Q3 2022 CureVac NV Earnings Call
Greetings and welcome to <unk> third quarter, and first nine months 2022 financial results and business updates at this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad.
As a reminder, this conference is being recorded it is now my pleasure to introduce your host Sara Fucky, Vice President Corporate Communications and Investor Relations. Thank you you may begin.
Thank you good morning, good afternoon, and welcome to our conference call. My name is Sarah Funky and I'm, the Vice President of corporate Communications and Investor Relations.
Please let me introduce todays speakers on the call with me from Covid Fund Center hubs, the Chief Executive Officer, Bill if he could not focus our interim Chief Development Officer Ronen, just took our senior Vice President Science, and innovation and Cherokee Mueller Chief Financial Officer Sheila.
Please note that this call is being webcast live and will be archived on the events and presentations section under Investor Relations on our website.
Before we begin a few forward looking statements the discussions and responses to your questions on this call reflect management's view as of today Wednesday November 16th 2022.
We will be making statements and providing responses to your questions that state or intentions beliefs expectations or predictions of the future.
These constitute forward looking statements for the purpose of the Safe Harbor provisions.
These statements involve risks and uncertainties that could cause actual results to differ materially from those projected.
<unk> disclaims any intention or obligation to revise any forward looking statements.
For more information please refer to our filings with the U S Securities and Exchange Commission I will now turn the call over to clay.
Thank you, Sarah ladies and gentlemen, and a warm welcome to this conference call from us here at cubic.
2022 has been a highly productive year for our company.
We have significantly grown our operational bandwidth across the organization and most importantly, our stroke three core competencies broad technology platform robust product development pipeline and large GMP manufacturing capacities.
Let me give you a short overview of four key developments in these areas first in our prophylactic vaccine product pipeline, we continue to execute on our broad clinical development program in COVID-19, and flu, which started earlier in 2022 in collaboration with <unk>.
Our partner GSK.
The ongoing clinical trials that have successfully extended our broad technology platform into modified as well as multivalent mrna approaches are on track to deliver meaningful clinical data early next year.
Second beyond beyond our progress in prophylactic vaccines. The next growth driver, we are moving forwards with maximum speed and focus is oncology.
With the acquisition of frame cancer Therapeutics and partnership with my Neal We have made an impressive impressive start to the implementation of our expanded oncology strategy. Today. There is an enormous gap between state of the art analytical methods that provides vast amounts of data.
About the patient's individual cancer and current treatment options.
Immuno oncology is particularly suited to bridge that gap.
We intent to access and translate available data into a meaningful pipeline of new mrna cancer vaccine candidates driven out of the former frame cancer therapeutic site in Amsterdam.
We plan to make our cancer antigen discovery hub.
Third we progressed on the development of dedicated oncology enable us first and foremost the RNA printer, our automated manufacturing solution for GMP grade mrna vaccines and therapeutics.
In October this year, we submitted applications to the regulatory authorities for the first manufacturing licenses to support oncology roadmap.
So the more we are advancing the development of <unk>.
Terry lipid nanoparticle or LNP technology that in oncology, we expect to provide additional advantages for the delivery of novel mrna cancer vaccine candidates.
Fourth.
We are we also presented data from the phase one expansion study of our non coding RNA CVA, one or two at the meeting of the society for immunotherapy of cancer City earlier. This month C V. H one O two demonstrated a solid safety profile and preliminary efficacy in heavily.
Pre treated patients with advanced melanoma.
In addition to those four developments, we closed the third quarter of 2022 with a solid cash position of 549 million euros and peer relate to talk you through the financial details.
On slide five let me briefly highlight the cubic pipeline to show you. How we are leveraging our strong mrna expertise across our three therapeutic areas of prophylactic vaccines oncology and molecular therapy addressing diseases with high unmet medical need.
Our most advanced area prophylactic vaccines is driven by the technological advances.
Our versatile second generation mrna backbone this backbone broadly spence unmodified and modified mrna as well as monovalent and multivalent vaccine formats to diversify and advanced our product development pipeline.
All of these approaches are currently being validated in four phase one clinical trials in COVID-19, and flu that we are conducting together with GSK.
The clinical insights we expect to gain.
From these four studies will also accelerate the ongoing expansion of our oncology program.
This area of our strategic priority is the development of our portfolio of novel cancer vaccine candidates that can elicit strong systemic anti tumor directed immune responses based on our second generation backbone.
Through the implementation of synergistic technologies.
Established a high efficient antigen discovery engine.
This will allow us to develop product candidates featuring differentiated new antigens as well as tumor associated antigens.
Already highlighted our clinical oncology candidate CB eight one or two is currently being assessed in a phase one dose escalation trial in solid tumors and an expansion study in patients with PD, one refractory melanoma.
We'll come back to the data we presented on CB eight one or two at the city.
There's a third therapeutic area molecular therapy.
We are developing optimize mrna therapeutics together with several calibration partners.
That are intended to address therapeutic proteins to treat rare and metabolic diseases.
On slide six let me briefly touch on a detailed overview of the full key phase one dose escalation trials that we are currently conducting in COVID-19, and flew together with GSK. The studies are driven by a broad technology approach to select the best performing <unk>.
That's for later stage clinical development for <unk>.
COVID-19 on the left.
The tested candidates include CV, or 501, and modified candidate, including the immigrant variant and CV to cough and unmodified candidate in coding the original virus.
For flu on the right we.
Testing flu SV mrna, our monovalent modified candidate and Cvs SKU IV, an unmodified quadrivalent candidate.
All four candidates are being tested.
One shots booster setup.
Based on our advanced second generation backbone. They will provide an important clinical validation of our technology platform and corresponding product development.
Initial external reporting for both indications will be triggered by data that are comprehensive and meaningfully enough.
To allow selection of the most promising candidates and determine the optimal dose for subsequent clinical trial, we expect to report on these data in early 2023.
Moving on from prophylactic vaccines to oncology I will now hand over to you <unk> to walk you through our recent updates and brokerage in this area.
Thank you France.
Before we dive into the details I would like to principally draw your attention to our previously reported three pillar strategy in oncology.
Please tell us illustrates a roadmap for expanding our oncology footprint. The next growth driver. We are rapidly advancing beyond are progressing prophylactic vaccines.
How about the last several months, we have either started or continue to execute on each of these strategic pillars with a clear focus on the development of a differentiated cancer vaccine pipeline.
So technology is a frame cancer therapeutics at my new will enable us to access novel classes of tumor antigen and identify those with the highest chance of success for potential clinical testing.
In alignment with a pillar in the middle and the right.
Okay.
This antigen discovery engine, maybe supporters fuzzy on a printer.
The automated end to end manufacturing solution is expected to contribute to the availability of clinical trial materials to rapidly screen you I'm on a vaccine construct and early stage clinical studies.
As already mentioned that France. We are currently in regulatory review to obtain some soft manufacturing licenses 40, only printer to support initial validation of a second generation backbone in oncology.
This validation includes testing or second generation backbone with different classes of tumor antigens to assess T cell mediated immune responses.
It's covered by the strategic pillar on the left.
I'll come back to the strategic pillar later in the presentation.
Uh huh.
Let us take a closer look at the antigen discovery technologies, we are currently establishing and how they integrate with our three core competency is in oncology.
On slide eight you can see an illustration of how the advanced technology and bioinformatics expertise.
Frame cancer Therapeutics as my new complement our core competencies and process development and manufacturing.
The synergistic technology strongly extend our reach to the latest technologies in oncology, while being highly compatible with our own mrna technology.
They provide a powerful front end to deliver antigens that can then be developed into a deep pipeline of novel cancer vaccine candidates.
Our existing expertise.
Let me now hand off the quarter runoff Susana frame cancer Therapeutics to walk you through the details of frame highly sophisticated and differentiated technology.
Thank you.
The technology, which has become part of the <unk> technology platform with the acquisition earlier. This year is dedicated to transforming the treatment of cancer by harnessing the immune system to recognize and fight tumors.
Over the next three slides I would like to give you an overview of this technology and what it says what sets it apart from current industry standards.
The field of immunotherapy has advanced with the progression of available technologies to extract data from patient samples such as next generation sequencing.
And the last 10 years, the focus was on the exome, which is all the protein coding parts of a human genome, but this represents only 1.5% of the total genetic information within that one 5% platforms have been specialized on the efficient identification of point mutation status.
Nice to antigens that can most of you will only be found in tumor cells and cancer. If indeed this targets for cancer vaccine candidates.
More recently breakthrough developments in sequencing capacity has enabled the extraction of fastie larger amounts of data.
To date, we can sequence the entire genome of every patient.
The tumor for about $3000 and prices are still going down.
Enables us to utilize the remaining 98, 5% of genetic information, while the bulk of the <unk>.
<unk> of the tumor resides.
This is why we start our new antigen discovery engine, we perform whole genome sequencing for every patient sample and combined with short as far as long read RNA sequencing.
This way, we come up to full inventory of genomic changes I know precisely what is being expressed and what is not.
Downstream of the sequencing, we generated a powerful software package to integrate all the data to retrieve the exact changes in the DNA of the tumor cells compared to healthy cells.
Correlation of this data with changes in the RNA transcription of the tumor cells results in a tiny new and potentially antigenic tumor antigens.
We've called these new entities frames, which is short for neo open reading frame proteins.
We plan to apply these frames as targets for our portfolio of entirely new cancer vaccine candidates. We've demonstrated we can go from tumor sample to vaccine design within two weeks.
I'm now on slide 10 to further illustrate the depth of the genetic data are the dollar approach provides access to <unk>.
Here you can see the analysis of our real sample of a lung cancer patient from our own work. The outer circles are both speakers number the 22 chromosomes plus the X and y chromosomes.
The inner circles of both figures show mutations per chromosome depicted as blue dots each blue dot represents a potential cancer vaccine target.
The left illustrates the data we obtain if we choose to do only conventional exome sequencing.
The number of new DOCSIS restricted by sequencing only the protein coding parts of the tumor DNA.
The figure in the middle illustrates the data we obtained from whole genome sequencing you of course, you get many more <unk> mutants, but more importantly, you came much more meaningful data on top of that the case in point is the multitude of lines in the middle of the figure which depict chromosomal rearrangement of chromosomes are tied to other chromosome.
Well it should not be.
While this is a common occurrence in cancer. The number for Ya arrangement is still staggering overall that can be hundreds of such rearrangements and colon lung cancer sample.
What is the difference between both datasets mean for the development of potent cancer vaccines.
Well. The main difference is that point mutation says the next place represent single nucleotide changes in the accounting DNA and consequently, the express protein only features single U amino acids.
Current personalized cancer vaccines applying this approach covering at Max around 30 of such point mutation. So about 30 changed amino acids in the vaccine. This means that the vaccine is for the most part based on healthy or regular a wild type genetic content.
The ability to activate the immune system based on a vaccination against it mostly wild type antigen is that of course limited.
In contrast, we are taking a very different approach.
Incorporating the totality of the genetic changes, including all the rearrangement give rise to long stretches of genetic content that are entirely foreign to the body.
This results in new antigens that are not only entirely foreign to the body, but also uniquely expressed in the tumor and not in healthy tissue.
Cool.
These frames the frame on you.
You can see the frame of the lung cancer sample on the right.
The line here represents an uncoated new protein with every coloring that line showing a separate.
Asset.
The callers this add up to approximately here about a thousand new amino acids in the sample.
And that's a number that can easily be encoded on a small number of or even a single messenger RNA I'll start.
And as far as this cost strike will look like a virus to the immune system and is expected as also suggested by preclinical experiments to raise a much stronger immune response.
At the end of the day to five between the tumor and immune system is a numbers game and we believe that our approach provides the best opportunity to win that game.
I think focus so far on this strongly extended data that we can obtain today from individual patient tumor samples. Let me now show you on slide 11, we can leverage our approach across different benches, with the same cancer or even across different cancer types.
But you can see here frames up two different lung cancer patients. We found that some of the same frames are shared between patients in fact chat things as.
As well as she had tumor associated antigens occur in many different cancer types.
And they offer us the potential to develop cancer vaccine candidates that could be applicable to a larger group of patients.
That's why we are following two approaches for our cancer vaccine development. The first approach assesses tumor antigens shared by different cancer patients for the development of off the shelf cancer vaccines to benefit larger groups of patients in the second approach is paying off.
A patient's individual tumor profile.
With that let me hand back the call to weaken to discuss how these approaches fit within our current oncology roadmap.
Thank you very much.
Nonslip yourself to walk you through our development plans in oncology for 2023 and beyond and how we plan to translate our Ami technology into new cancer vaccine candidate.
You might remember that the source of our three strategic pillar highlights the validation of a second generation <unk>.
Backbone in oncology to address this pillar, we will assess how would improve performance off the second generation backbone translates interest induction of T cells in a clinical setting.
To this end we have already started preparations to initiate two phase one proof of principal studies in the second half of 'twenty three to assess safety and Immunogenicity of the second generation backbone and coding established tumor antigens.
The first proof of principle study expected to start in the first half of 'twenty, two we will assess and M on a construct including multiple epitopes from eight tumor associated antigens in patients with surgically resected cloud Blastoma Marty pharma.
Second proof of principle study expected to start in the second half of 'twenty, three which has put them on a construct featuring a full length tumor associated antigen in patients with solid tumors.
Initial focus on melanoma.
They are expected to provide a solid foundation of clinical data to accelerate the development of cancer vaccine candidates and to support subsequent regulatory review processes.
In parallel we will be advancing the application of our antigen discovery engine to identify and validate new antigens as well as through my associated antigens.
Tens for clinical testing.
We're extremely benefit from the additional support of what we call oncology enable us.
These include primarily the on a printer, which would support the rapid and flexible availability of clinical trial material.
Additionally, we aim to optimize the design of cancer vaccine candidates based on our new and proprietary LNP program for improved him on a delivery.
Both work streams I expect too much in 2024 based on data from the proof of principal studies and successful antigen selection in order to stop cancer vaccine development programs.
Programs within composite to approach the Serrano test highlighted development of off the shelf cancer vaccines to benefit groups of patients and cancer vaccines tailored to a patient's individual tumor profile.
Let me go more into detail about these two approaches.
Next slide.
Looking at the concept of shared antigens introduced earlier in this presentation data suggests that an off the shelf vaccine addressing for example, so far most frequently share tumor associated antigens for breast cancer can address about a quarter or even a third of our triple negative breast cancer patients do towards.
The prevalence of these shared antigens.
With a high debt out of these four shaft antigens at least two will turn out to match a patient specific tumor.
With all access to tumor associated antigen frames and other classes of antigens from antigen discovery engine as well as our collaboration with my new even evaluate possibilities to further increase the coverage of specific patient populations we serve.
Relevant offer SaaS cancer vaccine candidates.
Our second approach is a fully personalized approach, which has the advantage of precisely tailoring accounts a vaccine to the antigens that are specific to a patient's individual tumor and so I'm not sure it was out of patients.
Ultimately it will depend on the tumor and whether it can be best addressed by an off the shelf of Clos in the lifestyle combined approach.
With that let me now shift gears and talk about the latest data update for oncology program CB eight products.
On Slide 14, let me briefly remind you that see the eight 102 is a non coding on a optimized to activate on a receptors that normally detect viruses, including toll like receptor seven eight as well as to make one.
See you at one or two is injected directly into the tumor that mimics a viral infection that can activate the immune system to reject tumor.
See you at one or two is currently being evaluated in a phase one study consisting of two parts. That's assessed the CVA at one or two as a single agent and in combination with anti PD one antibodies.
The dose escalation part in a range of solid tumors have already been completed.
The data on respond as illustrated on the slide comes from expansion part of the study, which assesses 40 heavily pretreated patients with PD, one refractory melanoma at a dose of 600 micrograms.
So data represent a cutoff date from August this year and show preliminary efficacy in the cohort of 30 patients treated in combination with anti PD. One antibodies, 40% of these patients were pretreated with anti <unk> four antibodies.
Five out of.
Of these 30 patients or 17% experienced a partial response according to research.
He observed responses with water for up to one year from start of treatment.
We did not observed objective responses in the 10 patients also single agent cohort.
And this group, 50% of patients were pre treated with anti <unk> four antibodies.
Additional immune profiling data from the phase one expansion study is shown on slide 15 and is based on tumor biopsies are injected in non injected tumors from a subset of patients as well as blood samples from patients.
So tumor biopsy sample shown on the left further confirms the previously reported infiltration of T cells in the tumor environment characterized by both city 48 T cells and a corresponding decrease of the tumor cell contended one off the partial responses and the combination cohort.
On the right side of the slide the balloon plot illustrates what gene said enrichment analysis safe on RNA sequencing from what blood samples taken before and 24 hours. After the first administrations of CVA product too.
The analysis confirms the previously reported activation of our defense pathway slipped by the induction of interferon.
Final data of the complete phase one study is expected to be submitted for publication in a peer that huge genre in the first half of 'twenty three.
Well for us.
The positive data also CV at one or two phase one expansion study further demonstrates the previously reported robust safety profile and strong ability to mobilize the immune system I guess objective as well as non injected tumors.
In the context of our strategic focus on the development of mrna based cancer vaccine candidates the target tumor specific antigens.
Initially validated immuno modulator characteristics of C V eight one O to represent a valuable and potentially complementary technology.
He was therefore only consider a potential further clinical development of CVA is one or two based on an integration into a cancer vaccine development. For example, as a strong immuno modern luxury adjunct to a defined amount a cancer vaccine candidates.
This let me hand back the call to France.
Thank you Erica.
To round up the components of our oncology roadmap on slide 16, and 17, let me briefly address it to oncology enablers that Rico already highlighted on slide 12.
The first being a new and appropriate Terry lipid nanoparticle or LNP program for potential application with our cancer vaccine candidates.
The new LNP consists of an improved and Pac three lipid composition preclinical experiments in mice showed highly localized transcription of Arabia space mrna formulated with either the new nonpaying LNP.
Or a control LNP.
Distribution was limited to the immune compartment empty intramuscular injection site.
It's showing no expression and distant organs, such as the liver spleen and lung.
As treatment with a therapeutic cancer vaccine requires repetitive administration maximizing expression of the including antigen in the immune compartment is an important goal.
We know from public studies that there seems to be a linear correlation between the amount of the activated antigen presenting cell.
The immune compartment and the resulting abundance of tumor fighting CD eight T cells.
Correspondingly the highly localized mrna delivery was accompanied by strong seller, but also humoral immune responses.
As shown on the right side of the slide the.
Arabias mrna formulated with the non peg LNP generated systemic interferon alpha levels in the same range as the control LNP was show and was shown to raised comparable amounts of ending June of antigen specific T cells measured via interferon gamma <unk>.
Let's see.
An important advantage of the new LNP program addresses the cold chain logistics, that's still pose challenges for the distribution in long term storage of mrna based vaccine.
The new LNP program was shown to enable a so called try to presentation of our formulated mrna referring to the vaccine as a solid powder rather than the solution for better stability and store ability.
The figures on slide 17 show data from an ongoing stability study at 25 decrease centigrade or 77 degrees Fahrenheit demonstrating that the mrna is intact and securely formulated for at least 11 weeks.
Overall, we are extending our technology core competencies and LNP research to add new approaches for vaccine design optimization.
Moving onto the second oncology enabler on slide 18, I would like to look at the role of the RNA printer is envisaged to play not only in the internal expansion of our oncology pipeline, but also in the opening of new avenues for personalized mrna.
Cancer therapies.
As you know the RNA printer is our integrated and automated solution for the rapid manufacturing of GMP grade mrna vaccines and therapeutics design.
Designed for flexible smaller scale quantities, the RNA printer seamlessly integrates.
With our antigen discovery technologies and the development of our cancer vaccine pipeline.
At the same time, the RNA printer is expected to be uniquely suited to close the gap between the vaccine sequence and the provision of new cancer vaccines to either treat smaller group of patients or provide a fully personalized therapy.
<unk> therapeutics setup.
This integration of the RNA printer could also catalyzed possible end to end digitization of data and data management, along the entire personalized or off the shelf vaccine therapy workflow with this let me hand over to Pierre for a review of our financial data.
Thank you, France, and good morning, and good afternoon to everyone on the call.
Looking at our current cash position on slide 19, we closed the third quarter and the first nine months of 2022 with a strong cash position of $540 9 million euros.
Financial statements for the first nine months of the year reflective X advanced phase of transitioning out of its exposure to its first generation candidate.
Cvs and Kohl's cash used in operations was mainly allocated to purchases of already material and settling CMO contracts as part of the wind down activities for Cvs <unk> vaccine program and to capital expenditures for our new production facility.
Moving on to our profit and loss statement revenues decreased by $18 1 billion euros to $11 2 million euros for the third quarter of 2022 and decreased by $6 1 million euros to $55 7 million euros for the first nine months of 2022 compared to the same periods in 2021.
The decrease for the first nine months period was based on a higher 2021 revenues due to the termination of the Boehringer Ingelheim collaboration and its subsequent recognition of 10 million euros for the first nine months ending September 2021.
Revenues for <unk>.
Revenues for up to GSK collaborations increase year on year and amounted to a total of $52 7 million for the first nine months of 2022 compared to 49, $49 6 million euros.
The previous year.
Operating loss was $52 4 million euros for the third quarter of 2022.
<unk> and $90 7 million Euro decrease compared to the third quarter of 2021 four.
For the first nine months ended September 32022, operating loss decreased by $278 8 million to a total of $127 9 million year over year.
The operating result was affected by several key drivers.
Cost of sales decreased primarily due to lower expenses for CMO services.
Prior in 2021 was highly impacted by significant expenses for the setup of a European CMO network with TVN cough.
This was partially offset in 2022 by an increase in write off for raw materials procure to supply manufactured goes to GSK.
These are no longer these are now no longer expected to be used following the transfer to GSK of reserves production capacity at our CMO.
R&D expenses decreased primarily due to significantly lower development expenses related to the completion of the large phase two b III clinical trial for <unk>.
In line with the declining number of continuing study participants in 2022 and renegotiation of existing contracts and the first nine months of 2022.
<unk> clinical trial cost estimate decreased resulting in the reversal of $36 8 million euros from the provision recorded as of December 31 2021.
Additionally, in the first quarter of 2022.
R&D cost was positively impacted by a net gain for a change in volume estimate following the transfer to GSK of reserve production capacity at our CFO .
Other income decreased but was positively impacted by $32 5 million euros from GSK for reimbursement of prepayments and production activity setup at our CMO.
In 2021 other income was primarily attributed attributable to amounts recognized from grants from the German Federal Ministry of Education, and research will be MBS.
Financial results for the third quarter increased by $5 1 billion to $4 7 million for the third quarter of 2022, and about $8 7 million to $7 5 million euros for the first nine months of 2022 compared to the same period in 2021.
Positive financial results were driven by foreign exchange gains and interest on cash investments.
Pre tax losses were $47 7 million euros in the third quarter and $120 4 million euros for the first nine months of 2022.
With this I would like to hand back to France for today's key takeaways.
Thank you peer.
And also thank you use zika and rollout.
Let me quickly summarize the key takeaways from today's presentation.
Over the past several months, we continued to strongly increase our operational capabilities that enabled us to maximize applications for our mrna technology.
The three core competencies, including technology product development and manufacturing.
We have expanded our clinical development pipeline by a total of four clinical trials in prophylactic vaccines, this year and COVID-19, and influenza together with GSK.
All four trials.
On track and provide meaningful data with the goal to select the best performing candidates early next year and advanced preparations for potential subsequent latest stage clinical developments in 2023.
These data will also support development of our own core oncology program, where we have significantly expanded our technology expertise by the acquisition of frame cancer therapeutic and its cutting edge genomics and bioinformatics platform.
In 2023, we plan to start two clinical trials in oncology to integrate this highly differentiated platform with our versatile second generation mrna backbone to strengthen our clinical development pipeline with novel cancer vaccine candidates supported by the RNA printer and our new <unk>.
<unk> technology.
Lastly, our strong cash balance in the third quarter shows the benefit from our diligent work to resource and reallocate prior commitments from our first generation vaccine candidates and positions us well to continue the execution on our priorities.
With this we conclude our presentation and I would now like to open the webcast for your questions.
Thank you we will now conduct a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.
A confirmation tone will indicate your line is in the question queue.
Press Star two if you would like to remove your question from the queue.
For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
One moment, while we poll for first question.
Our first question comes from Geoff Meacham with Bank of America. Please proceed.
Hi, Thanks for taking my question I'm, just curious when we should be looking for a next update on your rabies program and can you also walk us through how you're thinking about that market opportunity there. Thank you.
Thank you Jeff.
With regard to the Arabia, certainly our core efforts, where with all of it together with our partner.
GSK looking into first of all making a difference to the pandemic, which is not over yet therefore, the effort certainly concentrated.
On the Covid as well as on the flu clinical trials suddenly the readout on these clinical trials will tell you something about the technology platform in infectious disease.
Which is why I cannot answer your question with regard to rabies at the moment still we are waiting for the data to come because this will be telling us more for other indications and then certainly for the markets in these indications as well.
Yeah.
Our next question comes from Evan Wang with Guggenheim. Please proceed.
Great. Thanks for taking my question, great to see the clinical data for the Covid them with programs on track for <unk> can.
Can you remind us how you plan to present that should we expect it in a press release or at a medical meeting.
Or are they plan to be presented together and.
In terms of the go no go decision between the modified an unmodified.
How exactly.
Will that decision be made any color there would be helpful.
Yeah.
Thank you Evan.
It is a bit too early now to say, how we are going to present on the stage are first we want to see the data.
But you can be assured that this is a core of the discussion we're having at the moment with GSK together.
In order to find exactly where your finger pointing on what is the difference between modification non modified RNA.
RNA construct.
In <unk>. The one is really what is the first generation backbone versus the second generation backbone with a second generation backbone just on the RNA level, having a higher potency as you know the first generation CV and cough was non modified to see really what you can do on the RNA level, but then together with the chemical modification.
Which certainly plays a role for the reactor Genesis, especially if youre going multivalent with Hollywood higher dosages, because youre, putting more RNA into that so these are the critical questions and you really put your finger exactly on these points, which were only able to answer when we see the data.
Certainly we have high expectations of according to the improvements we have been doing so far and this will certainly then trigger also how we are going to present.
Our mutual.
With our with our partner GSK on our mutual projects, we are running here. So therefore, unfortunately, it's a bit too early to talk about exactly this.
As a follow up what kind of data do you expect to present and <unk> in terms of any kind of color you can provide in terms of the scale of the dose cohorts number of patients.
We'll see tomorrow and T cell response.
And then as a follow up you know in terms of later stage development for influenza Covid.
Is.
There is.
Is it possible to have.
Or is it kind of in consideration have a later stage programs before they start in the next kind of a flu.
Susan.
Yeah. Thank you yeah. So.
The expectation and this is what we tried to put into the presentation there as well.
The readouts.
What we want to see is certainly chemically modified versus non chemical modified as we tried to explain that the second generation backbone is playing a role on our technology level. Then also for oncology, we want to start clinical trials.
And the next year, so it's going far beyond infectious disease, therefore, non chemically modified as well as chemical modify then certainly at.
The monovalent versus the multi valent.
Which is the first clinical trial, we started in South America earlier this year to see exactly this one because this is a technological effort there as well if you put more Rnas into the same vial, especially starting with a low dose and then certainly of core is.
There are three other points. So one is the reactor Genesis D, which was giving us a bit of a problem in the first Cvs <unk> as you know the second one is the immunogenicity. So what is really the antigen.
<unk> expression in various neutralizing titers.
Third one is certainly also the T cell presentation, which then again plays a role beyond infectious disease for oncology there as well. So these are the main points were looking into next two what does it mean and this is to address your last part of the question what does it mean for further product development in Covid as well as in flu.
Great looking for to data I'll.
I'll jump back in the queue. Thanks.
Thank you once again, ladies and gentlemen to ask a question. Please press star one on your telephone keypad, we ask that you limit your questions to one and a follow up our next question comes from Jonathan Miller with Evercore. Please proceed.
Hi, guys. Thanks for taking my question.
Maybe on those Covid trials, how much visibility do you have currently into the unmodified product because it seems like obviously that was expected. This year. It seems like it's getting pushed back a little bit.
To share the stage with the modified.
RNA, it's fair to say Youre waiting on those modified results before you want to message anything on the unmodified and to what extent is that decision being driven by GSK holding disclosures back here versus the results that youre seeing from the unmodified background.
And then secondarily I'd love a check in on the IP law suits that are ongoing on the Covid products, where are you in the process now and whats the typical timeline to visibility on those lawsuits in German courts, and any plans you have to pursue similar suits in other jurisdictions.
Yes. So thank you for this question.
On the data it was always considered when we started these clinical trials that we didn't want to compare and.
Separately.
That we didn't want to communicate separately on chemically modified versus non chemical modified into the same indication here. Because this would just not makes sense, we are and Thats a goal what does the next step for product development and for that you need to have the completion of the data on the modified as well as a non modified and this has nothing to do with holding back data.
This is exactly meeting the expectations when we started this program.
And therefore, the visibility is not high at the moment because the readout is really to see okay. What is the next step for product development and this is why.
Why we both GSK and us.
Ben.
Structuring exactly these clinical trials and then certainly also the Readouts and to report on this one to give the full picture.
On the <unk>.
IP timelines.
Well the process is.
We're talking about here the.
The claims we have started against biotech.
Here in Germany.
This is you can consider a very complex file, which we handled in which will be responded.
Bye Bye bye.
<unk> and this will take a while in order for the court to look into and to evaluate there has been no public hearing, which then certainly would give us an insight how the court at least would see this so with this one I just can say that the process has been started is following the normal rules of the protein.
We are waiting for our first since from from the court.
And followed the process from here definitely nothing in this year does it as much as I can say now.
Okay Fair enough and then maybe I guess on the uncle vaccines Ron.
Could you guys go into a little bit more detail about the usage of non coating areas for antigen identification how frequently the appointment patients in non coding regions result in expressed antigen that's targeted.
In context.
Yes. Thank you very much for that question, we've done the numbers for a couple of them for quite a series of tumor samples and roughly you could say that out of every junction where one chromosome gets coupled to another chromosome about one in 10 actually results in that activating <unk>.
Putting sequence to become part of Athene, which you saw on the other side of the injunction and therefore being becoming translatable.
Also detectable if we look at that and sell that we've studied.
<unk> cells taken from tumor cells <unk> also cell lines in cells taken from from mice as well. So it's about one in 10 cases, where that actually results in such a expressed.
Sequence.
Yeah.
For this chromosomal rearrangement, not obviously not just point mutations in non coding regions.
That's right I would say that a point mutation in a non coding region doesn't contribute much to the answer to necessity right. Because there is no reason why it will be coding and we haven't followed that up at all so.
Expanding the sequencing to the 98, 5% non coding is in my view, especially.
Interesting for detecting those really arrangements that lead to stretch is being expressed and not to the point of view to sit in those strategies.
And then as a follow up to that obviously chromosomal rearrangements are relatively frequent in tumors overall.
But how often are those rearrangement.
Basil to the tumor that is to say, how often is it tumor clonal furloughs coating re arrangements across all the cells.
In the tumor.
So two different questions were actually writing a manuscript to give you all the numbers.
We've looked at many cancer types.
And also looked at data generated by a salesman depended upon the public databases and indeed in different indications the frequencies of such really arrangements differ.
Sometimes in an interesting way for example client was stoma is obviously poor important mutants because brain cells or impairments protected from the environment that we find there's still much to be relatively rich and such a chromosomal rearrangement. So that's an interesting point to look at indeed as you point out.
The second is the choice of the antigens for designing vaccines and personalized.
And then what.
It's much crucial is what in technical terms this quarter variable allele frequency that means if we know because we sequence the tumor, let's say 100 times deep. So every site in the genome sequences 100 times, so we know rather precisely whether the tumor sample.
Surgeon or do a biopsy Bruce and has given us is 25% tumor material 30 or 40. So we know precisely whether a certain rearrangement is present in all of the tumor cells only in a subset of them and we basically.
Everything on the ones that are clonal.
The sample so as far as we can know from that sample are present in all of the two of them material.
Does that answer your question.
Our next question comes from Roy Buckingham with JMP Securities. Please proceed.
Hi, great. Thanks for taking the questions I guess the first one is financial how should we think about the expense trajectory for 2023, how much are you planning to spend on implementing that the RNA printer in the clinic and can you remind us where the GMP fore sight isn't development and how much is funded by the.
German government and then finally on the printer have you had any engagement with the FDA our plans to engage ahead of potentially using it in a trial.
Hi, Roy how are you, it's Pierre I'll take a couple of questions probably pass on the FDA discussion.
We don't we don't break down you know the the allocation of our cash burn.
For item like the printer or a gym before but when we look at the year to come.
We are closing our budget process now so it's still.
Subject to some changes, but the idea is that with the cash position. We have we should be able to sell through the whole of next year and a bit of the following year right. So and at the same time make sure that we continue to fuel.
The strengthening of the platform and I think we went through a long strides in the presentation to try and give you a sense of what we're doing.
And on <unk>, So the way it works you're right we have this a pandemic.
But they make preparedness contract with the German government. The idea here is that we we basically pay upfront and then we get a a fee a yearly fee from the German government rates. So we would have to make sure that the plant is ready to go and fully I would say resource, but then all of that is more than pay for.
By the German government.
Yes, so there.
There was a question on the do we discuss with the idea of the printer and this is maybe you can tell you I thought we plan.
Several health authority interactions during the course of 'twenty, three including interactions with FDA and this will also address breath questions related to the printer.
Okay, Great and then maybe a follow up the two cancer phase ones that youre talking about where are they going to be conducted in what's the deliveries. It I am I V are using Alan piece, it sounds like Youre using Alan Pete. Thanks.
Yeah, actually I mean see countries and locations will be communicated in due time.
Second part of your question was about the LNP and yeah. We will use the same LNP formulations, we are using for our comp prophylactic vaccine candidates.
And that will be injected intramuscularly.
Great. Thank you.
Yeah.
Our next question comes from Z Swain shoe with Bamberg. Please proceed.
Thank you very much I have two.
Two questions.
First on the debt.
The cancer vaccine.
Pipeline.
All lines today I wonder for the human proof of concept proof of principal studies are going to do the first on the go.
I guess can you provide additional rationale why.
Going to first use robust nomads, a proof of concept and why now.
It's a tough cancer to crack.
Any color there would be.
Yeah. So thank you for that question so indeed.
This is a tough cancer, but also an indication with very high unmet need and where we see a potential clinical window of opportunity to apply the explanation.
At a point in time, where patients have completed the surgical resection and standard of care of radiation therapy, that's a point in time.
As of Tomorrow is being controlled residual tumor is limited.
Yeah, we see them still.
It's still a space for vaccines to make an impact in the future.
We'll also invest in discoveries of new and additional antigens and that indication that's what I'm gonna tests elaborated and also look for potential to apply combination treatments with potentially synergistic agents to overcome the immunosuppressive microenvironment, perhaps also.
On top of them to say that with the technological advancements we've been doing over the last few months even.
This multi epitope approach certainly can be covered by mrna from a technology point of view exactly.
Got it and then second question.
On yours.
Proprietary nonregulated LNP I guess, just looking at the data released on page 16.
It looks like.
The humor MRO activity higher.
And at the time.
Does that.
Protein expression from the MRI based on all your new new and <unk> formulation.
Sorry could you repeat the question.
Breaking up there for a minute.
Sure I'm, sorry on slide 16.
Some of the data on Nam populated LNP formulation and I think you showed she looked at three panels you showed.
The neutralizing antibody titers are higher based on your new technology I Wonder does that does that mean, the MRI protein expression is higher using your.
The new formulation.
Exactly I mean, they they are higher and this is a trend that we see and reconsider this positive trend, but at the moment.
More than a trend you'll see that I mean, it's a nice one because you see that interferon gamma interferon alpha is very much comparable but yes, there is a tendency to slightly higher neutralizing antibody titer.
So I guess do you envision this to be used in the cancer vaccine.
Platform or more on the infection.
Franchise.
So we see that this is an improvement of the LNP and certainly that's exactly the franchises. We have the one is oncology prophylactic vaccines and then also molecular therapy and that's exactly what we are investigating so we see this as part of our technology and then to be applied or even optimized in the field, where it's going to be used but certainly oncology is a field.
Even though we start with Zika was saying before we start with the available.
Lnp's, which are on the vaccines at the moment certainly we will bring our own Lnp's then into expected these different areas in oncology certainly this core.
Great. Thanks, very much congrats on that.
Our next question comes from Luisa Borgata with Amp and please proceed.
Hi, Thank you for taking my question I, just have one towards the cancer vaccines.
What do you predict will be the ratio for the off shelf or personalized cancer vaccine.
Yeah.
Yes.
Right.
You mean the ratio between.
And numbers of because we're developing both and developing trials for each of those approaches and they are in the development, but they were both so.
Developed in full.
And as was pointed out in the introduction, we see but that's a long term view of course that there will be patient groups through which one will be applicable in patient groups for which the other one will be let's say required because by an off the shelf you cannot reach enough.
I think there's space for both does that answer your question.
Yes, do you have that.
Maybe any idea what is the percentage of one and the other in terms of number of patients have eliminated.
Now it's early to tell.
It's really early to say, it's also an entirely different approach you have to keep that in mind right because if it's off the shelf that of course scalability is favorable.
But if it's required for efficacy then what needs to go fully personalized and time will tell.
Thanks.
We have a follow up from Roy Buckingham with JMP. Please proceed.
Hi, great. Thanks for taking the follow up I appreciate the detailed timing for the Covid and flu trials in the first quarter I'm. Just wondering if you have a sense of which one might read out first.
That's a very good question, we cannot say because the recruitment has not fully finalized here.
Therefore, it's very hard to say very hard to say, but we hope that everything will come close.
We will have a complete readout.
As I said the recruitment, especially if you go down in the elderly. This will take there is a certain sequence of events on the recruitment.
This is exactly what it is.
What will.
Decide on the timelines here and as it is not completed yet it's very hard to say.
Okay got it and then a detailed question I guess on the workflow on slide 18, you have fill and finish great out I assume that's because that's not <unk>.
Relevant in the personal a vaccine setting or is there. Some other reason can you just explain that.
You are asking about their workflow.
Slide 18, so yeah. So the.
Yeah.
The timing there is that the sample is taken and within two weeks. We can go from the sample to design of the vaccine and then of course it needs to be manufactured.
Manufacturing and quality control.
And in reasonable clinical practice.
Be done within six to eight weeks of Max which is what we're currently working on this is as you have been referring to the fill and finish this is exactly where the printer should make.
Should play a role, but then you have got everything at the same spot.
Then the small scales affiliate finished would not be a limiting factor here is either.
Okay got it thank you.
Thank you at this time I would like to turn the call back over to management for closing comments.
With this we would like to conclude this conference call. Thank you very much for your participation stay safe. Please don't hesitate to contact US should you have any further questions. Thank you and goodbye.
This concludes today's teleconference. You may disconnect your lines at this time and thank you for your participation.