Good morning, ladies and gentlemen. Welcome to our Q4 and full year 2020 highlights and financials. My name is Jan Ekbergs, and I'm Chairman of the Board. And I'm here together with Lars Niebuhr, our Interim CEO, Manelita Bronset, our CFO and Marco Marnoli, our CEO. Over the past year, I've acted somewhat I was an Executive Chairman spent quite a bit of time with the company.
Also my colleague board members have worked very intensely over the past year. First of all, I want to acknowledge this has been a very difficult year and a somewhat disappointing year for all of you and all our shareholders since our stock price has not performed at all over the past year. Unfortunately, we had to spend that year focusing on a number of very important operational fixes, which unfortunately resulted that we had very little news to report. But I'm very pleased that I think Today, we can report some very positive news to you, and I know you have been waiting for a long time with that. The next presentation that Lars and Malena and Marco will share with you will show you that we have now more than doubled our recruitment rates from about roughly 12 patients during the 1st 3 quarters in 2020, so over the period of 9 months, 12 patients to 14 patients over the most recent 3 months.
So up over the 3 quarters of last year, about 3 per quarter to 14 over the most recent 3 months, and that's a period from mid November to mid February. So a very significant improvement in our recruitment rates. And this all in spite of the fact that today we're still in the middle of a second wave of the corona epidemic, which had a huge impact on our ability to run had a huge impact on the ability of running non COVID related clinical studies. Real hospitals were locked down and were closed for those kind of initiatives. I'm also very pleased to report that we were able to reduce the number of required patients for submission due to the protocol changes that we have implemented during 2020.
Now we only have 47 patients to go to completion of paradigm, so a significant reduction. We also expect that this recruitment rate will further improve to about 8 patients per month or so in the late spring, early summer of this year. And some of those further improvements in the recruitment rate to the 8 I just mentioned will come from both some ongoing operational improvements, but also from lessening of the corona impact after the second wave, which we expect to all abate during the summer, but also more and more people getting vaccinated. So a further significant increase in our recruitment rates. Just to refresh your memory, pretty much exactly 1 year ago, We embarked on a very major organizational refocusing.
We appointed Lars as our Interim CEO, Malena as our new CFO and later in the year, Cristina, as our Chief Medical Officer. In addition, very early on last year, we made a number of very significant operational changes, significantly reduced operating costs, reduced our headcount by 25%, which really extended our runway. Unfortunately, In that process of reducing the headcount with 25%, we had to let go some of our excellent people. In addition, we also revisited our clinical protocol. Based on the interim analysis that we conducted in the middle of the year and that we released in early August, The external independent safety monitoring team recommended that we should drop 1 of the 2 arms of our paradigm study.
So until halfway last year, as you remember, we had 2 arms and now we have only 1 arm. And the reason for this is, Given the great safety profile, the Monitoring Board felt that we should take the best performing arm And that because of the safety profile, we should be able to lift some of the restrictions we had on our clinical protocol. From that moment on, we were able to include patients with lower patient counts, but also patients who have had who had bone marrow transplantation. These two facts, the lower platelet count and the patients that were coming included with Bone marrow transplantation, we have had bone marrow transplantation in the past, will increase the number of eligible patients We could potentially include in our clinical study by depending on the country, depending on the local practices in a different country, anywhere from about 30% to 70% more patients that could be included in the clinical study. So very important addition that would make more patients eligible for the clinical study.
After that decision, we also need to get approved by the local regulatory authorities. And as of this month, we just completed the entire process of getting all the local regulatory authorities to approve these protocol changes. In addition, we with the help of Karen Meyer, one of our Board members, We implemented a significantly improved management of our CRO, our clinical research organization. We also implement improved patient recruitment tools, in particular in the U. S.
So a number of additional measurements and decisions that really will help us improve our recruitment. So in summary, I think we're very positive where we are. We have only 47 patients to go To complete the PARADIGM study, our recruitment rate has increased from about 3 per quarter during the past year to 14 patients over the most recent 3 months and that all in spite of the fact that we're still in the middle of a very significant second wave of corona. And like I mentioned earlier, we expect our recruitment rate to increase even further to around 8 patients per month in the late spring, early summer. In short, we reiterate and repeat our guidance of our key Probably the question you want to ask, why did it take so long?
And because of the nature of biotech and the fact that beta lutin treats very sick patients, Any change you'd like to make to a protocol like dropping one arm or broaden inclusion criteria takes a long time to implement because you do need regulatory approval in each of the countries where you're operating the clinical study. Again, we fully realize 2020 has been a very difficult year for our shareholders, but we're really optimistic where we are and that we really have changed the corner now and can leave the phase where we need to implement all the required operational and organizational changes to fix our recruitment rate And now we can focus on the more exciting phase of the submission and towards the market launch. We're not there and we're not at the Submission yet, obviously, we need to complete the clinical study, but we definitely feel that the operational changes have now all been implemented. And I really want to acknowledge all the hard work that has been done by the team, particular Lars, our Interim CEO Malenis, our CFO Marco, our CEO, Christine and the rest of the management team. But also really was a lot of operational support from the Board, In particular, people like the Chair of our Clinical Strategy Committee, Jean Pierre Reu, together with Johanna Horabin and Rainer.
They have been very intimately involved in all the drafting of the protocol changes and some of the discussions with our regulatory authorities. Also Karen Meyer was very instrumental in the improved management of our CRO. And Hilde as Chair of our Audit Committee with Per and myself I'll be very intimately involved in the financing. I think that our new CMO, Christina Wilkerson, Summarizing best a couple of weeks ago during the team meeting when she said, and I quote her, we're beginning to see an encouraging improvement in the enrollment rate of paradigm. And based on the changes of the trial protocol and the initiatives that we are implementing to improve the execution of the trial, and this is where the important section is.
We now have clarity on the key regulators on the clinical data set that's expected as a basis for our filing. This clarity in conjunction with the improvement improving enrollment rate And to continue recruitment initiatives gives us confidence that we can meet our goal of having preliminary 3 months top line data in the second half of this year. So really, we feel very confident we're now on our track to submit to have the 3 months data by the end of this year. Again, This has been a true team effort working with management and the Board working hand in glove. So that's kind of what I want to summarize.
And I would now like to hand over to Lars, who will take you through the rest of the presentation And Marlene and Marco?
Thank you, Jan. Thanks for my side. Good morning, everyone. And as Jan mentioned, let me guide you in more detail through our Q4 update. I will start with the most important update on Paradigm.
As Jan mentioned, we have made a significant improvement to our And recruitment rate. So we have accelerated our recruitment rate from approximately 2 to 5 patients per month despite COVID. And also we are expecting that COVID is lessening. And as soon as that happens, the rate can further increase to at least 7 patients On average per month in late spring. Where did that improvement rates come from?
We have significantly improved the management of our CRO and also retained specialized firms to further improve our recruitment. We have converted our PARADIGM trial from a 2 arm into a single arm trial. And we also introduced simplification And the execution for our clinicians. We have a very good positive safety data set From the interim analysis and that also allowed us to broaden our inclusion criteria. We are now able to include patients with lower platelet counts and also after autologous stem cell transplantation.
That pool Our eligible patients increased depending by country between 30% 50%. Hence the analysis of interim data showed that number of patients to complete paradigm can be reduced. So we were able to present us to the health authorities and we can reduce the number of patients to 120 And that means we only have to have another 47 patients to go to finalize paradigm for the regulatory submission. With all of that, we reiterate our target to report preliminary 3 months top line data In the second half of this year, let me go in more detail through the highlights. We have now 73 patients enrolled as of yesterday.
And to remind everyone, we had 59 patients as of November 'eighteen. That means we have 14 patients enrolled In the last three months, we had only 3 patients from August to November 2020. So there you can see that all of our actions We really come to validation, and we are very confident that we can even go higher. Our protocol amendments have now been implemented in all 24 countries. Last ones, we're approving it last week.
The final patients have been enrolled in our 2nd cohort for ARCHER1, our second line, the dilution trial And also in the LINBIT-three thousand seven hundred and five phase where we are treating DLBCL patients. Preliminary data readout is expected in the first half of this year. Both trials now have been forced spending the analysis of data And the evaluation of further plans and development. We also were able to publish in Journal of Nuclear Medicine The results of our preclinical studies demonstrating that beta leukine reverses tumor resistance to rituximab in non Hodgkin lymphoma disease models. So all of that is really very, very positive and we are on the right track.
Now Reminding everyone what beta lutein is. Turning to Slide 7. Beta lutein has a compelling, unique and differentiated value proposition for non Hodgkin lymphoma patients. As a short reminder, We have an anti CD77 antibody. CD37 is highly expressed on B cells.
We do have the T cell with half life of 7 phase That's a reactive compound and the mechanism of action of our antibody drug conjugate is Internalization and cell death and very important, the crossfire effect of the T SUM, Which gives us really very, very good results. Now the key benefit, Especially during the pandemic, we should not forget and our elderly patients, we only have a single dose treatment, so none of our competitors have that. We have a direct response in elderly and heavily treated patients. Our safety profile Very good. We have a predictable and manageable side effect burden.
And very importantly, Most of the treatments today are anti CD20 treatments and we do have an alternative target to CD20, Which is suitable for rituximab refractory patients. Now As we promised, when I had to go away in February, that we wanted to revise our clinical strategy and that we are focusing on paradigm. So that is what really happened over the last year. So we brought forward PARADIGM and PARADIGM is Our first to market in the trial, so the indication is certain relapsedrefractory follicular lymphoma. We are of course together with the data out of ARCHER 1 and LIMRID 3,705, Which I mentioned, they're finalized and we are analyzing the data.
We're looking with all of that data together to really analyze the optimal strategy To advance in earlier lines. And since we do have also pretty good results in marginal zone lymphoma, We're also looking on the opportunity how to move ahead with Marginal Zone Lymphoma. Now going shortly to Part A, sorry for everybody who has heard that several times. I think it's still a very impressive story. So what you can see here on the waterfall diagram is the amount of shrinkage Of the tumor size, what you can see there in our 74 patients which we had in the 3701 Part A trial That about 90% of the patient has shrinkage or reducing in tumor size.
And Slightly other description is that we have an overall response rate of 67% and 24% of CR in Rituximab refractory patients, as I mentioned, these are really the ones which are suffering most from not having any therapy available. Our medium response rate for all responders is more than a year and even more than 2.5 years we do have for our complete responders. So that's really a very impressive result With progression free survival of around 9 months. Now that is also important for how we position better lutein in the market. As Jan mentioned, we are now preparing it.
I would like to remind everyone, our patient characteristics is that we have elderly patients. The Midian is 68 years old and there is no huge difference between Part A and Part B. They've been heavily pretreated with advanced stage disease and that is also pretty similar between Part A and B, overall, we have a very good safety data set and efficacy data set in that patient population. Betelution was also very it's very well tolerated. That is why we also can now treat patients with lower platelets and total local stem cell transplantation.
The interim analysis, as mentioned by Jan, we had it in July last year. We had before a 2 arm trial with a lower dose and a higher dose, so the lower dose was the 15 megabecarab per kilogram Betelacine And the pretreatment of the cold antibody with 40,000,000 tons flat of lilotamab and higher dose arm was 20 megabecquival per kg And beta lutein and 100 meg per meter is clearly load them up. So these were the 2 months and the Safety Review Committee looked at all of the data in very much detail and recommended to go ahead with the 4,015 arm. So as mentioned, we have 73 patients enrolled as of yesterday And the trial is to 120 patients with 47 patients to go. We have 95 sites open in 24 countries.
We have promised And our number one priority since I took over is the improving of trial execution. Let me recap a little bit what we have done. So the program management has been mentioned already. It's now approved in all 24 countries. The broadening of the including criteria has increased The pool size by 30% to 50% depending on the country.
The decision to make PARADIGM, a single Let's have a reduction in patient numbers needed to complete paradigm for BLA filing. 47 patients I now needed to finalize it. The site specific action plan has been implemented. Senior leadership at Nano and our CRO Deeply involves in continuous monitoring the site performance metrics, which are also increasing significantly. CMO is hosting virtual meetings with trial investigators and the teams to promote Paradigm.
So Kristine is very active here. She had more or less every PI on the call And they are appreciating that very much. The specialist firms we have appointed Are there to focus on further improving our rate of recruitment, including targeted social media campaigns. The major focus currently is North America and there in particular the U. S.
There's also some other facts from our competitors. The 3 trials for our competitors have been finalized and the bispecific one bispecific antibody trial And it's on clinical hold. So that also might give us a few additional patients. And very important also here is The vaccination rollout is expected to reduce restrictions imposed on COVID-nineteen. And as you know, our patients Are on average 68 years old.
They are in the group which needs to be protected. So from that It is very important for our patient population that the vaccination is going on very fast. Our regulatory strategy to gain rapid approval. CLA filing With the FDA for accelerated approval based on paradigm data and mission of comparator Phase III trial. That is important.
We will go ahead with our Phase IIb paradigm trial. We do have often drug designation for And a third line follicular lymphoma granted in the U. S. And in the U. S.
We do have Fast Track granted For both, for example, for my margin zone and in the U. K, we do have also the promising innovative medicine status. And of course, we are always exploring other routes to bring beta lutein faster to our patients. Now coming to the positioning of better luting, going to Slide 16. What you can see here is what we mentioned before as well.
It is a unique product profile Of all third line lymphoma patients. And If you progress at a very early stage in the 3rd line, you have great medicines like the stem cell transplantation, which I mentioned or also the CAR T, Which close to approval, as they are looking, it's very promising results. They're expensive. They do have high side effects. Only a very few patients are eligible for CAR T for the CAR T therapy.
Bi specific antibodies Also having promising results to have very high side effects, which we can see on the clinical hold of the Regeneron Bi specific antibody. Going further to the other Lanthell patients, I mean, the green circle here. If you're looking around that, there's not a lot out there for our patient population. We do have the old Revolint, we We do have rituximab and rituximab refractory is not very effective. We do have PI3 kinase inhibitors, So 3 of the first generation and 1 of the second generation has been improved.
Their side effects are very high And they are rarely used. We do have a competitor with Tazemetostat, Good results, but only in a very minor fraction of patients who do have a certain mutation, which Corresponds to approximately 15% of the overall patients in follicular lymphoma. So overall, that means there is still a high unmet need. And with our safety profile, with our single injection, We are very well positioned to serve these patient population and patients with comorbidities that prevent And the use of both chemotherapies or other therapies associated with the highcitabine, They are very well positioned for belalutine. And what we have shown is the durable response is a very good safety profile in the administration has mentioned, so really very well positioned for that.
And that is also the feedback we are getting more and more From our customers, the efficacy observed in 3701 is seen as a major strength. Our response rate and the medium duration of response and complete response is very compelling to Himans. And the combination of potential benefit is what that that is in a part. The one time treatment, The variable efficacy, manageable and benign safety profile and the simplicity for patients and physicians. So Hmong, your elderly and frail patients, which are majority of the patients with follicular lymphoma With comorbidities, including patients with refractory to rituximab, as the ideal beta lutein patients.
With that, I will hand over to Jumaal.
Thank you very much. Let's take a look at the financials. So as you can see, we have still a good control over the finances. We spent 107 In the last quarter, which is compared to 139 last year. And of course, we see here some of the effects Of the reduction we did in, unfortunately, staff, but other things as well earlier or in Or 2020.
As you can see also and then we will continue to, of course, to look for further savings. When that said, we do not, of course, want to jeopardize the start. We do want to complete on time. So it is Most important now to spend the money on the right thing, which means, of course, clinical and also our CMC activities. On the next slide here, you could just see that the cash run rate, which is now extended into Q3 2021, so this year.
And it gave us, in the end of the year, a cash position of 294 As we will continue, as I said, to look for savings, so we can push it as far as we can. And as I said, NOK
294,000,000 in the bank at
the end of the quarter, which is, of course, a result of The financing round that we did in September. With that, Lars, I will hand it back to you.
Thank you, Malveina. So we are 100% focused on delivering on our PARADAME trial. We are highly confident The potential of beta-fifteen to fulfill the important unmet clinical needs. The goal is to complete paradigm And we are targeting our preliminary streamline top line data in the second half of this year. We have reduced the trial size That means we only have to have 47 patients to go to complete paradigm for BLA filing.
We have significantly improved the rate of patient recruitment into Paradigm despite the 2nd wave of the corona pandemic. Our inclusion criteria has been broadened. We have shown that we have a very good safety profile and we are even going further with additional initiatives to further enhance the rate of improvement. Our promising clinical efficacy and safety data seen from our One time administration in relapse refractory in oleit lavoshkin lymphoma. And very important to mention is that allogene is 100 Owned assets, we are targeting a total NN and D and A opportunity to approximately US26 $1,000,000,000 by 2026.
So and of course, we are actively pursuing Flexible regional commoditization strategies to maximize more value. So with that, I only need to remind everybody on the next dates From the financial calendar, the AGM will take place on the 15th April. You will hear our Q1 results End of May on 26th and the first half the half year results on the 27th August. So with that, we are open for questions.
Yes, good morning. We do have quite a lot of questions here, but many of them are Similar. So we're trying to address the main questions here now. First question is about Financing. And we have a couple of questions here related to the future financing plan.
Referring to In the Q3 report, you said something about the extended cash runway could be done with different tools. And how will the company work looking forward to secure the financial situation from Q3 2021 and forward?
Jan, will you take that question?
Yes. As we mentioned during our pre release quarterly, We do need to raise some money during the first half of this year, and we clearly want to raise money beyond what we consider the key value point, which is the 3 months data readout later this year. So management, together with the Board, are evaluating various options. We will hear more about in the nearby future. But this is clearly a recognition, which we mentioned during the previous quarter release that we need to raise money at some stage during the first half of this year.
Thank you, Jan. We do have a lot of questions It's about the Paradigm study, of course. And some of them have been addressed and answered during the presentation, But some of them are also new. So first one, what is the impact of COVID-nineteen on Follow-up visits and data collection for Paradigm.
A very good question. So what we are doing is, as mentioned, we have really very good interaction with our CRO and also with our From the investigators in the hospitals, so the overall facilities are now in that way that we always have Somebody in the hospital who can take care of that. However, a visit is possible. Of course, we are doing the visits, but why not? And we have implemented procedures that Our corona conform and that we can get all of the data and most of the visits Maite, as mentioned in the protocol.
Thank you, Lars. The second question about Paradigm is On recruitment, can you indicate anything on the geographical split of where most patients have been recruited from so far?
So far, as we mentioned before, our best recruiting countries have been historically UK and France, what we are seeing now is that wherever the corona pandemic is going down, we do see The huge impact on the patients are coming back. From that point, we are expecting as soon as the corona is going down that also All of the other countries will come back.
Thank you. And there is also a question about The split between the 4,015 dose and the 120 dose among the 37 patients that have been recruited so far?
The 37 patients?
Sorry, the 73 patients?
Yes, of course. There was a split because we have until the interim analysis, we went ahead with the 2 arms. We have done the interim analysis at 47 patients. And as soon as we got the approval for the single arm, we are focused on the single on the 4,015 trial. And the patients which have been dosed to 120 are, of course, counting to the overall patient number of the 120.
Thank you. Another question is, do you see any safety issues with regards Sorry, that question disappeared right now. Do you see any safety issues With regards to the patients treated under the new protocol?
No. We don't see anything there yet, but we need to be careful here Because we, of course, need to wait for the 3 months data of the patients. And as mentioned, the protocol has been approved in all 24 countries. And we have patients coming in on this new protocol, but we have not reached yet the 3 month data set.
We have not had any material adverse changes and that would have been reportable, just to be clear. There are no material adverse changes at all. It's a very Safe has a very strong safety profile of the compound. Oprylate, there are patients with comorbidity, which means we have multiple other diseases, we're dealing with very sick patients, but we have not seen any indication of any problems with the compound itself.
Okay. Next question is, could you comment further on the target for the 3 month top line data in second half of twenty twenty one With respect to when you then would need to be fully recruited and what rate of enrollment would be reached required to reach this?
What we mentioned, we are very confident that we can reach our preliminary 3 month top line data This year and as mentioned in the presentation, we are very confident that we can increase our rate of Recruitment to at least 7 patients per month.
Thank you. There is another Question about MZL and whether it's possible to provide an update regarding MZL?
Yes, the update you said, of course, we are working together with our clinical strategy committee With the Board on how we can how can we move ahead. And as Jan mentioned in his introduction, that is So Arthur, strategic question. So we are looking on where do we position the company best. And we have very good results in Marginal Zone. We are working on a clinical protocol there.
And as soon as we know more, we will inform you.
Thank you. Could you also say something about Alpha 37, how that is going?
Also that one, it was only in my presentation yet. I have put our research activities on hold. So we are looking as soon as We do have a clear path forward there that we might want to go ahead or but yet, As mentioned before, we focus everything on Paradigm. And with that, we have put it on hold.
Thank you. We do also have some questions about regulatory approval and market access. And there's a question about where we do stand when it comes Fast Track.
So Fast Track is a regulatory status. So as soon as we have submitted, then The FDA is agreeing to handle that with the fast rate pathway. So from that point, we are still having, of course, Fast Track, but since we haven't submitted yet, there is no Fast Track pathway yet. We expect As soon as we have the data that we are reaching out to the health authorities so that we can have the submission in 2022.
And you mentioned both FDA interactions and internal review provides you Confidence that 120 patients is enough for a filing for accelerated approval. The question is, did the FDA approve of that 120 patients number. And what color can you give on what gives you confidence?
As we mentioned before, we have regular interactions with the health authorities, And we did get very good feedback and interactions with the health authorities, And that is why we are absolutely confident that the 120 patients is Good for submission. Of course, depending on the clinical data.
Thank you. And Another question is, is there a minimum amount of U. S. Patients specifically that you need to recruit to support an FDA filing?
There is no specific Requirement for U. S. Patients, so there's a rule or any law or something like that In the FDA regulations, it is more that there is, of course, an expectation that you have to have Some U. S. Patients as we have seen with our competing trials.
And we are in a good range there That we are confident that we reach sufficient U. S. Patients to meet the expectations of the FDA.
The other thing to keep in mind is that the FDA is now accepting also patients from countries that you kind of have a mutual recognition. So not just in the United States, but also some other Anglo Saxon countries.
Thank you. The next question is, can you file in Europe based on paradigm or is that unlikely?
Marco, in that case, I need to hand over to you. I think you have looked into that in very much detail on our European approach.
I think in general, European regulatory authorities have been A bit more rigid in terms of approving products based on Phase IIb trials. But most recently, drugs that have demonstrated a strong clinical advantage over available therapies We've been able to obtain conditional approval. So our first priority is, of course, filing with the FDA, but we will explore All options to support a filing with the EMA authorities as well with the current trial. I hope that satisfies the question.
Thank you, Marco. We are going to raise the last question here. And after that, there might still be some questions that have not been answered yet, but the more detailed questions will be Handled by e mail in order to not to go into much detail here. So the last question is about partnerships. The usual questions, Are there any big pharma companies that are interested in making a deal with you?
Or have you been contacted by big pharma? Are you thinking about such cooperations?
Sure. We are always thinking is our beauty. So as a company, so we are always investigating Different business development opportunities. And as usual, we will revert to you and to markets with updates if and when any of these Discussions materialize.
Thank you, Lars. That concludes the Q and A session. And as I said, There might be some questions that have not been answered yet of the more detailed kind, and we are going to respond to those by e mail. Thank you.
Thank you, Kari. Thank you, everyone. With that, I think we can conclude Certain, Jan, any single points, final words?
Again, I want to thank everybody. I want to acknowledge that last year has been a very difficult year for our shareholders, But I really think the company has now turned the corner and we're now really at the phase of moving forward towards the submission of beta lutin and going to the market. So I think we are entering a very exciting phase and both Board and management are very optimistic about the future. So I want to thank you all for your support over the past year. Again, acknowledge it was not an easy year, but I think we're going to the finish line now.