Ladies and gentlemen, thank you for standing by and welcome to the BioNTech's Fourth Quarter and Full Year Operational Progress and Financial Results Call. At this time, all participants are in a listen-only mode. There will be a presentation followed by a question-and-answer session.

I must advise you this call is being recorded today, Tuesday 31st of March 2020. And I would now like to hand the call over to the Vice President Investor Relations and Business Strategy, Sylke Maas. Please go ahead..

Thank you for joining us today for BioNTech's fourth quarter and full year 2019 update call. Before we start, we encourage you to view the slides for this webcast as well as the financial results press release issued this morning; both of which are accessible on our website in the Investor section.

Slide 2 and 3 provide legal disclosures related to the pending acquisition of Neon Therapeutics. As shown on Slide 4, during today's presentation, we will be making several forward-looking statements.

These forward-looking statements include but are not limited to the timing for enrollment and completion and reporting of data from our clinical trials and preclinical programs, the potentially registrational nature of certain of our clinical trials, expectations regarding the timing for completion and potential benefits of the Neon acquisition, the impact of the COVID pandemic on our business and our financial outlook.

Actual results could differ from those we currently anticipate. You are therefore cautioned not to place undue reliance on any forward-looking statements which speak only as of the date of this conference call and webcast.

Speaking and available for questions today will be Ugur Sahin, Chief Executive Officer; Özlem Tureci, our Chief Medical Officer; Sean Marett, Chief Business and Commercial Officer; Ryan Richardson, Chief Strategy Officer; and Sierk Poetting, Chief Financial and Operating Officer. I now hand the call over to Ugur Sahin, BioNTech's CEO..

Thank you, Sylke. It is a pleasure to welcome you all to our first quarter and full year 2019 conference call. I will start with a few introduction remarks followed by an update of our significant efforts to address the COVID-19 pandemic that is having a severe impact around the globe.

I will invite Ryan Richardson to provide a mid update on the pending Neon Therapeutics acquisition announced in January of this year, and Özlem Tureci will provide some topline updates, then Poetting will provide [ph] our financial results. I will then make a few closing remarks on the outlook for 2020 before opening up the call for questions.

To start on Slide 5, over the past year, we have taken a number of important steps towards our vision of building a global next generation immunotherapy company. We have built a broad suite of novel therapeutic platforms to explore the full potential of the immune system.

We are advancing along with our pharmaceutical collaborator, our broad pipeline of first-in-class immunotherapies for the treatment of cancer. We have built a growing number of programs targeting infectious disease.

Most importantly, one of the programs is our recently announced mRNA vaccine program of preventing of COVID-19 which we initiated earlier this year as part of our project Light-Speed in response to the global coronavirus pandemic. Our COVID-19 vaccine program based on our deep experience [indiscernible] and growing footprint in infectious diseases.

To address this epidemic we are applying the full spectrum of our capabilities. Our broad mRNA vaccine platform, our integrated GMP manufacturing infrastructure, and our broad base of global world class propagator. I will come back to the COVID-19 in a few minutes and provide an update on the status of our program.

Turning to Slide 6, our accomplishment in 2019 and so far in 2020 demonstrate our ability to execute on our vision. 2019 was a transformational year for BioNTech. We have continued the strong momentum in this year against a challenging market backdrop. I want to quickly highlight a few of these key achievements.

Consistent with our stated objectives we have increased the number of product candidates in clinical testing from seven to 10 since the completion of our IPO in October last year and have announced our intention to initiate late-stage studies over the next 12 months.

We have also increased our pharma partnerships with the recent expansion of our Pfizer collaboration and the announcement of our first Asian partnership strategic alliance with Fosun Pharma.

Early in January of this year we announced the signing of a merger agreement and our offer to acquire Neon Therapeutics which if Neon shareholders vote in favor of the merger and if the other conditions to closing are met then expect to bring us some exciting new pipeline candidates in cell therapy stages.

With our complementary technology and our and the U.S. R&D hub will support the growing number of studies we are conducting in [indiscernible]. And we completed two successful financings; our Series B and of course the NASDAQ IPO which together both got proceeds 374 million for the company.

Lastly, we made good progress in our multiyear investment programs to expand our in-house mRNA therapy manufacturing capacities. Manufacturing remains a key strategic priority for us as we expand our pipeline of product candidates towards the market.

I will now turn to Slide 7 and discuss COVID-19, the growing global hash tag that has dominated the world's attention over the past weeks. Earlier this month we announced that we are developing a vaccine which aims to induce immunity and prevent COVID-19.

We initiated a project Light-Speed because this year we have the duty to fully utilize our technology and immunotherapy expertise to have to address this pandemic in urgency aided by the global steps of the dangerous pathogen. For our COVID-19 program we are leveraging our [indiscernible] mRNA platforms for infectious diseases.

Our fully owned GMP manufacturing [indiscernible] of mRNA vaccine production and our global clinical development capabilities. We have partnered with Pfizer for worldwide development of the vaccine and have also established a strategic alliance with Fosun to develop a vaccine in China.

We have been in close contact with regulatory and scientific authorities around the world and in ongoing discussions with such organizations. We anticipate initiating clinical testing in late April subject to regulatory approval. We expect to conduct a global development program spanning Europe, United States, and China.

Our mRNA vaccine for COVID-19 explores a highly potent Lipid-Nano-Particulate or LNP messenger RNA vaccine product. We believe that mRNA vaccines are highly reputed for this challenge. mRNA vaccines have been shown to be highly immunogenic and induce neutralizing antibodies as well as T-cell responses.

mRNA is a naturally occurring molecule with well characterized safety properties. Furthermore, mRNA vaccines are well defined biopharmacological with high [indiscernible] and our animal material suite.

We believe mRNA vaccines may offer several advantages of a positional vaccine approach including an ability to precisely design and manufacture rapidly in a large quantity.

Sean, do you want to say a few words about our recently announced collaborations for our COVID-19 vaccine?.

Thanks Ugur. For COVID-19 we are collaborating with one of the world's largest pharmaceutical companies, Pfizer and one of the leading healthcare groups in China, Fosun Pharma.

Just a few weeks ago we signed a letter of intent with Pfizer regarding development of BNT162 outside China and expect to provide more details of the financial terms behind our collaboration soon.

As we already have a successful collaboration with Pfizer for infectious diseases aimed at developing influenza vaccines, we have been able to immediately start work to rapidly advance BNT162 towards clinical testing for the prevention of COVID-19.

We are currently utilizing multiple research and development sites for both BioNTech and Pfizer and look forward to providing further updates on the fast moving collaboration in the future. We also recently announced our strategic alliance with Fosun Pharma, our first strategic collaboration in Asia to jointly develop BNT162 in China.

Together with Fosun Pharma, we intend to conduct clinical trials in China leveraging our mRNA vaccine technology and manufacturing and Fosun extends their clinical development regular trade and commercial capabilities in the country. Under the agreement, both companies will collaborate to conduct clinical trials in China.

Fosun Pharma has the right to commercialize the vaccine in China and will pay BioNTech up to U.S.$135 million, that's €120 million in upfront and potential future investment and milestone payments. The two companies will share future gross profits from the sales of the vaccine in China..

Thanks Sean. Before I move on, I would like to note that we are current in monetary litigation and we got to the potential impact of COVID-19 from our observation.

SM is going to be providing additional detail later in the call, but there has been impact to some of our previously communicated prior timelines, in particular, to plan studies starts for 2020. We will continue to monitor the situation and provide updates as appropriate.

I will now ask Ryan to provide a brief update on our announced offer to expand BioNTech projects. First however, I wanted to highlight Ryan's appointment as Chief Strategy Officer. He has significantly contributed to multiple key corporate development initiatives, including the acquisition of Neon.

And he was instrumental in successfully taking BioNTech's projects in a challenging market environment. I want to thank him for his accomplishments so far and look forward to his continuous efforts in helping to execute our shareholder [ph] core strategy.

Ryan?.

Thank you, Ugur. Turning to Slide 8, in January we announced entry into definitive merger agreement under which BioNTech would acquire Neon in an all-stock transaction. The transaction remains subject to a vote of Neon's shareholders which we expect to take place during the second quarter.

For those who are not familiar with Neon, it is a biotechnology company based in Cambridge, Massachusetts developing novel neoantigen based T-cell therapies. From a strategic standpoint, this acquisition has a strong feel on multiple levels.

One, it will bring us some exciting preclinical programs including NEO-PTC-01, a personalized neoantigen targeted T-cell therapy candidate consisting of multiple T-cell population that target the most therapeutically relevant neoantigens from each patient's tumor. It also brings NEO-STC-01 a T cell therapy candidate targeting shared RAS neoantigens.

In addition, Neon has assembled libraries of high quality TCRs against various shared neoantigens across common HLAs, which we believe will complement our own technology toolkit.

Neon's pipeline is underpinned by several complementary platform technologies including RECON its machine learning bioinformatics platform and also NEO-STIM, its proprietary process to directly prime, activate and expand neoantigen targeted T-cells ex vivo.

The acquisition will enable us to significantly expand our presenting capabilities in the United States which remains a strategic priority for us. Under the terms of the agreement Neon would become a wholly owned subsidiary of BioNTech upon closing.

As previously indicated, subject to a favorable vote of Neon shareholders we expect the transaction to close during the second quarter of 2020. We look forward to closing the acquisition and beginning the integration process. I will now hand over to Özlem to discuss key updates in our development progress..

Thank you, Ryan. Today, I am going to provide updates for our pipeline since our last call in November. I will start with some detail on the effects of the coronavirus pandemic on the timing of our vaccine and co-trials. The short message is that we do expect some impact to the timelines we have previously communicated.

As shown on Slide 9, while our revenue of the impact is ongoing we are developing and implementing the three point plan to manage the still evolving disruptions that the pandemic has created. First, we still intend to initiate a Phase II trial for BNT111, BNT113 and the iNeST program as originally planned.

We assume that the anticipated back dates of end of year 2020 provides time for stabilization of the clinical trial environment. We believe that the trial of BNT111 and BNT113, these are our FixVac products for melanoma and for HPV positive cancer have the potential to be registrational studies.

Therefore continuing the activities to progress towards initiation of these trials is a key priority for the company. Second, we will manage our ongoing Phase I exploratory and dose escalation trials to support timely completing.

We have seen evidence offloads [ph] enrollment in our trials given the restrictions at clinical sites and travel restrictions for patients. We expect BNT111 and BNT114, the TNBC and melanoma FixVac trials to be less effective given that these trials are near completion of enrollments.

The recently initiated programs such as BNT112 which is prostate cancer FixVac are more likely to be affected these delays. So we expect that there will be delays to some of our first in human studies planned to commence this year.

So now we maintain timing guidance for our COVID program, BNT211, the late state of first in human Phase I studies may occur for our RiboMab program BNT141 and BNT142, our RiboCytokine program BNT151, BNT152 and BNT153, and our TLR7 agonists program BNT411 and also for our influenza program and our rare disease program.

At this time, we estimate the delay for these trials at approximately three to six months. Overall, as the coronavirus situation remains dynamic, we will continue to monitor the situation as it evolves. We will update investors as appropriate.

Now I will discuss key updates to our clinical pipeline as shown on the next slide where we have 10 products and 11 ongoing trials. First an update on BNT111, our FixVac candidate for the treatment of advanced melanoma. Data from our Phase I trial in advanced melanoma is on track to be published soon.

Shows our regulatory discussions have occurred regarding next steps and I will provide more detail later. BNT112 is our FixVac candidate for the treatment of prostate cancer. Dosing of patients in the Phase I/IIa study has been initiated. Eligible patients who are dose titration have metastatic castration-resistant prostate cancer.

In the expansion part also patients with newly diagnosed high risk localized prostate cancers are eligible and will be treated with BNT112. BNT114 is a program that evaluates range of novel antigens for the treatment of TNBC for immunogenicity in the Phase I/II trial.

Data was previously expected to be presented at [indiscernible] Annual Meeting scheduled for May. Given the postponement of the conference due to the COVID pandemic BioNTech is evaluating the appropriate opportunity to present the data later this year.

Moving on to our individualized neoantigen specific immune therapy or iNeST program, earlier this year at our JPMorgan presentation, we provided some additional clinical data from the Phase I trial for BNT121, the precursor to RO7198457 or BNT122.

This data update demonstrates its stable disease in melanoma patients who are up to 16 months post vaccination. For BNT122 we disclosed with Genentech that two additional Phase II clinical trials in the adjuvant setting are planned for initiation in 2020.

The first adjuvant Phase II study will evaluate the efficacy, safety pharmacokinetic and immunogenicity and biomarkers of BNT122 plus at least RiboMab compared with others or RiboMab alone in patients with stage 2/3 non-small cell lung cancer who are positive for fixed circulating tumor DNA following surgical resection and have received standard of care [indiscernible] tablet chemotherapy.

The second indication has not been yet disclosed. Regarding the iNeST Phase II trial in first line melanoma, we still tend to provide detailed interim data in 2021 and then enrollment update in H2 2020. We expect the interim data in 2021 to include topline efficacy and safety data as of the interim date.

Now turning to our intratumoral immunotherapy program partnered with Sanofi, the data updates from the ongoing Phase I/II trial of BNT131 in solid tumors remains on tract. I am also pleased to report that our next generation checkpoint immune modulatory program partnered with Genmab is moving rapidly.

Topline data from the Phase I/II trial BNT211 in mild episodic tumors is now expected in the second half of this year ahead of our previous expectations for data readout in the first half of 2021. And finally, progress has been made in our clinical program for BNT321.

The first patient has been dosed in the resumed Phase I/II study evaluating the Phase and recommended Phase II dose of BNT321 in patients with pancreatic and other CA19-9 positive malignancies. I will now move to Slide 11 and provide some quick updates on our preclinical pipeline.

First for our FixVac portfolio BNT116, has been added to our product portfolio and is currently in preclinical development for non-small cell lung cancer. As I mentioned earlier, BNT211 our CAR-T program targeting solid tumors is on track to go in the clinic in the summer this year.

This program combines our CAR-T therapeutic approach with our mRNA vaccination and uses our proprietary tumor selective target guarding. For our TLR7 agonist, BNT411 the IND was allowed in Q4 2019. We expect Phase I initiation later this year.

Lastly, project life, as Ugur mentioned earlier, we expect to dose the first patients in our clinical program testing BNT162 our COVID-19 vaccine candidate in April of this year. Now, on Slide 12, I want to get some additional detail on two of our most advanced immune oncology programs, BNT111 and BNT122.

For BNT111 our melanoma FixVac, we expect data from our Phase I trial in advanced melanoma to be published in the medical journal in late H1 2020. As I mentioned earlier, we have had further discussions with regulatory authorities regarding net depth and the design of our registrational trial.

Based on those discussions we believe there may be potential to conduct a registrational Phase II trial instead of a Phase III trial. We are not providing design details at this time, but we can say that we expect the arm to include BNT111 in combination with a checkpoint inhibitor and controls.

This study population will be patients who are checkpoint inhibitor. We expect to provide further update on the extra trial design in Q3 2020. For BNT122 data update for the Phase I/II trials in multiple solid tumors was planned AACR Annual Meeting which due to the COVID-19 pandemic has been rescheduled for August 2020.

Our data is embargoed until to that presentation date. We are very pleased that iNeST was included during the recent Genentech Research and Early Development or gRED event for those that may have missed the presentation, Genentech highlighted iNeST potential to provide a personalized cancer vaccine for a broad range of cancer patients.

I will now hand the call over to Sierk to discuss our current financial results of the fourth quarter and full year 2019..

Thank you, Özlem. But before presenting the financial results, I would like to provide you information on our measures that we put in place in order to mitigate the potential impact of the coronavirus pandemic on our operations.

In response to the coronavirus outbreak, we continue to monitor the potential impact to our supply chain and manufacturing operations, which includes mRNA manufacturing for FixVac and iNeST platform products, as well as our CAR-T manufacturing sites. So far our manufacturing operations are unaffected and still running at full capacity.

In terms of our personnel, we have instituted measures to ensure the safety for precautionary reasons. We are closely monitoring any employee that has potentially been in contact with affected individuals or in affected areas and we are limiting access to BioNTech facilities as appropriate.

Now, I would like to summarize our financial results that are shown on Slide 13. Cash and cash equivalents as of December 31 2019 were €519.1 million. As we indicated earlier in the year, we expect net cash used in operating activities and other investments to total approximately €300 million for the full-year of 2020.

At this time, we are maintaining that guidance. Total revenue consisting primarily of revenue from collaborative agreements was €28 million for the fourth quarter of 2019, compared to €63.8 million for the prior-year period. The decrease was primarily due to decreased revenues from our collaboration with Sanofi.

Total revenue consisting primarily of revenue from collaborative agreements was €108.6 million for the full-year of 2019 compared to €127.6 million for the prior-year. The decrease was primarily due to decreased revenues from our collaboration with Sanofi.

The decrease in revenue from Sanofi is primarily driven by revenue of €33.2 million for a one-time reimbursement of certain sublicensing costs that was fully recognized in the year 2018. Research and development expenses were €65.4 million for the fourth quarter of 2019 compared to €51.8 million for the prior-year period.

The increase was primarily due to an increase in headcount and higher expenses regarding our collaboration projects. Research and development expenses were €226.5 million for the full-year of 2019 compared to €143 million for the prior year.

The increase was primarily due to an increase in headcount, the full-year impact of our ESOP program and higher spending for purchased services and laboratory supplies for the projects. General and administrative expenses were €11.1 million for the fourth quarter of 2019 compared to €10.1 million for the prior year period.

General and administrative expenses were €45.5 million for the full-year of 2019 compared to €26.3 million for the prior-year.

The increase was primarily due to an increase in headcount, the full-year impact of our ESOP program, and the charge in connection with certain - withholding tax payments for intellectual property licenses that was recorded in the year 2019.

Net loss was €58.2 million for the fourth quarter of 2019 compared to net loss of €1.5 million for the prior-year period. Net loss was €179.2 million for the full-year of 2019 compared to net loss of €48.3 million for the prior-year. Shares outstanding as of December 31, 2019 were approximately €226.8 million.

With that, I will return the call back to Ugur for concluding remarks..

Thank you, Sierk. Following a strong and productive 2019, there are several important milestones ahead of us in 2020 as shown on Slide 14. It includes six trial updates including publishing BNT111 FixVac Melanoma Phase 1 data in a peer reviewed journal.

We look forward to the initiation of the trial for our BNT111 FixVac Melanoma candidate which we released at registrational potential. We also expect the initiation of two additional iNeST trials in adjuvant stage cancer this year. By the end of next month, we expect the initiation of the clinical testing of our COVID-19 vaccine candidate BNT162.

I would like to point out that we expect to start a Phase 1/2 trial using CARVac BNT211 in CLDN6+ solid tumors. Hence we want to start a Phase 1 trial of our TLR7 program BNT411 in solid tumor. Lastly, we will work to integrate our U.S. Hub in Cambridge, Massachusetts, following the expected closing of the Neon acquisition in the second quarter 2020.

We look forward to updating investors and other stakeholders throughout 2020. We thank our shareholders for their trust and support. We will now take any questions you may have.

Operator?.

Thank you very much. [Operator Instructions] The first question we have today comes from the line of Cory Kasimov from JPMorgan. Please go ahead..

Hey, good morning guys, and thank you for taking my questions.

A couple of them for you, I guess to start, your COVID-19 program BNT162 is what are the gating factors to getting this product into the clinic and can you maybe discuss at a high level how your vaccine approach might be differentiated?.

Yes, thanks for the question. The development of our COVID vaccine is based on our in-house platforms. We have free messenger on these platforms which can't be exploited for development of COVID vaccines exploiting different epitopes. So it's the modified messenger on a platform.

Then the gene mRNA based platform which we are using currently for treatment of cancer patients and the self [ph] and design on a platform.

The sequence of development events is based on preclinical evaluation of signals and on GMP manufacturing of the materials GLP toxicology and discussions about the clinical trial design with the regulatory authorities in Germany, China and with the FDA and related ethics committees.

We are on track in the development of our vaccine and expect a time we start of the third clinical trial in Germany in the second half of 2020.

The differentiation factors of our vaccine platform is one intention is that we get develop a vaccine, which is not only safe, but it enables immune responses neutralizing antibodies with those possible dose..

Okay, and then from a timeline point of view, would you expect this to follow a similar path to other vaccines that have been publicly commented on?.

To which type of vaccines do you want?.

Other COVID-19 vaccines that we've heard about from other companies that have been commented, they have talked about and they talked about timelines and talked about things like 12 to 18 months in a situation like this, potentially get it from start to finish? Do you think that's kind of a realistic expectation for your program as well?.

So maybe SM can….

Yes, I can take this one. These are plausible sounding timelines. At the end of the day, this will - the timelines will depend on positions of regulatory authorities and based on which type of data such a vaccine would be made available to a larger population. So this will need to be really worked out in the ongoing discussions.

We and also the other companies you are referring to have with the regulators and the data which we can all present from our trials..

Okay, that makes sense.

And then one non-COVID-19 question if I may, could you just give us a sense of where you are in terms of dose escalation for BNT311 and how much data we should maybe expect in the second half of this year?.

That is the DuoBody, we are - you refer to PD-L1 4-1BB DuoBody which we are developing in cooperation with our partner Genmab. We are pretty advanced in our dose escalation.

So have cleared a number of dose levels which were planned and the data disclosure presentation would definitely include data, referring to safety of different doses, probably also the Phase II dose..

Okay, very helpful. Thank you for taking the questions..

Thank you very much. The next question today comes from the line of Tazeen Ahmad from Bank of America, please go ahead..

Hi, good morning. Thanks for taking my questions.

With regards to your publication that you mentioned in your prepared remarks that's expected in the second half of the year of Phase I data for Melanoma, can you give us an idea of what level of detail you expect to have in that article? And as it relates to a potential for registrational study, what in your discussions with FDA gives you confidence that you would be able to potentially use the next study as registrational versus having to do a full Phase III? Thank you..

So the first question, referring to our publication, here the data we will publish is data which comes from our Lipo-MERIT trials of dose escalation, dose expansion trial with our melanoma FixVac in heterogeneous population of patients with advanced melanoma and what we will publish, the focus here is primarily on the mode of action of the vaccine which we show for the first time in humans in particular, also the immune responses, their magnitude, their type and their kinetics, but also some safety and activity data..

Okay, thank you.

And as it relates to your discussions with FDA on the potential for registrational study?.

Yes, so the discussion with the FDA was of course based on the design of the clinical trial, the statistical parameters required for showing the endpoints of the clinical trial and treatment and control arms. And based on this discussion and we will further provide updates, specific updates about different arms and the size of the arms later on.

Based on the discussion with the FDA, we are confident that if we can deliver the request of the study of the desired study design, then the FDA would be in agreement with the registrational nature of the trial..

And would that require an in-person meeting once you deliver the study design?.

Sorry, can you repeat?.

Sure, once you deliver the study designed to the agency, would you then need to have an in-person meeting with the agency to determine if this can be registrational?.

In general, the agency also enables non in-person meeting through the phone conferences. So that would be also in this case be sufficient..

Okay, thank you..

Thank you very much. The next question today comes from the line of Shanshan Xu from Berenberg. Please go ahead..

Hey, good morning.

Regarding BNT162, that's the COVID-19 vaccine among as men [ph] proteins, what could be your targets? And are you thinking about receptor binding domains? And you also mentioned that you saw neutralizing antibodies generated in the BNT162 preclinical study, can you share with us which epitopes you observed for these neutralizing antibodies? And do you think titer of neutralizing antibodies can serve as surrogate clinical efficacy endpoint in COVID-19 vaccine development? And I have one follow-up..

Thank you, Shanshan for the interesting question. So, yes, we are evaluating different epitopes including the full length spike protein, but also sub-domain, we are going to provide details of our [indiscernible] vaccines, vaccines in the coming weeks and immune responses that we observed against the full length protein and the sub-domain parts.

We have established a number of assays studying immune responses in mice including antibody responses, T-cell responses, neutralizing antibody responses using pseudo type and viral state neutralization assays. And based on the assays, we are confident to reduce the spectrum of candidates to a meaningful number to be tested in the clinical trial..

Okay, thank you. And another question regarding the RNA format and also the delivery formulation. So modRNA that's the modified RNA, that is the mRNA format you used in your Zika vaccine. To us it is not highly immunogenic.

Can you tell us what is the scientific rationale of using it in infectious disease vaccines? And also for your delivery formulation, the Lipid-Nano-Particulate LNP, you saw that with this delivery technique, it was modified to shift the immune response more towards TH2 cells not TH1 cells.

Can you share with us what modifications have been done on this LNP formulation to increase TH2 activation? Thank you very much..

Yes, you’re welcome. So, actually we have a set of mechanistic data that the different platforms, which we are using or could use different levels of TH1 responses.

So, it is also the modified RNA platform together with a novel formulation has T follicular helper immune responses, and most importantly, induces highly neutralizing antibody responses which are in our working hypothesis are the most important immune response parameters required to control COVID-19.

We used the unmodified mRNA platform, since it comes with TLS7 co-stimulatory activity to evaluate if the additional TLS7 agonistic activity can further reduce the dose and we are using [indiscernible] on a based approach to further elaborate and that due to the test application based on the vaccine, vaccine amplification after delivery, we can further reduce the dose days.

As evidenced in the preclinical settings, we have published data showing that this is the case for HIV and this is the case for Influenza vaccines and therefore also based on preclinical data that we have seen for COVID-19, which are encouraging we decided also to evaluate this platform in our clinical trials..

Perfect, thanks..

Thank you very much. The next question today comes from Navin Jacob from UBS. Please go ahead..

Hi, yes, thanks for taking my question, Navin from UBS.

So a couple of questions, just as it relates to targeting this spike protein, can you give us any kind of color on how you're thinking about whether mutations around the spike protein could create selective pressure? And then with regards to that, how you're thinking about timelines? What data do you need to see to ensure that that is not going to be - that that won't be an issue? And then separately or along the same sort of line, now are you thinking about antibody dependent enhancement? Thank you so much..

Yes, thanks for the interesting question. So, first of all, first of all, there are now emerging publications showing the genetic profile of different COVID sequencing data. And the positive conclusion from the studies is that COVID-19 genome is relatively stable.

We have also done a deeper look particularly to the epitopes that we are targeting and we see minimal differences in different in COVID variants isolated in different regions of the planet. So that we’re confident that escape of the spike protein is not an issue..

Perfect. Thank you so much..

Thank you very much. The next question today comes from the line of Daina Graybosch from SVB Leerink. Please go ahead..

Hi, thank you for the question. First, a couple on COVID-19 and I want to ask one about your oncology work.

We've heard some people speculate that coronaviruses may need a T-cell immunogenicity response in addition to an antibody, and you've talked mostly about an antibody response, and I wonder if you can talk about a cellular response and how important that is in your preclinical work? And the second question is, there's a lot of speculation how durable immune responses are to coronaviruses broadly in COVID-19 specifically, and can you help us understand how you're thinking about durability protection with your vaccine and your hypothesis on necessary boost schedule?.

Yes, yes. First of all, all of our - induced in the combination with the formulation which we are using, powerful CD4 as well as CD8 T-cell response. So that's, that's not the issue.

The second is the durability of the immune response induced by the virus infection itself is something different and then durability of the immune response induced by a vaccine. So, we are using here a vaccine with an inherent adjuvant effect.

And we see with this type of vaccine, regardless of the epitopes that we are using, long lasting immune responses. They have shown that for all of our platforms, that we observed long lasting neutralizing antibody responses for more than one year, the different platforms and T-cell responses, long lasting T-cell responses.

So we are not concerned with regard to the durability of the immune responses that we are generating by the vaccine. With regard to the durability of immune responses that are generated by the COVID-19 infection we just to see because the data emerging and long-term observational data needed..

Great. And then on oncology, you've talked a lot about delays. But we've heard the reports of other challenges in conducting trials that are already enrolled, say protocol violations like miss scans.

And I think that's so important for your early Phase I trials and I wonder how you're monitoring that and if you're taking any mitigating action to make sure the data you get is what you need early to understand problems in the data?.

Sure, so you’re perfectly right.

That indeed is one of the major activities namely monitoring the situation, understanding the specific impacts on what is happening at the clinical side, how regulatory authorities see four times the potential deviation and how to mitigate those deviations we identify as potentially emerging patterns and the current situation is one of major actions taken.

Here in our company you may have heard that some regulatory authorities give guidance in particular for deviations, how to document them for example, in order to ensure that they can then be addressed by regulators, appropriately given the situation, the entire clinical trial landscape is in, but fully agreed, this is one of major aspects which are implemented into the way we are dealing now in this emerging situation with the way we conduct our clinical trials and decide upon how the individual trials should be adapted or further conducted..

Very helpful, thank you very much..

Thank you very much. The next question today comes from the line of Akash Tewari with Wolfe Research. Please go ahead..

Hi guys, I have a few questions.

So Ross made some comments that there's tweaks and optimizations that can be made to the iNeST program, any color on what those tweaks are? And I think more broadly, where's the ideal setting for a personalized cancer vaccine? And would that be in the late stage more bulky solid tumors or perhaps an earlier setting? Next on your COVID vaccine, can you talk about yourself amplifying mRNA platform in the context of your vaccine and given your current manufacturing capacity, what's the largest dose you think is commercially feasible to serve a broader population? And then finally, there's been a lot of work recently that's shown the growing role of B-cells and tertiary lymphoid structures in the role of IO responses.

What's your opinion on some of this emerging research in the context of your cancer vaccine platform and also your PD-L1 4-1BB bispecific. Thanks so much. .

Okay. Many questions, that's right.

So starting with our personalized vaccine approach, so we have of course ongoing trials with our actually third generation Messenger RNA platforms running with in collaboration with Genentech and of course we are further developing the platform and continuously evaluating improvements like for example improvements in antigen design, improvements in formulation, optimization improvements in the number of epitopes that we are delivering and improvement in the extent of TNR stimulation, which is included with our vaccine.

And we are in the next 12 months, we are going to publish a number of collaborative studies with Genentech showing our next generation vaccine could look.

With regard to the positioning of personalized cancer vaccine, we and Genentech believe that particularly tumors with the lower tumor load and particularly tumors with adjuvant stage could be ideally suited for the vaccine in combination or even without checkpoint located.

For diseases which are more in the advanced and later stage that might be necessary to add additional combinations of IO classified samples cytokines to further increase improve the activity of a vaccine in these prior settings. So what was the last question, saRNA.

So with regard to the saRNA, we have published a number of preclinical studies and done one of the interesting insights in using saRNA is that the saRNA can reduce the dose which is required to induce a strong antibody and service can reduce the dose up to 60 to 84 as compared to a non-antibody and this is of course an exciting opportunity to elaborate and to test in a setting where the manufacturing of the sufficient period of vaccine could be a challenge.

We are currently continuously increasing our manufacturing scale. We will update about the target care for manufacturing, manufacturing in the coming weeks and months, but it is clearly our vision to test sufficient capacity to deliver to hundreds of millions of individual doses of vaccines in a reasonable time period.

There was another question that's related to the B-cell infiltration in human tumors.

Yes, I think there is a series of publications, there is a series of publications showing that different type of infiltrates, including infiltrates with dendritic cells and B-cells are associated with improved prognosis and corresponds to checkpoint locale [ph] and of course we are of the studies.

We for example for all of our iNeST studies we are evaluating with some type of tumors and are able to see which type of infiltrated associates with type of immune response and based on this type of information we can of course, exploit different types of immunomodulatory treatments..

Thanks so much..

Thank you very much. And we have time for one more question. That question comes from the line of Arlinda Lee from CG. Please go ahead..

Hi, guys, thanks for taking my questions. First one is the COVID vaccine, you mentioned that you were working with the German, Chinese and U.S. Governments. I’m wondering if you could provide some color on your conversations and maybe your strategy on potentially manufacturing at risk.

Secondly on, we had the chance to speak to some COVID cancer care changes during COVID and I was wondering if you could comment on modifications to your clinical trials or enrollment criteria? And also you're doing a lot of biomarker studies.

I'm wondering if some of these assays can be done on archival samples, and how that might be affected? Thank you..

So we are talking to regulatory authorities in China, Germany and the U.S.

And part of the dialogue is of course harmonization of the clinical trial designs in different countries and not only harmonization but also having complementary trial designs which allow to maximize the amount of information that can be generated and interestingly the situation, the situation whereas Europe and U.S.

now came to hotspots of the infection, the infection rate in China is cooling down.

So giving us different opportunities in different regions affected with different frequency of infections and this is also a good to have situation because based on the situation we can generate safety and activity, efficacy and affectivity data in different regions of the world.

With regard to the biomarkers position, of course we need to evaluate antibody responses before vaccination and after vaccination and this is quite forward approach. This is an established industry for collecting samples, for analyzing samples we have already identified to supporting us here, but this will not be a challenge..

Yes, and maybe just to add to that Arlinda, in terms of the manufacturing at risk part of your question, I think it was our strategy from the beginning to try to get a global consortium in place and we leveraged our partnerships, both existing and also new to do that.

And so we are continuing to evaluate how best to scale-up the manufacturing effort and fund it through our, through those relationships with existing partners and also potential new sources of capital..

Great, thank you. And then maybe just following up on your oncology pipeline, just since biopsy volumes are down, I'm just curious. If the enrollment criteria that you have in place enables use of archival tissue and how you're collecting biomarker data for your oncology trials collecting and processing.

And then maybe lastly, can you talk about your strategy for your cytokine pipeline? Thank you..

Okay, okay. So the archival tissues for development of oncology cut.

Yes, SM would you like to answer that?.

I will answer the question. So it depends on really the drug we are investigating in those trials, in trials in which we want to see and collect biospecimen in order to see the effect of the drug and we need a baseline and under treatment sort of biopsy of blood samples.

There is no flexibility to work with archival tissues or samples because this is really about seeing the impact of a drug. In studies, we for example want to test whether the patient has a certain marker which is stabilized. We work in fact with archival tissue from this patient.

So it really depends on which question needs to be answered and we have a mixture of both fresh tissues and materials and archival materials..

And if your question refers to the enrollment of patients into iNeST studies, yes, we can use and the ideas in archival materials just haven't passed in that, so that means there is no essential need to do fresh biopsies..

Thank you very much.

Would you like to make some closing remarks?.

So, thank you. Thank you for today's call and we look forward for meeting you in near future. Thank you..

Thank you very much. That does conclude the conference for today. Thank you for participating. You may all disconnect..