Good afternoon. My name is Sarah, and I will be your conference operator today. At this time, I would like to welcome everyone to the Vaxcyte Fourth Quarter and Full-Year Financial Results Conference Call. All lines have been place on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] I would now turn the call over to Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. Please go ahead, sir.

Thank you, Operator, and good afternoon everyone. I'd like to welcome you to Vaxcyte's earnings conference call to discuss the financial results for the quarter and full-year ended December 31, 2020, and to provide a business update. I am joined today by our CEO, Grant Pickering; our COO, Jim Wassil; and our VP of Research, Jeff Fairman. Earlier this afternoon, Vaxcyte issues a news release announcing the company's results. Copies of our news releases, latest corporate presentation, and SEC filings can be found in the Investors and Media section of our Web site. Before we begin, I'd like to remind you that during this call we'll be making certain forward-looking statements about Vaxcyte which are subject to various risks and uncertainties. These includes statements regarding the anticipated process and timing of the development of our vaccine candidates, the timing of our IND application submission and top line data from our clinical proof-of-concept study for VAX-24, the potential benefits and market of our vaccine candidates and technology platform, and impact of the COVID-19 pandemic on our business, the payments of milestones, and our expected uses and sufficiency of cash and other funding to support our development programs and other operating expenses. Andy forward-looking statements are based on facts and assumptions as of today, and we undertake no obligation to update them. Our actual results may differ materially from these statements. Investors should read the risk factors set forth in Vaxcyte's Form 10-K for the year ended December 31, 2020, and any subsequent reports filed with the SEC. With that, I would now like to turn the call over to Grant Pickering. Grant?

Thanks, Andrew. And all of you on the call and webcast, thanks for joining us today. The past year has been transformational for Vaxcyte as we have made meaningful progress across all areas of our business. This was highlighted by the progress of our vaccine pipeline, which continue to illustrate what we believe are the unique competitive advantages and scalability of our technology platform to enable us to deliver broader spectrum and/or more immunogenic vaccines. Our lead vaccine candidate is VAX-24, a 24-valent investigational pneumococcal conjugate vaccine, or PCV. For this program, we have achieved several key manufacturing milestones to support our IND application submission to enable the initiation of our clinical proof-of-concept study. VAX-24, along with VAX-XP, forms the basis of our PCV franchise strategy, targeting the existing $7 billion pneumococcal vaccine market. VAX-24 is designed to improve upon the standard of care in this market by covering the additional strains that are responsible for the majority of residual pneumococcal disease currently in circulation. Based on the data we've generated to date, we believe VAX-24 has the potential to protect against the strains collectively covered by the leading PCV, Prevnar 13, and the older less immunogenic form of vaccine, called Pneumovax 23. We believe that VAX-24 has the opportunity to replace both standard of care vaccines with a single broad spectrum PCV. Our site-specific conjugation technology creates a competitive advantage that allows us to engineer broader spectrum PCVs designed to avoid carrier suppression in ways that we believe will afford our PCV franchise an opportunity to surpass the coverage of our competitors, which has been the key adoption determinant in this market. For VAX-XP, we continue to lay the groundwork to support a level of readiness to push the spectrum of coverage even further to address newly emerging strains…

Thanks, Grant. Before I get into our accomplishments for VAX-24 and status update, I think it would be helpful to review the manufacturing process for this program and the remaining activities necessary to enable the IND application submission. As we previously shared, the manufacturing process for VAX-24 included the following four steps. First, we manufacture eCRM, our proprietary protein carrier. Second, we manufacture 24 pneumococcal polysaccharides, one for each of the serotypes included in VAX-24. Third, we manufacture 24 conjugated drug substances, which consist of three discrete stages; first, each of the 24 polysaccharides to size to a targeted molecular weight, then a leaker is attached to each of the 24 sized polysaccharides to generate 24 activated polysaccharides. And finally, the 24 activated polysaccharides are conjugated or covalently linked to the eCRM carrier protein resulting in the 24 conjugated drug substances. The fourth and final step of the process includes manufacturing of the drug product by mixing the 24 conjugated drug substances and filling into vials. To-date, we’ve made significant progress towards our IND filing, including a number of key accomplishments in the past year. We’ve successfully completed the GMP manufacturer testing and release of both the eCRM carrier protein and the 24 pneumococcal polysaccharides. For the conjugated drug substance, we’ve now successfully sized and activated each of the 24 polysaccharides and are in the midst of the manufacturing of each of the 24 conjugated drug substances. Earlier this year, we successfully manufactured our initial drug product batches with our 24 conjugate at Lonza. These batches will serve as the source of our lead block stability data for our IND. We also successfully completed manufacturing of drug product batches used in the GLP toxicology studies, and initiated the GLP toxicology study in the first quarter of this year. Now, before…

Thanks, Jim. VAX-A1 leverages one of the key applications of our cell-free protein synthesis platform. The ability to produce site specific polysaccharide protein conjugates, the resulting conjugate is designed to ensure optimal exposure of both the B and T cell epitopes on the protein carrier to confer robust, boostable and durable protective immune responses. VAX-A1 was designed to confer broad protection against subtypes of Group A Strep. It includes a conserved polysaccharide polyrhamnose conjugated to a Group A Strep specific immunogenic protein carrier using our site specific conjugation technology, along with two highly conserved protein virulence factors that when left unchecked, interfere with the body's ability to respond to the infection. By using these conserved antigens, we believe that our investigational vaccine could address the full range of pathogenic serotypes of Group A Strep. We continue to make solid progress with this program. Earlier this year, we nominated our final vaccine candidate consistent with our target timeline. In connection with this nomination, we recently completed the first phase of our award under our agreement with CARB-X. In addition, at the beginning of this year, we announced the publication of preclinical data from our program in the infectious microbes and diseases. In the published study, which was carried out in collaboration with researchers at the University of California, San Diego, VAX-A1 showed broad and significant protection against systemic and soft tissue infection after animals were challenged with near lethal amounts of Group A Strep bacteria. Broad-based cross-reactivity with multiple serotypes of Group A Strep was observed in the serum of vaccinated animals. No cross-reactivity was detected with human heart or brain proteins, which is a key leading indicator of vaccine safety. Looking ahead, we expect to initiate IND enabling activities in the second-half of this year, and are currently working with…

Great. Thanks, Jeff. Before turning it over to Grant for some closing remarks, a few financial highlights. First, with respect to the income statement, the details of our fourth quarter and year-end 2020 results are reflected in our press release 10-K filing along with the key variance drivers. In summary, the year-over-year increase in R&D expenses was primarily a function of the advancement of our VAX-24 program. While the increase in G&A expenses was driven primarily by our transition to public company status and our overall growth. As we look forward, based on our plans to advance our pipeline programs led by VAX-24 and to increase the size of our organization to support these efforts, we expect R&D and G&A expenses to increase substantially over 2020 levels. Second, rest of the balance sheet and cash runway, we ended 2020 with a strong balance sheet with $386.2 million in cash and cash equivalents compared to 397 million as of the prior quarter end, and up substantially from the prior year-end due to the Series D and IPO financings during the year. Going forward, we expect that a balance sheet will be sufficient to fund her operating expenses and capital expenditure requirements through at least the completion and announcement of the top line data from our Phase 1/2 clinical proof-of-concept study of VAX-24 in adults, which, as noted, we expect between late 2022 and early 2023, and to continue to advance our pipeline of other vaccine candidates. With that, I'll now turn the call back over to Grant for some closing remarks before we open up the line for Q&A. Grant?

Thanks, Andrew. Our mission at Vaxcyte is to improve global health by developing superior and novel vaccines designed to prevent or treat some of the most common and deadly infectious diseases worldwide. In light of all the external headwinds in 2020, our progress last year, and the continued momentum this year represent substantial strides toward achieving our mission. I want to thank all of our employees and collaborators, including the team at Lonza, for persevering through a tremendously challenging moment in history. For the remainder of 2021, our primary areas of focus would be to deliver on our remaining VAX-24 IND-enabling milestone, invest in VAX-XP to maximize our PCV franchise optionality and value, advance VAX-A1 into IND-enabling activities, nominate the final vaccine candidate for VAX-PG, and advance our earlier-stage discovery programs. With that, I want to thank you all again for joining us today, and your continued interest in Vaxcyte. Before we close our prepared remarks, I'd like to thank Kurt von Emster, who previously had held the position of our Board Chair, for agreeing to serve in this role on an interim basis as we initiate a search for a permanent Board Chair. We look forward to your questions today, and to speaking with you in the weeks and months ahead. Operator?

Thank you. [Operator Instructions] Our first question comes from the line of Jason Gerberry with Bank of America. Your line is now open.

Hi, guys. Thank you for taking my questions. Can you remind us and apologies if I missed this, but how many of the conjugated drug substances have Lonza successfully completed? Just trying to get a sense of where you're at in that process. And, ultimately, that the range of outcomes for timing of IND submission is like six months. Can you give us a sense of what are the key variables that drive that range ultimately? I assume it's not the GLP tox study, I assume that's pretty straightforward once you complete some of the other steps along the process. And if you can also just remind us how long the stability testing is? Thanks.

Yes. Hey, Jason, thank you for that question. So, as we mentioned in the prepared remarks, this DS campaign consists of three different stages. So, we've completed those first two stages. And as you say, we're now in the process of making the 24 conjugates themselves. We're going to stay away from getting into full specificity as to the number that we made. But I could characterize it as being well on our way to have made the 24. And ultimately, we'll only be able to declare victory once we made all 24 of those, and they pass all of the analytical tests required that meet our critical quality attributes. So, you got it exactly right, that the GLP tox study is already underway. We don’t expect that to be rate limiting. So, the deliverables that are going to actually result in the ultimate IND submission timing are this completion of the DS conjugates, and then being formally released. So, we have to make them and then complete that battery of analytical tests. Once we complete that that will allow us to follow through with the drug product campaign to make each of the three different doses that we'll take into the clinical study. And then, of course there'll be an analytical series of tests that are run on those in order to declare victory there. And then as it relates to the stability, we've already put the tox lots of the drug substances and the DP on stability. So these lead lot stability studies have already started. And then what we'll need to deliver with regard to the stability ultimately to permit the IND filing, Jim, correct me if I'm wrong, I think it's one month stability. But Jim, you should correct me if I'm off on that.

No, that's correct. And Jason, this is Jim. Allow me to chime into your question about the range of the guidance we've provided. As we talked about, kind of these process-related adjustments are really are expected and standard in the course of drug development. And we look forward at this point, if we see -- and we expect them going forward. If we see fewer than we expect, that will put us in a position of delivering the IND submission at the early end of the range, so call it the early part of 2022. If we see more than we anticipate, that would put us at the back-end of the range. So that's the rationale for the window we provided.

Got it. Okay, thank you.

Thank you. Our next question comes from the line of Biren Amin with Jefferies. Your line is now open.

Yes, hi, guys. Thanks for taking my question, maybe just one on VAX-24. Clearly, if you're at the back-end of the range, in June 2022, for IND, and your guidance for top line data at late 2022-early 2023, how feasible is that early 2023 timeframe?

Yes, I think --

Yes, go ahead, Andrew.

Yes, I was going to say that the top line data range, Biren, generally corresponds with the IND application submission range. So, if we're in a position to deliver the IND application submission in the early part of '22, we believe that would put in a position of having the top line data by the end of the year. If, alternatively, we're at the back-end of the application submission range in, call it, Q2, up to June '22, in that scenario we're more likely to have data in the early part of 2023.

Okay. And then I guess a question on VAX-XP, so congrats on the progress there, can you just maybe talk about, you know, [read-throughs] [Ph] that you can take on VAX-24 manufacturing to the XP program? And whether manufacturing can be expedited as a result of the key learnings that you've made on VAX-24?

Yes, thanks, Biren. Yes, we're really excited about the VAX-XP data. Obviously, this just further shows the sort of scalability that the platform can deliver with regard to [respect on the] [Ph] on the coverage. And we all know that's been the key adoption feature in this market, so very encouraged with this immunogenicity data. And just to put a slightly finer point on it, so the incremental conjugates that are on top of VAX-24 that were included in this study, these are conjugates that were made at Lonza. These are conjugates that were made a substantially larger scale than we had produced previously here at Vaxcyte. So this is a 15-fold scale-up akin to what we had done with VAX-24. So, it's very encouraging to see the consistency of the immunogenicity across those incremental strains. But then I would also point out, the 24 conjugates that were included that are in VAX-XP that are also in VAX-24, these were the conjugates that we made in the tox batch that we made, at Lonza, that went into the non-clinical tox study. So, we're seeing this continued immunogenicity across, now, over 30 conjugates. But another data point with the 24 that are in VAX-24 that look really encouraging, and show non-inferiority relative to all of the strains in Prevnar. And then, certainly, superior immune responses to polysaccharide-only, including all 23 that are in Pneumovax, and then, obviously, quite a number beyond that.

And when can we expect the IND for XP?

It's too early to say what that timing is going to look like for that, Biren. It's going to pivot off the ultimate timing for the VAX-24 IND. We're also going to key off the epidemiological data, and the demand for some of these incremental strains, that we're already seeing them becoming more and more important. But as that data evolves, that's also going to guide us. And to a lesser extent, we're obviously going to be monitoring the competition as well. But for us, VAX-24 is the fastest path to the market. Those 24 strains are really the most important strains that we need to get a solution out there as soon as practicable. And we think that that is going to be very competitive relative to the other PCVs that are in development. And we believe that this would put VAX-24 in a position to not only be the broadest spectrum PCV, but the one that would enable the withdrawal of Pneumovax 23 from continued use which would open the door for a prime boost in adults where it would really be valuable for older adults to get that second significantly higher boost to create longer lasting protection.

Great, thank you.

Yes, thanks.

Thank you. Our next question comes from the line of Umer Raffat with Evercore. Your line is now open.

Are you there?

If your phone is on mute, please unmute the line.

Shall we move on to the next question?

Certainly. Our next question comes from the line of Louise Chen with Cantor Fitzgerald. Your line is now open.

Hi, congratulations on all the progress during the quarter and thanks for taking my questions here. Quite a few, first question I had is how do you think ACIP will update its guidelines as new PCVs get introduced, there are going to be two new ones likely in the near-term and then newer than others to follow that with broader coverage, do you think pricing is going to be a factor here and then the second thing, I want to ask you is just do you think COVID changes the importance of PCVs for patients, how doctors felt about that that you've spoken with and the last question I had for you is just on OpEx for 2021, you talked about a substantial increase. And I know you gave some guidance and how long your cash runway goes out until but maybe if you could just give us a little bit more color on what substantial, what qualifies for substantial in your mind and then that breakup between R&D and SG&A, how should we think about that? Thank you.

Yes, great. Thanks, Louise. So I heard three questions essentially I'll take one, I'll pass the other to Jim and then Andrew will comment on the financials. But maybe I can just start with the COVID related question before Jim who is our resident ACIP expert comments on how we expect some of these other PCVs to impact the market but certainly as we think about greater risk associated with circulating COVID, especially with the variants in older adults, I think it clearly shows the importance of having more broad vaccination with the pneumococcal vaccines that are out there and we saw that very early on as the pandemic took hold last year that the rate of vaccination in Europe and even in the U.S. was up substantially, that was prior to people sheltering and having poor access to physicians. But as we know these viral pandemics usually result in weakened immune systems in older adults which allows them to fall prey to existing bacteria and Strep pneumonia is precisely the bacteria that you'd be worried about. So I think this is only going to increase the rate of vaccination in adults with pneumococcal vaccines and is going to put additional pressure on the spectrum of coverage that's available to create protection for what's clearly a preventable infection. So yes, I think it only is going to have positive impact on the pneumococcal vaccine space as a business and as a societal benefit. With that, let me hand it to Jim to make some comments about the ACIP and then we'll hand it to Andrew, Jim?

Thanks, Grant. Louise, when you looked at the February ACIP presentations on pneumococcal vaccines, they did outlined basically what they think they're going to do, with the June ACIP, they're going to review cost effectiveness and do their evidence recommendation and their grading and they think that if the products are licensed that they potentially could have a vote in October. When you try and figure out what it is that they're going to make in terms of a recommendation, they made a list of policy questions that are under consideration by the working group as well as questions with regard to what they need to evaluate from a health economic perspective. And I think that gives us some insight into where they're going, they’re asking the question should PCV-15 or 20 be given at age 50 and above or 65 years of age and above. So, they’re potentially considering to lowering the age of recommendation down to 50, I think they'll keep 65, but it is interesting that they are considering lowering that to 50. They also asked if PCV 15 or PCV 20 should be recommended in younger adults with underlying medical conditions. I do think that they will recommend PCVs for the 18 to 49 or 18 to 65 in age group that have certain pre-existing conditions. Then finally they ask, should they give PCV 15 and 20 alone or in a series with Pneumovax 23 and all indications are pointing towards they will continue with giving the PCVs first and then a year later with PPSV 23 to ensure that they get the breadth of coverage. We're hoping of course with 24 covering all of the same strains in PCV 13 or 15 and 20 as well as Pneumovax 23 that ultimately we can reduce the number of shots and not have to do that series going forward. And Andrew, I guess you can answer the financial questions.

Yes, sure. Thanks, Jim. You're correct. We did not provide a point estimates or range estimates for 2021 operating expenses other than just say as you noted. We expect both G&A and R&D expenses to increase substantially, I guess a couple of data points I would offer as you think about that hopefully will be helpful. Our G&A expenses over the course of 2020 increased quarter-over-quarter as we continued to build our organization obviously upon the transition to a public company in June, where we saw the effect of things like DNO insurance expenses and higher stock-based compensation levels. We do expect year-over-year ‘21, compared to ‘20 to see a substantial increase in G&A. I think that increased if you look at annualized Q4 of 2020 that increases far more modest, because we've largely built out of that which is required to support a public company status. So relative to Q4 annualize, more modest growth from an R&D perspective, it’s a very different story. Unlike G&A, which kind of grows sequentially quarter-to-quarter, R&D expenses are far more volatile and fluctuate just given the nature of the underlying principally manufacturing activity. So depending on where we are for example with Lonza in the midst of a manufacturing campaign, and we've moved to testing phase that can very much dictates the flow of R&D expenses. So year-over-year again expecting a substantial increase. If you look at 2020, our peak R&D quarter was actually in the first quarter of 2020, just given the nature of activities that was occurring at that time. And we still expect a substantial increase in 2021, compared to the annualized R&D number, in Q1, although again, we expect that number to fluctuate more in 2021 just given the nature of the underlying activities over the course of the year.

Okay, thank you. You broke up a little bit when you said your peak R&D was which quarter?

Our peak R&D in 2020 was actually the first quarter just given the nature of the activities at that time, which were in eCRM and polysaccharide manufacturing activities. For 2021, we expect to see an increase over the annualize Q1 2020 level as well.

Okay, thank you very much.

Thank you.

Thanks.

Our next question comes from the line of Joseph Stringer with Needham & Company. Your line is now open.

Hi, everyone. Thanks for taking our question. Just a few quick ones on VAX-AL and VAX-PG, you laid out some highlights for IND enabling studies, could it be possible that both of those into the clinic preference for advancing either one of those programs at a faster pace or I guess prioritization on one program over the other, or would they be sort of in parallel fashion? Thank you.

Great, Joe. This is Andrew. I'll take the first part, and then maybe take a crack at the second one, and my colleagues to follow. I would say for each of the programs, VAX-A1 and VAX-PG, we are at this moment not providing guidance as you heard on the prepared remarks for VAX-A1 having nominated the final candidate in Q1, which was on our timeline. We expect to initiate IND enabling activities in the second-half of this year among the activities included for VAX-A1 are the selection of a CMO partner in the determinant of the CMC path forward. So it really, it wouldn't be until that point where it would be prudent for us to set forth IND guidance, but you should expect us to do that once we have a clear path with respect to the CMO partner. And then for VAX-PG, it's a little further behind at the moment. We have just to nominate our final candidate consistent with our previous timelines. We now expect to do so in the second-half of this year, again consistent with what we previously outlined. And then at that point much like, I mentioned for VAX-1, we would expect to select the CML partner in a path forward. At which time we likely will be in a position to offer our IND guidance. I would say overall in Jeff or Grant comment, just from a timeline standpoint VAX-1 is ahead on the timeline vis-à-vis VAX-PG at least at this point in time.

Yes. Hey Joe, this is Grant Pickering. I would chime in and just say that A1 is ahead. It also has the benefit of a substantial offset from CARB-X. So there’s a nice efficiency there. We’re really excited about the data that we’re seeing from that program where we’re buoyed by the notion. Now that there’s an opportunity to develop this vaccine is not only a potential addition to the pediatric regimen, but now it’s having potential as an adult vaccine as well. So really excited about that program and the VAX-PG program we think has huge potential as well. So we’re really not expecting to really pick one over the other. We’re anticipating that we’re going to move both those programs forward based on the potential that they each bring to the company. So for now, we’re moving them along and we’re in a position to do that.

Thank you.

Thanks, Joe.

Thank you. There are no further questions at this time. I would now like to turn the call back to Grant Pickering for closing remarks.

Yes. Thanks, Sarah. I just like to thank you all for your support of the company. We really appreciate you dialing in. Obviously we’re disappointed that we’re not going to be able to hit the original IND guidance. We made huge strides last year. We don’t feel that there’s anything in particular that is going to get now away. There’s a lot of operational activity required to deliver on a vaccine like VAX-24 with the level of complexity that we’re looking at. So, we’re confident in the guidance that we provided today. We really appreciate all of your support and I appreciate all the work that the team has put into this and our colleagues at Lonza as well. So thank you all very much for your attention today and take care.

Ladies and gentlemen, this concludes today’s conference call. Thank you for your participation. You may now disconnect.