Q3 2021 Affimed NV Earnings Call
Thank you for standing by and welcome to the <unk> third quarter 2021 financial results and corporate update conference call. At this time all participants are in a listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question. During the session you will need to press star one on your telephone as a reminder, today's pro.
<unk> recorded I would now like to introduce your host for today's program, Alex but yes.
Investor Relations. Please go ahead Sir.
Thank you Jonathan and thank you all for joining us today for our third 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 that it can be found on the Investor Relations section of our website on the call today, we have the following members of our management team Dr. Audi Hirsch, our Chief Executive Officer, and grants our streak of Chief Medical Officer Orange interiors.
Our Chief Scientific Officer, Wolfgang Fischer, Chief operating Officer, Ms. Denise Mueller, Chief business Officer, and Angus Smith, our Chief Financial Officer, the whole team will be available for the Q&A session. Before we start I will quickly go through the Safe Harbor statement today's discussion you can check.
These 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.
Asian 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 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.
Defied under the section entitled forward looking statements in the press release that we issued today and filed with the SEC.
That I will turn the call over to Audi Audi.
Yeah. Thank you Alex and good morning, everyone.
Yeah.
Thank you each for joining our third quarter update call and I am very pleased with the continued progress.
Oh, it's our goal of bringing new and innovative lifesaving medications to cancer patients.
Who need them pipeline positions us with several potential value, creating milestones through the end of 2022.
To date in addition to providing an update on our leading programs will spend a little bit of time to introduce you to <unk> 28, our most advanced preclinical entitling Gainsborough, which is expected to enter the clinic in 2022.
On slide three of the presentation that we made available to accompany our call today.
We summarized the ultimate strategy for developing our in exiting benches.
We introduced our three pronged development strategy to you about a year ago.
And we said to you then we believe this strategy allows us to explore different development approaches, thereby increasing the probability of success.
For each of our molecule.
What we have learned to date about the safety of our molecule is indeed supporting let's just mono therapy bundles of combination approaches.
The first approach where.
Where the patients own immune.
The immune system is still functional.
All of this development.
Turning a per molecule.
Eric.
Our combination therapy approach.
In novel therapeutic combinations, including combination with NK cell therapy, and other I O I O therapies, such as checkpoint inhibitors.
In the case of NK cell combination.
Combined go great car light and pay therapeutic.
Seek out and destroy tumors.
An example of that is our investigator sponsored clinical trial at MD Anderson Cancer Center.
On slide four we are showing where.
Where we are with our leading in ethylene gauges.
I mean from 13 and <unk> 24 in the reasonably added <unk> 28 and industrial.
All three of these in a selling Gainesville bind to <unk> eight on natural killer cells and macrophages with high affinity.
And old combined on specific targets on cancer cell to bring the innate immune system to fight against cancer.
This slide shows our eighth <unk> targets <unk> positive lymphoma, <unk> poor egfr expressing solid tumors and <unk> 28 on these candidates.
123 positive AML patients.
We are embarking on a bronc development strategy for each of our molecules, which we believe.
We will be.
We believe will be the basis for continuous data flow from our pipeline over the next several quarters.
I think we introduced you to our three pronged strategy.
Also made a lot of progress to the point the only thing.
We have published clinical and preclinical data that make us quite confident about the path that we have sent pharma companies.
Our goal in all of these efforts document is to bring innovative therapies to cancer patients.
Often out of these options when it comes to managing that.
These are very sick patients are frequently see that disease return after multiple lines of treatment.
Very proud to have been able to offer these underserved and frequently without hope patients another opportunity.
Might there be peace.
And as we have shown for example, with <unk> and in particular in combination with Mexico.
With that introduction, let me give you a quick update on our program.
Jumping now to slide six.
This shows a snapshot.
But why are we always say you comfort.
Our registration directed study of <unk> monotherapy in relapsed or refractory peripheral T cell lymphoma.
It's on track to complete enrollment in the first half of 2022, and we expect the product guidance about timing for data as we get closer to the completion of enrollment.
We're also very pleased to share with you that the investigator sponsored clinical trial at MD Anderson cancer Center evaluating cord blood derived natural killer cells create conflicts with <unk> going very well.
As of October.
A total of 18 patients have now been enrolled in this study, including Covid patients at the highest dose whether you tend to the eighth in pesos per kilogram basis.
Hollywood.
We can confirm that no dose limiting toxicities have been observed.
And we continue to be encouraged by the response rate.
To date, our key learnings are that the dosing regime is well tolerated and can drive for robust anti tumor responses in heavily pre treated patients.
Our goal is to continue to gather robust data on safety and efficacy.
<unk> 40 <unk>.
N D M D. Anderson have submitted a protocol amendment to allow for an expansion of this study to treat up to 40 patients at the highest dose now including lymphoma patients and so you just don't get positive non hodgkin lymphoma patients.
Finally, we plan to present updated data from this study as a company sponsored event in mid December.
To provide additional details.
On the date and time for this event in the coming.
We're also very excited about our progress with anthem 24, where we believe the execution upon our three pronged strategy will allow for a continuous data flow data over the next over the course of the next several quarters.
Our Chief Medical Officer will now tell you more about where we are with them.
Yes.
Okay.
Thank you Eddie and good morning, good afternoon to all of you.
It's my pleasure and my privilege to give you an overview of our development.
Program with ire from 24 to review some of the recent progresses.
That we estimate in this program.
If we move to slide eight this slide gives you an outline of the development strategy for you from 24.
And as you'll see it as a very comprehensive very broad development approach.
We expect to investigate <unk> from 24 as a monotherapy.
And in combinations with either a PD L. One inhibitor appears to lease them up or with ultra logos NK cells in a total of seven different indications across mine expansion cohort.
This broad approach is intended to deliver the highest probability of success for you from 'twenty for both a single agent and combination partner.
On slide nine we.
Demonstrate the process that we used to select indications and to maximize our probability of success.
So selection of indications for each study was based on a very thorough and very comprehensive analysis.
The use of data of more than 10000 patients across 144 tumor subtype.
And these were initially ranked based on 'twenty criteria, but included but are not limited to factors like EGF receptor expression.
Involvement in function of innate immune system in the tumor microenvironment.
But also looking at unmet medical need.
And potential path to market.
If we can move to slide 10, we show he was the general concept that applies to all of our studies.
All studies.
Basically as I said the selection of indications that the individual situations. We believe have the best chance of therapeutic success.
Yeah.
So the individual cohorts in each of these studies follow an optimized Simon two stage design.
This design provides us with an opportunity to make gated investment decisions.
As the first step each cohort will recruit a 12 to 18 patients.
After we would have a pre planned interim analysis.
This interim analysis associated with pre.
Client success threshold.
In the case of individuals' success thresholds are met.
We will recruit up to 40 patients in each cohort and.
And we believe that this number of patients who will give a solid data to start conversations with regulatory agencies about registration strategies.
Furthermore, since these are open label studies, we will have the opportunity for interim data readout.
With that said, let me update you on the development of AFM 24.
Our monotherapy study, which is shown on slide 11.
As you're all aware the initial part is a dose escalation spark in order to define the recommended phase two dose.
Okay.
It is important to reiterate that the goal of the dose escalation part, whereas to identify as you pharmacologically active and safe dose will play out from 'twenty four as fast as possible.
Therefore in the dose escalation part there was no selection of patients with tumors.
A more likely to respond to single agent <unk>.
It's defined by our indication selection process.
Slide 12 shows you'll hear recruitment status so far.
Up to now we have recruited 29 patients across six dose cohort.
As you can see the study population who covers a wide range of tumor indications.
With colorectal cancer, harboring, either Ross or rough mutations being the most frequent to tumor type.
Also important to note that all of these patients were heavily pre treated with a median number of previous therapies for a range of two to eight previous therapies.
All patients have exhausted all available treatment options for their given tumors.
On slide 13.
We provide a summary of the patients that were treated at the 480 milligram cohort.
Of note four out of six patients are still receiving therapy would pay up from 24.
They are deriving clinical benefit according to the assessment of the treating physician.
Two patients have shown stable disease beyond three months and continue treatment.
A specific note patient five one classified with progressive disease.
<unk> experienced a meaningful clinical benefit and also continue on treatment.
Yeah.
Yeah.
And we plan to submit detailed data from the dose escalation for a presentation at a medical conference in the first half of 2022.
Moving on we are pleased to announce that we have determined that 480 milligrams is a safe and pharmacodynamics active dose and will be all recommended phase two dose of four weekly administration.
As outlined in slide 14.
This decision is based on a comprehensive review of safety.
Pharma could kinetic.
Exposure and Pharmacodynamic data.
Including CD 16 receptor occupancy on peripheral NK cells.
And supported Pharmacodynamic data, we have also met with the permanent serum cytokines and markers of immune cell activation.
Exhibit continuous activation of NK cells at.
Doses of greater than 160 milligrams.
From a safety perspective, no dose limiting toxicities were observed it is a 320 or 480 milligrams.
And the next two slides, we feel the data on the pharmacokinetics and the receptor occupancy.
<unk> reported a recommended phase two dose decision.
Slide 15.
You'll see the PK profiles of all dose cohorts.
As shown on the left side, we observed a proportionality of dosing exposure at doses of 320 and 480 milligrams.
Which indicates that we achieve saturation of target mediated elimination by Egfr.
Meaning that Egfr.
Receptive at these doses are likely saturated.
And as the graph of the right side. You also see is that the trough levels that we are reaching the 320 and 480 milligrams.
Ronen Green and Blue box are comparable to solicit took seem up trough levels at the market picks them up dose indicated as the gray shaded area.
Okay.
If you move to slide 16.
We review here's the data that we have obtained was CD 16 receptor occupancy.
And I would take a minute to walk you through this slide.
On the left graph you see the measured CD 16 receptor occupancy on circulating NK cell.
As you can see that we initially see an increase in C. D. C. C. D 16 occupancy was increasing doses, which plateauing at 480 milligrams.
Indicating a saturation of CD 16 are in the periphery.
Now the important question is how does this translate into the tumor and how is this correlated to activity.
On the right you'll see two curves from our in vitro studies.
The blue curve is tumor cell, killing by NK cells in the presence of I guess in 'twenty four.
The Red curve is CD 16 receptor occupation.
As you can see maximum tumor cell killing.
If achieved this dose ranges that are associated with relatively modest three to 16 high occupancy.
It is important to note, though that when we speak about relative receptor binding that's fee of 10%. This does not mean that we have only activate at 10% of NK cells.
Every NK cell has found I F. 'twenty four but also the individual cell level, there was a 10% occupational available receptors, which already translates into maximum cytotoxicity.
No the vertical line here indicates a drug level from 24.
We expect into the tumor at the dose of 480 milligram.
For this calculation, we have taken a very conservative assumption.
Which is that I guess in 'twenty four concentrations in tumor tissue.
It'll be 200 fold lower than in circulating blood.
But as you can see that even under these very conservative assumptions 480 milligrams resulted in the CD 16, a occupancy in the tumor.
So that is sufficient for maximum NK cell activation.
In summary.
As stated on slide 17.
Or a decision before 400 milligram as our recommended phase two doses based on the good safety profile and so PK and PD PD data that I just showed.
As next steps, we plan to open expansion cohorts at 480 milligrams to explore antitumor activity.
Three selected indications.
In parallel we also plan to continue dose escalation I'll tell you from 24 to 720 milligram.
The court is currently open for patient enrollment.
Additional safety data and provides the basis for alternatives scheduling like once every two or once every three up lubrication Ophelia from 24.
If we now turn to the two combination studies.
Namely as a combination with NK defense Ultra logos NK cell AFM twenty-four one O three and it's a combination study with appear to lease them up a F 'twenty one or two.
For both of these trials the starting dose of I guess from 'twenty four it will be 160 milligrams.
Followed by dose escalation steps through which we will assess safety and to identify a recommended phase two dose for the combination.
These recommended phase two doses will then be used to the dose expansion phase as well.
As I described will follow a Simon two stage design.
Five of six cohorts with interim analysis after close to 18 patients and the ability to enroll up to 40 patients.
On slide 18.
You'll see the design of Q1 O two studies, where we combine <unk> 24, with a test would be some muck.
In this trial, we will focus on non small cell lung cancer gastric cancer and Hepatobiliary pancreatic cancer.
All areas of very significant unmet medical need.
C cohorts in non small cell lung cancer and gastric cancer.
Follows he described Simon two stage design.
The third cohort that can include petco cellular.
Answer biliary tract cancer and pancreatic cancer is designed as a signal identifying basket cohort with descriptive statistics.
Uh huh.
If we move to slide 18.
Here, we show of the design of our studies.
Before one O sleep combination of ASM twenty-four with adoptive NK cell transfer.
This study will focus on.
Non small cell lung cancer.
Colorectal cancer and head and neck cancer.
We will look.
Very different approach in these indications where patients endogenous NK cell numbers.
Our dysfunctional or only exist in sufficient numbers.
It's a good opportunity to show activity.
In contrast to the one O one study, where we also evaluate CRC, but.
Require previous treatment with Egfr antibodies.
And that's where most likely exclusively recruit CRC patients with Skyros why it's Todd.
You see us he caught in one of those three were focused mainly on patients whose key rough mutation.
Finally, anaya from 'twenty four you may have seen the presentation of the most recent triple meeting, where we showed that a F. 'twenty four enhanced cytotoxicity against Egfr positive tumor cells when combined with S. N K one to one.
Logos NK cell product.
The additional failure from 24 total August S N K, one O one self improve.
Improved cell, killing when compared to NK cell to known in Egfr positive tumor cell lines, regardless of the Egfr mutation.
Mutational status.
To summarize on slide 19.
The state of cell C. A F. 'twenty four program. We are very excited that we can now embark on a broad development program in several indications with significant unmet medical needs.
These studies have shown will generate a continuous flow of data in 2022 lets be honest.
With that I will turn the call over to my colleague Entre trader Joe's.
We will present, our novel fully owned I see I guess I'm 28.
Onto please.
Thank you Andreas and also for me good morning, and good day, everybody welcome to the call.
I'm really excited to introduce a <unk> 28 to all of you which is our newest addition or portfolio.
As shown on slide 21, we recently announced our newest innate cell engage various I'm 20, H, which is designed to bind C. D 123, and established targets and myeloid malignancies.
We chose CD 133, as it is almost universally expressed on leukemic blasts and leukemic stem cells in patients with AML, both apps diagnosis, and Ed relapse and independently of cytogenetic risk.
They have some 28 is being developed for the treatment of patients with acute myeloid leukemia.
We believe that as from 'twenty H could be the key to novel treatment approaches that can fulfill several unmet needs.
I would like to spend a few minutes to explain this and lay out why we are so excited about adding 828 to the arsenal against leukemia.
AML is the most common form of adult.
<unk> leukemia more than 40000 patients are diagnosed.
With this disease every year in the seven major markets.
<unk> have remained very poor and treatment options are generally limited.
Particularly for relapsed or refractory disease.
As shown on slide 22 in AML, most patients become refractory.
To standard induction treatment or relapse within one year.
Only one of three patients is alive after one year once they become relapsed or refractory and after five years. It is only one out of 10 patients.
It is obvious.
But new drugs are needed that reduce the high rates of relapse or prolong the time to relapse.
And using deeper responses by eradicating measurable residual disease or <unk> Rd.
In addition for patients who have relapsed.
Or are refractory to standard treatment alternative options to reduce remissions that are long lasting are urgently needed.
This all leads to be cheese for patient population the elderly.
Note that over 80% of patients are over 60 years old and can often not tolerate treatments associated with toxicity.
So these new approaches not only need to be more effective they also need to be safer.
Recent data have demonstrated that natural killer cell based in nature immunotherapy is emerging as a promising treatment option in AML base.
Based on the demonstrated susceptibility of leukemic blasts.
NK cell killing.
Clinical activity of allogeneic NK cell therapy, and relapsed refractory disease. Also these treatments are remarkably well tolerated yet these approaches rely on the cells natural ability to recognize leukemic cells.
These cells are not specifically targeted against the tumor.
Immune evasion from NK cell, killing is a well known phenomenon.
And escape of leukemic stem cells in AML has been described so to effectively deplete leukemic cells, including leukemic stem cells. A targeted approach. In addition to a natural cytotoxicity has the potential to induce more frequent and deeper responses.
We believe these statements are also supported by the data that we have generated with <unk> in combination with NK cells.
We designed a from 28 to be differentiated versus what's available therapy Andrew.
And to bring a truly novel approach to the treatment of AML.
As we show on Slide 23, and 28 binds with high affinity to both CD 123, and <unk> 68, and no such molecule currently exists to our knowledge.
Thereby strongly activates NK cells inducing a D C C and through binding to CD 123 causes depletion.
Leukemic blasts and leukemic stem cells.
We will be presenting preclinical data from 28 at Ash and plan to submit an IND application in the first half of 2022 and to start a clinical study in the second half of 2022 with that.
I'll hand, the call over to Angus to review the financials Angus.
Thank you art.
<unk> consolidated financial statements have been prepared in accordance with <unk> as issued by the international accounting standards Board or <unk>.
Consolidated financial statements are presented in euros, 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 ended the third quarter of 2021 with cash and cash equivalents of $198 7 million euros compared to $146 9 million euros 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 September 32021 was $25 6 million euros compared to $3 6 million in the third quarter of 2020.
Total revenue for the third quarter ended September 32021 was $8 7 million compared to $10 5 million euros for the quarter ended September 32020.
Revenue for the third quarter of 2021, mainly comprised of collaboration revenue from Genentech in right now.
Research and development expenses for the third quarter of 2021 was $20 6 million compared to $10 1 million for the third quarter of 2020.
The increase in R&D expenses compared to the same period last year, driven primarily by increased expenses for a 24.
<unk> cost for the production of clinical trial material and increase in costs associated with other early stage programs and infrastructure and an increase in share based payment expense.
General and administrative expenses for the third quarter of 2021 were $6 8 million euros.
Compared to $3 5 million euros.
In the quarter ended September 32020.
The increase relates largely to higher personnel expenses higher premiums for insurance higher consulting expenses and increased share based payments.
Net finance income for the quarter ended September 30 of 2021 with $1 5 million compared to net finance loss of $3 1 million in the quarter ended September 32020.
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.
Net loss for the quarter ended September 30 of 2021 was $17 1 million euros or <unk> 14 per common share compared with a net loss of <unk> 6 million or seven cents per common share for the quarter ended September 32020.
The weighted number of common shares outstanding for the quarter ended September 30 of 2021 was $119 $8 million with that I'll turn the call back to Amit for closing remarks.
Thank you Angus.
As you've heard we've made.
<unk> progress.
Our two lead program thing you from 13 in 'twenty four and soon we plan to have it and engage huh.
That's unprecedented cold Dania from 28 in the clinic.
As we now look ahead.
On slide 24, we expect the rest of this year and 2022 will be busy as we have numerous clinical trials from which we expect to report data.
We expect the key milestone Rs positive.
I'm wondering if I'm thinking we will host an investor event in December where we plan to provide a data update on our ongoing trials in combination with Mexican ourselves.
An additional quite you compared to monotherapy in peripheral T cell lymphoma, we expect to complete enrollment in our registration directed study in the first half of next year.
With broadly explain where we stand with a F. 'twenty four and Pomona therapy. We are now planning to open the expansion cohort before the end of this year.
We need to submit an abstract with data from the dose escalation for presentation at a medical conference in the first half of 2022.
And then as we move forward with the expansion cohort report initial data in 2022.
We have set up two additional started 20, some 24 combinations either with natural killer cells.
With the anti PD, one is a lease them up.
We are expecting to complete the first dose escalation cohort in each study during the first half of 2020 to start with the dose cohort expansion.
Safety is favorable and thereby also be able to provide update as we progress.
What are you from 28.
Very new candidate that we carefully selected in order to address the high unmet need.
After the ash data update on the next milestone.
<unk> submission in the first half of 'twenty through 'twenty, two and subsequently the initiation of clinical studies, we're planning again as explained before.
In monotherapy and.
Combinations in particular in combination with Mexico.
We are preparing the company to meet these opportunities and look forward to bringing.
Innovative medicines to patients that need them.
Now on behalf of the entire team I would like to once again express my gratitude to everybody who's contributing to these efforts.
We're now ready to take any questions that you may have operator.
Certainly ladies and gentlemen, once again, if you have a question. Please press Star then one.
Our first question comes from the line of Dana Great loss from SVP Leerink. Your question. Please.
Hi, Thank you for the questions just looking at the data that you presented on 24, maybe a two part question.
Remind us why you think these three extent planned expansion cohorts will be most amenable to single agent activity. So the theory T. K Ras Wild type Egfr mutant lung and RCC and then it is I guess those tumor types, where you did see that the stable disease or that pay.
With progressive disease that continues on treatment I can just.
Or anything more about those patients that they have on high Egfr expression are where they are refractory to other egfr targeted therapies. Thank you.
Thanks Dana.
Over to Andreas please.
Yeah.
Yeah, Hi, Dana so.
But let's start with probably with a second question or second part first.
So the patients that we have treated on 480 milligrams.
It helps us to patients with Egfr mutant non small cell lung cancer and.
All colorectal cancer patients.
Important to note we.
Fixed or we decide which couldnt be nate or which.
Tumor types will go into which helps the studies prior to seeing the data and as I.
This decision was really driven on this comprehensive analysis that we showed where we looked at the data for more than 10000 patients and then really looking at.
Biology, all CNI at immune system.
Activating and inhibiting factors NK cell biology.
So what do we see now here on slide six again very small on a call. It six very small patient numbers.
It's a little bit maybe on the early confirmation of our selection process. If you look at the colorectal cancer patients with wild type patients number one all of this would be a patient who would have qualified for the expansion cohort patient number three egfr mutant non small to another patient that they would have quantified and patient five again, Jeff I'm using would be patients that would have quality.
Slide all the other two patients two and four where we have a follow up data patients six it's very early in this treatment would have not quantified for the expansion cohort as monotherapy.
So again the sequence was different.
Look at the biology, first and then decided to which are the most likely.
Cohort can almost like a tumor types that can respond again with this very small data set there seems to be a trend that's exactly what these two months really to do quite well on.
<unk> 24, a mono therapy.
We have measured GFR across or cohorts, most patients have moderate to high expression.
I don't have any individual patient numbers on data, but I wouldn't expect us to egfr mutant non small cell lung cancer patients have a rather high expression of egfr receptor and so require months I hadn't needed to exhaust all previous lines of therapy. So all of these patients have been pre treated and have become real.
Isn't it.
Egfr targeting therapies once they get to <unk> or antibodies.
Very helpful. Thank you.
Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Your question. Please.
Hi, Good morning, Good day, everyone and congrats on the updates and thanks for taking my questions.
I had a question on the air from 24 to <unk> for that one you showed a lot of helpful. PK and PD data I'm wondering if you can tie it together with what Youre seeing in the six patients at 480, Megs, particularly in respect to anti tumor activity as you approach steady state and if you can talk more about what youre seeing on cytokines and NK cell activation.
<unk> markers as exposure increases.
Yeah.
I can take the first part and then they handle the two arent regarding cytokine.
So you're asking if youll see all of these patients are treated at two 480 milligrams. So this will see dose level, where we achieve.
Dose proportionality, so we have basically.
Saturated egfr binding as we showed we also achieve CD 16 receptor occupancy and then correlating.
Figures into tumors that.
According to our experiments are sufficient to maximum activation of.
Tumor residing NK cells.
We have not broken down these data on an individual patient level yet but.
Or is it something that we will have to do in the future.
And maybe.
And talk on the NK so yeah.
Yeah sure happy to do so so you noted maury, we didn't share that data because we want to disclose that.
As discussed at an upcoming conference in 'twenty, two what we see what I can share with you in terms of the cytokines to give you. An example in for gamma TNF Alpha important point, because I'll activation.
This is at or above.
Above 160, when we look at the steady state levels, we see a steady increase.
Didn't see a real difference between 320 in for 80, but we see that clearly was rising above 160, making the point again that this is clearly a pharmacologically active in terms of the activation markers. Similarly, we wanted to share that data when it's also a little bit more matured.
But the same trends that we see at doses above 160, we saw an increase of those activation markers again, showing that we have consistent NK cell activation.
Hopefully that helps with your question.
Yes, yes, that's very helpful and maybe one other question on the AFM 13, plus on cord blood NK cell combo study just wondering if you can talk more about expectations on durability for this upcoming.
Update and also just checking if you have plans to move this study over to this sponsorship at <unk> at some point.
Andreas can you take the question.
Yes.
Oh, yeah, so what do you see or what you realize is when.
Compared to the status that we have basically by the middle of June or so.
We have added a very significant number of patients over the last couple of months. So I would say that for the highest dose cohort.
Time to progression or duration of response data will be key.
Quite immature in December and since many of these patients.
Simply stop the treatment within the last three four months.
So of course on the lower doses, we have a longer follow up but against these would not be as a therapeutic doses.
We'll move into our experience from cohort and you subsequently.
Now in terms of sponsorship are we have not.
Syed.
We always said we are working on with <unk>.
Although most to <unk>.
For.
<unk> process, we are in the process of doing that.
And we'll provide updates once we have more concrete data to share.
Got it okay. That's helpful. Thanks for taking my questions.
Thank you. Our next question comes from the line of Cooper Deborah concept from twist Securities. Your question. Please.
Hey, guys. Thank you so much for taking my question and congrats on all the progress.
Have a follow up question on the FM 13th.
The cord blood NK cell combo can you talk a little bit about the decision to.
Expand into both HL and NHL patients.
What should we expect the split to be sure.
Or are you looking to enrolled more NHL patients.
And maybe talk a little bit about how that if at all this changes your strategy in what you're focused on whether it's a chandler.
And each other.
Thank you so much.
And so again Andreas.
Andreas answering your question Andreas.
Oh, yeah. So as you know CD 30 is a target that is expressed on hodgkin's, but also on.
Non hodgkin's lymphoma like like T cell lymphoma subset of CD 30 positive B cell lymphomas.
Currently we are following if you will a two pronged approach.
Clearly our main indication.
It was the first indication I would say, we'll be Hodgkin's lymphoma, where we have fully.
The wells so stay tuned who we have seen this very impressive responses already in the first four patients.
This is the study is the smell designed that it will recruit facility.
Hodgkin patients at the recommended phase two dose, which we believe gives us good data set to move on was Hodgkin's on the registration Paas.
Now the second part is a little bit opportunistic again, just also very significant medical need and in peripheral T cell lymphoma, and diffuse large b cell lymphomas.
So we thought that we at least should explore NK cell based I guess from certain based combinations in these diseases that could potentially result in a second or a second and a third.
Development pathway. So this is really broadening the indications, but for now Hodgkin will be our lead indications, where we will try to move ahead with full steam.
Great. Thank you and just a follow up question on the FM twenties for the data that you presented them you know you've been dose escalating for a while but have you seen any indication, especially if its in overdoses, where patients have been treated for a longer period of time, a deepening of responses.
Well, we have yeah.
We have.
Okay. So <unk> seen some disease stabilization has to see lower doses.
But again according to our data rooms.
Mexican pharmacokinetic and Pharmacodynamic axis or activity was set on set in around 160 to 320.
It was Friday being our selected dose right now so these are really anecdotal.
Anecdotal observations.
As we set out of 480 milligram cohort four of six patients are still on treatment.
This was an interesting two cohorts to watch whether we do see a deepening of responses.
Great. Thank you very much.
Thank you. Our next question comes from the line of Nick Abbott from Wells Fargo. Your question. Please.
Oh good morning, Thanks for taking my questions and thank you for all the detail on that.
[noise] ton tool.
First question is on <unk> 28.
Can you speak to why TD, one synergies three and in the context of the C. D. Three big thirty-three engaging you built for am Salina compares PD 123 to <unk> 33 in <unk> and NHL to T cells.
In this application and I am now thanks.
Oh, Yeah, we're happy to take this question arent.
Yes, happy happy to do that because we I think we already also.
Provided some some background information as you Ivy Samson.
CD 33, I think a very valid targets of course in combination with a C. Three of the T cell engagement.
Why are we why have we selected maybe let me speak about our rich Rage CD 123. One is it is very broadly expressed on the leukemic blasts. Its also expressed equally leukemic stem cells.
And.
Fortunately non most on the healthiest stem cells. So we have a very high selectivity.
We've also followed our approach in selecting those when we look at in a way that's.
Programs that have been out there like an FC enhanced CD 123 talking to an antibody that was comes from cutoff.
Johnson <unk> Johnson, while ago Tulloch could choose them up that was not continued because as an FC enhanced antibody without the additional mechanisms of actions that we believe we add in terms of also the efficacy in terms of the let's say chewning engineer with the molecule.
We see a great potential.
To address that medical needs. Indeed also with those approaches telecom Susan.
Occasional.
Complete responses were seen where we are specifically size. It is in the prospect of course testing monotherapy, but then very quickly combining if I'm 28 with allogeneic NK cells, why because we know in AML was a myeloid disease and.
K cells, and macrophages will not be fully at least fully functional or not functional so adding in a way you could say the payload of the mechanism of action with allogeneic NK cell transfer, we see a very high probability of success to getting to those deep responses that we're looking at which is this.
Very high medical need to really get to also minimal residual disease negative patients hopefully that kind of addresses your question.
Yeah, and I think I get the point of NK cells T cells emphasizes this safety advantage, you're seeing on the range for that.
NK cells or T cell engagement.
Yes, absolutely.
That is an important one we have now seen consistently across our innate cell engages excellent safety profile I mean, some of the early hours that we have seen very well manageable schedule pre treatments. So NK cells are just by the knee.
Sure of their biology.
Very effective.
Much safer them T cells again, I think we know the principal by now it's not only the cytokines storm, but it's it's also really the.
All three immune effects that we see where T cells once unleashed, just not selective and kind of targeting for.
Attacking the tumor versus health situations bearish NK cells, very well distinguish clearly thus very much better safety profile and as I laid out I think when you look at the very elderly patient population that we have frail patients.
It will not tolerate some of them.
The high dose chemotherapy, we see this as a very differentiated good profile with an NK cell engagement.
Perfect and then maybe just last one for me.
Solid tumors.
We've described pretty elegantly a three pronged strategy.
Already elucidated to an NK cell combo Sun.
28 at least two problem is there a three pronged strategy that you think are applicable for F. 'twenty eight myeloid disease.
That's a really good question happy also for Audi or on dress to jump in.
We have currently you know also publicly said we want to make the combination with allogeneic NK cells, a priority because of the reasons I've been giving there may be cases for also the go to a third pillar.
Not something that we have fully thought through and two with updates accordingly.
Move on with our plans.
Perfect. Thank you very much.
Thank goodness.
Thank you. Our next question comes from the line of Brad Canino from Stifel. Your question. Please.
I. Thank you and appreciate the updates today just quickly on the protocol Amendment for AFM 13, NK was that driven by M. D Anderson or by your team and if you could talk more about the reason behind that.
And then I'm also interested in the breakdown of the six AFM 24 patients you had at the 480 Meg cohort you highlight all three of these would have been eligible for the monotherapy expansion cohort, but they had four to seven prior lines of therapy. It looks like in the expansion cohort should we expect this new.
Number of prior lines of therapy or will you be looking for patients that may be earlier, one or two prior lines. Thank you.
I guess my question.
Yeah, Yeah, so let's start with with the amendment of the protocol.
I think.
Importantly, we have a very good very close working relationship with MD Anderson so.
I would say it was basically a joined joined F. A joint decision initial.
Initially the protocol was only designed to evaluate safety.
So it was a pure a phase one safety protocol.
Then I would say even for us a little bit unexpectedly we saw this really significant antitumor activity.
Already at the lower dose levels and.
So we immediately developed.
Desire to gather more efficacy data.
Basically puts us.
Compound on the development path.
So we use the existing protocol to allow for more patients at the recommended phase two which will give us a sufficient number of patients to really have a good solid estimation of efficacy in Hodgkin's lymphoma, and as we always said will provide a few basis too.
<unk> was healthcare with regulators.
For the most appropriate under the fastest path towards approval. So this was a joint decision on it was really driven by our enthusiasm both MD Anderson power centers he hasn't been about the data that we see.
Now in terms of the expansion cohorts in.
The one O one youre right because these patients are heavily pretreated.
And I think I'm taking.
Taking this into account seems this degree of activity.
In late line at least for US, it's really very encouraging.
Whether there will be less pretreated patients in the expansion cohort a little bit hard to say.
The expansion cohort still requires that patients have exhausted all available treatment options for their respective diseases. So.
I would say, we will see the majority of patients with three to four lines of previous therapy.
Again, we are doing here in an area of very significant unmet medical need.
Generates a higher bar.
And but on the other hand, we believe also.
<unk> for a potential accelerated approval process. If you can show robust and reproducible activity in patients who have no treatment alternatives left.
Okay.
Thank you.
Yeah.
Thank you once again, ladies and gentlemen, if you have a question at this time. Please press Star then one.
And this does conclude the question and answer session as well as todays event third.
Third quarter update call. Thank you, ladies and gentlemen for your participation you may now disconnect good day.
[music].
Yeah.
Okay.
[music].
Yes.
[music].
Okay.
Yes.
Yeah.
Okay.
Okay.
[music].
Yes.
Okay.
[music].
Okay.
Hum.
[music].
Hum.
Yes.
Okay.
[music].
Yes.
[music].
Okay.
[music].
Okay.
[music].
Okay.
[music].
Okay.
[music].
Okay.
Okay.
[music].
Yeah.
Yes.
[music].
Okay.
Yeah.
[music].
Yeah.
[music].
Okay.
Yeah.
Okay.
Okay.
Okay.
Okay.
Yes.
[music].
Okay.
Yeah.
Okay.
Okay.
Okay.
Sure.
Yes.
Sure.
Okay.
Okay.
Okay.
Sure.
Yes.
Yes.
Okay.
Yes.
Okay.
Uh huh.
Okay.
[music].
Okay.
Okay.
Okay.
[music].
Yes.
[music].
Okay.
Yes.
Okay.
[music].
Sure.
Yeah.
Okay.
Okay.
Okay.
Sure.
Okay.
Okay.
Okay.
Yeah.
Right.
Yes.
Yes.
Yes.
Okay.
Okay.
Okay.
[music].
Okay.
Okay.
Yes.
Yes.
Yeah.
Okay.
Okay.
Yes.
Okay.
Okay.
Yes.
Hum.
Sure.
[music].
Okay.
Okay.
Okay.
Okay.
Right.
Sure.
Okay.
Okay.
[music].
Okay.
Yes.
[music].
Yes.
[music].
Thanks.
Yeah.
Okay.
Yeah.
[music].
Okay.
Okay.
[music].
Yes.
Yeah.
Okay.
Okay.
Yes.
[music].
Okay.
[music].
Okay.
[music].
Okay.
[music].
Okay.
Okay.
Great.
Okay.
Okay.
Okay.
[music].
Okay.
[music].
Hum.
Yes.
Yeah.
Right.
Okay.
Okay.
Okay.
Sure.
Okay.
Okay.
Yes.
Okay.
Right.
Okay.
Yeah.
Okay.
Okay.
[music].
Okay.
[music].
Right.
Hi.
Yes.
Okay.
Hum.
Yes.
Yes.
Okay.
[music].
Yeah.
Right.
Sure.
Okay.
Okay.
Okay.
Yes.
Yes.
Okay.
Yes.
Okay.
Okay.
Yes.
Okay.
[music].
Yes.
Yes.
[music].
Okay.
[music].
Yeah.