Affimed Therapeutics (NASDAQ:AFMD) Q4 2015 Earnings Conference Call March 30, 2016 8:30 AM ET
Adi Hoess - CEO
Florian Fischer - CFO
Jonathan Chang - Leerink Partners
Good day and welcome to the Fourth Quarter and Year End 2015 Financial Results and Corporate Update Conference Call. At this time, I would like to turn the conference over to Mr. Adi Hoess. Please go ahead sir.
Thank you very much for the introduction and I’d like to welcome you to our investor and analyst call on the fourth quarter and year end results 2015.
Before I start the corporate update and comment on the financial results, please note that this call and the Q&A session contain forward-looking statements, including statements regarding our future financial condition, business strategy and our plans and objectives for future operations. These statements represent our beliefs and assumptions only as of the date of this discussion. 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 forward looking statements due to the 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 cautionary statement regarding forward looking statements in our Form 20-F filed with the SEC earlier today. Thank you for your understanding.
Affimed engineered targeted immunotherapies seeking to cure patients by harnessing the power of innate and adaptive immunity. We have an unencumbered clinical and preclinical stage pipeline of next generation immune cells engagers based on bi-and-trispecific TandAb antibodies and we use our platform to develop engagers for two distinct type of immune cells, namely natural killer, or NK-Cells, and T-Cells. Our approach to redirect NK cells is unique in the industry and we intend to continue leveraging this approach as both standalone and combination therapies to treat haematological cancers as well as solid tumors.
Since our NASDAQ IPO in September 2014, we raised about $120 million in gross proceeds and our cash position is about €76 million, later on more details. We employ about 60 people with our headquarter located in Heidelberg, Germany and offices in New York and Boston.
On the next slide, our 2015 highlights are summarized. Together with our collaboration partner, Stanford University, we presented pre-clinical data at ASCO and ASH of last year on the synergistic effect of our lead candidate, AFM13, a bispecific CD30/CD16A NK-engaging antibody, in combination with anti PD-1, checkpoint inhibitors indicating AFM13’s unique ability to trigger the body’s natural immune cascade.
We showed consistently in four individual studies of in vivo PDX models with human CD30-positive Hodgkin lymphoma tumors that AFM13 in combination with anti-PD-1, but not anti PD-1 alone, rapidly enriches the tumor microenvironment with natural killer cells, followed by subsequent tumor infiltration by T-cells as well as substantially elevated levels of cytokines.
Based on this exciting and encouraging data, we were able to close a deal with Merck in the US which we announced earlier this year. We entered into a collaboration with Merck to evaluate AFM13 in combination with Merck’s anti PD-1 checkpoint inhibitor KEYTRUDA in Hodgkin lymphoma.
While currently preparing a Phase 1b clinical trial, designed to establish a dosing regimen for this combination therapy and assess the safety and efficacy in Hodgkin lymphoma patients, relapse refractory to chemotherapy, including [FFS] [ph]. Affimed is the sole sponsor and Merck will supply us with KEYTRUDA for this study. We are on track to initiate the study in the first half of 2016.
Our wholly-owned subsidiary AbCheck, and Pierre Fabre Pharmaceuticals entered into a strategic research partnership in the field of human antibody discovery and optimization, expanding their ongoing collaboration. And together with its partner Distributed Bio, AbCheck developed a novel, potent technology enabling accelerated humanization of rabbit antibodies.
We completed two major financings in 2015. In May, we closed the follow-on offering on the NASDAQ Global Market raising a total of about $37 million in net proceeds and in October we raised about $22 million from Aeris Capital, a long-term existing shareholder. Proceeds from these two transactions are expected to fund operations, including clinical development and further discovery and early development activities, until the first quarter of 2018.
Affimed was added to two performance indices, the Russell 2000 Index in June and the NASDAQ Biotechnology Index in December.
In June 2015, we formalized a Scientific Advisory Board comprising renowned scientists and physicians from a broad range of areas relevant to Affimed’s approach including immuno-oncology, natural killer cells, lymphoma and leukemia.
Over the course of 2015, we established operations in the US and strengthened our new US presence with key hires of Caroline Stewart as Head of IR, Oscar Kashala as VP, Medical, US, and Andrew Curtis who joined Affimed as Head of Corporate Strategy and Business Development.
We also strengthened our management team through the addition of Dr. Joerg Windisch as Chief Operating Officer which we announced in early 2016. With his broad expertise in pharmaceutical and regulatory affairs, quality control and project management and his proven track record in the development and manufacturing of marketed biologics, Dr. Windisch will support our expanding clinical pipeline. At the same time Dr. Bernhard Ehmer joined our Supervisory Board in January 2016. Dr. Ehmer is a seasoned expert in the industry with extensive international clinical development experience in biopharmaceuticals.
Slide 6. We are a global leader in natural killer cells based immuno-oncology approaches and we continue to believe that AFM13 is the most advanced NK-Cell engaging antibody in clinical development. The bispecific TandAb AFM13 binds to both the NK cells and the tumor cells and thereby brings immune cells into proximity to tumor cells and this leads to an activation of the NK cells and subsequent killing of the tumor cells.
We designed AFM13 as an antibody specific trigger receptor CD16A which we believe is the most potent known on/off switch on NK cells. This approach is unique in the industry and could potentially become a second cornerstone for novel therapies in addition to T-Cell redirection through CD-3, an approach pursued by several different companies.
To solidify our leadership in the space, we are developing further NK cell engaging TandAbs that we expect to enter R&D enabling studies in 2016.
Slide 7. NK cells are a part of innate immune system and also the gatekeeper of adaptive immunity. Once engaged NK cells can ignite the entire immune cascade beginning with antigerm presentation and leading to T-Cell activation. Hence NK-Cells play a key role in stimulating the adaptive immune response.
As mentioned, our lead candidate AFM13 is the clinically most advanced NK-Cell engager to-date. As a monotherapy, AFM13 was well tolerated and demonstrated clinical and pharmacodynamic activity in heavily pretreated HL patients. Due to its [very good] [ph] safety profile, we are thinking of combining AFM13 with a variety of anti-cancer drugs, including checkpoint inhibitors.
In preclinical experiment, we most recently have shown that AFM13 acts in synergy with checkpoint modulators and furthermore was able to increase T-Cell infiltration in the tumor micro environment. Efficacy was assessed by in vitro cytotoxicity and in patient derived xenograf in vivo models – the models that developed actual human tumors with AFM13 and a variety of checkpoint anti-bodies. In vivo synergy of AFM13 with checkpoint inhibitors in combination was observed and what’s most impressive for the combinations of AFM13 with PD-1. In the same models we were able to show that AFM13 induces cross-cell between innate and adaptive immunity.
30 days after treatment of AFM13 in combination with anti-PD-1 the tumor micro-environment was enriched not only within natural killer cells directly activated by AFM13 but also with T-cells, which shows that AFM13 can indeed activate the entire immune cascade.
Based on the data from our analysis of AFM13 dose in monotherapy and in combination with checkpoint we believe that our NK cells TandAb platform and in particular AFM13 have the potential to become a transformative approach to treat cancer.
On Slide 8, AFM13 is shown as a dual opportunity both as a drug with the potential to be a safe and more efficacious treatment for CD30 positive malignancies and we also believe that it will validate the CD-16A NK cells platform for applications to solid tumor indication. AFM13 currently is the only specific NK-Cell engager in the clinic increasing natural killer cell tumor penetration. This approach has the potential to restore the anti-immune cascade for a more robust and lasting fight against cancer cells. To-date the NK-Cell approach has demonstrated impressive safety, no CRS, with no MTD reached in the AFM13 Phase I study. Very importantly, we have broadened our clinical development approach and we’re creating an opportunity for mono and combination therapies.
In terms of milestones, we are planning to report interim data on the Phase 2 monotherapy study in the second quarter of 2016 and primary endpoint data by year end. We further plan to initiate a combination study of AFM13 with Merck’s anti-PD-1 antibody KEYTRUDA in Hodgkin lymphoma in the first-half of this year. Based on our preclinical data, this clinical work is of high interest to us as we believe that in addition to NK cells tumour infiltration, cytotoxic T-Cell infiltration might also be enhanced through AFM13. Providing this in the clinical setting will position our NK-Cells platform as being widely applicable to tumors to enhance efficacy of anti-PD-1 or even to demonstrate efficacy where anti-PD-1 until now has shown limited effects.
We’re also supporting an investigator-sponsored translational study of AFM13 in CD30-positive lymphoma with cutaneous manifestations that could broaden the market potential. This study is designed to enable multiple biopsies and we will thereby gain critical insight into recruitment of NK-Cells into the tumor over time. This trial and additional preclinical work will enable us to better understand NK-Cell efficacy in the tumor environment and its influence on the adaptive immune system.
The Phase 1b/2a trial is sponsored by Columbia University and Columbia has recently submitted an IND to the FDA which has become effective.
Slide 9. We have been generating further NK-Cells engagers in solid tumor indications. In 2015 we presented data on several scientific conferences showing that the NK-Cell TandAbs AFM22 generated against the tumor specific variant III of the EGF receptor showed similar cytotoxic and in vitro potency as AFM21 or T-Cell TandAbs against the same target EGF receptor variant III. In detail, we generated and characterized high affinity NK cell engaging antibodies and AFM22 fulfills all biophysical requirements. It shows unique specificity for the deletion mutant compared to other therapeutic antibodies and potently kills EGF receptor variant III expressing target cells but not cells from antigen negative cell lines. And importantly there is no cross-reactivity with EGF receptor wild type. We have initiated cell line development for AFM22.
We are also developing NK cell TandAb targeting EGFR-wild type, called AFM24. EGF receptor wild type is a validated tumor antigen in several solid tumors, including colorectal, lung and head and neck cancers. AFM24 shows very strong antigen binding and cytotoxic activity in vitro and is cross-reactive to cyno EGF receptor and CD16A. We have identified a lead molecule and initiated cell line development. AFM24 is differentiated from Cetuximab. It is potent in killing EGF receptor wild type expressing cells as shown here with the A431 tumor cell line. It induces tumor cell killing independent of mutational status and potent activation of NK cells through AFM24 is combined with checkpoint modulation.
Slide 11. In addition to our unique position in NK-Cell based cancer immunotherapy, we’re also one of the leaders in the T-Cells recruitment, a highly potent approach to eliminate tumor cells. For T-Cells based approaches, it is important to note that conventional antibodies cannot overcome the tumor cells escape mechanism via T-Cell engagement because T-Cells lack anti-gamma receptors. Hence other options are required for specific T-Cell engagements and are currently being pursued with a variety of approaches, including bispecific antibodies, Chimeric antigen receptor modified T-Cells and other cell based platforms.
Efficacy with bispecific T-Cell engagers has been demonstrated in blood cancers and the first T-Cell engager Blincyto has been approved in the U.S. and Europe for the treatment of ALL. Other promising data have been published showing effect in blood cancers. However, all data is at a fairly early stage. Important were the report, the side effects needed to be carefully managed and the bispecific T-Cell approach in ALL showed that interruption of dosing was an effective way of resolving critical issues. Overall convenience and COGs remain key issues.
Slide 12. Our lead T-cell engager AFM11, a tetravalent that unites the PD3 [ph] molecule has been developed as a potential competitor to Blincyto and has a well differentiated target product profile. We believe that AFM11 has clear advantages over its competitors in terms of potency, convenience and efficacy at low T cell numbers and we see a strong market potential in large indications such as NHL and ALL.
In 2014, we initiated a Phase I dose escalation in non-Hodgkin lymphoma, ALL patients with an intensive dosing regimen. However in August 2015, we amended the Phase 1 protocol optimizing their regimen to a less frequent dosing. In addition, we have split the NHL and ALL indications into two separate studies within the Phase I allowing differentiation for the ALL indication. The revised protocol has been accepted by the regulators in the third quarter of 2015 and patient enrolment continued into the Phase 1 study of AFM11 in NHL in October. We expect first data to be available by the end of this year and we further expect to initiate the trial in ALL in the first half of 2016.
We are developing AFM21 as a T-Cell engager as shown on Slide 13, targeting the tumor specific variant III of EGF receptor, the same target as for NK cell engager AFM22. As mentioned, both AFM21 and 22 are truly specific for the vIII deletion mutation and shows similar cytotoxic and in vitro potency. We generated and characterized high affinity T-Cell engaging antibodies TandAb and like AFM22 in NK cells, AFM21 fulfills all biophysical requirements showing unique specificity for the vIII deletion mutant compared to other therapeutic antibodies and potently killing EGF receptor variant III expressing target cells but not cells from antigen negative cell lines. In vivo AFM21 kills more efficaciously [ph] than Cetuximab. And again, there is no cross-reactivity to EGF receptor wild type. We have initiated cell line development for AFM21.
Slide 14. In terms of preclinical programs, we also have our CD33 and CD3 collaboration program with Amphivena/Janssen for the treatment of AML for which we presented preclinical data at ASCO. This program validates the robustness of our TandAb platform, and the data give corroborative evidence of direct correlation between binding affinity and potency.
With our Trispecific platform, we are enabling combination of tumor targeting, checkpoint modulation and immune cell engagement. Our Trispecific Abs are designed to allow for a dual targeting of tumor cells, binding to two different targets that are both expressed on the same tumor cells and a third target for the recruitment of T or NK cells. In our Trispecific program we have established proof of concept for for dual targeting in multiple myeloma where we could show specificity through bivalent binding i.e. avidity.
Slide 15. In summary, our pipeline comprises five programs directed against targets such as CD30, CD19, EGF receptor variant III, EGF receptor wild type, CD33 and non-disclosed multiple myeloma types. Our NK cell engager AFM 13 will be investigated in 3 clinical studies. For AFM11, we have made a major amendment in our clinical development strategy as we are now testing a much less frequent dosing regimen in NHL. In addition, the ALL indication will now be pursued in parallel offering a second therapeutic option in addition to NHL.
Our third program is targeting EGF receptor variant III bearing tumors. With this program we now have the unique opportunity to compare NK-Cell and T-Cell engagement side-by-side for their application to solid tumor, with our TandAb AFM22 and AFM21.
Our fourth program is evaluating an NK cell engager specific to EGF receptor wild type, a validated tumor target.
The fifth program is investing investigating T-Cells TandAb directed against CD33 and developed in AML. Our trispecific approach takes advantage of the four domain nature of our platform allowing the generation of multi-specific antibodies.
Our initial goal is to generate Trispecific Abs that recognize two different cancer cell antigens in addition to an effective cell antigen. This could result in high affinity and importantly increased selectivity for malignant tissues as compared to healthy tissues. This platform would offer an expansion of the target space for selective targeting of T-Cells versus healthy cells and we have initiated a discovery program for the therapy of multiple myeloma for which we have also been awarded a research grant from the German government in early 2015.
I will now hand over our call to our CFO Florian Fischer who will provide further details on the financial figures. Florian?
Thank you, Adi. 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 here in this call unless otherwise noted will be in euros. The numbers referring to Q4 2015 and Q4 2014 are unaudited whereas annual numbers for 2015 and 2014 are audited.
The financial results for the year ended December 31, 2014 include certain non-operational and non-cash effects due to our corporate reorganization in connection with our IPO in September 2014. Our consolidated statement of comprehensive income and loss for the full year 2014 was largely affected by the change of the estimated fair value of our share based payment awards. In addition, our preferred shares were classified as liabilities prior to our corporate reorganization in connection with our IPO and thus had to be measured by the fair market value.
Additional information regarding these results is included in the notes to the consolidated financial statement as of December 31 2015 and the management’s discussion and analysis of financial conditions and results of operations which are included in Affimed's Form 20-F as filed with the SEC earlier today.
Cash and cash equivalents totaled €76.7 million on December 31 2015 compared to €39.7 million on December 31 2014. The increase was primarily attributable to Affimed's follow-on offering of its common share on May 12 2015 and the sale of additional shares to Aeris Capital on October 9, 2015.
Net cash used in operating activities for the fourth quarter 2015 was €4 million compared to €5.4 million for the fourth quarter 2014. Net cash used in operating activities was $18.5 million for the 12 months ended December 31, 2015 compared to €10.5 million for the 12 months ended December 31, 2014. The increase was primarily related to higher cash expenditure for R&D in connection with our development and collaboration programs and to higher G&A expenses.
Affimed expects to have cash to fund our operations until the first quarter 2018. This provides runway for the planned development of our clinical programs as well as for further discovery and early development activities.
Revenue for the fourth quarter 2015 was €1.7 million compared to €100,000 for the fourth quarter 2014 due to revenues earned under the Amphivena collaboration in the 2015 period. Revenue for the full year 2015 was €7.6 million compared to €3.4 million for the full year 2014. Revenue in both periods is primarily derived from Affimed’s collaboration with Amphivena and the LLS as well as from third party services rendered by AbCheck.
R&D expenses for the fourth quarter 2015 were €7.0 million compared to €4.1 million for the fourth quarter 2014. For the full year 2015, R&D expenses were €22 million compared to €9.6 million for the year 2014. The increase was primarily related to higher expenses for AFM13, other preclinical programs and infrastructure.
G&A expenses for the fourth quarter 2015 were €2 million compared to €1.7 million for the fourth quarter 2014. For the full year 2015, G&A expenses were €7.5 million compared to €2.3 million for the year 2014. The increase is primarily related to a credit to the share-based payment expense resulting from a re-measurement gain at consummation of the IPO in 2014.
Net loss for the fourth quarter 2015 was €6.3 million, or €0.19 per common share, compared to a net loss of €5.3 million, or €0.22 per common share, for the fourth quarter 2014. Net loss for the full year 2015 was €20.2 million, or €0.71 per common share, compared to a loss of €0.3 million, or €0.01 per common share, for the full year 2014. The increase in net loss for the full year 2015 is primarily related to non-operational and non-cash effects in 2014 upon the corporate reorganization at the time of the IPO in September 2014 and higher operational expenses in 2015.
Additional information regarding these results is included in the notes to the consolidated financial statements as of December 31, 2015 and “Item 5. Operating and Financial Review and Prospects,” which is included in Affimed’s Annual Report on Form 20-F as filed with the SEC.
I will now turn the call back over to Adi for a summary of our two clinical programs in our pipeline. Adi?
Thanks very much, Florian. Affimed’s strategy is to maximize the value creation represented by our pipeline and platform. We’re leveraging our lead product AFM13 to establish a market in CD30 positive lymphoma. We are therefore initially focusing on the HL salvage settings enabling a fast development path and allowing the establishment of a cost efficient marketing and sales infrastructure.
In addition, investigating AFM13 dose as monotherapy and in combination with KEYTRUDA reduces its development risk. Our very encouraging pre-clinical data generated in collaboration with Stanford University have underlined the promise AFM13 holds as a combination therapy partner. Overall our preclinical and clinical strategy is designed to broaden the scientific leadership of our unique NK cell platform.
Another cornerstone of our strategy is to use our pipeline and technologies to create value through our next generation products and deal opportunities. With AFM11, we have an advanced molecule in development in the T-Cell engagement space to establish proof of concept in both non-Hodgkin lymphoma and ALL. With the NK cell platform we have a unique approach to recruit innate immune cells which can be applied to solid tumors. We're generating further NK cells and T-cell TandAbs such as AFM21, 22 and 24 in solid tumors and will advance the ideal candidate in two IND enabling studies and we will pursue the multiple myeloma indications through development of TandAbs and Trispecific Abs.
In addition, we plan to add value by forming a further high value technology platform partnership with an industry leader. Overall we believe that Affimed is well positioned in the emergent space in immuno-oncology with industry leadership in NK cell based approaches. Thank you very much.
The call is now open for questions.
[Operator Instructions] We will now take our first question from Brian Abraham from Jefferies.
Hi, this is Morey [ph] on for Brian. Thank you for taking my question. So I'm wondering for the AFM13 plus KEYTRUDA trial, if you can comment on Merck’s involvement in the process and how actively they're participating in the process?
Thanks for the question, so, as we have announced in early January through our press release, Merck and Affimed are collaborating in the following fashion, so we have – Affimed is taking the responsibility to conduct the trial. So Affimed is the sole sponsor of the trial. However in the process of establishing such an agreement, there was an intense exchange on the design of the clinical trial so Merck’s involvement in the set up of the design and all the kind of analytics to perform has been quite material. Nevertheless Affimed was keen to be a sole sponsor so that we can run this trial under our leadership. And obviously thereby we have much more control over the process. Obviously we will share data with Merck in that context and key contribution therefore by Merck is that they will provide the drug for free for this clinical trial.
And for the investigator led trial with Columbia, can you comment on when that may begin and also on the trial design for it?
In terms of answering your first question, so as I have said, we have the [INDs] [ph] being approved. So we're now in the final stages of basically initiating the centers. So we should enroll the first patient within the next month and thereby hope that we can present the first data towards year end. The idea is to provide AFM13 with different dosing regimens and also different dosing schedules. So we will have -- we will treat patients with lower doses of AFM13 up to the highest doses of 7 mg/kg. And we will treat patients with dose regimens where we provide the drug three times per week and compare that to once-weekly.
And my last question is for AFM21, 22 or 24, just wondering if when those move to the clinic, if you would combine them with the checkpoint inhibitor – that’s something you considered?
Well, that’s a very good question but obviously that’s the idea. So what we have learned from AFM13 is that there is a synergistic effect that we have not only seen in terms of tumor shrinkage but also in the infiltration of the different lymphocytes into the tumor and by a much higher production of cytokines within the tumor, most importantly interferon-gamma. So we believe that that could be re-treated -- could be true also for other tumors as well. Obviously we will test that again pre-clinically for us in order to see that such synergy is existing, but the obvious idea is that we will move forward with combinations of our pre-clinical candidates with some checkpoint inhibitors which we haven't determined, which it would be in the clinical setting.
We will now take our next question from Michael Schmidt with Leerink Partners.
Hi, this is Jonathan Chang stepping in for Michael. Thanks for taking my questions. First, on AFM13, can you talk about the progress of the Phase 2a study in Hodgkin’s lymphoma and what kind of data and how much data we can expect in the Q2 ‘16 update?
So we will – as I said, at the moment we have mentioned that we would like to provide an update in the second quarter on what we call the first stage of our AFM13 monotherapy trial. And then we will provide later in the year an update on the primary endpoint. The primary endpoint of that study is objective response rate, three months after the initial treatment.
And then secondly, can you talk about the hurdles for AFM11 in the competitive CD19 targeting space in non-Hodgkin’s lymphoma and ALL?
Sorry, can you repeat the question? Are you asking the hurdle?
Yes, just how high is the hurdle for AFM11 in targeting CD19 in NHL and ALL.
Interesting question, I don't think specifically what you mean -- can you just elaborate a little bit further on what you exactly mean by hurdle?
I guess, what do you think you need to show –
Okay. You mean on the end points, obviously we’re in a Phase 1 study, so the first hurdle that we are addressing is that we can demonstrate a therapeutic window, and that’s being quite narrow for all other therapies out there for the moment so that’s number one. And very important, the safety features at all. So we have seen some significant side effects both on CRS and neuro-toxicity, so those data will just have to be similar as it is for Blincyto, and in the efficacy setting, I guess, it’s obvious that what I said in the beginning were, we will be competing with Blincyto and we're expecting that we can show a good efficacy, also in the Phase 1 study obviously the numbers will be small, yet to make a full conclusion on the optimal efficacy of our drug.
So it’s primarily a Phase 2 trial and the Phase 2 parameter will be the most important one, so establishing a therapeutic window is key for AFM11.
We will now take our next question from Jim Birchenough from Wells Fargo.
Good morning. It’s Nitin [ph] for Jim this morning. Just follow up on the KEYTRUDA combination trial and I believe, you said this is going to be an [Indiscernible] refractory patients which obviously [Indiscernible] from the [Seattle Genetics and the anti-eye] [ph] trials ongoing. Do you have a definition for [Indiscernible] refractory and is it no progression obviously on drug or within six months of completing [Indiscernible] course for example, and does the trial design allow this to be expanded such that one could use it for a potential filing? And then I have a follow-up.
Thanks for the question. Very good question. Unfortunately I do not have the details on the patient enrolment criteria in front of me. So I need to follow up with you separately on that specific question.
In terms of the design, does it allow you or does it – still I guess, I am trying to figure out potentially what the role is. But does the design allow you to expand this trial to a number of patients who would be sufficient or filing under the [Indiscernible]?
No, that’s a Phase 2 trial and we will have about 22 patients so that – the design is currently that we can treat about 20 patients on [Indiscernible]. And with that data we will then have to discuss a registration trial.
So that, that would be a completely separate discussion -- completely separate agreement, there is no –
Yes, correct. For the time being this is exactly.
And then in terms of the EGFR targeting, you mentioned that, there is an NK cell line development decision being taken. Does that mean that you've chosen the NK cell line route or is it 21 cell line either being developed or planning to be developed? And then for 24, obviously toxicity must be top of mind. Is your goal to develop this as an EGFR inhibitor with the same toxicity profile as Cetuximab without the restriction of K-Ras testing?
Well, an answer to your first question, all three candidates 21, 22, and 24 are currently in cell line generation and are pursuit in parallel after the level of cell development. Once, so that will take a short while until we have achieved that status and then we can take a decision which of the candidates to move forward. So there is still a flexibility, quite some flexibility on our side yet to take that decision.
On the AFM24, your assumption might be a correct one, that there is toxicity expected as we already have seen certain toxicities from Cetuximab. However the differentiation is that currently Cetuximab is used in patients primarily for the competition with a ligand, so in order to prevent EGF receptor wild type activation. Hence mutations that constitutively expressed activated the receptor cannot be treated with Cetuximab as there is no expected effect. It also shows that there is a limited effect of ADCC in such antibodies. And one of the reasons might be because the IgG constant domain of Cetuximab for several reasons may not be potent enough in order to activate NK cells in a substantial manner at the site of tumors.
There is no specificity for natural killer cells, so these IgGs also recruit a large amount of neutrophils but most importantly, there is a difference in affinity of about a thousand fold between an IgG to bind an NK cell and a TandAb to bind an NK cell, and that higher affinity as we have shown by variety of experiments, also meets the higher potency of the drug. So we are thereby expecting that we can indeed deliver in NK cell toxicity in a substantially different manner as Cetuximab and thereby can achieve a therapeutic window. That’s the idea behind the AFM24. In addition, we're obviously exploring the combination with checkpoint inhibitors which may enhance the efficacy hopefully at a level where toxicity is still controlled.
And then my final question relates to trispecific. You indicated proof of concept for multiple myeloma. Can you discuss what the targets were – I am assuming it was not a tumor target, the checkpoint inhibitor, given the dose data are relatively new, and perhaps what your plan is for a trispecific in multiple myeloma?
So we have not disclosed the identity of the targets. In doing this, we have investigated. The occurrence of two targets expressed on a – co-expressed on a multiple myeloma cells, while these two targets will not be expressed on any other – not be co-expressed on any other healthy cell. We have created a proof of concept based on that principle, so we have cell lines available that co-express the two targets or express just one of the two targets and we could show in our first results that we would be only killing those tumor cells that co-express, both targets. And that’s the idea behind the entire platform, so you are correct. The approach is not directed against a checkpoint inhibitor but obviously it could include checkpoint inhibition as well. Those targets are selected primarily for the co-expression and over expression.
And the second criteria is that they are not co-expressed on healthy cells. And thereby checkpoint inhibitor could be involved but it's not necessary to be involved.
End of Q&A
[Operator Instructions] We have no further questions at this time.
Yes. And I wish to thank all participants for the call and we’re closing now our year end fourth quarter conference call. Thank you very much.
Ladies and gentlemen that will conclude today’s conference call. Thank you for your participation. You may now disconnect.
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