Anca Alexandru - Head of Communications Adi Hoess - Chief Executive Officer Florian Fischer - Chief Financial Officer.
Brian Abrahams - Jefferies Jonathan Chang - Leerink Partners LLC Do Kim - BMO Capital Markets Olivia Lamb - Laidlaw & Company Nick Abbot - Wells Fargo Securities, LLC.
Good day and welcome to the Affimed Fourth Quarter and Year-End 2016 Financial Results and Corporate Update Conference Call. Today’s conference is being recorded. At this time, I would like to turn the conference over to Anca Alexandru. Please go ahead..
Thank you. I would like to welcome you to our investor and analyst call on the results for the fourth quarter and year-end of 2016. On the call with me today are Adi Hoess, CEO of Affimed, who will present the corporate update and Florian Fischer, Affimed’s CFO, who will walk you through the financial.
Before we start, please note that this call and the Q&A session contains 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 by 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 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 statements regarding forward-looking statements in our Form 20-F filed with the SEC earlier today.
Thank you for your understanding. And I will now hand the call over to our CEO, Adi Hoess, who will provide the corporate update..
Thank you, Anca. I am now on Slide 3. We chose that Affimed engineers’ target is immunotherapies, seeking to cure patients by harnessing the power of innate and adaptive immunity. Our approach is to eliminate tumor cells by recruiting NK-cells or T-cells.
We have clinical and preclinical assets in our pipeline of next generation immune cell engagers is based on tetravalent bi and trispecific antibody formats. We are an industry leader in NK-cell engagement and our lead product candidate AFM13 is to our knowledge, the most advanced NK-cell engager in clinical development.
We also have a well-differentiated T-cell based approach with AFM11 and I'll provide an update on these clinical programs as well as our preclinical programs later. We have ongoing partnerships with industry, academia, and advocacy groups.
We employ about 75 people with our headquarters located in Heidelberg, Germany, and affiliate offices in the U.S., that is Affimed Inc., and our subsidiary AbCheck in Plzen, in the Czech Republic. Slide 4. We hit a number of highlights and corporate update in 2016 and early 2017. We initiated two new clinical trials.
In May 2016, we initiated a Phase Ib communication trial of our lead NK-cell engager AFM13 with Merck’s, Keytruda. We are so respond of the trial when Merck provides Keytruda for the study. In September 2016, we initiated a Phase I monotherapy for our T-cell engager AFM11 in acute lymphocytic leukemia or ALL.
In addition to the collaboration with Merck, we entered into an exclusive collaboration with the University of Texas, MD Anderson Cancer Center to evaluate AFM13 with MD Anderson’s proprietary NK-cell product which we announced in early January obviously.
Also announced in January, our wholly-owned subsidiary AbCheck achieved the first clinical milestone in their collaboration with Eli Lilly. The milestone is the commencement of patient enrollment for a Phase I study of an antibody discovered under the collaboration agreement.
It has triggered an undisclosed milestone payment to AbCheck from Eli Lilly and represents an important validation of AbCheck’s technology suite and its capability to reliably deliver high-quality antibodies suitable for clinical development.
In November 2016, we repeat the existing loan facility and entered into a new loan agreement of up to €10 million. We raised further €16.5 million or $17.7 million in net proceeds earlier this year in an underwritten follow-on financing. In August 2016, we announced the departure of our CMO, Jens-Peter Marschner.
In the interim Anne Kerber is serving as acting CMO. Under his leadership, we made very good progress in our clinical trials and I will outline later. We recently entered into a termination agreement with Dr. Jörg Windisch, COO who will be leaving the Company at the end of June 2017. Dr.
Windisch has accepted a position on the executive committee of a non-competing company focusing on the large-scale manufacturing of biologics and the development of biosimilars. We indeed look forward to working with Jörg over the next month and we are very happy that he will continue to support Affimed as a consulting expert following his departure.
Slide 5. Before I provide an update on our clinical and preclinical pipeline, I would like to explain the main characteristics of our technology. As compared to most competitors, Affimed is using a unique approach with its tetravalent bispecific antibody.
The bivalent binding to two receptors on two different cells enables high affinity binding through the avidity effect, which is advantages to obtain high specificity. This is important to achieve a good safety profile. Furthermore, our platform allows multi-specificity and a Tailored PK.
On Slide 6, we're showing that we're broadening our immune cell engager capabilities and add it further antibody formats. These novel formats have the potential to tailor immune-engaging therapy to different indications and target populations offering varying PK/PD property.
Slide 7, we have an unencumbered clinical and preclinical pipeline of NK and T-cell engagers, with our NK-cell engagers being developed in hematological diseases and solid tumors.
Based on our NK-cell platform, we have one clinical and two preclinical programs in development and based on our T-cell platform, we have one program in clinical development and for another T-cell based program Amphivena, a company of which we own 23% is planning to enter clinical development in due course. Slide 8.
Our expertise and leadership in natural killer cell based approaches is one of our key assets and we believe that targeting CD16A, a dominant activating receptor on innate immune cells is key for efficient recruitment of and killing by NK-cell and macrophages.
Indeed NK-cells are potent killers of cancer cells and the gatekeepers of adaptive immunity. They ignite the entire immune cascade, beginning with antigen presentation and leading to T-cell activation.
We have further shown synergy with checkpoint modulator and have been exploring preclinical further combination opportunities to enhance efficacy such as with cytokines. We believe that the safety profile of NK-cell engagers is highly differentiated from T-cell engagement and may confirm much lower toxicity.
This will be a potentially better treatment choice for elderly patients in hem/onc such as in multiple myeloma or AML and could further position the NK-cell platform, as a leading platform in solid tumor indication.
We have published further data that demonstrate that our NK-cell platform is strongly differentiated from regular IgG or Fc-enhanced IgG antibodies. I comment theme in all different cancer types is the ability of the tumor cell to evade recognition by the immune system and specifically natural killer cells.
Normally natural killer cells are capable of killing foreign or aberrant cells, but tumor cells have acquired mechanisms to escape the so-called immune surveillance. As a result, such NK-cells cannot recognize tumor cells as foreign or aberrant and therefore cannot fight them.
Our platform has the potential to overcome these limitations by disabling the tumors' evasion mechanisms. Defines immune cells through the CD16A specific molecule with high affinity and specificity in using NK-cell activation, which triggers an integrated immune response mediated by both innate and adaptive immune cells.
Slide 10, our lead product candidate, the CD30/CD16A in a specific NK-cell engager AFM13 is a first-in-class antibody suitable for mono and communication therapy. It has demonstrated safety and clinical pharmacodynamic activity in heavily pretreated Hodgkin Lymphoma patients in a Phase I study.
Preclinical it has further demonstrated synergy in combination with anti-PD-1 another check point, which has been the basis indeed of our Phase Ib trial in relapsed or refractory Hodgkin lymphoma in combination with Merck’s Keytruda, which we initiated in May 2016.
To-date, no dose limiting toxicity is for the communications were observed in the first and second dose cohorts of the study. The overall safety profile determined for the combination was unchanged from that described for each drug alone in these cohorts.
Data read-out is ongoing and the study has recently completed recruitment into the third dose cohort. A further update on this study will be provided in the second half.
For our investigator-sponsored Phase IIa monotherapy of AFM13 in Hodgkin lymphoma together with the German Hodgkin Study Group we have revised the overall study design in order to adapt to the changing treatment landscape, namely the availability of anti-PD-1 antibodies.
The study will now include Hodgkin lymphoma patients relapsed or refractory to treatment with both brentuximab vedotin and anti-PD-1 and different dosing protocols of AFM13 are being explored to allow for improved exposure in this more heavily pretreated patient population. We anticipate providing an update on the study in the second half of 2017.
Slide 11, additional opportunities for our NK-cell engagers include combinations with adoptive NK-cell transfer, which we are investigating with our partner MD Anderson.
As mentioned in January 2017, we announced an exclusive strategic clinical development and commercialization collaboration to evaluate our tetravalent bispecific immune cell engager technology in combination with MD Anderson NK-cell product.
The collaboration comprises research, development, and eventually commercialization of novel oncology therapeutics resulting from this combination of products. MD Anderson will be responsible for conducting preclinical research activities and these are intended to be followed by a Phase I clinical trial.
Affimed will fund research and development expenses for this collaboration and the agreement includes a provision for the potential expansion of the partnership. Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration.
Leveraging MD Anderson expertise in NK-cells and translational medicine, and Affimed’s capabilities to develop tumor-targeting bispecific tetravalent immune cell engagers, the combination is initially planned to investigate Affimed’s AFM13 with MD Anderson NK-cell product in Hodgkin lymphoma.
Harnessing the advantages of both antibody-based and cell therapy approaches, this combination has the potential to better exploit the therapeutic activity of NK-cells in Hodgkin lymphoma and beyond, for example in other medically underserved indications such as multiple myeloma or acute myeloid leukemia.
And further opportunity is the combination of our antibodies with cytokines. In recent preclinical studies, we have demonstrated that AFM13 induced upregulation of specific interleukin receptors on NK-cells in a target-dependent manner and sensitized such NK-cells for Interleukin-2 or Interleukin-15-mediated expansion.
This now provides a rationale for clinical combination of NK-cell engagers with such cytokines or newer product aiming for deeper clinical responses. Affimed plans to provide an update on preclinical data supporting this approach at the upcoming AACR Annual Meeting next week.
We are also planning a translational study of AFM13 in patients with CD30 positive lymphoma. Slide 12, we continue to develop first-in-class in NK-cell engagers to address the critical unmet need to effectively treat EGFR expressing solid tumors such as lung, head & neck or colon cancers.
AFM24, an EGFR/CD16A targeting bispecific antibody, is designed to improve both efficacy and safety of current therapeutic monoclonal antibodies. It’s indeed well differentiated from cetuximab with more potent cytotoxicity in vitro and in vivo, including RAS mutation cell lines.
Through its novel mechanism of action and safety profile, it has the potential to overcome intrinsic or acquired resistance, which is described for many patients. Safety profile offers the rationale for combination of AFM24 with PD-1/PD-L1 antibodies, for example non-small cell lung cancer or head and neck cancer.
We intend to present data on our EGF Receptor targeting antibodies at AACR next week and anticipate providing an update on the development strategy for the program in the first half of 2017. Slide 13. Our second preclinically program is called AFM26, which is to treat multiple myeloma, which is the second most common hematologic cancer.
AFM26 is a first-in-class tetravalent bispecific antibody targeting BCMA/CD16A. Multiple myeloma is characterized by high serum levels of monoclonal immunoglobulin, so-called M-protein and most patients eventually relapse with and/or become refractory to the currently available treatments.
AFM26 introduces a novel mode of action conferring high-affinity to both target and NK-cells, which leads to a prolonged cell retention. AFM26 indeed shows high cytotoxic activity towards BCMA-expressing myeloma cell line, and importantly it NK-cell binding appears to be virtually unaffected by the presence high levels of IgG.
Based on these characteristics, AFM26 might potentially be positioned in first line as communication with adoptive NK-cell transfer during stem cell transplantation or in salvage setting. It is potentially safer than a T-cell-based approach which could allow for faster development timelines.
We intend to present data on our BCMA targeting antibodies at AACR next week. Slide 14. Our efforts in T-cell engagement have led to the development of differentiated products as well as novel platform.
AFM11 targeting CD19/CD3 is designed to address the high unmet need in Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma that remains despite recent CAR-T data.
It addresses limitations of other bispecific such as the need for CIV administration or low efficacy and has demonstrated higher potency at low T-cell numbers as compared to comparative molecules. In September 2016, we initiated a Phase I dose escalation trial of AFM11 in patients with relapsed and refractory ALL.
The trial is ongoing and trial sites in the Czech Republic, Poland, Russia, and Israel have been initiated. In our Phase I study in NHL for AFM11 several additional trial sites were opened throughout 2016 and the trial is ongoing and recruiting. We expect to provide a progress update on both trials in the first half of 2017.
In July 2016, an IND for the bispecific CD33/CD3 T-cell engager AMV564, a molecule developed from Affimed’s TandAb platform, became effective. AMV564 is being developed by Amphivena therapeutics to address the high unmet need in AML. The drug is well-differentiated with its potent and selective cytotoxic activity and robust tumor growth inhibition.
Amphivena has announced its intent to initiate a Phase I dose escalation trial for the drug in AML patients. Together with the existing investor consortium, Affimed is financially supporting clinical development of AMV564. We have further developed a noveltechnology platform to open up that therapeutic target space.
The platform is designed to generate antibodies targeting disease specific MHC-peptide complex. Access to these intracellular target is highly attractive for both T and NK-cell recruitment and we have generated and preclinically investigated T-cell engager specifically binding such MHC-peptide complex.
In preclinical studies, the lead candidate shows selective, potent in vitro killing of tumor cells endogenously expressing the targeted MHC-peptide complex. We expect to present based on this program at AACR next week.
As shown on Slide 16, our NK-cell platform comprises three programs, the lead drug AFM13 is currently investigated in two clinical trials and we have developed further options to broaden its application. In addition, we have two more drugs, AFM24 and AFM26 in preclinical development.
Regarding T-cell engagement, we're focusing our efforts on AFM11, which is being investigated in two clinical studies. We have further developed a novel platform that enables the targeting of MHC-peptide complex. Next week, we will have an oral presentation and multiple posters at AACR that will provide a further update on these programs.
Furthermore, we expect to generate significant – throughout 2017, providing updates on all our clinical and preclinical programs. I will now hand over the call to our CFO, Florian Fischer, who will provide further details on the financial figures..
Thank you, Adi. Affimed’s consolidated financial statements have been prepared in accordance with IFRS that issued by the International Accounting Standards Board or IASB. Consolidated financial statements are presented in Euro, 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. Any numbers referring to Q4 2016, Q4 2015 and February, 2017 are unaudited, whereas annual numbers for 2016 and 2015 for audited.
Cash and cash equivalents and financial assets totaled €44.9 million as of December 31, 2016, compared to €76.7 million as of December 31, 2015. The decrease was primarily attributable to Affimed’s operational expenses.
After the consummation of our follow-on financing in January and February 2017, cash and cash equivalents and financial assets totaled €68 million as of February 28, 2017. Net cash used in operating activities for the fourth quarter of 2016 was €6.6 million compared to €4 million for the fourth quarter of 2015.
Net cash used in operating activities was €32.1 million for the 12 months ended December 31, 2016 compared to €18.5 million for the 12 months ended December 31, 2015. The increase was primarily related to higher cash expenditure for research and development in connection with our development and collaboration programs.
Affimed expect perhaps cash to fund our operations at least until the end of 2018. This provides runway for the plan development of our clinical programs as well as for the further discovery and early development activity. Revenue for the fourth quarter of 2016 was €1.4 million compared to €1.7 million for the fourth quarter of 2015.
Revenue for the full-year 2016 was €6.3 million compared to €7.6 million for the full-year 2015. Revenue in both periods was primarily derived from Affimed’s collaborations with Amphivena and LLS as well as from third-party services rendered by AbCheck.
R&D expenses for the fourth quarter of 2016 were €5.7 million compared to €7.0 million for the fourth quarter of 2015. For the full-year 2016, R&D expenses were €30.2 million compared to €22 million for the full-year 2015. The increase was primarily related to higher expenses for AFM13, AFM11, other preclinical programs and infrastructure.
G&A expenses for the fourth quarter of 2016 were €2.1 million compared to €2 million for the fourth quarter of 2015. For the full-year 2016, G&A expenses were €8.3 million compared to €7.5 million for the full-year 2015. The increase was primarily related to higher share-based payment expenses.
Net loss for the fourth quarter of 2016 was €5.4 million, or €0.16 per common share, compared to a net loss of €6.3 million, or €0.19 per common share, for the fourth quarter of 2015. Net loss for the full-year 2016 was €32.2 million, or €0.97 per common share, compared to a loss of €20.2 million, or €0.71 per common share for the full-year 2015.
The increase in net loss for the full-year 2016 was primarily related to increased spending on R&D for AFM13, AFM11, preclinical programs and infrastructure. In addition, the result was affected by lower revenue and lower finance income.
Additional information regarding these results are included in the notes to the consolidated financial statements as of December 31, 2016 and “Item 5. Operating and Financial Review and Prospects,” which will be 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 summary of our two clinical programs and our pipeline.
Adi?.
Thanks, Florian. As we said in [10 years,] our strategy is to maximize the value in our pipeline and platform.
We are leveraging our lead product AFM13 plus CD30 positive lymphoma initially focusing on the can Hodgkin lymphoma salvages setting enabling a fast development path and now allowing the establishment of a cost efficient marketing and sales structure.
In addition, we believe investigating AFM13 both as monotherapy and in combination with Keytruda reduces its development risk. A very encouraging preclinical 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 NK-cell platform with CD16A as proprietary target and we are continuing to expand the preclinical and clinical activities of our NK-cell TandAb platform in solid tumors with our preclinical candidate AFM24 and in hematologic diseases, where we intend to leverage additional opportunities for AFM13, for example in combination with adoptive NK-cells.
In addition, we’re developing trispecific antibodies applying both a dual targeting and co-targeting approach against several targets. We also developed T-cell engagers and allow lead T-cell engager AFM11 is being investigated in two ongoing ALL and NHL trial.
AMV564, a T-cell engager developed from our TandAb platform is anticipated to be clinically developed by Amphivena to treat AML. From our MHC-peptide complex targeting platform, we have developed our molecule, which we are preclinically investigating. Thanks a lot for your interest. Call in now open for questions..
Thank you. [Operator Instructions] The first question comes from Brian Abrahams from Jefferies. Please go ahead. Your line is open..
Hi, thanks for taking my questions. First question is on AFM13 Keytruda and that study obviously seems like things are progressing well. Good news that safety looks clean.
Just wondering, do you think you're approaching potentially therapeutic doses there and what degree of data maturity should we be expecting with the next update from the study in the back half of the year?.
Yes. So the study is – as you may recall is divided into a dose escalation and then in a does cohort expansion. In the dose escalation, it’s a classic three plus three design and we have been using three different dose levels for AFM13.
The first dose level was below its therapeutic dose, the second and the third are at the low and high end of its therapeutic dose. We will analyze obviously also the efficacy in these patient groups and we have currently only published data on the first dose, which came back with two responses, two objective responses.
Out of three patients, we are now analyzing the second dose cohorts group and in a few months from now, we will also have the third dose cohort then available for analysis. In terms of numbers, the numbers still may be small, but obviously we're looking into a first idea on how the efficacy is developing..
Got it.
And then on the MD Anderson collaboration, just wondering if you could talk about what the next steps might be for exploring AFM13 plus their natural killer, other NK product and then maybe if you could just touch on some of the other types of products that you might look to explore within that collaboration?.
Yes. So as we said, the collaboration is divided into two components. First, it’s a preclinical safety study and that's currently ongoing. And what we are currently doing, what we can say is, we first need to determine and analyze this preclinical safety before we can give any outline on the further approaches what we can clinically investigate.
So there is an important first step and unless that’s concluded, it will be too speculative to come back with some clinical ideas. But let's assume this goes well. And to you give you an answer on your second question is what we upside.
So obviously Hodgkin lymphoma is a market where transplant plays a role, but it's not the biggest market and the much bigger market out there is multiple myeloma. And as in our pipeline, we are engineering a BCMA CD16A antibody called AFM26. This will be the – let say in our mind the real future applications.
So that's what we would like to focus beyond AFM13 and for that purpose we have structured also this collaboration..
Got it.
And make some work with AFM13 potentially reduce the development time for AFM26 within this collaboration potentially?.
You are asking a very good question. Thanks. Indeed we have to establish, first, several procedures.
As I say, we need to get some idea on the safety, obviously we can do this for AFM13 now, but also for AFM26 because we don't need clinical material, so we can do this studies much earlier, but the much more important is then once we have determined the preclinical safety, we then can go immediately ahead with AFM13.
And this will give us a first idea on how these two drugs and how these two approaches work together and there's obviously several ideas currently kicked around on how to best administer this, so you can administer these two approaches separately or you can develop a pre-mixing approach.
And this is something that we would wish to establish with AFM13 which then would basically take that burden of development away from any future products because we will already have a strategy in place on how to inject these two approaches..
Got it. Thanks very much, Adi..
We will now take our next question from Michael Schmidt from Leerink Partners. Please go ahead..
Hi. This is Jonathan Chang stepping in for Michael. Thanks for taking my questions. First, just a follow-up from previous question.
For the AFM13 plus Keytruda combination study should we expect safety and efficacy data from the first three dose cohorts at the second half 2017 update or more?.
So what we have said is that we have now enrolled the third dose cohorts and just to give you a perspective on what our timelines are what we are assessing.
The safety is assessed six weeks after the third patient is being dosed in each cohort and we will do the efficacy assessment after three months and after six months and then we will follow on patients until they relapse or become refractory to the treatment.
So with this timelines in mind, we now definitely have to wait minimum of six weeks or let see. Roughly six weeks before we have concluded the safety and then their respective time and the assessments will just happen as I outlined..
Great, thanks.
And then for AFM26 and you touched on this in your prepared remarks, can you expand on how your anti-BCMA NK-cell approach compares to T-cell-based anti-BCMA approaches being developed from multiple myeloma?.
Again, very good question, but obviously that’s more on the speculate event, but let’s just in general look on what kind of data have been published.
And what we have learned from T-cell approaches in general is that – I'm talking about many different indications and different approaches, so like targeting CD19, targeting CD20, targeting CD33 or CD123 is T-cell-engagers.
What we have seen in the past years that it took every company relatively long until they could generate either the first safety or efficacy data. And when you say many years, we have seen Phase I development timelines being longer than three years. When this is compared to NK-cell engagers those escalation in NK-cell engagers could go much faster.
So you can start already with much higher doses while with T-cell engagers you start with very low usually ineffective doses. So there are particular advantages and you maybe able to use for the NK-cell engagers and thereby you may have your safety established instead of in three years maybe already asked 12 months to 18 months.
So that's a particular advantage on the NK-cell platform. Again most of that is drawn from data that we have generated on AFM13 and thereby maybe not be generalized, but at least it's a fair assumption that we can make an hour end.
Obviously what we also can measure if the – for example the side effects that we are anticipate, so the cytokines releases and indeed will show first datasets at AACR on our BCMA molecules that we have generated our first data that also may point to a better tolerability of an NK-cell engagers versus T-cell engagers..
Great, thank you..
We will now take our next question from Do Kim from BMO Capital Markets. Please go ahead..
Thanks for taking my questions. Adi, are you first – if your four presentations at the AACR meeting.
Are there any particular ones that you think we should focus on and maybe if that and what we will learn from them?.
So the real new data that we're presenting relates to both AFM24 and AFM26.
So these are another data that we have generated in a very recently and especially on AFM24, we're quite excited not only to show that our drug has differentiated efficacy from cetuximab, but we will also present first data on the safety of our drug in tox studies that we have conducted in cynomolgus monkeys.
So in addition to adding to a better efficacy versus cetuximab, we also have now the potential to talk about a real safety advantage. And as you may recall one of the issues with cetuximab are skin toxicity. This is again early, but as I say we'll have our first data on the poster..
Great and could you remind us when you would expect to file an IND for AFM26 and what more needs to be done before that could happen?.
Yes, so as we are currently working and investigating all these molecules, I just like to give an update during the next earnings call and just basically don't give your clear answer yet on these questions.
What's the reason? As I have explained, we have also developed another platform and we have now a different set of molecules available and where at the moment comparing the features of all these different molecules.
So we have gone beyond our original TandAbs and have now molecules available that offer virtually a different PK/PD ratio and this is what we are recurrently investigating. So as long as we're studying these data, we just basically were waiting for the results before we can give clear guidance on which truck we can take forward..
Okay. Okay, I understand. And on AFM11, we see response rate data in the next update and when we do see efficacy data for AFM11.
Could you remind us what would be considered successful to move to the next stage of…?.
Yes, so what we're doing with AFM11 as we have set with running at dose escalation both in ALL and HL and that usually includes either one or three patients for those levels. So at that stage we have – we’re at still in the dose escalation pace.
So we’re still optimizing that dosing regimes and we will continuously update on where we are and I just need to basically ask for patients until the next earnings calls, if it is the next or later we just no need to see.
But what's really positive for us in the past, we've had real issues into recruiting patients and moving along in the dose escalations we had a lot of corrections that we had to undertake for example move with the study into new countries and really run the process is there. What I can say at the moment that it seems to pay back.
So we have a constant recruitment of patients now and the sites are delivering with high quality and that's been important to us. So the East of Europe was an excellent choice for us to-date and we just now see patients coming in at even better than expected rates, so this has been very positive. But just keep in mind ALL is still a rare disease.
So that means that patients are coming in on a much rarer basis than in NHL. So as it looks at the moment it's good, and we could have some data in the second half of this year, but for the time being we just need to see how we continue..
Okay, great. Thank you for taking my question..
We will now take our next question from Yale Jen from Laidlaw. Please go ahead..
Hello, good morning. This is Olivia Lamb here stepping in for Yale Jen. So I just – I’ve got two questions. The first one is a follow-up for AFM13 Keytruda combo study update.
What do you anticipate might be the number of patients analyzing that update expected in the second half this year? And then my second question is given Regeneron’s NHL program, also using bispecific antibody was not robust.
What are your thoughts of your AFM11 in NHL program right now? Does it give you greater concern or lesser concern?.
So the study I’ll say AFM13 in communication with Keytruda is designed as a dose escalation and dose cohort expansion part. Dose escalation is nine patients and the cohort expansion is about 20 patients. And if recruitment works as continuously seen, we are expecting that we can basically report data in the second half to 2017.
In terms of your second question, the competition landscape out there indeed the drug that we have seen at the moment having the most profound data is Blincyto.
If you may recall Blincyto has been developed already in the Phase IIa study in NHL patients and had come back with a very reasonable response rate and Blincyto at that time looks indeed already much superior than many of the other competitors programs. We feel that when we compare AFM11 with Blincyto that we may have a more potent drug.
At least preclinically, we have seen quite some distinct features of AFM13, so eventually we can end up with some sort of a superior efficacy. But just keep in mind, currently in NHL in the setting where we're developing the drug, which would focus on Mantle Cell Lymphoma or Diffuse Large B-Cell Lymphoma.
In the salvage setting, there is no other drug to get out there that would block the development and also the commercial development of AFM11. So this is still although highly competitive, but it's an open space.
And so taken together, we have not seen yet any drug as I just mentioned with strong data in that particular setting that we think will be preventive for AFM11 and its continuous development. So it is a very reasonable trend that we can move along. And that just includes drugs from Regeneron, but as you know there is other drugs out there as well.
So we're not just focusing on that particular one, but the data that were presented at ASH came back with a relatively modest efficacy to-date..
Okay, great. Thanks. That’s helpful.
Actually I just have one more question, for the AMV564 in AML, do you anticipate providing some more color on the preclinical data before the Phase I study is initiated?.
So again, this is a program developed for Amphivena and all the updates that are presented by Amphivena in that context. So Affimed does not intend to present any data on this program. We are shareholder in this Company.
So we're still very – involved with the processes and we are heavily supporting their development, but in terms of releasing data and further communications this is handle by [MPV9] itself..
Okay. All right. Thank you. Thanks for taking the questions..
Thank you..
[Operator Instructions] We will now take our next question from Jim Birchenough from Wells Fargo. Please go ahead..
Good morning. It’s Nick in for Jim this morning. Looks like it's going to be an exciting year Adi. Anyway just starting off, you indicated now this alternative structure, I’ll call it a box structure that staying good with a [gold royalty] in your cartoon.
So can you elaborate on where you think that your conventional tetravalent linear structure might offer advantages of the box structure and – as I take it from your comments that 26 could be a box, could 24 be a box as well and what do you think is the first box version of TandAbs?.
Obviously there is a good reason yet why we're not yet elucidating what the gold box is, but is a good analogy. So I like this color gold in that context because it may just be in certain settings it could be an advantage.
However, at the same time what we're doing is at the moment in very broad investigations and there are a lot of IP relevant topics that we are – that we have been observing, and thereby we cannot disclose any details beyond the point what we have been doing at that stage simply for IP reason.
We are in the process of filing patents on these approaches. General patents on the platform specific approaches on individual programs. But what we can do just to give you a little bit of idea. These molecules may not only have a different PK which allows a different dosing, but they may also have different tissue distributions.
And that in some cases could allow you to – for example reduce certain toxicities of molecules. So if you are [legend] of desire is for example expressed in certain solid tissues, you may not want to move your molecule into those particular tissues and our structures allow for exactly tailoring the distribution.
So these are aspects that we are currently investigating and thereby we can decide in every specific setting either for a through standard structure or maybe something or maybe then on our new structures. We also have other applications that we're currently discussing with the key players outside of Affimed with industry players.
For example, there maybe potential application of our platform to additional indications outside of oncology, I just mentioned neurology. And in some instances for certain applications you may want to have molecules that indeed have a shorter half-life and in such settings the TandAb can be more beneficial.
What we're learning overall from the field that there is no solution one fits all. So if you just have a long half-life none of the molecules that are developed.
For example as T-cell engagers yet came back with convincing data and one has to carefully select the molecule and one has to drive the choice of a molecule much more from the aspect of disease and target and not so much just from convenience.
I think especially in oncology, the sequence is still efficacy, safety and latest is convenience, so we need to improve in many indication efficacy of patients and the safety of the drugs and this is now what the new platform will allow us to do..
Okay. Thank you. Just moving on to the MD Anderson collaboration, obviously there's been some questions on this, this morning, so is there NK-cell study that's ongoing at MD Anderson. I'm not saying it’s very limiting, but you're waiting for that.
I know they have TandAb 15 strategy and do they generally use post DLI IL-2 given your preclinical data now of sensitizing NK-cell to IL-2. Is that what you would be anticipating? Is that there would be some sort of NK-cell memory NK or engineer NK plus IL-2? And then how they are either add mixing your TandAb or adding theTandAb.
I mean what do you think first application looks like?.
Yes, so indeed I must say that we are very careful in broadening investigated the adoptive NK-cells and there are still early, but a number of players out there. So the MD Anderson to us is a very important option, as I – we’re working together. But I'd say that we're not ignoring even other players.
So it could be in our mind and could be but we are open to the product combinations, but what we are seeing in general we see in adoptive NK-cells space is upcoming. And it's definitely something where it looks like that you can rather develop an Off-The-Shelf principle.
So the MD Anderson gives us an excellent position and a situation where we can start early investigating that's already in the clinical sittings. Just recall many of the other players out there biotech companies are just starting the first Phase II trials.
So that means that those – all these players are generating data while the MD Anderson already has and established safety of the molecules. And you're right to say a lot is ongoing in this dynamic field in order to enhance the efficacy of NK-cells and we're definitely seeing that these cytokines play an important role.
I mean otherwise, we wouldn't have done the experiments and we wouldn't be very lucky to see that synergy with to IL-2 and IL-15 and that synergies and be triggered by a specific mode of action of AFM13 in that context.
So this makes a lot of sense to combine these and how the eventual product looks like if it comes from MD Anderson or if it may come from another party is yet have to be determined, but as I say we’re playing in the forefront. We can have that clinically now and we feel that with our immune cell engagers, we have a very, very distinguished feature.
It's a very high affinity binding to AFM13 NK-cells. And a very high affinity means that we have very long cell retention. We will show data on that again at one of the posters at AACR.
But it is something that we are focusing on to optimize this combination of the two approaches and if it is in our 2015 eventual we'll have to feel but we are currently playing there and that's important..
Okay, thank you. And then just a couple other quick ones. On AFM26, I mean I recall when you were looking at EGFRvIII, you are very clear about the engineering ability to identify what is difficult target [indiscernible]. Clearly, with BCMA, we have soluble BCMA, which could act as I think particularly for potent drug that’s dosed in a low dose.
So is there a way to target that membrane-bound number [indiscernible] away do you have to worry about soluble BCMA or do you have a clever engineering solution to avoid the potent?.
A very good question, but let me comment on another finding that you are having is what there you may recall AFM13, when we did the dose escalation. We did not reach the MTD. At the same time these patients all had very high levels of circulating CD30. What we're seeing is that our dose escalation was started at point 0.1 mg/kg and went up to 7 mg/kg.
And interesting is when we came to the effective dose AFM13 at 1.5 mg/kg. We already were able to clear all circulating CD3 on the first dose. So even if there is circulating molecules with the NK-cell approach, we should have an advantage because if there is no MTD, we can dose high enough to overcome these limiting aspects.
Comparing that T-cell engagers, that could be rather more problematic and I’d say if you one wants to engineer T-cell engager, one would have to focus much more on such differentiating antibody.
In our case, we feel that with an NK-cell engager we may be able to address that simply overdosing or with dosing?.
Okay.
Thank you and then my last question is really just on finds for cash runway, you indicated with cash to year-end 2018? Can you just high level outline what kind of clinical investigation that you could support through the year-end 2018?.
Hi, Nick. It’s Florian. The way we've calculated that we basically that we're taking the pipeline that you're seeing and that the key clinical trials that are currently ongoing that those are covered by those funds. So everything that you see on the pipeline chart and the trials that are outlined that are ongoing those are covered.
If your question is with regard to, is there anything that we will initiate on the clinical side or preclinical side in 2018 that is not on this pipeline chart. This would not be covered.
So to give you an example, if we were to ask now post that are currently ongoing – or the ongoing combination trial with Keytruda and were to add a follow on trial, that’s follow on trial in 2018 would not be covered, but basically the coverage of the ongoing portfolio..
Okay. It’s very clear. Thanks Florian..
And the idea is to – and the financing strategy made behind that is that we are saying there will be catalysts coming up throughout 2017 that will enable the Company to refinance beyond the year 2018..
Great..
We will now take our next question from Hartaj Singh from Oppenheimer. Please go ahead..
Hi, Adi. This is [Emma] on for Hartaj. Thanks for taking the question. So you mentioned that we can expect update on the development strategy for AFM24 in the first half of this year.
If you do move ahead with that program in solid tumors, what your plans for the back of care AFM21 and AFM22 in terms of like [bispecific] continued development?.
Yes. Just to recall what AFM21 and AFM22 were AFM21 is EGF Receptor variant III T-cell engager and AFM22 is the EGF Receptor variant III NK-cell engager. Talking about AFM22, this is meant as a back-up to AFM24 if we would have seen any unexpected toxicity.
We are outlining now our first tox experiment at AACR and we can discuss that by the strategy if we need to turn back to AFM22 or again continue with the AFM24, but in between the lines you're going to see that AFM24 is at the moment very – is performing very nicely..
Our molecule, EGF Receptor variant III is very potent, is very specific and we have further only investigations on target expression ongoing and once these experiments are concluded and we can determine again their relevance of variant III in certain tumors, we may come back to reprioritize AFM21 T-cell engager.
So that’s a separate asset and as it is with T-cells it's meant to be probably also associated with some more side effects. We are indeed in a good position to have identified such a specific antibody of that virtually not binding to any wild-type antigen.
So we have two approaches that we could do in the future, the NK-cell approach with AFM24 is definitely of very high priority as it take us into solid tumors, but AFM21 also tracking what others are doing. We may revisit and thereby can bring it back into our development strategy..
Okay, great. Thank you..
We will now take our next question from [Ken Colin], a Private Investor. Please go ahead..
Hi Adi, just a couple of questions for you on AFM13, is the Phase Ib trial was Keytruda successful, do you continue to plan to advance the registrational trial? And my second question for you as we know that in the first cohort, we had two partial responses, what kind of response rate or results are you looking from the second and third cohort to see significant response between AFM13 and Keytruda?.
Okay. Yes, indeed.
So in terms of answering your first question, do we see ourselves in an opportunity to move ahead with this trial under the Affimed leadership? That particular approach would most likely be aimed for a third line treatment, currently Keytruda is tested against brentuximab in that particular setting and the data will be based on PFS, so hence duration of response and from what's currently has been published, it seems that Keytruda has a better PFS as compared to brentuximab vedotin.
Obviously, these were independent studies when there was no direct comparison, but the difference in PFS is quite remarkable. So that means that obviously Keytruda could end up in a third line setting and this is exactly what we're currently would be going forward in the future. So our goal is to show efficacy over Keytruda alone.
What we have currently seen is that either Octavio or Keytruda come back at least after three months with very similar objective response rates. Octavio has shown roughly 10% CR rate and Keytruda has shown three months objective response rate of roughly in the range of 13% to 14%. So we're definitely looking to improve that.
However, it will still remain quite challenging to draw any conclusions. After the first nine patients, the numbers that we can – so that the patient number will still be far too small and in order to draw a conclusion, we have to wait until the dose cohort expansion has been completed..
Okay. Thank you. End of Q&A.
There are no further questions from the telephone..
Thanks a lot for your interest and for your questions, very compelling and we look forward to providing an update in due course in our next earnings call. Thank you very much..
That will conclude today's conference call. Thank you for your participation. Ladies and gentlemen, you may now disconnect..