Affimed N.V. (NASDAQ:AFMD) Q4 2021 Earnings Conference Call March 31, 2022 8:30 AM ET
Company Participants
Adi Hoess – Chief Executive Officer
Angus Smith – Chief Financial Officer
Alex Fudukidis – Head of Investor Relations
Andreas Harstrick – Chief Medical Officer
Arndt Schottelius – Chief Scientific Officer
Denise Miller – Chief Business Officer
Conference Call Participants
Daina Graybosch – SVB Leerink
Kripa Devarakonda – Truist Securities
Maury Raycroft – Jefferies
Brad Kimmino – Stifel
Li Watsek – Cantor Fitzgerald
Yale Jen – Laidlaw & Co.
Zhiqiang Shu – Berenberg
Do Kim – Piper Sandler
Operator
Good day and thank you for standing by. Welcome to the Affimed 2021 Financial Results and Corporate Update Conference call. At this time, all participant lines are in listen-only mode. After the speaker’s presentation, there will be a question-and-answer session. [Operator Instructions]. I’d now like to hand the conference over to Alex Fudukidis, Head of Investor Relations. Please go ahead.
Alex Fudukidis
Thank you, Liz. And thank you all for joining us for our call today. Before we begin, I would like to remind everyone that we issued the relevant press release earlier today, which can be found on the Investor Relations section of our website. On the call today, we have the following members of our management team. Adi Hearse, our Chief Executives Officer, Andreas Harstrick, our Chief Medical Officer, Arndt Schottelius, Our Chief Scientific Officer. Wolfgang Fischer, our Chief Operating Officer, Denise Miller, our Chief Business Officer, and Angus Smith, our Chief Financial Officer. The team will be available for the Q&A after the prepared remarks. Before we start, I would like to remind you that today’s presentation contains projections and forward-looking statements regarding future events.
These statements represent our 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 subjects — subject to risks and uncertainties and actual results may differ materially from those expressed or implied in these statements due to various factors, including but not limited to those identified under the section entitled Risk Factors in our filings with the SEC, and those identified under the section entitled forward-looking statements. And the press release that we issued today and filed with the SEC. With that, I’ll turn the call over to Adi. Adi?
Adi Hoess
Thank you, Alex. Good day, everyone. And thank you for joining us for our full-year 2021 financial results and operational progress update call. I would like to start the call today by taking a moment to thank all of our employees, collaborated in patience, for their dedication, passion, and commitment to our work, and the strong execution in 2021, which again was a very challenging year given the ongoing pandemic. We could have not accomplished all of that without everyone’s dedication, passion, and the belief in our work. Affimed employees and ever-growing multinational team, are talented individuals from around the world, in particular from all places in Europe. Indeed the events that have recently unfolded in the Ukraine are of particular concern to me,all our colleagues at estimate. I must say I’m very proud of the way that our colleagues have pulled together in support of Ukraine in whatever ways we can. We have a few employees in our organization and then you realize how much you have to stand behind the Ukraine.
And we will continue to do that — whatever we can do in order to support its people, including our indeed ukrainian colleagues and those we have laughed once and family in that country. With that, I want to turn over to give you an update on the progress that’s not just being given by me, but all my colleagues will contribute. 2021 was a year of many transformative achievement for us in the company. A year-end, in which we laid the groundwork for what we help to accomplish in 2022 and beyond, and for creating a number of important catalyst for our company. We have been making exceptional progress in all our programs and in particular, with work that we’re conducting when we combine our Innate engagers with nitric killer cell.
By the end of 2022, we expect to have three Innate engagers in the genic, which we believe will be the basis for continuous data flow over the next several quarters. As shown on Slide 3 of our presentation, development efforts with each of our innate cell engager day job is focused on patients where we see significant unmet medical need that may allow for fast-to-market development approach. We have built a very strong rationale for the development of all our innate cell engager molecules as mono-therapy and in combinations. We are very pleased to have clinical proof-of-concept data for AFM13, which provides key value addition for our approach to developing our molecules as monotherapy in combination with natural killer cells and checkpoint inhibitor. This proof of concept support the three pronged approach that we’re applying to development strategy for all our other Inter-Tel engage [Indiscernible]. We believe that by giving patient novel treatment options, we have an opportunity to potentially develop blockbuster therapies. As an example, AFM13 now is shown on Slide 4, targeting several three to 30 positive lymphoma way be able to address several patient population, starting initially with relapsed and refractory peripheral T-cell.
The development approach in T-cell lymphoma will be able to impact the life of approximately 1500 patients just in Europe. Earlier this year, we announced the completion of enrollment in our redirect study, which focuses on peripheral T-cell lymphoma. And we are on track to report topline data from this study in the second half of 2022. This indication however, represent only a small fraction of the entire CD30 opportunity, which includes patients with Hodgkin T-cell and B-cell lymphoma. And according to our analysis, these indication has an annual incidence of approximately 20 thousand patients in the U.S. alone. Now in December of last year, we presented compelling data of AFM13 in combination with [Indiscernible] killer cell. As you may recall, a unique feature of our index selling data is very high affinity and the specificity to CD 16A allowing the pre complex Ng of network killer cells with AFM13, which now form sustainable car like in pay complex.
In addition, we are further dosing with AFM13 mono-therapy. A unique option for our index selling richer and differentiated from what you can do with current K-cells. We believe that the AFM13 infusions are retargeting donor-derived and patient found in k Zales and potentially macrophages thereby contributing to the efficacy. In that trial, we reported on unprecedented 100% objective response rate after just a single 5G of treatment, for 13 patients treated at the recommended Phase two dose. Now based on this impressive data, we — we believe that you can address the unmet need in additional indications that I mentioned earlier through the same development approach of combining AFM13 with nitric killer. Now our initial target population is relapsed refractory peripheral T-cell lymphoma and Hodgkin lymphoma, which now comprises 3,500 patients just in the US. But we have the plan to expand the label to include frontline peripheral T-cell lymphoma and relapsed refractory B-cell lymphoma.
In the second grade, which now creates an opportunity to address about 7.5 thousand patients in total in the US. Importantly, our initial market research also indicates that we may have an opportunity to price the AFM13 and k Zelle combination therapy at a premium to CAR T therapies as the safety of our combination has a profile that eliminates the ancillary costs associated with the management of safety events with Carty approaches. In additional our ambition for AFM 13 is to make it globally available to patients who need these treatment either as monotherapy or in combination with natural killer. The combination of all of these factors now gives us confident in a very significant market opportunity for AFM13. Now let me switch to eight from 24 our each year far expressing targeting in a selling basis, where we have embarked on a broad development strategy. The opportunity for AFM–the market opportunity for AFM24 is shown on slide 5 of net presentation. End of last year, we achieved a key milestone for eight from 24 through the identification off the recommended Phase two dose of 480 milligram flat dose weekly.
And Tier 2, we are implementing our three pronged development strategy, which includes the initiation of three studies investigating various each year far expressing solid tumor indications. Now, in a total of line core. Remember what I said earlier that we already have clearly improved of concept play from 13 as monotherapy. And in all these combinations, now let’s have a look at the market opportunity. Non-small cell lung cancer is represented in all three studies. Colorectal cancer is represented in two out of the three studies. Enter a further targeting other key EGFR expressing tumor types, such as renal cell carcinoma, head and neck, and gastric. Now rectal colon cancer and colorectal cancer are by far the largest ETF are expressing indications with a combined relapsed refractory patient population in the U.S. over 130,000 patients. So this number clearly tells you that these are in high need of noble therapies that are differentiated.
Here again, there is a significant opportunity as these patients need drugs with better response rates and the duration of response over existing therapies that, as we have already outlined, have clear limitations not just on the efficiency side but also on the same scope. Let me switch shortly to over AFM28, yet a pre-clinical drug. But we will spend some time explaining you the background of AFM28 and why this becomes very important for us summit. So AFM28, our CDN123 tumor expressing targeting innate cell nature, we’re initially planning to target patients with relapsed and refractory acute myeloid leukemia, short AML. AML is the most common form of leukemic with over 40,000 patients diagnosed in the seven major markets every year and over 11,000 in the relapsed refractory setting in the U.S. alone.
So Ethan 28 is currently prepared for clinical evaluation. And as Arndt will explain later, we believe that AFM28 is ideally suited to address the needs of AML patients. And we’re planning to submit an IND application during the second quarter of this year following a pre R and D meeting with FDA, we expect to initiate the first in human study in the second half of 2022, we have been and are continuing to work with MD Anderson, our CIVA, and k. Chen and other third-parties to ensure access to an off-the-shelf crowd preserves [Indiscernible] killer cell for further development with our Innate Cell Engagers therapy. We expect to provide additional updates on NK Zall Development during the second half of this. Our progress data and the opportunity represented by [Indiscernible] Asia programs has also captured the attention of potential future partners. In particular, our data that we published in December. There was a very good momentum around our ability to clinically execute our programs supported by strong data.
And there is interest from the pharmaceutical industry to further explore how our Rupp platform and [Indiscernible] our molecules, can add value to these parties existing pipeline and oncology franchise. We’re also continuing to advance our work with our existing cards. Us a key feature that has an ABL. These partnerships is the differentiated performance of our index selling Asia when compared to standard IGE based format with a particular advantage in addressing tumors, Ulz with low target expression and also with a unique feature that we have shown for the combination of opportunities in the case of Genentech. We have made progress in various preclinical programs and have begun to hand over molecules to genetic for further development.
Our partnership with ROI event on AFM32 is strong and AFM32 has moved into R and D, enabling study Detailed updates on these programs are or is at the discretion of our part. What remain eligible for additional proceeds from these key collaborations in the near-term. Including being eligible for pre-clinical milestones, as well as milestones based on early regulatory achievement and also clinically progress. Finally, well to strengthening our organization and to advanced our [Indiscernible] and our recruiting highly talented scientists and industry expert to help us execute our vision. Now with this, I will turn over the call to Andreas to give you more color on the progress of our programs. Andreas?
Andreas Harstrick
Thank you, Adi. And also from my side, warm welcome to our audience. This my pleasure to review with us the progress of our clinical programs that we have achieved in 2021. Let me start by highlighting our progress for, I guess rooms. 13, which you can see on slide six, as you know, we have two ongoing studies was AFM13, including your registration directed study for AFM13 has monotherapy in relapsed and refractory PTCL patients. Also known as see redirect study. And in addition, our Phase 1-2 study in collaboration with MD Anderson, where we evaluating cord blood-derived Natural Killer cells pre complex with AFM13 and followed by a single AFM13 in Patients with relapsed and refractory CD [Indiscernible] positive for lymphomas.
As we mentioned, we are very proud that we have completed enrollment into the redirect study in registration relevant PTCL cohorts in January, we believe that this is an important milestone in the light of a very challenging environment that we have been facing over the last two years. A total of 108 patients with relapsed or refractory T-cell lymphoma has been treated or are being treated with AFM certain in this trial. And we expect top line data for the second half of 2022. The focus of this initial data will be the overall response rate as success by a blinded independent review committee and also a preliminary assessment of duration of responses. Of course, taking into account that the maturity of the duration of response data will depend on the actual duration of these responses. You may remember that we recently announced that we decided to terminate enrollment into Cohort C in this study.
This Cohort C was an observational cohort for patients who was transformed because of [Indiscernible] and since COVID is still impacting the treatment and the response assessment of these patients, why this decision was taken. I think it’s important to remember that this cohort see was [Indiscernible] from just patients, was observational only and not part of the intended registration package, therefore not impacting our ability to submit. See cohorts in peripheral T-cell lymphoma. Let’s now turn to our second active study with AFM13. Study AFM13-104 where we are evaluating the efficacy and tolerability of cord blood derived natural killer cells. Pre complex with AFM13 and followed by AFM 13 mono-therapy in patients with relapsed and refractory CD30 positive lymphomas. In December, we reported interim data showing a response rate for the first 19 patients enrolled in the study.
This included the response rate after two cycles for the first six patients that were treated at the lower dose levels of one times ten to the six, and one times ten to the seven cells respectively. And the response rate after only the first cycle for the thirteen patients treated at the recommended Phase II dose of one times ten to the eight cells. At that time, we had demonstrated an impressive anti-tumor activity with 100% objective response rate and a 38% complete response rate for patients treated at recommended Phase 2 dose after only one cyclo therapy. We are very excited that the abstract submitted to AACR by MD Anderson Cancer Center and [Indiscernible] for study AFM13-104 has been accepted at a very prominent place for oral presentation and the clinical trials plenary session. This session will be hosted from 1:00 PM to 3:00 PM on Sunday, April 10th In addition to MD Anderson, presentation will also be featured at the AACR press conference on Sunday, April 10th.
It’s this AACR presentation, jago and yet Joe from MD Anderson due principally investigator of the trial, will provide updates on the first 19 patients enrolled in the study. Of Note, the update will include the response rates, overall response right? And complete response rate for those 13 patients treated at the recommended Phase II dose. Now, after two cycles of therapy, and was also show additional follow-up data as compared to the data presented in December. As you know, we have seen some evidence. Also deepening of responses at the lower dose cohorts between cycles one and cycles two. And therefore, the final response right after two cycles of therapy four patients at the recommended Phase II dose will allow a very good assessment of Citigroup potency offices treatment.
Also, FDA has approved an amendment for us is study, which allows us to increase the patient population treated at the recommended Phase II dose to cert up to 40 patients with CD30-positive lymphomas and allows us for the treatment of patients was more than two cycles of therapy. As investigators discretion. Let’s turn now to AFM24 on Slide 7. During 2021, we identified 480 milligrams of AFM24, once weekly. It’s a recommended Phase II dose, follow monotherapy. With this key milestone behind us, we have now initiated enrollment into the expansion phase of the monotherapy AFM24 trial. It’s a recommended Phase II dose. The expansion cohorts include patients with renal cell carcinoma, non-small cell lung cancer EGFR mutant and colorectal cancer. In parallel, we have continued the dose-escalation to collect additional safety information and have completed enrollment in cohorts seven treating patients at 720 milligrams.
We will present data from the dose-escalation phase of AFM24, one on one trial at AACR Annual Meeting, mainly focusing on pharmacokinetic and pharmacodynamic data and highlighting irrational and the foundation for the RP2D [Indiscernible]. The poster will be presented during the Phase 1 clinical trial session on Monday, April 11th. As a reminder, on our Q3 earnings call we gave an update on the key pharmacokinetic pharmacodynamic inputs that informed our decision to select 480 milligrams at a recommended Phase 2 dose. And we provided the status of clinic and response assessment for patients through Cohort 6. The AACR presentation will include more granular analyses of these data points. And as a cutoff date of October 29 for the AACR presentation, there were 29 patients dosed with AFM24. More recently, we have also initiated two combination studies.
The first study, AFM24-102 is investigating the combination of AFM24 with Roche’s PD-L1 inhibitors atezolizumab. To treat patients with non-small cell lung cancer. [Indiscernible] whites type, gastric and gastroesophageal junction adenocarcinomas and pancreatic hepa to biliary. And biliary tract cancers. The second study, AFM24-103, is investigating the combination of AFM24 with SNK01. ex – vivo expanded and activated auto logos and case cell product from NK Gen biotech. Here we’re treating patients with non-small cell lung cancer, squamous cell carcinoma of the head and neck, and colorectal cancer. Through the three ongoing studies we will be evaluating safety and efficacy of AFM24 in nine indication-specific cohorts with a particular focus on non-small cell lung cancer, which was represented in all three studies and colorectal cancer represented in two of the three studies.
As announced earlier, we expect to have more to report initial data from each of these studies during the second half of 2022. With this overview of our clinical program. Now let’s turn to our new candidate, AFM28. And I’m happy to hand over to Arndt who will give you an overview, obviously rational, and our plans for this program. Arndt, please.
Arndt Schottelius
Thank you, Andreas. And good morning and good day to everyone on the call. So for me, today is Adi rate introduced? I would like to discuss with you the story behind AFM28. Let’s start with the high nets medical need in AML as shown on Slide eight. First available treatments that are effective in a and L, often toxic and tolerated only buy a fractional patients. Second, efficacy of currently available treatments is still limited and either primary incomplete responses or early relapses usually within the first 18 months are common. And third, once refractory or relapsed, the outlook this low with only three of 10 patients will last up to one year and only one out of 10 patients after five years because of a lack of effective treatments for relapsed or refractory disease. What is urgently needed are treatments that work in most patients are effective and safe prevent or delay relapsed, and work in relapsed or refractory disease with AFM28 and it’s NK cell based mode of action.
We believe we can address these needs, can provide more context. I would like to give you a brief overview of the current treatment options and explain why we strongly believe in the potential of AES in 28. Approved treatments for adult patients with newly diagnosed AML. Chemotherapy, mostly sort era main daunorubicin with or without Mylotarg [Indiscernible]. Was it good myosan, the NTC 33 antibody drug conjugate, and the only approved anybody. For three inhibitors, IDH1 and IDH2 inhibitors, we need to KLX plus hypomethylating agents, a society in the Caribbean or an ASR KLX plus low-dose cytarabine. The choice of treatment depends on where they’re patients can tolerate intensive remission induction therapy on cytogenetic risk. And the presence of targetable mutations.
However, even though these treatments can be initially effective and reduce remissions, the majority of patients with failed to achieve a long lasting complete remission or will relapse early. About 60% of patients will show progressive disease within a year. Sick patients may be candidates for allogeneic hematopoietic stem cell transplantation which is still considered the already curative option for patients with AML. Options available to patients who are not eligible for allogeneic transplant or relapse after transplants are limited. Treatment options available to these patients include further chemotherapy, aggressive or less aggressive, depending on patient status and use of hypomethylating agent or targeted agents like MYLOTARG, that three inhibitors, IDH, IDH2 inhibitors, indeed, treatments in the context of a clinical trials recommended.
A multitude of therapeutic options have been our investigated clinically and relapsed refractory patients, including targeted agents. ADCs, monoclonal antibodies, and T-cell based therapy is how ever so far, none have provided convincing evidence for broad effective this and durable responses in relapse and refractory disease over the past years, it has become clear that conventional therapeutic approaches, for example, monoclonal antibodies directed against different targets, like CD33 or CD123, or even effector function enhanced antibodies have not resulted. in meaningful therapeutic efficacy in AML patients despite the use of targets that play a role in AML disease biology. Also, T-cell Engagers and CAR Ts irrespective of target choice, such as CD33, CD123 or CLL1r CEO cetera, have not achieved acceptable tumor response rate and durability.
Over the picture looks different, a little different when clinical data of ADCs are analyzed, it’s not efficacy that’s lacking, the issue is the challenging toxicity. This context, we view Mylotarg, the CD33 targeting ADC, as a molecule that in principle is effective in AML that is therapeutic use is limited by the fact that this molecule is not employing the promising effector function of antae cells, which by themselves have shown clinical efficacy in AML. There’s further clinical data from other ADCs targeted against CD-33 that have shown higher efficacy, but are limited due to their toxicity. In addition to Mylotarg, CD123 directed ADC, GEN 632 is currently in clinical studies.
When we looked at all the available research literature, we concluded that CD33 and CD123 directed approaches show efficacy in AML, however, it could be an advantage to use a novel effector function. This is where the NK cells come in. As a highly promising approach. As recent clinical data of the use of donor-derived cord plant or peripheral NK cells to treat [Indiscernible] have demonstrated encouraging activity. The next analyzed, which of the above approaches monoclonals, T-cell engagers, CAR T-cells, ADCs, or Innate Cell Engagers, can best address the needs to increase the Bazel efficacy of NK cells. Except for monoclonals none has the option to activate NK cells. And even monoclonals have huge limitations and they’re ability to redirect NK cells as such, it became obvious to us that this is this is an ideal set up to generate and an eight cell engage of, based on our Rock Cut form.
Let me explain in more detail why we feel that our Nate selling gauge can be broadly effective and AML, and why we see particular potential in its combination with adoptive NK cell therapy. First naked and K-cells have been used in the treatment of AML in different settings in the past and have shown promising efficacy. And approximately 30-40 with about approximately 30% to 40% overall response rates. Second, Ethernets, Innate Cell Engagers, or highly differentiated bi-specific antibodies designed to specifically bind the NK cells with high affinity. Third, we’ve recently shown that the combination of an ICE AFM13 with NK cells produces impressive overall response and CR rates and very difficult to treat patients. And fourth, with selected CD123 as the target for AFM28 as it is not only expressed on the blast of AML patients, but importantly, it is also expressed on the leukemic stem cells, which are the constant source of malignant cells in AML.
To induce deeper and longer lasting remissions. Re-eradication of these leukemic stem cells is crucial. This is in contrast to, for example, CD33 targeting antibodies or antibody direct chronic goods which lack the ability to also target leukemic stem cells and have also exhibited toxicities. The AFM28 ICE is designed through elicit, deeper and longer lasting responses by depleting leukemic stem cells, as well as AML glass. AFM28 has significant improvements versus normal or Fc enhanced antibody and its ability to effectively recruit and NK cells to kill tumor cells. And I will — And I will explain these differentiating factors. We believe in ICEA offer advantages in targeting CD123 has this target is only moderately expressed and we believe high affinity and specificity targeting of CD16A is an essential factor nd redirecting NK cells to kill cancer cells. As you can see on Slide 9, we highlighted our preclinical work, which we recently shared at ash, shows that AFM 28 activates and K-cells more potently than an Fc enhanced anti – CD123 antibody [Indiscernible], resulting in increased efficacy.
More over when compared to this Fc -enhanced anti-CD123 antibody, based on 28 was also more active against primary A&L [Indiscernible] from patient peripheral blood and bone marrow, and also more active against cells with low CD133 expression. As a result, we expect that AFM 28 will be less affected by baseline characteristics and differences and CD123 expression and has the potential to induce deep responses, including high efficacy against AML cells book low levels of CD123 expression. This could be a strong differentiator from 28 vis -a – vis on-target competitor antibody drug conjugates in the space IMG and 632, which appears to be effected by differences in CD123 expression.
Based on prior testing of Talacotuzumab in Fc-enhanced Andy CD-3 123 IgG1 in a Phase one clinical trial and all patients in complete remission with measurable minimal residual disease and our pre -clinical data suggesting superiority of AFM28 over Talacotuzumab. It would not be unreasonable to expect single agent activity of AFM 28, in particular in patients with low volume disease, such as MRD positive AML. Conversion of patients to MRD negativity is we expect it to be clinically meaningful based on the prognostics significance of MRD status on PFS, hence overall survival. Our pre -clinical studies with AFM28 have also demonstrated low-risk of cytokine release syndrome, which further differentiates the strong truck conjugates from CD123, CD3 bispecific T-cell recruiting antibodies currently in development for AML, which all exhibit varying degrees of cytokine release syndrome including CRs related death.
We’re particularly excited about the potential of AFM28 in combination with adoptive NK cell therapies, which as I’ve mentioned, have demonstrated some promising clinical activity in relapsed refractory AML as single agents already. By combining AFM28 with adoptive NK cell therapy, meaning by redirecting on generic NK cell to CD123 tumor cells. We believe AFM28 increase the depth and duration of response necessary to meaningful, improve outcomes. We plan to initiate combination development at the earliest possible time point. And as soon as adequate information about safety and tolerability of single agent AFM28 is available from the first in-human dose escalation trial. The optimal strategy and to initiate combination development will need to be discussed with regulatory authority is when we plan to provide additional details at a later point in time. With that, I’ll hand the call over to Angus to take you through the financials. Happy to take any questions during Q and a. Angus.
Angus Smith
Thank you, Arndt. Balance sheet and income statement highlights are on Slide 10 and 11 of our presentation. First, I’d highlight that AffiMed’s consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standards Board or IASB. The consolidated financial statements are presented in euros, which is the company’s functional and presentation currency. Therefore, all financial numbers that I will present on this call, unless otherwise noted, will be in Euros. We ended 2021 with cash and cash equivalents of €197.6 million compared to a €146.9 million on December 31, 2020. Based on our current operating plans and assumptions, we anticipate that our cash and cash equivalents will support operations into the second half of 2023, net cash used in operating activities for the year ended December 31st 2021 was €86.6 million compared to €19.4 million in 2020, when comparing 2021 to 2020, it’s worth noting that 2020 cash flow from operations was enhanced by the upfront proceeds received from our collaboration with Roivant, as well as a milestone payment received pursuant to our collaboration with Genentech.
Total revenue for the year ended December 31st 2021 was €40.4 million compared with €28.4 million for the year ended December 31st 2020 revenue for 2021, 2020 predominately relate to Genentech and ROI math collaborations. Collaboration revenue for the year ended December 31, 2021 amounted to €39.3 million with €21.6 million coming from the Genentech collaboration and €17.7 million coming from the ROI event collaboration. Collaboration revenue for the year ended December 312020 amount of €27.8 million was €26.2 million coming from the Genentech collaboration, and €1.4 million coming from the RoyMac collaboration. R&D expenses for 2021 increased 63% from €50 million in 2020 to €81.5 million in 2021 and this was primarily due to increased expenses for AFM24 and AFM2 — including costs for the production of clinical trial material, as well as an increase in costs associated with other early stage programs and infrastructure and an increase in share-based payment expenses.
R&D expenses for the fourth quarter of 2021 also include an accrual for a milestone payment owed to MD Anderson for the initiation of the Phase two portion of the trial investigating AFM13 pre-complexed with cord blood-derived natural killer cells. General and administrative expenses increased 77% from €13.7 million in 2020 to €24.2 million in the year ended December 31st 2021. The increase predominantly relates to higher share-based compensation expense in 2021 and then increased premiums, higher consulting expenses. Net finance income for the year ended December 31st 2021 was $6.5 million compared to a net finance loss of $6.6 million for the year ended December 31st 2020. Net Finance Income loss is largely due to foreign exchange gains or losses related to assets denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and the euro during the year.
Net loss for the year ended December 31st 2021 was $57.5 million or $0.48 per common share compared with a net loss of 41.4 million or $0.50 per common share for the year ended December 31st 2020. The weighted number of common shares outstanding for the year ended December 31st 2021 was a 119.5 million. We encourage shareholders to also review our 20th filings for the year, which will be filed with the SEC. Today. I will now turn the call back to Adi for closing remarks. Adi?
Adi Hoess
Yes. Thank you, Angus. And as you’ve heard 2021, despite there will be issues out there. It’s been really fantastic year for us summit, so we brought programs full, but we have this unprecedented data. Twenties from 13 and non-cash position is strong as shown on slide 12, we’re now moving forward with multiple programs. I will read us today. You 13 is registration directed study. And we can report the results in second half of this year. More important to us now that we have found a way to address the full breadth of CD30 positive lymphoma. And obviously that’s based on the recently published data on AFM 13 in combination with the natural killer cells. We have not a key presentation at AACR and also later in the year we will have the opportunity to go watch the impact of our treatment on both not just Hodgkin lymphoma but we also believe in Non-Hodgkin lymphoma patients, which would mean that we have now all the ambition to make anything 13 available to patients with a wide range of CD30 positive lymphoma.
And as I said to going to provide more update on that in the second half of this year. In addition to our way forward with the intake hole. AFM24 is a completely novel drug that we designed with a strong inert component and we have now reported the initial data in 2021 and we felt that achieving this milestone with a recommended Phase two dose at 480 milligrams is now a key milestone 12 because we’re now testing AFM24 as a mono-therapy, but also in different combinations in the indications with the highest likelihood of a response. We’re very excited that these studies are ongoing and look forward to present early in 2022 as we are proceeding. And as we have learnt with AFM28, we’re are addressing an indication where there is a significant medical need. And as Alex(ph) explained, we believe that our platform is ideally suited to build upon based on efficacy of natural killer cells and potentially induce the deeper, longer-lasting responses.
Again, with a strong rational now derived from AFM 13 and the very meaningful responses we have seen that, income with metric kiloton. So all of us adapter meet our dedicate to now giving back patients their ability to fight cancer. I’m convinced that with a recent data and the thoughtful selection of our programs, we can help many patients that currently has no or very, very limited options. And as we’re now learning, the result are more interest from the pharmaceutical industry in this space. We also believe, driven by our strong data of AFM13. Now, thank you again for listening today and for our continued interest in our work. And we are now ready to take any questions.
Question-and-Answer Session
Operator
[Operator Instructions] your question, press the pound key. Our first question comes from Daina Graybosch with SVB Leerink.
Daina Graybosch
Thank you for the questions and the update. I just couple on AFM13 and the region rep study. First, I wonder if you could talk about the bar you expect for accelerated approval for or and duration of response and given that bar for duration of response, how much follow-up you think you’ll likely need to be able to exceed that bar. And then the second question is, given you could get accelerated approval here. When will you start thinking about commercialization? And could we see some early spend on prepping for launch
Adi Hoess
[Indiscernible]
Andreas Harstrick
I would take the first two parts and Zen when it comes to commercialization, probably hand back to you or to Denise. So Dennis, as you know, we talked with FDA about saudi sign-offs study and then head-to-toe alignment on the design. FDA will never give you a clear guidance on what they wanted to see. If we consider the environment, there a couple of trucks that have achieved accelerated approval regranted accelerated approval. Inperipheral T-cell lymphoma, or this includes h. JAK inhibitors, as well as Andy metabolites consistently these trucks have shown response rights in the 27%, 28% respond range and duration of response to somewhere around 8 to 10 months.
So I think this constitutes some kind of [Indiscernible], if you will, or lower basis of what you would need to achieve for also be considered accelerated approval.
Now, in terms of the follow-up, again, it will depend on the year duration of responses. We do have roughly close to a two-year recruitment period. So this will have an impact, also almost a follow-up. We have not done real modeling yet. We will do so when we get closer to our topline results that we plan to share with you Second half of 2022. And I think for the commercialization aspect, as our Adi or Denise
Denise Miller
I’m happy, I’m happy to jump in here. So thanks for the question. Gay now. So you’re right. So if we are in a situation where we received an accelerated market development and needs could be asking pretty much now. So what we’ve done as an organization is we’re adding key talent, including experienced oncology marketers, who will be joining this month in order to do the appropriate market development. We have key positions and K-well engagements that have been recently added. And we’re also adding a key talent in the area of market access and payer strategy, who will be joining us in about a month time. All of these talents that have been added to the organization augment what we already have. We have about three of us who have marketing and our background probably 90 years of pharmaceutical marketing and launch experience across multiple indications.
So we feel that we’re well-positioned to do the appropriate pre -launch market development activities in a very efficient, effective, and focused manner in order to de -risk any commercialization that could happen income with an accelerated approval.
Daina Graybosch
That’s very helpful. Thank you very much.
Operator
Our next question comes from Kripa Devarakonda, with Truist
Kripa Devarakonda
Hey guys congrats on all the progress and thank you so much for taking my question. I wanted to ask a little bit about setting expectations for data and second half from AFM13 the cbNK combo. Now that the FDA has approved multiple cycles, you and you’ve talked about this being more of material update. Can you help us understand how many patients, I know it maybe a little too early, but just ballpark. And also, when you talk to the FDA later this year, how are you thinking about using this multiple dose strategy in this context, and finally, can we expect anything at ATCO?
Adi Hoess
Andreas, you want to take it off?
Andreas Harstrick
I will start. So as you know, the study at MD Anderson is ongoing and we’re continuing to enroll patients. The amendment allows us asset for 40 in totals. Our initial focus will be on Hodgkins but we do have non-Hodgkin lymphoma patients on the study as well. The amendment covers and non-Hodgkin lymphoma patients with CD study are positivity. So we will expand our knowledge and our database beyond Hodgkins. Now, as I mentioned, we have already seen deepening of responses in the low doses. So of course, AACR will give a better overview on so as recommended Phase 2 dose response rate and CR rate after two cycles. And as we see individual patients, again, the option to administer more than two cycles is at investigators discretion, but we believe there will be patients who benefit even from more cycles.
Also, given the very excellent toxicity profile. Now, this totality of data with longer follow-up with more patients with multiple cycles will form our database for as the discussions with FDA and md things we will bring a couple of different strategies forward, as Adi said our focus will really be to align with FDA and identify with FDAs approved the pass that brings this important treatment to the patients in the shortest possible period of time. Was there something outstandings there were so many questions like this month.
Kripa Devarakonda
No, no. You covered everything. I just had one more question. Should we expect anything at ASCO. I know you’ve said second half is where we can expect this, but any updates planned at ASCO.
Andreas Harstrick
[Indiscernible]
Adi Hoess
I can take it. We’re discussing this with MDN, [Indiscernible]. So any additional updates currently in this stage are planed together with MD Anderson. So just stay tuned until we announced it appropriately.
Kripa Devarakonda
Okay. Great. Thank you.
Operator
Our next question comes from Maury Raycroft with Jefferies.
Maury Raycroft
Hi, thanks for taking my questions. I was going to ask one on AFM24. You said in the past for the individual AFM24 dose expansion and combo cohorts that you’d make a go, no-go decision based on initial data in approximately 10 to 12 patients and then expand. Just wondering if you can provide more specifics on what you’re going to be looking for in terms of number of patients in response rate and durability. And what could be included in some of the updates that we see later this year.
Andreas Harstrick
Thank you. So as you know, the all of you nine expansion cohorts are built on a Simon two stage design, which has the first interim look at 10% to 12 patients. And then where we decide whether the specific cohort will continue. We have not disclosed retargeted response rates per cohorts has also very across, across cohort. If you look at the [Indiscernible] pancreatic, it will be a little bit different than in diseases like a renal cell carcinoma. If these are open-label studies, of course, we could also give interim updates, which we planned for the second half of 2022. Now, remember that both of combinations studies from the in case cell combination study as well as we — [Indiscernible] up combination study have safety run in with a little bit lower dose of AFM24 before we can escalate up to the full dose of cells, there will also be an emphasis, especially in this dose-escalation on safety. So this will probably be the data package that you will see at end 2022.
Maury Raycroft
That’s helpful. Maybe a quick follow-up. Just clarify, for your poster at AACR, is that going to include follow-up data on the six patients at recommended Phase 2 dose and will there be any data in the poster from the 720 mg dose cohort?
Andreas Harstrick
There will be some follow-up, as we said, our main focus here is on PKPD and really showing all of the rationale that went into the 480 milligram definition as a recommended Phase two dose. The 720 milligram cohort is still ongoing treating patients, so we will not have data on 720 at the poster.
Maury Raycroft
Got it. Okay. Thanks for taking my questions.
Operator
Our next question comes from Brad Kimmino with Stifel.
Brad Kimmino
Thank you and nice enrollment progress across the programs. Maybe just a follow-up on Dana’s question on AFM 13. And how much durability data would be available at the top-line release, because you mentioned the trial has been enrolling for about two years and it finished this past January So would be reasonable to expect a median follow-up of around one year. And if that’s true, would that be sufficient durability to be ready to go towards the registrational Pratt pretty soon after that. Thank you.
Adi Hoess
Andreas.
Andreas Harstrick
I said we have not done a detailed modeling. Singular assumptions that we should have follow up around 12 months was probably correct. Began we will have to look at the Kinetics of the progressions to make a call how matures these data are how many potential events are still outstanding. After the interim analysis that we conducted. After 20 patients, we have really not looked into the database to protect the integrity of sleep data. So this was something that we will address when the data come in between now and see a disclosure of the high level data.
Brad Kimmino
Okay. Thank you.
Operator
Our next question comes from Li Watsek with Cantor Fitzgerald.
Li Watsek
Hey guys, thanks for taking the call. Maybe first on the upcoming AACR presentation. Just wondering if you can how to set the expectations for advisors. I mean, it’s a main focus from [Indiscernible] the second cycle or is there anything that we should be focusing on? And also can you share what kind of data that you need to see before you approach the FDA regarding the registrational path for the combo. And can you also talk about maybe different outcomes that you’re preparing for. Thanks.
Adi Hoess
Andreas? Again.
Andreas Harstrick
So for ACR, as I said, we will have them focus of course, on response data, now that all 13 patients are fully treated with two cycles. Of course there is longer follow-up, so there will be also these data available. There will be toxicity data, there will be some initial translational research data. I think it’s quite, quite comprehensive package and link being selected for the planned recession. This is probably also an interesting [Indiscernible] side remark. So we’re really looking forward to this data. Now in terms of FDA discussion, as I mentioned, we, of course look into broadening our experience was a more heterogeneous patient’s population which will enable us to discuss a couple of different pass ways.
Is that you said we are also looking at NK cell biology and k cells sources. So this will play into the timing of offer potential FDA discussion and we expect to give an update us how you said second half of this year.
Li Watsek
Okay got it, I have a follow-up on AFM24 24. You’re testing a lot of settings in expansion cohorts and just wondering if you could give us some guidance on the cadence, the data for this year. Should we expect data from certain cohorts maybe to radar earlier than others? And should we assume that we might see some interim data readout from any other cohorts this year? Thanks.
Andreas Harstrick
I think it’s too early to specify which and whether cohorts will enroll at a different pace. Of course, there are some differences in the frequency of certain diseases, non-small-cell lung cancer, colorectal cancer, probably Probably a little bit more frequent as we’re interested in all of these indications we have on the clinical operations front, specifically added also some sites with higher volumes of see who, if you will, a rare occurrences like hepatobiliary Kansas or renal cancer. So before we see the enrollment in those various such, I think it’s too premature to speculate whether certain cohort maybe faster than the now’s are we beliefs that see biological rationale for all of these cohort is very sound and that’s also the feedback we’re getting from our investigators. We have. come on board. All three studies are open and enrolling patients. Again, we are confident with our guidance to show initial data second half of 2022, in which cadence as this will comes, I think will shape out as we get a little bit more experience across the different sites and across the different cohorts.
Li Watsek
Got it. Thank you.
Operator
Our next question comes from Yale Jen, with Laidlaw.
Yale Jen
Good morning and thanks for taking the questions. I got one from an investor, which is that recently some of the single arm or maybe rent non-randomized study initially signal for accelerated approval has been. Sort of rejected by FDA and do you see any sort of potential impact on the rate direct future, past or you feel this is a very different sort of a type of drug versus others being treated that way.
Andreas Harstrick
Accelerated approval. It’s very hard to make any kind of conclusions from one study or one setting to the other setting. So I guess FDA has been quite clear in what’s like to see. First before you need to perform your study in an area of unmet medical need. Which after discussion with FDA, I think we have a good definition here. And then you have to provide a robust dataset that is likely to predict through surrogate marker. Finally, clinical benefit. And again, this certainly in oncology really various where we have certain settings where response rate alone as predicted for clinical benefit, certain settings where response rate in combination with durational response will be regarded as less than adequate surrogate. And do you have also — so I think our response rate does not correlate was clinical benefit. And these settings of course are not of suitable for an accelerated approval.
We addressed all these points in our initial discussions with FDA. So we would not see where I would not see any kind of cross effect. From the fact that certain study in certain setting with not granted accelerated approval to renew the direct study. It’s always suspended loan issue with these variables that I said. But if you control and then show these variables, I think you’re going to have an approval of a data set.
Yale Jen
Okay, great, maybe just on quick follow-up body would just a you mentioned us after the reporting of AFM13 data’s last N7 last year you getting additional sort of partnership, I guess discussions. Do you feel that AFM13 could be potential also to be partnered or it is something you want keep in-house for moving. Further.
Adi Hoess
Good question. So where and what we have been doing since December. We’ve had numerous meetings with the with the pharmaceutical industry and we’re still consolidating the interest we’re seeing. So in essence, we have been starting to prepare commercial team that is capable of taking drunks forward. Now the partnering can have a lot of assets. It can be a pure out-licensing. It can be a co-commercialization. So we are now exploring business, what the benefit is about. What I should say is the interest in what we do is broader than trust AFM13 and AFM13 has a strong read through into AFM24 and AFM28. So there are numerous opportunities including our pipeline. We haven’t mentioned that we have early-stage candidates identified similar to AFM32, so you see it’s a whole menu. What are we focusing on? So we’re not just like somebody comes and can pick, we have put a model behind every of our drugs, what we would want to achieve.
We have looked at the cost on how to bring these drugs to market. Basically we have [Indiscernible] built internally under which conditions we would want to do this or we wouldn’t want to do this and then it could make sense. So that gives us all the optionality from a point of where we have a high degree of knowledge know-how in order to move forward. Another answer is, for example, do we have to partner? No, we do not… it remains at discretion of Affimed what we want we want to do and what we can. Main reason is we have a reasonably strong cash position or you would say, and a lot of data coming up so we can also in parallel fee on the interest of all our investors, of all our shareholder. In order how this is supported. So we’re very flexible and that’s something that is important to us.
Yale Jen
Okay, great. That’s very helpful and congrats on the all the progress at this point.
Adi Hoess
Thank you.
Operator
Our next question comes from Zhiqiang Shu with Berenberg.
Zhiqiang Shu
Great. Thank you very much. And have a few questions on the FMS 13 program. Maybe the first one to follow-up on the potential accelerated approval in PTCL, if I recall correctly, the last actuary approval was granted probably more than ten years ago, and given the evolving landscape, actually evolving added from the FDA on the single addbacks area approval. Or your point on surrogate endpoint of, But we also see last year Bristol’s a personal pulled pulled out there. HDAC inhibitor in to see indication. Granted is I guess different mode of action. But how do you see that I can’t change the dynamic with the FDA. And then just related to that, have you planned any Phase 3 confirmatory trials to support this accelerated approval?
Adi Hoess
Along [Indiscernible]
Andreas Harstrick
As I said, I think it’s very hard to make any predictions or conclusions from one case of accelerated approval, or non granting of accelerated approval to another case. And as I said, when we were when we discussed many of the characteristics that would be required for a dataset that could support Exxon, right? In approval. We have not or I would not say that the landscape has fundamentally changes. Again, the removal of obviously HDAC inhibitor was a very specific story. And so I do not see us read through to what we discussed this FDA – NID when we started really direct study. Of course, there is a prerequisite is at the data, a strong and consistent to support such surrogate endpoint and likely association because was clinical benefit, but that’s something that we will learn simply when we have our top-line data available.
Now, one of your requirements for accelerated approval, of course, is that you will have to have a confirmatory Phase III study and we are currently looking into different options. Health Phase III study could look like we have had an advisory board with PTCL experts to discus some of these options. We will follow up. So if we should decide based on the data to go for accelerated approval, I think we also will have appropriate trace fee or confirmatory strategy signs to discuss with FDA.
Zhiqiang Shu
Great. And maybe just to follow up on the F and 13 with EnCase out pretty pre complex trial. And last time you discussed the potential to make the trial become a company-sponsored trial? I wonder what. Or what’s the progress there unless I’m me disclose you’re working with have identified a CDMO and maybe you can you provide some updates on that?
Adi Hoess
Nothing has changed on what we want. What we said in the past that we’re working on the CDMO, we are working in order to produce the NK-cells Product. Ambition is to obviously to have a cryopreserved NK cell product. We’re exploring all our Engagers with different NK cell products from other companies. So we have been indeed learning a lot around the opportunity to either pursue our own independent cell or to than do this in collaboration. We’ll let you know more about that in the second half of this year as all of that is progressing. That will also include then the strategy on how to take this drug forward into a registration directed study. Obviously the strong base to that we are currently generating is the basis we now have a Hodgkin lymphoma and there is this claim that this can expand to additional lymphoma.
All that obviously is valuable once we have a robust data set. We’re aiming at getting to this robust dataset, and once all that together, we can then take basically the strategy where they bring it to you. If you get premature P2P speculated as of today but it’s all maturing on our end.
Zhiqiang Shu
Great. Thank you. And maybe if I can squeeze one last question for AFM24. Maybe for Andreas, can you talk about the overall confidence in H cancer types? Do we expect to have a go, no-go decision in the second half for each cancer type? Thank you.
Andreas Harstrick
We cannot make predictions on how many of these cohort’s progress at which speeds as we are starting right now, we have selected fees from cohorts very carefully. We believe that each of these cohorts has a potential to show activity that could be or will be clinically meaningful. While as so, it’s exciting for us and [Indiscernible], we are currently enrolling patient’s non-suite studies. So we will see a good data and Second half of 2022.
Zhiqiang Shu
Great. Thank you very much.
Operator
Our next question comes from Do Kim with Piper Sandler.
Do Kim
Hi Adi and team. Thanks for taking my question. Just one on AFM24, the combination with NK cells. I was hoping what you could tell us about EnCase gens, autologous and case cell process. Does it have the standard lymphodepletion? Is there a bridging therapy involved? And maybe — is this a potential options for the AFM13 combo or are you sticking with donor and K-cells there?
Adi Hoess
Andreas? [Indiscernible]
Andreas Harstrick
Let’s start with, with the protocol that we currently have so, the SNK01 cell is an auto logos cell. So that’s very different from the MD Anderson approach, where we have allogeneic cells. So the auto logo cell, is basically derived from the patients. We, we’re getting sales through Luca for RESIS. And then NK Gen has developed a methodology to significantly expand and activate cells X-VIVO and then ten, we are reinfusing the NK-cells. Now the number of NK-cells that are infused, reinfusing are significantly higher. It’s four times ten to nine, but also unlike MDN doesn’t, we’re giving weekly and case cell infusion. So Emdeon doesn’t as one infusion per cycle and some followed by a three-weeks. So for AFM 13 here we are giving AFM24 weekly and NK-cells weekly. So four times tens was in line NK cell per week to these patients.
So very different concept. Now, since these NK cells are derived from the patient individually, we do not need for depleting therapy. There’s the roll-off lymph for depleting therapy and then case cell based treatment is to suppress the patient’s own T-cell, which would otherwise reject the allogeneic and NK cell. And we have learned that with one course of lymph for depleting therapy, you have a window of approximately two weeks and then the patient’s own NK cell — own T-cell compartment comes back and would reject allogeneic K-cells. So there is a reason why we cannot, for example, do weekly allogeneic and K-cells. No We selected the NK-Cell specifically as they have shown, activity moderate or activity or modest activity, but activity in combination with pembrolizumab in non-small cell lung cancer and also in combination with EGFR targeting agents in I’ll some sarcoma. So there is based on activity and we believe that synergy between an ICE.
And as these NK – cells in some sing worldwide to be explored. Now, we also have suffice it, look at different other and NK-cells sources. There is clearly the option to also look at allogeneic and k cells in the context of solid tumors. But as I said, the current study is addressing all two logos and K cell products.
Do Kim
Great, congrats on all the progress. Thank you.
Operator
I’m showing no further questions in queue at this time. Ladies and gentlemen, that concludes today’s conference call. Thank you for participating. You may now disconnect.
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