Q4 2021 Vaxcyte Inc Earnings Call

February 28, 2022

Good afternoon. My name is Josh and I will be your conference operator today at this time I would like to welcome everyone to <unk> fourth quarter and full year financial results Conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you would like to ask a question during this.

Operator: Good afternoon, my name is Josh and I will be your conference operator. 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 placed on mute to prevent any background noise.

Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, press the pound key. Thank you. I will now turn the call over to Andrew Guggenhime, president and chief financial officer of Vaxcyte. Please go ahead.

Time simply press Star followed by the number one on your telephone keypad. If you would like to withdraw your question press. The pound key. Thank you I will now turn the call over to Andrew Guggenheim, President and Chief Financial Officer of that site. Please go ahead Sir.

Thank you operator, and good afternoon, everyone.

Andrew Guggenhime: Thank you, Operator, and good afternoon, everyone. I'd like to welcome you to Vaxcyte's earnings conference call to discuss our 2021 results and provide a business update. I'm joined today by our Chief Executive Officer, Grant Pickering, our Chief Operating Officer, Jim Wassil, and our VP of Research, Jeff Fairman. Earlier this afternoon, we issued a news release announcing our results. Copies of this and our other news releases, our latest corporate presentation, and SEC filings can be found in the Investors in Media section of our website.

Like to welcome you to <unk> earnings conference call to discuss our 2021 results and to provide a business update.

I'm joined today by our Chief Executive Officer Grant Pickering, Our Chief operating Officer, Jim Wassail, and our VP of research Jeff Sherman.

Earlier. This afternoon, we issued a news release announcing our results copies of this and our other news releases latest corporate presentation and SEC filings can be found in the investors and media section of our website.

Andrew Guggenhime: 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 include statements related to the benefits of our vaccine candidates, the process and timing of the anticipated future development of our vaccine candidates, including the timing and availability of top-line data from the Vax24 Phase 1-2 Clinical Proof of Concept Study, the demand for our vaccine candidates, our expected uses and sufficiency of cash and other funding to support our development programs and other operating expenses, and other statements that are not historical facts. Any 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 expectations.

Before we begin I'd like to remind you that during this call we'll be making certain forward looking statements about back site, which are subject to various risks and uncertainties.

These include statements related to the benefit of our vaccine candidates the process and timing of anticipated future development of our vaccine candidates, including the timing and the availability of topline data from the <unk> 24 phase two clinical proof of concept study the.

The demand for our vaccine candidates are expected uses and sufficiency of cash and other funding to support our development programs and other operating expenses and other statements that are not historical facts.

Any 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 <unk> Form 10-K for the year ended December 31, 2021, and any subsequent reports filed with the SEC.

Grant Pickering: Investors should read the risk factors set forth in Vaxcyte's Form 10-K for the year ended December 31, 2021, and any subsequent reports filed with the SEC. With that, I'll turn the call over to Grant Pickering. Grant.

That I will turn the call over to grant Pickering Grant.

Thanks, Andrew and to all of you on the call and webcast. Thanks for joining us today.

Grant Pickering: Thanks, Andrew, and to all of you on the call and webcast. The past year has been an extremely important one for Vaxcyte. We made significant advancements across our business, which remains focused on eradicating bacterial infections such as invasive pneumococcal disease, group A strep, and periodontitis. We advanced our pipeline, demonstrated the potential of our novel vaccine platform, and recruited the right expertise to help us transition into the clinic and prepare for manufacturing scale-up and late-stage development.

The past year was an extremely important one for back site, we made significant advancements across our business, which remains focused on eradicating bacterial infections, such as invasive pneumococcal disease group, a strep and periodontitis.

We advanced our pipeline demonstrated the potential of our novel vaccine platform and onboard the right expertise to help us transition into the clinic and prepare for manufacturing scale up and late stage development.

While we all witnessed the global impact of vaccine innovation on a scale not seen since the 19 fifties bacterial infectious diseases have not historically received adequate attention.

Grant Pickering: While we all witness the global impact of vaccine innovation on a scale not seen since the 1950s, bacterial infectious diseases have not historically received adequate attention. As a result, the global incidence of pneumococcal disease continues to climb, driven by emerging serotypes not covered by currently available vaccines. Although the available pneumococcal conjugate vaccines, or PCBs for short, are effective, the underlying chemistry appears to have reached its limit in terms of its ability to permit addition of serotypes to broaden protection without diminished overall immune responses, jeopardizing their long-term protection.

As a result, the global incidence of pneumococcal disease continues to climb.

Driven by emerging serotypes not covered by currently available vaccines.

Although the available pneumococcal conjugate vaccines or <unk> for short are effective the underlying chemistry appears to have reached its limit in terms of its ability to permit. The addition of Sara types to broaden protection without diminished overall immune responses jeopardizing their long term protection.

Grant Pickering: Our strategy is to overcome such limitations by applying advanced chemistry and modern synthetic techniques, including the XPRESS-CF cell-free protein synthesis platform, to produce vaccines that are uniquely capable of breaking down bacteria's complex defense mechanisms while preserving immunogenicity across a broader spectrum of coverage.

Our strategy is to overcome such limitations by applying advanced chemistry, and modern synthetic techniques, including the express CF cell free protein synthesis platform.

To produce vaccines that are uniquely capable of breaking down bacteria is complex defense mechanisms, while preserving immunogenicity across a broader spectrum of coverage.

Grant Pickering: Our site-specific conjugation technology allows us to engineer broader-spectrum PCVs designed to avoid carrier suppression in ways that we anticipate will afford our PCV franchise an opportunity to surpass the coverage of other pneumococcal vaccines. With this competitive advantage, we believe Vax24, our lead 24-valent vaccine candidate, has the opportunity to be a best-in-class vaccine in both adults and pediatrics in an already $7 billion global market that is poised Our recent achievements with Vax24 have paved the way for a surge in momentum in 2022 as we reach key anticipated milestones.

Our site specific conjugation technology allows us to engineer broader spectrum Pcbs designed to avoid carrier suppression and ways that we anticipate will afford our PCB franchise and opportunity to surpass the coverage of other pneumococcal vaccines.

With this competitive advantage, we believe vacs 24, our lead 24 valent vaccine candidate has the opportunity to be a best in class PCB in both adults and pediatrics in them already $7 billion global market that is poised to undergo significant further growth.

Our recent achievements with that 24 have paved the way for a surge in momentum in 2022, as we reach key anticipated milestones.

Grant Pickering: Just last week, we announced the dosing of the first participants in the Vax24 Phase 1 portion of our Phase 1-2 clinical study in adults and anticipate announcing the top-line results of both the Phase 1 and Phase 2 portions by year-end. This study is designed to determine the optimal dose of Vax24 based on safety and immunogenicity and to inform how we power a future pivotal Phase 3 immunogenicity study in adults. The immunogenicity data from the Phase 2 portion of this study should tell us if one or more of the Vax24 doses can meet or exceed the non-inferior immune response threshold on a serotype by serotype basis that is required for regulatory approval. If achieved, this milestone has the potential to represent a major inflection point for the company.

Just last week, we announced the dosing of the first participants in the <unk> 24 phase one portion of our phase <unk> clinical study in adults and anticipate announcing the top line results of both the phase one and phase II portions by year end. This.

This study is designed to determine the optimal dose of <unk> 24, based on safety and Immunogenicity and to inform how we power our future pivotal phase III Immunogenicity study in adults.

The Immunogenicity data from the phase II portion of this study should tell us if one or more of the <unk> 2004 doses can meet or exceed the non inferior immune response threshold on a stereotype by serotype basis that is required for regulatory approval.

If achieved this milestone has the potential to represent a major inflection point for the company. We remain excited about the adult pneumococcal vaccine market given it represents approximately $2 billion in annual sales and has the opportunity to grow significantly based on a number of key factors.

Grant Pickering: We remain excited about the adult pneumococcal vaccine market, given it represents approximately $2 billion in annual sales and has the opportunity to grow significantly based on a number of key factors. First, we've seen premium pricing justified for broader-spectrum PCVs, including both of the recently FDA-approved products, Pfizer's 20-valent PCV, Prevnar 20 or PCV 20, and Merck's 15-valent PCV This validates the value associated with broader disease coverage once again.

We've seen premium pricing justified for broader spectrum pcbs, including both of the recently FDA approved products Pfizer's, 20, valent, PCV prep or 'twenty or PCB, <unk>, and Merck's 15, valent PCB PCB piece.

<unk> 15.

This validates the value associated with broader disease coverage once again.

Grant Pickering: Second, late last fall, the CDC's Advisory Committee on Immunization Practices, or ACIP, recommended a PCB for certain risk groups ages 19 to 64, which further expands the adult market given that approximately 30% of adults aged 50-64 fall into one of these identified risk groups. During this same ACIP meeting, there was a strong desire expressed by several committee members to lower the universal adult vaccination recommendation from 65 years of age and up down to 50 years of age and up. This move alone would significantly expand the potential size of the adult market.

Late last fall the Cdc's Advisory committee on immunization practices or ACI Pea recommended.

Recommended a PCB for certain risk groups ages, 19% to 64.

Which further expands the adult market given approximately 30% of adults aged 50 to 64 fall into one of these identified risk groups.

Third.

During the same AC IP meeting there was a strong desire expressed by several committee members to lower the Universal adult vaccination recommendation from 65 years of age and up down to 50 years of age and that this move alone would significantly expand the potential size of the adult market.

Grant Pickering: And lastly, by lowering the age recommendation to 50, we may see the door open to a prime-boost PCV regimen in adults, which would further grow this market and provide longer-term protection to the elderly population. This could be enabled if a broader-spectrum PCV, such as Vax24, were approved, which would eclipse the coverage of the older polysaccharide-only vaccine, Pneumovax 23, and could Therefore, we believe Vax24 is very well positioned in the current market and will have an opportunity to capitalize on additional growth drivers given its potential spectrum of coverage.

And lastly by lowering the age recommendation to 50, we may see the door open to a prime boost PCB regimen in adults, which would further grow this market and provide longer term protection to the elderly population.

This could be enabled if a broader spectrum PCB such as box 24 were approved which would eclipse the coverage of the older Polysaccharide only vaccine Pneumovax 23, and could lead to its removal from the treatment schedule.

So we believe <unk> 24 is very well positioned in the current market and we'll have an opportunity to capitalize on additional growth drivers given its potential spectrum of coverage importantly positive results from the ongoing phase one two study will put us in a position to trigger additional development activities.

Grant Pickering: Importantly, positive results from the ongoing Phase 1-2 study will put us in a position to trigger additional development activities with our PCV franchise. Upon completing the Phase 1 portion of this study, we plan to expand the VAX-24 program into the 65 and up population and, upon positive data from the Phase 2 portion, into the well-established and large pediatric segment. Subject to a pre-IND meeting with the FDA, we would expect to be able to submit a pediatric IND application in the first half of 2023.

With our PCB franchise upon completing the phase one portion of this study we plan to expand the <unk> 24 program into the 65, and our population and deposit and upon positive data from the phase II portion into the well established and large pediatric segment sub.

Subject to a pre IND meeting with the FDA, we would expect to be able to submit a pediatric IND application in the first half of 2023.

Grant Pickering: As part of our PCV franchise strategy, we continue to aggressively invest in VaxXP, our PCV candidate with an expanded breadth of coverage of greater than 30 strands. This parallel investment has put us in a position to provide guidance for the anticipated submission of the adult VAX-XP I&D application following the announcement of top-line results from the VAX-24 Phase 1-2 study. Beyond our PCV programs, we continue to make progress with our other pipeline capabilities. VaxA1, our vaccine to prevent Group A strep infections, is now in IND-enabling activities. We anticipate providing clear guidance on the expected timing for our VaxA1 IND application submission in the second half of this year.

As part of our PCB franchise strategy, we continued to aggressively invest in backs XP.

<unk> PCV candidate with an expanded breadth of coverage of greater than 30 Strange. This parallel investment has put us in a position to provide guidance for the anticipated submission of the adult <unk> IND application. Following the announcement of topline results from the <unk> 24 phase one two study.

Beyond our PCB programs, we continue to make progress with our other pipeline candidates.

One our vaccine to prevent group a strep infections is now in IND, enabling activities, we anticipate providing clear guidance on the expected timing for our back say one IND application submission in the second half of this year.

Grant Pickering: The global need for a vaccine to prevent Group A strep is compelling in both children and adults, making this an exciting follow-on opportunity behind our PCV franchise that would allow us to once again target a large and broad population. And finally, VaxPG, our vaccine designed to treat periodontal disease, continues to progress, and we intend to nominate the final candidate by the end of this year. To support these programs, we strengthened our balance sheet by completing a $115 million follow-on offering earlier this quarter.

The global need for a vaccine to prevent group a strep is compelling in both children and adults.

Making this an exciting follow on opportunity behind our PCB franchise that would allow us to once again target a large and broad population and finally, vacs PG or vaccine designed to treat periodontal disease continues to progress and we intend to nominate the final candidate by the end of this year.

To support these programs, we strengthened our balance sheet by completing a $115 million follow on offering earlier this quarter with this incredible incremental capital. We believe we have the resources to fund our operations for at least 12 months past the anticipated announcement of the <unk> 'twenty.

Grant Pickering: With this incremental capital, we believe we have the resources to fund our operations for at least 12 months past the anticipated announcement of the VAX 24 Phase 1-2 top-line results, which, as noted, is expected by year-end. I'm incredibly proud of what we have achieved and look forward to what promises to be the most important year in the company's history thus far. I'll now turn it over to Jim Wassil, who will share additional information about Vax24, including the Phase 1-2 clinical study design and our VaxXP and VaxA1 programs. Thanks Grant.

For phase two topline results, which as noted is expected by year end.

I'm incredibly proud of what we've achieved and look forward to what promises to be the most important year in the company's history, thus far.

Now turn it over to Jim <unk>, who will share additional information about <unk> 24, including the phase <unk> clinical study design and our <unk> XP and vaccine programs.

Thanks Grant.

Jim Wassil: Before I get into the key accomplishments for Vax24 and our anticipated milestones as we advance our clinical program. I want to reiterate what Grant shared with you about the significance of the PCB opportunity. The public health community continues to affirm the need for broader-spectrum pneumococcal vaccines to prevent pneumococcal.., infection caused by Streptococcus pneumoniae bacteria that can lead to invasive disease such as meningitis and bacteria, and non-invasive disease, including... Our PCV franchise is intended to improve upon existing vaccines by covering the serotypes responsible for most of the remaining pneumococcal disease currently in, while maintaining an immunogenicity profile comparable to, if not better than, preventive.

Before I get into the key accomplishments for <unk> 24, and our anticipated milestones as we advance our clinical program I wanted to reiterate what grant shared with you about the significance of the PCB opportunity in front of us.

The public health community continues to affirm the need for broader spectrum pneumococcal vaccines to prevent pneumococcal disease.

Infection caused by Streptococcus pneumonia bacteria that can lead to.

Disease, such as meningitis, and bacteremia and noninvasive disease, including pneumonia.

Our PCB franchise is intended to improve upon existing vaccines by covering the serotypes responsible for most of the remaining pneumococcal disease currently in circulation.

While maintaining an immunogenicity profile comparable to if not better than prevalent.

Jim Wassil: With our novel technology, we believe we can go beyond traditional vaccine approaches, as well as some new technologies like mRNA when it comes to addressing bacterial infections. As a result, our objective is for Vax24 to replace the collection of standard-of-care vaccines with a single, broad-spectrum PCV that includes all of the serotypes covered by the currently-marked, Now let's turn to the significant progress we have made with Act 24 and what's ahead. In the fourth quarter of 2021, we completed the manufacturing process for the Vax24 GMP drug product and submitted our IND application

With our novel Technology, We believe we can go beyond traditional vaccine approaches as well as some new technologies like mrna when it comes to addressing bacterial diseases.

As a result, our objective is for <unk> 24 to replace the collection of standard of care vaccines with a single broad spectrum PCB that includes all of the serotypes covered by the currently marketed back.

Now, let's turn to the significant progress we have.

Made with <unk> 2004, and what's to come in.

In the fourth quarter of 2021, we completed the manufacturing process for the <unk> 2004, GMP drug product and submitted our IND application to the FDA.

Jim Wassil: With the Vax24 Phase 1-2 clinical study now underway, we expect to announce the top-line safety, tolerability, and immunogenicity results by the end of the year. On receipt of these top-line data, we will have a good indication of the probability of success of Vax24 for adults. Now I'm going to walk you through the key study, design, and success. This is a randomized, observer-blind, dose-binding, controlled study designed to evaluate the safety, tolerability, and immunogenicity of Vax24 in healthy people.

With the vaccine for phase one two clinical study now underway.

First to announce the top line safety Tolerability and Immunogenicity results by the end of the year.

Upon receipt of these topline data.

Have a good indication of the probability of success of that.

For for the adult indication.

Now I am going to walk you through the phase one two key study objectives design.

Design and success criteria.

This is a randomized observer blind those funding controlled study designed to evaluate the safety Tolerability and Immunogenicity of <unk> 24 in healthy adults.

Phase one portion will enroll approximately 64 healthy adults, aged 18% to 49% to assess the safety and tolerability of each of <unk> 2004 doses and compared to <unk> <unk>. The standard of care selected first.

Jim Wassil: The Phase 1 portion will enroll approximately 64 healthy adults age 18 to 49 to assess the safety and tolerability of each of three Vax24 doses and compare them to PCV. Standard of Care Select, participants will be randomized equally into four separate arms, and will be evaluated for safety 8 and 29 days after the dose. The DMC will evaluate these data, to which we will remain blind, to make a go-no-go decision to enable us.

Participants will be randomized equally into four separate arms and will be evaluated for safety in 2009 days after dosing.

The DMC will evaluate these data, which we will remain blinded before making a go no go decision to enable us to proceed to phase III.

Based on our preclinical data and product profile, we anticipate the safety and Tolerability of <unk> four will be generally consistent with that of <unk>, a vaccine with more than 1 billion doses administered worldwide.

Jim Wassil: Based on our preclinical data and product profile, we anticipate the safety and tolerability of Vax24 will be generally consistent with that of Prevnar, a vaccine with more than one billion doses. The Phase II portion is significantly larger and will enroll about 800 healthy adults aged 50 to 65. We will evaluate immunogenicity along with safety and tolerability for the same three doses of Vax24 and compare it to, immunogenicity will be assessed based on the antibody response using IgG and OPA for the 20 serotypes in common with... For the additional four stereotypes contained in Vax24 and PneumaVax23, but not in PCV20, immunogenicity will be measured based on a four-fold rise in antibody titers.

The phase II portion is significantly larger and will enroll about 800 healthy adults aged 50 to 64.

We will evaluate immunogenicity, along with safety and Tolerability for the same three doses of <unk> 2004, and compared to <unk> 20.

Immunogenicity will be assessed based on the antibody response, using IGT and <unk> for the 20 serotypes in common with PCB 'twenty.

So the additional four serotypes contained in Vaca <unk> for Pneumovax 23, but not in PCB 20, maybe.

Tennessee will be measured based on our portfolio ryzen antibody titers.

Participants will be randomized equally into four separate arms and approximately 28 days after participants are those samples.

Jim Wassil: Participants will be randomized equally into four separate arms in approximately 28 days after participants are done. Samples are collected to assess immunity. Our top-line data will be based on the results as of this one-month assessment, as well as the safety and tolerability observations throughout.

Samples are collected to assess immunogenicity.

Topline data will be based on the results as of this one month assessment as well as the safety and Tolerability observations throughout this period.

Jim Wassil: For immunogenicity, our goal is to show non-inferiority versus PCV20 on a serotype-by-serotype basis. Regulatory Approval Requirement for, We may see some stereotypes in Vax 24 outperform PCB 20 and set a new bar for providing protection. It's important to remember that this is a proof-of-concept study, so there are a range of potential and acceptable outcomes, as we have seen with other FDA approaches. All participants in the Phase 1-2 study will be followed for a total of six months after dosing to assess whether...

For Immunogenicity, our goal is to show non inferiority versus <unk> 20 on a theoretical basis, which is the regulatory approval requirement for a phase III study.

We may see some serotypes and back 24 outperformed <unk> set a new bar for providing protection.

According to remember that this is a proof of concept study.

So there are a range of potential an acceptable outcome as we have seen with other FDA approved.

All participants in the phase one two study will be followed for a total of six months after dosing to assess safety and tolerability.

Jim Wassil: Ultimately, this study will help determine the optimal dose of Vax24 relative to PCV24 and how we will power the Pivotal Phase III Immunogenicity Study. In the Phase III study, a primary endpoint will assess non-inferiority versus the standard of care based on OPA, a measure of functional antibody responses against pneumococcus on a serotype-by-serotype basis. Non-inferiority is defined as greater than or equal to 50% of the OPA responses to the lower limit of the confidence interval relative to PCB.

Ultimately this study will help determine the optimal dose of <unk> relative to <unk> 'twenty, how we power the pivotal phase III Immunogenicity study.

The phase III study the primary endpoint was non inferiority versus the standard of care based on our measure of functional antibody responses against pneumococcal serotypes.

Serotype by serotype basis.

Non inferior isn't defined as greater than or equal to 50% of the okra responses to the lower limit of the confidence interval relative to <unk> 'twenty.

Jim Wassil: This is the same endpoint that served as the basis for the recent FDA approvals of PCV15 and PCV20 in the adult population. For these approvals, as well as the prior approval of PCV13 in infants, field efficacy studies were not required. We plan to pursue the same path for FACS 24 with regulators. This study is just the beginning of multiple milestones for Vax24 as we continue to build momentum. To add to our body of data in adults, we plan to conduct a second Phase II study.

This is the same endpoint that served as the basis for the recent FDA approvals of PCB <unk> and PCB 'twenty in the adult population.

For these approvals as well as the prior approval of PCB <unk> field efficacy studies were not required.

We plan to pursue the same path back to 24 with regulators.

This study is just the beginning of multiple milestones for <unk> 24, as we continue to build momentum.

To our body of data in adults, we plan to conduct a second phase III study.

Jim Wassil: This is an adult 65 and older upon the successful completion of the phase one portion of the ongoing trial. The top-line data from this study is anticipated in the first half of 2020. As Grant noted, we also plan to move into the pediatric segment with an IMD application submission in the first half of 2020, submitting positive top-line data from our ongoing clinical study and a pre-IND meeting. VaxxXP is also an important part of our strategy as it includes strains that cover over 90% of pneumococcal disease currently circulating in the U.S. Preclinical data presented last fall during ID Week showed Vaxxyte exhibited conjugate-like immune responses for all 31 stereotypes, as demonstrated by IgG immune responses that were superior to polysaccharide-based vaccines and comparable to Prevnar. Additionally, all As Grant noted, we continue to invest in this program towards an IND.

And adults 65 and older.

Successful completion of the phase one portion of the ongoing trial.

The topline data from this study is anticipated in the first half of 2023.

As Greg noted, we also plan to move into the pediatric segment with an IV application submission in the first half of 2023 pending positive topline data from our ongoing clinical study and a pre IND meeting with the FDA.

<unk> is also an important part of our strategy as it includes strength that cover over 90% of pneumococcal disease currently circulating in the U S.

Preclinical data presented last fall during IV weeks showed <unk> exhibited conjugate like immune responses for all 31 serotypes.

As demonstrated by IGT immune responses that were superior to polysaccharide based vaccine and comparable to <unk> 13.

Additionally, all serotypes <unk> elicited a T cell dependent immune response as demonstrated by the increase in IGT titles.

As Greg noted, we continue to invest in this program towards IND filings.

Jim Wassil: Beyond our PCB franchise, our VaxA1 program also leverages unique features of our platform technology. VaxA1, our novel conjugate vaccine candidate designed to prevent infection caused by group A strep, targets a white space where we have an opportunity to break new ground and address substantial disease in both adults and children. Rebate strep is a pervasive disease that results in 700 million cases of illness each year, and is one of the leading infectious disease-related causes of death and disability worldwide, with an estimated 500,000 deaths globally. Yet, the majority of group A strep infections lead to pharyngitis, commonly known as strep throat.

Beyond our PCV franchise, our vaccine program also Leverages unique features of our platform technology.

One our novel conjugate vaccine candidate designed to prevent infections caused by group a strep target the white space, where we have an opportunity to break new ground and address substantial disease in both adults and children.

Group, a strep is a pervasive disease that results in 700 million cases of illness each year.

He is one of the leading infectious disease related causes of death and disability worldwide with an estimated 500000 deaths globally.

The majority of group, a strep infection fleets of pharyngitis, commonly known as strep throat, which is highly prevalent installation kit.

Jim Wassil: Highly Prevalent Employee; Studies have indicated that antibiotic resistance to group A strep has significantly increased over the past decade, leaving the CDC to categorize group A strep as a concern. VaxA1 leverages a proprietary conserved polysaccharide androgen conjugated to a group A strep-specific protein carrier. The site-specific conjugation technology allows us to precisely bond the polysaccharides to the protein carrier, avoiding both the T-cell and B-cell epithelium, so as to optimally present both the polysaccharide and the protein to the immune system. We look forward to providing guidance on the anticipated I&V submission timing in the second half. With that, I'll turn it over to Jeff to provide a fax CG program. Thanks, Jim.

As I've indicated that antibiotic resistance to group a strep has significantly increased over the past decade, leading the CDC are categorized group a strep is a concerning threat.

That's a one leverages our proprietary conserve polysaccharide endogen conjugated to a group a strep specific protein carrier.

Our site specific conjugation technology allows us to precisely bond the polysaccharides the protein carrier avoiding both the T cell and B cell epitope.

To optimally presents both a polysaccharide in protein to the immune system.

We look forward to providing guidance on the anticipated INV submission timing in the second half of 2022.

With that I'll turn it over to Jeff to provide our CV program update.

Jeff Fairman: VaxPG is our novel therapeutic vaccine candidate designed to treat periodontal disease. It leverages a key application of our cell-free protein synthesis platform, which is the ability to make tough-to-make protein antigens. Periodontal disease impacts approximately 65 million adults in the United States. Globally, severe periodontal disease affects 10 to 15% of the adult population, resulting in productivity losses that are estimated at nearly $54 billion per year.

Thanks Tien <unk>.

<unk> is our novel therapeutic vaccine candidate designed to treat periodontal disease.

Leverage is a key application of our cell free protein synthesis platform, which is the ability to make tough to make protein antigens.

Periodontal disease impacts approximately 65 million adults in the United States.

Globally severe periodontal disease effects, 10% to 15% of the adult population, resulting in productivity losses that are estimated at nearly $54 billion per year.

Jeff Fairman: VaxPG targets Porphymonis gingivalis, the key pathogen responsible for periodontitis. VaxPG incorporates protein antigens that we believe are uniquely enabled with our technology due to their inability to be produced in conventional production vectors, either at all or at sufficient yields to permit commercial-scale supply. We continue to make progress on our early-stage work for this program and, as Grant shared, are planning to nominate a final VaxPG candidate by the end of 2022. Additionally, beyond our named programs, we continue to leverage our novel platform to develop new vaccine candidates to prevent or treat bacterial infections. The Express-CS cell-free protein synthesis platform and strain-promoted Qlik chemistry allow us to produce vaccines that are uniquely capable of breaking down bacteria's complex defense mechanisms while preserving immunogenicity.

Thanks, PGE targets poor for bonus change about the key pathogen responsible for period on title.

<unk> incorporates protein antigens that we believe are uniquely enabled with our technology due to their inability to be produced and conventional protected production vectors.

Either at all or at sufficient to permit commercial scale supply.

We continue to make progress on our early stage work for this program and as Greg shared or planning to nominate a final backs PT candidate by the end of 2022.

Beyond our named programs, we continue to leverage our novel platform to develop new vaccine candidate to prevent or treat bacterial infection.

Express T cell free protein synthesis platform.

And stream promoted click chemistry allow us to produce vaccines that are uniquely capable of breaking down bacteria is complex defense mechanisms.

<unk> Immunogenicity.

Andrew Guggenhime: Numerous papers were published in 2021 which have validated our platform approach. I would now like to turn the call over to Andrew, who will provide a financial update. Great. Thanks, Jeff.

Numerous papers were published in 2021, which has validated our platform approach.

I would now like to turn the call over to Andrew who will provide a financial update.

Andrew Guggenhime: I'll briefly cover a few financial points before turning it over to Grant for our closing remarks. With respect to the income statement, the details of our fourth quarter and year-end 2021 results and the reasons for the variances to the comparable 2020 periods are reflected in our 10-K filing and summarized in a press release. In summary, the year-over-year increase in R&D expenses was primarily the result of an increase in costs related to our VaxXP program and headcount growth, partially offset by a decrease in Vax24-related costs. The increase in G&A expenses was driven primarily by costs associated with our headcount growth and our first full year of operations as a public company.

Great. Thanks, Jeff I'll briefly cover a few financial points before turning it over to grant for our closing remarks.

With respect to the income statement the details of our fourth quarter and year end 2021 results into the reasons for the variances to the comparable 2020 periods are reflected in our 10-K filing and summarized in our press release.

In summary, the year over year increase in R&D expenses was primarily the result of an increase in costs related to our <unk> program and head count growth, partially offset by a decrease in <unk> 24 related costs.

The increase in G&A expenses was driven primarily by costs associated with our head count growth.

And our first full year of operations as a public company.

Andrew Guggenhime: As we look forward, we expect a substantial increase in 2022 expenses over full year and Q4 2021 annualized levels, particularly in R&D. The expected significant increase in R&D expenses is primarily a function of advancing Vax24 into the clinic, scaling up our manufacturing activities in anticipation of a Vax24 Phase 3 program, and IND enabling activities for VaxXP. Turning to the balance sheet and cash runway, we continue to maintain a strong balance sheet. We ended 2021 with $273.1 million in cash, cash equivalents, and investments, and earlier this year, we completed a follow-on offering in which we raised an estimated $107.6 million in net proceeds.

As we look forward, we expect a substantial increase in 2022 expenses over a full year and Q4 2021 annualized levels, particularly in R&D.

The expected significant increase in R&D expenses is primarily a function of advancing backs 24 into the clinic.

Scaling up our manufacturing activities in anticipation of about 24 phase III program and IND.

Enabling activities for <unk> XP.

Turning to the balance sheet and cash runway, we continued to maintain a strong balance sheet. We ended 2021 with $273 1 million in cash cash equivalents and investments and early this year, we completed a follow on offering in which we raised an estimated $107 6 million.

And net proceeds.

Grant Pickering: Going forward, we expect that our balance sheet will be sufficient to fund our operating expenses and capital expenditure requirements through at least 12 months past the announcement of the top-line data from our Phase 1-2 clinical study of Vax24 in adults. We will continue to remain disciplined in our allocation of capital based on our priorities and progress. 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?

Going forward, we expect that our balance sheet will be sufficient to fund our operating expenses and capital expenditure requirements through at least 12 months past the announcement of the topline data from our phase one two clinical study of <unk> 24 in adults.

We will continue to remain disciplined in our allocation of capital based on our priorities and progress.

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.

Brent.

Grant Pickering: Thanks, Andrew. What we have achieved over the past year has been remarkable, given the level of complexity associated with manufacturing a 24-valent PCV, and I would like to recognize the entire Vaxcyte team and our partners at Lonza for their many contributions. The coming year is an important one for the company, and we will remain focused on executing the Phase 1-2 VAX-24 clinical study to announce the anticipated top-line data by year-end, expanding the Vax24 clinical program into additional populations and preparing for manufacturing scale-up and late-stage development, investing in VaxXP to ensure optionality with our PCB franchise, and continuing to make progress with VaxA1 and VaxPG. We look forward to With that, let's take ask some questions. Operator?

Thanks, Andrew what we have achieved over the past year has been remarkable given the level of complexity associated with manufacturing of 24, valent PCV and I would like to recognize the entire back site team and our partners at launch for their many contributions the coming year is an important one for the company and we will remain focused on.

Executing the phase one to <unk> 24 clinical study to announce the anticipated top line data by year end.

Expanding the Vacs 24 clinical program into additional populations and preparing for manufacturing scale up and late stage development.

Investing in <unk> to ensure optionality with our PCB franchise and continue to make progress with <unk> and <unk>.

We look forward to sharing further updates as the year progresses and appreciate your interest by joining us today with that let's take some questions operator.

Operator: Thank you. Ladies and gentlemen, if you wish to submit a question for today's question and answer session, you will need to press the one key on your touchtone telephone. If your question has been answered and you wish to withdraw your polling request, you may do so by pressing the pound key.

Thank you, ladies and gentlemen, if you wish to register for a question for todays question and answer session you will need to press. The one key on your Touchtone telephone. If your question has been answered and you wish to withdraw your poling requests you may do so by pressing the balance sheet. If you are using a speakerphone please pick up.

Up your handset before entering your request one moment. Please for our first question.

Our first question comes from <unk> Patel with Bank of America. You May proceed with your question.

Pavan Patel: Thanks for taking my questions. So my first question is, what would management view as a highly positive outcome from its phase one adult vaccine study? And what are the key parameters?

Hi, everyone. Thanks for taking my questions.

So my first question is what would management view as a highly positive outcome from its phase one adult vaccine study and what are the key parameters.

Pavan Patel: Why, with which management will judge the success of the of the trial? And then for the multivalent pneumococcal vaccine development, what are your latest thoughts on the sort of product profile needed to facilitate a Shingrix-like winner-takes-all market scenario? Thanks for that question, Pub and was that it?

Why with which management will judge the success of the of the trial.

And then for the multi valent pneumococcal vaccine development what are your latest thoughts on the sort of product profile needed.

Sure Ashish <unk> like winner takes all market scenarios.

Thanks for that question.

Was that it.

Yep.

Grant Pickering: Yep. Okay, very good. So, two parts to that one. I'll let Jim Wassil, our Chief Operating Officer, answer the question with regard to what we would consider a success in the Phase 1-2 study. Jim, do you want to go ahead?

Okay very good so two parts to that one I'll, let Jim <unk>, our Chief operating officer answer the question with regard to what we would consider a success out of the phase one two study.

Jimmy wanted Scott sure. So in the phase one two as I said on the call we were going to be starting with a phase one safety analysis, and then we're going to be shifting quickly into phase III for.

Jim Wassil: Sure. So, in Phase 1-2, as I said on the call, we're going to be starting with a Phase 1 safety analysis, and then we're going to be shifting quickly into Phase 2. For phase 2, we will be doing a comparison of the immunogenicity of our Vax24 and PCV20. I think what we are expecting is, because of our platform, because of our site-specific conjugation, that we're going to be able to achieve a geometric mean ratio that is at least as good, if not better, than PCV20 on a serotype-by-serotype basis. And that's what we'll be looking at.

<unk> for the phase III.

We'll be doing a comparison of the immunogenicity between.

<unk> 24 in PCB 'twenty.

What we're expecting is because of our platform because of our site specific conjugation that we're going to be able to achieve a geometric mean ratio that is at least as good if not better than PCB.

'twenty on a serotype by serotype basis.

And then that's what we'll be looking at obviously, we will be doing a dose.

Jim Wassil: Obviously, we'll be doing a dose choice to move into phase three. So we'll be making the choice of which dose to move forward with. But, you know, just to mention that even if we aren't able to demonstrate, you know, superiority on a stereotype by stereotype basis, the FDA has set a requirement of having at least half the stereotype response as the standard of care to be able to move forward to phase three and ultimately to licensure. So even if we're not able to achieve superiority, we believe we've got a large room where we can make a sufficient immune response and move forward. Great

Joyce to move into phase III, So we will be making the choice of which dose to move forward.

But just to mention that even if we arent able to demonstrate superiority.

Stereotype by serotype basis, the FDA has set a requirement of having at least half. The serotype response as the standard of care to be able to move forward to a phase III and ultimately to licensure. So even if we're not able to achieve superiority. We believe we've got a large room, where we can make.

A sufficient immune response and move forward.

Grant Pickering: And then with regard to your second question, the second part, as it relates to potentially getting Vax24 on track for a preferred recommendation a la Shingrix's recommendation relative to Zostavax. Yeah, I mean, I think, you know, there are two key aspects of why we think that Vax24 is well positioned to potentially obtain a preferred recommendation. And that is the relative incremental coverage that Vax24 could provide over and above PCV20. So the 10 to 15 advantage that Prevnar20 had relative to the 15-valent vaccine for Merck, which allowed it to be recommended as a standalone vaccine, is similar to the amount of coverage that we would expect to have over and above the 20. So that's one aspect of the reason why we have a high level of confidence.

Great.

And then with regard to your second the second part.

As it relates to potentially getting back 24 on track for our preferred recommendation, our <unk> recommendation relative to Zostavax. Yeah. I mean, I think there are two key aspects of <unk>.

Why we think that <unk> 24 is well positioned to potentially obtain a preferred recommendation and that is the relative incremental coverage that backs 24 could provide over and above.

PCB 'twenty.

So the 10% to 15%.

Advantage that <unk> had relative to the 15 valent vaccine from Merck, which allowed it to be recommended as a standalone vaccine.

Grant Pickering: But then there's an important additional dimension, which is the current standard of care recommendation in adults from the ACIP is either PCV20 or PCV15 plus Pneumovax. So the reality is that the current coverage of either of the PCVs are not adequate to fully cover the 23 strains that are in Pneumovax. And that older polysaccharide-only vaccine, you know, continues to be part of the regimen. And with a 24-valent PCV like Vax24, it would entirely eclipse the coverage of Pneumovax23 in a way that could allow the ACIP to remove that vaccine altogether, which would obviously simplify the regimen to a single vaccine altogether and would open the door to a prime boost for PCVs in the adult population, which of course is the same approach that we use in children. And that's been a key sticking point that's prevented a lowering of the universal recommendation age below 65.

Bridge of either of the Pcbs are not adequate to fully cover the twenty-three strains that are in pneumovax and that older polysaccharide only vaccine continues to be part of the regimen at.

And with a 24 vaillant PCV like Vax 24, it would entirely eclipsed the coverage of Pneumovax twenty-three in a way that could allow the ACI P too.

Remove that vaccine altogether, which would obviously simplify the regimen to a single vaccine altogether and would open the door to a prime boost for Pcbs in the adult population, which of course is the same approach that we use in children and that's been a key sticking point.

That's prevented a lowering of the universal recommendation age below 65, there are discussions at the last October 8th CIP meeting, where they discussed lowering the age down to 50, but there was real anxiety about having pneumovax used in a way that could interfere with a boost with the <unk>.

Grant Pickering: You know, there were discussions at the last October ACIP meeting where they discussed lowering the age down to 50, but there was real anxiety about having Pneumovax used in a way that could interfere with a boost with the PCV later on.

Later on so.

Operator: If we can deliver that kind of incremental coverage, which we believe we will, and be able to remove pneumovacs from the regimen, we think that could be a compelling argument that could justify a preferred recommendation in the adult market. Thank you so much. Yep, thanks, Bob. Thank you, our next question comes from Louise Chen on Canto. You may proceed with your question. Hi, congratulations on all the progress this quarter and thanks for taking the time to answer my questions.

If we can deliver that kind of incremental coverage, which we believe we will and be able to remove pneumovax from the regimen, we think that could be a compelling argument that could justify a preferred recommendation and the adult market.

Thank you so much.

Yep Thanks, Bob.

Thank you. Our next question comes from Luis said with cancer. You May proceed with your question.

Hi, congratulations on all the progress this quarter and thanks for taking my questions. So first question I had for you is a recommendation aside how do you think you will effectively compete with some of these larger companies and the space.

Operator: So first question I have for you is, ASIF recommendation aside, how do you think you will effectively compete with some of these larger companies in the space? And then secondly, how do you see the market playing out if both your Vax24 and Vax.., make it to the market? How do you plan to market two of them together?

And then secondly, how do you see the market playing out if both your back 24, and Max X P make it to the market. How do you plan to market two of them together and then last question I have for you is just how did you think about that four fold rise an antibody titer corresponding to.

Good F S efficacy in the phase two portion of your back 24 study. Thank you.

Grant Pickering: So how are we going to compete with the oligopolists? How would we think about Vax24 and VaxXP potentially coexisting? And then there is the fourfold rise piece.

Great. Thank you Louise I think that was a three part question. So how are we going to compete with the oligopolistic.

How would we think about backs 24 and <unk>.

Potentially coexisting and then the fourfold rise fee. So maybe I can take the first two parts of that and then ask Jim to comment on the rationale for the four fold rise piece, so yeah I think Ah.

Grant Pickering: So maybe I can take the first two parts of that and then ask Jim to comment on the rationale for the fourfold rise piece. So, yeah, I think, you know, obviously Pfizer and Merck are extremely formidable competitors who have a very vested interest in maintaining their stake. But I think, you know, the way that we view this is that there has been substantial precedent over the years for broader-spectrum vaccines usurping lesser-valent vaccines.

Obviously.

Pfizer and Merck are extremely formidable competitors, who have a very vested interest in maintaining their stake, but I think.

The way that we view. This is there has been substantial precedent over the years for broader spectrum vaccines usurping lesser vaillant vaccines, and we've seen that time and time again.

Grant Pickering: And we've seen that time and time again, whether it was trivalent to quadrivalent flu vaccines, whether it was Gardasil versus Cervarix in the HPV market, which led to greater coverage for Gardasil, eventually resulting in the withdrawal of use of Cervarix in the U.S. altogether.

Whether it was trivalent to quadrivalent flu vaccines, whether it was gardasil versus server X in the HPV market, which led to the greater coverage from Gardasil.

Eventually, resulting in a withdrawal of use of <unk> in the us all together.

Grant Pickering: So, you know, the path that we're on is one where we are able to leverage the same basic components that have resulted in such an effective approach to prevent these types of bacterial infections, but we found a way to put us on a path to produce broader spectrum versions. And so for us, if we're able to deliver along the lines of what I just described in terms of what would justify a preferred recommendation, it should put us in a position to have a compelling case to the key decision makers, both from a regulatory perspective and then a conduct perspective through the ACIP.

So.

The path that we're on.

Is one where we are able to leverage the same basic components that have resulted in such it effective approach to prevent these types of bacterial infections, but we found a way to.

Put us on a path to produce broader spectrum versions and so for us if we're able to deliver along the lines of what I. Just described in terms of what would justify a preferred recommendation it should put us in a position to have a compelling case.

Two the key decision makers.

From a regulatory perspective, and then a conduct perspective through the CIP. So if we can deliver that kind of profile and if we can deliver the sort of volume that would allow for a supply of a universal recommendation sort of magnitude I think it will put us in a really strong position and this is not a market.

Grant Pickering: So if we can deliver that kind of profile, and if we can deliver the sort of volume that would allow for a supply of a universal recommendation sort of magnitude, I think it'll put us in a really strong position. And this is not a market where you need to deploy, you know, thousands of sales reps to drive adoption.

Where you need to deploy thousands of sales reps to drive adoption, it's really critical singular bodies and each sovereign nation that are making these decisions about coverage. So I think we're well positioned and we've been well capitalised and we're not going to sell ourselves short but.

Grant Pickering: It's really critical singular bodies, you know, in each sovereign nation that are making these decisions about coverage. So I think we're well positioned and we've been well capitalized, and we're not going to sell ourselves short, but that's kind of how we're thinking about it in this moment. Obviously, we've got a long way to go.

Kind of how we're thinking about it in this moment, obviously, we've got a long way to go as it relates to that.

Grant Pickering: As it relates to... Vax24 and VaxXP, you know, we've realized that we do have this unique ability to add incremental coverage without facing the same immunological diminution that conventional chemistry has resulted in. And so, we do have VaxXP, you know, waiting in the wings, if you will. But in terms of actually bringing products to market, you do have this cascade that occurs by virtue of initially developing these vaccines in the adult population. It's a shorter path.

That's 24 and backs XP, we've realized that we do have this unique ability to add incremental coverage without facing the same immune immunological diminution that the conventional chemistry has resulted in and so we.

We do have.

Vax XP waiting in the wings, if you will but in terms of actually bringing the products to market. You do have this cascade that occurs by virtue of initially developing these vaccines in the adult population. It's a shorter path. It's a single dose in this moment as opposed to the pediatric indications.

Grant Pickering: It's a single dose in this moment, as opposed to the pediatric indication where they receive four vaccines over a 15-month time frame. So, it naturally puts adult pace of development ahead of infants. So, you could imagine a scenario where if everything goes as we hope, where Vax24 could obtain initially an adult approval and recommendation followed by an infant approval and recommendation, and then VaxXP could come in thereafter in adults and then again cascade into infants.

Where they received for vaccines over a 15 month.

Timeframe. So it naturally puts adult pace of development ahead of infants. So you could imagine a scenario, where if everything goes as we hope.

<unk> 24 could obtain initially an adult approval.

Approval and recommendation followed by an infant approval and recommendation.

And then backs XP could come in thereafter in adults and then again cascade into infants. So there is a natural progression to how these work and that's why we want to keep <unk> within striking distance because these vaccines have been so effective historically when that when you vaccinate with them those <unk>.

Grant Pickering: So there is a natural progression to how these work, and that's why we want to keep VaxXP within striking distance because these vaccines have been so effective historically when when you vaccinate with them, those included strains are effectively taken out of circulation, and it only makes those incremental strains more epidemiologically relevant, and that's the rationale behind VaxXP as a fast follower, and that's how we see them cas It would be more of a replacement sort of strategy.

<unk> strange are effectively taken out of circulation and it only makes those incremental streams.

More.

The email address glee relevant and that's the rationale behind backs X P. As a fast follower and that's how we see them cascading into the market, but to have both in the same indication would be unlikely it would be more of a replacement sort of strategy.

Grant Pickering: So if that answers the first two parts, I'll ask Jim to comment on the four-fold rise approach. Sure, thanks Grant. For the four-fold rise, it's sort of a two-part answer. The first is that we looked at the recent approvals of PCV20 and PCV15. PCV20 used a comparison of non-inferiority versus Pneumovax to determine whether or not they could get licensure. However, PCV15 looked at a four-fold rise, so they looked at a statistically superior four-fold rise versus PCV13.

So if that answers the first two parts I'll ask Jim to comment on the four fold rise.

Approach sure. Thanks Grant.

For the fourth will arrive.

It's sort of a two part answer the first as we looked at the recent approvals of PCB 20, and PCB 15, PCB 20 use a comparison of noninferiority versus pneumovax to determine whether or not they could get licensure. However, PCB 15 looked at fourfold rise so they looked at a statistically <unk>.

<unk> four fold rise versus PCB 13, So we had two options available to us based on precedent to be able we felt to get.

Jim Wassil: So we had two options available to us based on precedent to be able, we felt, to get an approval for Vax24. Now, with the ACIP in October making a recommendation, we were going to do the comparison, and we still are doing a comparison against PCV20. Well, the recommendation is to use PCV15 and Pneumovax or PCV20. Since PCV20 is our comparator, we decided to use that and go with the 4-pole rise.

An approval for about 24.

Now with the <unk> in October making a recommendation we were going to do the comparison then we still are doing in comparison against PCB 20, with a recommendation as to use PCB 15, and Pneumovax or PCB 20. Since PCB 20 that are compared are we decided to use that and to go with the poor full rise and.

Jim Wassil: And we believe that, based on the regulatory precedent, as well as the recommendation by the ACIP, will give us a good indication of success for phase three. Thanks, Louise. Thank you. And as a reminder, to ask a question, you will need to press star 1 on your telephone. Our next question comes from Joseph Stringer with Needham & Company. You may proceed with your question. Hi, this is Ben Ricard on behalf of Joey Stringer.

We believe that that based on the regulatory precedent as well as the recommendation by the Asa IP will give us a good indication of success for phase three.

Okay.

Lewis.

Okay.

Thank you and as a reminder to ask a question you will need to press Star woman and telephone. Our next question comes from Joseph Stringer with needed with the company who May proceed with your question.

Hi, This is Ben Ricard on for Joey Stringer, Thanks for taking our questions just one about the COVID-19 related impacts if you could just talk about.

Operator: Thanks for taking our question. Just one about sort of the COVID-related impacts. If you could just talk about any potential impacts on the upcoming VAX-24 trial based on having a larger-than-anticipated winter COVID season or a smaller one coming up. Thanks a lot. So this is Jim Wassil.

Any potential impact on the upcoming box 24 trial based on having a larger than anticipated winter COVID-19 season, or a smaller one coming up thanks a lot.

Uh-huh.

So this is Jim Watson overseeing clinical program as well.

Jim Wassil: I'm overseeing the clinical program as well. We don't expect COVID to have an impact. Our initial study is in 18 to 49-year-olds, and the healthy 18 to 49-year-old cohort is sufficiently large that we don't foresee that we'll have any issues with enrollment. The phase two is age 50 to 64, same thing, sufficient cohort there. Our main exclusion criteria for enrollment is actually not having an experimental vaccine either before, during, or six months after.

We don't expect Covid to have an impact our initial studies and 18 to 49 year olds.

And the healthy 18 to 49 year old cohort is sufficiently large that we don't foresee that will have any.

Issues with the enrollment.

The face to his age 50 to 64 same thing.

Sufficient cohort there.

Our main exclusion criteria for enrollment is actually.

Not having an experimental vaccine either before during or six months after.

Jim Wassil: Given that the majority of individuals have already received all of their COVID shots, we are able to enroll sufficient subjects without having any exclusions. So we feel we'll be able to move along just as fast as we originally anticipated. Yeah, and it may be worth pointing out, Ben, that, you know, there isn't a seasonal component to executing these trials.

Given the majority of individuals have already received all of their Covid shot.

We are able to enroll sufficient subjects without having any exclusion. So we feel we will be able to move along just as fast as we originally anticipated.

Yeah, and it may be worth pointing up and that.

There isn't a seasonal component to executing these trials that one of the nice aspects of developing a follow on pneumococcal conjugate vaccine is that these are just studies focused on safety and immunogenicity. So there isn't an infection rate component to this we don't have to.

Grant Pickering: You know, one of the nice aspects of developing a follow-on pneumococcal conjugate vaccine is that these are just studies focused on safety and immunogenicity. So there isn't an infection rate component to this. We don't have to follow the subjects who've been vaccinated to confirm that they don't contract a strep pneumonia infection. These are just immunizing the subjects and following them for 30 days in this phase one study to study the phase two study in particular, where we're looking at immunogenicity.

Follow.

The subjects who've been vaccinated to confirm that they don't contract Ah Strep pneumonia infection. These are just immunizing the subjects and following them for 30 days in this phase one to study the.

The phase two study in particular were looking see immunogenicity. So we don't need to run those big field efficacy studies that are the convention. When you have to show efficacy. These are validated <unk> surrogate an immune and points. So that's not an aspect of of executing these particular trials.

Grant Pickering: So we don't need to run those big field efficacy studies that are the convention when you have to show efficacy. These are validated surrogate immune endpoints. So that's not an aspect of executing these particular trials.

Operator: Great. Thank you. Thanks, Beth. Thank you. And I'm not asking any further questions at this time.

Great. Thank you.

Thanks Bye.

Thank you and I'm not showing any further questions. At this time I would now like to turn the call back over to Greg Pickering for any further remarks.

Grant Pickering: I would now like to turn the call back over to Grant Pickering for any further remarks. Well, I just want to thank you all for your interest and for participating in the call today, and have a good rest of your week. Thank you very much.

Well I just want to thank you all for your interest and for participating in the call today and have a good rest of your week. Thank you very much.

Operator: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.

Operator: [music] David Risinger, David Risinger, David Risinger, [inaudible] [music] Good afternoon, my name is Josh and I will be your conference operator. 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 placed on mute to prevent any background noise.

[music].

Okay.

[music].

Okay.

[music].

Yeah.

[music].

Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press the pound key. Thank you. I will now turn the call over to Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. Please go ahead.

Good afternoon.

Afternoon, My name is Josh and I'll be your conference operator today.

At this time I would like to welcome everyone to the back side fourth quarter and full year financial results Conference call.

Lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question press. The pound key. Thank you I will now turn the call over to Andrew Guggenheim.

Didn't then chief financial Officer of that site. Please go ahead Sir.

Andrew Guggenhime: Thank you, Operator, and good afternoon, everyone. I'd like to welcome you to Vaxcyte's earnings conference call to discuss our 2021 results and provide a business update. I'm joined today by our Chief Executive Officer, Grant Pickering, our Chief Operating Officer, Jim Wassil, and our VP of Research, Jeff Fairman. Earlier this afternoon, we issued a news release announcing our results. Copies of this and our other news releases, recent corporate presentations, and SEC filings can be found in the Investors in Media section of our website.

Thank you operator, and good afternoon, everyone.

I'd like to welcome you to <unk> sites earnings conference call to discuss our 2021 results and to provide a business update.

Im joined today by our Chief Executive Officer Grant Pickering, Our Chief operating Officer, Jim <unk>, and our VP of research Jeff Berman.

Andrew Guggenhime: 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 include statements related to the benefits of our vaccine candidates, the process and timing of anticipated future developments of our vaccine candidates, including the timing and availability of top-line data from the Vax24 Phase 1-2 Clinical Proof of Concept Study, the demand for our vaccine candidates, our expected uses and sufficiency of cash and other funding to support our development programs and other operating expenses, and other statements that are not historical facts. Any 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 expectations.

Before we begin I'd like to remind you that during this call we'll be making certain forward looking statements about back site, which are subject to various risks and uncertainties. These.

These include statements related to the benefits of our vaccine candidates the process and timing of anticipated future development of our vaccine candidates, including the timing and the availability of topline data from the <unk> 24 phase two clinical proof of concept study the demand for our vaccine candidates are expected uses and sufficiency of.

Cash and other funding to support our development programs and other operating expenses and other statements that are not historical fact.

Any 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.

Esters should read the risk factors set forth in fact sites Form 10-K for the year ended December 31, 2021, and any subsequent reports filed with the SEC.

With that I'll turn the call over to grant Pickering Grant.

Grant Pickering: Thanks, Andrew. And to all of you on the call and webcast, thanks for joining us today. The past year was an extremely important one for Vaxcyte. We made significant advancements across our business, which remains focused on eradicating bacterial infections such as invasive pneumococcal disease, group A strep, and periodontitis. We advanced our pipeline, demonstrated the potential of our novel vaccine platform, and recruited the right expertise to help us transition into the clinic and prepare for manufacturing scale-up and late-stage development.

Thanks, Andrew and to all of you on the call and webcast. Thanks for joining us today.

The past year was an extremely important one for that site, we made significant advancements across our business, which remains focused on eradicating bacterial infections, such as invasive pneumococcal disease group, a strep and periodontitis.

While we all witnessed the global impact of vaccine innovation on a scale not seen since the 19 fifties bacterial infectious diseases have not historically received adequate attention.

As a result, the global incidence of pneumococcal disease continues to climb.

Driven by emerging serotypes not covered by currently available vaccines.

Although the available pneumococcal conjugate vaccines or <unk> for short are effective the underlying chemistry appears to have reached its limits in terms of its ability to permit. The addition of Sara types to broaden protection without diminished overall immune responses jeopardizing their long term protection.

Our strategy is to overcome such limitations by applying advanced chemistry, and modern synthetic techniques, including the express CF cell free protein synthesis platform.

To produce vaccines that are uniquely capable of breaking down bacteria's complex defense mechanisms, while preserving immunogenicity across a broader spectrum of coverage.

Grant Pickering: Our site-specific conjugation technology allows us to engineer broader-spectrum PCBs designed to avoid carrier suppression in ways that we anticipate will afford our PCB franchise an opportunity to surpass the coverage of other pneumococcal vaccines. With this competitive advantage, we believe Vax24, our lead 24-valent vaccine candidate, has the opportunity to be a best-in-class PCV in both adults and pediatrics in an already $7 billion global market that is poised to undergo significant further growth.

Our site specific conjugation technology allows us to engineer broader spectrum PCB is designed to avoid carrier suppression and ways that we anticipate will afford our PCB franchise and opportunity to surpass the coverage of other pneumococcal vaccines.

With this competitive advantage, we believe vacs 24, our lead 24 valent vaccine candidate has the opportunity to be a best in class PCB in both adults and pediatrics and then already $7 billion global market that is poised to undergo significant further growth.

Grant Pickering: Our recent achievements with Vax24 have paved the way for a surge in momentum in 2022 as we reach key anticipated milestones. Just last week, we announced the dosing of the first participants in the Vax24 Phase 1 portion of our Phase 1-2 clinical study in adults, and anticipate announcing the top-line results of both the Phase 1 and Phase 2 portions by year-end. This study is designed to determine the optimal dose of Vax24 based on safety and immunogenicity, and to inform how we power a future pivotal Phase 3 immunogenicity study in adults.

Our recent achievements with Thats 24 have paved the way for a surge in momentum in 2022, as we reach key anticipated milestones.

Just last week, we announced the dosing of the first participants in the <unk> 24 phase one portion of our phase one two clinical study in adults and anticipate announcing the top line results of both the phase one and phase II portions by year end.

This study is designed to determine the optimal dose of <unk> 24, based on safety and Immunogenicity and to inform how we power our future pivotal phase III Immunogenicity study in adults.

Grant Pickering: The immunogenicity data from the Phase 2 portion of this study should tell us if one or more of the Vax24 doses can meet or exceed the non-inferior immune response threshold on a serotype-by-serotype basis that is required for regulatory approval. If achieved, this milestone has the potential to represent a major inflection point for the company.

The Immunogenicity data from the phase II portion of this study should tell us if one or more of the vacs 24 doses can meet or exceed the non inferior immune response threshold on a stereotype by serotype basis that is required for regulatory approval.

Grant Pickering: We remain excited about the adult pneumococcal vaccine market, given it represents approximately $2 billion in annual sales and has the opportunity to grow significantly based on a number of key factors. First, we've seen premium pricing justified for broader-spectrum PCVs, including both of the recently FDA-approved products, Pfizer's 20-valent PCV, Prevnar 20, or PCV 20, and Merck's 15-valent PCV This validates the value associated with broader disease coverage once again.

First we've seen premium pricing justified for broader spectrum pcbs, including both of the recently FDA approved products Pfizer's 20, valent, PCV, <unk> or 'twenty or PCB, <unk>, and Merck's 15, Valent PCB PCB PCB 15.

This validates the value associated with broader disease coverage once again.

Grant Pickering: Second, late last fall, the CDC's Advisory Committee on Immunization Practices, or ACIP, recommended a PCV for certain risk groups ages 19 to 64, which further expands the adult market given that approximately 30% of adults aged 50-64 fall into one of these identified risk groups. During this same ACIP meeting, there was a strong desire expressed by several committee members to lower the universal adult vaccination recommendation from 65 years of age and up down to 50 years of age and up. This move alone would significantly expand the potential size of the adult market.

Late last fall the Cdc's Advisory committee on immunization practices or ACI Pea recommended a PCB for certain risk groups ages, 19% to 64.

Which further expands the adult market given approximately 30% of adults aged 50 to 64 fall into one of these identified risk groups.

<unk>.

Grant Pickering: And lastly, by lowering the age recommendation to 50, we may see the door open to a prime boost PCV regimen in adults, which would further grow this market and provide longer-term protection to the elderly population. This could be enabled if a broader spectrum PCB, such as VAX24, were approved, which would eclipse the coverage of the older polysaccharide-only vaccine, Pneumovax 23, and could lead to its removal from the treatment schedule. So we believe Vax24 is very well positioned in the current market and will have an opportunity to capitalize on additional growth drivers given its potential spectrum of coverage.

This could be enabled if a broader spectrum PCB such as <unk> 24 were approved which would eclipse the coverage of the older Polysaccharide only vaccine Pneumovax 23, and could lead to its removal from the treatment schedule.

So we believe that's 24 is very well positioned in the current market and we'll have an opportunity to capitalize on additional growth drivers given its potential spectrum of coverage importantly positive results from the ongoing phase one two study will put us in a position to trigger additional development activities.

Two a pre IND meeting with the FDA, we would expect to be able to submit a pediatric IND application in the first half of 2023.

Grant Pickering: As part of our PCB franchise strategy, we continue to aggressively invest in VaxXP, our PCB candidate with an expanded breadth of coverage of greater than 30 strands. This parallel investment has put us in a position to provide guidance for the anticipated submission of the adult VAX-XP I&D application following the announcement of top-line results from the VAX-24 Phase 1-2 study. Beyond our PCB programs, we continue to make progress with our other pipeline capabilities.

As part of our PCB franchise strategy, we continue to aggressively invest in <unk> P.

Our PCV candidate with an expanded breadth of coverage of greater than 30 Strange. This parallel investment has put us in a position to provide guidance for the anticipated submission of the adult <unk> IND application. Following the announcement of topline results from the <unk> 24 phase one two study.

Beyond our PCB programs, we continue to make progress with our other pipeline candidates back say, one our vaccine to prevent group a strep infections is now in IND, enabling activities, we anticipate providing clear guidance on the expected timing for our back say one IND application submission.

Grant Pickering: VaxA1, our vaccine to prevent group A strep infections, is now in IND-enabling activities. We anticipate providing clear guidance on the expected timing for our VaxA1 IND application submission in the second half of this year. The global need for a vaccine to prevent group A strep is compelling in both children and adults, making this an exciting follow-on opportunity behind our PCV franchise that would allow us to once again target a large and broad population.

In the second half of this year.

The global need for a vaccine to prevent group a strep is compelling in both children and adults, making this an exciting follow on opportunity behind our PCV franchise that would allow us to once again target a large and broad population and finally, vacs PG or vaccine designed to treat period.

Grant Pickering: And finally, VaxPG, our vaccine designed to treat periodontal disease, continues to progress, and we intend to nominate the final candidate by the end of this year. To support these programs, we strengthened our balance sheet by completing a $115 million follow-on offering earlier this quarter.

Until disease continues to progress and we intend to nominate the final candidate by the end of this year to.

To support these programs, we strengthened our balance sheet by completing a $115 million follow on offering earlier this quarter.

Jim Wassil: With this incremental capital, we believe we have the resources to fund our operations for at least 12 months past the anticipated announcement of the VAX 24 Phase 1-2 top-line results, which, as noted, is expected by year-end. I'm incredibly proud of what we have achieved and look forward to what promises to be the most important year in the company's history thus far. I'll now turn it over to Jim Wassil, who will share additional information about Vax24, including the Phase 1-2 clinical study design and our VaxXP and VaxA1 programs. Thanks, Grant.

This incremental capital we believe we have the resources to fund our operations for at least 12 months past the anticipated announcement of the Vacs 24 phase two top line results, which as noted is expected by year end.

Im incredibly proud of what we've achieved and look forward to what promises to be the most important year in the company's history, thus far.

I'll now turn it over to Jim <unk>, who will share additional information about <unk> 24, including the phase <unk> clinical study design and our <unk> XP and vaccine one programs.

Thanks Grant before I get into the key accomplishments <unk> 24, and our anticipated milestones as we advance our clinical program.

Let me reiterate what grant shared with you about the significance of the PCB opportunity in front of us.

The public health community continues to affirm the need for broader spectrum pneumococcal vaccines to prevent pneumococcal disease.

Section caused by Streptococcus pneumonia bacteria that can lead to disease, such as meningitis bacteremia.

Noninvasive disease, including the Mone.

Our PCB franchise intended to improve upon existing vaccines by covering the serotypes responsible for most of the remaining pneumococcal disease currently in circulation while.

While maintaining an immunogenicity profile comparable to if not better than <unk>.

Jim Wassil: With our novel technology, we believe we can go beyond traditional vaccine approaches, as well as some new technologies like mRNA when it comes to addressing bacterial. As a result, our objective is for Vax24 to replace the collection of standard-of-care vaccines with a single broad-spectrum PCV that includes all of the serotypes covered by the currently-marked, Now let's turn to the significant progress we have made with Vax24 and what's, In the fourth quarter of 2021, we completed the manufacturing process for the Vax24 GMP drug product and submitted our IND application to the FDA.

With our novel Technology, We believe we can go beyond traditional vaccine approaches as well as some new technologies like mrna when it comes to addressing bacterial diseases.

Now, let's turn to the significant progress we've made with <unk> 2004, and what's to come.

In the fourth quarter of 2021, we completed the manufacturing process for the <unk> 'twenty for GMP drug product.

Our IND application to the FDA.

Jim Wassil: With the Vax24 Phase 1-2 clinical study now underway, we expect to announce the top-line safety, tolerability, and immunogenicity results by the end of the year. On receipt of these top-line data, we will have a good indication of the probability of success of Vax24 for adults. Now I'm going to walk you through the key study design, and success. This is a randomized, observer-blind, dose-binding, controlled study designed to evaluate the safety, tolerability, and immunogenicity of Vax24 in healthcare.

With the vaccine for phase one two clinical study now underway, we expect to announce the topline safety Tolerability and Immunogenicity results by the end of the year.

Upon receipt of these topline data.

Hello.

Good indication of the probability of success of <unk> 24 for the adult indication.

Now I'm going to walk you through the phase <unk> study objectives.

<unk> and success criteria.

It is a randomized observer blind those funding controlled study designed to evaluate the safety Tolerability and Immunogenicity of <unk> 24 in healthy adults.

Jim Wassil: The phase 1 portion will enroll approximately 64 healthy adults age 18 to 49 to assess the safety and tolerability of each of three Vax24 doses and compare them to PCV. Standard of Care Select. Participants will be randomized equally into four separate RMS, and will be evaluated for safety 8 and 29 days after the dose. The DMC will evaluate these data, to which we will remain blind, to make a go-no-go decision to enable us.

Phase one portion will enroll approximately 64 healthy adults, aged 18% to 49% to assess the safety and tolerability of each of <unk> 'twenty four doses of <unk> compared to <unk> <unk>. The standard of care selected for our study.

Participants will be randomized equally into four separate arms and will be evaluated for safety eight and 29 days after dosing.

The DMC will evaluate these data, which we will remain blinded before making a go no go decision to enable us to proceed to phase III.

Jim Wassil: Based on our preclinical data and product profile, we anticipate the safety and tolerability of Vax24 will be generally consistent with that of Prevnar, a vaccine with more than one billion doses. The Phase II portion is significantly larger and will enroll about 800 healthy adults aged 50 to 65. We will evaluate immunogenicity along with safety and tolerability for the same three doses of Vax24 and compare it to Immunogenicity will be assessed based on the antibody response using IgG and OPA for the 20 serotypes in common with... For the additional four stereotypes contained in Vax24 and Pneumovax23, but not in PCV20, immunogenicity will be measured based on a four-fold rise in antibody titers.

The phase II portion is significantly larger and will enroll about 800 healthy adults aged 50 to 64.

We will evaluate immunogenicity, along with safety and Tolerability for the same three doses of <unk> 24, and compares to PCB 20 <unk>.

Immunogenicity will be assessed based on the antibody response, using IGT and <unk> for the 20 serotypes in common with <unk> <unk>.

So the additional four serotypes contained in Vaca <unk> for Pneumovax 23, but not in PCB 20, Immunogenicity will be measured based on our portfolio ryzen antibody titers.

Jim Wassil: Participants will be randomized equally into four separate arms in approximately 28 days after participants are dosed, and samples are collected to assess immunity. The top-line data will be based on the results of this one-month assessment, as well as the safety and tolerability observations throughout the year.

Participants will be randomized equally into four separate arms and approximately 28 days after participants are dose.

Samples are collected to assess immunogenicity.

Topline data will be based on the results as of this one month assessment as well as the safety and Tolerability observations throughout this period.

Jim Wassil: For immunogenicity, our goal is to show non-inferiority versus TCP20 on a serotype-by-serotype basis. And it's the regulatory approval requirement for. We may see some stereotypes in Vax24 Outperform TCB20 and set a new bar for providing protection. It's important to remember that this is a proof-of-concept study, so there are a range of potential inaccessible outcomes, as we have seen with other FDA approaches. All participants in the Phase 1-2 study will be followed for a total of six months after dosing to assess whether

For Immunogenicity our goal is to show non inferiority versus <unk> 20 on a series by series type basis, which is the regulatory approval requirement for a phase III study.

We may see some serotypes and back 24 outperformed PCB <unk> and set a new bar for providing protection.

According to remember that this is a proof of concept study.

So there are a range of potential an acceptable outcome as we have seen with other FDA approved.

All participants in the phase <unk> study will be followed for a total of six months after dosing to assess safety and tolerability.

Jim Wassil: Ultimately, this study will help determine the optimal dose of Vax24 relative to PCV24 and how we will power the pivotal phase III immunogenicity study. In the phase 3 study, a primary endpoint will assess non-inferiority versus the standard of care based on OPA, a measure of functional antibody responses against pneumococcus on a serotype-by-serotype basis. Non-inferiority is defined as greater than or equal to 50% of the OPA responses to the lower limit of the confidence interval relative to PCVD.

Ultimately this study will help determine the optimal dose of <unk> relative to <unk> and how we power the pivotal phase III Immunogenicity study.

The phase III study the primary endpoint was non inferiority versus the standard of care based on Oprah and measure functional antibody responses against pneumococcus serotype by serotype basis.

Non inferiority isn't defined as greater than or equal to 50% of the ultra responsive to the lower limit of the confidence interval relative to <unk>.

Jim Wassil: This is the same endpoint that served as the basis for the recent FDA approvals of PCV15 and PCV20 in the adult population. For these approvals, as well as the prior approval of PCV13 in infants, field efficacy studies were not performed. We plan to pursue the same path for FACS 24, and this study is just the beginning of multiple milestones for Vax24 as we continue to build momentum. To add to our body of data in adults, we plan to conduct a second phase two study in adults 65 and older upon the successful completion of the Phase I portion of the ongoing trial.

This is the same endpoint that served as the basis for the recent FDA approval of the PCB <unk> and PCB 'twenty in the adult population.

Are these approvals as well as the prior approval of PCV 13 in field efficacy studies were not required.

We plan to pursue the same path back 24 with regulators.

This study is just the beginning of multiple milestones for <unk> 24, as we continue to build momentum to add to our body of data in adult we plan to conduct a second phase III study.

And adults 65 and older upon the successful completion of the phase one portion of the ongoing trial.

Jim Wassil: The top-line data from this study is anticipated in the first half of 2020. As Grant noted, we also plan to move into the pediatric segment with an IMD application submission in the first half of 2020, pending positive top-line data from our ongoing clinical study and a pre-IND meeting. VaxxXP is also an important part of our strategy as it includes strains that cover over 90% of pneumococcal disease currently circulating in the U.S. Preclinical data presented last fall during ID Week showed Vaxxyte exhibited conjugate-like immune responses for all 31 stereotypes, as demonstrated by IgG immune responses that were superior to polysaccharide-based vaccines and comparable to Prevnar. Additionally, all serotypes in VaxxXP elicited a T-cell dependent immune response as demonstrated by the increase in IgG titers post-treatment.

The topline data from this study is anticipated in the first half of 2023.

As Grant noted we also plan to move into the pediatric segment with an IV application submission in the first half of 2023 pending positive topline data from our ongoing clinical study and a pre IND meeting with the FDA.

<unk> is also an important part of our strategy as it includes strengths that cover over 90% of pneumococcal disease currently circulating in the U S.

Preclinical data presented last fall during <unk> exhibited conjugate like immune responses for all 31 serotype as demonstrated by IGT immune responses that were superior to polysaccharide based vaccine and comparable to <unk> 13.

Additionally, all serotypes and <unk> listed in the T cell dependent immune response as demonstrated by the increase in IGT titles.

Jim Wassil: As Grant noted, we continue to invest in this program towards an IND. Furthermore, beyond our PCB franchise, our VaxA1 program also leverages unique features of our platform technology. VaxA1, our novel conjugate vaccine candidate designed to prevent infection caused by group A strep targets a white space where we have an opportunity to break new ground and address substantial disease in both adults and children. As a reminder, strep is a pervasive disease that results in 700 million cases of illness each year, and is one of the leading infectious disease-related causes of death and disability worldwide with an estimated 500,000 deaths globally.

As Greg noted, we continue to invest in this program towards an IND filing.

Beyond our PCB franchise, our vaccine program also Leverages unique features of our platform technology.

I'd say, one our novel conjugate vaccine candidate designed to prevent infections caused by group a strep target the white space, where we have an opportunity to break new ground and address substantial disease in both adults and children.

Group, a strep is a pervasive disease that results in 700 million cases of illness each year is.

One of the leading infectious disease related causes of death and disability worldwide with an estimated 500000 deaths globally.

Jim Wassil: Yet the majority of group A strep infections lead to pharyngitis, commonly known as strep throat, highly prevalent in full-age. Studies have indicated that antibiotic resistance to group A strep has significantly increased over the past decade, leaving the CDC to categorize group A strep as a concern.

The majority of group, a strep infection fleets of pharyngitis.

<unk> known as strep throat, which is highly prevalent installation kit sales.

States have indicated that antibiotic resistance to group a strep has significantly decreased over the past decade, leaving the CDC to categorize group a strep is a concerning threat.

Jim Wassil: VaxA1 leverages a proprietary conserved polysaccharide androgen conjugated to a group A strep-specific protein carrier. The site-specific conjugation technology allows us to precisely bond the polysaccharide to the protein carrier, avoiding both the T-cell and B-cell epithelium, so it's to optimally present both the polysaccharide and proteins as immune. We look forward to providing guidance on the anticipated IND submission timing in the second half. With that, I'll turn it over to Jeff to provide a fax CG program. Thanks, Jim.

That's a one leverages our proprietary conserve polysaccharide androgen conjugated to a group a strep specific protein carrier.

Site specific conjugation technology allows us to precisely bond the polysaccharides the protein carrier avoiding both the T cell and B cell epitope.

Ultimately presents both a polysaccharide in protein to the immune system.

We look forward to providing guidance on the anticipated INV submission timing in the second half of 2022.

With that I'll turn it over to Jeff to provide our CV program update.

Thanks <unk>.

<unk> is our novel therapeutic vaccine candidate designed to treat periodontal disease.

Leverage is a key application of our cell free protein synthesis platform, which is the ability to make tough to make protein antigens.

Periodontal disease impacts approximately 65 million adults in the United States.

Globally severe periodontal disease, FX, 10% to 15% of the adult population, resulting in productivity losses that are estimated at nearly $54 billion per year.

Thanks, PGE targets portion alone exchange about the key pathogen responsible for paradigm titles.

<unk> incorporates protein antigens that we believe are uniquely enabled with our technology due to their inability to be produced and conventional product production vectors.

Either at all or at sufficient to permit commercial scale supply.

We continue to make progress on our early stage work for this program and as Greg shared or planning to nominate a final backs PGE candidate by the end of 2022.

Jeff Fairman: Beyond our named programs, we continue to leverage our novel platform to develop new vaccine candidates to prevent or treat bacterial infections. The XPRESS-CS cell-free protein synthesis platform and strain-promoted click chemistry allow us to produce vaccines that are uniquely capable of breaking down bacteria's complex defense mechanisms while preserving immunogenicity.

Beyond our named programs, we continue to leverage our novel platform to develop new vaccine candidates to prevent or treat bacterial infection.

Express T cell free protein synthesis platform.

Strained promoted click chemistry allow us to produce vaccines that are uniquely capable of breaking down that curious complex defense mechanisms, while preserving immunogenicity.

Numerous papers were published in 2021, which has validated our platform approach.

I would now like to turn the call over to Andrew who will provide a financial update.

Great. Thanks, Jeff I'll briefly cover a few financial points before turning it over to grant for our closing remarks.

The increase in G&A expenses was driven primarily by costs associated with our head count growth and our first full year of operations as a public company.

Andrew Guggenhime: As we look forward, we expect a substantial increase in 2022 expenses over full year and Q4 2021 annualized levels, particularly in R&D. The expected significant increase in R&D expenses is primarily a function of advancing VAX 24 into the clinic, scaling up our manufacturing activities in anticipation of a VAX 24 Phase III program, and IND enabling activities for VAX-XP. Turning to the balance sheet and cash runway, we continue to maintain a strong balance sheet. We ended 2021 with $273.1 million in cash, cash equivalents, and investments.

As we look forward, we expect a substantial increase in 2022 expenses over a full year and Q4 2021 annualized levels, particularly in R&D.

We expected significant increase in R&D expenses is primarily a function of advancing <unk> 2004 into the clinic scaling up our manufacturing activities in anticipation of about 24 phase III program and.

IND, enabling activities for <unk> XP.

Turning to the balance sheet and cash runway, we continue to maintain a strong balance sheet. We ended 2021 with $273 1 million in cash cash equivalents and investments and earlier. This year, we completed a follow on offering in which we raised an estimated $107 6 million and <unk>.

Andrew Guggenhime: And earlier this year, we completed a follow-on offering in which we raised an estimated $107.6 million in net proceeds. Going forward, we expect that our balance sheet will be sufficient to fund our operating expenses and capital expenditure requirements through at least 12 months past the announcement of the top line data from our phase one, two clinical study of act 24 and adults. [inaudible] We will continue to remain disciplined in our allocation of capital based on our priorities and progress. 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. Thanks, Andrew.

Net proceeds.

We will continue to remain disciplined in our allocation of capital based on our priorities and progress.

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.

Brent.

Grant Pickering: What we have achieved over the past year has been remarkable, given the level of complexity associated with manufacturing a 24-valent PCV, and I would like to recognize the entire Vaxcyte team and our partners at Lonza for their many contributions. The coming year is an important one for the company, and we will remain focused on executing the Phase 1-2 VAX-24 clinical study to announce the anticipated top-line data by year-end, expanding the Vax24 clinical program into additional populations and preparing for manufacturing scale-up and late-stage development, investing in VaxXP to ensure optionality with our PCB franchise, and continuing to make progress with VaxA1 and VaxPG. We look forward to sharing further updates as the year progresses and appreciate your interest by joining us today. With that, let's take take some questions. Operator?

Thanks, Andrew what we have achieved over the past year has been remarkable given the level of complexity associated with manufacturing of 24, valent PCV and I would like to recognize the entire <unk> team and our partners at <unk> for their many contributions the coming year is an important one for the company and we will remain focused on.

Executing the phase one to <unk> 24 clinical study to announce the anticipated top line data by year end.

Expanding the Vacs 24 clinical program into additional populations and preparing for manufacturing scale up and late stage development.

Investing in <unk> to ensure optionality with our PCB franchise and continue to make progress with <unk> and <unk> we.

We look forward to sharing further updates as the year progresses and appreciate your interest by joining us today with that let's take some questions operator.

Operator: Thank you. Ladies and gentlemen, if you wish to register for a question for today's question and answer session, you will need to press the one key on your touchtone telephone. If your question has been answered and you wish to withdraw your polling request, you may do so by pressing the pound key.

Thank you, ladies and gentlemen, if you wish to register for a question or today's question and answer session. You will need to press. The one key on your Touchtone telephone. If your question has been answered and you wish to withdraw your poling requests you may do so by pressing the balance sheet. If you are using a speakerphone please pick up.

Operator: If you are using a speakerphone, please pick up your handset before entering your request. One moment, please, for our first question. Our first question comes from Pravan Patel with Bank of America. He may proceed with your question. Hi everyone, thanks for taking my questions. So my first question is, what would management view as a highly positive outcome from its phase one adult vaccine study? And what are the key parameters, why, with which management will judge the success of the trial?

Your.

Handset before entering your request one moment please for our first question.

Pavan Patel: and then for the multi-gallon pneumococcal vaccine development, what are your latest thoughts on the sort of product profile needed to facilitate a shingricks-like winter takes all market? Thanks for that question, Pub, and was that it? Okay, very good. So two parts to that one. I'll let Jim, the large chief operating officer, answer the question with regard to what we would consider a success out of the phase one, two study. Jim, do you want to go ahead?

Our first question comes from Pavan.

<unk> with Bank of America, you May proceed with your question.

Hi, everyone. Thanks for taking my questions.

So my first question is what would management view as a highly positive outcome from its phase one adult vaccine study and what are the key parameters.

Why with which management will judge the success of the of the trial.

And then for the multi valent pneumococcal vaccine development what are your latest thoughts on the sort of product profile needed stability.

<unk> like winner takes all market scenario.

Thanks for that question.

Was that it.

Yep.

Grant Pickering: Sure. So in the phase one, two, as I said on the call, we're going to be starting with a phase one safety analysis, and then we're going to be shifting quickly in the phase two. For the phase two, we will be doing a comparison of the immunogenicity between our Vax24 and PCV20. I think what we are expecting is because of our platform, because of our site-specific conjugation that we're going to be able to achieve a geometric mean ratio that is at least as good if not better than PCV20 on a serotype by serotype base. And that's what we'll be looking at.

Yes, okay very good.

Two parts to that one I'll, let Jim <unk>, our Chief operating officer answer the question with regard to what we would consider a success out of the phase one two study.

Sure. So in the phase one two as I said on the call.

Starting with a phase one safety analysis, and then we're going to be shifting quickly in the phase II.

For the phase III.

We'll be doing a comparison of the immunogenicity between.

<unk> 24 in PCB 'twenty.

What we are expecting is because of our platform because of our site specific conjugation that we're going to be able to achieve a geometric mean ratio that is at least as good if not better than PCB.

'twenty on a serotype by serotype basis.

And then that's what we'll be looking at obviously, we will be doing a dose.

Joyce to move into phase III, So we will be making the choice of which dose to move forward.

But just to mention that even if we arent able to demonstrate superiority on a stereotype by serotype basis. The FDA has set a requirement of having at least half the serotype response.

As the standard of care to be able to move forward to a phase III and ultimately to licensure. So even if we're not able to achieve superiority. We believe we've got a large room, where we can make a sufficient immune response and move forward.

Grant Pickering: And then with regard to the second part as it relates to potentially getting Vax24 on track for a preferred recommendation a la Shingrix's recommendation relative to Zostavax. Yeah, I think there are two key aspects of why we think that Vax24 is well positioned to potentially obtain a preferred recommendation. And that is the relative incremental coverage that Vax24 could provide over and above PCV20. So, the 10 to 15% advantage that Prevnar20 had relative to the 15-valent vaccine from Merck, which allowed it to be recommended as a standalone vaccine, is similar to the amount of coverage that we would expect to have over and above PCV20. So, that's one aspect of the reason why we have a high level of confidence.

Great.

And then with regard to your second the second part.

As it relates to potentially getting back 24 on track for our preferred recommendation, our <unk> recommendation relative to Zostavax. Yeah. I mean, I think there are two key aspects of why we think that <unk> 24 is well positioned to potentially obtain.

Our preferred recommendation and that is the relative incremental coverage that <unk> 24 could provide over and above <unk>.

<unk> 'twenty.

So the 10% to 15%.

Advantage that <unk> had relative to the 15 valent vaccine from Merck, which allowed it to be recommended as a stand alone vaccine.

Similar to the amount of coverage that we would expect.

To have over and above the <unk>. So thats one aspect of the reason why we have a level of confidence, but then there is an important additional dimension.

Grant Pickering: But then there's an important additional dimension, which is the current standard of care recommendation in adults from the ACIP is either PCV20 or PCV15 plus Pneumovax. So the reality is that the current coverage of either of the PCVs is not adequate to fully cover the 23 strains that are in Pneumovax. And that older polysaccharide-only vaccine, you know, continues to be part of the regimen. And with a 24-valent PCV like Vax24, it would entirely eclipse the coverage of Pneumovax23 in a way that could allow the ACIP to remove that vaccine altogether, which would obviously simplify the regimen to a single vaccine altogether and would open the door to a prime boost for PCVs in the adult population, which, of course And that's been a key sticking point that's prevented a lowering of the universal recommendation age below 65.

Which is the current standard of care recommendation in adults from the ACI P is either PCB 20, or PCB 15, plus pneumovax. So the reality is that the current coverage of either of the Pcbs are not adequate to fully cover the 'twenty three strains that are in <unk>.

<unk> and that older polysaccharide only vaccine continues to be part of the regimen.

And with a 24 valent PCV like Max 24, it would entirely eclipse the coverage of Pneumovax 23 in a way that could allow the ACI Pete to remove that vaccine altogether, which would obviously simplify the regimen to a single vaccine altogether and would open.

The door to a prime boost for Pcbs in the adult population, which of course is the same approach that we use in children and that's been a key sticking point that's prevented a lowering of the universal recommendation age below 65, there are discussions at the last October .

Grant Pickering: You know, there were discussions at the last October ACIP meeting where they discussed lowering the age down to 50. But there was real anxiety about having Pneumovax used in a way that could interfere with a boost with a PCV later on. So. If we can deliver that kind of incremental coverage, which we believe we will, and be able to remove Pneumovax from the regimen, we think that could be a compelling argument that could justify a preferred recommendation in the adult market. Thank you so much.

ACI meeting, where they discussed lowering the age down to 50, but there was real anxiety about having pneumovax used in a way that could interfere with a boost with the PCB later on so.

Thank you so much.

Grant Pickering: Yep, thanks for- Thank you, our next question comes from Louise Chen with Cantor. You may proceed with your question. Hi, congratulations on all the progress this quarter and thanks for taking my questions. So first question I have for you is, ASIP recommendation aside, how do you think you will effectively compete with some of these larger companies in the space? And then secondly, how do you see the market playing out if both your Vax24 and Vax.., make it to the market? How do you plan to market two of them together?

Yeah. Thanks, Bob.

Thank you. Our next question comes from Louise Chen with Cantor You May proceed with your question.

Louise Chen: And then last question I have for you is just how did you think about that four-fold rise in antibody titer corresponding to good efficacy in the phase two portion of your Vax24 study? Thank you. Great. Thank you, Louise. I think that was a three-part question. So how are we going to compete with the oligopolists? How would we think about Vax24 and VaxXP potentially coexisting? And then there is the fourfold rise piece.

Hi, congratulations on all the progress this quarter and thanks for taking my questions.

First question I had for you is afib recommendation.

How do you think you will effectively compete with some of these larger companies in the space.

And then secondly, how do you see the market playing out if youre back 24, and Max XP may.

It to the market how do you plan to market two of them together and then last question I have for you is just how did you think about that four fold rise in antibody titer corresponding to assess the efficacy in the phase two portion of your back 24 study. Thank you.

Great. Thank you Louise I'll take that with a three part question. So how are we going to compete with the oligopolistic.

How would we think about <unk> 24 and <unk>.

Potentially coexisting and then the poor fold rise piece, so maybe I can take the first two parts of that and then ask Jim to comment on the rationale for the fourfold rise piece. So yes I think.

Obviously.

Pfizer and Merck are extremely familiar competitors, who have a very vested interest in maintaining their stake, but I think.

The way that we view this as there has been substantial precedent over the years for broader spectrum vaccines usurping lesser valent vaccines, and we've seen that time and time again.

It was trivalent to quadrivalent flu vaccine, whether it was gardasil versus server acts in the HPV market, which led to the greater coverage from Gardasil.

Eventually, resulting in a withdrawal of use of <unk> in the U S altogether.

So.

The path that we're on.

Is one where we are able to leverage the same basic components that have resulted in such an effective approach to prevent these types of bacterial infections, but we found a way to.

Two the key decision makers.

Both from a regulatory perspective, and then a conduct perspective through the CIP. So if we can deliver that kind of profile and if we can deliver the sort of volume that would allow for a supply of universal recommendations sort of magnitude I think it will put us in a really strong position and this is not a market.

Grant Pickering: And this is not a market where you need to deploy, you know, thousands of sales reps to drive adoption. It's really critical singular bodies, you know, in each sovereign nation that are making these decisions about coverage. So I think we're well positioned, and we've been well capitalized, and we're not going to sell ourselves short, but that's kind of how we're thinking about it in this moment. Obviously, we've got a long way to go.

<unk>, where you need to deploy thousands of sales reps to drive adoption, it's really critical singular bodies and each sovereign nation that are making these decisions about coverage. So I think we're well positioned and we've been well capitalized and we're not going to sell ourselves short.

That's kind of how we're thinking about it in this moment, obviously, we've got a long way to go.

Grant Pickering: As it relates to, Vax24 and VaxXP, you know, we've realized that we do have this unique ability to add incremental coverage without facing the same immunological diminution that the conventional chemistry has resulted in. And so we do have VaxXP, you know, waiting in the wings, if you will. But in terms of actually bringing the products to market, you know, you do have this cascade that occurs by virtue of initially developing these vaccines in the adult population.

As it relates to.

<unk> 24, and backs XP, we've realized that we do have this unique ability to add incremental coverage without facing the same immuno immunological diminution that conventional chemistry has resulted in and so we.

We do have.

Vacs XP waiting in the wings, if you will but in terms of actually bringing the products to market. You do have this cascade that occurs by virtue of initially developing these vaccines in the adult population. It's a shorter path. It's a single dose in this moment as opposed to the pediatric indication.

Grant Pickering: It's a shorter path. It's a single dose at this moment, as opposed to the pediatric indication where they receive four vaccines over a 15-month time frame. So it naturally puts the adult pace of development ahead of infants.

Where they received for vaccines over 15 months.

Timeframe. So it naturally puts adult pace of development ahead of intense so you could imagine a scenario, where if everything goes as we hope.

Grant Pickering: So you could imagine a scenario where if everything goes as we hope, where Vax24 could obtain initially an adult approval and recommendation, followed by an infant approval and recommendation, and then VaxXP could come in thereafter in adults and then again cascade into infants. So there is a natural progression to how these work and that's why we want to keep VaxXP within striking distance because these vaccines have been so effective historically that when you vaccinate with them, those included strains are effectively taken out of circulation and it only makes those incremental strains more epidemiologically relevant and that's the rationale behind VaxXP as a fast follower and that's how we see them cascading into the market but to have you know both in the same indication would be unlikely. It would be more of a replacement sort of strategy.

<unk> 24 could obtain initially in adult.

Approval and recommendation followed by <unk>.

<unk> approval and recommendation.

And then <unk> XP could come in thereafter in adults and then again cascade into infants. So there is a natural progression to how these work and that's why we want to keep backs XP within striking distance because these vaccines have been so effective historically when that when you vaccinate with them those <unk>.

<unk> strains are effectively taken out of circulation and it only makes those incremental strains.

Sure.

E mail logically relevant and that's the rationale behind backs XP as a fast follower and Thats, how we see them cascading into the market but.

Both in the same indication would be unlikely it would be more of a replacement sort of strategy.

Grant Pickering: So if that answers the first two parts, I'll ask Jim to comment on the four-fold rise approach. Sure. Thanks, Grant. For the four-fold rise, it's sort of a two-part answer.

So if that answers the first two parts I'll ask Jim to comment on the Port fold rise China.

Sure. Thanks Grant.

For the fourth will rise.

It's sort of a two part answer the first as we looked at the recent approvals of PCB <unk> and PCB 15, PCB 20 used a comparison of non inferiority versus pneumovax to determine whether or not they could get licensure. However, PCB 15 looked at fourfold rise so they looked at a statistically soup.

Jim Wassil: The first is we looked at the recent approvals of PCV20 and PCV15. PCV20 used a comparison of non-inferiority versus Pneumovax to determine whether or not they could get licensure. However, PCV15 looked at four-fold rise, so they looked at a statistically superior four-fold rise versus PCV13.

Here are four fold rise versus PCP 13, So we had two options available to us based on precedent to be able to we felt to get.

Jim Wassil: So we had two options available to us based on precedent to be able, we felt, to get an approval for Vax24. Now with the ACIP in October making a recommendation, we were going to do the comparison and we still are doing a comparison against PCV20. Well, the recommendation is to use PCV15 and Pneumovax or PCV20.

An approval for <unk> 24.

Now with the <unk>.

October making a recommendation we were going to do the comparison and we still are doing a comparison against PCB 20, well. The recommendation is to use PCB <unk> and pneumovax or PCB 20, since PCB 20 of our comparator, we decided to use that and to go with the poor full rise.

Jim Wassil: Since PCV20 is our comparator, we decided to use that and go with the four-fold rise, and we believe that, based on the regulatory precedent, as well as the recommendation by the ACIP, will give us a good indication of success for phase three. Okay. Thanks, Louise. Thank you. And as a reminder, to ask a question, you'll need to press star 1 on your telephone.

We believe that that based on the regulatory precedent as well as the recommendation by the ACP will give us a good indication of success for phase III.

Okay.

Luis.

Okay.

Thank you and as a reminder to ask a question you will need to press Star woman and telephone. Our next question comes from Joseph Stringer with Needham and company. You May proceed with your question.

Operator: Our next question comes from Joseph Stringer with Needham & Company. You may proceed with your question. Hi, this is Ben Ricard on behalf of Joey Stringer.

Hi, this is been ricard on for Joey Stringer.

Joseph Stringer: Thanks for taking our question. Just one about sort of the COVID-related impacts. If you could just talk about any potential impacts on the upcoming VAX-24 trial based on having a larger-than-anticipated winter COVID season or a smaller one coming up. Thanks a lot. So this is Jim Wassil.

For taking my question.

Just one about sort of the COVID-19 related impacts if you could just talk about.

Any potential impacts on the upcoming backs 24 trial based on having a larger than anticipated winter COVID-19 season, or a smaller one coming up thanks a lot.

Yes.

So this is Jim last one, but we're seeing the clinical program as well.

We don't expect Covid to have an impact our initial studies in 18 to 49 year olds.

The healthy 18 to 49 year old cohort is sufficiently large that we don't foresee that that will have any.

Issues with enrollment.

Phase II is a 50% to 64 same thing.

Sufficient cohort there.

Jim Wassil: Our main exclusion criteria for enrollment is actually not having an experimental vaccine either before, during, or six months after. Given that the majority of individuals have already received all of their COVID shots, we are able to enroll sufficient subjects without having any exclusions. So we feel we'll be able to move along just as fast as we originally anticipated.

Our main exclusion criteria for enrollment is actually.

Not having an experimental vaccine either before during or six months after.

Given the majority of individuals have already received all of their Covid shot.

We are able to enroll sufficient subjects without having any exclusion. So we feel we'll be able to move along just as fast as we originally anticipated.

Grant Pickering: Yeah, and it may be worth pointing out, Ben, that, you know, there isn't a seasonal component to executing these trials. One of the nice aspects of developing a follow-on pneumococcal conjugate vaccine is that these are just studies focused on safety and immunogenicity. So there isn't an infection rate component to this. We don't have to follow the subjects who've been vaccinated to confirm that they don't contract strep pneumonia.

Yes, and it may be worth pointing out than that.

There isn't a seasonal component to executing these trials.

One of the nice aspects of developing a follow on pneumococcal conjugate vaccine is that these are just studies focused on safety and immunogenicity. So there isn't an infection rate component to this we don't have to follow the.

The subjects who've been vaccinated to confirm that they don't contract.

Pneumonia infection. These are just immunizing the subjects and following them for 30 days in this phase <unk> study.

Grant Pickering: These are just immunizing the subjects and following them for 30 days in this phase 1, 2 study, the phase 2 study in particular, where we're looking at immunogenicity. So we don't need to run those big field efficacy studies that are the convention when you have to show efficacy. These are validated surrogate immune endpoints. So that's not an aspect of executing these particular trials.

The phase II study in particular, we're looking at Immunogenicity. So we don't need to run those big field efficacy studies that are the convention. When you have to show efficacy. These are validated surrogate endpoints. So that's not an aspect of of executing these particular trials.

Grant Pickering: Great. Thank you. Thanks, Beth. Thank you, and I'm not showing any further questions at this time. I would now like to turn the call back over to Grant Pickering for any further remarks. Well, I just want to thank you all for your interest and for participating in the call today, and have a good rest of your week. Thank you very much. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Great. Thank you.

Thanks Pat.

Thank you and I'm not showing any further questions. At this time I would now like to turn the call back over to Gregg <unk> for any further remarks.

Well I just want to thank you all for your <unk>.

Interest and for participating in the call today and.

Have a good rest of your week.

Thank you very much.

Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.

Q4 2021 Vaxcyte Inc Earnings Call

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