Good day, ladies and gentlemen, and thank you for standing by. Welcome to today's conference call by Affimed N.V. and Artiva Biotherapeutics. As a reminder, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. Please note this conference call is being recorded. Now I'd like to hand the call over to your host for today, Alex Fudukidis, Director, Investor Relations at Affimed. Please go ahead.
Thank you, Howard, and thank you all for joining us today to review today's exciting developments, the partnership with Artiva Biotherapeutics, and a brief overview of the updated data from the combination study of AFM13 with cord blood-derived natural killer cells. We issued the two relevant press releases earlier today, both of which can be found on the investor relations section of our website. Please note that the associated presentation is also on the website. On the call today, we have management team from Artiva and Affimed. From Artiva, we have Dr. Fred Aslan, President and Chief Executive Officer, and Dr. Peter Flynn, Chief Operating Officer. From our team, we have Dr. Adi Hoess, our Chief Executive Officer, Dr. Arndt Schottelius, our Chief Scientific Officer, and Ms. Denise Mueller, our Chief Business Officer.
Following today's presentation, there will be a Q&A session with members of both management teams, available to answer your questions. As always, today's presentation contains projections and forward-looking statements regarding future events. These statements represent beliefs and assumptions only as of the date of this call. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. These forward-looking statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the statements that we made today due to various factors, including but not limited to those identified under the section entitled forward-looking statements in the press releases that we issued today.
I'll turn the call over to Adi now. Adi.
Thank you, Alex. Thanks to those who joined us online for this indeed very important update call. By now, I trust that you likely have read the two press releases that we issued this morning. The first one, an update on data from the AFM13-104 clinical trial based on an abstract released this morning for ASH in December by Dr. Nieto in the MD Anderson Cancer Center. As you know, this study is a combination of the innate cell engager AFM13 and cord blood-derived natural killer cells in relapsed and refractory CD30-positive lymphomas. I'm very pleased to share that we continue to see extraordinary results as the study has been progressing. A second press release and the primary focus of today's call was issued shortly after the ASH press release.
It's an important business update announcing a new strategic partnership between Affimed and Artiva Biotherapeutics to now jointly develop, manufacture, and commercialize the combination of Affimed's innate cell engager AFM13 and Artiva's cryopreserved off-the-shelf allogeneic NK cell product candidate AB-101. Details on the terms of the arrangement were provided earlier. Moving to slide four. We're very excited about this partnership, and today, together with our partners at Artiva, we look forward to sharing additional details on the next steps for advancing AFM13 combined with AB-101 in the clinic. As Alex already mentioned, and as you can see on slide number four, I'm joined on this call by two of my colleagues from Affimed, Denise and Arndt, and also representing Artiva's leadership team, I'm joined by Fred and Peter.
Fred now will be speaking about Artiva's NK cell strategy and platform and provide his perspective on today's announcement and what it means for Artiva. Pete will highlight the science behind Artiva's NK cell AB-101 and their manufacturing capabilities. Let me jump back to Affimed and Arndt will then review preclinical data, looking at the combination of AFM13 and AB-101 that forms the basis to move forward with clinical development. Denise will provide details on the terms of the partnership, while I will outline how we plan to move forward before moving to the Q&A. Now let's get started. Looking at slide number five. Through our study with MD Anderson, we continue to generate outstanding clinical results that frankly have transformed patients' lives.
All the patients in this trial have been through many lines of therapy, and for many, their last hope was participating in a clinical trial. As just reported in our press release this morning, the data from the trial combining AFM13 with cord blood-derived natural killer cells continues to be nothing but extraordinary. As a reminder, at this time, we are limited to sharing only data that is contained within the abstract published this morning. As of now, the July cut-off date for the abstract, 11 additional patients were enrolled since our last update in April at AACR. As you may have read, we have maintained a 100% objective response rate in what is now a total of 24 patients treated at the highest dose level, which is 1 × 10^8 cells per kilogram body weight.
The PR rate, it has improved further and is now at 70.8%, coming up from 61.5%. Additionally, there were no dose-limiting toxicities, and the therapy had an excellent tolerability profile and is highly active in patients with heavily pre-treated CD30-positive lymphomas. On Saturday, December 10th, Dr. Nieto will orally present the newest update at ASH, where he will provide additional details on what is contained in the abstract. Before now moving on behalf of everyone at Affimed, I would like to share our sincere gratitude with Drs. Rezvani, Shpall, and Nieto and their team, as well as everyone at MD Anderson who has played a role in this trial for their dedication and commitment to moving this important work forward and to providing patients additional treatment options as they battle this horrible disease.
Of course, a special thank you also goes out to the patients and families of those who have participated in the trial. Now, the picture we are looking at on this slide shows the impact that this treatment regimen had on a patient in the clinical trial, and it is the reason we are here today and why we are excited about the announcement of our partnership with Artiva. While to the left, the patient had multiple lesions spread throughout the body after treatment with AFM13, and in this case no tumor mass could be detected. This is the case now for the majority of patients. Now, results like these that we are seeing in this trial are truly remarkable. In fact, they are what every oncology company strives to achieve.
Based on these results and the importance of ensuring additional treatment options with manageable safety profiles are available for relapsed refractory Hodgkin's lymphoma patients, it is now our responsibility to execute the strategy to bring this treatment forward for patients in a way that considers both the fastest path to market and the greatest probability of success. After considering many options, we've determined that the fastest way to bring the combination to patients was by collaborating with a leading NK cell manufacturer to bring a co-administered therapy forward into a multi-site clinical trial. As Arndt will describe later, this approach is supported by preclinical data, very solid preclinical data that we have generated to date. Specifically, we needed an NK cell product that is off-the-shelf, has manufacturing at large scale to address the clinical development studies and can be used for commercial needs.
With this background in mind, let me talk about the Artiva partnership, how together we plan to achieve this vision. Moving to slide six. As many of you know, Affimed and Artiva have been in a collaboration for two years now, combining their respective products in the generation of a targeted NK cell therapy. Over this time, we have developed an excellent working relationship. Now, with the expanded partnership created to advance the combination therapy of AFM13 and AB-101, we believe we have the right pieces to play to advance this important treatment option as fast as we can into a multicenter clinical study. As such, we already requested a pre-IND meeting with the FDA in early September. Because at Affimed, we believe that every patient deserves more options and every patient deserves another chance.
The collaboration is a natural evolution for the AFM13 plus NK cell program as we move from early-stage development into late-stage development and begin to position the combination for commercial success. Now, with Artiva as our strategic partner on this journey, we believe we have a highly effective off-the-shelf allogeneic NK cell product that, when combined with AFM13, will be available to patients with high unmet need. When we set out to find a strategic partner to help us bring this treatment forward, focusing your attention on to slide seven, we did extensive diligence to confirm we had a partner with the right knowledge, expertise, capacity, and passion to give this therapy the best opportunity for success.
Guiding us throughout this process were our key criteria that we believe were critical to bringing this therapy forward now, including a strong preclinical data set, which includes data supporting the co-administration approach, clear the IND and clinical data of both programs. A cryopreserved off-the-shelf product offering consistent and high CD16 expression. A GMP-grade manufacturing site with the right scale for clinical trials and future commercialization, and with a viable cost structure. With Artiva, they hit all the critical checkpoints. These technical points, along with Artiva's synergistic vision and mission, made them the right partner for Affimed and AFM13. With that, let me turn it over to Fred, who will share his perspectives. Fred?
Thank you, Adi. We at Artiva are very excited to be entering this collaboration with Affimed around our AB-101 and Affimed's AFM13. We have been developing AB-101 as an off-the-shelf allogeneic NK cell therapy exactly because of the broad potential applicability of its ADCC-enhancing activity when combined with monoclonal antibodies or NK cell engagers such as AFM13. If we take a step back and look at the clinical datasets that have generated the most excitement for the NK cell field, I believe the data Affimed has generated with AFM13 plus umbilical cord-derived NK cells in Hodgkin's lymphoma ranks as one of the most compelling. The response rates seen to date are unprecedented in this refractory patient population. The tolerability is consistent with community administration, and if the long-term durability meets all of our expectations, this combination could be a real breakthrough for patients with this disease.
I wanted to spend a couple of minutes providing an overview of Artiva for those on the call that do not know us. Artiva was founded a little over three years ago with the mission to develop off-the-shelf, safe, and effective NK cell therapies. To date, we have raised close to $200 million between our Series A and Series B financings from a stellar group of investors outlined at the bottom of this slide. We are located in San Diego and have approximately 80 employees. What differentiates us from our peers in the NK cell space is that we started with what we call a manufacturing first approach, which means our NK cell technology and platform were built on the back of 10 years of research by our partner, GC Cell, in Korea.
Thanks to their pioneering work and our subsequent improvements, today, we have a highly scalable manufacturing process. Having CMC largely worked out by the time development starts can be hugely advantageous. There are two aspects to our manufacturing first approach. The first is we select umbilical cord units with a high-affinity CD16 variant and a B-KIR haplotype, which potentially gives our NK cells the ability to be more active than NK cells with other phenotypes. The second is we have a massively scalable process, where from a single umbilical cord unit, we can generate potentially thousands of doses of cryopreserved off-the-shelf product with very long shelf lives. Our platform lends itself to two product strategies. The first is to use NK cells as ADCC enhancers. Our first product here is AB-101, a non-genetically modified off-the-shelf NK cell therapy.
We have been in the clinic with AB-101 for over a year now, establishing the safety of the product, and are currently pursuing AB-101 in combination with rituximab in patients with non-Hodgkin's lymphoma. Today, we are announcing our intent to also pursue AB-101 in combination with AFM13 in CD30-positive cancers with Affimed, and we have plans for additional combinations, either on our own or with potential partners. As an illustration of our manufacturing first approach and the scalability and maturity of our process, we can already manufacture AB-101 doses consisting of 1 billion NK cells for $1,300. The second product strategy is around CAR NKs. Here, we genetically enhance our NK cells by adding a CAR for targeting and soluble IL-15 for potential expansion and persistence.
Our first CAR NK is AB-201, an off-the-shelf CAR NK targeting HER2, and we recently announced that our IND for AB-201 was allowed. Coming behind AB-201, we have a number of proprietary CAR NK's for heme malignancies and a collaboration with Merck around CAR NK's for solid tumors. In closing, and before I pass it to Pete Flynn, Artiva's COO, I'm extremely enthusiastic about this collaboration for three reasons. First, there's a substantive unmet need in CD30-positive cancer patients that fail approved therapies. Based on the data we have seen to date, both companies believe AB-101 plus AFM13 has the potential to make a real difference for patients. Second, our ability to gain Affimed's vote of confidence is quite validating for our manufacturing first approach and for AB-101. Third, this collaboration differentiates Artiva in what is a very crowded NK cell field.
In my opinion, as the field matures, we will all be judged by the quality of the therapies we bring to market and the partners we attract in this rapidly evolving field. AB-101 plus AFM13 could potentially lead to one of the first approvals for an Allo NK cell therapy. With that, I'll turn it over to Pete.
Thanks, Fred. Starting with slide 12, I'd like to spend a few minutes introducing Artiva's technology with a focus on AB-101. As Fred mentioned, we are utilizing our platform to develop both specifically targeted CAR NK's and ADCC enhancer NK products.
The ADCC enhancers are universal allogeneic off-the-shelf NK cells for use with ADCC mechanism monoclonal antibody therapies and innate cell engagers such as AFM13. AB-101 is the first example of the ADCC enhancer profile. It is generated via our AlloNK platform to be a highly active NK product with high and consistent expression of tumor-engaging receptors and maintenance of the high-affinity variant of CD16 without the requirement for genetic modification. Moving to slide 13. Our AlloNK manufacturing platform utilizes umbilical cord blood donors. This enables massive expansion of NK cells and consistent batch-to-batch and donor-to-donor drug product generation. We source our cord blood from U.S. banks that have a registered cord blood product under a BLA.
As Fred introduced, we pre-select cords with two attributes, the natural polymorphism for the high-affinity variant of CD16 and the KIR-B haplotype, both of which have the potential to deliver a more active NK cell product. We utilize a proprietary two-step expansion method. The first expansion of NK cells from the cord blood generates a master cell bank. For AB-101, we generate between 80 and 100 units of master cell bank, and we have multiple master cell banks available, providing the flexibility to transition between donors. The second expansion step uses one unit of master cell bank to seed a 50 L bioreactor. Each bioreactor generates approximately 100 vials of AB-101 drug product, where each vial contains 1 billion pure NK cells. These are cryopreserved in an infusion-ready medium, enabling cold chain logistics and outpatient administration.
We have two years shelf life stability completed, and this drug product currently is supporting a multi-dose, multi-cycle, and multi-clinical site study here in the U.S. Because of this established scale of production, we have the potential ability to treat thousands of patients per cord blood, and our cost of goods today is approximately $1,300 for a vial of 1 billion cells. Moving to slide 14. We have established state-of-the-art infrastructure over two sites to support our AlloNK platform. Today, we manufacture our NK cell therapy candidates at our corporate partner, GC Cell's GMP facility in Seoul, South Korea. This is a multi-suite commercial supply cell therapy facility that was completed in 2018. We have now also completed a built-to-purpose multi-suite GMP manufacturing facility at our own corporate headquarters here in San Diego, and this will be certified for GMP use in early 2023.
Both facilities utilize the same 50 L bioreactors, cryopreservation, and fill finish systems and can support multiple internal and partners NK therapy programs here in the U.S. Moving to slide 15. As an example of the utility of the therapeutic potential of AB-101, in the U.S., over 100,000 patients per year are treated with ADCC mechanism therapeutic antibodies. Retrospective studies have shown that both a patient's NK cell levels and CD16 polymorphism affinity can have an impact on outcomes. Therefore, the use of a universal, highly active but non-genetically engineered allogeneic cell, NK cell such as AB-101 could provide therapeutic benefit to patients on monoclonal therapy and potentially in innate cell engager therapies such as AFM13.
In preclinical studies completed internally and that will be presented at upcoming SITC and ASH conferences, we have demonstrated ADCC enhancing activity in combination with a range of antibodies, including Rituxan, GAZYVA, Erbitux, Herceptin, DARZALEX, and SARCLISA. As Arndt will describe shortly, the same is true when combining AB-101 with AFM13. The preclinical in vitro and in vivo datasets combining AB-101 with anti-CD20 antibodies is shown on the right of this slide and led to our first human clinical study that is described on the next slide. Moving to slide 16. This schematic displays the treatment regimen of our current multi-center Rituxan combination trial for the treatment of non-Hodgkin's lymphoma patients. Patients are dosed weekly with either 1 billion or 4 billion AB-101 NK cells for four weeks per cycle, and further can potentially be treated with up to four repeat cycles.
We have cleared the 1 billion monotherapy cell dose enabling Rituxan combination, dose escalation, and most importantly, the potential to combine AB-101 with other products such as AFM13. With that, I will hand over to Arndt to describe the AB-101 AFM13 combination preclinical data.
Thanks, Pete. Okay, moving on to slide 18. I'm excited to share preclinical data showing the highly synergistic antitumor activity of the combination of AFM13 with AB-101 NK cells, which we have generated in collaboration with Artiva as part of our preclinical collaboration. In order to test the antitumor activity of the combination of AFM13 with AB-101, we employed different in vitro cell models and a mouse tumor model. We combined AFM13 and AB-101 cells in two different ways. For pre-complexing, AFM13 was mixed with AB-101 cells, washed, and then cryopreserved. For co-administration, AFM13 was added to thawed AB-101 cells, which had previously been cryopreserved. One of our selection criteria for the best-suited NK cell combination partner for AFM13 was high and consistent expression of CD16. Confirming data generated by Artiva, we detected high and consistent expression of CD16 on AB-101 cells.
When adding AFM13 to thawed AB-101 cells after cryopreservation, we observed that more than 90% of AB-101 cells can be armed with AFM13, demonstrating saturated CD16A receptor occupancy. Moving on to the next slide, 19. When we tested the ability of AFM13 pre-complexed with AB-101 to kill CD30-positive tumor cells, we saw that this combination strongly activated these NK cells and significantly enhanced their degranulation for CD107 expression, enabling them to kill tumor cells. Looking at the left panel when you compare the blue and orange bars. As you can see in the middle panel, pre-complexing with AFM13 also significantly enhanced the cytotoxic activity of AB-101 towards CD30-positive tumor cells. The strong increase in the ability to kill tumor cells was confirmed in several independent experiments, as you can see on the panel on the right. Moving on to slide 20.
Importantly, comparable in vitro results for increase in degranulation and cytotoxicity of AB-101 cells towards CD30-positive tumor cells were also observed when AFM13 was co-administered with AB-101, meaning that AFM13 was added to thawed AB-101 cells after cryopreservation. These data demonstrate that arming AB-101 cells with either pre-complexed or co-administered AFM13 leads to a strong and comparable increase of tumor cell killing of these now targeted NK cells. Moving on to slide 21. We further sought to confirm these convincing data in human xenograft tumor mouse models in NOD immunodeficient mice expressing human IL-15. Mice were irradiated, received IV administration of tumor cells, and then were treated six times with either vehicle control, AB-101 cells alone, or with a combination of AFM13 co-administered intravenously with AB-101.
As you can easily see, treatment of these mice with vehicle control or AB-101 alone led to an aggressive growth of these CD30-positive tumors. See the gray and the blue lines of the graph. Whereas the combination of AFM13 co-administered with AB-101 led to a near complete tumor growth control in mice. See the magenta line. This impressive result becomes also very evident when looking at the actual individual mice of this study on the right-hand panel. The colors represent heavy tumor load for all animals in the vehicle or AB-101-treated mice, the two groups on the left. Whereas mice treated with AFM13 co-administered with AB-101 were almost completely tumor-free. That's the group on the right.
Now overall, based on the preclinical data generated with combining AFM13 with AB-101, as well as previous experience of administering AFM13 with a similar cord blood-derived NK cell product with a positive benefit risk profile in the AFM13-104 study, we're confident that AFM13 administered in combination with AB-101 has the potential to generate a robust ADCC response and clinical activity in patients with relapsed or refractory Hodgkin's lymphoma and CD30-positive peripheral T-cell lymphoma. Now I'll turn it over to Denise to provide an overview of the key terms of our partnership. Denise?
Thank you, Arndt. What was really important to us in this deal is that it really needed to enable us to effectively leverage the financial resources of both parties while allowing us to continue our respective growth strategies in an unencumbered fashion. The structure of this deal actually achieves this objective. We consider it to be an innovative biotech-to-biotech deal because I think you don't often see a deal that contemplates success through to commercialization. With that, I'll touch on some of the key terms you might be interested in slide 23. Just reiterating that the goal of this partnership is to rapidly advance this combination to as many patients as possible. From a regulatory perspective, Affimed will be in the lead of the phase II and confirmatory studies.
For registration, the parties will use the data from the contemplated studies to file their own BLAs. Each party is responsible for securing regulatory approval for their respective products and for use in combination with each other. From a funding perspective, the way to think about this deal is really a co-investment approach. Affimed is covering the phase II study costs, and Artiva is investing by supplying the NK cells and the cost of the IL-2. At the time that we contemplate a confirmatory study, the cost will be shared 50/50. Each party will be responsible for establishing their distribution, securing ex-U.S. pricing, and booking of their own sales. Affimed will be responsible for the promotional strategy, those promotional activities and costs for the combination therapy.
Revenues of the combination therapy will be shared by both companies, where Affimed will be receiving 67% and Artiva 33% of the revenue generated by this combined therapy. I'll turn it over to Adi.
Thanks, very much, Denise, Arndt, Pete, and Fred. Now moving to slide 24, which is our final slide. Indeed, it feels very good for me to have been able to conclude this partnership where two innovative biotech companies have been dedicated their research to activating the innate immune system and our joining forces. Moving to the final slide of our presentation, we want to share with you the timing and next steps for advancing the combination of AFM13 plus NK cells, and then we'll move to the Q&A. In September of this year, we already submitted a request for a pre-IND meeting to the FDA, and the FDA has informed us that we will receive feedback from that request in the first quarter of 2023.
Specifically, we are seeking FDA feedback on a phase II, ideally registration-enabling study design. Thanks to the robust data package we have for AFM13 monotherapy, Artiva has for AB-101 monotherapy, and the preclinical data generated through an earlier collaboration, we're well positioned to begin a clinical trial in 2023. Our goal is to submit an IND in the first half of 2023 to evaluate the combination therapy in relapsed refractory lymphoma. We're eager to hear from FDA on our study design and look forward to quickly initiating a clinical study in this high-need patient population.
I mean, that said, based on the results we have seen in the AFM13-104 trial and the learnings we have taken from the trial, we're quite confident that we have built a very solid case with compelling supportive data that will allow us to gain alignment with the FDA on a path forward for a registration-directed trial so that we can get this therapy to patients in need as fast as we can. In closing, I want to thank everyone at Artiva and Affimed who worked tirelessly to demonstrate the synergy of our two drugs and to make this partnership happen. This closes our presentation today. Thank you to all of you for joining us, and we look forward to taking your questions now. Alex?
Ladies and gentlemen, if you have a question or comment at this time, please press star one one on your telephone keypad. Again, if you have a question or comment at this time, please press star one one on your telephone keypad. Please stand by while we compile the Q&A roster.
Okay. We have the first question from Daina Graybosch at SVB Securities. Daina?
Thank you all. Thanks for the really nice comprehensive presentation. Congratulations on the deal. One multi-part question from me. Can you talk about any potential differences that you know or maybe that you would like to further explore between AB-101 and the MD Anderson cord blood product that's currently being used in the clinical trial? Do you expect any impact of these differences on the clinical results, either efficacy and safety? That's the first question. As I assume you probably won't know for sure till you actually look at this in the clinic, do you anticipate any run-in part of this registration-directed study to look at dose finding or other optimization or things like switching donors versus using the same donor? Thank you.
Thanks, Daina. I'll have this question addressed by different people on the call from our teams. I suggest that Pete starts in order to explain the manufacturing of AB-101 cord blood derived cells, and how he compares that to the MD Anderson product. Pete, can you move ahead? I would suggest that Arndt jumps in in order to then again point to the data that we have generated preclinically. Pete, please.
Yeah. Thanks, Adi, and thanks for the question. Yeah. You know our understanding of the MD Anderson cell is obviously, as with ours, it's a umbilical cord blood-derived product. It's an expanded product, and it's pre-incubated with a cocktail of cytokines to potentially enhance its activity and persistence. Clearly it's a very active cell, as demonstrated both pre-clinically and in combination with AFM13 clinically, as you all know. All I can say is that AB-101 is a
Highly active NK product. We have our own proprietary manufacturing system that I walked through at a very high level. The basis of that manufacturing system is a stimulation of NK cells, in our case, using an engineered feeder cell that displays factors on its surface that drives a highly active and consistently active NK cell product. I think the key differences that we were highlighting were that whereas the MD Anderson cell is a fresh cell and so limits its ability to be used in a multicenter trial, ours is cryopreserved with over two years shelf life stability, and most importantly, we retain all of that activity and activation post-thaw, which is, you know, a tricky thing with NK cells. They're quite sensitive to freeze-thaw.
The preclinical data, Arndt walkthrough, I'll hand over to Arndt to describe, and I think there was a clinical question there as well, but I'll let Adi field that one. Arndt?
Yeah. Thank you, Pete. Just to add, thank you for the question, Daina. Maybe to compare, you know, we have said repeatedly high and consistent expression of CD16 was important to us. We did see that, you know, very high consistent expression with AB-101, which we always also see with the MD Anderson product. Interestingly, we see a higher full receptor occupancy with the AB-101 cell that is seen a little bit lower with the MD Anderson cell. Debatable if that makes a difference, that is a small difference. While we do not have side-by-side comparison, we used, you know, in-house the consistent and comparable models. Again, the data I showed you, I'll start again with consistent high expression CD16, which can be fully saturated, very high synergistic increase in ADCC, so cell killing, pre-complexed with AB-101, as well as with co-administration.
When we compare that in a way historically in these systems, the increase in synergism is quite comparable. Also, when we look in the in vivo models, you know, the models are a little bit different that were used by MD Anderson NSG mice, NRG mice here, but overall, quite comparable, where we see with both products and very convincingly now with the AB-101 product, the combination AFM13 with AB-101 fully abrogated tumor growth, so really flattened that curve. You know, as you've also seen in the mice, the tumors were almost completely gone. Hopefully that answers the question, yeah.
Thank you, Arndt. I will now move on with Andreas in order to give a perspective on the clinical study.
Yeah. Hi, Daina. The question was, if I recall correctly, whether we expect a formal dose escalation before we can go into the recommended or into the dose that we want to use for further development. With FDA, you only know once you have talked to FDA. If we look at the NK cell fields, almost consistently and also in line with what the AB-101 protocol is using, once you have established safety of your individual components or safe dose of your NK cell and the safe dose of your targeting agent, FDA has allowed to combine both at full dose without asking for formal dose escalation. We believe, as we have established doses for both products, we can start right away with effective doses of both products.
We have suggested to FDA or will suggest to FDA a staggered enrollment of the first handful of patients to address any potential safety needs, but we believe that a formal dose escalation study is unlikely to be required.
Thank you. Daina?
Daina, did you have a follow-up question? Are you still there?
The line's been removed, sir.
Oh.
Okay, let's move to the next question, please.
The next question comes from Kripa Devarakonda at Truist Securities. Kripa?
Thank you so much for taking my question, and congratulations on the partnership announcement. Adi, for you, question is, you know, you have Artiva now with the AFM13 combination and Roivant Sciences for AFM24. Just thinking ahead, it looks like combinations with NK cells probably provides the best possible outcome for patients. With additional pipeline assets, do you expect to investigate additional partners, or do you think, you know, for now this is where the focus is going to be? And then maybe for Fred, in addition to Artiva, I know there are other companies that are using cord blood units as sources of NK cells and maybe even T regs now. One question about the NK cells is you talked about the activities maintained post-thaw. Just wondering how these cells maintain activity in the patient.
Is that something that you've already investigated? Is that an important feature of differentiation for these cells? Thank you so much.
Thanks, Kripa. I'll give you a traditional answer on the question, what we are, how we are thinking about these additional innate cell engagers.
We have, y ou could see that we already took AFM24 into a clinical study, which at that time seemed the fastest one to generate clinical data. The study of AFM24 with NK cells is ongoing and we look forward to data updates as the study progresses. As you know, we are in a small dose escalation, as I call it, starting with 160 mg moving to 480. That's what we have achieved. Now we are just finishing off that treatment before we can expand into the different indications. That helps us to establish proof of concept. With the other engagers, we have in principle, as we outlined, the same ideas that we would want to progress with combinations of NK cells.
In terms of focus with every energy to get this deal done now with Artiva and haven't thought much for the other molecules, there is a little more time. The pressure on AFM13 in order to move forward with this great data and the expectations now patients have outside was definitely high. I'm very happy that we could deliver and get a very exciting deal done between two biotech companies. That's as I would say a big achievement that two very solid biotech companies can now move ahead. We will take the next weeks and months to review our additional innate cell engagers and the strategies behind that.
As you know, we have recently filed AFM28 in the EU, and get feedback very soon on that. Maybe we already have an update at our next earnings call. With that, in concluding this year, we'll have time now to provide the strategy for AFM28 as the next molecule. I will hand over to Fred here and give Fred the podium to give you an answer on the question you had.
Thanks, Adi. Your question is related to AB-101 and retention of activity. I'm gonna pass it to Pete to address that.
Hi there. Yeah, sorry. Could you? My line broke up there. Could you repeat the question?
One of you talked about the activity of these NK cells being maintained post-thaw. Wondering what you know about the cells maintaining activity in the patients. Obviously, you're seeing antitumor activity, but you know, how is it sustained? And is this an important feature of differentiation versus different NK cells or NK cells from different
Yeah.
Companies who are using cord blood units?
Yeah. No, yeah, absolutely. I mean, a big part of moving beyond obviously preclinical studies, and this goes for all NK companies, is gaining a robust translational science data set. That's really one, tracking your product within the patient, seeing not only how long it persists, but where does it go. To your point, tracking the activity and the receptology of the cell once it's in the patient. We're actively doing that on our rituximab combination study ongoing, and we plan to present some of that data once we have you know a large and robust data set, obviously, so that we you know that we can do that with confidence. That'll probably be into next year.
We'll obviously also do that in combination with AFM13, and it'll be interesting to see if there's you know any interesting differences between rituximab and AFM13. We don't anticipate that to be the case. Yeah, we're actively doing that and you know more to come.
Okay, great. Thank you so much.
I see that Daina is back. Daina, did you have a follow-up question? All right. I guess we'll move-
FDA. Thanks for the answer that FDA, you know, you think you won't need to dose escalate. My question was more, what do you want to do in terms of optimization because you have a different product? Like, could a different dose be optimal? Or could you wanna, you know, explore switching donors or keeping the same donors? Or may this product want to add IL-2, for instance? I wonder how you're thinking about for yourself, the optimization of the therapy.
Yeah, that's a question again for Andreas and then Pete, because switching product is something that Artiva is if they can comment. Andreas?
I can speak for the AFM13 part, and here we will use the established dose of 200 mg flat, which has a very well-established safety profile and has shown activity both in PTCL, in Hodgkin's and non-Hodgkin's. Most importantly, at this dose, we also have seen this striking activity in combination with NK cells in the 104 study. Now I'll probably hand over to Pete to address the questions about the NK cell doses.
Yeah, no, absolutely. I mean, I think the key question here, and this is really what is frankly intriguing about our manufacturing platform, is the ability to generate thousands of doses of product from any given cord blood, but then not being limited to an individual donor. In our case, AB-101, because of the release specs defined with the agency, is always AB-101, irrespective of the cord blood donor that we put into the system. We have multiple master cell banks, as I mentioned, laid down from different donors, and each of those master cell banks can generate thousands of 1 billion cell doses. That gives us a lot of flexibility as far as dosing with a single donor, potentially switching between donors intra-patient, potentially to overcome immunogenicity questions.
Most importantly, what we see now is absolute consistency from donor to donor in the final drug product. We know that the quality of the product is always the same, then you're just talking about, you know, switching for potential HLA advantages. I'll leave that there.
Okay. Can we move on to Maury Raycroft from Jefferies? Maury, are you there?
Thanks for taking my questions. For the AB-101 plus rituximab combo study, it describes a dosing schedule that includes use of IL-2 in combo with the therapeutic dose and weekly dosing of cells. I guess is IL-2 necessary for the AFM13 combo, and can you clarify that the AB-101 cell dose is expected to be 1 billion cells per dose? Is there anything else about dosing schedule specifics you can comment on as you head into the registrational study discussions?
Yes, I'll hand this to Pete and Wolfgang can also step in.
Yeah, Pete, you know, maybe I'll start just with where we are with the AB-101 study, and then I'll pass it to you to comment on the IL-2. You know, talking about the dose of AB-101, because AB-101 is a non-genetically engineered product, dose escalation is more streamlined. In our initial cohort, we dose patients at 1 billion cells per dose times four weekly doses, as you mentioned, right? That means 4 billion cells in a cycle. We cleared that initial monotherapy cohort and started dosing in combination with rituximab. We continue to investigate different doses of Cyflu and anticipate to be testing shortly 4 billion cells per dose times four weekly doses in monotherapy, which would mean 16 billion cells per cycle.
We are trying to add as much flexibility as possible in the near- term for the clinical decisions that we will be making. Maybe I'll pass it to Pete to discuss IL-2.
Yeah. Yeah, absolutely. Cytokine support of NK cells has been seen with multiple NK products that, whether it's IL-2 or IL-15 as examples, can support persistence of those products. In our current Rituxan study, as you mentioned, we're using IL-2. The intention today is to use IL-2 in combination with AFM13 as well. I will say that in the background, we're investigating the use of IL-2 or the use of other cytokines as well as part of our underlying Artiva platform. But today to get into the clinic with AFM13, we will be using IL-2. Wolfgang, would you like to have a regulatory question?
Yeah. Hi, Maury, this is Wolfgang. As Andreas mentioned at the beginning, right, the first handful of patients will approach a staggered approach for safety to investigate that. Of course, we have developed a concept and a proposal for the FDA, where we build on the experience from Artiva regarding the dosing regimen for the NK cells. We will investigate two different dose levels, and now we need to wait for the FDA feedback on the regimen to provide more information on that.
Got it. Makes sense. One other question just around rationale for an exploratory arm in the next study to evaluate the combo in PTCL. I guess, how does this factor into your plans regarding AFM13 monotherapy in PTCL, and is there a status update on the monotherapy PTCL readout expected by the end of this year?
I'll take this question. In terms of updates, as we have communicated, we plan to release the data at around ASH, not at ASH. The data has not been in the company in order to submit an abstract. We'll have the opportunity to disclose top-line data. Based on the top-line data, we can also then communicate the strategy forward for AFM13 in PTCL. Our next steps is plan to meet up with FDA and then discuss data and, depending on the feedback from FDA, we can then disclose the next steps for AFM13 monotherapy. The strategy hasn't changed for AFM13 monotherapy. No.
With the NK cell, we have already a small number of patients that we can treat in the MD Anderson study. We're gonna see first data in PTCL already, if efficacy is comparable to Hodgkin lymphoma. Depending on the data set, we can include such an exploratory arm, or we can just go straight and also set up a registration-directed study in PTCL as we're planning to do with Hodgkin lymphoma. That's an optionality we're building in. What we're believing is that AFM13 plus an NK cell, again, can enhance the efficacy and may then represent the opportunity to think much bigger for AFM13, i.e., to bring in frontline.
With such data, this discussion is already ongoing, and ultimately, where are the best options not just to remain in the last line setting, we have outlined a number of patients there. We think that between Hodgkin's and PTCL, we may be able to address them, let's say 3,000-4,000 patients in the U.S. If we can move to earlier lines or PTCL to front line, that can easily be double. We're now speaking of 5,000-7,000 patients just in the U.S. Then obviously we have the opportunity to approach B-cell lymphoma. We're in the meantime seeing that this is also a strategy for Adcetris. There seems to be a good rationale also to treat a population that is CD30 positive.
Our numbers show that this could be a quarter of overall BCL patients or diffuse large B-cell lymphoma patients. This is what we have in mind. As I said, the monotherapy is important because it can give us the fastest path to market and then build up the forces. Important is that we now have a drug combination behind that can really be built in order to establish us fully in this market. As I said, there is an opportunity of creating a value that's similar to what's considered for CART.
If we are coming with similar value appreciations, we can have a high-end product that even with fairly, let's say small number of patients can create a very large blockbuster market opportunity. This is how we're seeing AFM13 and the strategy remains go first with PTCL and then follow through in all other indications with the combination.
Got it. That makes sense. Thank you.
Thank you, Maury. We have time for a couple more questions, quick ones. Li, the next question comes from Li Watsek at Cantor. Li?
Hi, can you hear me?
Yes, we can hear you.
Yes.
Awesome. Thank you. This is Rosemary on behalf of Li. First of all, congratulations. Thank you for taking my question. Just two quick ones. You've spoken about plans to gain approval from the FDA for AB-101 AFM13. In terms of tacticality, can you speak to the actual, like, regulatory experience that you and Artiva have with off-the-shelf cryopreserved NK cells, and how confident you are that you can satisfy the regulatory requirement? My second question is regarding your ASH update. Among the 24 patients that you've treated, can you tell us how many have received four cycles, three cycles, etc.?
With the increased complete response rate, could you tell us if that was driven by a deepening response from the original set of patients or if it's from the 11 additional? Thank you.
Yeah, thanks for the question. I'll hand over the first question to Artiva before Andreas then can give you the insight into what we can release at the moment as data and what will be released at the presentation itself. Fred, you go first on regulatory.
Yeah. Pete, do you want to make any remarks on our interactions with FDA? I'm not sure that there's, you know, we can share what our experience has been to get the product into the clinic and then into combination with Rituximab, but go ahead.
Obviously AB-101 has been in the clinic, as Fred said, for over a year now. That's so there's an IND on file. That obviously forms the basis of the ability to reference that as we in the future are looking to combine with AFM13. Combining the two IND, so to speak, in a reference format. Further, we recently announced the IND allowance of a more complex product, AB-201, which is our HER2 CAR NK. Again, full FDA review obviously of the IND including the manufacturing, the off-the-shelf nature, the cryopreservation nature of our products, and again, passed the IND allowance.
Andreas, on the clinical data.
Yeah. I mean, as Adi said in his introductory remarks, we cannot go into more detail at this point as what is provided in the abstract. What you see in the abstract is that at the cutoff date in July, there were three patients each who had three and four cycles respectively. Now, of course, as time progresses, there will be more patients with these additional cycles. At the final presentation you will see increased numbers of patients with three and four cycles as well as a longer follow-up against the cutoff date of the abstract was July. There are four more months of maturing data and additional patients receiving prolonged treatment. We cannot give more details on that, not to jeopardize his presentation at ASH.
Thank you.
Uh.
Quick follow-up for
Um.
If there's-
We're running out of time for a follow-up. You know, we have many people on the queue still wanting to ask questions.
Okay.
We hope to cover those in some of the one-on-one conversations that are coming up. For the rest of the people in the queue that want to ask questions, please feel free to reach out to me either via email or telephone number, and we'll see what we can schedule. With that, Adi, did you have any final remarks for the team?
Yes. You see our focus, it's the patient. We see this remarkable data, and obviously hearing that many patients want to get onto the study in order to receive this treatment. It's not only highly effective, but there is also a very good safety profile. Today you saw our commitment we're having in order to move forward and indeed exceptionally happy to now be able to work with Artiva. As you learned, that has established a very active cell and a very high-end manufacturing process. As Fred has said, it's rewarding for each side to work together in order to then bring this forward to patients. We're very excited now to hear the feedback from FDA.
We've been already submitting the briefing book to them, but as I said, due to some constraints in FDA, the feedback may last until Q1 before we hear from them, Q1 2023, probably in the earlier timeframe. That's the situation at the moment. With this, I want to conclude. I hope that you can share this optimism with us to really bring together two very exciting programs that in combination could change the life that absolutely in need. Thank you very much.
Thank you everyone. Speak soon.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.