Ladies and gentlemen, thank you for standing by. Welcome to the BioLine Rx Fourth Quarter and Full Year 2020 Results Conference Call. All participants are at present in a listen-only mode.
Following the management's formal presentation, instructions will be given for the question and answer session [Operator Instruction]. I would now like to turn over the call to Timothy McCarthy of LifeSci Advisors to read the safe harbor statement, Tim, 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, 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 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, quarterly reports filed in the 6K 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 Mr. Phil Serlin, Chief Executive Officer of BioLineRx.
Thank you, Tim and good morning everyone. And thank you for joining us on our fourth quarter earnings conference call today. Earlier this morning, we issued our Q4 results press release, a copy of which is available in the investor relations section of our Web site. It was also filed as a 6K.
As is our custom, I will begin with some brief prepared remarks and then Mali Zeevi, our Chief Financial Officer, will provide a short discussion of our financial results.
We will then open up the call to your questions. Also joining the call for Q&A are, Avi Vainstein, our Chief Medical Officer; and Ella Sorani, our Chief Development Officer. The fourth quarter 2020 was our most significant yet as we produced positive data sets from two key programs, stem cell mobilization and metastatic pancreatic cancer, or PDAC. I would like to begin with a brief discussion of stem cell mobilization. In October, we announced positive results from pre-planned interim analysis of our GENESIS Phase 3 study, evaluating our lead clinical candidate motixafortide in stem cell mobilization for patients undergoing autologous hematopoetic stem cell transplantation. Stem cell mobilization is an area of significant unmet need as 50% to 70% of patients are poor mobilizers, necessitating multiple aphoresis sessions.
In addition, a portion of these patients require one to four daily injections of mozibil on top of G-CSF, the current standard of care in order to reach the required level of stem cell mobilization and collection. The primary objective of the GENESIS study was to demonstrate that only one dose of motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize greater than 6 million CD-34 positive cells and up to two aphoresis sessions. We were pleased to announce that the results of the interim analysis were overwhelmingly positive, as the interim analysis found highly statistically significant evidence for the primary endpoint favoring treatment with motixafortide. Upon the recommendation of the independent data monitoring committee, study recruitment was terminated early at a 122 out of a planned 177 patients.
We are planning to announce top line data in early Q2 of this year, including full primary and secondary efficacy end points. These data are exciting for two very important reasons; first, we hope that the data will show that the combination of motixafortide and G-CSF is well positioned to become the new standard of care in autologous stem cell transplantation; and second, stem cell mobilization is our most expedient path to registration. It goes without saying that if motixafortide is ultimately approved for this indication, it would be a transformational event for our company. To that end, we are already proceeding with all activities in support of an NDA submission in this indication, which we are targeting for the first half of 2022, including a pre NDA meeting with the FDA in the second half of this year.
Now turning to our PDAC program. In December, we announced final results from the Phase 2a COMBAT/KEYNOTE-202 study of motixafortide in combination with Merck's PD-1 inhibitor, KEYTRUDA and chemotherapy, as a second line therapy in stage four metastatic PDAC. A total of 43 patients initially diagnosed with unresectable stage four metastatic PDAC who had progressed following first line gemcitabine based therapy were enrolled in a triple combination arm. Patients received motixafortide monotherapy prime treatment for five days, followed by combination cycles of motixafortide, KEYTRUDA and chemotherapy Onivyde, 5-fluorouracil, leucovorin in combination until progression.
As is well known, PDAC is among the most difficult cancers to treat in patients with this diagnosis have historically had very poor prognosis, with five year survival rates of just 9% overall and just 3% of the greater than 50% of patients initially diagnosed at stage four. Many patients are first diagnosed with advanced stage four disease due mainly to the fact that this cancer is a symptomatic while it is metastasizing. And as mentioned, the patients in our COMBAT/KEYNOTE study were initially diagnosed at stage four, so this was a patient population with an extremely poor prognosis and perhaps worse than the patient populations evaluated in previous PDAC studies to date. It is against this backdrop that the date that we announced in December are all the more encouraging. The data demonstrated substantial improvement across all study end points as compared to historical data, including overall survival, median progression free survival, confirmed overall response rate, overall response rate and disease control rate. This is a big differentiation factor from other studies in this indication, which showed improvement in only one specific endpoint.
Let's recap the results. Median overall survival in months with 6.5 months in our COMBAT/ KEYNOTE study versus 4.7 months of historical data. Median progression free survival was 4.0 months in our COMBAT/KEYNOTE study versus 2.7 to 3.1 months of historical data.
Our confirmed overall response rate in the COMBAT/KEYNOTE study was 13.2% versus 7.7% in the historical data.
Our overall response rate was 21.2% versus 16% relating to historical data. And finally, our disease control rate in the study was 63.2% versus between 30% and 50% relating to historical data.
As you can see, again, the data demonstrated is substantial improvement across all study end points. We refer you to our press release dated December 16th for more detail, as well as important references to accompany the historical data.
We are currently planning the next development [phases] for this program, including discussions with potential collaboration partners and development of a protocol for a randomized controlled study. At this point, I'd like to very briefly recap two investigator initiated trials that are also evaluating motixafortide. Also in PDAC, Columbia University is leading a Phase 2 study evaluating motixafortide in combination with the anti PD-1 cemiplimab, known by its brand name Libtayo and standard of care chemotherapy gemcitabine and nab-paclitaxel. Notably, this is an entirely new study that is evaluating this combination as a first line treatment as compared to the COMBAT study, which is second line. This investigator initiated Phase 2 study will initially enroll 10 to 12 PDAC patients and will be expanded to a total of 40 patients following an evaluation of the initial 10 to 12 patients based on predefined criteria. Data from this study is anticipated in mid 2022.
Although, since this trial is not a company sponsored trial, the timelines are ultimately driven by the independent investigators, and therefore, could be subject to change. A second investigator initiated trial of motixafortide is ongoing in patients with COVID induced acute respiratory distress syndrome, or ARDS. The open label single arm Phase 1b study is being conducted at Wolfson Medical Center in Holon, Israel, and will enroll up to 25 hospitalized COVID patients. An interim analysis is planned after 10 patients have completed the initial treatment period, after which a decision to continue or not will be conducted. These preliminary results could be announced as early as the second half of this year.
Although, as with the Columbia University study, the timelines are driven by the independent investigators and could be subject to change.
Regarding our second clinical candidate AGI-134. Recall that we are evaluating safety and tolerability at the recommended dose in multiple solid tumor types in a Phase 1/2a study. The study is designed to evaluate a wide array of biomarkers and to validate AGI-134’s mechanism of action.
We will also assess clinical and pharmacodynamic parameters. In September 2019, we announced positive safety data and later that same month, we moved quickly to initiate part two, which is a dose expansion phase. We previously talked about enrollment delays caused by COVID-19, particularly as the pandemic impacted the UK and Israel particularly hard. And while this has caused delays, enrollment has now resumed and new sites and countries have been added and we remain on track to report data in the back half of this year. This is unchanged from the guidance that we provided last quarter. I would now like to turn the call over to Mali Zeevi, CFO, who will give a brief overview of our key fourth quarter financial statement items. Mali, please go ahead.
Thank you, Phil. In our financial discussions, we’ll 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 contains our financials, operating and financial review and press release for additional information. Research and development expenses for the year ended December 31, 2020 were $18.2 million, a decrease of $5.2 million compared to $23.4 million for the comparable period in 2019. The decrease resulted primarily from termination of the BATTLE clinical study for motixafortide in 2019 from lower expenses associated with motixafortide COMBAT clinical trial and from lower expenses associated with the AGI-134 study, as well as a decrease in share based compensation and payroll, company wide salary reduction related to the COVID-19 pandemic.
Turning to cash. The company held $22.6 million of cash, cash equivalents and short term bank deposits as of December 31, 2020. Subsequent to year end, we completed the financing that raised gross proceeds of $34.5 million and received another $9.8 million in gross proceeds from the exercise of outstanding warrants. And with that, I'll turn the call back over to Phil.
Thank you, Mali. In closing as is our custom, I'd like to take a few moments to summarize our key upcoming data milestones; first, final results from the GENESIS Phase 3 study and stem cell mobilization in early Q2 of this year; second data from the Phase 1/2a study of AGI-134 in multiple solid tumor types in the second half of this year; also a pre-NDA meeting with the FDA for stem cell mobilization in the second half of this year; and finally, an NDA submission for stem cell mobilization in the first half of 2022. In summary, we have achieved two very significant milestones during the fourth quarter with positive results of our GENESIS and COMBAT/KEYNOTE studies, suggesting that motixafortide is proving to be a versatile molecule capable of enhancing standards of care in multiple cancer types.
We are pleased with our continued progress, particularly in light of the disruptions caused by the pandemic, and I look forward to providing future updates. With that, we have now concluded the formal part of our presentation. Operator, we will now open up the call to questions.
[Operator Instructions] The first question is from Jason McCarthy of Maxim Group. Please go ahead.
It’s Dave on the line for Jason, thanks for taking my questions.
So regarding the Phase 2 study in PDAC. Can you shed some color on how the toxicity profile of the combination treatment being evaluated compared to the current standard of care? And do you plan on meeting regulators in any other regions globally with regards to potential commercialization? Thanks.
Avi, do you want to take the first part of that question about the toxicity?
[Technical Difficulty] and the combination of motixafortide and chemotherapy and KEYTRUDA has less toxicity in some of the parameters like neutropenia and infection, and this is based on the mechanism of action of BL-8040. And in the other parameters, we didn't see any increase in the signs, means that this combination is safe as given each one of the drugs separately. I hope this answers your question.
That was the first part.
The second part was whether we're considering having any discussions with regulatory authorities in this indication. Am I correct?
Yes, in other regions, like in the European Union, for example.
Are you talking about in PDAC, are you talking about in stem cell mobilization?
Well, for both, for motixafortide…
So I mean, right now we're focusing you know -- we're laser focused on moving forward in the US and meeting with the FDA, having the pre NDA meeting and then doing the NDA submission.
We are of course contemplating discussing and moving forward with registering and speaking with the authorities in Europe, for example, but that's going to be at the next stage. Right now as a small company, we feel that it's imperative for us to move forward as quickly as possible to get the drug approved in the US.
As far as the other indications, PDAC, that's something that we are considering, you know doing some kind of end of Phase 2 meeting or type C meeting. But right now, I think we're, again, laser focused on trying to develop the clinical protocol for the next study and having numerous discussions with parties that maybe collaboration partners with us on the next study.
The next question is from Joe Pantginis from HC Wainwright.
So a couple of questions, you answered one of them already. But I guess maybe what would be a bit of your wish list for this randomized control study in PDAC? Do you think there might be an interim look that could allow you for accelerated approval ahead of finishing the entire study because of the unmet need?
We think that's a possibility. It's not clear to us. We may consider. Again, a lot depends on the collaboration partner that we end up working with. It maybe a Phase 2/3 study with an interim analysis. It might be a large Phase 2 study. It's hard to say right now.
I think it's something that we're probably trying to put together a couple of possibilities.
Of course, since this is in an unmet medical need depending on the data, the robustness of the data, there is the possibility of getting conditional approval. But right now I think that right now, we're focusing on building the protocol and then we'll have to bring the data and see how it happens.
And then sticking with motixafortide, obviously, you're really having a corporate shift over the next year, as you look towards an NDA as you put it, as you said for next year.
So can you describe a little bit of what I guess I would portray as very important behind the scenes activity in preparing for that NDA, and what do you think are some of the major outstanding things that you have right now and where you stand on manufacturing?
Yes, of course, the entire CMC tests will be submitted to FDA.
We are currently -- not just the CMC, all the -- so NDA supporting activities that -- with regard to the preclinical CMC clinical pharmacology, the entire package has to be put together and prepared in a way expected in order to be able to submit it.
And to your question about the drug probably it’s part of the NDA submission and of course we are prepared for that as well.
Yes, of course, including the validation batches and everything that is required.
So, I mean, I think as I'm sure you're aware, it's a huge project and we're putting massive efforts on this.
As I said, we're laser focused to move this forward as quickly as possible.
[Operator Instructions] There are no further questions at this time.
Before I ask Mr. Phil Serlin to go ahead with his closing statements, I would like to remind participants that a replay of this call is scheduled to begin two hours after the conference. In the US, please call (188) 782-4291, in Israel, please call 03925-5904. Internationally, please call (9723) 925-5904. Mr. Serlin, will you like to make your concluding statements?
Yes, I would. Thank you. This concludes our call this morning. I'd like to thank you again for your interest in BioLineRx at this critical and transformative time for our company. And we look forward to our next comprehensive update in May. Be safe and have a great day. Thank you very much for your time.
Thank you. This concludes the BioLineRx' fourth quarter and full year 2020 conference call. Thank you for your participation.
You may go ahead and disconnect.
