Morning, ladies and gentlemen. Welcome to the update on the Paradigm and the new timeline for Nordic Nanofactor. My name is Jan Ekberts, and I'm the Chairman of the Board of Directors of Nordic Manufactor. Today is here with me are Malleiter Bronberg, our Interim CEO and CFO and Marco Rinaldi, our Chief Operating Officer. First of all, we'd like to share some slides with you where we give you a little bit more detail regarding the current situation and then subsequently we have some time for some questions.
So hereby, I'd like hand over to Malena to take us through the presentation together with Marco.
Good morning, ladies and gentlemen. Thank you very much. As Jan said, my name is Malena. And I'll take you through a couple of slides and then I'll hand it over to Marco after that. As you can see that we announced the day before yesterday evening that we have a Unfortunately, I have to come up with a new timeline on Paradigm.
That said, we are continuing to focus on, of course, completing Paradigm As quickly as possible. As you also saw during 2020, we made significant improvements to the both the trial design And also how we and we implemented a multiple of initiatives to improve the execution. And with that result, we saw some good improvements in 2021 compared to 2020, but not unfortunately as much as we had anticipated. As of the 3rd August, we had 92 Enrolled patients out of a target of 120 and this is up from 83 as we announced on the 25th May 2021. We've also made the decision to not to invest further funds into our ARCHER trial.
But that said, it's very, very important to say that that Data insight will help in designing the protocol for the confirmatory Phase III clinical trial And because as you know, it is very positive data that we have in that time and that is important. We have also decided We will do in Q4 R and D Day. And of course, it is with the current COVID situation, it is very difficult To say the exact timing right now, but here we would like to discuss the position and the next step for the bisileuci development And as well also give an insight into other value enhancing opportunities we believe we have in the pipeline. So as I said, we unfortunately have to revise the paradigm timeline. And this is, of course, a very serious situation with the COVID.
And we have seen an uptick, but unfortunately, as you also know, the delta variant hit hard. And where we started first with the delta variant is here in the U. K. Where I'm sitting because unfortunately I can't travel into Norway right now. And then it spreads throughout because we have seen a good trend in the patient enrollment.
But unfortunately, The delta variant didn't help us. So we did decide to, unfortunately, to revise the timelines After we had, of course, discussions with our clinical advisers and the CRO who managed our trial, And we have, of course, continued to focus on the increased interest in enrolling patients in regions where we've seen that COVID is Under better control. And we are, of course, confident that we can maintain and improve Margarita, the current rate of the recruitment despite the COVID situation. When that is said, it's also worth mentioning that August is always, just so you have that in mind, when we report in the end of August where we're going to again give an update On our numbers of recruitment, it's always a weak month because of just the nature that in most European countries, that's The holiday season. And of course, unfortunately, with the COVID, that doesn't help.
When that's all that Seth, then the new timeline for PARADIGM is that we are targeting preliminary 3 months data readout during the first half of twenty twenty two. And with that, I would hand the next slide to Marco, please.
Yes. Good morning, ladies and gentlemen. Our confidence And the value of beta lutein remains very strong. Not only beta lutein is the most advanced Radiopharmaceutical in clinical development, but it's also one of the most attractive compounds in this setting. The reason why our confidence is so strong is because beta lutein targets a disease, a complex disease where the unmet medical need is high.
Despite new therapies have been made available, Quite a few targeted therapies in the follicular lymphoma setting even one CAR T, but there is a portion of the relapsed refractory patient population suffering from NHL and follicular lymphoma, which is underserved by existing therapies. This is the population of the elderly, of the frail patients with a poor performance status with serious comorbidities. These are patients that as a nature of their age or as a nature of the comorbidities Associated to prior therapies do not tolerate, cannot accept or are not willing to undergo either chemotherapy or even the novel agents that have been approved, the PI3K inhibitors, The CAR T cell therapies, because both physicians and patients know that while these therapies may be effective, They are associated to a high side effect burden. And I think it's worth stating that for patients entering into the 3rd Line of therapy after devastating prior lines of therapy with chemotherapy, Remission is an important goal, but these patients look for more than remission. They look for a better quality of life.
They want a more balanced type of treatment that ensure remission, but also ensures a more tolerable profile. And this is exactly what beta luting can offer. We can satisfy that need for a chemo free effective and tolerable treatment. And that's why we believe that we have a tremendous opportunity in this set of patients. And in third line, this is not a niche population.
This is more than 70 The bisalutin is not just the 3rd line follicular lymphoma indication, Even if that's a very promising indication. Vitolutin holds Multiple opportunities to expand in follow on indications. You have heard from Alena, we are preparing To start the Phase 3, which will enable us to secure a second label in second line follicular lymphoma, we have now more information on what the next Steps will be for diffuse large B cell. We have multiple opportunities to further exploit the market potential for this compound. With that, I'd like to hand over back to you, Malena.
Thank you very much, Martin. And I just want to round off our presentation here just with a reminder about the next events that we have. So as I said, the 27th August, that's when we report the Q2. I do hope that I will be able Marco, we will be able to travel into Oslo. But as right now, It looks difficult unfortunately.
And we will have the R and D day as also said, and we would like to have it in the Q4 just So we have time to prepare and hopefully we will see an improvement on the travel, so we can be impossible for that day. And then finally, of course, we have the Q3, which would be the 18th November. With that, I would like to hand it over to the question of the questions, please.
Thanks, Malena. So the first question we have is how is the hunt for a new permanent CEO going?
So Jan, I think that's a question for you, please.
My apologies. I was muted. We currently have a very active search process. We have retained an executive search firm who is helping us and we are talking to various potential candidates. So that's ongoing.
Okay. Moving on to some questions about Paratane. It says, will recruitment be completed be announced as soon as possible? How long will it take from the last patient goes to top line data? Will this be announced directly to the market?
Or will you wait for a suitable conference?
We will if I can start and then I'll hand it over to Marco. And We will announce when we've completed the enrollment. And as I said, we would do everything and the management team works really well together and we also of course work with the boards to do everything that we can To get it going as fast as we can. And when it gets to the We need from the patients in, we roughly need 3 months where we then can then come out with the preliminary top line data. Mark, we don't know if you have anything further to
add. No, I think you covered it very well. As you know, we had an assessment of 3 months after the patient received vtolutin, we of course will clean patients in stacks as they progress. You can expect maybe for the patients in the last month some additional weeks to claim the data, but in essence 3 months after The last patient in, we will be able to provide preliminary top line data.
Okay. Next question. Is it possible to have a 3 month readout after the first 100 patients just to inform the market of the results.
As you kind of understand, we need to have All patients in and that's of course important. And it's of course Yes, important that the data cleaning takes place in the way it has to take place, of course. Mark, we don't know if you've got anything further on this.
I think we have agreed with the regulatory agencies that we will do formal analysis only At certain points in time, which is when all patients are enrolled and after certain amounts of time following the enrollment, So we have to comply with what we have agreed.
Next question. Can you start writing the NDA application when preliminary results 100 or 110 patients are available and then include the final 10 to 20 just before submission.
As going back to saying, we need the 120. I don't know, Marco, have you got any further on the question?
I think we can start preparing for other elements of the BLA application. The BLA application is a very complex endeavor and our regulatory team is coordinating these massive efforts. This includes non clinical CMC and clinical data and we are advancing all of these Workstreams in parallel and we can certainly keep priority to certain areas until when the full clinical data set is available. And we of course, since we have received Fast Track, we even have the possibility of exploring The rolling BLA concept. So yes, what is being asked is possible.
We can have different Information documentation being provided at different times, but we will wait until the 120 patients are enrolled To finalize the clinical documents.
I just want to be clear that is the plan. The plan is a rolling admission that we providing information to the agency as soon as it is available. Again, the data integrity with the point about can you break the code after 100 patients. That's a very important point to the regulatory authorities like the FDA. You really do not want to have been very negative towards breaking this code halfway.
Next question. About 2 years ago, a significant emphasis was made on CMC strategies in respect to BLA readiness According to public job listings, the company have also made a number of hires in this field. Lately, however, there has been limited investor Communication around manufacturing, are there any changes to your go to market strategy?
Marco, I think I will hand that over to you.
No. The requirements for a BLA filing as far as CMCs It's required and not changed. We are committed and actually are on our way To satisfy the requirements that the agency, the FDA poses in terms of CMC readiness, And all the performance process performance qualification activities are underway and proceeding well. So all that we had described a couple of years ago during one of our R and D Day On their way and maybe we'll find opportunities to update the market on all these activities.
If I could, sorry, Jan.
Jan, the word CMC or people have not heard or the acronym CMC stands for chemistry, manufacturing and control, which is basically the catch all phrase for manufacturing issues. So in case people kind of wonder what CMC means.
Thank you, Jan.
Yes. And if I can follow-up on that, I can just say and also allude to the fact that I have said in the last many quarterly calls that we, of course, Do continue also with the spending in CMC because I've also said that that is, as Marco also said, a very important part of getting ready. So we are of course continuing on that path.
Where in the world is recruitment highest in paradigm? And how many patients do you currently have in screening?
We don't give a insight, unfortunately, into It's country nor each region. And also, we don't give into the To the screening, what we will continue to do is we will continue to update every quarter On how we are going with how the enrollment is going. And as I also said before, we have in the areas Where that is was less hit by COVID, we saw an uptick in the areas and the countries where we saw a big impact of COVID. Of course, We saw that we were more hit. I don't know, Marco, if you got.
No, I have nothing to add, but COVID has impacted which are the most enrolling countries. And we have seen countries that were enrolling extremely well and that were hit by COVID and therefore decreased their enrollment rate and others came up. So it's really an inconsistent pattern dictated more by COVID
Next question.
Yes. Can you say which 10 sites you have closed due to low recruitment or in which countries they're in?
No, we don't provide that detail. But what is, of course, very important to say is that We do we always evaluate what we do and we do that all the time. And of course, it's we would Spend the money with the best way we can, of course. And of course, we do need to take initiative if we can see that something is It's not working. We can put the money at places where we think that's a better investment.
And that is a day to day assessment that we do. And because, of course, we're fully aware that it's the money it's the shareholders' money. So that's very important, of course. Mark, I don't know if you've No.
Nothing to add. We optimize to be more effective. That's what we do.
Next question. Historically, you've referred to the PARADIGM trial as a pisavil tool trial, but you do not do that anymore. Can you discuss your current thinking on the regulatory process for beta dilution based on PARADIGM? Is it possible to file for an accelerated Approval based on paradigm or do you think you need to complete confirmatory Phase III trial before filing?
We believe based on our conversation with the FDA that we can file With the data generated through the PARADIGM trial for accelerated approval at the time of filing with the data generated From the PARADIGM trial, of course, pending results, we need to have a Phase 3 confirmatory trial started. That is what the FDA requires for any compound filing for accelerated approval with a Phase 2 study. So that's reality. Of course, we are looking for the data that will determine the robustness of the data. But yes, Paradigm is can be sufficient to file for accelerated approval.
Thanks, Marco. Next question. Based on the interim results from last summer, do the management and the Board believe that beta lutin will come to market? Absolutely. Yes, absolutely.
The interim analysis confirmed Strong activity for both dosing regimens and a tolerability and safety profile in line with expectations. There was a clear recommendation from the independent review committee to go for the 4,015 dose, which the company acknowledged and which was later discussed with the agency. That's why we have proceeded with the new single agent study for the 2nd part of the paradigm. But clearly strong sign of activity. So we are confident that the drug Through the PARADIGNE, the rest of the PARADIGNE trial will confirm its efficacy level.
Next question. What year do you estimate that betalutin will be on the market? Do you have interest from other pharma companies in betalutin? Would you consider that interest as high?
Jan, would you please step in or Mark?
Mark, take the timing. I will take the other one.
Yes. I think it's It's a bit early to guide on approval timelines. I think what we can clearly confirm as we had previously As anticipated during the quarterly call, we still expect to start the BLA process in 2022. And of course, the approval of the Compound will depend on the review, whether it's a priority review, it's a standard review by the agency and all formalities. But I think, again, we want to confirm our intent to start the BLA filing process in 2020 I'll hand over to Jan in regard to the partner lending strategy and interest from other partners.
Yes. So thank you. So our business development team has discussions with various parties. The reality is that these compounds typically do not get Any formal agreement with any partner until there are more definitive data regarding the performance of the product. I've been long on the other side of the equation, working for big Pharma.
And typically, we usually wait until we have very definitive results of clinical studies. But yes, we are talking to a lot of different people and different companies on an ongoing basis.
Thanks Jan. The next question, given the recruitment issue in Paradigm, how does Nordic Nanovector expect to market betalutin and sell it By themselves in certain regions. And in light of the recruitment progress, does it not make sense to partner up in all markets?
It's a partnering question. So, I mean, the Board actively is doing investigating various partnering approaches. The most likely outcome is a mix, where in the larger market we would have a partner, small markets, we probably would not have a partner that's smaller, more local markets, like for instance, Scandinavia. But that's not definitively decided yet, Just a pure hypothesis that where we are. But no, there's likely a hybrid model like many of these smaller Biotech companies, when you go to market with the first compound tend to have a hybrid strategy.
And I would expect, there's no definitive decision yet, but I would back to do the same for our company.
Thanks, Jen. Just Moving on to ARCHER. What are the consequences of Stopping further studies of ARCHER 1 now. Many people see this as perhaps the company's most important asset in terms of valuation. Do you already have enough data to be able to say that ARCHOR-one will be attractive combination medicine?
I can take that. I think the decision to stop investing resources in Archer It's a very positive decision because it means that we have collected enough information from this study. As you recall, ARSCHARD 1 was a mainly a study to assess the safety and tolerability of the combination of vtolutin plus rituximab as well as the preliminary activity of the combination. And we have seen that this combination does not alter significantly The profile of BT Lutin when it comes to safety and tolerability, which is one of the most important features of this profile. We've also seen that the combination strengthened the efficacy of the compound.
Therefore, we had all the information we needed to inform the next stage of development for 2nd line follicular lymphoma. As you know, our Phase 3, which We have to start at the time of BLA filing. We'll target second line follicular lymphoma. So again, we welcome the decision Put an end to Archer 1 as a positive decision because it means we have gathered enough information to inform the next stages of development.
Thank you, Marco. With rituximab off patent, how many biosimilar partner opportunities exist for the future ARCHOR-one combo treatment regimen?
Yes. There are many biosimilars on the market. As you know, biosimilar, The biosimilar business model is not a model that leverages scientific collaboration. It's a model that leverages tenders, pricing discount, first entry advantage. Therefore, There is a limited synergy that can be gained from a scientific collaboration with any of these companies.
But clearly the prevalence of many rituximab biosimilars means the rituximab will remain a significant component in the treatment algorithm and therefore choosing for example to combine with that
Thank you, Marco. This is a Phase 3 study consisting of betalutin plus rituximab as a combination in one arm and mantle cell lymphoma in the other aimed at 2nd line FL and 3rd line FL are possibility.
We will probably provide some update on our Ideas relative to the Phase 3 design later in the year once we've had the opportunity to discuss the current proposal with the agency. But in general, I can say that a Phase 3 study It basically compares the drug that we want to assess in our case beta lutein whether in combination with another drug or as consolidation to another treatment versus a comparator In 1 or more NHL subtypes. Again, we cannot comment at this point in time because we are in the process of finalizing our Phase III design, but we want to first have a conversation with the AAGES. When the company is ready, we will provide more updates With the market. I don't know if Malenia or Jan wants to add anything to this.
No, I I totally agree. As you could just hear, we have a lot of things going on. And as I said, working To first paradigm, of course, to get that completed. And then, of course, we also, at the same time, as Markku just said, working on the Phase III design.
How many Archer patients are still in remission?
I do not have that exact number on top of my mind. I believe it's 6 out of 7, but we would need to check with our Chief Medical Officer who is not on the call and will be able to provide an update maybe at the
Maybe we should move on to talking about financing questions, financial questions.
Yes.
Can you discuss the financial implications of the delay, please? In connection to your last capital increase, you stated that you did not plan to raise any more capital until you had presented the 3 month follow-up data from Paradigm. Is this still realistic given the recruitment rate, the follow-up time and the company's burn rate?
Yes. Well, as I said, We would do everything that we can to complete as quickly as possible, and we will let you know when we have completed, and we will continue on the quarterly updates. We also said that we expect the preliminary top line data in the first half twenty twenty two. And we have And we will reiterate that statement also that we have funds going into the second half of into 'twenty two. We will, of course, and we do that all the time as you've heard with some of the initiatives we've taken.
We look at the And our botches and try to spend the money where the money should be spent. And of course, it's important We spend the money so we get the enrollment going as fast as possible. But as I said, it is second half twenty twenty two that we have the money and we expect To be able to have the beta top line preliminary data in the first half.
Thank you, Malena. How does scoping investment in Archer affect the budget and the yearly cash flow?
Well, of course, It has an impact, of course, on that. But as I said, the most And also as Mark said, the most important thing is that we now feel that we have we learned what we should from the ARCHOR 1. And that, of course, is very important. It is. And that's where we take the decision.
Of course, there is a money implication as well, but that Where we took the decision on that it is the learning that we feel we've now got from it. Okay.
What is the cost impact of closing the 10 sites in Paradigm?
It will have an impact. That said, we will also some of that money, we will spend them on the move them into other things, Other initiatives where we see that that could have an impact on the recruitment, Because here, the task is really to get that going as fast as possible. And that, of course, means that we are not slowing down On the spending on Paradigm.
Then there
will be other areas that of course we and we do that all the time, look into And whether we can find some savings, but not inherent and that's of course the key.
The money will be reinvested in patient acceleration initiatives focused on the other sites that we've seen have worked very well in certain countries. So It will actually give us the chance to make the sites which are more productive even more productive.
Exactly.
I think this is most probably the last question. It says, what is the rationale for spending time and resources and preparing for an R and D in the current situation? What does the company hope to achieve?
The thing is a long time ago since we last had an R and D day. And of course, We feel that we have some as we've spoken about before, some want to give an update on other projects. So it's not just Paradigm because Nordic Nanovector is more than Paradigm. And we would have liked to have it before that, we can also see with the current COVID situation that it is impossible. And we would like, of course, to have time to plan because as we had In 'nineteen, where we have the day on 17th September, we had a day where we also had some external experts in.
And it just takes time to plan that. And with the current situation, that's why we basically set Q4. We would I'd like to add it before I go on, Marco.
You covered it very well. If I may just add that the company is field reviewed through the lens of paradigm and third line follicular lymphoma. And there is a lot of progress we have made In both the clinical development plans and commercialization plans, we are working actively on the design of the Phase 3. We have progressed on the understanding of what the next steps of development for diffuse RHB cell. Vitolutin is much more than just third line follicular lymphoma and we feel that we have updates for the market on this.
Secondarily, we have projects that have merit, that have the potential to represent important contributors to the value creation of the company. And we feel Even if we understand the market is waiting for Paradigm, these elements will be important to improve the appreciation of what this
Thank you, Marco. We just had a couple more questions. What is the preliminary medium duration of response for the ARCH or study?
I As I pointed out, we I'm aware that 6 patients are still on remission. So I do not know when the next Plan assessment, median duration of response is new. So I have to refer this question To my colleague, Christine, and we may provide an update in one of the upcoming meetings.
Thank you, Marco. I think we've covered nearly all of the questions I'll comment on most of and I think all of the topics that the questions cover. So I'll hand it back to Malena.
Well, thank you very much. Before I hand it back to Jan, I would just say thank you very much. As you can hear, it is a team effort here. And as Jan also said, we are searching for a CEO and well underway. And we will do everything in the meantime, the team that's here to get the enrollment going as fast And with that, Jan, I would hand it back to you.
Yes. Thank you very much. I think we covered it. Thanks for your attention. And obviously, August 27, we will have our quarterly release.
We'll give you some more information. We don't expect too much difference between today and 27, but It's always an important milestone, the quarterly results. So thanks so much for your attention and your support. In a sense, it was a disappointing meeting, but that's a bit of the reality of Biotech. So all the best.
Take care.