BioNTech SE (BNTX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the BioNTech Conference Call. [Operator Instructions] I must advise you that this call is being recorded today, Wednesday, the 1st of July 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 conference call to provide preliminary Phase I results for 1 candidate from our BNT162 vaccine program against COVID-19. You can access the press release issued this morning as well as the slides that we'll be presenting by going to the Investors section of our website. 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 ongoing clinical trials. 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 today will be Ugur Sahin, Chief Executive Officer; Özlem Türeci, Chief Medical Officer; and Ryan Richardson, Chief Strategy Officer, will be available for the Q&A session. And now I hand the call over to Ugur Sahin, BioNTech's CEO.

Thank you, Sylke. So good morning, everyone, and thank you for joining our call. Today, we released the first data from our BNT162 vaccine program and are pleased to provide our first clinical data for Project Lightspeed, our coronavirus vaccine program, which is executed together with our partner, Pfizer. I want to note that the data we will be presenting today are interim data. That means the trial is ongoing. The data has been submitted for publication in a peer-reviewed journal and is currently available online on a preprint manuscript server net archive. Let us start on Slide 3. So as [ recount ] to you, we initiated Project Lightspeed in late January of this year after we have seen the news to the coronavirus outbreak in China and after the SARS-CoV-2 Genetic Sequence was published on January 12. So we started early on to generate more than 20 message RNA vaccine candidates and performed a series of preclinical studies to select 4 candidates, which were selected to go into the clinic. So these 4 candidates together are collectively known as our BNT162 vaccine program. So then, in March, we announced a collaboration with Pfizer to develop BNT162 workload excluding China, because for China, we have established a separate partnership with Fosun Pharma to develop the program in China. We initiated a First in Human clinical trial with this candidate in Germany late April. And we dosed the first subject with a COVID-19 vaccine in the European Union and initiated a tie, along with our partner, Pfizer, in the U.S. in early May. So that means we have 2 clinical corresponding. The preliminary results we are going to share with you today are 1 of the 4 vaccine candidates, which entered into clinical testing. We refer to this candidate as BNT162b1. And this result are results from the ongoing Phase I part in the U.S. only. So this result do not include the German participants. So I'm going to quickly run you the principles of the virus infection. So Slide 4, please. So it begins with the exposure to a virus. The virus enters to cell where it utilizes the host to replicate. The virus copies are then released from the host cell and spread to other cells, and the process is repeated. And by this amplification process, the magnitude of the infection can become significant very quickly. As shown on Slide 5, vaccine delivers both the virus antigens and the appropriate immune-activating stimulus. And this, ideally together, induces an immune control, which brings 2 components: one, utilizing antibodies and T cells. While outside the host cell, the virus is accessible to this antibody. Inside the host cells, it can be targeted by T cells. So antibodies and T cells cooperate. Antibodies inhibit the spread from cell to cell, but also from individual to individual. An -- antibody-producing B cells can adopt a memory function. Once induced, this memory function can stay active for years. T cells are able to cure infected cells and are able, thereby, to reduce the overall virus load. CD4 T cells, these are also known as helper T cells. There're multiple purposes, including providing a memory function to induce rapidly a T-cell response when the immune system is encountering the virus again. So Slide 6 provides an overview of our 4 vaccines -- vaccine candidates, which are currently in the clinic. Our vaccine program leverages clinical candidates against 2 distinct targets. The one is the full length spike protein. And the second is a much smaller optimized receptor-binding domain, which is also known as RBD and which is just a part of the spike protein, which is essential for the uptake of the virus into a host cell. So to our knowledge, we are the only company, so far in the clinical stage, with a vaccine targeting the receptor-binding domain alone. So having vaccine targeting different domains is relevant since we, at the moment, or the whole field, at the moment, does not know which is the optimal antigen to induce a vaccine response. Our BNT162 program also includes different messenger RNA forms. 2 of our 4 candidates uses -- use a nucleoside-modified mRNA backbone. One includes the uridine-containing messenger RNA and the first vaccine candidate utilizes the self-amplifying messenger RNA. Today, we will focus only on BNT162b1, which targets the RBD domain and is based on the nucleoside-modified mRNA construct. So on Slide 7, it is shown that BNT162b1 encodes a natively folded receptor-binding domain. So we have included a trimerization motif, which enables functional trimerization, and together with our Pfizer colleagues, they have shown that by electronic microscopic analysis of recombinant produced protein, showing that this receptor-binding domain indeed has a trimerization. And moreover, we have shown that this trimer receptor-binding domain is able to bind to the ACE2 receptor. And it means it comes really with the right folding, which is relevant because, we, of course, want to get antibodies, which are directed against the currently folded protein. So on Slide 8, you see the design of our Phase I study. This Phase I/II study is intended to determine safety and immunogenicity, and we will also -- we use also different doses to define a dose level for our vaccine candidate and then to select a further dose for Phase II/Phase III studies. The first step check, immunized in stage 1 of the study are healthy individuals in the age of 18 to 55 years old. Older adults will be immunized with a given dose level of a vaccine candidate once testing of that candidate and the dose level in younger adult has provided initial evidence of safety and immunogenicity. In the German portion of the trial, the dose-escalation portion of the Phase I/II trial includes about 200 healthy subjects in the age of 18 to 55 and also target, a dose range of 1 to -- a 1 microgram minimum and 100 microgram maximal dose. The data today is from the ongoing U.S. Phase I/II randomized trial, which is a placebo-controlled, observer-blinded study, which evaluates the safety, tolerability, immunogenicity of escalating dose levels of BNT162b1. The initial part of the study included 45 healthy subjects in the age of 18 to 45 -- 55 years of age. The preliminary data was evaluated for 24 subjects who received 2 injections of 10 microgram and 30 microgram and 12 subjects who received a single injection of 100 microgram as well as 9 subjects who received 2 doses of placebo control. So in terms of the demographics, the mean age range was 35 years old, and the age of the participants was 19 to 54 years and with an almost equal gender distribution. Summary, safe information for BNT162b1 is outlined on Slide 9. The most commonly reported local rejection -- reaction was injection site pain, which was mild to moderate, except in 1 subject who received 100-microgram dose. Systemic reactions, including fever, they are more common after the second dose than the first dose. Following those 2, 8% of the participants who received 10 microgram and 75% of participants who received 30 microgram of the vaccine candidate reported fever greater than or equal 38 degrees Celsius. Most local reaction and systemic events peaked at day 2 and those were fully resolved on day 7. No serious adverse events were reported in the subjects. In summary, BNT162b1 was well tolerated at the doses of 10 microgram and 30 microgram. So now let's move to Slide 10. The participants received 2 doses of the vaccines, 21 days apart of placebo, 10 microgram or 30 microgram of BNT162b1 and/or received a similar dose of 100 microgram of the vaccine. So because of a strong vaccine boost effect, the high neutralizing targets were observed 7 days after the second dose of 10 microgram and 30 microgram on day 28 after vaccination. The neutralizing geometric targets were 168 and 267 for the 10 microgram and 30 microgram dose levels, corresponding to about 1.2 to 2.8x of neutralizing -- neutralization targets of observed in 38 sera from subjects who had contracted SARS-CoV-2 and recovered. In all 24 subjects who received 2 vaccinations at, 10 microgram and 30 microgram dose levels of BNT162b1, elevation of RBD-binding IgG concentrations were observed after the second injection with geometric mean concentrations in the range of 4,800 or 27,800 units per milliliter at day 28, that means 7 days after immunization. These concentrations are 8 to 46x higher than the geometric mean concentrations observed in the convalescent serum panel. At day 21, after a single injection, 12 subjects who received 100 microgram of BNT162b1 at an RBD-binding of 1,778 units and SARS-CoV neutralizing titer of 33, which is 3x or 0.3 point times of the GMCs and GMT of the convalescent serum. So let us move to the open questions on Slide 11. So these results are positive, but the study at the moment has several limitations. First of all, we use convalescent sera. It's a comparator for neutralizing antibodies and T-cell responses are not yet available. T-cell responses are measured in the Germany -- German study, which will be published in the next weeks. The level of immunity and the pattern of B and C contribution needed to protect from the COVID-19 are unknown at the present. It means we have high neutralizing antibody titers, but we don't know if this passes as sufficient to induce a protection. Further, this analysis of the available data did not assess the immune response of safety beyond 2 weeks after the second dose of the vaccine. So that means we don't know how to titer to follow on when monitored for longer period. And this is, of course, important for public health use of the vaccine because ideally, a vaccine should have high titers over longer periods of time. So we will continue that. So follow-up will continue for all participants and include collection. Also of serious adverse events for the next 6 months, potential COVID-19 infection and we will have multiple additional immunogenicity measurements to up to 2 years. So another limitation is that this is -- this population is just about healthy at -- of 55 years or younger, and we -- and therefore, it does not accurately reflect the population at the highest risk for COVID-19. So this will be adult 65 years of age or older. And this population is being currently enrolled into the studies and result will -- we will have a product when we have generated sufficient data. So a later phase of the study will also prioritize enrollment of more diverse population, including those with chronic underlying health conditions, and of course, also from racial and ethnic groups adversely affected by COVID-19. So I want to end my prepared remarks by highlighting key next steps for the BNT162 program, as shown on Slide 12. A manuscripted additional data from the U.S. trial of BNT162b1 has been submitted for publication in peer-reviewed journal and is currently available online on the preprint manuscript server net archive. In addition, data from ongoing German trial for BNT162b1 is expected to be released within the next few weeks. The preliminary data will be used together with additional data being generated to select a lead candidate and dose for the initiation of our large Phase IIb trial anticipated to start by late July. Finally, we and Pfizer working closely together on manufacturing scale-up, supply chain and network planning. I will now hand over to the operator to open the line for questions. Operator?

[Operator Instructions] And we already have our first question coming from the line of Robert Bearings. Sorry, I have to redefine that. It's Cory Kasimov, who asks the first question, excuse me.

Great to see the early progress here. So first question I have for you is in terms of the convalescent sera samples that were used from patients who recovered from COVID-19, can you speak to the severity of their infections and whether this has a meaningful impact on the subsequent antibody levels you were using as a comp in this scenario? Or do you not know that information? And then I have a follow-up.

Yes, Cory, this is an important question. We have partial information that at least some of the patients that had more severe infection, we have, of course, also compared the data that we have from this patient to publish data, for example, from a Chinese patient population, which were characterized by more or less severe pulmonary infection. So it is well known that patients with a severe disease tend to have higher titers, but we have also seen patients with severe infection with a relatively low titers. And we believe that the collection of the sera, which we have is a good representation of the disease cause of patients -- of COVID-19 patients, including those which do not require hospitalization, but could also reflect those which has hospitalization. So there are patients who have titers above 5,000, but we have also seen a number of patients with titers below 30. So this is -- I think the selection reflects a meaningful collection of -- yes, of sera.

Okay. That's helpful. And then my follow-up question is just in light of FDA's guidance that was released yesterday around COVID-19 vaccines, does that change at all how you think about designing the Phase III trial? Or how you think about potential approval time line should ongoing development continue to be successful?

No. We were prepared for this type of announcement. And accordingly, our plan with Pfizer foresees to go the path, which is described in the FDA announcement.

We will now take our next question and that question comes from the line of Daina Graybosch. Hopefully you can hear me?

Yes. The first one is, if you had a chance to characterize the IgG and the neutralizing antibodies against strains that have some of the more common mutations in the receptor-binding domain. And after that, I'll have a follow-up.

Yes. So these are ongoing studies and we will report about the findings in the coming weeks.

Okay. I thought -- and I just want to maybe to ask you to speculate a little bit on the really strong boost effect on the neutralizing titer, and I wonder if that teaches you anything about the biology of what's needed to generate an immune response. I also saw comparing to the adenovirus vaccine, you're getting much higher titer. Does that tell, anything, us about the immune response? Does that inform you at all about the need for long-term boosting?

Yes. So this is an excellent question. So I think this is one of the key advantage of using a messenger RNA vaccine. But if you have a viable vaccine, regardless which type of virus you use, you get a pretty good prime response. But since you get also immune response against the virus itself, the boost response is limited by the immune response against the virus and the virus spectrum. So that means the viral vaccines have the limitation that the boosting is really difficult. Therefore, there is -- there are -- these models, they're heterologous prime-boost vaccines are used. So virus 1 for the prime and boost for the second. The nice thing about messenger RNA vaccine is, it has really a very clean backbone. So there is no viral backbone. This is just pure antigen. And the lipid nanoparticle itself is not immunogenic or minimally immunogenic. That means it gives you an excellent chance to get this boost response because the second injection provides the antigen in the same clean form and it's not limited by a backbone immune response. That's the reason why we see this wonderful boost after the second injection.

We now have a question from the line of Akash Tewari.