BioLine RX Ltd (BLRX) 2022 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the BioLineRx 2022 financial results conference call. (Operator Instructions) I would now like to turn over the call to John Lacey, Head of Investor Relations and Corporate Communications, BioLineRx. Please go ahead.

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, competence, 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 BioLineRx's business, financial condition, and other operating results. These include, but are not limited to, the risk factors and other qualifications contained in BioLineRx's annual report on Form 20-F, quarterly reports filed in a 6-K, and other reports filed by BioLineRx 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. BioLineRx 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 Serlin, Chief Executive Officer of BioLineRx.

Thank you, John, and good morning, everyone. Thank you for joining us on our full-year 2022 Financial 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 6-K.

As is our practice, I will begin with an overview, then Mali Zeevi, 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 on the call for Q&A are Tami Rachmilewitz, MD, our new Chief Medical Officer; Ella Sorani, our Chief Development Officer; and Holly May, President of BioLineRx USA.

I want to begin this morning with an update on our lead program for motixafortide, now known by its trade name APHEXDA, in stem cell mobilization for autologous transplantation in multiple myeloma patients. Recall that in November, we announced that the FDA had accepted our new drug application for APHEXDA in stem cell mobilization and assigned a PDUFA target action date of September 9, 2023.

The NDA was based upon our very successful GENESIS Phase 3 clinical trial, which met all primary and secondary endpoints with a very high degree of statistical significance. The combination was also found to be safe and well-tolerated.

Notably, nearly 90% of patients treated in the APHEXDA arm collected an optimal number of cells for transplantation following a single administration of APHEXDA plus G-CSF and in only one apheresis session. These results were superior to G-CSF alone.

In addition to potentially improving transplant experiences for patients, we believe the use of motixafortide as a standard of care mobilization agent would confer significant benefits to transplant centers as well. And to that end, we presented full results from a pharmacoeconomic study of motixafortide at the 64th American Society of Hematology, the ASH annual meeting, which was held in December.

The study indirectly evaluated the cost-effectiveness of using motixafortide as a primary stem cell mobilization agent in combination with G-CSF against plerixafor in combination with G-CSF in multiple myeloma patients undergoing autologous stem cell transplantation. The analysis demonstrated significant net cost savings using motixafortide plus G-CSF with a greater proportion of patients achieving successful mobilization of optimal amounts of stem cells in a single apheresis day. This in turn allows transplant centers to make more efficient use of the apheresis units, which are often in short supply.

As we have indicated several times in the past, market research that we commissioned concluded that the stem cell mobilization market represents a $360 million opportunity in the US and $500 million globally and growing steadily. There are many drivers of this growth, but older patients undergoing stem cell transplantation together with more effective induction regimens are making subsequent mobilization of an adequate number of stem cells required for transplantation quite challenging.

Given that a large majority of stem cell transplant procedures in the US are conducted at a relatively small number of key sites, approximately 80 transplant centers out of 212 perform approximately 80% of stem cell procedures. We announced in September of last year that we plan to commercialize APHEXDA independently.

We evaluated a number of different go-to-market strategies, and we believe commercializing independently puts us in the best position to speed the drug's availability to patients through very focused outreach to these centers, thus maximizing the value of the asset for our company.

Looking at the total of efficacy, safety, and tolerability and pharmacokinetic data that we have compiled on APHEXDA in stem cell mobilization to date, we are very hopeful that it will ultimately be approved. And in anticipation of that, we have been extremely busy moving ahead with critical prelaunch activities.

In particular, while the agency has been reviewing our NDA, and in advance of our September 9 PDUFA date, we have been building out our US commercial infrastructure, including the assembly of a world-class commercial team. In June of last year, we announced the addition of Holly May, who leads our US activities. Holly's background includes more than a dozen career commercial launches, including specific expertise in stem cell mobilization and gene therapies. This experience will prove invaluable not only as we prepare to launch APHEXDA in stem cell mobilization, but also for our lifecycle management activities, which I will discuss in a moment.

More recently, we were also very pleased to hire hematology and transplant commercial veteran Kevin Campbell as Head of US Sales and Market Development. Kevin has the ideal background and skill set for this role, having previously served as Head of Transplant at Sanofi, where he led a 23-person commercial team whose portfolio included plerixafor for stem cell mobilization. Before that, he served as US Marketing Director for plerixafor at Genzyme until the acquisition of that company by Sanofi in 2011. Given the steady growth and expanding use of plerixafor, we believe Kevin is the ideal person to help make APHEXDA the new standard of care mobilization agent, initially for multiple myeloma patients undergoing autologous stem cell transplantation, and potentially for other indications as well.

Along with Kevin, we've also added a number of very qualified and experienced individuals to lead critical commercialization functions, such as supply chain, marketing, market access, patient advocacy, and field medical affairs. We're extremely fortunate to have added many, many decades of very relevant and specific expertise to our US team, and I believe we have the ideal personnel to execute a successful commercial launch.

We also announced a key addition at the corporate level with the hiring of Dr. Tami Rachmilewitz as our new Chief Medical Officer. Tami brings to our team many years of experience overseeing clinical development programs across a wide range of therapeutic areas and drug development modalities, including oncology, immunology, and neurodegeneration. Her expertise will be invaluable to advance the NDA review process, expand motixafortide's clinical development into additional therapeutic areas, assess our next clinical development steps for AGI-134, and add new assets to our development pipeline.

Turning now to our second clinical program for motixafortide, metastatic pancreatic cancer, or PDAC. Recall that motixafortide is being evaluated in an investigator-initiated metastatic PDAC trial in collaboration with Columbia University. That Phase 2 study is evaluating motixafortide in combination with the anti-PD-1 LIBTAYO and standard-of-care chemotherapy in first-line metastatic PDAC patients. That study continues to progress, and we anticipate data from the first cohort of patients this year.

We also previously announced a collaboration with GenFleet Therapeutics, pursuant to which GenFleet will execute a rigorously designed randomized Phase 2b clinical study assessing motixafortide in combination with a PD-1 inhibitor and standard-of-care chemotherapy in approximately 200 first-line metastatic PDAC patients in China. The collaboration follows the positive results that we reported from our Phase 2a COMBAT/KEYNOTE-202 triple combination study of motixafortide in combination with the anti-PD-1 Keytruda and chemotherapy in second-line patients.

As a reminder, data from the Phase 2a 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. We anticipate that the GenFleet Phase 2b trial will initiate by the end of this year.

In addition to our two core clinical programs just mentioned, we are also working to evaluate motixafortide's clinical utility in additional high unmet need indications. One of these is hematopoietic stem cell mobilization for gene therapies in sickle cell disease. Sickle cell disease is one of the most common genetic diseases globally. It is typically diagnosed early, around six months of age.

The clinical manifestations of sickle cell disease include anemia and blood vessel occlusion, which can lead to both acute and chronic pain, as well as tissue ischemia across multiple organ systems. The cumulative impact of these complications significantly impacts morbidity and mortality for patients with sickle cell disease.

Autologous hematopoietic stem cell-based gene therapies now offer curative potential for patients with sickle cell disease, but they are dependent upon the collection of significant quantities of stem cells, including early progenitor stem cells. The common mobilization agent, G-CSF, is contraindicated in patients with sickle cell disease, significantly limiting their stem cell mobilization options. The development of novel mobilization regimens has the potential to overcome this unmet need for patients.

Recognizing the clear unmet need for a more effective mobilization regimen and leveraging our work in stem cell mobilization, we entered into a clinical trial collaboration with the Washington University School of Medicine to evaluate motixafortide for stem cell mobilization in sickle cell disease. The trial, which is expected to launch in 2023, will evaluate motixafortide both as monotherapy and in combination with natalizumab. This represents a very logical expansion of our development pipeline.

Of further note, last month we attended the 2023 Tandem meeting in Orlando, Florida. Tandem is the combined annual congress sponsored by the American Society for Transplantation and Cellular Therapy and the Center for International Blood and Marrow Transplant Research. It is the foremost congress in this space, bringing together leading experts to present the latest cutting-edge science in hematopoietic cell transplantation and cellular therapies.

Meetings such as Tandem and other widely attended congresses on cell transplantation and cellular therapies are an important and effective way for BioLineRx to raise its profile among all related constituencies, and we plan to attend and present where appropriate at all such meetings going forward.

Turning now to our second clinical candidate, the investigational intratumoral anti-cancer vaccine, AGI-134. We believe 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 recently announced results from a Phase 1/2a study of AGI-134 in metastatic solid tumors. The first-in-human, single-agent study met its primary endpoint for safety and tolerability and demonstrated immune activity across multiple biomarkers. At this time, we are evaluating potential development program pathways in consultation with the program's scientific advisory board.

I would now like to turn the call over to Mali Zeevi, our CFO, who will give a brief overview of our main financial results. Mali, please go ahead.

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, 20-F, and first release for additional information.

Research and development expenses for the full year ended December 31, 2022, were $17.6 million, a decrease of $1.9 million, or 9.7%, compared to $19.5 million for the full year 2021. The decrease resulted primarily from lower expenses related to NDA supporting activities related to motixafortide, as well as lower expenses associated with the completed motixafortide GENESIS clinical trial, offset by an increase in expenses associated with the AGI-134 study and increase in payroll and related expenses.

Turning to cash, the company held $51.1 million in cash, cash equivalents, and short-term bank deposits as of December 31, 2022. This does not include $30 million available to us under our debt agreement with Kreos Capital, which is tied to the payment of certain milestones. We believe we're well financed to fund our operations as currently planned into the first half of 2024.

And with that, I'll turn the call back over to Phil.

Thank you, Mali. In closing, as is our custom, I would like to take a few moments to summarize our key upcoming milestones. Potential FDA approval of APHEXDA in September 2023. Potential US launch of APHEXDA in stents immobilization shortly after approval. Initiation of a clinical trial in collaboration with Washington University School of Medicine to evaluate motixafortide as monotherapy and in combination with natalizumab for CD34-positive hematopoietic stem cell mobilization for gene therapies in sickle cell disease in 2023.

Initiation of a Phase 2b randomized clinical trial with 200 patients assessing motixafortide in combination with the PD-1 inhibitor and standard of care chemotherapy as a first-line metastatic PDAC therapy with collaboration partner GenFleet in 2023. And initial cohort data from the ongoing Columbia University Investigate Initiated Trial evaluating motixafortide in combination with the PD-1 inhibitor LIBTAYO and standard of care chemotherapy in first-line metastatic PDAC patients also in 2023.

With that, we have now concluded the formal part of our presentation. Operator, we will now open up the call to questions.

(Operator Instructions) Mark Breidenbach, Oppenheimer.

Hey, guys. Thanks for taking our questions. Phil, it sounds like you've really brought in some relevant commercial talent to oversee the launch of APHEXDA. I'm hoping or just wondering if you can comment on what work still needs to be done in terms of launch preparations and also what fraction of the targeted US transplant centers already have experience with motixafortide from, for instance, the clinical trials. And I have a follow-up.

Okay. Great. First of all, good morning, Mark, and thanks for joining the call. I will turn that question over to Holly May. She's ready to answer that question.

Yeah. So thank you so much. So we're well on our way with our commercial preparations in the activities that we have as well as the personnel that we're hiring. So I believe I have spoken previously about our medical affairs team, that we've had them in the market talking and making, building relationships. And I think that Phil also did a nice job talking about our presence at Tandem, which was just very much of a pivot point for us because we've made so many connections with physicians, thought leaders, et cetera.

So we continue to build our plans. We've got -- we've built an account team that will be calling on other stakeholders like, you know, payers and financial people. And then we're also right now in the process of building out a small and targeted sales team. Phil did mention that we've brought on a very strong sales leader and under his direction, we are looking at people who have experience in the transplant space.

In addition to that, we've done a lot of foundational market research to understand qualitative and quantitatively the market, the patient journey, the unmet need, and we're using all of that as we prepare our standardized marketing and market access plans. We've done some deep analysis and we continue to do deep analysis around the pricing and value in this marketplace.

So as I see -- and we're completely -- I think we're going to be very much ready from a supply and distribution perspective for whatever our approval date is. So we have contingency plans as well to be able to put product in channel very quickly.

I know I've spoken in the past about the things that we've done there, so we're well set with our 3PL and we are now working very diligently on our distributor contracts and we are well, well along the way on the long lead time items such as serialization, as well as the state licensing, and all of those things that you need to do to be able to sell right away. So we are completely prepared or will be prepared for even the potential of an early approval if we get one prior to our PDUFA date. I don't know if that was specific enough for you, but I think we're doing a lot of, you know, activities to prepare.

I would say that was very specific.

Okay. (laughter)

Mark, as far as the second part of your question, the number of sites, we haven't really disclosed that. We had somewhere between 15 and 20 sites overall, and I believe somewhere around 10 to 15 of them were in the US.

Okay. That's super helpful. And just, like, a quick follow-up, I guess, on the upcoming data from the Columbia University sponsored trial, you mentioned we would see the data from first cohort. Can you give us a sense for how many patients that includes and if it would be mainly response rate data or if you're expecting it to be mature enough to also have PFS and OS data included in that readout?

Ella, would you like to take that question?

Yeah, sure. Hi, Mark. This is Ella. So the data will probably include 10 patients in the Columbia study, and it will focus mainly on response data, yes.

Okay. Response rate. Got it. Thank you. And congrats on the progress.

Great, Mark. Have a good day.

Joe Pantginis, Wainwright.

Hey, everybody. Thanks for taking the question, and good luck on the upcoming PDUFA. So looking towards some of Holly's comments, I was just curious, obviously, you're not rightsized yet with regard to commercial personnel because you said you're bringing on a focused sales force or in the process of doing that. How should we consider the phasing of that? Is it going to be gated on the approval, or will any of these people be in place first?

Yeah.

Go ahead, Holly.

Yep, sure. So thanks for the question, Joe. So we understand that you need to invest some money to make money, so we believe we are investing the right amount of money in kind of those pre-launch activities that we need to go to market. That said, we are also very conscious that we are a small company and that we need to be prudent in how we think about our people and our investments.

So we are staging the field people who are calling on stakeholders appropriately, and we know that the medical affairs folks who are already in the field, they're there. And the next personnel that we're staging into the field will be those who can speak more economically to the payer and state and the account management type people. And then we are going to be hiring our sales professionals because we want them in field ready to go in just enough time so that there's a little bit of being able to get to know the accounts and get to know some customers, but that they're not going to be in field for months and months prior to our PDUFA date.

The way that we have things staged right now, though, we do believe that they will be in the field in enough time if we happen to get an early PDUFA, I mean an early approval. So I haven't given you the specific dates, but we have a very well thought out plan of making sure that we get people on board, get them trained, and get them ready for a potential earlier date if that should come. And then certainly, with the full complement of launch assets and materials by September.

Got it. No, that's helpful. Thank you. And then I guess this sort of also goes to the broader profile for motixafortide, but if you look at stem cell mobilization right now, how should we be viewing at this moment in March 2023 your ex-US views for commercialization? Obviously, US is very focused, but with regard to the single -- the individual geographies, the individual reimbursement patterns for each country and what have you, and from a broader concept, how does that factor into any potential ongoing discussions right now for indications in oncology beyond stem cell mobilization?

Wow, that's a broad question. Okay. Let me discuss first of all about other territories. So I think we've said this a number of times, and I'll just repeat it again. We want to look at other territories, but we are not going to do anything until we first get this product approved in the US and launch it in the US. Following the approval and the successful launch, we will then look at other territories. Not on our own, though.

We will -- we are already speaking with potential partners, but we may get into obviously more detailed discussions later on regarding other territories, but we will not commercialize on our own in other territories. But there are certain territories, for example, the approval process is easier. They rely somewhat on the US approval. We are, of course, looking at Europe, but again, I think that right now, we realize with the resources we have and the talent we have right now, our focus is clearly on the US.

I was just going to say broad question for potential broad opportunities, but go ahead, Phil.

Okay. Now, as far as other indications, we are already well invested, so to speak, in pancreatic cancer. We have a number of trials that are ongoing with our partner, GenFleet, in China with Columbia University. We are also, as you know, looking at stem cell mobilization for gene therapy in sickle cell disease patients. And so, those are areas that we are going to continue to focus on and probably look to broaden.

We're very excited about gene therapy. It seems to be an area that requires that there's a real, real unmet medical need. The gene therapy requires a huge amount of cells. They are -- G-CSF is contraindicated for sickle cell disease patients, and so therefore, currently, their only alternative is plerixafor, and they need to undergo multiple cycles of mobilization and apheresis sessions, et cetera.

And we believe, and we're hoping to see that in the investigative initiatives study that we're going to be, that Wash University is going to be executing. We believe that we're going to see that our drug can provide significant benefits and mobilize significantly greater amounts of cells. But that, again, has to be proven. I hope that --

No, that's great. Thanks. And if I can ask just a more focused question regarding tank. I just want to make sure, is the protocol set for the randomized Phase 2b, or is this something that is sort of up in the air a little bit with regard to any ongoing BD discussions as well?

Ella, would you like to take that?

Yeah. Hi, Joe. This is Ella. So the protocol is set.

(laughter) Short answer.

Yeah. I got it. Broad to short. I love it.

I mean, do you have any other specific, anything more specific about pancreas or this trial? I mean, we're happy to answer. I just, like I said --

No, (multiple speakers).

Okay. Great. All right. Have a great day. Thanks, Joe.

John Vandermosten, Zacks.

All right. Thank you. And hello, everyone. I wanted to continue on the gene therapy question, and obviously there's a big opportunity there. Are there -- or what are some other indications in the gene therapy can address that are particularly amenable to using motixafortide to gather the stem cells?

Holly, would you like to take that?

Well, I'm going to take that because I come from that world, so, you know, I don't want to -- this, because the person who's commercializing, I don't want you to infer anything from that we are absolutely doing this, that, or the other thing, but I will tell you I come from this world, and so I have a really kind of clear picture.

For any of the cell or gene therapies that kind of use that lentiviral approach, and so often the ones that are kind of more near term are those ex-vivo, lentiviral approach. I came from a company that was focused on the lysosomal storage disorders, and so that's an area I know that if you look at some of the other indications that, say, Bluebird Bio has and will be launching in -- So some of those rare disease indications where there is a lentiviral approach, and right now most of those are ex-vivo where the stem cells are being removed through mobilization, and then manufactured, and then conditioning is, the patient goes through conditioning, and then the cell therapy or the gene therapy is administered.

We're looking at the horizon, though, and we know there's other lentiviral kind of like in-vivo type approaches, too, which we find to be very, very interesting, so stem cell mobilization is still a factor there. So whether it's in-vivo or ex-vivo. But if it requires the mobilization of stem cells, there are several indications in the rare disease space, especially, like I said, in those like lysosomal storage disorders where there could be some utilization.

Now that's not to say, Ella, you might want to comment that we have our eye on clinical programs there. We just know that there is a high demand in those sorts of therapeutic areas.

Okay, and it seems like, you know, with the success of this study that has been done so far, there might be a lot of demand to perhaps use this in some investigative-led studies. Have you seen demand like that?

We have. We can't disclose anything right now. We've only disclosed the Washington University, but we are speaking with other potential sites and hospitals and universities about some other things as well in gene therapy, yes.

Great, and I had a couple questions on AGI-134. Do you expect any kind of expedited treatment as we move along for this?

Can you -- expedited development? Is that what you mean?

I don't know. Expedited treatment from the FDA and regulatory agencies in terms of some kind of quicker, perhaps approval on Phase 2 data or something like that, or expedited treatment in terms of more accelerated review or closer contact with the FDA.

Yes, so, I mean, we're still -- this is still quite early. We just completed a first-in-man study. We had some very interesting data from the study. We are looking at what our next steps are throughout 2023, so I think at this point, it might be a little early to ask from the FDA for any type of expedited program. I think the next step would theoretically be a Phase 2 of some sort, and again, we just finished our first-in-man study, so I think it's probably too early.

Ella, would you like to add anything to that? Okay.

Okay, great. And then a little bit more specific question on 134. I was reading through the press release, and it said that some of the patients had been on checkpoint inhibitor therapy. Was that monotherapy, or was that combination checkpoint therapy?

So, hi, this is Ella. The therapy in our study was monotherapy with the AGI. Just previous treatment, some of them were previously treated -- prior to participating in the study were treated with the checkpoint inhibitor. So, it was not -- no treatment during our study. It was previously treated. They failed on checkpoint inhibitor and then were treated with our drug.

Right. So, their checkpoint therapy that they had prior to AGI-134, was that in combination with another immunotherapy or some other kind of therapy, or was it just checkpoint inhibitor therapy alone prior to going into your study?

It was probably a combination, John, but we don't have that data in front of us. That's a very specific question at this point. It could be both. It's hard to say. But, I mean, and we haven't really disclosed that data in any event.

Okay. Yeah, because, just checkpoint therapy is a lot more efficacious when it's used in combination. Sometimes if it's used alone, it doesn't always work as well. All right. Well, I appreciate you taking my questions. Thank you so much.

Great. Thanks so much, John. Have a great day.

(Operator Instructions) There are no further questions at this time. (Operator Instructions) Mr. Serlin, would you like to make your concluding statement?

Yes. Thank you, operator. To summarize, we entered 2023 with significant momentum. We are preparing for the potential US approval of our first therapy in stem cell mobilization and have successfully completed the formation of our US commercial leadership team. We are also making notable progress with our PDAC program and anticipate important data from a first-line investigator-initiated study later this year, as well as the initiation of our GenFleet collaboration study. We have also taken additional lifecycle management steps by entering into a collaboration to execute a clinical trial with motixafortide as a mobilization agent in gene therapies.

I am extremely pleased with our progress during the fourth quarter and the full year, and I am excited about what we are on the cusp of achieving this year.

Thank you all very much for your continued interest in BioLineRx, and we look forward to providing our next comprehensive update in May. Be safe and have a great day.

Thank you. This concludes the BioLineRx 2022 financial results conference call. Thank you for your participation. You may go ahead and disconnect.