Altimmune, Inc. (ALT) Earnings Call Transcript & Summary

Hello, everybody, and thank you for attending our presentation on AdCOVID, our single-dose intranasal vaccine for COVID-19. My name is Scot Roberts, and I'm the Chief Scientific Officer at Altimmune, and I'm joined today by Dr. Sarah Browne, who heads our clinical vaccine development program. Here's our safe harbor statement. So in addition to a number of clinical stage vaccines that Altimmune is developing using our proprietary intranasal vaccine platform technology, we also have a next-generation peptide therapeutic approach that we're using for both NASH and for hepatitis B. Here's our development pipeline. At the top, you'll see our vaccine indications, including the ongoing Phase I study in COVID-19 with AdCOVID. We've completed Phase I studies with our NasoShield anthrax vaccine, and we've conducted a Phase II study with NasoVAX, our seasonal and pandemic influenza vaccine candidate. In addition, we are developing T-COVID, which is based on the same technology that is being used as a therapeutic for COVID-19, and that is currently in a Phase I/II study that should be reporting here shortly. And then at the bottom there, you'll see our peptide-based approaches for liver disease, that includes NASH and chronic hepatitis B. So Altimmune is well positioned to fund these programs forward. And we look forward to sharing data on a number of these programs in 2021. So let's turn our attention to AdCOVID. This is based on our adenovirus serotype 5 vaccine platform. All of our candidates have been developed using the intranasal route of administration and AdCOVID is no different. When we began this development program, we made 3 different vaccine candidates. One expressing the full-length spike protein, another expressing just the S1 domain and a third that expressed just the receptor binding domain, or RBD. And in preclinical studies, it was clear that the RBD expressing vaccine was the most immunogenic of the 3, especially when it came to serum-neutralizing antibody titers. And so it's the RBD version that we took forward into our ongoing Phase I clinical study that we have and share with you top line data here later on this quarter. So our approach with the intranasal vaccines, in general, and specifically for AdCOVID, has the potential to improve upon currently authorized vaccines. Clearly, the ability to use the intranasal route of administration for greater ease and comfort is important. And our preclinical studies showed that when you administer the vaccine via the intranasal route, no systemic dissemination of the vector was observed. And that's important given some of the news that's been in the headlines recently. In addition, intranasal administration of AdCOVID results in a very broad immunity. And by that, I mean the induction of systemic immunity as manifested by serum-neutralizing antibody titers as well as T cell responses, in addition to the nasal mucosal immunity that can only be developed following an intranasal route of administration. Because the SARS-CoV-2 virus both infects and is transmitted from the nasal cavity and the upper respiratory tract, the ability to generate a localized immunity, like mucosal immunity, is the best tool for blocking both infection and transmission. On the practical side, our product candidate also has a very outstanding stability profile, with several months of stability at room temperature and years of stability at common refrigerator temperatures. We believe that stability profile can allow for easy distribution of the vaccine without any sort of cold chain and simple and convenient storage at routine pharmacies and doctors' offices, making the deployment of the vaccine very, very simple. Another advantage of the platform technology is its safety profile. To date, we've conducted 4 placebo-controlled studies in healthy volunteers of our different vaccine candidates. And in each of those studies, when we examined the adverse events or side effects, the number of AEs as well as the severity of the AE was comparable to placebo. So we have essentially a placebo-like tolerability profile, placebo here being intranasal saline. So very well tolerated. And another characteristic that we saw in our Phase II study of NasoVAX, our seasonal influenza study, and that I'll show you here in a little bit with preclinical data of AdCOVID, is a very prolonged antibody response. So in that flu study, we looked at the serum antibody responses in subjects that received just a single intranasal dose of NasoVAX, And what we saw was that those antibody levels were maintained at a plateau level for at least 13 months following vaccination. That was the last time that we looked. We also included an active comparator net study with Fluzone, the commercial flu vaccine that's an intramuscular injection. And there, by contrast, we saw that the serum antibody titers were already beginning to wane significantly by 6 months. So as you're all aware, the SARS-CoV-2 virus has a high tropism for the upper respiratory track and the nasal cavity. And that's because that's where the highest concentration of the viral receptor, the ACE2 receptor, resides. And as you go down the respiratory track, the abundance of the receptor decreases. And so the majority of the viral replication occurs in the nose and in the upper respiratory tract. And so our ability to generate mucosal immunity in that compartment offers the best defense against both infection and transmission. Mucosal immunity was evolved to be the first line of defense against the environment and yourself, the host. And so in areas where you're in direct contact with the environment, such as the respiratory cavity or such as the GI tract, mucosal immunity is an important sentry to block the infection of the virus. So in the next few slides, I'll share some of our preclinical data with you. And in it, you'll see that while we induce mucosal immunity in the nasal cavity and respiratory track, we also induce a strong systemic immune response. And by that, I mean systemic neutralizing antibody titers and spike binding titers as well as T cell responses in both the lung and in the periphery. We'll show you the antibody responses in the serum and in the nasal cavity, in the mucosal immunity are long-lived. And we'll also show you that the T cell response is really quite differentiated in that it's primarily CD8 killer T cells. It's primarily present in the lungs, although you find it in the systemic periphery. And it also is earmarked by a special type of T cell called a resident memory T cell. So let's look at some of the data that we obtained in mice. Again, this is with AdCOVID, which expresses the RBD domain of the spike protein. On the left, we see the serum binding antibody responses in mice following a single intranasal dose. And what you can see is that a very significant antibody response occurs as early as 2 weeks. That's representing approximately 5% of the total serum antibody in the mouse was directed against the spike protein. And then by day 28, the titer increases a bit more. On the right-hand side, you see the mucosal IgA antibody response in the bronchial alveolar lavages of the animals. And again, here, you can see that over 21 days, we had a significant induction, nearly 30-fold, in IgA specific for the spike protein. I mentioned that the antibody response was quite long lived. And here, we see the data for both the serum IgG binding antibody. And again, you can see that the titers from day 15 all the way out to 6 months are essentially unchanged. And on the right-hand side, you can see that the mucosal anti-spike IgA in these BALs also maintained for at least 6 months. So very long antibody response, reminiscent of what we saw in our clinical NasoVAX study. If we turn our attention to serum-neutralizing antibody titers, these were obtained with wild-type virus, a live virus assay, focused reduction neutralization titer 50. And in 2 strains of mice, you can see robust neutralizing titers of approximately 1 to 600. This is after a single intranasal dose. We're quite excited about that level of neutralizing antibody from this sort of approach. If we turn our attention to T cells now, we see, as I mentioned earlier, that the majority of the T cell response is in the lung. If you'll note the scale on the Y axis, the lung has the primary response. But there's also a significant response in the spleen and in the periphery lymph nodes. If we focus on the lung and ask what sorts of T cells are present and what is their phenotype, we can see that there are both CD8 killer T cells and CD4 helper T cells that are present in the lung. And a percentage of those are resident memory T cells. Now these are T cells that are not circulating in the blood and transiting through the lungs, these are T cells that have left the circulation and are in the tissue awaiting to respond to a viral infection. We've conducted a number of experiments looking at the efficacy of the vaccine and challenge studies. These studies were conducted with a transgenic mouse model, the K-18 transgenic mouse. And on this slide, we show the survival curves for animals that received either placebo or a single intranasal dose of AdCOVID 1 month before challenge with 10,000 focus forming units of a wild-type SARS-CoV-2 isolate. And what you can see is that while the placebos also come to infection by day 10, the vaccinated animals completely resisted the infection. And if you look at the weight loss in that group, you see that those animals actually gained weight. So not only were they able to survive the challenge infection, but they are able to do so without any clinical signs of infection. We also looked at the RNA present in various respiratory tissues of the animals. On the left here, we're looking at total viral RNA and this is several copies. And looking into both BAL, nasal wash or lung tissues in animals that were either -- received placebo, the controls, or received a single dose of AdCOVID. And what you can see is that, first of all, this model supports a high degree of replication and viral titer, nearly 8 logs in these tissues. And that vaccination results in a 1,000-fold or more reduction in the amount of total viral RNA present in those tissues. On the right-hand side, we're doing a subgenomic RNA analysis, and that looks only at the replicated viral RNA. And here, you can see again in each of these tissues, the amount of viral RNA is approximately 1,000 to almost 10,000 fold higher in the control animals than in the animals that received the vaccine. So clear effects on viral replication. And we will be quantifying the replicated RNA in the near future, being able to report whether or not these titers were in fact sterilizing or not. Now with that, I'd like to turn it over to Dr. Sarah Browne. She'll walk you through our ongoing Phase I clinical study and talk a bit more about our clinical development plans. Sarah?

Thanks, Scot. Hi, everyone. I'm Sarah Browne, I'm Senior Director for Vaccine Development at Altimmune. And I want to thank you for the opportunity to share some information about our clinical development program for AdCOVID. We're pleased to report that our Phase I trial of AdCOVID is well underway. The study includes healthy volunteers, 18 to 55 years of age, who are randomized to receive AdCOVID or placebo. We're looking at 6 cohorts at 3 dose levels, prime and prime boost 28 days apart. Although we're optimistic based on our data with the platform that we'll be bringing a single-dose regimen forward for development. We'll be looking at the typical stuff for early phase vaccine development, including local and systemic reactogenicity for 7 days post dose, all AEs for 28 days post-dose and then serious events as well as occurrence of symptomatic and asymptomatic SARS-CoV-2 infection for 1 year. And then in terms of immunogenicity data, we're going to be looking at the serum total binding spike IgG and neutralizing antibody titers. We'll also be looking at T cell responses and T cell subsets. And then importantly, to assess the mucosal immunogenicity elicited by our intranasal vaccine, we're going to be looking at the SARS-CoV-2 spike IgA. Lastly, we'll be assessing the impact of pre-existing Ad5 seropositivity on vaccine-induced immunogenicity. But based on published data with our influenza vaccine, NasoVAX, we're pretty optimistic that this effect will be minimal. And then we expect to report our interim data this quarter. So I'd like to spend the next couple of slides, just highlighting some of the important differentiating attributes for AdCOVID. Again, as Scot mentioned, based on studies employing the same platform, we anticipate exceptional tolerability. In fact, as he also mentioned, these vaccines were indistinguishable from placebo with regard to local and systemic reactogenicity in randomized and blinded trials. We also think that our nasal approach will be particularly well received by children and adolescents, but even for adults who would rather avoid a shot. We'd like to acknowledge that children do experience severe disease from SARS-CoV-2 infection, necessitating development of pediatric vaccines. But again, the tolerability will really be key to support a favorable risk-benefit assessment given that they frequently have asymptomatic or mild disease. And then we think because of these features, that use of AdCOVID in children could have a really important impact, both on the establishment of herd immunity and getting children back into school. So we're also enthusiastic about the role AdCOVID could play as a booster vaccine for a number of reasons. Again, referring back to our influenza vaccine, NasoVAX, we saw robust hemagglutinin inhibition antibody responses. And I think this is particularly germane to the current and future state of SARS-CoV-2 epidemiology, which like flu, we can expect most of the population will be SARS-CoV-2 experienced, whether by natural infection or vaccination. So we expect that the local and then -- the local mucosal IgA and mucosal T cell responses via the prime-pull mechanism will be really important. And we also expect to -- that the tolerability will be key to maintain high rates of vaccine uptake with repeat vaccination to maintain high degrees of immunity against the variants of concern. So I'd like to spend a couple of slides now looking forward to what we have planned for later in the year. We'll be bringing AdCOVID with variant strains to the clinic. And as noted here, we'll be focusing on the E484K mutants, given how they've risen independently and spread efficiently in many regions. Based on our experience with influenza, we're confident our vaccine can efficiently respond to strain change needs and that the mucosal immunity to block shedding and transmission could be an important tool for also reducing the emergence of new variants. So to further cover development plans for this year and to highlight a number of studies we're actively planning, I just want to mention our Phase II study in LMIC. This will be in adults 18 years of age and older, and we anticipate initiating it very soon. It will support later-phase development and also special populations. And then because shedding, while we know it's a marker for transmission, it doesn't evaluate the clinical and public health outcome of interest, which is actual transmission. So we're working with field experts to design a household transmission study with transmission as that clinical endpoint. And then these studies as well as studies in children, in an age de-escalation fashion and maternal immunization studies, will pave the way for our pivotal Phase III trial, which we anticipate starting at the end of 2021.

Thank you, Sarah. So in summary, we're very excited about the potential of AdCOVID to make a meaningful difference in the worldwide approach towards controlling and eradicating the pandemic. We think that there are a few vaccines that are able to combine so many important attributes into a single vaccine candidate. And by that, I mean the ability to elicit strong systemic neutralizing antibody titers and T cell responses, the unique ability to generate mucosal immunity where the virus is replicating and where it's being transmitted from and an exceptional safety profile that is essentially indistinguishable from saline placebo. Add to that the ability to ship and store the vaccine very easily, we think that AdCOVID has a lot of potential for making an important contribution to the global COVID-19 effort. Thank you, and we appreciate you tuning in for the presentation.