concludes the Q&A session. Before I ask Mr. Philip Serlin to go ahead with his closing statement, I would like to remind participants that a replay of this call is scheduled to begin 2 hours after the conference. In the U.S., please call 1-888-929-5263. In Israel, please call 03-925-5904, and internationally, please call 972-3-925-5904. Mr. Serlin, would you like to make your concluding statement?
Yes, I would. Thank you. Before closing today's call, I want to thank everyone again for taking the time to join us for what is the most important achievement in the company's history to date. As mentioned, we have been advancing pre-commercial activities in anticipation of FDA approval of APHEXDA, and as a result, we are well positioned to hit the ground running and look forward to entering the market in the next few weeks.
While we have been laser focused on executing the successful launch of APHEXDA, we have continued to advance important lifecycle growth areas for motixafortide with our clinical partners, including a bridging study in China for stem cell mobilization and multiple myeloma that can support approval in Asian territories, two large randomized Phase 2 and Phase 2/3 studies in first-line metastatic pancreatic cancer, and a Phase 1 study in stem cell mobilization for gene therapies in sickle cell disease. We believe these programs, together with today's approval in stem cell mobilization for multiple myeloma patients, reflect the potential versatility of motixafortide to improve patient outcomes across a range of complex diseases while creating enduring value for our shareholders. Thank you again for your continued interest in BioLineRx, and have a good day.
Thank you. This concludes the BioLineRx investor call. Thank you for your participation. You may go ahead and disconnect.