Q4 2021 Affimed NV Earnings Call
Good day, and thank you for standing by welcome to the <unk> 2021 financial results and corporate update conference call.
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After the speaker's presentation, there will be a question and answer session.
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I'd now like to hand, the conference over to Alex <unk> head of Investor Relations. Please go ahead.
Thank you Liz and thank you all for joining us for our call today before we begin I'd 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.
Audi Harris, our Chief Executive Officer, Andreas hard strike, our Chief Medical Officer Arent Shaquille, Yes, our Chief Scientific Officer, Wolfgang Fischer, Chief Operating Officer, Denise Mueller, 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 is.
These forward looking statements.
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 look.
These statements and the press release that we issued today and filed with the SEC.
With that I'll turn the call Thats why I D.
Thank you Alex Good day, everyone and thank you for joining us for our full year 2021 financial results.
Operational progress update.
I would like to start the call today by taking.
A moment to thank all of our employees collaborators and patients.
For the 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 everyones dedication passion and belief.
In our work.
I could make employees an ever growing multinational team.
Very talented individuals from around the world in particular from all places in in Europe .
Indeed, the events that have recently unfolded in the Ukraine.
Of particular concern to me.
All our colleagues at estimate.
Let's say I'm very proud of the way that our colleagues have pulled together in.
In support of Ukraine in whatever ways, we can we have a few employees.
Organization and.
That 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.
Cranium colleagues and those who have loved ones and family.
That country.
With that I want to turn it over.
To give you an update on the progress that snapshot has been given by me but.
All of my colleagues will contribute to.
2021, once a year of many transformative achievement for us in the company.
A year, indeed in which we laid the groundwork for what we hope to accomplish in 2022 empty on and.
And for great in 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 independent gateways with that metric.
By the end of 2022, we expect to have three is highly engaged.
<unk>, which we believe will be the basis for continuous data flow over the next several quarters.
As shown on slide three of our presentation development efforts for each of our <unk> selling data 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 units that engage our molecules as mono therapy.
And in combination.
We are very pleased to have clinical proof of concept data.
Or aes in 13.
Which provides key validation for our approach to developing our molecule as mono therapy.
In combination with natural killer cells and checkpoint inhibitor.
This proof of concept support the three pronged approach that we are applying to development strategy for all our other cell engaging molecule.
We believe that by giving patients novel treatment options, we have an opportunity to.
<unk> to potentially develop blockbuster therapies.
As an example.
<unk> now as shown on slide four.
Targeting several <unk> positive lymphoma, we'll be able to address several patient population.
<unk> initially with relapsed and refractory peripheral T cell.
The development approach.
T cell lymphoma will be able to impact the life of approximately 500 patients just in the U S.
Earlier this year, we announced the completion of enrollment in our <unk> study, which focuses on peripheral T cell lymphoma.
And we are on track to report top line data from this study in the second half of 2020.
This indication however represent only a small fraction of the entire <unk> opportunity, which includes patients with Hodgkin T cell and B cell lymphoma.
And according to our analysis. These indications hasnt annual incidence of approximately 20000 patients in the U S alone.
Now in December of last year.
We presented compelling data of <unk> in combination with metrics.
As you May recall, a unique feature of our internet selling data as the very high affinity.
And the specificity to <unk> 69 allow.
Allowing the pre complexing of natural killer cells, with <unk>, which now forms a stable call like.
In paint complex.
In addition.
We are further dosing with <unk> monotherapy.
Our unique option for our selling data and differentiated from what you can do with car NK cells.
We believe that data from 13 infusions.
Alright, targeting donor derived and patients own NK cells, and potentially macrophages, thereby contributing to the efficacy.
In that trial, we reported an unprecedented 100% objective response rate after just a single cycle of treatment for.
13 patients treated at the recommended phase two dose.
Now based on this impressive data.
We believe that we can address the unmet need in additional indications that I mentioned earlier through the same development approach of combining Ags <unk>.
<unk> with natural killer cells.
Now our initial target population is relapsed refractory peripheral T cell lymphoma and talks can pullback.
Which now comprises 305000 patients just in the U S.
But we have the plan to expand the label to include frontline.
Protein cell lymphoma, and relapsed refractory b cell lymphoma in the.
Second wave, which now creates an opportunity to address about 7% in the hospitals and patients in total in the U S.
Importantly, our initial market research also indicates that we may have an opportunity to price the AFM 13, NK cell combination therapy.
Premium two 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 car T approaches.
In addition, our ambition for you from 13 is to make a globally available for patients.
Oh need these treatments either as monotherapy or in combination with metrics.
The combination of all of these factors now gives us confidence.
A very significant market opportunity for <unk>.
Now, let me switch to a 24 hour egfr expressing <unk>.
Targeting immune cell engagement.
Wherever you have embarked on a broad development strategy.
The opportunity for <unk> in.
The market opportunity for <unk> from 2004 as shown on slide five.
Of that presentation.
End of last year.
We achieved a key milestone for <unk> from 2004 through the identification of the recommended phase two dose of 480 milligram flat dose weekly and.
And here too we are implementing our three pronged development strategy, which includes the initiation of three studies investigating various egfr expressing solid tumor indications now totaled nine court.
Remember what I said earlier that we already have clinical proof of concept play from 13 as mono therapy 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 electric content.
Colorectal cancer is represented in two out of the three studies.
Andrew we are further targeting other key egfr expressing tumor types, such as renal cell carcinoma.
Head and neck and gastric cancer.
Now non small cell lung cancer and colorectal cancer are by far the largest EGF are expressing indications.
With a combined relapsed refractory patient population in the U S. Over 130000 patients. So this number clearly tells you that these are in high need of novel therapies that does differentiate.
Here again, there is a significant opportunity.
These patients need better response rates drugs with better response rate and the duration of response Ob existing therapies that as we have already outlined to have clear limitations not just on the efficacy side, but also on the same.
Let me switch shortly to over over to two.
<unk> thousand eight yet a preclinical.
But we will spend some time, explaining you the background of <unk> from 2008, and why this becomes very important or estimate.
So are you from 2008, our CD 123 tumor expressing targeting selling data.
Initially planning to target patients with relapsed and refractory.
Acute myeloid leukemia.
So with AML AML is the most common form of leukemia with over 40000 patients diagnosed in the seven major markets every year.
And over 11000 in the relapsed refractory setting in the U S alone.
So I guess in 2008 is currently prepared for clinical evaluation.
And as I will explain later, we believe that any from 2008 is ideally suited to address the needs of AML patients.
And we are planning to submit an IDE application during the second quarter of this year.
Following a pre R&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 chief NK churn and other third parties to ensure access to an off the shelf crowd precise metric for further development.
With our.
<unk> engaged a therapy.
We expect to provide additional updates on NK cell development now during the second half of this.
Our progress.
Data and the opportunity represented by our tolling data program has also captured the attention of potential future partner in particular, our data that we published in December .
There was a very good momentum around our ability to clinically execute our program supported by strong data and there is interest from the pharmaceutical industry to further explore our rock platform and sell engage a molecule.
Can add value to these parties existing pipeline and oncology franchises.
We also continue to advance our work with our existing card a key feature that has enabled these partnerships is the differentiated performance of our <unk> selling nature when compared to standard based tumor with a particular advantage in addressing tumor cells with low.
Target expression and also with a unique features that we have shown for the combination of opportunities.
In the case of <unk>, we have made progress in various preclinical program and has begun to hand over molecules to genentech for that development.
Our partnership with ROI event on <unk> 32 is strong.
<unk> has moved into R&D, enabling studies.
Updates on these programs.
Alright, it is at the discretion of our partners.
We remain eligible for additional proceeds from these key collaborations in the near term.
Including being eligible for preclinical milestone and smallest milestones based on regulatory achievement and also clinical progression.
Finally growth strengthening our organization and advanced our Lithia.
And our recruiting highly talented scientists and industry experts to help us execute our mission now with this I will turn it over the call to Andreas to give you.
More color on the progress of our programs.
Andre.
Yes. Thank you.
Also from my side, a warm welcome to our audience.
It is 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 13.
Which you can see on slide six.
As you know we have two ongoing studies will tell you that from 13.
Including the registration directed study.
Oh for AFM certain as mono therapy.
In relapsed and refractory <unk> patients.
Also known as redirect study.
And in addition, our phase one two study in collaboration with MD, Anderson, where we evaluating a cord blood derived natural killer cells pre complex.
13, and followed by a single agent <unk> in.
In patients with relapsed and refractory <unk> positive lymphoma.
As you mentioned.
Very proud that we have completed enrollment into the redirect study.
Registration relevant PTC cohorts in January .
We believe this is an important milestone.
In the light of very challenging environment that we have been facing over the last two years.
A total of 108 patients with relapsed or refractory peripheral T cell lymphoma <unk>.
Has been treated or are being treated with AFM 13 in this trial.
And we expect top line data for the second half of 2022.
The focus of initial data will be the overall response rate.
So assessed by a blinded independent review committee.
And also a preliminary assessment of duration of responses.
Of course, taking into account that the majority of it.
Maturity, obviously 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 wasn't observation cohort for patients with transformed mycosis <unk>.
And fifth Covid is still impacting the treatment.
The response assessment of six patients.
Decision was taken.
I think it's important to remember that this cohort C was mucosal fungal <unk> patients was observational only and not part of the intended registration package therefore not impacting.
Ability to submit three cohorts in peripheral T cell lymphoma.
Let's now turn to our second active study with <unk>.
Awesome 13, 1% for.
Where we are evaluating the efficacy and tolerability of cord blood derived natural killer cell pre.
Pre complex with AFM 13, and.
And followed by AFM 13 mono therapy.
In patients with relapsed and refractory <unk> positive lymphoma.
In December we reported interim data showing a response.
On the response rate for the first 19 patients enrolled into the study.
This included the response rate after two cycles for the first six patients.
That were treated at lower dose levels of one times 10 to the sixth and one times 10 to the southern South respectively.
And the response rate after only the first cycle for the surge in patients treated at the recommended phase II dose of one times 10 to the eighth cells.
At that time, we had demonstrated an impressive antitumor activity was 100% objective response rate.
And just 38% complete response rate for patients treated at the recommended phase two dose after only one cycle of therapy.
We are very excited that the abstract submitted to ACR by MD Anderson cancer Center.
For study <unk> 104 has been accepted at a very prominent place for oral presentation in the clinical trials plenary session.
This session will be hosted from one PM to three PM on Sunday April 10.
In addition to MD Anderson.
This presentation will also be featured at the AACE Our press conference on Sunday April 10.
It's this ACR presentation Jago near two from MD Anderson, who is the principal investigator of the trial.
I'll provide updates on the first 19 patients enrolled in the study.
Of note. The update will include the response rates overall response rate and complete response rate.
For certain patients treated at the recommended phase two dose now after two cycles of therapy.
<unk> Ultra show additional follow up data as compared to the data presented in December .
As you know we have seen some evidence.
Of deepening of responses.
The lower dose cohorts between cycles, one in cycles too.
And therefore, the final response rate after two cycles.
Therapy for patients at the recommended phase two dose.
I'll allow a very good assessment of the true potency of this treatment.
Also FDA has approved an amendment for the study.
Which allows us to increase the patient population treated at the recommended phase two dose to 30 to 40 patients with <unk> positive lymphoma.
And allows us for the treatment of patients with more than two cycles of therapy.
Westy Gate Us discretely.
Let's turn now to <unk> 20.
<unk> 24 on slide seven.
During 2021, we identified 480 milligrams of <unk> for once weekly.
That's the recommended phase two dose for our mono therapy.
With this key milestone behind US we have now initiated enrollment.
The expansion phase of the mono therapy from 2004 trial at the recommended phase two 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 as the dose escalation to collect additional safety information and have completed enrollment in cohort seven treating patients at 720 <unk>.
We will present data from the dose escalation phase of <unk> from 24 101 trial.
Thats the ACR annual meeting.
Mainly focusing on.
Pharmacokinetic and Pharmacodynamic data.
And highlighting irrational and the foundation for the RP two do you see that.
The poster will be presented during this phase one clinical trials 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 the recommended phase II dose.
And we provided the status of the clinical response assessment for patients through cohort six.
<unk> presentation will include more granular analyze this helps these data points.
And as a cutoff date of October 29 for the ACR presentation. There were 29 patients dosed with <unk> from 24.
More recently, we have also initiated two combination studies.
The first study from 24 102 is investigating the combination of 24.
Roche PDL, one inhibitor at Liza Liza.
To treat patients with non small cell lung cancer.
Egfr Wild type <unk>.
Guests trick and Gastroesophageal junction adenocarcinoma.
And pancreatic hepatobiliary and good early tract cancers.
The second study.
For one of three.
Is investigating the combination of <unk> hundred 24 with <unk>.
K O one.
So ex vivo expanded and activated ultra logos NK cell product from NK Gen biotech.
Here, we are treating patients with non small cell lung cancer.
Squamous cell carcinoma, obviously head and neck.
And colorectal cancer.
Through the three ongoing studies, we will be evaluating safety and efficacy I'll tell you from 2004.
Nine indication specific cohorts with a particular focus on non small cell lung cancer, which was represented in all three studies in colorectal cancer represented to us to switch studies.
As announced earlier, we expect to have 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 <unk> 2008.
I'm happy to hand over to arent, who will give you an overview of the rationale and our plans for this program Orange. Please.
Thank you Andreas and good morning, and good day to everyone on the call. So for me.
Today has already introduced I would like to discuss with you the story behind <unk> and 'twenty eight.
Start with the high <unk>.
Thats medical need in AML as shown on slide eight.
First available treatments that are effective in AML, often toxic and tolerated only by a fraction of patients second Africa.
Efficacy of currently available treatments is still limited.
And either primary incomplete responses or early relapses you.
Usually within the first 18 months are common and third once refractory or relapsed. The outlook is dismal with only three of 10 patients will lap up to one year.
One out of 10 patients after five years because of a lack of effective treatments for relapsed or refractory disease.
What is urgently needed.
Treatments that work and most patients are effective and safe.
Then towards the late relapsed and work in relapsed or refractory disease.
With 828, and it's NK cell based mode of action. We believe we can address these needs.
I'll provide more context I would like to give you a brief overview of occurred treatment options.
And explain why we strongly believe in the potential of <unk> from 28.
Approved treatments for adult patients with newly diagnosed AML chemotherapy, mostly urban Don Robinson with or without <unk>.
On that positive milestones the MTS CD 33.
Antibody drug conjugate and the only approved antibody with.
<unk> three inhibitors <unk> inhibitors, we need to collect plus hypo methylate agents a society.
<unk> bin.
Or.
<unk> plus low dose cytarabine.
The choice of treatment depends on where the patients can tolerate intensive mission induction therapy on cytogenetic risk and the presence of <unk> mutations.
However, even though these treatments can be initially effective and used for emissions. The majority of patients will fail to achieve a long lasting complete remission or will relapse early.
About 60% of the patients will show progressive disease within a year.
Hip patients may be candidates for allogeneic hematopoietic stem cell transplantation, which is still considered only curative option for patients with AML.
Options available to patients who are not eligible for allogeneic transplant.
Or who relapse after transplants or limited.
Treatment options available for these patients include further chemotherapy aggressive or less aggressive depending on patient stages and use of hypo methylated agents or targeted agents like <unk> three inhibitors <unk>.
<unk> two inhibitor is indeed treatments in the context of a clinical trial has recommended.
A multitude of therapeutic options have been are investigated clinically in relapsed refractory patients, including targeted agents adcs monoclonal antibodies T cell based therapies. However, so far none have provided convincing evidence for broad effectiveness and durable risk.
Sponsors and relapsed and refractory disease.
Over the past years, it has become clear that conventional therapeutic approaches for example, monoclonal antibodies directed against different targets like CD 33, or <unk> 23, or even effector function enhanced antibodies have not resulted in meaningful therapeutic efficacy in AML patients.
The use of targets.
Play a role in AML disease Biology, also T cell engagements and car Ts.
Respective target choice, such as CD 33 to the 123 of our CLO lung et cetera have not achieved acceptable tumor response rate and durability.
Although the picture looks different little different when clinical data of Adcs are analyzed.
Not efficacy that's lacking the issue is the challenging toxicity.
In this context review model it's hard.
The CD 33 targeting ADC.
As a molecule that in principle is effective in AML.
Therapeutic use is limited by the fact that this molecule is not employing the promising effector function of NK cells, which by themselves have shown clinical efficacy in AML.
There is further clinical data from other adcs targeted against CD 33 that have shown higher efficacy high efficacy, but are limited due to their toxicity.
In addition to Molotov CD 123, directed ADC GM.
Gen 632 <unk>.
It's currently in clinical studies.
When we looked at all the available research literature, we concluded that CD 33, and CD 123, directed approaches show efficacy in AML. However.
Could be an advantage to using 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 blood or peripheral NK cells to treat ml have demonstrated encouraging activity.
When analyzed which of the above approaches monoclonal <unk> T cell engages car T cells, adcs or innate cell engages can best address the needs to increase the basal efficacy of NK cells.
Except for monarch fault colonial's non has the option to activate NK cells, and even monoclonal <unk> have huge limitations in their ability to redirect NK cells as such it became obvious to us that this was.
This is an ideal set up to generate an innate cell engage of based on our rock platform. Let me explain in more detail why we feel that our innate cell engagement can be broadly effective in AML.
And why do we see particular potential in its combination with adoptive NK cell therapy first.
<unk> NK cells have been used in the treatment of AML and different settings in the past and have shown promising efficacy.
Proximately 30 to 40.
With approximately 30% to 40% overall response rates second.
<unk> innate cell engages a highly differentiated bispecific antibody is designed to specifically bind the NK cells with high affinity.
Third.
With recently shown that the combination of an ICU 13 with NK cells produces impressive overall response, and CR rates and very difficult to treat patients and fourth with selected CD 123 is the target from 28 as it is not only expressed on the glass itself AML patients, but importantly.
It is also expressed on the leukemic stem cells.
Which are the constant source of malignant cells and AML.
June us deeper and longer lasting remissions eradication of these leukemic stem cells is crucial.
This is in contrast to for example, CD 33 targeting antibodies.
Our antibody drug conjugates, which lack the ability to also target leukemic stem cells and <unk>.
Also exhibited toxicities.
<unk> 28, Ics designed to elicit a deeper and longer lasting responses by.
By depleting leukemic stem cells as well as AML blasts.
April 28 is significant improvements versus normal or FC enhanced antibody and its ability to effectively recruit NK cells to kill tumor cells.
Ill explain these differentiating factors.
We believe in Ice's may offer advantages in targeting CD 123 is this target is only moderately expressed and we believe high affinity and specificity targeting of <unk> as an essential factor and redirecting NK cells to kill cancer cells as you can see on slide.
Nine.
Highlight that our preclinical work, which we recently shared at Ash shows that F. 'twenty eight activates NK cells more potently than an FC enhanced anti CD 123 antibody telecom Susan.
Resulting in increased efficacy.
When compared to this FC enhanced anti CD 123 antibody based on 28 was also more active against primary AML blasts from patient peripheral blood and bone marrow and also more active against cells with low <unk> expression.
As a result.
We expect the data from 28 will be less affected by baseline characteristics.
Francis and CD 123 expression.
And has the potential to induce deep responses.
<unk> Hyatt efficacy against AML cells with low levels of CD.
100000 free expression.
This could be a strong differentiator from 28 bps on targets competitor antibody drug conjugates in the space IMG and $6 three two which appears to be affected.
Differences in CD 123 expression.
Based on prior testing of telecom system of an FC enhanced anti CVT 423, <unk>, one and a phase one clinical trial in AML patients.
And complete remission with measurable.
Minimal residual disease, and our preclinical data, suggesting superiority of <unk> 28 over <unk>.
It would not be unreasonable to expect single agent activity of <unk> 28 in particular in patients with low burden disease, such as <unk> positive AML.
Conversion of patients to MLD negativity isn't expected to be clinically meaningful.
On the prognostic significance <unk> status on PFS and overall survival.
Our preclinical studies with <unk> from 28 have also demonstrated low risk of cytokine release syndrome, which further differentiates the strong drug conjugates from CD 123, CD three Bispecific T cell recruiting antibodies currently in development for AML, which all exhibit varying degrees.
Of cytokine release syndrome, including Crs related death.
We are particularly excited about the potential of <unk> 28 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 <unk> from 28 with adoptive NK cell therapy, meaning by redirecting allogeneic NK cells to CD 123 tumor cells, we believe <unk> could increase the depth and duration of response necessary to meaningful.
Prove 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 data from 28 is available from the first in human dose escalation trial.
<unk> strategy to initiate combination development will need to be discussed.
Regulatory authorities, we plan to provide additional details.
A later point in time.
With that I'll hand, the call over to Angus to take you through the financials.
To take any questions during Q&A.
Thank you art.
Our balance sheet and income statement highlights on slide 10, and 11 of our presentation.
I would highlight that <unk> consolidated financial statements have been prepared in accordance with IRS issued by the international accounting standard board or ISP.
The consolidated financial statements are presented in Euro, which is the companys functional and presentation currency. Therefore, all financial numbers that I'll present on this call unless otherwise noted will be in Europe .
We ended 2021 with cash and cash equivalents of $197 6 million euros compared to $146 9 million euros in December .
December 31 2020 base.
Based on our current operating plan 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 31, 2021 was $86 6 million euros 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 broadband as well as the milestone payment received pursuant to our collaboration with Genentech.
Total revenue for the year ended December 31, 2021 was 40.
4 million euros, compared with $28 4 million for the year ended December 31 2020.
Revenue for 2021, and 2020 predominantly relate to Genentech and ROI math collaborations.
Collaboration revenue for the year ended December 31, 2021 amounted to 39 3 million euros with $21 6 million coming from the Genentech collaboration and $17 7 million coming from the ROI of that collaboration.
Collaboration revenue.
For the year ended December 31, 2020 amounted to $27 8 million euros with $26 2 million coming from the Genentech collaboration and one 4 million coming from the ROI math collaborations.
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 FM 24 and <unk>.
Including cost 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 II portion of the trial investigating AFM 13 pre complex with cord blood derived natural killer cells.
General and administrative expenses increased 77% from $13 7 million in 2020% to $24 2 million euros in the year ended December 31 2021 the.
The increase predominantly relates to higher share based compensation expense in 2021.
And increased earned premium higher consulting expenses.
Net finance income for the year ended December 31, 2021 was $6 5 million euros compared to a net finance loss of $6 6 million for the year ended December 31 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 31, 2021 was 57 $5 million 48 per common share compared with a net loss of $41 4 million.
<unk> 50 per common share for the year ended December 31 2020.
The weighted number of common shares outstanding for the year ended December 31, 2021 was $119 $5 million we.
We encourage shareholders to also review our 20-F filing for the year, which will be filed with the SEC today I will now turn the call back to <unk> for closing remarks Ali.
Yes, Thank you I guess.
And.
So you've heard a ton.
2021.
Why don't we.
Issues out there and it has been.
Really fantastic year for proximity.
What programs forward, but we have this unprecedented data.
<unk> and our cash position is strong as shown on slide 12.
We're now moving forward with multiple programs our lead asset <unk> registration directed study.
<unk>.
We can report the results.
In the second half of <unk>.
We see a more important to us now that we have found a way to address the full breadth of.
I think as <unk> positive lymphoma.
Obviously thats based on the recently published data of <unk> in combination with that with metrics.
Within natural killer cells.
We have not only presentation key presentation at ACR and also later in the year, we will have the opportunity to go after the impact of our treatment on both luxury Hodgkin lymphoma part, but you also believe in non Hodgkin lymphoma patients.
Which would mean that we have now all the ambition to make any from 13 available to patients with a wide range of <unk> 13.
<unk> positive lymphoma.
Im going to provide more update on that in the second half of this year.
Addition to our way forward with here with the NK cells.
<unk> is a completely novel drugs that we designed.
With a strong.
Component and we have now reported the initial data.
In 2021.
We felt that achieving this milestone with a recommended phase II dose at 480 milligram is now a key milestone for us because we are now testing.
Oh from 22 point as a mono therapy, but also in different combinations in that.
Indications with the highest likelihood of a response we are very excited that these studies are ongoing and look forward to present early 'twenty.
2022.
As we're proceeding.
And as we have learned with any from 2008.
We're addressing an indication where there is a significant medical need and there's arent explained we believe that our platform is ideally suited to build upon.
Basically if you could see of natural killer cells, and potentially inducing a deeper longer lasting response again.
With a strong rationale now derived from <unk> and the very meaningful responses, we have seen that in combination with <unk>.
With a metric kilograms.
So all of us the doctor might dedicate to giving back patients that you had the ability to fight cancer.
Vince.
With the recent data that's thoughtful selection of our programs.
Can help many patients that currently have no or very very limited options.
And as they're now learning the result of more interest from the pharmaceutical industry.
In this space, we also believe drip.
Driven by our strong data off and you can now thank you again for listening today and for continued interest in our work and we're now ready to take any questions.
If you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone telephone.
To withdraw your question press the pound key.
Our first question comes from Dana <unk> with SBB Leerink.
Hi, Thank you for that question and the update just a couple on ASM 13, and their rates are up study.
Firstly I Wonder if you could talk about the bar you expect for accelerated approval for our <unk> and duration of response and given that bar for duration of response and how much follow up do you think you'll likely need to be able to exceed that bar and then the second question is you know given you could get accelerated approval here.
When do you start thinking about commercialization and could we see some early.
Then on prepping for launch.
Yeah.
Thanks, Ron gradually address youre already on it.
Yes, I will take the first two parts and then when it comes to commercialization.
Back to you or to Denise.
So as you know we talked with FDA about the design of the study and then had to alignment on the design.
We never give you a clear guidance on let's say wants to see.
If we consider the environment there are a couple of trucks.
Achieved accelerated approval granted accelerated approval in peripheral T cell lymphoma. This includes H duck inhibitors.
And in that type of lives.
Consistently as these trucks have shown response rates in the 2007, 2008% response range.
Duration of response was somewhere around eight to 10 months.
So I think this constitutes some kind of a floor, if you will or lower basis.
You would need to achieve for them for us would be considered excellent right at approval.
Now in terms of C. A follow up again, it will depend on the duration of the responses.
We do have roughly.
Close to a two year recruitment period. So this will have an impact also on months of follow up.
We have not done.
Really modeling, yes, we will do so when we get closer to our topline results that we plan to.
<unk> second half of 2022.
And I think for the commercialization aspect.
Denise.
I'm happy I'm, having I'm happy to jump in here. Thanks for the question Dana.
Right. So if we are in a situation, where we receive and accelerate approval the market development.
We have seen pretty much now so what we've done as an organization and we are adding key talent.
<unk> experience.
Collagen marketer.
Who will be joining us next month in order to.
And the appropriate market development, we have key positions and Kols engagement that had been recently added and we are also adding a key talent in the area of market access and payer strategy coldly, joining us and in about a month's time.
All of these talents that have been added to the organization augment what we already have we have about.
Between about three of US who will have marketing and our background, probably 90 years in pharmaceutical marketing and launch experience across multiple indications. So we feel that we're well positioned to do the appropriate.
Prelaunch market development activities in a very efficient effective and focused manner.
In order to de risk any commercialization that could happen and come with an accelerated approval.
That's very helpful.
Thank you very much.
Our next question comes from prepaid Americana truest.
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 expectation for data in second half from Ethan 13th.
CB NK Commvault now that the FDA has approved multiple cycles.
And you've talked about this being a more material update can you help us understand how many patients I know it maybe a little too early but just ballpark and also.
Can 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 <unk>.
Yeah.
And Chris do you want to take it all.
I will start so as you know.
The study at MD Anderson.
Ongoing Android we continue we're continuing to enroll patients.
The amendment allows us asset for 40 in total.
The initial focus will be on Hodgkin's, but we do have non hodgkin lymphoma patients on the study as well and.
We will also be amendment covered and non Hodgkin lymphoma patients with PD study.
Positivity, so really expand our knowledge and our database beyond Hodgkin.
No.
As I mentioned, we have already seen deepening of responses in the low doses.
Of course.
We'll give a better overview answer actually recommended phase two dose response rate in CR rate after two cycles.
And as we see individual patients.
Again, the option to administer more than two cycles, you said investigators discretion, but we believe there will be patients who benefit even from more cycle also given the very excellent toxicity profile.
Now this totality of data with longer follow up with more patients with Monica from cycles move form our database for is it discussions with whatsapp.
With SBA.
I think we will bring a couple of different strategies forward as already said, our focus will really be to align with FDA and then.
<unk> is approved would pass that bring Sis important treatment to the patients in the shortest possible period of time.
Yes.
Thank you Rick.
Sure.
Was there something outstanding there were so many questions.
Uh huh.
I just had one more question.
Back to anything at all.
I know you have said second half is where we can expect this but any update planned it at all.
I'm, sorry, I think I can take it.
Discussing this with.
With MD Anderson.
Any additional updates currently in this stage.
Our plan together with.
And so just.
So stay tuned until we announce it appropriately.
Okay, great. Thank you.
Our next question comes from Maury Raycroft with Jefferies.
Hi, Thanks for taking my questions.
I was going to ask one on AFM 'twenty four you said in the past for the individual <unk> and 'twenty four 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 youre going to be looking for in terms of.
A number of patients in response rate and durability and what could be included in some of the updates that we see later this year.
Yeah.
Thank you Mark.
As you know the.
All of mine expansion.
Cohorts are built on a Simon two stage design.
Has the first interim look.
At 10 to 12 patients.
And then what.
Or would you start with a specific cohort. We continue we have not disclosed the targeted response rates per cohort is also.
Also vary across across cohort Mark if you look at these deals like pancreatic come with it will be a little bit difference than in diseases like renal cell carcinoma.
As these are open label studies of course, we could also give interim updates.
Which we planned for the second half of 2022 now.
Now remember that also see combination studies.
NK cell combination study as well as the.
Because at least roadmap combination study have safety run in with a little bit lower dose of 24.
Before we can escalate up to the full dose.
So that will also be an emphasis especially in this dose escalation safety.
<unk> probably be the data package that you will.
At the end of 2022.
Got it that's helpful and maybe a quick follow up just to clarify for your poster at AAC or is that going to include follow up data on six patients at a recommended phase II dose and we will.
Will there be any data in the poster from the 720 Meg dose cohort.
There will be some follow up as we said our.
Our main focus here is on PK PD, and then really showing all Oxley retro know that went into the 480 milligram distributions recommended phase II dose.
720 milligram cohort is still ongoing treating patients. So we would not have data on 2020.
Got it okay. Thanks for taking my questions.
Our next question comes from Brad Canino with Stifel.
Yeah.
Okay.
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 topline release, because you mentioned the trial has been enrolling for about two years and it finished this past January so it would be reasonable to us.
Expect a median follow up of around one year and I guess, if that's true would.
Would that be sufficient durability to be ready to go towards a registrational path pretty soon after that thank you.
I'm sorry.
That said, we have not done.
<unk> modeling.
Thank you our assumptions that we could have a meaningful up around 12 months is probably correct.
We will have to look at the kinetics of see progressions.
To make a call how maturity state or how many potential events are still outstanding.
After the interim analysis that we conducted after 20 patients we have really not anticipated base too.
Protect the integrity of data. So this was something that we will address.
To come in between now and.
<unk> disclaims drops.
High level data.
Okay.
Okay. Thank you.
<unk>.
Our next question comes from Lee <unk> with Cantor Fitzgerald.
Hey, guys. Thanks for taking the call maybe first on the upcoming ACR presentation.
Wondering if you can how to sort of setting expectations for your answers I mean, it's a painful okay.
It sounds after the second cycle or is there anything else that we should be focusing on and also can you share what kind of data.
<unk> for you.
The FDA and with Coty.
Restriction on path for that can come down.
Also talk about maybe different outcome.
Okay.
Andreas.
<unk>.
Oh.
So for ACR.
<unk>.
We will have in focus of course on response data.
Or is it all 13 patients are fully treated with two cycles.
Of course, there is longer follow up so that will be most of these data available.
There will be toxicity data there will be some initial translational research data so I think it's.
It's a quite.
Quite comprehensive package trend.
I think being selected for the planned recession.
Probably also an interesting remark.
So we are really looking forward to this greater.
Terms of FDA discussions as I mentioned, we of course.
Look into broadening our experience with a more heterogeneous patient population, which will enable us to discuss a couple of different pathways.
How do you said we are also looking at NK cell.
Biology NK cells.
So we play into the timing of a potential FDA discussion.
We expect to give an update as how would you say the second half of this year.
Okay got it.
I also have a follow up on <unk> and 'twenty four.
I mean, you are testing a lot of settings and expand.
Cohorts and just wondering if you cut came out with some guidance on the cadence of the data for this year and then should we expect data from certain cohorts maybe too.
<unk> laid out earlier than others.
Should we assume that we might see some interim data.
Data read out from any of the cohorts this year.
I think it's too early to specify which was.
Corporates will enroll.
That's a different.
Okay.
Of course, there are some differences in the frequency of certain diseases, most small cell lung cancer colorectal cancer.
Probably a little bit more frequent.
We are interested in all of these indications.
On the clinical operations front, specifically added also some sites with <unk>.
Higher volumes of if you will a rare cancers like two.
Biliary cancer renal cancer.
Before we see the enrollment and those sorts of things, it's too premature to speculate whether a certain cohort can maybe faster than another.
We believe that the biological rationale for all six cohorts.
As shown in that.
Correct, we are getting from our.
Yes, the guidance, we have come on board.
All three studies are open.
<unk> patients.
Again, we are confident with our guidance to show initial data second half of 2022, but.
And with the cadence of this will come as well.
So we get a little bit more experience.
Across the different sites and across the different cohorts.
Got it thank you.
Our next question comes from Yale Jen with Laidlaw.
Good morning, and thanks for taking the questions.
Got one strong and investors and just which is that <unk>.
Recently, some of the single well maybe rent non randomized study initially.
Initially thinking for authority approval has been sort of rejected by FDA and.
Do you see any potential impact on the right direct.
Uh huh.
He was your path or do you feel that this is a very different sort of a type of drug versus others.
<unk> being being being treated that way.
Yes, I think.
Accelerated approval.
It's very hard to make any kind of conclusions from one study of <unk> setting tool together setting. So FDA has been quite clear in what they like to see Chris.
First of all you need.
It needs to perform your study in an area of unmet medical need.
After discussions with FDA I think we have a good definition here.
And then you have to provide a robust data set.
Is likely to predict to assure a good marker.
Finally clinical benefit and again this.
Quality really various wherever we are.
Settings, where our response rate alone predicted clinical benefit circumstance, where our response rate in combination with duration of response will be regarded as an adequate surrogate in Europe .
I think from a response rate does not correlate with clinical benefit in these settings of course I'm not.
Suitable for accelerated approval.
We addressed all these points in our initial discussions with the FDA. So we would not see where I would not see any.
Kind of cross crush.
Yes.
Correct.
Correct.
Got it.
Granted accelerated approval.
It's almost a standalone issue with these variable.
But if you control and controls is variable.
I think after the approval of the data center.
Okay, Great maybe just one quick follow up body weight, just a you mentioned after the reporting of the 13 data lastly.
Lastly, in our velocity are you getting.
Additional sort of partner ship I.
I guess the discussions.
Do you feel that.
13 could be a potential also to be partnered or this is something you want to keep in house for moving further.
Good question somewhere in what we've been doing since December we've had numerous meetings with the.
The pharmaceutical industry and.
We're still consolidating.
The interest we're seeing so.
We have been starting to prepare commercial team that is capable of taking drunks full but now the partnering can have a lot of assets. It can be a pure licensing it can be a co commercialization.
So we're now exploring business see what the benefit is.
But what I should say the interest in what we do is is broader than just any from 13.
<unk> hundred 13 is a strong read through into a year from 24 and down from 28. So there are numerous opportunities including our.
Pipeline, we haven't mentioned that we have some early stage candidates identified assume that's why you consider tier two.
So you see it as a whole menu.
And are we focusing on so we're not just like somebody comes in can pick we'd have to put a.
Our models behind every of our drugs, what we would want to achieve we have looked at the core.
On how to bring these drugs to market and then we are eventually wear.
Basically we have firm to actually built.
Built internally under which conditions, we would we would want to do this so we wouldn't want to do it or somebody could make sense.
That gives us all the optionality from a point of where we have a high degree of knowledge Knowhow in order to move forward.
Another question. Another entries for example, do we have to partner we don't know.
Completely it remains a discretion of Azimut want what we want we want to do and what we can do it.
Main reason is we have a reasonably strong.
Our cash position all he would say.
And.
And a lot of data coming up so we can also in parallel fee on the interest of all our investors of all our shareholders in order.
Supported.
We're very flexible and that's something that is important to us.
Okay, Great that's very helpful and congrats on the progress at this point.
Thank you.
Our next question comes from Xiaomi Chu with Bahrenburg.
Great. Thank you very much.
So a few questions on the.
On the <unk> 13 program, maybe the first one to follow up on the potential accelerated approval in PTC al.
If I recall correctly.
<unk> accelerated approval was granted probably more than 10 years ago and given the evolving.
But landscape.
Actually evolving attitude from the FDA on the single arm et cetera approval.
As you pointed out a surrogate endpoint of IRR.
But we also see last year Bristol Bristol.
Put out there.
<unk> inhibitor into syndication.
Granted.
Different mode of action, but how do you see.
That.
I can't change the dynamic with with the FTC.
And then just related to that have you planned any phase III confirmatory trials to support an accelerated approval.
Okay.
Yes so.
Okay.
Yeah.
As I said.
I think it's very hard to make any.
Prediction or conclusions from.
One case.
Accelerated approval or non granted accelerated approval to NASA case.
And as I said, when we were with FDA. We discussed many of the correct juristic set would be required for a data set that could support accelerated approval.
We have not.
Not to say that the landscape has.
Fundamentally changes.
Again, the removal of <unk> inhibitor was a very specific story.
And so I do not see a read through to what we discussed with <unk> to redirect study.
Of course, it is a prerequisite is if the data are strong and consistent to support.
Much.
So a good endpoint.
Unlikely association because of clinical benefit, but that's something that we will simply when we have our topline data available.
Now one of the requirements for accelerated approval of course is that you.
<unk>.
We will have to have a confirmatory phase III study and we are currently looking.
Into different options, how a phase III study could look like we have had an advisory board with.
PTC all experts to discuss some of these options we will follow up so if we should decide based on two things.
To go for an accelerated approval.
I think we also will have an appropriate phase III.
Corey study designed to discuss with FDA.
Great.
Just to follow up on the <unk>.
F <unk> with with NK cell piece.
Great.
Pretty complex trial.
Last time, you discussed the potential too.
Two.
To make the trial become a company sponsored trial.
I wonder what's the progress there last time, you disclosed youre working with.
<unk> identified a CMO, maybe you can use.
Some.
Based on that.
Yes.
I think thats changed on what we know what.
What we said in the past that we're working on with the CMO. We are working in order to produce the.
NK cell product.
Ambition is to obviously.
Crop protection NK cell product.
Exploring all our engagements with different entities.
Sell product from from other companies.
So we have been indeed learning a lot.
Around the opportunity to either pursue our own independently sell or to then do this in collaboration.
I would like to know more about that in the second half of this year.
All of that.
Aggressive that will also include then the strategy on how to take this drug forward.
Into a registration directed study, especially the strong data that we're currently generating use the basis. We now have a tour of Hodgkin lymphoma.
That just kind of expand to additional lymphoma.
All of that obviously is.
Valuable once we have.
A robust dataset, we're aiming at getting to this very robust dataset.
And one of the OLED is together we can we can then take that basically the strategy for months and bring it to you.
It's again premature to speculate it as of today, but it's all maturing one hour.
Great. Thank you.
I can squeeze one one question last question for F. 'twenty four patent maybe for Andrew can you talk about the overall confidence in each cancer types do we expect to have a go no go decision in the second half for each cancer type.
Thank you.
As I said.
We.
Sure.
We cannot make predictions on.
Many of these cohorts progressive.
Which speeds access we are starting right now.
We have selected these cohorts very carefully we believe that each of these cohorts has the potential to show activity that could be cleaner will be clinically meaningful.
So it's exciting for us and.
So we are currently enrolling patients in all three studies.
So we will see a good data in second half of 2020.
Great. Thank you very much.
Our next question comes from do Kim with Piper Sandler.
Yeah.
Hi, Audi and team thanks for taking my question.
Just one on <unk> 20 for the combination with NK cells.
I was hoping.
What you could tell us about NK Jens autologous NK cell <unk>.
Process.
Does it have the standard level of depletion.
Bridging therapy involved.
And maybe is this a potential option for the AFM 13 combo.
Or are you sticking with donor NK cells there.
Andreas sort of Atlas.
Let's start with <unk>.
It was a protocol that we currently have so.
<unk> once <unk> is an ultra local sell so that's very different from the MD Anderson approach, where we have allogeneic cells.
So the autologous cell is basically derived from the patient.
We were getting.
Sell through Leukapheresis.
And then Jen has developed a methodology to significantly expand and activate T cells.
Ex vivo and then we are re infusing the NK cells.
Now the number of NK cells that are infused re infused are significantly higher at four times 10 to nine.
But also unlike MD Anderson, we are giving weekly NK cell infusion. So MTN doesn't this one.
Fusion per cycle, and then followed by in three weeks.
13.
Giving a year from 24 weekly NK cells weekly so four times 10 to the mine NK cells per week to these patients.
So very different concept now since these NK cells are derived from the patient.
Residually, we do not need to infill depleting therapy.
As a rule of thumb for depleting therapy, an NK cell.
The treatment is.
To suppress the patient's own T cells, which would otherwise reject the allogeneic NK cell.
And we have learned set with one.
Of course, we're fulfilling for depleting therapy you have.
Window of approximately two weeks and then the patient's own NK cell.
T cell <unk>.
When it comes back on with reject allogeneic NK cells. So this is the reason why we cannot for example to weekly allogeneic NK cells.
We selected the <unk> specifically as they have shown.
<unk> moderate activity of a modest activity, but activity in combination with <unk> in non small cell lung cancer and also.
In combination.
With the Egfr targeting agents.
<unk>.
Some sarcoma based on activity and we believe that the synergy between <unk> and <unk>.
Seeing a worst wanted to be explored.
Now we also have surfaced that look at different other NK cell sources. Charles there is clearly has the option to also look at allogeneic NK cells in the context of solid tumors.
As I said the current Scott is addressing.
No question.
Great Congrats on all the progress thank you.
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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