Q2 2021 Arcturus Therapeutics Holdings Inc Earnings Call

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Operator: Greetings and welcome to the Arcturis Therapeutics second quarter 2021 earnings call. At this time, all participants are in a listen-only mode. Question and Answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press Star Zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce Netta Safarzada, Senior Director and Head of Investor Relations, Public Relations, and Marketing. Thank you. You may begin.

Greetings and welcome to the Arcturus Therapeutics second quarter 2021 earnings call. At this time, all participants are in a listen only mode.

On an answer session will follow the formal presentation.

If anyone should require operator assistance during the conference. Please press star zero on your telephone keypad.

As a reminder, this conference is being recorded.

It is now my pleasure to introduce notice the parts of that senior director and head of Investor Relations Public relations and marketing. Thank you you may begin.

Thank you operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO, Andy Sassine CFO. Dr. Pacifico Lassi is so on seal and Dr. Steve Hughes, our Chief Medical Officer.

Neda Safarzadeh: Thank you, operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO, Andy Sassine, CFO, Dr. Pat Chivakula, CSO, and C.O., and Dr. Steve Hughes, our chief medical officer. Before we begin, I would like to remind everyone that, except for statements of historical facts, the statements made by management, and any responses to questions on this conference call constitute forward-looking statements that involve potential risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995.

Before we begin I vote luxury remind everyone that except for statements of historical facts. The statements made by management on any responses to questions. On this conference call constitute forward looking statements that involve potential risks and uncertainties for purposes of the safe Harbor provided by the private Securities litigation.

Asian Reform Act up 1995.

Any statements other than the statements of historical facts included in this communication, including those regarding our plans anticipated or potential development manufacturing and commercialization activities or events, including with respect to funding initiation design or completion of.

Neda Safarzadeh: Any statements other than the statements of historical facts included in this communication, including those regarding our planned, anticipated, or potential development, manufacturing, and commercialization activities, or events, including with respect to funding, initiation, design, or completion of clinical trials, the likelihood of success of the company's coronavirus COVID-19 vaccine candidates or other product candidates, the company's manufacturing and other operations, and the company's current and future cash and financial position are forward Actual results and performance could differ materially from those projected in any forward-looking statements as a result of many factors, including, without limitation, an inability to develop and market product candidates, unexpected clinical results, and general market conditions that may prevent such achievements or performance.

Clinical trials the likelihood of success of the company's core Novartis COVID-19 vaccine candidates or other product candidates, the company's manufacturing and other operations and the company's current and future cash and financial position our forward looking statements.

Actual results on per formats could differ materially from those projected in any forward looking statements as a result of many factors, including without limitation and ability to develop and market product candidates unexpected clinical results and general market conditions that may.

It prevents such achievements or performance.

So I try to movements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading risk factors in Arcturus. Its most recent annual report on form 10-K, with the SEC and in other filings that Arcturus makes with the SEC.

Neda Safarzadeh: Such achievements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading risk factor in Artress's most recent annual report on Form 10K with the SEC and in other filings that ArtRES makes with the SEC. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events, or circumstances, or otherwise. Now, it is my pleasure to pass the call to Joe Payne, President and CEO. Joe, please go ahead.

Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward looking statements, which speak only as of the day to day were made whether as a result of new information future events or circumstances or other.

Wise.

Now it is my pleasure to pass the call to Joe Payne, President and CEO Joe. Please go ahead.

Joseph E. Payne: Thank you, Netta. Good afternoon to all.

Thank you Anita and good afternoon to all and thank you for joining the <unk> the.

Joseph E. Payne: Thank you for joining the Arcturus quarterly call today. Arcturus is developing a powerful new class of MRN-based vaccines and therapeutics. Over the last decade, our team has developed a differentiated platform technology, as well as highly promising pipeline candidates. We believe that our approach has the potential to directly address the underlying molecular basis of many serious diseases and could make a transformative difference in the lives of patients confronting many life-threatening conditions.

The Arcturus this quarterly call today.

Arcturus is developing a powerful new class of mrna based vaccines and therapeutics over the last decade. Our team has developed a differentiated platform technology as well as highly promising pipeline candidates.

We believe that our approach has the potential to directly address the underlying molecular basis of many serious diseases and could make a transformative difference to the lives of patients confronting many life threatening conditions.

Joseph E. Payne: This quarter has been an exceptionally productive period for Arcturus, where we have made substantial progress with our MRN-based vaccines, our therapeutic programs, as well as the advancement of our underlying core technologies. In addition, we have also been effective at obtaining non-dilutive financial support to drive our pipeline forward in a very capital-efficient manner.

This quarter has been on exceptionally productive period for Arcturus, where we have made substantial progress with our mrna based vaccines are therapeutic programs as well as the advancement of our underlying core technologies. In addition, we have also been effective at obtaining non dilutive financial support.

To drive our pipeline forward in a very capital efficient manner all.

Joseph E. Payne: I'll begin with the progress we've made with our vaccine programs targeting COVID-19 and starting with ARCT-021, our lead program. ARCT-021 is a differentiated, single-shot COVID-19 MRNA vaccine candidate that clinically exhibits a promising T-cell response profile, and this profile is attributed to the star, or self-transcribing and replicating MRNA technology.

I'll begin with a discussion of the progress we've made with our vaccine programs targeting COVID-19, and starting with <unk> T O 2.1 or most of it.

Lead program.

<unk> 021, as a differentiated single shot COVID-19 mrna vaccine candidate that clinically exhibits a promising T cell response profile and this profile is attributed to the star or self transcribing and replicating mrna technology.

Joseph E. Payne: We believe that our approach may provide meaningful advantages compared to currently available vaccines for COVID-19. We believe this single-shot dosing regimen would be highly favored, even required in certain regions of the world, compared to the two-shot regimens employed with currently authorized MRNA vaccines for emergency use. We have an ongoing fully enrolled ARCT-O21 Phase 2 study. We have previously discussed the encouraging preliminary tolerability and immunogenicity data from this study, as well as from our prior completed Phase 1 study.

We believe that our approach may provide meaningful advantages compared to currently available vaccines for COVID-19, we believe this single single shot dosing regimen would be highly favored even required in certain regions of the world compared to the 2 shot regimens employed with currently authorized mrna vaccines for.

For emergency use.

We have an ongoing fully enrolled on <unk> 1 phase III study, we have previously discussed the encouraging preliminary tolerability and Immunogenicity data from this study as well as from our prior completed phase 1 study specifically immunogenicity data from this study showed greater than 90 per cent seroconversion.

Joseph E. Payne: Specifically, immunogenicity data from the study shows greater than 90% serial conversion for IgG antibodies binding to the full-link spike protein at day 28 following a single-shot dose of ARCTO21. The full results from the Phase II study remain blinded, and we expect to obtain those data later this year.

<unk> antibodies binding to the full length Spike protein at day 28, following a single shot dose of <unk>..1 the full results from the phase 2 study remained blinded and we expect to obtain those data later this year.

Joseph E. Payne: Based on the available support data, we've made excellent progress advancing ARCT-021 to Phase 3 development. We are very pleased to report today that ARCT 021 has been selected by a global entity for inclusion in a phase 3 vaccine trial against COVID-19. And we expect this study to begin imminently. After the specifics of the Phase 3 study are announced, we will provide more details with respect to this program. We can disclose that this will be a multinational, placebo-controlled phase three study designed to enroll tens of thousands of participants and will evaluate a five-micogram dose of ARCTO21 administered as a single injection regimen. Again, this is a differentiating feature of ARCTO21.

Based on the available supportive data, we've made excellent progress advancing <unk> to phase III development.

We are very pleased to report today that <unk> 21 has been selected by a global entity for inclusion in our phase III vaccine trial against COVID-19, and we expect this study to begin imminently. After the specifics of the Phase III study are announced we will provide more details with respect to this.

Program.

We can disclose that this will be a multinational placebo controlled phase III study designed to enroll tens of thousands of participants and we will evaluate a 5 microgram dose of <unk>, our CTO to 1 administered as a single injection regimen again. This is a differentiating feature of <unk> to 1.

Joseph E. Payne: Importantly, this large Phase 3 study, upon commencement, will be sponsored and funded by the global entity. We are understandably very grateful for their support, and we very much look forward to the initiation of the ARCTO 2-1 Phase 3 study, as we look to bring this vaccine to communities in need across the world as rapidly as possible. I will also note that, outside of Singapore, Vietnam, and Israel, Arcturus retains full global economic and distribution rights to ARCTO21.

Importantly, this large phase III study upon commencement will be sponsored and funded by the global entity.

We are understandably very grateful for their support and we very much look forward to the initiation of the <unk> 1 phase III study.

As we look to bring this vaccine to communities in need across the world as rapidly as possible.

I will also note that outside of Singapore, Vietnam, and Israel, Arcturus retains full global economic and distribution rights to <unk> 1.

Joseph E. Payne: We've also made progress providing access to our vaccine technology in order to broaden the ability of individuals across the world to access COVID-19 vaccines. Earlier this month, we announced an agreement within BioCare to establish a manufacturing facility in Vietnam for the manufacturer of Arc Turus' investigational COVID-19 vaccine. VinBioCare will build out a manufacturing facility in Hanoi, and Arcturus will provide access to its proprietary manufacturing technology. In exchange, VinBioCare has made a substantial $40 million upfront payment to Arc Puris.

We've also made progress providing access to our vaccine technology and in order to broaden the ability of individuals across the world to access COVID-19 vaccines earlier this month.

We announced an agreement within bio care to establish a manufacturing facility in Vietnam from the manufacturer of Arcturus has investigational COVID-19 vaccines.

<unk> will build out our manufacturing facility in Hanoi, and Arcturus will provide access to our proprietary manufacturing technologies and.

In exchange <unk> has made a substantial 40 million dollar upfront payment to arcturus.

Joseph E. Payne: VinBiopair will also purchase the MRNA drug substance from Arcturus and pay a royalty on the doses manufactured. This is a strategically important transaction for Arcturus, and we believe it is also financially attractive, providing valuable capital to support the manufacturing efforts and continued development of our pipeline.

Then <unk> will also purchase the mrna drug substance from Arcturus and pay a royalty on the doses manufactured.

This is strategically important this is a strategically important transaction for arcturus and we believe this is also financially attractive providing valuable capital to support the manufacturing efforts and continued development of our pipeline.

Joseph E. Payne: While we have driven forward our lead vaccine candidate, along with our manufacturing capacity, we've also advanced our next generation self-amplifying M RNA vaccines targeting the highly prevalent SARS-COV-2 variants that are circulating across our planet. As we all know, cases have been growing at a concerning rate, driven in large part by the highly transmissible Delta variant. Here in the U.S., daily cases again topped 100,000, and alarming increases in transmission have been seen in many other countries across the world.

While we have driven forward our lead vaccine candidate along with our manufacturing capacity. We've also advanced on next generation self amplifying mrna vaccines targeting the highly prevalent Sars COVID-19.2 variance that are circulating across our planet.

As we all know cases have been growing at a concerning rate driven in large part by the highly transmissible Delta variant here in the U S Daily cases again topped 100000.

And alarming increases in transmission have been seen in many other countries across the world.

Joseph E. Payne: Our expectation is that this delta variant and additional SARS-COV-2 variants will remain endemic in the human population for years to come. Fortunately, we at Arcturus can rapidly update our MRNA vaccines as needed to address variants of concern. We identified ARCT 154, a next-generation two-shot MRNA vaccine that has been optimized to elicit high levels of neutralizing antibodies against this delta variant. Preclinical data has shown that our next generation vaccines result in substantially increased levels of neutralizing antibodies to the variants of concern. If the observed increases of neutralizing antibodies in primates translate to similar fold increases in humans, then ARCT 154 could be an excellent vaccine to protect against the variants of concern, including the Delta variant.

Our expectation is that this delta variant and additional <unk> variance will remain endemic in the human population for years to come.

Fortunately, we at Arcturus can rapidly update our mrna vaccines as needed to address variance of concern.

We identified <unk> $1.50 for a next generation 2 shot mrna vaccine that has been optimized to illicit high levels of neutralizing antibodies against the variance.

Preclinical data has shown that our next generation vaccines result in substantially increased levels of neutralizing antibodies to the variance of concern.

If the observed increases of neutralizing antibodies in primates translate to similar fold increases in humans, then a RCT $1.54 could be an excellent vaccine to protect against the variance of concern, including the Delta variant.

Joseph E. Payne: ARCT 154 utilizes STAR technology, that is, the self-amplifying MRNA molecule. Therefore, it retains a promising T-cell profile in primates as well. In all of our studies, preclinically and clinically, we observe self-amplifying MRNA to generate better T-cell responses than conventional MRNA. The robust T-cell responses are attributed to the self-amplifying MRN mechanism of antigen expression. I'll now turn the time over to Dr. Steve Hughes, our chief medical officer here at Arcturus, to discuss our efforts targeting viral variants in more detail, including our clinical development progress, as well as the progress we have made with our MRNA therapeutics franchise.

<unk> $1.54 utilizes Starr technology, that's the self amplifying mrna molecule. Therefore, it retains a promising T cell profile in primates as well.

And all of our studies pre clinically and clinically we observed self amplifying mrna to generate better T cell responses than conventional mrna.

Our robust T cell responses are attributed to the self amplifying mrna mechanism of antigen expression.

I'll now turn the time over to Dr. Steve Hughes, our Chief Medical Officer here at Arcturus to discuss our efforts targeting viral variance in more detail, including our clinical development progress as well as the progress we have made with our mrna therapeutic franchise, Steve Thanks Jack.

Steve Hughes: I'll start with a progress update on our novel vaccine programs designed to target widely circulating SARS-COV2 variants, including the highly contagious delta variant that is now prominent across many countries. Arcturus has advanced ARCT 154 and ARCT-165 to next-generation star MRNE vapsing candidates that have been designed to effectively target SARS-CoV2 variants of concern. ARCT 154 utilizes an optimized star MRI sequence where we have incorporated multiple modifications, including for stability and increased translation, as well as changes made to increase the immunogenicity of the spike protein. Preclinical data demonstrate strong neutralizing immunogenicity in non-human primates to SARS-CoV2, alpha, beta, gamma, and delta variants. And we have provided additional experimental data in the press release issued this morning.

Start with a progress update on our novel vaccine programs designed to target widely circulating Sars COVID-19.2 variants, including the highly contagious Delta variant that is now permanent across many countries.

Arcturus has advanced <unk> $1.54, and <unk> 65 to next generation store mrna vaccine candidates that have been designed to effectively target Sars COVID-19.2 variance of concern.

<unk> 154 utilizes an optimized store MLR on a sequence, where we have incorporated multiple modifications, including for stability and increased translation as well as changes made to increase the immunogenicity of the spike protein <unk>.

Preclinical data demonstrates strong neutralizing immunogenicity in non human primates to Sars Covid, 2 alpha beta and gamma and Delta variance and we have provided additional experimental data in the press release issued this morning.

Steve Hughes: Preclinical non-human primate data demonstrate that ARCT 154 elicits meaningfully higher neutralizing antibodies than ARCT 021, including neutralizing antibodies against the Delta variant. Also, as we observed with ARCT 021, we have observed robust T-cell responses with ARCT-154. Based on this strong, supportive preclinical data, we have taken steps to rapidly advance these novel vaccine programs towards clinical development in multiple studies. Earlier this month, we announced approval of a clinical trial application from the Singapore Health Sciences Authority to enable advancement of ARCT 154 and ARCT 165 into a Phase 1-2 clinical trial. This study will evaluate the vaccines both as a primary vaccination series and as a booster following initial vaccination with commonity.

Preclinical non human primate data demonstrate that <unk> $1.54, and this is meaningfully higher on neutralizing antibodies, then <unk> zone, 2.1 including neutralizing antibodies against the Delta there and also as we observed with <unk> zero to 1 we have observed robust T cell.

As with <unk> 154.

Based on this strong supportive preclinical data, we have taken steps to rapidly advance.

Novel vaccine programs towards clinical development and multiple studies.

Earlier this month, we announced approval from a clinical trial application from the Singapore Health Sciences authority to enable advancement of <unk> 154, and <unk> 65 into a phase 1.2 clinical trial. This study will evaluate the vaccines. Both is upon me vaccination Suez and as a booster following initial explanation.

And with commodity.

Steve Hughes: We have been working with our partner in BioCare to initiate a pivotal trial with ARCT 154, and CTA approval from the Vietnam Ministry of Health was recently received to advance ARCT 154 into a phase 123 clinical study. The trial, which is being sponsored and funded by VimbioCare, is a randomized and double-blind placebo control design that will assess the safety, immunogenicity, and efficacy of the drug in up to 21,000 participants, with potential for emergency use authorization by the Vietnam Ministry of Health as early as December 2021.

We have been working with our partner <unk> to initiate a pivotal trial with <unk> 154 and.

Cta approval from the Vietnam Ministry of Health was recently received to advance <unk> 154 into a phase 123 clinical study.

The trial, which is being sponsored and funded by them <unk> is a randomized observer blind placebo controlled design that will assess the safety immunogenicity and efficacy and up to 21000 participants with potential for emergency use authorization by the Ministry of health as early as December 2021.

Steve Hughes: I will now turn to ARCT 810, our therapeutic candidate for or nathine transcarbamilis or OTC deficiency. ARCT 810 utilizes the Arcturus lunar lipid-mediated delivery platform to deliver OTC messenger RNA to the lever, the primary target tissue in OTC deficiency. Expression of the normal orinthine transcarbamalyze enzyme in the liver of patients with OTC deficiency has the potential to restore urea cycle activity, preventing neurological damage and the need for liver transplantation.

I will now turn to <unk> 10.

Future candidate for on Athene trends called <unk> or OTC deficiency.

<unk> 10.

<unk> utilizes arcturus lunar lipid mediated delivery platform to deliver OTC messenger RNA to the liver.

The primary target tissue in OTC deficiency.

Expression of the normal trends called <unk> zone in the liver of patients with OTC deficiency has the potential to restore urea cycle activity, preventing neurological damage on the need for liver transplantation.

Steve Hughes: To date, we have completed a Phase 1 Healthy Volunteer Dose Escalation Study with ARCT-810, which demonstrated that administration of ARCD-810 was associated with favorable tolerability and an attractive pharmacokinetic profile up to the top dose of 0.4 milligrams per kilogram, which is within the anticipated therapeutic range based upon data from our preclinical studies. Based upon these encouraging data, we have advanced this program to mid-stage development, and last month, we obtained approval from the UK Health Research Authority to initiate a phase two multiple-dose clinical trial for ARCT-8-10, and we are currently recruiting sites.

To date, we have completed a phase 1 healthy volunteer dose escalation study with <unk> <unk>.

The study demonstrated that administration of <unk> 10 was associated with favorable Tolerability and then attractive pharmacokinetic profile up to the top dose of 4 milligrams per kilogram, which is within the anticipated therapeutic range based upon data from our preclinical studies.

Just upon these encouraging data we have advanced this program to mid stage development and last month, we obtained approval from the UK Health Research authority to initiate a phase 2 multiple dose clinical trial for <unk> 10 on we are currently recruiting sites.

Steve Hughes: The ARCT 810 Phase 2 study is a randomized, double-blind, placebo-controlled, nested, single and multiple ascending dose design that includes adolescents and adults with OTC deficiency. ARCT 810 phase 2 study interim results from a subset of participants are expected in the second half of 2022. Before I close, I will also mention that our collaborator, Ultrogenics, recently received orphan drug designation and IND allowance for a Phase 1-2 study to evaluate safety, tolerability, and efficacy of UX-053 in patients with GSD3.

<unk> hundred 10 Phase II study is a randomized double blind placebo controlled nested single and multiple ascending dose design that includes adolescents and adults with OTC deficiency.

<unk> Phase II study interim results from a subset participants are expected in the second half of 2022.

Before I close our low so I mentioned that our collaborator <unk> recently got orphan drug designation and India allowance for a phase 1.2 study to evaluate safety tolerability and efficacy of UX zone 5.3 in patients with GST 3.

Steve Hughes: And the study is expected to begin in the second half of 2021. UX-053 is an investigational MRNA-based therapy encoding full-length glycogen debranching enzyme encapsulated in a lipid nanoparticle and was developed by the Arcturus R&D team. We are very pleased to see this program advancing to clinical development. Furthermore, we believe that the progress made with UX053 represents another example of the broad application that is possible with our MRNA technology platform. I will now pass the call on to Andy, our CFO.

And the study is expected to begin in the second half of 2021.

<unk> 3 is an investigational mrna based therapy encoding full length glycogen debunching enzyme encapsulated in a lipid nanoparticle on was developed by the Arcturus R&D team.

We are very pleased to see this program advance into clinical development. Furthermore, we believe that the progress made with <unk> represents another example of the broad application that is possible with our MLR on a technology platform.

I'll now pass the call on to Andy our CFO.

Andrew H. Sassine: Thank you, Steve, and good afternoon, everyone. The press release issued earlier today includes financial statements for the second quarter of fiscal year 21 and provides a summary and analysis of year over year and sequential performance. In a consolidated balance sheet, the second column should be dated as of March 31, 2021, and not March 31, 2020. Please refer to our 10 Q for more details on financial performance. Today, I will elaborate on the major changes impacting our cost and operations as we transition to a later stage clinical company with multiple programs in our pipeline. I will also provide some details regarding our manufacturing strategy as we prepare for the potential of emergency use authorization in multiple vaccine programs. Finally, I will provide some insights regarding our cash position and expected runway.

Thank you, Steve and good afternoon, everyone.

The press release issued earlier today includes financial statements for the second quarter of fiscal year 'twenty, 1 and provides a summary and analysis of our year over year and sequential performance.

On our consolidated balance sheet. The second column should be data as of March 31, 2021, and not March 31.2020.

Please reference our 10-Q for more details on the financial performance.

Today I will elaborate on the major changes impacting on our cost and operations as we transition to a later stage clinical company with multiple programs in our pipeline.

He will also provide some details regarding our manufacturing strategy as we prepare for the potential of emergency use authorization and multiple vaccine program.

Finally, I will provide some insights regarding our cash position and expected runway.

We are fortunate that a global entity has selected our 'twenty 1 vaccine to be included on a global phase III trial.

Andrew H. Sassine: We are fortunate that a global entity has selected our ARC21 vaccine to be included in a global phase three trial, which they will sponsor and fund with participating countries. We are also very fortunate to partner our ARC-154 vaccine program with VinBioCare, who will sponsor and fund our stage phase three clinical trials targeting the Delta Variant. VinBioCare Biotechnology is a part of the VIN group, one of Vietnam's largest corporations.

Which they will sponsor and fund with participating countries.

We are also very fortunate to partner <unk> $1.54 vaccine program within bio care, who will sponsor and fund our stage phase III clinical trial targeting the Delta barragan.

<unk> biotechnology, the part of the <unk> group, 1 on Vietnam largest corporations.

Andrew H. Sassine: Partnering these two vaccines will save us well over $300 million in clinical trial expenses. I will now talk about our global manufacturing footprint. We continue to build out our global manufacturing strategy by adding two key partnerships during the quarter and expanding our capabilities with another strategic partner. We have diversified our manufacturing footprint with strategic partners in Asia, Europe, and the USA.

Partnering these 2 vaccines will save us well over $300 million in clinical trial expenses.

I will now talk about our global manufacturing footprint.

We continue to build out our global manufacturing strategy by adding 2 key partnerships during the quarter and expanding our capabilities with another strategic partner.

We have diversified our manufacturing footprint with strategic partners in Asia, Europe, and the USA.

Andrew H. Sassine: Last week, we announced a key partnership with the VIN group to produce up to 200 million doses per year in Vietnam starting in 2022. Recently, we signed a joint venture agreement with Axelide in Japan to form a joint venture, Archalis, to produce MRNA drug substance beginning in 2023. Axelit is a Japanese company that formed a comprehensive, collaborative partnership with Hitachi to develop solutions for next-generation biopharmaceuticals. We also expanded our relationship with Resci Farm in Germany to significantly expand drug product capabilities, including fill-finished production of our liopalized vaccines. We are also fortunate to have maintained strong relationships with Aldevron and Catalan in the United States and Polymune in Austria.

Last week, we announced a key partnership with <unk> group to produce up to 200 million doses per year in Vietnam, starting in 2022.

Recently, we signed a joint venture agreement with Axa lead in Japan to form a joint venture or cows to produce mrna drug substance beginning in 2023.

Actually it is a Japanese company that formed a comprehensive collaborative partnership with Hitachi to develop solutions for next generation biopharmaceutical.

We also expanded our relationship with the rest of the farm in Germany to significantly expand drug product capabilities, including fill finish production of our Lyophilize vaccines.

We are also fortunate to have continued strong relationship with al Dev wrong.

In catalyst in the United States and Poly Moon in Austria.

Andrew H. Sassine: We continue to plan for the potential that one or more of our vaccines could receive emergency use authorization later this year or early next year. Along with our global manufacturing partners, we expect to have the capacity to produce hundreds of millions of doses annually. I want to provide some color on our quarterly expenditures and forecasted cash runway. Our total recurring operating expenses averaged about 55 million in each of the first two quarters of fiscal year 21.

We continue to plan for the potential that 1 or more of our vaccines could receive emergency use authorization. Later this year early next year.

Along with our global manufacturing partners, we expect to have the capacity to produce hundreds of millions of doses annually.

I wanted to provide some color on our quarterly expenditure than forecasted cash runway.

Our total recurring operating expenses averaged about $55 million in each of the first 2 quarters of fiscal year 'twenty 1.

Andrew H. Sassine: Approximately 10 million are attributed to G&A, and that should increase by one or two million for the remainder of 2021. The remaining 45 million in R&D expenses relate to our current pipeline, supporting our OTC, cystic fibrosis, lunar flu, and COVID vaccine programs, including stockpiling long-lead time raw materials and vaccines for EUA. This amount is expected to increase in the second half of 21 as we ramp up our production of ARCT 154 vaccines. The cash balance at the end of the second quarter was $434,000, and we received the remaining $30 million for our upfront payment from VINBioCare last week.

Approximately 10 million is attributed to G&A.

That should increase by 1 or $2 million for the remainder of 2021.

The remaining $45 million on R&D expenses relate to our current pipeline supporting our OTC cystic fibrosis lunar flu and Covid vaccine programs, including stockpiling long lead time raw materials and vaccine for EUA.

This amount is expected to increase in the second half of 'twenty 1.

We ramp our production of <unk> 154 vaccines.

Our cash balance at the end of the second quarter was $434 million and we received the remaining $30 million for upfront payment from <unk> last week.

Based on our current pipeline the company's cash position is expected to be sufficient to support operations for more than 2 years.

Joseph E. Payne: Based on our current pipeline, the company's cash position is expected to be sufficient to support operations for more than two years. I will now pass the call back to Joe. Thanks, Andy.

I'll now pass the call back to Joe.

Thanks, Andy.

As we can hear from this call already that this has been a very productive quarter and Arcturus has made substantial progress advancing our mrna based therapeutic and vaccine platforms.

Joseph E. Payne: As we can hear from this call, this has been a very productive quarter, and Arcturus has made substantial progress advancing our MRNA-based therapeutic and vaccine platform. We believe that we have developed a powerful technology with the potential for broad applications across multiple diseases with both MRNA vaccines and MRNA therapeutics. To recap our recent progress, number one, we advanced ARCTO21, our lead vaccine program, and obtained external support and funding by a global entity for inclusion in a multinational placebo-controlled phase three vaccine trial.

We believe that we have developed a powerful technology with the potential for broad applications across multiple diseases with both mrna vaccines in mrna therapeutics to recap our recent progress number 1 we advanced <unk> 1 our lead vaccine program at obtained external support and funding by a global entity for inclusion in on.

National placebo controlled phase III vaccine trial.

Joseph E. Payne: Secondly, we identified ARCT 154 as a next-generation vaccine designed to elicit potent neutralizing immunogenicity against widely circulating SARS-COV-2 variants and obtained CTA approvals in multiple countries to support its clinical development, including a staged phase three study in Vietnam fully funded by Vin Biocan.

2 we identified <unk> $1.54 is our next generation vaccine designed to elicit potent neutralizing immunogenicity to widely circulating <unk> variance and obtained Cta approvals in multiple countries to support its clinical development, including a staged feet a phase III study.

On Vietnam fully funded by <unk> care.

Third we have been approved to transition our Cta 10, our lead systemically administered mrna therapeutic into a multiple dose phase II clinical study and finally, we've also made considerable progress strengthening our core capabilities and increased our manufacturing capacity.

Joseph E. Payne: Third, we have been approved to transition ARCTA-10, our lead systemically administered MRNA therapeutic, into a multiple-dose phase two. And finally, we've also made considerable progress strengthening our core capabilities and increasing our manufacturing capacity. So we expect to have an exciting second half of the year ahead with a number of anticipated milestones with our vaccine and therapeutic candidates, and we look forward to keeping you informed of our progress. At this point, we can now go ahead and open the line for questions.

So we.

Expect to have an exciting second half of the year ahead with a number of anticipated milestones with our vaccine and therapeutic candidates and we look forward to keeping you informed of our progress.

At this point, we can now go ahead and open the line for questions.

Joseph E. Payne: Operator, please, Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question Q. You may press star Q if you would like to remove your question from the question Q. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for your questions.

Operator. Please proceed.

Thank you we will now be conducting a question and answer session. If you would like to ask a question. Please press star 1 on your telephone keypad.

A confirmation tone will indicate your line is on the question queue.

You May press star 2 if he would like to remove your question from the queue for participants using speaker equipment may be necessary to pick up your handset before pressing the star keys, 1 moment. Please while we poll for your questions.

Our first questions come from the line of Yasmin Rahimi with Piper Sandler. Please proceed with your questions.

Joseph E. Payne: Our first questions come from the line of Yasmin Rahimi with Piper Sandler. Please proceed with your, Hi, team. Thank you so much for all the great updates. I have three questions for you. Maybe the first one is, can you tell us what the secret sauce behind 15-5-4 is that drives almost a 15 to 20-fold higher nap versus 21 and maybe versus other self-amplifying MRNAs that we have

Hi team. Thank you so much for all the great updates I have 3 questions. So maybe the first 1 is can you tell us what is the secret sauce behind 154 that drives almost a 15% to 20 fold higher NAV various day 21, and maybe versus other self amplifying mrna that we have seen.

Yasmeen Rahimi: The second question for you is, did you run the human convalescence theory?

Second question for you is it.

Do you run convalescent human convalescent Sera and your NAV.

Yasmeen Rahimi: in your NAP analyses, and can you provide the

Analyses and can you provide the ranger and the severity of that and then I have a follow up question in regards to 'twenty 1.

Yasmeen Rahimi: ranges and the severity of that, and then I have a follow-up.

Joseph E. Payne: And then I have a follow-up question in regards to 21. Great questions, yes, thanks for joining the call. I'll pass the mic over to Pad to address your question as to why ARCT 154 exhibits high neutralizing antibodies.

Great questions, yes, thanks for joining the call I'll pass the mic over to Pat to address your question as to why <unk> $1.54.

Exhibits high neutralizing antibodies.

Thanks, Joe.

Padmanabh Chivukula: Thank you, Joe. You know, obviously, we've learned a lot over the last year in terms of improving the immunogenicity of these spike protein-based constructs. So some of the key optimizations that we've done for the 154 include modification and stability of the RNA and increasing the translability of the replicate. So that's a key important change that we've made.

Obviously, we learned a lot over the last year in terms of improving immunogenicity.

These spike protein based construct so some of the key optimizations that we've done for the 154.

It includes the modification and stability of the RNA.

And increasing the translate the ability of the of the replicate so that's a key important change that we've made.

Padmanabh Chivukula: And then we've also changed the spike protein to be more immunogenic. Some of the improvements in the spike protein include adding some key amino acid substitutions to make it more immunogenic. We've also expressed the spike protein in its pre-fusion state, and then finally inactivated the furin cleavage site. We found preclinically that all of these modifications led to enhanced stability and immunogenicity of the contract.

And then we've also changed despite protein to be more immunogenic some of the improvements on.

Slide 14 includes our we've added some key amino acid substitution.

To make it more immunogenic well, we've also expressed the spike protein and its profusion state.

And then finally inactivated the purion cleavage side.

We have found pre clinically.

That all of these modifications leads to enhanced stability and immunogenicity of the construct.

And then with respect to the human Convalescent Sera panel.

Steve Hughes: And then with respect to the human convalescent syrup, you know, I can refer to maybe Steve. I know clinically we had a number of approximately 147, but

I can refer to.

Maybe Steve I know clinically we had a number of approximately 147, but.

Yes.

Steve Hughes: Yeah, so the human convalescence era. We've tested our human clinical samples against it. We haven't tested the non-human primate samples against those yet, but just as a comparison, the geometric mean tighter from the human convalescence serum that we had, as Joseph was around about 147, with tighters at the low end down to 10 and at the high end up to 1,000 or more. but a mean value of around about 140. So in these essays, we would be considerably above that. But we do still need to follow up with the monkey testing in comparable convalescent serum samples.

The human convalescent Sera we've.

We've tested all human clinical samples and we havent tested the non human primate samples against those yet, but just as a comparison.

On the geometric mean titer from the <unk>.

Human convalescent serum.

As Joe said was around about 147.

With total.

<unk> is at the low end.

Ken and at the high end.

Up to 1000 or more.

On the main value of around about 140 <unk> in this in these assays.

We would be considerably above that.

But we do still need to follow up with the with the monkey testing in a comparable comprehensive sales samples.

Yasmeen Rahimi: Thank you, Steve. And then, if I may ask a last question, so the phase three for 21 is funded by a global entity. Does this global entity have this global entity?

Thank you, Steve and then if I may ask a last question.

So the phase III for 'twenty, 1 it's funded by a global entity.

Has this global entities selected other vaccines from other sponsors for running a phase III. How soon could we be expecting the completion of a large phase III study that is funded by this global entity.

Yasmeen Rahimi: selected other vaccines from other sponsors for running phase three and

Yasmeen Rahimi: How soon should we be expecting the completion of a large phase three study that is funded?

Yasmeen Rahimi: is funded by this global input.

And could you get which geographies could you get.

Yasmeen Rahimi: And could you get, which geographies could you get emergency authorization for? Just a little bit more detail in terms of this very big announcement would be helpful for us. No, it's great questions. At this time, we can't comment on any more details until the details of phase three are announced. Once they are, we'll be able to speak more freely. I can't, the only sponsor of which you have been selected for this funding, or are there other sponsors?

Emergency authorization, just a little bit more detail in terms of that's a very big announcement would be helpful for us.

No.

Great questions.

At this time, we can't comment on any more detail until the details of the phase III or announced once they are we will be able to speak more freely.

Hi.

The only sponsor of which you have been selected for this funding or are there other sponsored.

Yasmeen Rahimi: I just want to, I, Maybe you can't comment on that, but I would love to know. Oh, we'd love to speak more in detail about this, and there will be an appropriate time to do so in the near future. But at this time, we can't go any further.

Wanted to I.

And maybe you can't comment that but I would love.

We'd love to speak more in detail on this and there will be an appropriate time to do so in the near future.

But at this time, we can't comment any further.

Okay. Thank you thanks, Joe Congrats from me.

Yasmeen Rahimi: Okay, thank you. Thanks, Joe. Congratulations. Yeah, thank you, yes. Thanks for joining the call. Thank you. Our next questions come from the line of Brian Chang with Cantor Fitzgerald. Please proceed with your question. Hi, Joanne team. It's great progress.

Yes. Thank you, yes, thanks for joining the call.

Yes.

Thank you. Our next question is coming from the line of Brian <unk> with Cantor Fitzgerald. Please proceed with your questions.

Hi, Julian team, it's great progress and thanks for taking my question. So maybe related to the trial in Singapore, and they will look at $1.54, and 165 assets as booster.

Brian Chang: And thanks for taking my question. Maybe it's related to the trial in Singapore that we'll look at.

Brian Chang: at 154 and 165 as a booster. So how should we think about the next step for these two assets?

So how should we think about the next step for these 2 assets beyond the phase 1.2 study.

Brian Chang: beyond the Phase I study. And maybe on a broader level, what is your latest research?

And maybe on a broader level what is your latest view on that.

Brian Chang: What is your latest view on the booster approach, particularly in the U.S. and EU markets? And I have one follow-up. Thank you.

The booster approach, particularly in the U S.

New markets and add 1 follow up thank you.

Steve Hughes: Uh, speculative questions, but Steve, do you want to address the booster market? Yes, so maybe if I take the questions in reverse order. So clearly, there is a booster market. The United States is working towards approval for giving booster injections, and more than one country in Europe has announced that they're going to be giving booster injections, I think Israel as well. So clearly, there is an evolving booster market, and that booster market is focused around emerging variants of concern.

Speculative questions, but Steve do you on addressed the booster market potential.

Essential on is that maybe because I think the questions in reverse order so clear.

Clearly there is a booster market.

United States is working towards approval.

Giving booster injections and more than 1 country in Europe is announced.

We're going to be giving booster injections I think Israel as well. So clearly it is an evolving boost the market and that boost the market is focused on emerging variants of concern.

Steve Hughes: So with respect to 154 and 165, obviously, we have that clearly in our line of sight in terms of addressing the market need. And as we mentioned earlier, you know, our platform approach allows us to very quickly pivot to address emerging variants of concern as well. One thing I would like to add though is that what we've seen in the monkey data is very, very similar responses to all of the variants of concern that we've tested. And so what we're anticipating is that we're on target. The hope is that these vaccines will allow us to cover emerging variants as well as the existing variants of concern.

With respect to 154 on 165, obviously, we got that clearly on our line of sight in terms of addressing the market need and as we mentioned earlier.

Our platform approach allows us to very quickly pivot to address emerging variance of concern as well on thing I would like to add though is that what we've seen for <unk> and.

The monkey data is very very similar responses to all of the variants of concern that we've tested and so what were anticipating is that these vaccines will will allow us to cover emerging variants as well as the existing balance of concern.

Great and then maybe on 810 and OTC deficiency.

Brian Chang: Great, and then maybe on 810 in OTC deficiency, can you provide some insights on the dose that you have thought about for the phase two study and what biomarkers investors should focus on to get a sense of the advocacy in the upcoming phase two study? Thank you for taking my questions. Okay, yeah.

Can you provide some insights on the dose that you have thought about for the phase III study.

And what Barack Biomarkers should investors focus on to get a sense of the efficacy.

On the upcoming Phase III study. Thank you for taking my question.

Okay, Yeah, great questions. Thanks.

Steve Hughes: Okay, yeah, great questions, thanks. So if you recall, in our phase one study in Healthy Volunteers, we tested all the way up to 4.4 milligrams per kilograms, sorry, mixing up the programs here, and the top dose was very well tolerated. So within the multiple dose study, we're testing 0.3 and 0.4 milligrams per kilogram, so we're at the top of our dose range, which sits very, very nicely in the anticipated therapeutic range that comes out of our animal.

So if you recall in our phase 1 study in healthy volunteers, we tested all the way up to full Mike for <unk> 4 milligrams per kilograms per like confusing between the programs day.

And the top dose was very well tolerated so within the multiple dose study we're testing.

On <unk> 4 milligrams per kilogram, so at the top of our dose range, which fits very very nicely and they anticipate a therapeutic range.

That come out of our animal studies.

Oh and Biomarkers that yes.

Steve Hughes: Oh, and biomarkers that, you know, on the biomarker side, really, the traditional biomarkers for this disease are the urea genesis essay and also looking at the 24-hour ammonia profile. So these are two key biomarkers for us, and then also the urinary orotic acid. Great, thank you. Thanks, Brian. Thank you. Our next questions come from the line of Nick Abbott with Wells Fargo. Please proceed with your question. So good afternoon, thanks for taking our questions and congratulations on some terrific progress here.

Yes.

Yeah on the on the <unk>.

Biomarker side very traditional biomarkers for this disease.

<unk> Genesis assay and also looking at the 24 hour ammonia profile. So these are to keep on markets for US and then also the <unk> acid as well.

Great. Thank you.

Thanks, Brian.

Thank you. Our next question is coming from the line of Nick Abbott with Wells Fargo. Please proceed with your question.

Good afternoon.

All questions and congratulations on terrific progress here.

Nick Abbott: So my first question is on 154, and that is, how good is a single dose of 154? I think Joe, he said in your prepared remarks that a single dose would be mandatory in certain geographies. Is there a plan to include a single dose in phase three? No, you know, that's a great question.

So my first question is on 154 and that is how good is a single dose of 150 full line can you tell you said in your prepared remarks on this.

Single dose will be mandatory in geographies is there a plan to include a single dose in the phase III.

No. That's a great question, it's something that we're going to be evaluating.

Joseph E. Payne: It's something that we're going to evaluate. But ARCTO21 is our single-shot vaccine asset with the clinically promising T-cell response profile, where ARCT 154, that's right now intended to be a two-shot vaccine or a one-shot booster optimized for high nabs targeting the variance, especially Delta. So we're viewing this as two separate assets.

But <unk> is our single shot vaccine asset with the clinically promising T cell response profile, where <unk> 154, that's.

Right now intended to be a 2 shot vaccine or a 1 shot booster optimized for high nabs targeting the variance, especially delta. So we're viewing this as 2 separate assets.

Joseph E. Payne: But having said that, are we going to be looking at blood samples and evaluating biomarkers after a single administration of 154? Yes. Is 154 a self-replicating MRNA vaccine, yes, which implies that it has a promising T-cell profile as well? So we'll be closely monitoring if that may have feasibility at some late date. Thanks, and then on 154, just looking at the graph you provide, which is very helpful, I mean, it appears to be around about half a lot less.

But having said that are we going to be looking at blood samples and evaluating biomarkers. After a single administration of 154, yes is $105 for a self replicating mrna vac.

Vaccine, yes, which implies that it has.

A promising T cell profile as well so we will be closely monitoring it.

That may have feasibility at some later point.

Okay. Thanks, and then on 1 Paul just looking at the growth you provide which is very helpful. I mean, it depends on where random in the hall from lung to less in terms of T cell response on <unk>.

On this part is that.

Is there a reason for that do you think or is this just noise between.

On a different experiments on with different times.

Yeah.

Yeah, It's a fair observation, yes, it's a good observation, but don't want to comment on that sure. Okay. Thanks, Joe.

Nick Abbott: in terms of T-cell response on the yellow spot, is that, is there?

You know our T cell data.

At least from our perspective, the T cell rate on a comparable as you can see that there is a couple of points that are above the median but I think from our understanding T cells that are important and were eliciting T cells for both both drugs, both $1 <unk> to 1.

Nick Abbott: Yeah, it's a fair observation. Yeah, it's a good observation. Pad, do you want to comment on it? Sure.

Padmanabh Chivukula: But nonetheless, it is a fair observation. A.R. CTO 2-1 does a great job at eliciting a T-cell response.

But nonetheless, it is a fair observation a CTO to 1.

Does a great job of eliciting T cell response so.

Padmanabh Chivukula: And that sort of brings me to tears.

Net brings me to keep it.

Padmanabh Chivukula: Sorry, the key thing is that if you look at the 021 graph, the data spreads more widely. So there's a couple of animals that scored much higher than the remaining animals, and that pushes the average up, whereas for 154, the data is tighter. So I think it's just variability, and if we tested more animals, those two sets of graphs would have come much closer together.

So this is the key thing is that if you look at the zero to 1 graph the data spread more widely.

A couple of on each of the things. There's a couple of animals that scored much higher than the remaining animals and that pushes the average up waivers for 1.5 for the data is tighter.

He is just variability and if we tested more animals that those 2 sets of growth would've come much closer together.

Padmanabh Chivukula: I think a key observation, though my takeaway from the graphs is the consistency of the responses for both 021 and 154. We're not seeing that it's staggeringly better against one and not so good against the others. We're seeing a nice, consistent response across all of the variants. Yeah, like you see variability with nabs, but not with T cells, and this could be a very important feature of our vaccine franchise. And you interpret that as you're targeting a conserved epitope or epitope.

A key observations on my takeaway from the glass is the consistency of the responses from both a day led to 1 on 1 side, we're not saying that is staggeringly better against 1 and not so good against the others. We are seeing a nice consistent response across all of the variants, yes, like you see variability with nabs, but not with T cells and this could be a very important feature of our.

<unk> seen franchise.

And you interpret that as you're talking to your concerns or.

Okay.

Exactly exactly.

Nick Abbott: And then you might just take one more from me and just go back to what you said earlier, Joe, will it be a trial of your one four, one five four?

And then just.

Maybe 1 more from me just going back to what you said earlier, Joe will it be a trial of <unk>.

1 on 1 side for us a boost through 'twenty, 1 and then my last 1 is what is the rationale and strategy per 165. Thank you.

Nick Abbott: for as a booster for 021. And then my last

Nick Abbott: And then my last one is, what is the rationale and strategy for 165? Thank you.

Joseph E. Payne: So yes, we do have plans to boost 021 with 154 and also 165 for that matter. We'll make a subsequent disclosure on that once we have approval for that trial to move forward. 165. I think we're trying to develop a broad vaccine portfolio so that we can have coverage against multiple variants in multiple different countries. We were very fortunate in being able to take two of our assets forward into phase three clinical trials.

So yes, we do have plans to add to.

Boost is there I'd say, 1 with with 154 and also $1.65 for that for that matter. So so Mike.

Subsequent disclosure on that.

Once we have approval for that trial to move forward.

165, I think.

We're trying to develop a broad vaccine portfolio. So that we can have coverage against multiple variance in multiple different countries.

We were very fortunate in being able to take 2 of our assets forward into phase III clinical trials 165, we're going to really assess how well it performs well.

Joseph E. Payne: 165, we're going to really assess how well it performs within the study in Singapore and whether there are any unique advantages in certain situations of 165 over 154 or over 021 before we decide how we move that one forward. We'll be doing neutralizing antibody testing and binding antibody testing and T-cell testing against multiple different variances of concern to profile those those vaccines in more detail. Great. Thanks for that.

Within the study in Singapore, and whether there's any unique advantages in certain situations of 165 over 154 overdo. It to 1 before we decide how we move that 1 forward, we will be doing neutralizing antibody testing and binding antibody testing and T cell testing against multiple different variance of concern.

To profile about those vaccines in more detail.

Nick Abbott: Great, thanks for the answer. Thanks, Nick.

Great. Thanks for the loans.

Thanks, Nick.

Seamus Christopher Fernandez: Thank you. Our next questions come from the line of Seamus Fernandez with Guggenheim. Please proceed with your questions. Oh, great, thanks, then. Congratulations on all the progress, guys. A couple of things, just for clarification.

Thank you. Our next question comes from the line of Seamus Fernandez with Guggenheim. Please proceed with your question.

Great. Thanks, and congrats on all the guy on the on all the progress guys.

A couple of things.

Just for clarification.

Seamus Christopher Fernandez: Just hoping to get maybe a better sense of how you're proceeding in Singapore specifically with your 154 and 165 programs. Specifically, I'm just wondering if you would happen to incorporate a parallel head-to-head immunogenicity study versus Pfizer's vaccine, in part because you're also doing your test on top of Kerminati.

Just hoping to get.

Maybe a better sense of how you're perceiving in Singapore specifically.

With your.

With the $1.4 and 165 program specifically I'm just wondering if you would happened to incorporate.

A parallel.

<unk> had immunogenicity study.

Vs Pfizer's vaccine.

In part because Youre also during your testing on top of <unk>.

<unk>, So just wanted to get a better sense of.

Seamus Christopher Fernandez: So just wanted to get a better sense of whether we're going to see head-to-head data, as we saw today, versus your historical vaccine, or if we might get something similar in the Singapore study from an immunogenicity perspective as a boost program. And then separately, once full approval of Kermanadi has been executed, is it possible to run ahead to head of 154 against, you know, the same exact model so that investors who might be skeptical of the magnitude of change here, obviously it looks quite substantial to me, but for those who might be skeptical, that might be one way to approach the comparison. Just wondering if you would consider doing something like that.

If we're going to see head to head data as we saw today versus your historical vaccine, if we might get something similar.

And the Singapore study from an Immunogenicity perspective.

As a boost program and then separately.

Either 1.

Full approval of <unk> has been executed.

Is it possible to run a head to head of 154.

Against.

Against the same exact models, so that investors who might be skeptical.

On the magnitude of change here, obviously, it looks quite substantial to me, but for those who might be skeptical.

That might be 1 way to approach.

The comparison, just wondering if you would consider doing something like that.

Seamus Christopher Fernandez: Yeah, we're already considering it. We've already received approval to proceed with evaluating 154 as a booster to not only other ARCT vaccines or tourist vaccines but also to Camernati. So we're already looking into that and evaluating that and considering, you know, and that data can be compared head to head to understand the value of this particular vaccine. With respect to anything else to add, Steve, well, I think that as you say

Yes, we're already.

Considering it we've already received approval to proceed with evaluating $1.54, as a booster to not only other RCT vaccine arcturus vaccines, but also to.

Okay Kamran Audi so.

We're already looking into that and evaluating that and considering on that data can be compared head to head and understand the value of this particular vaccine.

With respect to.

Anything else to add Steve.

Steve Hughes: Steve? Well, I think, as you noted at this point, we can't get the Pfizer vaccine to do the comparison. It's not commercially available, so within the study in Singapore, it's actually not possible right now to do a direct head-to-head comparison. And I think what we'll have is human data with real antibody levels in humans using well-validated assays that we can then compare with the existing Pfizer data. So I'm not sure there will actually be a need.

Well I think that as you noted at this point, we cant get Faiza vaccine to do the comparison is not commercially available. So within the study in Singapore, It's actually not possible right now to do a direct head to head comparison and I think what we'll have is the human.

The human data with real antibody levels in humans using.

Well validated assays that we can then compare with the existing funds or data. So I'm not sure there'll actually be a need 1 other important question really is how does the antibody levels. How are they maintained over time. So for the size of vaccinated individuals will know when they were vaccinated that we'll know from their baseline sample have fall that they are from the original.

Steve Hughes: One other important question really is what the antibody levels are, how are they maintained over time? So for the Pfizer-vaccinated individuals, we'll know when they were vaccinated. So we'll know from their baseline sample how far out they are from the original vaccination, and as we collect the data from our study over time, we'll be able to compare our antibody levels over time at a similar time point. So, for example, if somebody is six months out from their Pfizer vaccine and they've got an antibody level of X, we can have a look when we're six months out with our vaccine to see what the antibody levels are at that time as well. So we can do some indirect comparisons in that way. And I just think that the data emerging from the study will kind of overtake the need to do a direct comparison.

Explanation and as we collect data from our study over time, we'll be able to compare our antibody levels over time at a similar time point. So for example, if somebody was 6 months out from there for the vaccine and they've got a antibody level of X. We can have a low when they 6 months out with our vaccine to see what the antibody levels are at that time as well so we can.

Do some indirect comparisons in that way and I'll, just say that the data emerging from the study will kind of overtake the need to do a direct head to head comparison.

Joseph E. Payne: And I can do touch. Go ahead. No, no, no, please. No, go ahead, Joe.

And I can just touch but go ahead Scott.

No go ahead Joe.

Okay. No I was just going to add on to the your question about the primate data on how investors should lay holder.

Joseph E. Payne: Okay, no, I was just going to add to your question about the primate data and how investors should lay hold or be convinced of how important this data is. The entire vaccine community has been collecting data in both Sino and Rhes macaques this past year, and we've now gained considerable competence, and there's convincing evidence that immune responses against SARS-COV-2 are similar to those reported in humans, and authentic. represent COVID-19 observed in the human population.

Be convinced of how important this data is the the entire vaccine community has been collecting data in both channel and rhesus macaque. This past year and we've now gained considerable confidence in there is convincing evidence that immune responses against Sars Covid 2 are similar to those reported in <unk>.

Humans and authentically represent COVID-19 observed in the human population. So these primate models serve to be an excellent model and can be relied upon.

Joseph E. Payne: So these primate models serve to be an excellent models and can be relied upon. Great. And then just in terms of the timing of an OUS or just the utility of the VinBioCare clinical trial that's going to be run in Vietnam, can you just talk about how you can utilize that data to gain approvals in other markets and how far-reaching you think those data could actually end up being?

Great and then just in terms of the timing of.

And <unk>.

U S.

Or just the utility of the <unk>.

On clinical trial, that's going to be run in Vietnam can you just talk about the how you can utilize that data.

To gain approvals in other markets and how far reaching.

Those data could actually end up being.

Seamus Christopher Fernandez: So yeah, thanks. That's a great question as well.

Yeah. Thanks, that's a great question as well so the study has been designed to me International standard. So it's been designed so that they based on that day.

Steve Hughes: So the study has been designed to meet international standards, so it's been designed so that, based on the way the study is laid out, and the collection of the endpoints, and the way that we're analyzing the data, it would be acceptable in Europe, the United States, and other geographies as well. In terms of whether conducting the study in an entirely different form population will meet FDA standards. We plan to have those discussions in the very near future. So conceptually, we're planning to use the data to file applications wherever we can to get broad acceptance and make the vaccine broadly available in different geographies.

The way the study is.

As laid out on the collection of the endpoints from the way that way to analyzing the data that it would be acceptable.

In Europe, the United States and in other geographies as well.

In terms of whether conducting the study.

Entirely from population will meet the day FDA standards, we plan to have those discussions in the very near future. So conceptually we're planning to use the data to fall wherever we can to get bored of to get broad acceptance and make the vaccine broadly available in different geographies.

Okay.

Seamus Christopher Fernandez: I guess as just sort of my final question, in terms of gaining early use authorization, whether it be utilizing some of your the antibody tighter data or I guess one question is, is will you be looking at or be able to do a sub-study of antibody titers based on some of the updates that have been provided by the WHO versus different variants as a way to pursue broader authorizations in developed markets like Europe or potentially even the U.S.?

Yes.

Just my final question.

In terms of gaining early use authorization, whether it would be.

Utilizing some of your the antibody titer data or.

I guess 1 question is will you be looking at or be able to do a sub study of antibody titers.

Just on some of the updates that have been provided by the W. H O.

On versus different variance as a way to pursue.

Broader authorizations in.

In developed markets like Europe, or potentially even the U S.

Steve Hughes: Yeah, so we've got a substantial immunogenicity subset within the study where we're collecting serum over time at different time points, so we will be able to do those evaluations against emerging variants of concern. And if an antibody correlate becomes available in Europe or the United States or somewhere else, then we should be well positioned to take advantage of that.

Yes.

We've got a substantial immunogenicity subset within the study where we're collecting.

Overtime at different time points. So we will be able to do those evaluations against emerging variance are concerned so if.

On antibody call it becomes available in Europe, or the United States or somewhere else, then we should be well.

Positioned to take advantage of that.

Great. Thanks for the update.

Seamus Christopher Fernandez: Great. Thanks for the updates, and I'll jump back in the queue. Thanks. Thank you.

I'll jump back in the queue. Thanks.

Great. Thank you.

Thank you our next questions come from the line of Matthew Kumar with Goldman Sachs. Please proceed with your questions.

Madhu Kumar: Our next questions come from the line of Madhu Kumar with Coleman Sachs. Please proceed with your questions. Hey, this is Rob on behalf of Madhu.

Hey, this is Rob on from <unk>, just 2 questions how much of a GAAP do you think there are developmentally between <unk> 1 on 1.5 or 154 works well would you only pursue commercially commercialization of 1.5 or would you go after ball.

Rob: Just two questions. How much of a gap do you think there is developmentally between 021 and 154? If 154 works well, would you only pursue commercialization of 154? Or would you go after both? And then what kind of data should we expect from AR 810 OTC readout later, late in 2022? Would it be reasonable to expect scavenger therapy discontinuation and dietary change? The latter question, I'll have Steve comment on it. With respect to our intent pertaining to our two assets, we want to fully develop and market them.

And then what kind of data should we expect from.

Our 810 OTC readout later this weighted in 2022 would it be reasonable to expect scavenger therapy discontinuation and dietary change.

On the latter question I'll I'll have Steve comment on it with respect to our intent pertaining to our 2 assets, we want to fully develop and market them. That's the intent <unk> 'twenty 1 as a single shot vaccine with clinically promising T cell response profile and Thats needed.

Rob: That's the intent. ARCTO 21 is a single-shot vaccine with a clinically promising T-cell response profile, and that's needed, especially in certain regions. The single-shot nature, for example. While 154 has been optimized for high nabs, targeting Delta and the other variants, which is also a need, or as a booster or as a two-shot vaccine. So I think both of these have a market clearly, and we're addressing those in our face. With respect to the latter question, I don't. Steve, did you need him to read? No, I'll come up with the question. So yeah, ideally over-lars.

Especially in certain regions. The single shot nature for example, while $1.54 has been optimized for high nabs targeting delta on the other variance, which is also need it over.

As a booster, whereas the 2 shop vaccine. So I think both of these have a market.

Clearly and we're addressing those and our phase III studies with respect to the.

The latter question I don't Steve <unk>.

Joseph E. Payne: No, I can move on the question. So, yeah, ideally, over longer-term therapy, yes, scramager therapy would be reduced and withdrawn. This particular study won't go out long enough to allow us to do that because you need to maintain a level of stability of the ammonia, 24-hour ammonia curve, and ureogenesis assay before you start taking people off their meds. As this study moves out, almost certainly, the data's positive at that interim analysis will be looking at an open-label extension study. to roll the participants over into, and that's where we would be doing things like drawing on their scavenger therapies or trying to push out the dose interval to longer intervals between each dose.

No question.

So, yes, ideally over longer term therapy, yes.

Scavenger therapy will be reduced and withdrawn.

This particular study won't go out long enough to allow us to do that because you need to maintain a level of stability.

The ammonia 24 of them on.

On your curve and UA Genesis assets before we start taking people off their meds.

On.

As this study moves that we brought on by certainly the data is positive at that interim analysis will be looking at on open label extension study to low the participants over into and Thats why we would be doing things like we're doing there.

On the scavenger therapies or trying to push out the dosing interval.

Longer intervals between each dose.

Steve Hughes: Thank you. Our next questions come from the line of Ed R.K. with H.C. Wainwright. Please proceed with your questions. Hello everyone, this is Thomas here asking a couple of questions for Ed.

Okay.

Thank you.

Thank you our next questions come from the line of Ed.

RK with HC Wainwright. Please proceed with your questions.

Hello, everyone business on the CFS.

A couple of questions for Russia.

Ed R.K.: Congratulations on all the recent progress. First question about the Vinbal Care collaboration in Vietnam. So the goal is a potential EUA by the Vietnam Ministry of Health in December 2021. Go over some key catalysts and time frame between now and December. Steve, do you want to address some sort of interim data between now and the anticipated emergency use approval in December for Vietnam.

The rest of operations on all the recent progress.

First question about the Benbow care collaboration in Vietnam.

So to go in as a potential EUA by the day.

On a ministry of health.

On December 2021 gig over some key counters.

Timeframe between now to December.

Steve do you want to address some sort of interim data between now and the anticipated emergency use approval in December for the Vietnam study. So the emergency use authorization will be based on the interim analysis, so and that will be the first interim analysis of the data. So it's a pivotal studies.

Steve Hughes: So the emergency use authorization will be based on the interim analysis, and that will be the first interim analysis of the data. So it's a pivotal study, so we can't go taking multiple data cuts like we can in earlier phase clinical trials. So we anticipate having a first interim analysis of the study in the November time frame to enable emergency use authorization in the December timeframe.

We cant go taking multiple data cut slightly we can in an early phase clinical trials. So we anticipate having having a first interim analysis of the study.

On the November timeframe to enable emergency use authorization in the December timeframe.

Okay. Thanks for clarity.

Ed R.K.: Okay, thanks for clarifying and perhaps a question about the collaboration. You mentioned 40 million upfront payment, but also in the press release, it says the remaining 30 million received subsequent to quarter end. So was 10 million received in the first quarter or second quarter, and if so, how was that characterized? Yeah, the 10 million. This is Andy Sussain. The 10 million was received prior to the end of the quarter as a deposit and consequently was reflected as a current liability, an accrued liability on our balance sheet.

Perhaps a question about the collaboration.

You mentioned $40 million upfront payment, but also in the press release. It says the remaining 30 million received.

And so it was $10 million received.

First quarter or second quarter, and if so hours that are characterized.

Yes, the $10 million. This is Andy sustain the $10 million was received.

<unk> prior to the end of the quarter the deposits and consequently with reflected the current liability accrued liability on our balance sheet obviously.

Ed R.K.: Obviously, we executed the transaction and signed the deal subsequent to the quarter and got the remaining 30 million, so that accrued liability will disappear from our balance sheet. Hopefully, that helps clarify the accounting treatment of that 10 million deposits. Yes, it does, thank you.

We executed the transaction and sign the deal.

Subsequent to the quarter and got the remaining $30 million, so that accrued liability will disappear from our balance sheet, hopefully that helps clarify the accounting treatment of that $10 million deposits.

Yes. It does thank you.

Ed R.K.: And perhaps one last question from us regarding 165, when should we expect frequent data from perhaps a non-human primate study, and I can go over some similarities and measures between 165 and 154. Yeah, well, if you notice we've entered into collaborations or relationships with respect to ARCTO21 and 154, if we do the same thing with 165 because of its specific regional profile, then that will be an appropriate time to disclose more detail around the preclinical data.

And perhaps 1 last question from us.

<unk> 165.

When should we expect free clinical data.

From from.

Perhaps I'm not hearing what primate study and can you go over some similarities on the major differences between them.

74.

Yeah, well if you noticed we have entered into collaborations or relationships with respect to <unk> to 1 and 154, if we do the same thing with $1.6 5% because of its specific regional profile and that will be an appropriate time to disclose more detail around the preclinical data.

Ed R.K.: So whether, you know, when we get human data for it or when we do some sort of deal around it, if we do, that would be an appropriate time to disclose more detail on 161. We look forward to that and thank you for the kind of questions and look forward to the end of the phase three study. Okay, thank you, and say hi to Ed. Thank you. Our next question comes from the line of Yel Jen with Laid Law & Company.

So whether when we get human data for it or when we do some sort of deal around it if we do that would be an appropriate time to to disclose more detail on 165.

Okay sounds good.

Reported that.

Thank you for taking my questions.

Moving to.

The unveiling of the phase III study.

Okay. Thank you and say I would add.

Thank you our next questions come from the line of Yale Jen with Laidlaw <unk> Company. Please proceed with your questions.

Ed R.K.: Please proceed with your question. First, regarding 154, besides Binon, potential Singapore, do you guys own the global right to it for the rest of the world, including the United States? Yes, correct. Yeah, where we have the global rights to ARCT 150. Okay, the second question is that you popularized the press release and revealed that

Good afternoon, and thanks for taking the questions.

First of all regarding $1.54.

<unk> been on potentially the Singapore do you guys on the global right.

For the rest of the world, including the United States.

Yes, correct, yes.

We have global rights to <unk> $1.54.

Okay. The second question is that.

Yeah.

The press release and revealed that the comparison of neutralize the antibody to various alright.

Yel Jen: that the comparison of neutralized antibody of two various

Yel Jen: is a variant. You have used 7.5 Macs in 2019, and you will anticipate to use 5 mics instead for the trials. Was there a reason to use those? Was that just for a fair comparison, or there's another reason behind it?

You have used the 7.

I make.

In 2 zero.

Zero to 1 day, 1 and you anticipate to use 5 mix.

For the trials was there a reason to use it.

Was that because just the both fair comparison or there's other reason behind it.

No it's to do with timing of the study and when we actually set off on this study.

Steve Hughes: No, it's to do with the timing of the study, and when we actually set off on the study earlier on when we were anticipating moving into Phase 3 with a 7.5 microgram dose. As the data rolled out from our Phase 2 study, it showed very clearly that the 5 microgram dose performed as well as the 7.5 microgram dose and was a little bit better tolerated, and so we changed our Phase 3 dose from 7.5 to 5.

On.

Was early.

They are on when we were anticipating moving into phase III with a 7 and a half microgram dose as the data from our phase II study it showed very clearly that the.

The 5 microgram dose performed as well as the 7.5 microgram dose and was a low.

It'll be better tolerated and so we changed.

Phase III dose from 7.5% to 5 so is this just a timing on a legacy issue, but based upon what we know about what we've seen from recent publications about the translation from the mechanics studies in humans.

Steve Hughes: So it's just a timing and a legacy issue. But based upon what we know about, or what we've seen from recent publications about the translation from the macaque studies into humans and the fact that the five microgram dose performed at least as well, and probably a little bit better than the 7.5 micrograms, we would anticipate that if this had been a five microgram dose primate study, it would have looked very similar.

The fact that these 5 microgram dose performed at least as well as populated way better than the 7.5 micrograms, we would anticipate that if this had been a 5 microgram dose primates study that it would have looked very similar.

Okay and maybe last question here was about 165 understood understand you may not want to reveal all the inflammation at this point until later, but just.

Yel Jen: Okay, maybe the last question here was about 165. I understand that you may not want to review all the information at this point until later. But just in a conceptual way, were there any sort of general differences between one 65 and 154 you can sort of describe?

Second consecutive worldwide.

Was there any sort of channel differences between 1.

If we bought them.

Paul you can sort of described.

Pat: Yes, this is Pat and I. Sure. This is Pat, and I can, yeah, so we can tell you that the 165 molecule has a bias towards the beta variant, and we'll be talking more about that at a future time.

Yes. This is Pat and I share. This is Pat on that yes, we can tell you that the the 165 molecule has a bias towards the beta variant.

And we will be talking more about that at a.

Future time.

Yel Jen: Okay, great. Thanks, God, and congratulations on all the programs.

Okay, great. Thanks, a lot and congrats on all the progress.

Operator: Thank you. Our next questions come from the line of Kumar Raja with Brookline Capital Markets. Please proceed with your questions. Thanks for taking my questions.

Thanks, Yale I appreciate it.

Thank you our next questions come from the line of Kumar Roger with Brookline Capital markets. Please proceed with your questions.

Thanks for taking my questions.

Padmanabh Chivukula: So with regard to ARCT 154, how much manufacturing capacity do you have? And when is this 200 million capacity for WIDBioCare expected to come on board? And is it mostly for use by Winn BioCare?

So with regard to <unk>, 1 price pool, how much manufacturing capacity do you have.

And when is it 200 million Pax deepwater.

Okay, I expect it to come on.

Book and EBIT.

Is it mostly volume bye bye okay.

Andrew H. Sassine: Yeah, at this point, what we've disclosed is that the VIN BioCare facility will be able to produce up to 200 million doses annually, and we've been guiding that this will happen, probably in the second half of 2022. And so that's about all the information we can give you at this point with respect to that capacity. With respect to the other parts of our manufacturing relationships and collaboration, we really haven't given any specific details except to, you know, be able to tell you that we have the capability of producing hundreds of millions of doses annually with those relationships.

Yes at this point, what we've disclosed is that.

The <unk> facility will be able to produce up to 200 million doses annually.

We have been.

Guiding that it'll happen in probably the second half of 2022.

And so thats about all the information we can give you at this point with respect to that <unk>.

Capacity with respect to.

The other part of our manufacturing relationships and.

Collaborations, we really haven't given any specific detail.

To be able to tell you that we have.

On the capability of producing hundreds of millions of doses annually with the relationship as you can see we've expanded it quite substantially.

Andrew H. Sassine: As you can see, we've expanded it quite substantially, and in preparation for this opportunity with obviously being, you know, very capital efficient and working very closely with our partners. So two very, very important attributes that we wanted to execute on.

And.

In preparation.

For this opportunity.

<unk>.

Obviously being.

Very capital efficient.

And working very closely with our partners. So 2 very very important.

Attribute that we wanted to execute on hopefully that helps.

Padmanabh Chivukula: Hopefully, that helps. And with regard to this manufacturing, that can be shifted from 021 to 154 or, based on whatever data you're seeing, how seamlessly can that be done? Yes, that's correct. One of the advantages of this platform technology is you can modify the payload without very few modifications to the manufacturing process. Very streamlined. Finally, with regard to the preclinical pipeline, what's happening in terms of cystic fibrosis, you know, as well as the flu vaccine. Thank you.

And with regard to this manufacturing that can be shifted from zero to 1 the 1 pipe broad based on what other data are you seeing housing.

That would be done.

Yes, that's correct 1 of the advantages of this platform technologies, you can modify the payload without.

Little modifications to the manufacturing process, so its very streamlined.

Finally, with regard to the preclinical pipeline company.

Company income from cystic fibrosis.

Padmanabh Chivukula: Through the vaccine. Thank you.

Flu vaccine. Thank you.

Steve Hughes: The CF? Go ahead, Steve.

The CF.

Go ahead, Steve.

Steve Hughes: Go ahead, Steve. So the CF program, we're anticipating that we'll get a, we'll submit a clinical trial application in the early part of next year.

On the CF program.

Anticipating that we'll get.

We will submit for a clinical trial application in the early part of next year.

Padmanabh Chivukula: Okay, great, thanks. Thank you. Thank you.

The flow.

Okay, great. Thanks.

Thank you.

Thank you that is all the time, we have today for questions I would now like to turn the call back over to Joseph Payne for any closing comments.

Joseph E. Payne: That is all the time we have today for questions. I would now like to turn the call back over to Joseph Payne for any closing questions. Yeah, thanks everyone.

Thanks to everyone. It looks like our time's up and we're going to be closing the call now feel free to reach out to our team as always if you have any follow up questions, we'll be as efficient as efficient as we can and our responses and bye for now and look forward to seeing you again soon.

Joseph E. Payne: Looks like our time's up, and we're going to be closing the call now. Feel free to reach out to our team, as always, if you have any follow-up questions. We'll be as efficient as we can in our responses, and bye for now. I look forward to seeing you again soon. Thank you for your participation. This does conclude today's teleconference. You may disconnect your lines at this time.

Thank you for your participation. This does conclude today's teleconference. You may disconnect your lines at this time.

Have a great day.