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spk09: Ladies and gentlemen, thank you for standing by. Welcome to the BioLine RF third quarter 2022 results conference call. All participants are presently in a listen-only mode. Following management's formal presentation, instructions will be given for the question and answer session. For operator assistance during the conference, please press star zero. I would now like to turn over the call to John Lacey, head of corporate communications and investor relations. Please go ahead.
spk05: Thank you, operator. Before turning the call over to management, I would like to make the following remarks concerning forward-looking statements. All statements in this conference call, other than historical facts, are indeed forward-looking statements. The words anticipate, believe, estimate, expect, intend, guidance, confidence, target, project, and other similar expressions are used typically to identify such forward-looking statements. These forward-looking statements are not guarantees of future performance and may involve and are subject to certain risks and uncertainties and other factors that may affect BioLine RX's business, financial condition, and other operating results. These include, but are not limited to, the risk factors and other qualifications contained in BioLine RX's annual report on Form 20-F, quarterly reports filed in a 6-K, and other reports filed by BylineRx with the SEC to which your attention is directed. Actual outcomes and results may differ materially from what is expressed or implied by these forward-looking statements. BylineRx expressly disclaims any intent or obligation to update these forward-looking statements. At this time, it is now my pleasure to turn the call over to Phil Serwin, Chief Executive Officer of BylineRx.
spk03: Thank you, John, and good morning, everyone. And thank you for joining us on our third quarter results conference call today. Earlier this morning, we issued a press release, a copy of which is available in the investor relations section of our website. It was also filed as a 6K. As is our practice, I will begin with an overview of our third quarter, then Molly Zevi, our chief financial officer, will provide a discussion of our financial results. We will then open up the call and are looking forward to your questions. Also joining the call for Q&A are Abby Weinstein, our Chief Medical Officer, Ella Serrani, our Chief Development Officer, and Holly May, President of Violine Rx USA. The key highlight since our last quarterly update is unquestionably the submission and subsequent acceptance by the FDA of our new drug application for metixifortide, now known by its brand name Afexta, in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients. The agency has assigned a PDUFA target action date at September 9, 2023. The NDA was based on the overwhelmingly positive topline results from our Genesis Phase III trial, which compared a FEXTA on top of GCSF versus placebo on top of GCSF. Recall that we held a successful pre-NDA meeting with the agency this past December and gained alignment on key aspects of the filing, most notably that a single phase three study genesis would be sufficient to support a submission. The study met all primary and secondary endpoints with a very high degree of statistical significance, a p-value of less than 0.0001. Notably, approximately 90% of patients in the genesis study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of Aphexa and in only one apheresis session. compared to less than 10% of those receiving GCSF alone. In addition, patients in the Effecsta plus GCSF arm collected a median of approximately 11 million stem cells per kilogram in only one aporesis session, versus approximately two million in the GCSF arm. The combination was also found to be safe and well tolerated. This high success rate has a substantial clinical benefit, especially when considering that new induction treatments are more effective than ever before, but cause subsequent difficulty in mobilizing the target number of stem cells for transplantation. The high success rate may also confer significant benefits to transplant institutions through the more efficient use of apheresis units, where there is often a lack of available machines. Given that the potential benefits of Afexda over the current standard of care accrue to multiple healthcare stakeholders, We anticipate rapid uptake in the market if and when approved. We plan to commercialize Effecsta in the U.S. independently. We have made this decision after a careful and lengthy review of our options, led by Holly May, president of our U.S. operations. Commercializing Effecsta ourselves will both accelerate its availability to multiple myeloma patients, while at the same time allow us to maximize the value of the asset for our company. Recall the third-party market research that we commissioned earlier this year concluded that in 2001, the U.S. stem cell mobilization market was approximately $360 million annually and growing steadily, and it was in excess of $500 million annually on a global basis. We have indicated before that the stem cell mobilization market is highly concentrated as approximately 80 transplant centers out of 212 perform approximately 80% of stem cell procedures. Therefore, the commercialization expenses and footprint required would be limited relative to a more traditional oncology launch in a broader indication. With our NDA now accepted, we look forward to working with the agency during its review process, while in parallel advancing our multifaceted pre-launch plan, including the ongoing build-out of U.S. infrastructure so that we are well-positioned for a robust launch if and when approved. To ensure that we are financially well positioned to execute the most effective launch possible, subsequent to the submission of our NDA, we announced the completion of two financings that in the aggregate give us access to up to $55 million of additional funds. First, we announced a $40 million non-diluted debt financing agreement with Creos Capital. Creos is a leading provider of innovative and flexible debt solutions. to equity-backed pan-European and Israeli high-growth companies in the technology and healthcare sectors. Per the terms of the agreement, the first tranche of $10 million was made available to us upon execution of the definitive agreement. The remaining $30 million will be made available in two additional tranches, subject to the achievement of pre-specified milestones. The tranches are available for drawdown at our discretion at various time points through October 1, 2024. Borrowings under the financing will bear interest at a fixed rate of 9.5% per annum, approximately 11%, including associated cash fees. And in addition, Krios would be entitled to mid- to high-single-digit royalties on effects to sales, up to a predefined cap. Following the close of the debt financing agreement, we also completed a $15 million registered direct equity offering of American depository shares. With the funds received from these transactions, our cash balance at September 30, 2022 was $57.3 million, which, including the additional potential amounts available to us under the debt financing agreement, we believe positions us very well financially to execute the targeted commercial launch that we are planning should effectively be approved. Turning now to our Metixifortide Pancreatic Cancer, or PDAC, program, Recall that earlier this year we entered into a development collaboration agreement with Genfleet Therapeutics. Under the terms of this agreement, Genfleet plans to execute a rigorously designed randomized phase 2B clinical study in approximately 200 first-line metastatic PDAC patients in China. Importantly, we maintain full rights to metixifortide across all indications and geographies, while GenFleet would be entitled to a small, single-digit sales royalty should Affecta ultimately be approved. This collaboration is based on the positive results that we reported from our Phase 2A Combat Keynote 202 triple combination study of metixiportide in combination with Merck's anti-PD-1 Keytruda and chemotherapy as a second-line therapy. As a reminder, data from the Phase IIa study demonstrated a substantial improvement across all study endpoints as compared to historical data, including median overall survival, median progression-free survival, confirmed overall response rate, overall response rate and disease control rate. Based on their development capabilities in China, including experience in conducting combination trials in the immuno-oncology space, We believe we have found the ideal partner to advance effects in pancreatic cancer and look forward to the initiation of this trial in 2023. Also recall that motixifortide is being evaluated in a separate investigator-initiated PDAC trial in collaboration with Columbia University. That Phase II study is evaluating motixifortide in combination with the anti-PD-1 libtio, and chemotherapy as a first-line PDAC therapy. That study continues to progress, and we will share additional updates, including the potential timing of data, which we hope will be during 2023 when available. Our presence at important medical congresses is key to raising awareness of the potential of metixifortide, and the American Society for Hematology meeting next month, December 10th through 13th, is perhaps the most important of the year. We are very pleased this year to announce two poster presentations at ASHE. The first presentation will detail full results from our pharmacoeconomic study that indirectly evaluated the cost effectiveness of using motixifortide as a primary stem cell mobilization agent in combination with GCSF versus plurixifor in combination with GCSF in multiple myeloma patients undergoing autologous stem cell transplantation. Data from the study demonstrated meaningful net cost savings with metixifortide plus GCSF due to a significantly greater proportion of patients in the metixifortide arm successfully achieving mobilization of the optimal amount of stem cells following a single administration of metixifortide and in only one aporesis session. The second presentation would detail the design of a phase one trial that will assess metixifortide as part of a novel stem cell mobilization regimen to evaluate its ability to safely produce the sufficient quantity of hematopoietic stem cells required for the genetic manipulation processes used in gene therapy development. The study will further examine the quality of the mobilized stem cells, including immunophenotypic and single cell transcriptional profiling. The trial will include patients with sickle cell disease, one of the most common inherited genetic diseases globally, and a condition where GCSF mobilization is associated with severe adverse effects. Plurixifor alone has not demonstrated an ability to reliably yield optimal hematopoietic stem cell numbers for gene therapy applications. We think gene therapy is just one example of how we can ultimately leverage metixifortide into additional high need indications. Turning now to our second clinical candidate, the intratumoral anti-cancer vaccine AGI-134. We are evaluating safety, tolerability, and proof of mechanism in multiple solid tumor types in a phase one two-way study. The study is designed to evaluate a wide array of biomarkers and assess both clinical and pharmacodynamic parameters. We believe that AGI-134 coats tumor cells with alpha-gal to make them look like foreign tissue to evoke an immune response that both destroys existing tumors and provides a vaccine-like effect. We anticipate sharing data from part two of the phase one to eight trial by year end. I would now like to turn the call over to Molly Zevi, our CFO, who will give a brief overview of our key third quarter financial statement items. Molly, please go ahead.
spk10: Thank you, Phil. As is our practice, in our financial discussion, we will only go over a few significant items on this call. Research and development expenses and cash. Therefore, let me invite you to review the filings we made this morning, which contain our financials, operating and financial review, and press release for additional information. Resource and development expenses for the three months ended September 30, 2022, were $4.4 million, an increase of $0.5 million, or 11.3% compared to $4.9 million, for the three months ended September 30, 2021. The decrease resulted primarily from lower expenses related to Mutixa Fortide NTA supporting activities, as well as lower expenses associated with the completed Mutixa Fortide Genesis clinical trial, offset by an increase in payroll and related expenses. Research and development expenses for the nine months ended September 30, 2022, were $14.2 million, a decrease of $0.1 million, or 1% compared to $14.3 million for the nine-month ended September 30, 2021. The decrease resulted primarily from lower expenses related to NDA supporting activities related to motixofortide, as well as lower expenses associated with a completed motixofortigenesis clinical trial offset by an increase in expenses associated with the AGI 134 study. Turning to cash, the company held $57.3 million of cash, cash equivalents, and short-term bank deposits as of September 30, 2022. As Phil indicated, our cash includes $10 million from the CREAS agreement and $13.5 million in net proceeds from the Registered Direct Offering but does not include the additional $30 million available to us under the CRIAS agreement, which is tied to attainment of certain milestones. We believe we're well financed to achieve multiple potentially value-created milestones into the first half of 2024. And with that, I'll turn the call back over to Phil.
spk03: Thank you, Molly. In closing, as is our custom, I would like to take a few moments to summarize our key upcoming milestones. First, announcement of initial results for part two of the phase one two-way trial of AGI-134 in solid tumors by the end of the year. Then, the potential FDA approval of Afexta in Q3 2023. Also the potential US launch of Afexta in stem cell mobilization in Q3 2023. And the initiation of a phase two B randomized study of Afexta in PDAC under our collaboration with Genfleet in 2023. Finally, before turning the call over to questions, I'd like to personally thank our CMO, Abby Weinstein-Harris, for her many years of service to the company. Abby has recently decided to move to the U.S. with her family and will be departing the company effective December 31, 2022. Following that, she will be staying on as an advisor through at least the end of 2023, ensuring a smooth transition of responsibilities, including full support during the FDA review process. The company has started a search for a new CMO and will announce the new appointment at the appropriate time. With that, we have now concluded the formal part of our presentation. Operator, we will now open up the call to questions.
spk09: 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 1. To withdraw your question, press star 2. If you are using speaker equipment, kindly lift the handset before pressing the numbers. Your 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 Pangenis of HC Wainwright. Please go ahead.
spk01: Hey, everybody. Good morning and good afternoon. Thanks for taking the question. And let me start off by... wishing Abby well in her future endeavors, and it was great working with you here. So let me just focus on metixifortide first. So first, I just want to see, do you have any indication about whether the FDA might look to have an adcom?
spk03: Yeah, so the FDA has stated they're not currently planning to hold an advisory committee meeting to discuss the application.
spk01: Okay, perfect. And then maybe for everybody, but Holly especially, based on your comments, Phil, obviously this is a limited commercial. expense type of indication, very focused group. Holly, what do you think is the primary rate-limiting step for this launch? A lot of times a new drug might be education, bringing on a sales force, but this seems pretty focused, so I'm just curious what you feel are the primary rate-limiting steps to initial commercial success.
spk08: Yeah, I mean, I am not worried about any rate-limiting steps. Just to be clear, and part of it is for the exact reason that you spoke of. This is a very manageable sort of launch, concentrated launch, and it's the ideal for a company like BioLine to enter into the user's site. So what's the things? There's many things, though, that could be rate-limiting steps, but I feel like we are very much ahead of those. So there's a lot of what I would call long lead time items, like being able to actually have product in the marketplace through serialization, and we're well on the process there. We've selected a 3PL partner. We've got our secondary packager up and running. We are really well attuned to what the demand drivers are in this market, and even more so since the last time we spoke because we have done even deeper market research. I've got almost all of my frontline leaders on board now. They're all deep subject matter experts. And we have been doing what I think is just some of the best market research that I've been a part of on both understanding landscape. That's completed on top of that research around payer and value proposition and value messaging to really understand. And then on top of that will be the pricing and access type of insight generation. So I think we've got a really good plan What could have been a rate-limiting step and still remains kind of in the forefront of my mind is the ability to develop relationships. We know that takes time. So if I had to pick one thing, it could be that. That said, we are also on top of that because we now have a full complement of medical science liaisons who are going to these top transplant centers that Phil spoke of We've got a very targeted view on how to go about doing that for the fastest kind of market share uptake. So we're there too. I'm not worried. I'm really not that concerned and worried because I think we've thought about all of these various parts. But certainly, we do need to develop relationships and we do need to get the word out. So the last thing I guess I'll say is that We have now, through our pillar, started to formulate a scientific communication plan. Some of that Phil's already spoke about. You're going to see that at ASH. I would highly encourage you to look at the, there are going to be a couple posters, but one of the abstracts that was submitted and accepted that we're very excited about is not just the speaking of the pharmaco-economic story, which you've probably all heard in the past, but this poster is going to start to tie together the meaningful outcomes of both the clinical story and that pharmacoeconomic story. So we're really excited for that, and I would certainly encourage everyone to look for that coming out of ASH. I don't know if I answered your question because I think you need to be super concerned. I'm just not really concerned about this launch.
spk01: No, no, no. You certainly addressed my question. It wasn't from a point of concern. It was more of, look, I mean, a lot of times if it's a new drug to the market, you have to do a lot of education or what have you. But you certainly addressed my question, not from a concern standpoint. Thanks for that. And then I guess, Phil, from a broader standpoint of the company, it's great to see that, you know, PDAC's moving forward with GenFleet. It was, you know, a very nice partnership to sign for China. I guess, you know, now... how you would define the current status as you view PDAC and additional tumor indications for the rest of the world and sort of where that stands in your sort of business development, company view, you know, sort of wholesale views on this topic.
spk03: Yeah, so, I mean, we've always looked at PDAC as sort of a prototype product for, you know, other solid tumor indications. And so we're right now focusing on that collaboration in that phase 2B study. And I think as I pointed out in my prepared remarks, we also have a collaboration at Columbia University with Columbia University also in first-line, you know, stage 4 metastatic pancreatic cancer. So we're going to focus on those two trials right now. And once the data becomes available, obviously we will look to partner out the, you know, the solid tumor indications to a larger company to maximize the potential value in all indications.
spk01: Got it. Thanks for all the color, guys.
spk03: Okay. Thanks very much. Have a great day.
spk09: The next question is from Mark Breidenbach of Oppenheimer. Please go ahead.
spk07: Hey, thanks for taking the questions. Congrats, of course, on the PDUFA date. And, of course, we're sad to hear Abby is leaving. Just a couple of quick ones. Just a couple of quick ones. First of all, is there a particular forum in mind for the AGI-134 data? I know we're kind of running out of medical conferences, you know, this year. Are these data going to be announced at a conference or by a press release? And then I'm also wondering about the natalizumab-motixifortide combination that's, I guess, being studied as a mobilizing regimen in sickle cell patients. First of all, has natalizumab plus clorixofor been previously tested as a mobilizing combination? And if this combination that you're running in the study works in sickle cell, would you consider maybe testing this as a more general GTSF-free mobilizing regimen? Would love to hear comments on that. Thanks for taking my question.
spk03: Okay, Abby, do you want to first take the part about the gene therapy?
spk02: Yes. Thanks, Mark, for bringing us and giving us the opportunity to present this new project, let's say, for the BLAD40, for motixifortide. The patients with sickle cell anemia are not able to receive for autologous transplantation, GCSF, because GCSF produced veno-occlusive events. and doctors are seeking for new drugs for mobilization. Prorexafor has been used because there is no other choice. However, the number of cells that are mobilized might not be enough, or there is a need for several and several apheresis in order to get a huge number of cells. In order to do, in general, gene therapy, you need a large number of cells and primitive cells. And the idea here, when we combine with natalizumab, is that data from Washington University have shown that the combination of BLA4 inhibitors together with BLAT40 inhibitors have shown a robust mobilization of stem cells in preclinical models. And the idea is to bring this to the clinics and to have a proof of concept of this combination to give the possibility to these patients to go for autologous transplantation. The thing is that these patients in general can get potentially allogeneic transplantation, which is very difficult and have a lot of adverse events. Ideally, it's to give them the opportunity to have autologous transplantation with gene therapy, and we expect that this combination will allow individuals will allow the gene therapy to be available for this patient population.
spk07: So has it been previously tested with plurixifor? I'm just curious.
spk02: No, no. Plurixifor has been used as a monotherapy for patients with sickle cell anemia because, again, they cannot receive GCSF. but the number of cells might not be enough or the number of apheresis is very large. And we are seeking for, and the doctors are seeking for better mobilizers and better combination for mobilization. And we believe that the combination of BLA-4 inhibitors together with MOTIXA-4 type will allow us to have a very high number of cells Hopefully we do one aphoresis, probably two. The idea is to test how many aphoresis and how many cells we will be able to harvest.
spk03: Okay, but you're not, I'm sorry, but we're not aware of a study between folks.
spk02: No, no, no.
spk03: Right, okay. So that's the answer to the second part of your question. I'll go back to the first part, Mark, which was about AGI and the data. So we're planning to release a press release by the end of the year with data from the study. And, of course, we will also look to present at a conference, you know, sometime next year as well. But there will be data coming out, you know, in a press release by the end of the year.
spk07: Okay. Thanks so much for that clarity, and congratulations. All right.
spk03: Thanks so much. Have a great day.
spk09: The next question is from John van der Moesten of Zacks. Please go ahead.
spk04: Good day, everyone. As you build up towards the PDUFA date, what do you anticipate the size of the Salesforce will be, and how do you anticipate structuring it?
spk03: Yeah, Holly, would you like to take that, please?
spk08: Yeah, so we are, while we have preconceived ideas on what we think the size of the Salesforce is, we are at this point not giving exact numbers. What I can, because we're still going through more of the segmentation analysis, et cetera. And I'm in the process of hiring the sales leader who will help with that segmentation. I will say we have already hired a head of business insights and analytics, and he has been extremely instrumental in confirming many of our assumptions and helping us think through that segmentation. We will have sales professionals out ahead of launch. I can say that to make sure that we're doing the appropriate amount of communication with healthcare providers. But I'm not giving the exact number at this point in time because we're still going through some of our analytics on that side. What I can say is that we will be focused on the top, those top transplant centers and so If you are thinking about typical pharma biotech models, you can probably yourself also back into the fact that this is a fairly small national footprint in order to target those key accounts.
spk04: Okay. And will you build it up quarter by quarter, step by step as we arrive to September and the PDUFA date? Is that kind of how it is? And then... And then when you get there, do you plan to have the entire team in place, or are you going to make an initial entry into the space and then kind of build into 2024 as you develop those relationships further?
spk08: So initially, to be clear, there will be three field-facing teams. There already is a medical team, And they are doing the initial, you know, relationship building and very early discussion as medical teams can do around stem cell mobilization. We will have, it's the intention to also have a payer team in the field to make sure that we are communicating our value story appropriately. And then we will also have a failed team. And they are actually going to be phased in that, from a timing perspective, in that order. And it's my intention to have the full team in the field at launch. I do think, though, that, of course, we will be continuing to assess what our deployment plans are into the future and what utilization is and what lifecycle management is in order to make sure that we're meeting the demands of being able to create the noise that's necessary for a successful launch.
spk04: Great. Thank you, Holly. And then a question on R&D. You know, as we wind down the Metixa Forest Hide efforts and pick up in some of the other areas, how do we expect activity there to be in 2023 relative to 2022?
spk03: you're saying from a cost perspective or just, you know, overall?
spk04: Probably a cost perspective would be most helpful. And also, you know, just the activity. I know some of that is being worked on by your partners. So I'm, you know, just a... Right.
spk03: So, you know, so as I mentioned, you know, we're obviously, there's the study being run in China, which will have a limited effect on our budget, the Phase 2B in China, which will have a limited effect on our budget. going forward, you know, in 2023 and onwards. We still have some work that, you know, follow-up work, and Abby can maybe talk to a little bit, follow-up work for long-term, you know, endpoints in the Genesis study. And so that we will still be doing, obviously. And we are participating in some of these, you know, investigative initiative studies, including Columbia University. I'd say overall our spending is expected to go down. on the R&D side as we increase our spending, obviously, on the sales and marketing and commercialization side.
spk04: Okay. That's very helpful. And, Abby, did you have anything else to add on that? I think you answered most of my questions.
spk02: I just wanted to add that part of the, you can say, R&D expenses or medical affair expenses, we are not aiming to continue only with the multiple myeloma indication. The idea is to provide as much as we can as we are doing for the sickle cell anemia and for the pancreatic cancer. We are exploring opportunities. We are reviewing opportunities how to expand the indication and potentially in the future the label for Motexa forti.
spk04: Great. Thank you.
spk03: Thanks. Have a good day.
spk09: If there are any additional questions, simply press star 1. To withdraw your question, press star 2. Please stand by while we poll for more questions. There are no further questions at this time. Before I ask Mr. Phil Serlin to go ahead with his closing statement, I would like to remind participants that a replay of this call is scheduled to begin two hours after the conference. In the U.S., please call 1-888-295-2634. In Israel, please call 03-9255-904. Internationally, please call 972-39255-904. Mr. Sterling, would you like to make your concluding statement? Yes, I would. Thank you, Operator.
spk03: To summarize, we achieved a significant milestone during the third quarter with the submission and acceptance of our NDA for effects in stem cell mobilization and significantly strengthened our financial position ahead of potential approval next year. We are designing and implementing an efficient yet robust launch and commercialization plan that we intend to execute independently given the highly concentrated number of transplant centers across the U.S. that perform the vast majority of transplant procedures. We evaluated several different options and concluded that commercializing independently would get Afexda to multiple myeloma patients quickly while maximizing the value of the asset for our company. We believe we can capture a significant share of a U.S. market estimated to be in excess of $360 million and growing steadily. And from both a clinical and pharmacoeconomic perspective, we believe Afexda on top of GCSF can quickly become the standard of care and this important indication. At the same time, we are pleased to advance Motixa Fortide in PDAC through our GenFleet agreement, and we are rapidly approaching a key data readout for AGI-134. I am extremely pleased with the progress that we made during the third quarter, and I look forward to a catalyst-rich 2023. Thank you all very much for joining today's call, and have a great day.
spk09: Thank you. This concludes the BioLine RX third quarter 2022 conference call. Thank you for your participation. You may go ahead and disconnect.
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