Q2 2021 Affimed NV Earnings Call
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Good day, and welcome to <unk> second quarter, 2021 financial results and corporate update conference call.
At this time all participants are in listen only mode. So if you require operator assistance. Please press Star then zero.
After the Speakers' presentation, there'll be a question and answer session.
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As a reminder, today's conference call is being recorded.
I'd now like to introduce your host for today's conference call, Alex Food Akitas head of Investor Relations at alphabet. Please go ahead.
Thank you ladies I'd like to also welcome you all for joining us today for our second quarter 2021 results and operational update call before we begin I'd like to remind everyone that we issued the relevant press release earlier today and can be found on the Investor Relations section of our website on the call today.
Hey, we have are the following members of our management team doctors, Audi Hirsch, our Chief Executive Officer, and Brad How're strike, our Chief Medical Officer.
Andre <unk>, our Chief Scientific Officer, Wolfgang Fischer, Chief operating Officer, and Angus Smith, our Chief Financial Officer, the whole team will be available for the Q&A session.
Before we start quickly to go through the Safe Harbor statement today's discussion contains projections and forward looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this call except as required by law, we assume no obligation to update these forward looking.
Statements publicly or to update the reasons why actual results could differ materially from those anticipated in the forward looking statements, even if new information becomes available in the future. These forward looking statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied.
Statements and these statements due to various factors, including but not limited to those identified under the section entitled risk factors in our filings with the SEC and those identified under the section entitled forward looking statements in the press release that we issued today and filed with the SEC with that I'll turn the call over.
Two Audi Audi.
Yeah. Thank you Alex and good morning, everyone.
And.
Joining in for our second quarter update call.
Today, we're going to provide an update on our pipeline this person.
Progress on our ongoing <unk> 13 and.
If I'm a 24% from 28 studies in our plan.
What promises to be an exciting periods over the next few months for our company.
Before I do that quick summary off once we have accomplished so far.
In clinical and preclinical data confirms that our unique and innovative.
Turning eight shows are safe.
And has the potential to be effective in treating cancer patients.
Mono therapies.
And also in combination either with natural killer cells.
Or with checkpoint antibodies, such as PD, one PDL one.
Yeah.
As we move through ongoing clinical trials for what.
Our efforts are now focusing on identifying and targeting indications, where we believe our scientific discoveries will benefit patients.
By applying a three pronged approach mono therapy.
Therapy in combination with metric collateral and checkpoint inhibitors.
We're very happy to report that our pipeline remains on track for our registration directed study of <unk> from 13 monotherapy in relapsed or refractory peripheral T cell lymphoma.
We are recruiting well and on track to complete enrollment of this study in the first half of 2022.
And we expect to be able to provide further guidance about timing for data as we get closer to the completion of enrollment.
And the investigator sponsored clinical trial at MD Anderson cancer Center evaluating cord blood derived metrics, so pretty complex without heat from 13, we have completed the dose escalation part of the.
Got it.
With increasing doses you beat that by.
Three cohorts, whether used either tend to the six cells per kilogram.
Three patients that received tend to the seven.
Cells per kilogram and three patients that received tend to be eight cells per kilogram.
We're currently enrolling additional patients at the highest dose.
Funds tend to be eight cells per kilogram together robust data on safety and efficacy.
What would form the basis for discussions with regulators about appropriate approval strategy.
No dose limiting toxicities have been obsessed during the dose escalation and any of the three cohorts.
And we remain encouraged by the upsets or sponsors.
The next data update is planned for the fourth quarter at a major medical conference.
Regarding our efforts to take full but the combination of hanging from 13 with metric and that's all into a registration type study we have signed up.
A C D M O for the manufacturing of the NK cells.
And have generated additional data on cryo precise metric because it's all it's pretty complex with pay your symptoms.
As we have shared with you over the past few months.
This call like in key characteristics of our insights and engagements.
In combination with metric in itself is a major advantage over monoclonal antibodies.
The major difference being that.
When we look closer at the cell surface retention.
It wasn't necessarily engages won't fault, often combined therapy for a very long time.
Days later.
Whereas monoclonal antibodies are not retaining that for very long.
As a result, our research shows that.
It is not possible to China, it's a pretty complex product with monoclonal antibodies, but with each or something.
Moreover, our research demonstrate that the engagement of all of them and then sending data molecules, which natural killer cells at the bank the natural killer cells to kill tumor cells.
And our collaboration with the Karolinska Institute, we found that Ethan 13.
When compared to a monoclonal antibody mediated <unk>.
More potent activation of natural killer cells.
Leading to a significantly increased number of natural killer cells that exerted engagement with multiple target cells random these NK cells serial killer.
This exciting data has been accepted for poster presentation at the ITC annual meeting in November.
In our ongoing trial with M. D. Anderson at this hour goes to China right. The strong data package that would support discussions with the FDA and other agencies regarding next steps for the program.
Including a potential registration directed study.
Now, let me turn it over to Ace in 'twenty, four or Egfr directed gotcha.
Where are you from 'twenty four we continue to execute our three pronged strategy of mono therapy.
The nation with natural killer cells in combination with a checkpoint inhibitor of PD lone.
Our goal in this program is to evaluate a broad set of solid tumor indications in parallel.
Supported by a strong biological rationale.
We expect multiple inflection points this year and plan to have multiple additional data readout in 'twenty to 'twenty two.
Our monotherapy dose escalation study is on track.
Based on current data cohorts, five and six a pharmacologically active dose.
Therefore, we have to increase the size of cohort twice.
Turns out that 320 milligram.
And CT six patients are dosed at 180 milligram to generate additional pharmacokinetic and pharma.
Dynamic data that we expect with eight our selection of the recommended phase two dose.
As of today in each of the court.
Five and six.
Five out of six patients aren't and wrote it.
It is important to mention that to date in patients that have already completed the deal keep urea in each corner no dose limiting toxicities were observed.
So it's just mentioned we continue to see you go good safety profile.
24.
We confirm that we have not seen any of the classical egfr relate to target that.
Like ethnic form kin rash or Microsoft.
This is in line with a distinct mechanism of action from 24, which is very different from the motive action of Egfr pathway targeting antibodies likes it took some of what kind of two months.
These findings also confirms the data.
From a people can toxicology studies employing them all because monkeys.
That indicated a different kind of different profile for ace in 'twenty versus <unk>.
Infusion related reactions to remain the main side effect.
Manitoba with symptomatic treatment and modification something excuse me.
The ongoing dose escalation part into the patients with any egfr expressing solid tumors.
When assessing antitumor activity at those levels in the 320 milligram.
80 milligram cohort.
We are encouraged to see that.
Several patients on the study that had experienced disease stabilization beyond eight weeks.
And you are able to release additional funding.
Biomarker analysis of the patients point to the activation of T effector cells.
Shown by increasing expression of activation markers and a continuous secretion of cytokines.
It's a part of this observation is a continuous occupancy of the CD 16 receptor.
We are enrolling patients in the mono therapy study and independent of the selection of our recommended phase two dose we plan to continue to increase the dose and non selected patients.
Together further insight into the exposure.
This relationship.
Some 24, focusing on P D market and to confirm safety.
24 at an even higher dose.
Important to note that in addition.
In line with our guidance, we expect now to start enrollment of indication specific patients in the expansion cohort.
Using single agent <unk> 24 in the second half of 2021.
These costs have been chosen based on a detailed analysis of the tumor biology as we explained in the past.
And will enrich for patients that we believe has a high likelihood to respond to single agent and he's from 24.
These expansion cohorts include will include renal cell carcinoma.
That failed standard of care, which includes PK and PD one targeted therapy.
Second indication with non small cell lung cancer.
Upon mutant failing standard of care.
And the third indication colorectal cancer, failing chemotherapy plus egfr targeting antibody.
So we have selected three indications for the mono therapy studies.
In addition, we're now in the final stages of the setup phase for our combination studies of agents from 24th we suppose to lease them up.
Studies called <unk> from 24, one O two in the autologous NK cells.
Thank you Juan.
It's called <unk> some 24.
One O three.
We confirm our guidance that we expect both of these studies.
To start our start enrolling patients in 2020.
The tumor types, we plan to study we see anywhere from 24.
T. So combination are as follows again non small cell lung cancer in this case Egfr wild type.
[laughter] chemo and PD one targeted therapy.
Gastric.
And G and change.
Cancer, failing standard platinum based chemo.
I need a basket of egfr expressing tumors comprising pancreatic.
To sell or not and biliary tract cancer again, failing standards of therapy for the respective.
The other tumor types, we plan to studying and he's from 24 to one NK cell combination study.
Are as follows.
Again in non small cell lung cancer Egfr wild type.
Squamous cell carcinoma of the head and neck, failing chemo and PD one.
And colorectal cancer failing standard of care.
The indications for each of the three studies have been selected carefully based on the biology of each tumor type.
This approach allows us to investigate a broad set of solid tumors, while also providing multiple shots on goal.
For the more prevalent tumor types.
Such as non small cell lung cancer and colorectal cancer.
In summary, we're very satisfied with the progress of Tas from 24 program.
The data show that as from 'twenty full professors a different mode of action compared to conventional egfr targeting young people.
We see pharmacological activity based on CD 16 receptor binding and activation Buck.
And these are pharmacologically active doses, we see no classic Egfr relate to finally get that like Skinnier Covid took system.
And in addition, we've been seeing to see stabilization in these heavily pretreated patients.
At those levels, III 20, milligram and tweak your medicine.
We believe in this significant potential on telling you from 20 point with a planned expansion of the program, we're seeking to maximize this opportunity.
Dressing that Bronx, active matrix egfr expressing tumor indications.
And this strategy will allow us to provide a continuous flow of income.
Now, let me move to the third program Ace in 2020 from 28, we continued to advance the R&D, enabling studies and have submitted an abstract with initial preclinical data for a major medical conference later this year.
We plan to release information about the target and indication once we abstract becomes available.
We remain on track to submit the application in the first half.
Oh for 'twenty to 'twenty, two and our goal is to begin a clinical study in the second half of 2022.
In addition to moving forward things forward them to clinic, we're continuing to publish data that supports all of the book.
One such example is the reason could publish preclinical data that supports it.
The I N E filing an application of our insulin data from 24 injections in maps.
Aren't our CFO will discuss the key takeaways from the publication from desktop retention aren't.
Thanks, Audi and also for me a very warm welcome to everybody on the call.
As introduced by Audi I would like to summarize the key preclinical data for <unk> and 'twenty four describes in the recent publication in the journal perhaps.
This paper, we demonstrated the high affinity binding.
I'm 24 to <unk> 68.
All natural killer cells and macrophages.
Strong binding values below normal range importantly, as from 'twenty four bonds to series six a M.
NK cells and macrophages with high affinity at a site that is distinct from the binding of <unk> G. Such that as high concentrations of polyclonal <unk> G results and a minimal only two fold production and binding affinity in contrast.
Finding often FC enhanced high affinity anti Egfr RTG antibody was significantly inhibited.
Data again demonstrates the high surface retention of our IC molecules to NK cells, enabling the earlier described pre complex into NK cells with car like NK cell properties, which are not possible with normal or FC enhanced antibody.
We also show high affinity binding of 24, and the non MLR range to various egfr expressing tumor cells.
I'm 24 demonstrated to be highly differentiated from marketed anti egfr antibodies with its ability to potently and effectively kill tumor cells.
<unk> antibody dependent cell mediated cytotoxicity or a D. C C R.
Hey cells. Moreover, this ice's mediated potent antibody dependent cellular pago cytosis or ADC P bio macrophages in vitro.
If I'm 24 was also shown to be effective.
A variety of Egfr expressing tumor cells, killing these regardless of their egfr expression level and irrespective of their K roadhouse, or BRAF and BRAF mutational status and.
In addition.
Let's say from 24 has a lower affinity for Egfr and binds to a different epitope than it took some of it exerts in over 1000 fold lower inhibitory activity on Egfr signaling further underscoring its highly differentiated mechanism of action.
Now in terms of in vivo theater and tumor mouse models. We have published that ASC are this year's ACR showing dose dependent anti tumor activity of <unk> 24 in combination with freshly isolated NK cells.
Antitumor activity for F. 'twenty four in combination with NK cells has now also been demonstrated with pre complex and cryo preserve NK cells in vitro and in vivo within one of our preclinical collaborations this exciting data gives us confidence.
But the NK cell product, we used in combination with ace I'm twenty-four retains its potent anti tumor activity after cryopreservation in vitro and in vivo.
But coming to the toxicology studies.
Monkey is also described in the paper based on 24 was well tolerated up to the highest dose of 75 mix per gig when administered once weekly for 28 days remarkably good other cytotoxic toxicities.
As had been observed at these dose levels with Cetuximab and comparable central Monkey studies were not observed here.
Only transient elevation of interleukin six levels supposed to detected at all dose levels, which returned to baseline after 24 hours.
Moreover, an increase in circulating C D 40 of monocytes.
Was observed after the first dose of April 24, concurrent with a decrease of circulated NK cells for doses of greater or equal to eight grams.
So all of you showing the expected pharmacodynamic effect of this drug candidate as well.
Taken together these results emphasize the promise of our bi specific innate cell engage us as an alternative cancer therapies.
Demonstrates the potential for Afib traded core to effectively target tumors expressing various varying levels of egfr, regardless of their mutational status.
To answer any questions you may have about this in our Q&A and pronounce I'll hand, the call over to Angus to review the financials.
Thank you Ark.
I think that the consolidated financial statements have been prepared in accordance with IRS have issued by the international accounting standard board or I S. P.
Consolidated financial statements are presented in Europe, which is the company's functional and presentation currency. Therefore, all financial numbers that I will present in this call unless otherwise noted will be in euros.
We entered the second quarter of 2021 with cash and cash equivalents of $229.0 million euros compared to a $155.0 million on December 31.2020.
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 quarter ended June 32021, or $20.0 million euros compared to $15 million in the second quarter of 2020.
Total revenue for the second quarter ended June 32021 was $16.0 million in Europe, compared with $11.0 million for the quarter ended June 32020.
Revenue for the second quarter of 2021, mainly comprised of collaboration revenue from Genentech and Roche.
Research and development expense for the second quarter of 2021 was $29.0 million euros compared to $18.0 million euros for the second quarter of 2020, the increase in R&D expenses compared to the same period last year, driven primarily by increased expenses for F. 'twenty four including cost for the production of clinical trial material.
As well as an increase in costs associated with our other early stage programs and infrastructure and an increase in share based payment expense.
General and administrative expenses for the second quarter of 2021 increased by 109% to $9.0 million from $8.0 million in the second quarter ended June 32020.
Net finance costs for the quarter ended June 32021 increased by 63% from $1 million in the quarter ended June 32020 from $7.0 million.
During the second quarter of 2021.
The increase is largely due to foreign exchange losses related to assets denominated in U S dollars as a result of the weakening of the US dollar against the euro during the quarter.
Net loss for the quarter ended June 32021 was $26.0 million or 16 cents per common share compared with a net loss of $14.0 million or 16 cents per common share for the quarter ended June 32020.
The weighted number of common shares outstanding for the quarter ended June 32021 was $125.0 million.
I will now turn the call back to <unk> for closing remarks.
Okay.
Thanks, a lot Angus.
It's just explained how our company is making.
Significant strides full but by advancing points and demonstrating that I want you know tuning nature can play a leading role.
In enabling innate immune cells to identify and eliminate constable.
No place in 13 hours strategy development strategy allows us to target the Bronx Central <unk> positive.
Lymphoma.
Indeed, including various types of non Hodgkin's and Hodgkin lymphoma.
We're very excited about the potential market opportunity for income 13 in these indications.
We will have additional data for the NK cell combination study by the end of the year.
For any of them.
24, we're now executing a strategy that we believe.
We believe it gives us the highest probability of success.
We have reached active dose levels.
Patients study.
And we'll now use this to initiate.
This three pronged development approach in parallel.
Indeed across a broad set of solid tumor indications.
We expect that these are three studies will generate a continuous inflow okay.
Finally, we are executing on our preclinical pipeline to bring additional product candidates into the Kent I would do.
<unk> progress won't eat them 28, as indicators of our ability to further expand our pipeline by leveraging.
The unique rock platform and we're working on additional early candidate from the pack.
Many many people have contributed to bring our innovative therapies to patients who need additional options.
Kent.
These include patients and their families who entrust us.
With the life of their loved ones our employees.
And the Investor.
Who over the years have supported our efforts.
As always I'm very thankful for the trust you put into our.
Efforts. Thank you.
We're now ready to take any questions that you may have a pretty tough.
Ladies and gentlemen, if you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone phone to withdraw your question press the pound key.
Our first question comes from Dana Great Bosh with SBB Leerink.
Hi, all thanks for the question and for the pretty nicely comprehensive call.
Two for me and I asked them 24, the first.
And I believe you mentioned I just want to confirm that you saw stable disease and several patients beyond eight weeks and in that same sentence. You mentioned that you were including any egfr expressing solid tumors I'm wondering if you could clarify whether you saw the stable disease in patients that had more egfr expression was there any correlation with that.
Or even if you could tell us of the patients recruited at cohort five and six.
A question of them did have high Egfr.
You ended up with low Egfr.
The first question and the second question is can you confirm how you ultimately will select the dose given you haven't had any dose limiting toxicity.
Will you be going off a pharmacodynamic activation in periphery, what gives you confidence.
Got.
But that will track with your activity in the tumor will be going off occupancy of 2016 or Egfr or will you continue to try to dose as high as possible. So you do understand your highest tolerable dose. Thank you very much.
Thank you Dana I have to check it's Andreas it's still on the phone I'm sure you.
Could you follow the.
The questions and okay very good on growth.
Yeah I'm on the phone so I apologize I'm in Italy, So if I break up at some point.
Its institute of technology reasons, but I try to stay as long as I can so.
Let's start with your second part of your question first.
Also chime in.
So as we always said the selection of a recommended phase two dose will be based on Pharmacodynamic markers.
As I've mentioned, our mechanism of action is completely different from Egfr.
<unk> targeting agents likes it took them up well also tiki I so.
We were not expecting to see any dose limiting toxicity like skin mucosa.
And when it wasn't in fact seen clinically assess where you are reconfirming. This assumption. So I'll ask remains these side effects, which are very manageable.
I'm not seeing any skin toxicity became closer toxicity.
As we've said in terms of Pharmacodynamic markers, we have.
A whole array of <unk>.
Parameters that we look at.
Mostly to pull out because our markers of reactivation of circulating NK cells as well as the occupancy off.
The CD 16 receptor.
Well, we see values that are well above.
Those are some needed or experimental activities.
In vitro and in vivo.
So we feel very confident.
Working out.
Correct.
<unk>.
This is our doses that we would take forward into close to testing both as a single agent as well.
Combinations.
Irrespective of this we are.
They escalate one or two additional dose steps just to confirm.
Very good safety profile, a very good place to work but.
But not necessarily to do with this higher doses.
Further evaluation of clinical activity.
In terms of Egfr expression.
We are collecting the data.
Again, because the highest dose level, we have not all data in the house of course, the lower dose levels.
We could not see any correlation between the degree of Egfr expression and unlocks a clinical program.
But again, we will be going through for the two highest dose levels in terms of quantification hospital.
Yeah.
Got it thank you very much.
Our next question comes from Maury Raycroft with Jefferies.
Hi, good morning, everyone and good afternoon and congrats.
Congrats on the progress and thanks for taking my questions.
Also one question on F. 'twenty four you mentioned additional.
Additional inflection points for the program by the end of the year. Just wondering if you can recap what those inflection points are.
Okay.
Yeah.
Yeah, So one of the.
As we've mentioned we are now planning to.
Historically, a dose expansion cohort.
So that's an important milestone and we've also mentioned that there are two additional studies that are being initiated.
The one is the combination study with natural killer cells and the other one is the <unk> study with.
So Lisa month. So these are three.
Already important inflection.
Inflection points in our mind.
And in addition, we can provide updates.
As we proceed with a dose escalation study.
You have heard from Andre us, but we have it.
Expanded.
Cohorts five and six to include more patients those data will be collected and analyzed and once available. We are planning to share this data with you.
Got it that's helpful Marie.
Yeah Yeah.
And I'm just wondering if you're seeing anything additional about any more specifics on the activation markers and cytokines accretion that you're seeing.
Yes.
Arent.
Yeah. Thanks, Mark Good question at this point not specifically, we would like to share that I mean, we have said just to repeat maybe what address already said as we look at our activation and negotiate markers on circulating NK cells.
Infiltration with yourselves and some of the biopsies, we if we look at the cytokine levels, but of course as we have reported in addition to <unk>.
Exposure. So PK parameters also receptor occupancy and we will share that in more detail. Once all the data is Audi also mentioned will be.
We've collected together and then she will also share the specific markers yours.
Yes.
Got it Okay. And then also wanted to ask about the AFM 13, plus NK cell combo can you say if you ever sponsors at the highest dose at this point.
And how many patients total at the highest dose our plan for the study.
So we haven't disclosed any such detailed for the time being as.
As we are preparing for a.
Presentation later in the year.
As outlined so that'd be computer the composite but.
In short what then.
<unk> has been news that we have in.
In each cohort initially three patients.
And of course, it's one way to say Oh.
A certain number of NK cells, which has increased by a factor of 10 when safety is warranted.
And.
As I tried to send to the six cells per kilogram, they moved to tend to the 7% tends to be a.
In these.
Patients, we haven't seen any dose limiting toxicities or in.
Any other sort of get back to appear quite tape and.
And overall, what I can create here is that we're also very encouraged by the responses that we're seeing after the FDA because this estimate frankly additional patients are treated.
So we have continued to enroll patients or M. D. Anderson has continued to enroll patients.
The highest dose cohort and that's currently ongoing.
Got it.
Yeah. That's helpful. And then my last question then I'll hop in the queue in the prepared remarks, you said the program.
13%.
The program would be robust and could enable discussions with regulators for approval strategies.
Wondering if you think you'll have enough data by year end 'twenty one to enable these discussion.
In terms of timing we've been lucky.
Let you know as soon as we have such state tax in ice tea. So we're it depends on the M D. Anderson.
To enroll these are these patients.
And so I would tell you that we have to wait for a little while before we can confirm any of this next activities. This is an important activity, but as we feel it's not the only very important activity. The other one is that.
We can proceed with the NK cells and its manufacturing and I wish sharing tuned used today.
We've made good progress.
On the on this front as well first we're not working with the C. D M O.
For the manufacturing of the cord blood derived NK cells and you have to generate the first data off of crime persist if I'm a 13th.
Pretty complex NK cells and determined that our activities.
And in preclinical experiment.
Got it okay, Congrats again and thanks for taking my questions.
Thank you.
Our next question comes from Nick Abbott with Wells Fargo.
Oh good morning, Thanks for taking our questions and.
We're literally sounds a delightful I have to say I'm, just starting off maybe on an F N T.
You mentioned the C. D. M. O D is this using cord blood from M D. Anderson.
Over there I know that you've licensed the technology from them, but you're restricted to where the cord blood.
So come from which bank they come from.
So yes, we have a license to the entire technology.
And this would also include indeed in Europe on the craft preservation, that's being conducted by a N booking in terms of whole blood stoltzman not restricted.
To any specific source. So we can close the stuff from M. D Anderson, but those are independent.
Places.
And.
So in essence thing that's how we then pump we understand that but is there a specific reason why you were asking.
No not at all no. So I was just thinking if you were going to be you know I don't we don't know where the C. D. M. O. It is but if you were gonna have a C. D. A mill in Germany. For example, and you know shifting cold-blood from M D Anderson wouldn't be as convenient.
Some of them are in Germany.
Yeah, No. It's an international C. D M O. So that has footprint all over the ropes.
One of the very experienced one.
That was important to US again, and then C. J M O that has already.
And developed NK cell product.
So we're tapping into a specific know how already were.
This with its choice.
And at the moment, our focus is to work with this point in the U S.
Okay, great. Thank you and then just finally.
I'm, Tony core and a terrific now finally details of those expansion cohorts.
One thing that struck me in the monotherapy.
Not a K Ras mutated colorectal cohort.
You know the NK combo would appear to allow for K Ras mutated.
Colorectal, but did you consider or is there a reason why there isn't a K Ras mutated COVID-19, obviously, it couldn't be egfr pre treated and that's probably the reasons, but I thought I'd ask.
Andreas can you.
Help out here.
Yeah.
Pick up.
With that our selection on the <unk>.
Expansion cohorts.
Are all based on a pretty thorough analysis see underlying tumor biology honestly makeup of the different players.
Immune system.
When we look specifically at K Ras mutated colorectal cancers, it's not due to the corruption taste, but there appears to be a coincidence.
Many K Ras mutated colorectal cancers.
Have very limited.
And so.
Our numbers and then some other factors.
Indicated to us that I'll tell you, what's called a query Ralph mutated colorectal cancer would be one of these indications.
Whereas a patient would need support of an external NK cell source.
And that's the reason why they ended up basically the study will know Shri.
Beliefs that once you are able to supply these came off mute and Tom.
Colorectal cancers, with NK cells, and what's an appropriate engage or all that you could see a ninth immune system and in the best position could work against this very difficult to treat tumors.
So thank you very much and I'll hop back in the queue.
As a reminder that is star then one if you'd like to ask a question at this time.
Our next question comes from Daniel Chan with Laidlaw.
Oh, good morning, and afternoon and thanks for taking the question.
The first question is thoughtful and.
13, plus the.
Oh blood NK cell switch that.
According to clinical trials that are you have you know what.
They expect to.
The increase of about 30 patients.
Is the target still or do you anticipate or how is there any modification on that and what did that potentially could be a critical mass for a potential registration study discussion with FDA.
Yeah.
Andrea you might want to take that.
Yeah.
First of all if I can confirm is that.
But the protocol is written in a way that we.
In fact can recruit somewhere between 70 patients at the recommended dose level.
This could be a mixture of hodgkin and non Hodgkin series <unk> expressing lymphomas.
Again, whether it's mass always says this number will.
He is sufficient for any registration package of course will depend on the exact level.
And definitely this study will allow us probably even early up and.
Going up to the full recruitment to engage in discussions with FDA and I think Julian just discussions we will learn what what kind of patient numbers and are expecting.
So I think it's a robust study I think will give you pretty good dataset well.
This will enable us to look at different biology's wishing to see these <unk> expressing lymphoma space.
Everything else will really depend on our discussions with FDA.
Great. That's very helpful. Maybe just a quick follow up on this which is that is the data anticipated.
40 at ash or other venues.
<unk>.
Hum again believe your disclosure policy is mainly driven by our expectations.
We'll submit.
Some of these data for ash.
Okay, Great and maybe just one general question for the 24.
You have the monotherapy as well as the combo, specifically with NK.
Sale on boats.
I noticed that the renal cell carcinoma, with only a mono therapy, but not on the combo is there any.
Reason behind that or maybe more specific reason behind that.
Yeah Yeah.
So it's again, it's based on the analysis of biology.
And the setup of the different players of the innate immune system, a clear cell carcinoma renal cell carcinoma.
Already since a long time.
With tumors that whereas the Gulf.
Our system can exert some tumor control.
We specifically looked at the players in the innate immune system or we've found that RCC.
Is a good candidate that could benefit from monotherapy. So our first step here is to test monotherapy area from 'twenty four.
We believe that several police several important pieces are in place in RCC.
<unk> made solid engaged could work as a mono therapy.
Of course, if we should see good data that would not preclude that at some point, we may add some dimension of an NK cell or a PD one but again for the first evaluation of our system.
That's what helps us to miss where monotherapy could be quite beneficial because these patients.
Okay, Great and then maybe the last question, which is the housekeeping ones that are in the second quarter of this year the R&D expenditure.
Revenue has increased particularly the R&D expenditure increased quite significantly compared to the prior quarter.
So should we for modeling purposes should we anticipate the second quarter R&D expenditure would be something more.
The base movie going forward for at least for remaining of the year.
And thanks for the.
Yep.
Thanks, Yeah. So a couple of comments there I mean, what we we haven't provided specific guidance on our expenses, but we have provided guidance on our cash runway and what we've said is that we expect our existing cash which is about 200.
A little over 220 million euros.
Asked us are into the second half of 2023 so.
You know if you're if you do the math on that.
Eight to 10 quarters out.
Does that imply a cash burn in the low to mid twenties.
Any impact of additional proceeds from loans milestones et cetera.
So just doing based on that map you can assume that.
You know the expenditure levels that you're seeing in Q2 of this year is probably more relevant as we go forward then the expenses you've seen in previous quarters in particular.
Second quarter of last year.
But having said that we do expect that R&D.
R&D expense will be lumpy right way this quarter we've had.
On the call we've had.
<unk> 24, a lot of that is associated with <unk>.
Production of clinical trial material for our ongoing study at an upcoming studies. We've also had to ramp up since in our earlier stage programs from 28.32.
And you know when it comes to CMC investment can be a little bit lumpy, but long story short that's fair to assume that the R&D expenditure.
This quarter it is probably more and more in line with where we'll be in the future then.
Been in the past.
Okay, great. Thanks, a lot and again, congrats but a lot of progress here.
Thank you.
We have a follow up question from the line of Nick Abbott with Wells Fargo.
Alright, thanks for taking the follow up and.
Just going back to the hip.
24 trial I believe that currently the trial is being conducted at four sites in the U S U K and Spain.
And you mentioned a U S. C. D. M O. So can you talk maybe a little bit about.
The for.
For the three expansion cohorts.
You know how many sites you.
Expect to be running those trials that and whether they're going to be international coal in the U S and well, let's be a Simon two stage design for each of the cohorts. Thanks.
Okay. Yeah. Thanks for the question Oh, Nick I'll have either Wolfgang Andreas jumping in here if they can.
Yes.
Oh, Yeah I can.
So for the expansion cohorts of the monotherapy trial.
We are looking to increase the number of sites from four that we're currently having probably too.
Somewhere in between.
10, and 15.16 sites.
We will continue to be a mixture of our U S side International side. Scott You mentioned currently we have Europe.
Yes.
Hi.
Southeast Asia, mainly Korea.
Especially to recruit Egfr mutant patients.
Now the same is true for the PD one PDL one study.
Where we will have also a mixture of all current U S and ex U S sites.
Study, one O Swayze S N pay or one study.
We will initially be a U S only study with up to four sites.
The initial.
Initial part and then expanding to cover more sites, but the countries have plans for this specific study ought to be a U S. Only study.
Now in terms of study design.
Studies are designed to according to Simon two stage principal so we will have an initial phase.
Place with a defined number of patients of course.
Different disease types.
Go no go criteria.
Vary by disease type.
Type.
And then ultimately definitional another sponsor investment cost will be a little bit different.
In general.
With the Simon two stage design with an initial cohort of probably around close to inflation.
Looking at the pre defined success quite clear yet.
The ability to enroll up to 30 to 35 patients per cohort.
Two a very fine the initial assumption about some upside there.
The group's next time.
Great terrific. Thank you very much.
Yeah.
And that concludes today's question and answer session ladies.
Ladies and gentlemen, thank you for participating in <unk> second quarter, 2021 financial results and corporate update conference call.
This concludes the program and you may now disconnect.
Have a great day.
[music].
[music].
I'd like to also welcome you all for joining us today for our second quarter 2021 results and operational update call before we begin I'd like to remind everyone that we issued the relevant press release earlier today and can be found on the Investor Relations section of our website on the call.
Today, we have are the following members of our management team doctors, Audi Hirsch, our Chief Executive Officer, Andreas <unk>, our Chief Medical Officer.
Andre <unk>, our Chief Scientific Officer, Wolfgang Fischer, Chief operating Officer, and Angus Smith, our Chief Financial Officer, the whole team will be available for the Q&A session.
Well, we start quickly to go through the Safe Harbor statement today's discussion 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.
<unk> publicly or to update the reasons why actual results could differ materially from those anticipated in the forward looking statements, even if new information becomes available in the future.
These forward looking statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied in the statements and 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.
Right under the section entitled forward looking statements in the press release that we issued today and filed with the SEC with that I'll turn the call over to Audi Audi.
Yeah. Thank you Alex and good morning, everyone.
And thanks, a lot for joining in for our second quarter update call.
Today, we're going to provide an update on our pipeline.
Great progress on our ongoing are you from 13.
I'm a 24 nine from 28 studies our plan.
Well, what promises to be an exciting periods over the next few months for our company.
Before I do that a quick summary of what we have accomplished so far.
And get clinical and preclinical data confirmed that our unique and innovative.
Turning eight shows our assays.
And has the potential to be effective in treating cancer patients.
Mono therapies.
And also in combination either with natural killer cells.
Or with checkpoint antibodies, such as PD, one maybe PDL one.
Yeah.
As we move to the ongoing clinical trials for lunch.
Our efforts are now focusing on identifying and targeting indications, where we believe our scientific discoveries will benefit patients by applying our three pronged approach mono therapy.
Therapeutic in combination with Metro killer T cells and checkpoint inhibitor.
We're very happy to report that our pipeline remains on track for our registration directed study.
I am from 13 monotherapy in relapsed or refractory peripheral T cell lymphoma.
We are recruiting well and on track to complete enrollment of this study in the first half of 2022.
And we expect to be able to provide further guidance about timing for data as we get closer to the completion of enrollment.
And the investigator sponsored trial at MD Anderson Cancer Center.
18 cord blood derived metric hit us all.
Complex without used from 13, we have completed the dose escalation part.
Got it.
With increasing doses and pizza.
Three cohorts, whether used either tend to the six cells per kilogram.
Three patients that receive tend to the seven.
Cells per kilogram and three patients that you received tend to be eight cells per kilogram.
We're currently enrolling additional patients at the highest dose.
All of a sudden tend to eight cells per kilogram together robust data on safety and efficacy.
It would form the basis for discussions with regulators about appropriate approval strategy.
No dose limiting toxicities have been obsessed during the dose escalation in any of the three cohorts.
And we remain encouraged by the <unk>.
So if their sponsors.
The next data update is planned for the fourth quarter at a major medical conference.
Regarding our efforts to take full but the combination of anywhere from 13 with Mexican itself into a registration type study, we have signed up.
C D M O for the manufacturing of the NK cells and.
And have generated additional data on Cryopreserved natural killer cell, it's pretty complex with paid search.
As we have shared with you over the past few months before this call like NK characteristics of our units and engagement.
In combination with Mexican themselves as a major advantage over monoclonal antibodies.
The major difference being that.
When we look closer at the cell surface retention.
Our units and engages won't fault, often combined therapies for a very long time, including days later.
Whereas monoclonal antibodies are not to retain some very long.
As a result, our research shows.
That it is not possible to China, it's a pretty complex project with monoclonal antibodies.
Gotcha.
Moreover, our research demonstrate that the engagement of all of it and then sending data molecule with natural killer cells activate the natural killer cells to kill tumor cells.
And our collaboration with the Karolinska Institute, we found that any of them searching.
When compared to a monoclonal antibody mediated.
More potent activation of natural killer cells.
Leading to a significantly increased number of natural killer cells that exerted engagement with multiple targets those random these NK cells serial killer.
This exciting data has been accepted for poster presentation at the ITC annual meeting in November.
In our ongoing trial with MD Anderson at this hour go to generate a strong data package.
What's important discussions with the FDA and other agencies regarding next steps for the program, including a potential registration directed study.
Now, let me turn it over to Ace on 24 hour Egfr directed nature.
Where are you from 24, we continue to execute our three pronged strategy of mono therapy.
Nation with natural killer cells in combination with a checkpoint inhibitor of PD one.
Our goal in this program is to evaluate a broad set of solid tumor indications in parallel.
Supported by a strong biological rationale, we expect multiple inflection points this year and plan to have multiple additional data readout in 'twenty to 'twenty two.
Our monotherapy dose escalation study is on track.
Based on current data costs twice and six ophthalmic relaunch it keep asking.
Therefore, we have increased the size of cohort twice.
Patients are dosed at 322 milligram <unk>.
CT six patients are dosed at 180 milligram to generate additional pharmacokinetic and pharma.
Dynamic data that we expect with eight our selection of the recommended phase two dose.
As of today in each of the cohorts.
And fixed.
Out of six patients, arguing wrote.
It is important to mention that to date in patients that have already completed the deal keep theory in each cohort no dose limiting toxicities were observed.
So it's just mentioned we continue to see a good safety profile.
24.
We confirmed that we have not seen any of the classical egfr related targets.
Like Oh form skin rash or.
This is in line with a distinct mechanism of action, even 24, which is very different from the motive action of Egfr pathway targeting antibodies likes it took us about a penny to moment.
These findings also confirms the data.
From a pivotal toxicology studies in telling them all because monkeys.
That indicated a different car different profile for <unk> and 'twenty four versus it took.
Infusion related reactions will remain the main so I get that and one managed troubled with symptomatic treatment and modification something excuse me.
The ongoing dose escalation part into the patients with any egfr expressing solid tumors.
When assessing anti tumor activity at those levels in the 322 milligram.
180 milligram cohort.
We are encouraged to see that there are several patients on the study that had experienced disease stabilization beyond eight weeks.
And we're able to release additional scientists.
Biomarker analysis of the patients pointing to the activation of T effector cells.
Shown by increasing expression of activation markers and a continuous secretion of cytokines.
Indeed, some part D book. This observation is a continuous occupancy of the CD 16 receptor.
We all enrolling patients in the mono therapy study and independent of the selection of our recommended phase two dose we plan to continue to increase the dose and non selected patients.
Together further insights into the exposure in fact relationship.
Some 24, focusing on PD market and to confirm safety. After April 24 at even a higher dose.
Important to note that in addition.
In line with our guidance, we expect now to start the enrollment of indication specific patients in the expansion cohorts.
Using single agent data from 24 in the second half of 2021.
These costs have been chosen based on a detailed analysis of the tumor biology as we explained in the past.
And will enrich for patients that we believe have a high likelihood to respond to single agent <unk> and he's from 24.
These expansion cohorts include will include renal cell carcinoma.
That failed standard of care, which includes PK and PD one targeted therapy.
Second indication with non small cell lung cancer each.
[noise] upon mutant failing standard of care.
Detailing and the third indication colorectal cancer, failing chemotherapy plus egfr targeting antibody.
So we have selected three indications for the mono therapy studies.
In addition, we're now in the final stages of the setup place Wild combination studies of agents from 24th we suppose to.
So Lisa model.
Studies called Adas from 24, one O two in the autologous NK cell program I think to your one this study is cold and some 24, that's one O three.
We confirm our guidance that we expect both of these studies.
Start start enrolling patients in the 2021.
The tumor types you plan to study with the I mean, you have some 24.
To use a combination orange follows again, non small cell lung cancer in this case Egfr wild type failing chemo and PD one targeted therapy.
Got strict.
And G in chain.
Cancer, failing standard platinum based chemo.
And a basket of Egfr expressing tumors comprising pancreatic.
And perhaps a cellular and biliary tract cancer again, failing standards of therapy for the respective speaking.
The other tumor types, we plan to studying ace in 'twenty, four and think he or one NK cell combination study.
As follows.
Again in non small cell lung cancer Egfr wild type.
Squamous cell carcinoma of the head and neck, failing chemo PD one.
In colorectal cancer failing standard of care.
The indications for each of the three studies have been selected carefully based on the biology of each tumor type.
This approach allows us to investigate a broad set of solid tumors, while also providing multiple shots on goal.
The more prevalent and tumor types.
Such as non small cell lung cancer and colorectal cancer.
In summary, we're very satisfied with the progress of <unk> from 24 program.
The data showed that as from 'twenty food possesses a different mode of action compared to conventional egfr targeting young people.
We see pharmacological activity based on CD 16 receptor binding and activation Buck.
And these are pharmacologically active doses, we see no classical egfr relate to kind of get that like skinnier Makoto toxicity.
And in addition, we've been seeing to see stabilization in these heavily pre treated patients.
At those levels through 20 milligram and flaky medicine.
We believe in this significant potential on telling you from 20 point with a planned expansion of the program, we're seeking to maximize this opportunity.
Addressing a broad set of major egfr expressing tumor indications.
And this strategy will allow us to provide a continuous flow of data.
Now, let me move to the third program Ace in 2020 from 28, we continued to advance the R&D, enabling studies and have submitted an abstract with.
Initial preclinical data for a major medical conference later this year.
We plan to release information about the target and indication once we abstract becomes available.
And on track to submit the IDE application in the first half.
For 2022, and our goal is to begin a clinical study in the second half of 2022.
In addition to moving forward things forward into clinic, we're continuing to publish data that supports all of the book.
One such example is the reason could published preclinical data that supports it.
I N E filing do you have mutations in that selling day trial from 24 and the churns in maps.
Aren't our CFO will discuss the key takeaways from the publication from the public attention aren't.
Okay.
It takes Audi and also for me a very warm welcome to everybody on the call.
As introduced by Audi I would like to summarize the key preclinical data for 24 describes in the recent publication in the journal perhaps.
This paper, we demonstrated the high affinity binding of <unk> from 24 to <unk> 68.
All natural killer cells, and macrophages strong binding values below Nanomole range importantly, as from 'twenty four bonds to series six in a bundle.
NK cells and macrophages with high affinity at a site that is distinct from the binding of <unk> G such that as high concentrations of Polyclonal I G. G <unk>.
<unk> and a minimal only two fold production and binding affinity in contrast.
Finding often FC enhanced high affinity anti Egfr RTG antibody was significantly inhibited.
Data again demonstrates a high surface retention of our IC molecules to NK cells and <unk>.
The earlier described pre complex thing to NK cells with car like NK cell properties, which are not possible with normal or FC enhanced antibodies.
We also show high affinity binding of 24, and that's not a model of rates to various egfr expressing tumor cells.
I guess I'm twenty-four demonstrated to be highly differentiated from marketed anti egfr antibodies with its ability to potently and effectively kill tumor cells.
Through antibody dependent cell mediated cytotoxicity or ADC or NK cells. Moreover, this IC E mediated potent antibody dependent cellular phagocytosis or ADC P bio macrophages in vitro.
They have some 24 was also shown to be effective.
So it's a variety of egfr expressing tumor cells, killing these regardless of their egfr expression level and irrespective of their K, Ras or BRAF and BRAF mutational status.
Additionally.
Let's say some 24 has a lower <unk>.
84, Egfr and binds to a different epitope than it took them up it exerts in over 1000 fold lower inhibitory activity on Egfr signaling further underscoring its highly differentiated tobacco smoke action.
Now in terms of in vivo, it's eight or tumor mouse models. We have published that ASC are this year. So if you are showing dose dependent anti tumor activity of <unk> 24 in combination with freshly isolated NK cells.
Antitumor activity for F. 'twenty four in combination with NK cells has now also been demonstrated with pre complex and cryo preserve NK cells in vitro and in vivo within one of our preclinical collaborations this exciting data gives us confidence.
With the NK cell product, we used in combination with a sudden twenty-four retains its potent anti tumor activity after a cryo preservation in vitro and in vivo.
We're coming to the toxicology studies and Central Monkey is also described in the paper pay from 24 was well tolerated up to the highest dose of 75 mix per gig when administered once weekly for 28 days remarkably good and other cytotoxic tox.
So cities.
Had been observed in your store.
Those levels with Cetuximab and comparable.
Central Monkey studies were not observed here.
All of these trends and the elevation of interleukin six levels was detected.
All dose levels, which returned to baseline after 24 hours.
Moreover, an increase in circulating CD 40 of monocytes.
As observed after the first dose of April 24, concurrent with a decrease of <unk>.
Circulated NK cells with doses of greater or equal to eight sort of grants kick now.
All of you showing the expected pharmacodynamic effect of this drug candidate as well.
Taken together these results emphasize the promise of our bi specific innate cell engages as an alternative cancer therapies.
Demonstrates the potential for a fifth core to effectively target tumors expressing various varying levels of egfr, regardless of their mutational status.
To answer any questions you may have about this in our Q&A and pronounce I'll hand, the call over to Angus to review of the financial standards.
Thank you Ark.
I think that the consolidated financial statements have been prepared in accordance with Ifr S have issued by the international accounting standard Board or I E. S. P.
Consolidated financial statements are presented in Europe, which is the companys functional and presentation currency. Therefore, all financial numbers that I will present in this call unless otherwise noted will be in euros.
We entered the second quarter of 2021 with cash and cash equivalents of 222.7 million euros compared to a $155.0 million on December 31.2020.
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 quarter ended June 32021 was $20.0 million euros compared to 15 million euros in the second quarter of 2020.
Total revenue for the second quarter ended June 30th 2021 was $16.0 million in Europe, compared with $11.0 million euros for the quarter ended June 32020.
Revenue for the second quarter of 2021, mainly comprised of collaboration revenue from Genentech and Roche.
Research and development expense for the second quarter of 2021 was $29.0 million euros compared to $18.0 million euros for the second quarter of 2020, the increase in R&D expenses compared to the same period last year, driven primarily by increased expenses for AFM twenty-four including cost for the production of clinical trial material.
As well as an increase in costs associated with our other early stage programs and infrastructure and an increase in share based payment expense.
General and administrative expenses for the second quarter of 2021 increased by 109% to $9.0 million from $8.0 million in the second quarter ended June 32020.
The increase relates largely to higher personnel expenses higher premiums for our directors and officers liability insurance higher consulting expenses and increased share based payment expenses.
Net finance costs for the quarter ended June 32021 increased by 63% from $1 million in the quarter ended June 32020 to $7.0 million.
During the second quarter of 2021.
The increase is largely due to foreign exchange losses related to assets denominated in U S dollars as a result of the weakening of the U S dollar against the euro during the quarter.
Net loss for the quarter ended June 30th 2021 was $26.0 million or 16 cents per common share compared with a net loss of $14.0 million or <unk> 16 cents per common share for the quarter ended June 32020.
The weighted number of common shares outstanding for the quarter ended June 32021 was $125.0 million.
I will now turn the call back to <unk> for closing remarks.
Thanks, a lot the Angus.
It's just explained our company, making significant strides full but by advancing points and demonstrating that I want you know turning nature can play a leading role.
In enabling innate immune cells to identify and eliminate Huntsville.
No place in 13, our strategy development strategy allows us to target the Bronx sense of CD positive NIM.
Thanks Omar.
Indeed, including various types of non Hodgkin and Hodgkin lymphoma.
We're very excited about the potential market opportunity for <unk> in these indications.
And.
We will have additional data for the NK cell combination study by the end of the year.
For any of them 24, we're now executing a strategy that we believe.
We believe gives us the highest probability of success.
We have reached active dose levels.
Escalation study.
And we'll now use this to initiate.
This three pronged development approach in parallel indeed.
Indeed across a broad set of solid tumor indications.
We expect that these are three studies will generate continuous flow okay.
Finally, we are executing on our preclinical pipeline to bring additional product candidates into the Kent.
Our development progress 20, some 28 is indicative of our ability to further expand our pipeline by leveraging.
The unique rock platform and we're working on additional early candidate from the pack.
Many many people have contributed to bring our innovative therapies to patients who need additional options in Kent.
Kent.
These include patients and their families who entrust us with the life of their loved ones our employees.
And the Investor.
Who over the years have supported our efforts.
As always I'm very thankful for the trust you put into our.
Afterwards, thank you.
We're now ready to take any questions that you may have operator.
Ladies and gentlemen, if you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone phone.
Draw your question press the pound key.
Our first question comes from Dana Great Bosh with SBB Leerink.
Hi, all thanks for the question and for the pretty nicely comprehensive call. Two for me and ask me 24 a share.
I believe you mentioned and I just wanted to confirm that you saw stable disease and several patients beyond it we and in that same sentence. You mentioned that you were including any egfr expressing solid tumors I'm wondering if you could clarify whether you saw the stable disease in patients that had more egfr expression was there any correlation with that.
Or even if you could tell us of the patients recruited at five and SEC.
One of them did have high Egfr.
And what you ended up with low Egfr.
That's the first question and the second question is can you confirm how you ultimately they'll select the dose given you haven't had any dose limiting toxicity.
Kent will you be going off a pharmacodynamic activation in periphery, what gives you confidence that.
But that will track with your activity in the tumor will be going off occupancy of 2016 or Egfr or will you continue to try to dose as high as possible. So you do understand your highest tolerable dose oh, Thank you very much.
Thank you Dana I have to check it Andreas is still on the phone I'm sorry I.
Could you follow the questions and okay very good.
Yeah, I'm on the phone I'm, sorry apologize Simon it's a lease so if I break up at some point.
It's due to technology reasons, but I try to stay as long as I can so.
That's what I thought was a second part of your question first.
And also timing.
So as we always said the selection of a recommended phase II dose will be based on Pharmacodynamic markers.
Well as I've mentioned, our mechanism of action is completely different from Egfr.
<unk> targeting agents are likes it took to get them up well also TPI. So we were not expecting to see any dose limiting toxicity like skin mucosa.
And what wasn't in fact seen clinically it just really reconfirms this assumption.
<unk> remains the side effects, which are very manageable.
Seeing in skin toxicity, we tend to be coastal toxicity.
As we've said in terms of Pharmacodynamic markers, we have.
Full array of parameters that we look at.
Most leading to pull out because our markers of reactivation of circulating NK cells as well as the occupancy of the.
The CD 16 receptor.
Well, we see values that are well above that.
There are some EBIT or experimental electrical vakil.
Vivo.
So we feel very confident that we are currently working on a computer.
That's correct.
And.
This is our doses that we would take forward into phase two testing both as a single agent as well.
Some combinations.
Irrespective of this.
So like one or two additional steps just to confirm that we have.
A very good safety profile.
But not necessarily to do with this higher doses for further evaluation.
And off clinical excellence.
In terms of Egfr expression, we are collecting.
And then of course, the highest dose level, who have not all data in the house, causing lower though still have those.
We could not see any correlation between the degree.
Degree of Egfr expression on diagnostic clinical program.
But again because of the data for the two highest dose levels in terms of quantification also come down.
Got it thank you very much.
Our next question comes from Maury Raycroft with Jefferies.
Hi, good morning, everyone and good afternoon and congrats.
Congrats on the progress and thanks for taking my questions.
Also one question on F. 'twenty four you mentioned additional.
Additional inflection points for the program by the end of the year. Just wondering if you can recap what those inflection points are.
Okay.
Yeah.
Yeah, So one of the.
As we've mentioned we are now planning to.
Historically, a dose expansion cohort.
So that's an important milestone and we've also mentioned that there are two additional studies that are being initiated.
The one is the combination study with natural killer cells and the other one is the.
Study with.
So Lisa so these are three very important.
Inflection points.
Mind.
And in addition, we can provide updates.
As we proceed with a dose escalation study.
You have heard from Andre us, but we have that expanded.
The expanded.
Cohorts five and six to include more patients those data will be collected and analyzed and once available. We are planning to share this data with you.
Got it that's helpful Marie.
Yes, yes, I'm still here and I'm, just wondering if you're seeing anything additional about any more specifics on the activation markers and cytokines accretion that youre, saying youre providing anymore.
Aren't.
Yeah. Thanks, Mark Good question at this point not specifically, we would like to share that I mean, we have sets just to repeat maybe what a dresser already said, we look at our activation and exhaustion markers on circulating NK cells, we look at infiltration of yourselves and some of the biopsies. We if we look at the site.
Time levels, but of course as we have reported in addition to our exposure. So PK parameters also receptor occupancy and we will share that in more detail. Once all the data is audio also mentioned will be.
<unk> together and then she will also share the specific market issues.
Yes.
Got it Okay. And then also wanted to ask about the AFM 13, plus NK cell combo.
Can you say if you have responses at the highest dose at this point and how many patients total at the highest dose are planned for per se.
So we haven't disclosed any such detailed for the time being as.
Yes, we are preparing for a.
Presentation later in the year as far as outlined so that'd be computer the composite but in short. The plan has been is that we have in.
In each cohort initially three patients.
And of course, it's only let's say Oh.
A certain number of NK cells, which has increased by a factor of 10 when the safety is warranted.
And as.
As I tried to send to the six cells per kilogram, they moved to tend to the 7% tends to be a.
And these are patients.
Patients, we haven't seen any dose limiting toxicities or any any.
So let me get back to it.
So quite safe.
And overall, what I can say here is that the wheels are encouraged by the responses that we're seeing after the after because assessments.
Additional patients are treated.
So we have continued to enroll patients or M. D. Anderson has continued to enroll patients at the highest dose cohort and that's currently ongoing.
Got it okay.
Okay. That's helpful. And then my last question then I'll hop in the queue.
Repaired remarks, you said the program.
13% case, all Commvault program would be robust and could enable discussions with regulators for approval strategies.
Wondering if you think you'll have enough data by year end 'twenty one to enable these discussions.
In terms of timing we've been lucky.
Let you know as soon as we have such data, it's an ice tea. So we're it depends on the M D. Anderson.
To enroll these patients.
And so I would tell you that we have to wait for.
For a little while before we can confirm.
This next activities.
This is an important activity, but as we feel it's not the only very important activity. The other one is that.
We can proceeds with the NK cells and its manufacturing and I wish sharing tuned used today that we have.
Made good progress on the on this front as well first we're not working with a C. D M O.
For the manufacturing of the cord blood derived NK cells and you have to generate the first data off of kind of persist.
The 13th.
Pre context, NK cells and determined that our activities.
And in preclinical experiment.
Yeah.
Got it okay, Congrats again and thanks for taking my questions.
Thank you.
Our next question comes from Nick Abbott with Wells Fargo.
Oh good morning, Thanks for taking our questions and.
We're literally sounds delightful I have to say.
Just starting off maybe on an F N T.
You mentioned the C D M O D.
Is this using cord blood from MD Anderson.
However, there are no they licensed the technology from them, but.
Are you restricted to where the cord blood.
Sales come from which bank they come from.
So yes, we have a license to the our entire technology.
And this would also include indeed in Europe on the Kraft installation, that's being conducted by MTN.
And here I'm thinking in terms of whole blood to ultimately not restricted.
To any specific source. So we can close this stuff from M D Anderson, but also independent.
Places.
And so.
So in essence, saying, that's how we that's how we have set it up is that a specific reason why you were asking.
No not at all not so I'm just thinking if you are going to be you know.
Don't know where the C. D. M O. It is but if you were gonna have a CD or money in Germany. For example, and you know shipping cold blood from M. D Anderson wouldn't be as convenient.
Some of them are in Germany.
Yeah, No, it's an international city and most of it has footprint all over the ropes.
Lastly, one of the very experienced one.
That was important to us again and see Guillermo that has already.
And developed NK cell product.
So we're tapping into.
Specific know how already.
With this with this choice.
And at the moment, our focus is to work with us going through the U S.
Okay, great. Thank you and then just finally.
I'm Tony for the terrific now finally details of those expansion cohorts.
One thing that struck me in the monotherapy that theres not a K Ras mutated colorectal cohort.
You know the NK combo would appear to allow for K Ras mutated.
Colorectal, but did you consider is there a reason why there isn't a K Ras mutated COVID-19, obviously couldn't be egfr pre treated and that's probably the reasons, but I thought I'd ask.
Andreas can you.
How about here.
Yeah, that's a good pick up with that.
Our selection on the expansion cohorts.
All are all based on a pretty thorough analysis see underlying tumor biology M C.
A couple of different players what do you need the immune system.
When we look specifically at K Ross you take of colorectal cancer is not due to the corruption taste, but there appears to be a coincidence that many pay Ras mutated colorectal cancer.
Have very limited.
Okay. So.
Numbers and then some other factors.
<unk> indicated to us that.
Hey, Raj comment Craig about the new type of colorectal cancer one of these indications.
Whereas a patient would need support of an external NK cell source.
And that's the reason why I say ended up basically the study will know suite.
Beliefs that once you are able to supply these came off mute.
Colorectal cancers, with NK cells, and was inappropriate and gauge or I'll, let you put CNA to immune system and in the best position to to work against you, it's very difficult to treat tumors.
So I. Thank you very much and I'll hop back into queue.
Okay.
As a reminder that is star then one if you'd like to ask a question at this time.
Our next question comes from Bill Chen with Laidlaw.
Oh, good morning, and afternoon and thanks for taking the question.
The first question and stuff.
And 13 plus the.
Pulp blood NK cell, which that.
According to clinical trials.
You have.
Do you expect to.
The increase of about 30 patients.
Is the target still or do you anticipate or how is there any modification on that and adapt.
That potentially could be a critical mass for a potential registration study discussion with FDA.
Yes.
Andrea you might want to take that.
Yeah.
First of all if I can confirm is.
That's the protocol.
And in a way that we.
In fact 10 recruits are somewhere between 70 patients at the recommended dose level was this could be a mixture of hodgkins non hodgkins series <unk> expressing lymphomas.
Again, whether it's mass always says this number will be.
He is sufficient for any registration package of course will depend on the exact level.
And definitely this study will allow us probably even early out there.
And then going up to the full recruitment to engage in discussions with FDA and I think Julian just discussions we will learn what what kind of patient numbers and are expecting.
So I think it's a robust study and conclude with Europe pretty good dataset will.
We will enable us also to look at.
Different biology, Switzerland, Sweden, <unk> expressing lymphoma space.
Everything else will really depend on our discussions with FDA.
Great. That's very helpful and maybe just a quick follow up on this which is that is the data anticipated.
Reported at ash or other venues.
Hum again believe disclosure policy is mainly driven by MD Anderson our expectations.
Yes.
We'll submit.
Some of these data.
<unk>.
Okay, Great and maybe just one general question for 'twenty.
24.
Do you have the monotherapy as was the combo specifically with NK.
Sale on boats.
I noticed that the renal cell carcinoma, with only a mono therapy, but not on the combo is there any reason.
Or maybe more specific reason behind that.
Yeah.
So again, it's based on the analysis of biology.
And the setup of the different players of the innate immune system.
Yeah. So of course, you know I'm, a renal cell carcinoma.
Already since we got the wrong time.
This is the tumors that we have.
Well system can exert some tumor control when we specifically looked at the players in the innate immune system or we found that RCC.
It was a good candidate that could benefit from monotherapy. So our first step here is to test monotherapy area from 'twenty four we believe that several police.
The important pieces are in place in RCC.
Selling gatwick could work as a mono therapy.
Of course, if we should see good data that would not preclude that at some point, we may add dimension was an NK cell or a PD one but for the first evaluation system.
That's what helps us to Miss where monotherapy could be quite beneficial for these patients.
Okay, Great and then maybe the last question, which is a housekeeping ones that are in the second quarter of this year, the R&D expenditure as well as revenue has increased.
Go to the R&D expenditure increased quite significantly compared to the prior quarter.
So should we for modeling purposes should we anticipate.
Second quarter, R&D expenditure would be something more.
The base a movie going forward for at least for remaining of the year.
And thanks for.
Yep.
Thanks, Yeah. So a couple of comments there I mean, what we we haven't provided specific guidance on our expenses, but we have provided guidance on our cash runway and what we've said is that we expect our existing cash which is about 200.
A little over 220 million euros will last us into.
The second half of 2023, so you know if you.
If you do the math on that and you know that that's kind of eight to 10 quarters out.
Our cash burn in the low to mid twenties, excluding any impact of additional proceeds from loans or milestones et cetera.
So just doing based on that map you can assume that.
The expenditure level that youre seeing in Q2 of this year.
Probably more relevant as we go forward then the expenses you've seen in previous quarters in particular.
Quarter of last year.
But having said that we do expect that R&D.
R&D expense will be lumpy right away. This quarter, we've had as I said on the call. We had an increase in <unk> from 24, a lot of that's associated with.
Production of clinical trial material for our ongoing study at upcoming studies.
We've also had to ramp up since in our earlier stage programs like air from 28.32.
And you know when it comes to CMT investments both of those can be a little bit lumpy, but long story short fair to assume that the R&D expenditure.
This quarter it is probably more and more in line with where we'll be in the future then.
Been in the past.
Okay, great. Thanks, a lot and again congrats towards a lot of progress here.
Thank you.
We have a follow up question from the line of Nick Abbott with Wells Fargo.
Great. Thanks for taking the follow up and just just going back to the F.
24 trial I believe that currently the trial is being conducted at four sites in the U S U K and Spain.
And you mentioned a USD M O. So can you talk maybe a little bit about.
For the three expansion cohorts.
You know how many sites you.
Expect to be running those trials that and whether they're going to be international coal in the U S and let's be a Simon two stage design for each of the cohorts. Thanks.
Okay. Yeah. Thanks for this question Oh, Nick I'll have either Wolfgang Andreas jumping in here if they can.
Oh, yes, I can so for the expansion cohorts of the monotherapy trial.
We are looking to increase the number of sites from four that we are currently having probably too.
Hmm.
Between.
10, 15.16 sites.
We will continue to be a mixture of all U S side International side. Scott You mentioned currently we have Europe.
Yeah.
Okay.
In Southeast Asia, mainly Korea.
Especially to recruit Egfr mutant patients.
Now the same is true for the PD one PDL one study.
We will have also a mixture of current U S and ex U S sites.
Study, one O shreves ESN pay or one study.
Initially be a U S. Only study with up to four sites for the year.
Initial part and then expanding to cover more sites in other countries. The plans for this specific study ought to be a U S. Only study.
Now in terms of study design. All studies are designed according to a Simon two stage principles. So we will have an initial.
It's worth a defined number of patients of course.
Well different disease type C.
Go no go criteria they'll do that.
<unk> bye.
Mhm type.
And then also the definition of another one.
And of course, there will be a little bit different but.
In general.
Census, with the Simon two stage design with an initial cohort of corporately around close to inflation.
Looking at the pre defined success quite clearly.
Having the ability to enroll up to 30%.
35 patients per cohort.
To verify the initial assumptions, obviously outside of acoustics inside.
Great terrific. Thank you very much.