BioLineRx Ltd. (BLRX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by. Welcome to the BioLineRx Update Conference Call. [Operator Instructions] I would now like to turn over the call to Irina Koffler, Head of Investor Relations and Corporate Communications, BioLineRx. Please go ahead.

Thank you, operator, and welcome, everyone. Thank you for joining us as we discuss this morning's announcement that BioLineRx and Hemispherian have established a joint venture. Earlier today, 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. 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. At this time, it is now my pleasure to turn the call over to Mr. Philip Serlin, Chief Executive Officer of BioLineRx.

Thank you, Irina, and good morning, everyone, and thank you for joining us on today's call for this significant announcement. Earlier this morning, we announced that we have entered into an agreement with Hemispherian AS, a Norwegian privately held biotech company focused on small molecule cancer therapeutics to establish a joint venture to develop GLIX1, a highly innovative molecule for the treatment of glioblastoma and other cancers. I will begin with a few prepared remarks before turning the call over to Dr. Ella Sorani, our Chief Development Officer, to provide more information on GLIX1. I will then provide an overview of the JV structure and discuss next steps, after which we will take your questions. Mali Zeevi, our Chief Financial Officer; as well as Zeno Albisser, CEO of Hemispherian; and Dr. Adam Robertson, CSO of Hemispherian, are also available for Q&A. Since November of 2024, when we entered into an exclusive out-licensing agreement with Ayrmid Ltd. for our FDA-approved stem cell mobilization agent, APHEXDA, we have been focused on four things: First, evaluating early clinical stage assets in the areas of oncology and rare disease to regenerate our development pipeline where we can fully leverage our clinical and regulatory expertise and successful track record of drug development. Second, operating a very lean organization to preserve our cash runway that extends into the first half of 2027. Third, supporting our clinical trial partner, Columbia University under the collaboration supported by both us and Regeneron to advance the Phase IIb trial of motixafortide in pancreatic ductal adenocarcinoma, or PDAC, for which we retain the development rights globally other than Asia; and four, supporting our out-licensing partners, Ayrmid and Gloria in order to fully realize future royalties and potential future milestone payments under our collaboration agreements with them. Today, I'm very pleased to announce that following a relatively lengthy process of scouting and reviewing literally hundreds of potential projects since the beginning of the year as well as performing substantial due diligence on a number of very promising candidates that fit our search criteria, most notably a highly innovative asset with a clear unmet need as well as a clear and efficient path forward. We have entered into an agreement with Hemispherian AS to establish a joint venture to develop GLIX1, a first-in-class oral small molecule targeting DNA damage response in glioblastoma and other cancers. This joint venture combines our proven track record of clinical and regulatory success with Hemispherian's expertise in small molecule cancer drug discovery, specifically in the area of DNA damage response research, leveraging a unique mechanism of action that targets cancer cells. We are also very pleased with the deal structure in the form of a joint venture, which we believe is the optimal way for BioLine to bring in a new program and invest gradually in its development while maximizing synergies and sharing the development risk with our collaboration partner. Hemispherian's lead candidate, GLIX1 is being developed as a potential treatment for many types of cancers. Based on its mechanism as well as the highly impressive preclinical results, the first indication to be investigated will be glioblastoma or GBM, both newly diagnosed and recurrent. GBM is an extremely aggressive type of primary brain tumor with few effective treatment options. In a number of preclinical studies, GLIX1 demonstrated potent antitumor activity in multiple glioblastoma models, excellent blood-brain barrier penetration and a favorable safety profile. In August of this year, Hemispherian announced the U.S. Food and Drug Administration had cleared its IND. And with the joint venture now established, we are planning to initiate a Phase I/IIa clinical trial in the first quarter of 2026. We will provide more details on the trial in a moment. Glioblastoma is the most common and most aggressive form of primary brain cancer. Prognosis of patients is extremely poor with median survival of approximately 12 to 18 months following diagnosis. The current standard of care treatment, which was established in 2005, includes surgical resection followed by radiotherapy and concomitant in adjuvant chemotherapy, temozolomide. Importantly, 50% to 75% of patients do not benefit from treatment with temozolomide and those who do see a modest increase of approximately 2.5 months in overall survival. So this is among the most challenging cancer types where new therapeutic approaches are sorely needed. Glioblastoma occurs at all ages, peaking in the fifth and sixth decades of life with increasing incidents in light of the aging global population. New and better treatments are desperately needed that can improve survival, maintain quality of life and delay tumor symptoms and progression. The annual incidence of GBM is expected to be approximately 18,500 patients in the U.S. and approximately 13,400 across the EU 5, the U.K., France, Germany, Italy and Spain by 2030. This translates to addressable markets across both the newly diagnosed and recurrent settings of approximately $2.5 billion in the U.S. and approximately $1.3 billion across the 5 EU. This is a very open and uncrowded market with few competitors and represents a significant opportunity to bring innovation to patients while creating significant and enduring value for the JV and our respective shareholders, and we are truly excited by this opportunity. I would also like to emphasize the potential of GLIX1 in other cancers, both as monotherapy and in combination with PARP inhibitors. In addition, the JV also has a first look at other molecules in Hemispherian's pipeline, all focusing on DNA repair, although the initial focus of the JV will be GLIX1. Finally, in terms of intellectual property, GLIX1 for use in treating cancer of the central nervous system, such as glioblastoma is covered by patents granted in the U.S., Europe and 13 other countries. The patents will be valid until at least 2040 with a possible patent term extension of up to 5 years. GLIX1 for use in treating any cancer in which CD8 is not overexpressed, which is the majority of cancers, is covered by patents granted or pending in the U.S., Europe and other countries, which will be valid until at least 2040 with a possible patent term extension as well of up to 5 years. GLIX1, combined with a PARP inhibitor for use in treating HR-proficient cancers, also the majority of cancers, is covered by a pending international patent application. Corresponding national phase patents, if granted, will be valid until at least 2044, again, with a possible patent term extension of up to 5 years. So while glioblastoma will be our initial indication, GLIX1 is covered by a global portfolio of patents, both issued and pending that preserve our ability to evaluate it in the vast majority of cancer types, both as monotherapy and also in combination with standard-of-care therapies, including with PARP inhibitors. I'd now like to turn the call over to Ella to provide a bit more detail on GLIX1.

Thank you, Phil. GLIX1 has a unique mechanism of action that targets DNA repair vulnerabilities in cancer cells while sparing healthy tissue. It targets TET2, an enzyme that has a central role in DNA demethylation, a key process in the regulation of gene expression, cell differentiation and development. TET2 is responsible for initiating the DNA demethylation cycle, which downstream leads to single-stranded DNA breaks. In normal cells, this demethylation cycle occurs constantly and has no negative effect on the cell. Accordingly, stimulation of this cycle by GLIX1 in normal cells has no negative effect on the cell. In cancers, however, alteration and DNA methylation are common and TET2 activity is inhibited by oncometabolites, giving rise to increased DNA methylation in close genomic proximity. This is applicable in hematological as well as solid tumors and is particularly pronounced in glioblastoma. In cancer, the restoration of TET2 activity by GLIX1 generates large amounts of single-stranded DNA breaks in close proximity to one another, resulting in double-stranded DNA breaks, which overwhelm the repair capacity of the cell killing the cancer cells. As expected from this mechanism of action, toxicology studies demonstrated that GLIX1 is safe and well tolerated up to the highest feasible doses tested. GLIX1 has been tested in multiple glioblastoma mouse models, including two orthotopic xenograft models. In both of the orthotopic GBM models, GLIX1 completely prevented tumor growth compared to an approximate 20-fold increase in tumor size in the control groups. This also translated into a substantial improvement in survival of the GLIX1 treated animals. GLIX1 is a small molecule that effectively crosses the blood brain barrier. It is produced through a robust, straightforward synthesis method formulated as a capsule and demonstrates an excellent stability profile. In summary, its preclinical profile strongly supports the initiation of first-in-human studies. In addition to IND clearance by the FDA, GLIX1 has also been granted Orphan Drug Designation by both the FDA and the European Medicine Agency, the EMA, which is accompanied by an expedited review process and other financial benefits and may provide additional market exclusivity following approval. As mentioned, we are planning to initiate a Phase I/IIa trial in the first quarter of 2026. The Phase I part of the trial is expected to recruit up to 30 recurrent GBM patients. The objective of this dose escalation part of the study is to establish a maximum tolerated dose and/or a recommended dose based on safety, PK/PD and available preliminary efficacy. Data from Phase I part of the trial is anticipated in the first half of 2027. The Phase IIa expansion part of the trial is planned to include three patient cohorts: GLIX1 as monotherapy in recurrent glioblastoma, GLIX1 on top of standard of care in newly diagnosed GBM patients and GLIX1 in combination with PARP inhibitors in other solid tumors. It is worth noting that PARP inhibitors are only efficacious in HR-deficient cancer, which represents just 6% of all cancers. Early data suggests the potential for strong synergy of GLIX1 with PARP inhibitors by sensitizing HR proficient cancers representing 94% of all malignancies to PARP inhibitors. In addition, GLIX1 has shown antitumor activity in other cancer models. So, while glioblastoma remains our initial indication for the GLIX1 clinical program, we believe there is significant potential opportunity in other cancers as well. I now turn the call back to Phil.

Thank you, Ella. Reviewing the structure of the JV, Hemispherian will contribute the global rights of GLIX1 to the JV, and BioLineRx will be responsible for managing, performing and funding all JV development activities in accordance with an agreed development plan and budget. In consideration of our respective contributions, as of the JV's inception, Hemispherian will hold 60% of the JV's share capital, and we will hold a 40% stake with our stake increasing incrementally to a potential maximum of 70% in parallel with our continued investment in the program. There was no initial upfront payment associated with the transaction. Both parties agreed that all funding would go strictly to development in order to expedite this high potential program. The JV also has a first look at other molecules in Hemispherian's pipeline. Incorporating the contemplated investment in GLIX1, BioLineRx currently has a cash runway into the first half of 2027. So we are well positioned financially to support start-up activities and subsequent initiation of the GLIX1 development program. It is also worth noting that some funding for our programs will come from royalties and potential milestone payments from our development partners, Ayrmid and Gloria Biosciences, pursuant to the aforementioned previously announced license agreements with those companies. In terms of next steps, as mentioned, we are planning to initiate the first-in-man Phase I/IIa trial of GLIX1 in the first quarter of 2026. We are very pleased that the study will be conducted by world-leading investigators in the field of glioblastoma. Dr. Roger Stupp and Dr. Ditte Primdahl, of the Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center at Northwestern University will serve as principal investigators for the study. Hemispherian has been working to build strong relationships with leading patient advocacy groups, which the JV intends to maintain and expand. And given that patients are actively looking to join clinical trials for promising new therapies, we anticipate that enrollment will proceed efficiently. We also note that the trial is open label, so we will be able to see the data on an ongoing basis and plan to provide updates wherever possible. This concludes our prepared remarks. We will now ask the operator to open up the call to your questions.

[Operator Instructions] The first question is from Joe Pantginis of H.C. Wainwright.

Very intriguing announcement and looking forward to how the clinical program plays out. So a few questions first, Phil. So when you talk about your current runway, how does this play into -- how far does it get you into data catalysts, especially when you have some of the expenses offset by some royalties?

Yes. So we had -- first of all, it's a pleasure speaking to you, Joe, as usual. We had $28 million in cash as of our last financial date as well as royalties and potential milestones from our existing partners. So we definitely have enough resources to initiate and fund a significant portion of the trial. So that's sort of what I can say at this point.

I understand. And I guess if I just stand with the terms and the financials of the arrangement, would you disclose what the triggers are to get to your option to move to 70% ownership?

Everything is disclosed in the 6-K. There's basically a formula as we invest more, we acquire a larger percentage in the JV. But it's very well laid out in the 6-K that we filed.

Okay. Sorry, forgive me, I'm just wrapped together.

No. It's early in the morning, I understand. I do want to say -- again, you mentioned something about the milestones. I just want to say that since -- as we mentioned, since this is an open-label trial, we will be seeing the data, and we will try to utilize every potential opportunity to provide that data to the public, to our shareholders.

Got it. And from the drug itself side, just curious, and I know it's a small molecule, but anything we need to consider with regard to manufacturing and supply of the drug, number one. And then with regard to the actual targeting of the drug and clinical -- potential clinical profile, is there anything to consider with regard to underlying MGMT status of the patients? Or is this drug agnostic to that?

Okay. On the CMC side, I'll just say that the CMC is very well established. It's manufactured at a well-known, reputable international CDMO. We have enough drug product to initiate the study as planned, and we're planning to carry out a manufacturing run sometime next year in order to complete the study. But it's very stable. And as Ella said, there are no issues at all whatsoever with CMC. The second part as far as...

With regards to MGMT status, so generally speaking, based on its mechanism, GLIX1 should work in all cancers that express TET2. So it means it potentially should work also in -- either MGMT status should work. And actually, we also have seen data where in vitro, it works in temozolomide-resistant cells.

The next question is from Justin Walsh of Jones Trading.

Maybe to start off, wondering what you're looking to see in Phase I part of the trial that would give you confidence moving into Phase II, especially since you mentioned it's open label.

Go ahead.

Yes. With regards to the first part of the trial, as I said before, we are looking into safety, PK/PD, potential efficacy. So it's a standard first-in-human trial, where we will assess all these parameters in order to proceed to the expansion part of the study.

Got it. And in terms of the safety and tolerability, are there any specific signals that you're expecting based on the preclinical studies?

Yes. So with regards to the safety, this is actually an excellent question. Based on the mechanism of action of GLIX1, that's the beauty of the molecule, I would say, because it's completely safe. It's specific to cancer cells, but does not negatively affect normal cells. And indeed, in the GLP tox study, we had excellent safety results shown with this molecule. It was completely safe up to the highest feasible tested doses in both species tested. So in terms of safety, we expect actually -- hopefully, we will be able to show also in humans that it's safe. But what we saw so far is completely aligned with the mechanism, and it was extremely safe.

Got it. One more for me. I'm wondering if there's a sort of specific rationale. I know you mentioned you did preclinical studies, but beyond just seeing some synergy between GLIX1 and the PARP inhibitors versus other DNA damage repair inhibitors or other antitumor therapies. And related to that, I'm curious if there are certain solid tumor indications outside of GBM that you guys are -- think you might see more benefit in?

Adam, would you like to take that question?

Yes. So with regards to the PARP inhibitors, the mechanism of action of PARP inhibitors overlaps with that of the GLIX molecule. So that's why we predicted that we would see good synergy, and that's actually -- and we did indeed see that good synergy. So GLIX causes the formation of single-stranded breaks and PARP inhibitors prevents the repair of the single-stranded breaks. So that's why we'd expect to see synergy, and we then indeed did see synergy. To the second part of the question, which was, did we see other combination with other DNA damage response agents. So far, we haven't seen any synergy with GLIX1 and any of the other DNA damaging agents. So with that, that's kind of the status of it right now, but I think the PARP inhibitors are the way to go. In terms of other indications, we're looking towards blood cancers, but we do see good efficacy in many other cancer types. So we'll start with glioblastoma and then other blood cancers, but then we have a lot of options there.

The next question is from John Vandermosten of Zacks SCR.

I had a question on just other molecules in this class that may have been investigated for similar molecules. Is there anything else like that, that sets a precedent?

Adam, do you want to take that?

Yes. So we have -- so GLIX1 is one of 6 molecules that we found were good at targeting the TET2 enzyme. GLIX5 also has a similar effect. We found that -- of the 6 that we found, GLIX1 and GLIX5 were by far the best and GLIX1 had superior pharmacological properties. So that's why we decided to advance that first. I will mention that the JV has the option to advance GLIX5 as well. So that's potentially interesting, although that's not. We're not -- we don't have plans at this moment to advance GLIX5.

Okay. And I'm sorry, go ahead.

Yes. I'm not sure that if you meant other drugs from Hemispherian or generally speaking, because actually, the mechanism of GLIX1 is a first-in-class molecule. And although there are other studies that validated TET2 as a drug using genetics, but it's the first pharmaceutical to be advanced clinically, if that was your question.

Actually, yes, that was part of the question. So -- and then looking at GLIX1, I guess it's initially intended to be used after a failed standard of care in GBM. Is that the intention?

After what? Sorry.

After failed standard of care in GBM. Is that the initial question?

Well, the first -- yes, in the dose escalation, we are aiming -- we are starting with the current GBM because in order to gather safety, but the plan is in the expansion also to test it on top of standard of care in newly diagnosed GBM patients.

The next question is from Joe Pantginis of H.C. Wainwright.

So Phil, I just wanted to have a strategic question. So as of today, you have motixafortide royalties, you have Chemo4MetPanc and then you have the new GLIX1 asset. Is there anything we can consider in the sort of near to intermediate term for any potential pipeline expansion?

We're always looking for interesting opportunities, but I have to tell you right now, we're fully focused on what we have. I can't say that we won't see some other opportunities out there. But I think with our budget and with the cash on hand and with our capabilities, this is sort of going to keep us busy for quite a while. I will say though that -- I also want to point out that we also plan to perform and investigate or do perform a number of preclinical studies as well in this molecule to see other indications, et cetera, et cetera. So between everything, I think we're pretty well engaged at this point.

[Operator Instructions] 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 2 hours after the conference. In the U.S., please call 1 (888) 295-2634. In Israel, please call (03) 9255-904. Internationally, please call 9723-9255-904. Mr. Serlin, would you like to make a concluding statement?

Yes, I would. Thank you, operator. In closing, we are very pleased and excited to establish this joint venture, which allows us to expand our pipeline with a highly innovative asset such as GLIX1, with the potential to become an effective and safe treatment option for cancer patients with high unmet needs. Recall that our other molecule, the CXCR4 inhibitor, motixafortide, is currently being evaluated in the Phase IIb Chemo4MetPanc study in combination with the PD-1 inhibitor, cemiplimab and standard of care chemotherapies in first-line metastatic pancreatic cancer. That study is sponsored by Columbia University with equal support by Regeneron and BioLineRx. Enrollment continues to progress, and we're planning for a prespecified interim analysis when 40% of progression-free survival events are observed. We are excited to apply our clinical and regulatory experience to the development of GLIX1 and look forward to keeping you apprised of our progress. Thank you all very much for your continued interest in BioLineRx as we embark on this exciting new endeavor. Be safe, and have a great day.

Thank you. This concludes the BioLineRx investor call. Thank you for your participation. You may go ahead and disconnect.