Q3 2022 Affimed NV Earnings Call
Yes.
Okay.
Thank you for standing by welcomed.
Welcome to today's third quarter earnings and business update conference call the estimate N V.
As a reminder, all participants are in a listen only mode.
And the answer session will follow the final presentation.
Please note this conference call is being recorded.
I would now like to hand, the call over to your host for today, Alex for the TS director of Investor Relations. Please.
Please go ahead.
Shannon.
Thank you all for joining us for our call today.
Before we begin I'd like to remind everyone that we issued the relevant press release earlier today, which can which can be found on the investor Relations section of our website on the call today, we have members of our management team, including Audi Hirsch, Our Chief Executive Officer, Andreas <unk> strike, our Chief Medical Officer Orange juice.
Williams, our Chief Scientific Officer, Wolfgang Fischer Chief.
Keep operating officer, Denise Mueller, Chief business Officer, and Angus Smith, our Chief Financial Officer.
Our team will be available for Q&A after the prepared.
Before we start I'd like to remind you that today's presentation contains projections and forward looking statements regarding future events. These statements represent our beliefs and assumptions only as of the date of this call except as required by law, we assume no obligation to update these forward looking statements publicly or to update.
The reasons why actual results could differ materially from those anticipated in the forward looking statements, even if new information becomes available in the future. 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 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.
Thanks, Alex Good day, everyone.
Thanks for joining us for the third quarter update call.
Let me start with the most important updates that we announced earlier this month.
We are showing on slide four ophthalmic stem extensive evaluation of the available.
On November 3rd we announced a new collaboration with are keyed up.
Building on our already established relationship to take the combination treatment of <unk> and our team of Cryopreserved. This route cord blood derived NK cell product candidate called <unk> hundred one with cricket.
For Us this collaboration is a natural evolution of the AFM 13, plus NK cell program.
As we move this therapy from an early stage into late stage development.
And begin to position the combination for commercial success.
According to our analysis. This partnership represents the fastest option to make this combination therapy available to patients.
We are convinced that we made the right choice or <unk>.
Now through this collaboration we obtained access.
With a highly act.
Active NK cell program.
As shown on slide five.
We've generated preclinical data showing the highly synergistic anti tumor activity of the combination.
<unk> <unk> with <unk> 101.
Overall based on the breakdown of your data generated as well as our previous experience of administering <unk> with a cord blood derived NK cell product.
Compared to the Monopole study, we're confident that <unk> administered in combination with <unk> 101 has the potential to generate a robust ADC response.
In clinical activity in patients with relapsed or refractory Hodgkin lymphoma.
So you could say would be positive peripheral T cell lymphoma.
Okay.
Other factors were considered when selecting a <unk> 101, and this included the fact that <unk> 101 is already in clinical development with our key R&D.
And it's a cryopreserved off the shelf program.
To demonstrate consistent consistent and high <unk> expression.
A GMP grade manufacturing site with the right scale for clinical trials and future commercialization.
Available.
And the product is viable cost structure.
Moving to slide six it shows that the terms of the deal with our team to allow us to accelerate the development of the combination therapy now by leveraging the financial resources of the two companies.
Ultimate will initially pay for the clinical trial costs of the phase II study.
In our Tivo bolt supply.
Oh, one and out to for this study at their cost.
Cost of any confirmatory study will be safety.
Please proceed.
And those revenues will be shared with ultimate now receiving 67% of the revenues of the combination.
In our efforts to move forward quickly.
Also making progress on the regulatory front.
We already requested a pre IMD meeting with the FDA in early September and the agency has indicated that they will provide feedback to us by the first quarter of 2022.
This is a little later than the usual 60 days, which the agency has informed US is caught a significant backlog.
Still our goal is to submit the nine equaled a combination study in the first half of 2023 and begin to generate steady lengthening the.
We believe that we'll be able to move into the clinic quickly because of the robust clinical and preclinical data that has been generated for each product on its own.
The breakdown of the data that we've collected from our over two year collaboration.
And Theyre very good safety profile that we've seen in our combination study with <unk> and <unk> and Copeland.
Cord blood derived allogeneic NK cells.
So as you can appreciate we are at a very exciting point in the development of outcome.
In addition to the data and business updates we provided in the last few weeks, we are preparing to announce key catalysts that could have a meaningful impact for our company and the patients we serve.
These include top line data from the phase two redirect study of <unk> in peripheral T cell lymphoma in mid December .
Data from the combination of <unk> with NK cells.
Now to tell you more about our clinical programs and some of our recent data I'll hand over the call to Andreas.
The address.
Thank you.
Also a warm welcome from my side to everybody on the call.
I would like to take the opportunity and provide an update on our clinical programs and the progress that we have achieved.
Let us start with our AFM 13 program on slide nine.
Our registration directed monotherapy study of AFM 13.
In relapsed or refractory peripheral T cell lymphoma also known as redirect has completed enrollment earlier that here.
As previously communicated we expect to report data from this study.
At December .
The study has enrolled more than 100 patients with relapsed or refractory <unk>.
<unk> positive peripheral T cell lymphoma.
And the focus of the initial data release.
It'll be on the overall response rate.
So assessed by a blinded independent review committee.
Which is the primary endpoint of the study.
And our preliminary assessment of the duration of responses.
As well as in analyses of safety.
As a reminder.
Peripheral T cell lymphoma is a disease with significant unmet medical need.
And our estimates there are about 1500 patients in the U S alone with relapsed refractory P. T C L.
And treatment options remain a very limited and the prognosis for these patients is poor.
As also previously communicated we plan to initiate the discussions with the FDA following our analysis of <unk> data.
Secondly, I'm searching study that is ongoing.
Our phase one two study AFM 13, one O four in collaboration with MD Anderson Cancer Center.
Evaluating cord blood derived natural killer cells pre complexed with AFM 13.
Kevin.
One infusion.
Followed by three single agent AFM 13 treatments.
In patients with relapsed and refractory <unk> positive lymphoma.
On Slide 10, you can see as you highlights from the ash abstract from a couple of weeks ago.
We showed that as of July 31st.
The cutoff date for the annualized is that provided data for the abstract.
24 patients have been treated at the highest NK cell dose of one times 10 to the eight NK cells per kilogram body weight.
So this represents an increase of 11 patients since the data reported at AAC or earlier this year.
To highlight the overall response rate at this dose has been maintained at 100%.
The complete response rate increased to 78%.
An improvement over the 61, 5% CR rate.
We reported earlier this year at ACR.
As announced in our press release, Dr. Jago near term.
Professor of stem cell transplantation, and cellular therapy after University of Texas, MD Anderson Cancer Center and.
And principal investigator of the study.
We provide an update from the.
Ongoing phase two trial.
At Ash on December 10.
Now, let's turn.
Turning to <unk> 24.
Yeah.
Okay.
As you can see on slide 11, we show is that we are continuing to enroll patients in all three ongoing studies.
Including the expansion cohorts of our monotherapy study.
And see dose escalation cohorts for the combination studies with <unk>, so lease them up.
S N K L. One see autologous NK cell product from <unk>, respectively.
And see I guess I'm twenty-four monotherapy trial, we are continuing to enroll patients in the expansion phase at the recommended phase two dose of 480 milligrams weekly.
The expansion cohorts include patients with renal cell carcinoma.
Non small cell lung cancer with activating Egfr mutations.
And colorectal cancer, which are key Ross why its type.
Okay.
And the combination studies, we are continuing to enroll patients in the dose escalation phase of the two studies.
As a quick reminder, so the primary purpose of the dose escalation phase of studies.
Is to establish the safety of the two combinations and identify the recommended phase two dose for further testing.
In F 'twenty for one or two.
It's a combination study of AFM twenty-four given weekly with artists or lease them up at the recommended phase II. So recommended dose given every two weeks.
We are enrolling patients with non small cell lung cancer, which are egfr wild type.
Gastric or gastroesophageal junction adenocarcinoma and patriotic happy to sell you Larry biliary tract cancers.
We completed the first dose escalation cohort of 160 milligrams weekly of F. 'twenty four.
Without any dose limiting toxicities.
Yeah.
Furthermore, as the first three patients at 480 milligram dose.
And that will be enrolled and completed their dose limiting toxicity period without <unk>.
According to a protocol that we are enrolling additional three patients at this dose to confirm 480 milligram as he recommended phase two dose for this combination.
The second combination study of F. 'twenty four one O three.
Investigating the combination of AFM 24, with NK or one <unk>.
The ex vivo expanded and activated autologous NK cell therapy from NK Gen biotech.
And this study is both agent AFM twenty-four MTL K cells are given weekly too.
Two patients with non small cell lung cancer Egfr wild type scrape.
Squamous cell carcinoma, head and neck and colorectal cancer.
In this study we have completed the first dose escalation cohort, which treated patients at 160 milligrams of air from 24 with no dose limiting toxicities.
We are currently enrolling patients at the 480 milligram dose of <unk> 24.
On slide 12.
We are showing a summary of two presentations such represented at our fifth C Immunotherapy Congress last week.
First the monotherapy study.
Relative science data from the dose escalation portion of the study.
Provided interesting insights into the mechanism of action of <unk>.
Our findings showed that starting at low doses of <unk> 24.
NK cell activation could be seen in the peripheral blood.
The CD 16 receptor occupancy also increased in a dose dependent manner at lower doses.
But level off at a dose of 320 milligram into bus.
Indicating that this dose receptor occupancy was saturated.
We could also demonstrate activation of cytotoxic T cells from the periphery.
Pointing to a simultaneous activation of the adaptive and innate immune system.
Furthermore, when we looked into tumor biopsies by immunohistochemistry in gene expression profiling.
Translating the findings from the Paris lots to the tumor.
We saw that NK cells, and cytotoxic T cells increased in the biopsies of air from 24 treated patients.
Indicating.
So it's hard to toxic cell function of both NK and T cells are increasing significantly.
This data demonstrates that air from 'twenty, four activates the innate and adaptive immune system into tariff rate and in the tumor microenvironment.
And paces away for combinations with checkpoint inhibitors.
And NK cells.
So this brings me to the combination study with Telstra leased them up the phase one dose escalation study in the phase one dose escalation study.
Here you showed us that clinical activity was observed in two patients in the first dose escalation cohort of 160 milligrams of F. 'twenty four weekly.
As you can see on the slide well honestly patients was a patient with gastric cancer.
So this patient had already been treated with a temporary lease them up and chemotherapy combination in first line.
Followed by three lines of ferrous chemotherapy regimens before included into the trial.
Importantly, two September lease them up chemotherapy combination in first line. So patients had only achieved very short lasting partial response, which was followed by progression of metastasis, while still on a temporary visa map treatment.
Yeah.
It is important to note that this represents a <unk> profile without a response to single agent PD, one re challenge it's very unlikely.
The second patient a patient with pancreatic adenocarcinoma exhibited stable disease on the combination of <unk> from 24, plus artists or lease them up.
After showing progressive disease on three different previous chemotherapy regimens.
We are expecting submit to submit data from all three are from 24 studies two major scientific conferences in the second and third quarter of 2023.
Okay.
On slide 13 for F 'twenty eight.
We announced an abstract at ash, which will describe as a preclinical in vitro models using a panel of AML lines showing officials sea and.
And antibody dependent cell mediated cytotoxicity.
Against CD 123 positive tumor cells by.
By a combination of allogeneic NK cells and <unk> from 2008.
So it's combination induced highly potent and selective license of CD 123 positive leukemia ourself.
And included cytotoxicity against leukemic stem cells and programmed it yourself.
We believe that this is an important finding.
That's the ability to eradicate leukemic stem cells is associated with durable responses and.
And the potential for long term remissions in patients with refractory or relapsed AML.
Given the aggressive nature of the disease and a need for a viable treatment options.
Awesome 24, 28 program is of high priority for a few minutes.
And we remain committed to being able to offer this treatment options for relapsed and refractory AML patients as quickly as possible.
Accordingly, we move quickly to file clinical trial applications in a number of European countries.
With Spain, and France, leading the way.
Additional filings in different jurisdictions are expected in the next few months.
With that I will turn the call over to Angus to update you on our quarterly financial numbers.
Yes. Please.
Thank you Andreas balance sheet and income statement highlights are shown on slides 15, and 16 of the presentation.
<unk> consolidated financial statements have been prepared in accordance with the IRS issued by the International accounting standard board of our ISP.
Financial statements are prepared in euros, which is the companys functional and presentation currency. Therefore, all financial numbers are presented in this call unless otherwise noted will be in euros.
As of September 32022, cash and cash equivalents totaled $222 9 million euros compared to $197 6 million euros on December 31 2021.
Based on our current operating plan and assumptions, we anticipate that our cash and cash equivalents will support operations into mid 2024.
Net cash used in operating activities for the quarter ended September 32022, with $19 million compared to $25 6 million for the quarter ended September 32021.
Total revenue for the quarter ended September 32022 was $14 9 million compared with $8 7 million for the quarter ended September 32021.
Revenue predominantly relates to the Genentech and Roche collaborations.
Research and development expenses increased by 27% from $20 6 million for the quarter ended September 32021 to $26 1 million for the quarter ended September 32022.
The increase was primarily due to higher expenses associated with the development of <unk> and <unk> programs are result of an increase in procurement of clinical trial material clinical patient trial costs and manufacturing costs.
An increase in costs associated with other early stage programs and infrastructure and an increase in share based payment expense.
G&A expense increased 19% from $6 8 million euros in the quarter ended September 32000.
One to $8 1 million in the quarter ended September 32022.
Increased predominantly relates to higher personnel and share based payment expenses and an increase in insurance premiums and higher consulting costs.
Net finance income increased from $1 5 million for the quarter ended September 32021, or $2 7 million for the quarter ended September 32022.
Net finance income is largely due to foreign exchange gains related to assets denominated in U S dollars as a result of currency fluctuations between the us dollar and the euro during the year.
Net loss for the quarter ended September 32022 was $16 5 million euros or <unk> 11 per common share compared with a net loss of $17 1 million euros or <unk> 14 per common share for the quarter ended September 32021.
The weighted number of common shares outstanding for the quarter ended September 32022 was $149 3 million additional information.
Formation regarding these results is included in the notes to the consolidated financial statements as of September 32022, which will be included in <unk> filings with the U S Securities and Exchange Commission.
Now I'll turn the call back to <unk> for closing remarks.
Thank you Angus.
Now if you have seen our most advanced program is called AFM 13, and is validating our three pronged approach that has some very good safety profile with broad activity.
Now if everything works out as planned we expect to take the drug as monotherapy as well as in combination with <unk>, though.
Which could create significant value for patients and investors.
As shown on slide 18.
With monotherapy on the NK cell combination we can initially address the needs of about three and a half thousand patients in the U S. Only.
And then one more way develop in the EU and Japan.
With relapse.
In Refractories, we get very positive Hodgkin and peripheral T cell lymphoma.
You can even expand beyond to address about seminar in half thousand patients now again, just in the U S. Only again it will be more in Europe , Japan, and moving to earlier lines.
Considering the likely value based on current data off the AE from 13, NK cell therapy to patients and the payer feedback. We believe we can make a <unk> a major commercial opportunity for our company.
Now through the partnership with <unk>, we've achieved a major milestone that enables us to pursue this substantial market opportunities.
If you have harrigan parallel April 24, he's moving programs in all three studies you need addressing multiple major solid tumor indication.
Important overall, the safety of <unk> in 2020 as monotherapy.
In combination looks quite favorable.
Which now allows us to treat patients at the 400 180 milligram dose across all three.
The first date of April 24 in combination with <unk> presented at <unk> is highly encouraging and as shown on slide 19, we are on track to provide additional data updates throughout 2023.
Medicaid contract.
Our pipeline is further enhanced through a from 2008.
Which is in defining stage for a phase one study.
Right.
Also our ongoing partnerships.
Moving forward.
In the case of genetics, we have made good progress in various preclinical programs and handed over several programs to them.
Energy development.
Now a second collaboration.
Roizen just presented a poster at <unk>, which showed that <unk> represents a novel approach to treating folate receptor alpha expressing tumors.
Engaging the innate immune response what base in human.
Human health care.
<unk> announced that it is expecting to enter into phase <unk> trials in 2022.
Well definitely lithium for additional proceeds from these key collaborations in the near term, including preclinical milestones as well as milestones based on regulatory agency.
With this I'd like to thank you all your continued support.
Patients and their families.
And for our employees in the U S and Europe , who are continuing to do the best they can.
Supporting our efforts to move things forward.
We're now ready to take questions operator.
Thank you to ask a question you will need to press star one one on your telephone.
And the interest of time, we exit you. Please limit yourself to one question and one follow up to permit time for others to ask please standby, while we compile the Q&A roster.
Our first question comes from the line of <unk> with <unk>. Your line is now open.
Hey, guys. Thank you so much for taking my questions and congratulations on the podium presentations at the city.
The 24 PDL one approaches that you presented the patient inclusion of PR in gastric cancer, it's Cleveland to purchase <unk>.
Impact on the cutaneous lesion.
A little bit sorry, if I missed it but the impact on the primary tumor itself.
And also it looks like you continue to see a reduction in lesions with multiple doses can you remind me how long. These patients are expected to be treated Edward Jones. Thank you.
Andrea.
Yeah, I can Texas.
So the patient's manifestation of west mainly skin metastases.
Which were as you have seen as opposed to quite bulky.
The patients also had the primary tumor which was NZ gastric wall.
However, due to the difficulty to really objectively measure of thickening of the gastric wall. This lesion was more regarded as an evaluable lesions, but not as a real measurable lesion. We also saw some reduction in the gastric wall again was a limitation that it's very difficult to measure.
But again, a major reduction of C. A skin metastasis, which represented the vast bulk of obviously tumor load in this patient.
In terms of duration of treatment protocol is designed that we can continue treatment as long as the patient derive clinical benefit shows there is no upper limit of possible cycles that can be careful.
Got it thank you so much.
Thank you.
Our next question comes from the line of Maury Raycroft with Jefferies. Your line is now open.
Hi, Congrats on the progress and thanks for taking my question just.
Just wanted to check on the regulatory path going forward for AFM 13, and PTC al So given some of the regulatory updates with other oncology companies in this space as it relates to accelerated approval path and confirmatory studies can you talk about your plan for PTC all based on the redirect study and FDA feedback.
Gives you confidence around your accelerated approval path.
Web Com can you take this question.
Yes, sure Hi, Barry this is for Scott.
The once we will have the data.
We will consult with the FDA discussing the path forward, but because currently we do not know what the data looked like.
And this will also include a registration directed study yes.
Yes, we are aware that the FDA is also talking to other companies right.
Just last.
Last week or the week before about that company and that they are requesting that a consumer choice study is underway. However, we do not know what other factors.
Builder confidence here right. So we think we go with our data and discussed with the FDA.
Yeah.
Got it that makes sense and maybe one follow up just for.
<unk> 28.
If you do the dose escalation in Europe or start looking at combinations and the EU. How do you eventually plan to pivot back to development in the United States.
Andreas.
Yeah, I think we were generating initial data initial safety data as we have announced.
European jurisdictions.
Now as a requirement for FDA to use foreign data is such a patient population in treatment algorithms.
It represents the standard of care and see.
Usual population in the U S. I think both factors I give them a better selection of the countries that we have.
I mentioned, Spain, and France will lead the way so.
As soon as we have cleared initial dose cohorts and have demonstrated all sorts of clinical safety obviously program.
We should be able to revert back to the U S. And then embark onto a global development program.
We'll include U S. S. One is Europe .
Okay. Thanks for taking my questions.
Thank you.
Our next question comes from the line of Dana <unk> with <unk> Securities. Your line is now open.
Yes, I wanted to ask a question about the AFM 24 with thoughts in gastric cancer.
The cutaneous lesions are obviously, it's a very clear response and I wonder if there's something about cutaneous lesion and the mechanism of targeting Egfr. That's notable and of the other cancers that you're calling for if there's any similarity either in the monotherapy PD, one or NK cell.
Combinations with manifestations of cutaneous patients. Thank you.
Thanks, Dana Andreas.
Yeah. So thank you for the interesting questions.
I mean this patient actually.
I've seen happened to have skin metastasis.
And skin of course is an area, where you have a high egfr expression.
Biologically we think that this is not connected as egfr expression would be limited to hikes easier for would be limited to the enormous keratinocytes of normal cells.
The gastric cells still maintains their egfr expression pattern that say half are in the primary tumor. So to my knowledge has no indication of Egfr on tumor cells is up regulated Wednesday.
Home into the skin.
So as we announced previously we have conducted a very specific and very detailed analysis of the tumor microenvironment of.
A number of very different tumor histology.
Which forms the basis for selecting certain indications for.
Mono therapy for combination with PD, one and <unk> four combination with NK cells.
But skin metastasis or the likelihood of skin tests of this was not part of the consideration.
Again, we believe in and most biological data showed that tumor cells irrespective to whereas they metastasize will maintain their biological fingerprint or footprint.
And therefore, I think a gastric cancer cells at homes to the skin is biologically not very different from a gastric cancer cell because it may go to deliver ultrashort bonds or other more frequent metastasize locations.
I have a follow up I mean, do you see any impact potentially other companies will target normal or stromal cells around the tumor, let's say with SAP.
See any indication that other cells in the tumor microenvironment are surrounding normal could have an impact in your sort of nearing an in vitro model.
Okay.
I think for the in vitro model, if I could hand over to Orange I think clinically.
Again, the NK cell reactivity is very specific to the cell where is he.
In case of a Texas to Atlanta to the microenvironment I would not see a difference between skim locations of tumor cells or other locations.
Aren't maybe you can protect sees a trick question.
Yeah.
Let me see if I got the question correctly I mean, if you talk about sells in the vicinity in the tumor microenvironment of course, what we know.
We talk a lot about NK cells of course, we have also are quite clear.
Clear growing data macrophages. So of course in terms of the times they will be.
Recruited.
Don't have evidence for other neighboring cells.
Of course, the bulk of the data is for the NK cells and as Andreas pointed out.
These indications have also been carefully selected to see that's the innate immune system is accessible or actually the cells of the innate immune systems are there I mean above we have also seen as I've just described.
In the talk that since he posts are we to see the activation of the innate and adaptive immune system, which we think is a very natural.
Physiological way to get both systems going in the.
The immune oncology side.
Cycle, so much more.
Natural way getting adaptive immune cells in there as well I'm not sure if that answers your questions and we'll be happy to do follow ups also.
No. That's good thank you.
Thank you.
Our next question comes from the line of do Kim with Piper Sandler. Your line is now open.
Hi, Thanks for taking my question.
I also had a question on the F 'twenty four.
Poster that you presented at Citi.
And the patient had a partial response in gastric cancer.
Knowing that the patient failed Pembroke prior do you think a tesla was contributing to the anti tumor activity and does this partial response change how you think about the mono therapy or give you more confidence in advancing that monotherapy study.
Andreas.
Yes, so let's start with September lease them up at Liza Liza map question.
Again, we the literature.
<unk> quite limited.
We have not found.
Meaningful data for gastric carcinoma, and most of the experience really comes from a re treatment.
<unk> with PD, one PDL one in patients with non small cell lung cancer.
And if you look across the literature. What you see is set a response is possible to PD one re challenge.
But these responses are largely limited to patients who.
Have either stopped temporary lease them up or any PD, one inhibitor wireless still in a response or who had to stop temporarily because of immune related adverse events.
If you look at patients who have a demonstrated progression while receiving PD one.
Especially when the PD one was also given in combination with chemotherapy for.
The response rates off of PD, one re challenge are extremely low and many studies zero percent.
So we do not think sepsis patient belongs to a patient groups that would have responded to a PD one re challenge alone.
We attribute this activity clearly it was a combination of F 'twenty four and PD one.
And as Andre said thinks it's also increasingly supported by our preclinical and clinical data now that we really show also in patient activation of adaptive.
Adaptive immune system.
So now I have a long answer I forgot your second question could you repeat please.
Yeah second question was.
Does this response change how do you think about mono therapy or do you think that a tesla was important and.
Getting to this partial responses gastric patient.
I mean, if a mono therapy, we are currently collecting data.
And as.
As we said we will report initial data into a major scientific conference next year.
Whether it really changes our belief I think our belief from from the get go is that I hear from 'twenty. Four is an extremely potent drugs that can recruit NK cells and as I've mentioned can also very potently activate macrophages.
So clearly the combination with PD, one or PDL, one inhibitor is very promising.
Again, we believe that there are certain tumor indications out there, whereas the NK cell infiltration into the tumor microenvironment could be sufficiently enough to support monotherapy activity.
But we will learn more as we are generating more data.
Again for combination with any PD one inhibitor.
This is now the second data point in addition to the higher from 13 studies that we have seen in combination with temporary lease them up.
Where we saw a significant increase in complete response rate and overall response rate.
I think our combination with PD, one PDL, one inhibitors and Ice's in general look extremely promising.
Thank you that was very helpful.
Thank you.
Our next question comes from the line of Watford with Cantor. Your line is now open.
And thank you for taking my questions, maybe just two from that.
I guess first regarding maybe the confirmatory study.
Guaranteeing pricing would be one on one and though I guess is that kind of part of the discussions that you're having with FDA right now aside from the trial design and the potential phase two study.
And then second as you know in terms of the site selection for the potential phase III trial of Congo.
Can you give us a sense you know what parameters that you're looking for with a site monthly.
B and Ali Garlock centers, perhaps.
Our therapy experience, who are you looking at some.
Community sites as well.
Andreas do you want to take this question.
So let me start with the second question.
So when we are or are in terms of sites that we are anticipating to have on our combination trial in our phase. Two trial are we are not limiting these sites to academic sites or sites with NK cell or cell therapy experience.
Simply based on our experience with <unk>.
MD Anderson trial, which showed a remarkably good safety profile in fact, most of the patients received their patient on an out of their treatment in the outpatient space or so.
Other than other cell therapies like like car T cells. So we do not think that academia was just it's a treatment that will be restricted to academic centers, we believe such as Kim very well be given also an experienced community hospitals.
Now in terms of our discussions with FDA as Eddie mentioned, we have already submitted a pre IND requests.
Containing a lot of also clinical questions.
This will be of course, followed by an IMD then and.
Yes, we are planning to discuss with FDA and accelerated approval option on accelerated approval pathway for this treatment also discussions of potential confirmatory studies I think will be part of this <unk>.
Interactions with FDA.
Okay. Thank you.
Thank you.
Our next question comes from the line of James Chen with Wells Fargo. Your line is now open.
Hey, good morning, guys. Thanks for taking my question on.
Four and 13, one O four can you share whether you think the memory like type of yourselves may be contributing to the response.
And then secondly, given 81 and one will be co administered do you think the lack of IL 12, 15, and 18 causes somewhat of uncertainty or risk of matching what <unk> seen in Hodgkin's lymphoma.
Yes. Thank you so I'll start here in terms of.
Obviously, a very intensely look at NK cells and the way how they are produced and.
What.
We have learned from.
In particular marketing with our television and they do have a pre activation of almost all of his time to claims as well.
It's a it's a little different to what the MD Anderson does.
Overall from our internally experiments, we have very we have seen almost no differences.
Between different cell types. So we've studied cells that arent you might come to periphery from cord blood.
Although <unk> and <unk>.
There was one key denominator that was truly important it is the <unk> pricing so as long as the salesman manufactured expressed a significant level of or a good level of CD eight T cells <unk> extremely well with our unions and engagements we have the high affinity to cover them.
In and very high quantities as you know when does.
Established you can't really wants to adopt it forms a stable complex and then b cells become active so our own learnings been that there has been very little differentiation amongst many different cell types.
With the one denominator that expresses <unk>.
Reactivation. Thank you were mentioning.
Did not see.
An outstanding activity as compared to.
Other cell types now this is important and that's what gave us great confidence that we indeed have a number of options.
We wanted to partner with and our option.
Always with our Eva.
And because they are so far advanced in the manufacturing.
And that could indeed.
Or start initiating tenure.
Phase two clinical study.
Quickly with some debt that's very similar to the program. We eventually want to commercialize that was important.
And that's one.
He is bringing to us.
In this in this partnership.
No.
Other question I'll hand over to two two arent and once he wants to add.
So let me see if I understand.
I understand what the other question was I think maybe maybe referring to the James the preclinical data that we have shared and maybe most relevant the mouse model and in our wireless interrupt you quickly. It wasn't about co administration of <unk> complex and sorry.
Yes so.
What we have seen James and we shared that the calls.
We have summarized them one of the slides today when we look in the CD 30 positive copper cells and directly comparable pre complex and co administration, maybe one or one with 13. We saw yes, there was a slight Bachelor side of toxicity the co administration, but we.
See that in the same ballpark very comparable and when we review again the mouse model that we did with co administration.
We see a very excellent tumor growth inhibition and referencing back to your initial question while that was not on our side by side very similar results in the tumor the total tumor growth abrogation as we had seen with the MD Anderson itself. So.
Taken together.
What are the already said is we really do not see a difference pre clinically thus feel very confident with moving forward with maybe one of them wanted the co administration study.
So there are two additional data that one has published its.
Then we can determine the receptor occupancy opening from 2004.
When it used as monotherapy. So this shows that.
We can.
Engagement activating T cells in the body.
So this is a kind of.
Not following the co administration because the patient is.
It's bringing in pesos, but we can detect any from 'twenty four and binding to <unk>. That's how public state. So that gives us again very good comp again and you know why we are seeing the strong binding.
For several reasons one is the very high affinity that our engagement onto.
Onto <unk> plus their binding epitope that is not.
Impacted by circulating ITG. So this is the advantages and that's why we believe with co administration, we can achieve a very solid binding of B and T cells that we infused in this case EBIT 101.
Our second dataset, we have never published yet, but we have also looked at Athens searching and patient if it's binding to NK cells and again, we can we can see some 13 bound on patient's own NK cells.
So those are those set of data give us.
Reasonably good phases.
Followed through with the strategy of co administration on top we have generated obviously, a multitude of preclinical data that confirms that.
Co administration and pre complex risk.
The results in basically similar data in there.
With similar activity.
Thank you for the detailed response very much appreciate it.
Thank you as a reminder to ask a question at this time. Please press star one one you touched on the telephone.
Our next question comes from the line of Yale Jen with Laidlaw <unk> Company. Your line is now open.
Good morning, and thanks for taking the questions.
I know you mentioned a lot of similarity.
Between the MD Anderson and Teva.
Yes.
Do you anticipate you would speak with going to speak with FDA do you anticipate that could be.
I'm sort of a bridging study need.
Needed it before you move to that.
Full phase two study for the potential accelerated approval.
Welcome.
Yeah.
So.
How the FDA looks at these differences, but we cant say before we have to talk to them. So that's important but we believe that we have.
Our goods dataset.
Showing the similarity comparability between the cells right all as mentioned by 10 times faster than before.
The preclinical studies in vitro in vivo demonstrating similarity right. So.
We do not anticipate that we have to run a bridging study. However, we will we can give more guidance once we have spoken to the FDA.
Okay, great maybe as a follow up on this one is.
Let's assume if the bridging study might be needed.
Are you guys.
Any sort of setup or designed to fulfill that request if that happens.
And thank you.
Yes of course right in preparing for the for the FDA interaction.
Elevating all potential potential ways and yes, we have we are thinking about all these different classes and look for solutions for that.
Okay great.
You look at the clinical study of our Kiva.
You started with 1 billion sales as the first dose.
And arent meeting and now also Rituximab and they will only do one dose escalation to 4 billion. So with non modified cells you have on this hurdles in terms of running those escalations.
In this context, we can do.
Running.
That's what the most likely scenario will be that you may have to tweak initially three patients.
See if this is Nathan then you can continue to recruit.
<unk> launched a number of patients this is our assumption.
Most constantly assumption is right.
A number of experiments that we conducted.
Just.
To understand to make this understanding is treated over 200 patients with <unk>.
<unk> <unk> as monotherapy and also in combination. So we have a very thorough dataset on top we have <unk>.
So in a very good safety profile in combination with NK cells already so our base case assumption is that.
There is a safety run in and then we can start recruiting these patients. So there should not be any separate studies being conducted on this one.
Not concerned obviously, we're prepared to react to anything.
Because we believe that there is a high chance that this treatment.
It's coming through in an accelerated approval study.
Make patient lives very different just based on the data that you've seen the ash.
Thank you.
Okay. Thank you.
Thank you.
Our next question comes from the line of Chi Chow with Chu with Baird. Your line is now open.
Hi, good morning.
I'm going to ask also on App and 24 in combination with that has arisen that I like to ask you about the two pancreatic patients you reported a one I think has some durable stable disease I wonder from disease biology standpoint, any any color you can provide on why.
K engage or macrophage engage you can.
Sure work and that's sort of code tumor situation. Thanks very much.
Andreas.
Yeah.
Alright, pancreatic is probably one of the.
Most difficult to treat tumors with immunotherapy.
Now given the mechanism of action of air from 'twenty, four we belief that.
We could be able to should be able to.
Really get initial NK cells into these cold tumors.
We also believes that we have a chance to activate macrophages in these cold tumors.
And I think increasingly our data indicate that <unk> could kick start a really.
Sorted action of innate.
Innate and adaptive immune system.
So pancreatic cancer was selected based on these assumptions that we provide a completely different mechanism of action.
With both parts of the immune system activated.
And it's it's an area of very significant unmet medical need no immunotherapies has really worked here.
So what we wanted to give these patients are really a chance again I think we have some <unk>.
Quite good preclinical rationale.
That even pancreatic carcinoma could show some sour could drive some benefit from <unk> unique mechanism of action of fan from 24.
Great. Thank you and maybe if you could a quick follow up on your ally.
<unk>.
32, folate receptor Alpha program.
I guess can you remind us the economics over there and given there is.
As a child and you see it.
<unk> recently approved I guess any upside from that program that you see going forward. Thanks.
Yes.
Angus here I can probably chime in on that we have as Youre aware, we have license based on 32 to a subsidiary of ROI bands as part of that deal and through that deal.
That subsidiary will be responsible for running the.
Trial costs.
In return we're entitled to.
Milestones.
And royalties on net sales.
<unk>.
Great. Thank you.
Thank you.
I'm showing no further questions at this time.
You all for your participation. This does conclude today's call you may now disconnect.
Thank you. Thank you.
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
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