Q4 2020 Arcturus Therapeutics Holdings Inc Earnings Call

Greetings and welcome to the Arcturus Therapeutics fourth quarter and full year 2020 earnings call. At this time all participants are in a listen only mode. A brief 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 of this call.

Operator: Greetings and welcome to the Arcturus Therapeutics fourth quarter and full year 2020 earnings call. At this time, all participants are in a listen-only mode.

Operator: A brief 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 keyboard. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Neda Safarzadeh, Head of Investor Relations, Public Relations, and Marketing. Thank you, Neda.

Is being recorded.

Now my pleasure to introduce your host need us of ours, the head of Investor Relations public relations and marketing. Thank you Nita you may begin.

Thank you operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO, Andy Sassine CFO Doctor Apache the philosophy of so on steel Dr. Steve Hughes, our Chief Medical Officer, and Professor Lee Young Deputy director of emerging infectious diseases.

Neda Safarzadeh: You may begin. Thank you, Operator, and good afternoon, everyone. We are joined today by Joseph Payne, President and CEO, Andy Sassine, CFO, Dr. Pad Chivukula, CSO and COO, Dr. Steve Hughes, our Chief Medical Officer, and Professor Ouyang Inyong, Deputy Director of the Emerging Infectious Diseases Program from Duke NUS Medical School, who is also on Arcturus' Vaccine Platform Scientific Advisory Board. 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 during this conference call constitute forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995.

The program from Duke and U S Medical the school, who is also in the Arcturus vaccine last from scientific Advisory Board.

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. This conference call constitute forward looking statements that involve substantial risks and uncertainties for purposes of the safe Harbor provided by the private sicker.

The is the litigation Reform Act of 1995.

Any statements other than just stays myself of story of called Fox included in this communication, including those regarding the company's supply agreements and potential of supply agreements the potential future of manufacturing and other operations the status and the results of clinical development programs the <unk>.

Neda Safarzadeh: Any statements other than the statements of historical facts included in this communication, including those regarding the company's supply agreements and potential supply agreements, the potential future manufacturing and other operations, the status and results of clinical development programs, the planned initiation, design, or completion of clinical trials, the likelihood of success of the company's coronavirus COVID-19 vaccine candidate or other product candidates, and the company's current and future cash and financial position, are forward-looking statements 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.

Planned initiation of design or completion of clinical trials the likelihood of success of the company's coronavirus, COVID-19 vaccine candidates or other product candidates and the company's current and future of cash and financial position our forward looking statements.

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

Per formats.

Such statements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading risk factor and Arcturus has the most recent annual report on form 10-K with the S. E C and in other filings that are of trust makes with the S. E C.

Neda Safarzadeh: Such statements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading risk factor in Arcturus' most recent annual report on Form 10-K with the SEC and in other filings that Arcturus 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 to 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.

Neda Safarzadeh: 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 of Arcturus. Joe, please go ahead.

The Joe Payne, President and CEO of Arcturus, Joe. Please go ahead.

Hey, Thank you Nita.

Joseph E. Payne: Thank you, Neda. Good afternoon to all. Thank you for joining Arcturus's quarterly call today. I'd like to begin by congratulating J&J on their recent approval of their one-shot COVID vaccine. I'm sure their team has been working very hard, and it's great to see their efforts being rewarded with success.

Good afternoon to all.

Thank you for joining the Arcturus has quarterly call today I'd like to begin by congratulating J&J on their recent approval of the one shot Covid vaccine I'm sure. Their team has been working very hard and its great to see their efforts being rewarded with success.

No doubt the world wants access to one shot vaccines of this year in 2021 and it appears that Covid is here to stay for years to come. It's now of global pathogen very contagious airborne and new challenging variance are of rising the endemic market will very likely be addressed through periodic single administration.

Joseph E. Payne: No doubt the world wants access to one-shot vaccines this year in 2021, and it appears that COVID is here to stay for years to come. It's now a global pathogen, very contagious, airborne, and new challenging variants are emerging. The endemic market will very likely be addressed through periodic single administrations, so a vaccine that is re-dosable is also important. Additionally, a vaccine with an immunological profile that could potentially provide broader variant coverage is important. A vaccine technology that is rapidly updatable as needed is also important. Arcturus is developing a differentiated next-generation class of mRNA-based medicine. And we're very excited about the prospects for our company and our rapidly maturing pipeline.

Therefore of vaccine that is re dose of bolt is also important of.

<unk> seen with the immunological profile that could potentially provide broader variant coverage is important of VAT.

Axiom technology that is rapidly update of ball as needed is also important.

Arcturus is developing differentiated next generation class of the.

M RNA based medicines and we're very excited about the prospects for our company and are rapidly maturing pipeline.

We believe that mrna therapeutics have now come of age as a therapeutic modality to provide enormous benefit to human health not just in vaccines, but also for a wide range of transformative medicines for serious diseases. During the last several months there has been an increasing appreciation for the promise of mrna approaches with the <unk>.

Joseph E. Payne: We believe that mRNA therapeutics have now come of age as a therapeutic modality to provide enormous benefit to human health, not just in vaccines but also for a wide range of transformative medicines for serious diseases. During the last several months, there has been an increasing appreciation for the promise of mRNA approaches, with the clinical successes and widespread use in tens of millions of individuals of the first wave of mRNA vaccines. We believe that this is only the beginning.

Cynical successes in widespread use in tens of millions of individuals of the first wave of mrna vaccines. We believe that this is only the beginning.

And that our platform has the potential to generate vaccines with the differentiated profile compared to those in use today as well as to create medicines for numerous other diseases.

Joseph E. Payne: And that our platform has the potential to generate vaccines with a differentiated profile compared to those in use today, as well as to create medicines for numerous other diseases. Arcturus has made substantial progress during 2020 and during the beginning of this year with our lead clinical pipeline candidates, our promising preclinical candidates, and in advancing Arcturus' core capabilities and underlying science. We have continued to move our leading chemistry forward, expanded our intellectual property estate, and rapidly advanced our CMC, our manufacturing capabilities. I'll begin with an overview of ARCTO21.

Arcturus has made substantial progress during 2020 and during the beginning of this year with our lead clinical pipeline candidates are promising preclinical candidates and in advancing Arcturus has core capabilities and underlying science.

We have continued to move our leading chemistry forward ex.

Expanded our intellectual property estate and rapidly advanced our CMC or manufacturing capabilities.

I'll begin with an overview for our CTO of 21, Yeah. That's our differentiated COVID-19 vaccine candidate based on our self transcribing and replicating mrna also known as self amplifying mrna technology.

Joseph E. Payne: That's our differentiated COVID-19 vaccine candidate based on a self-transcribing and replicating mRNA, also known as self-amplifying mRNA technology. When we consider the COVID-19 pandemic at a macro level, our expectation is that it will be a prolonged global issue that will require the vaccination of billions of individuals for years to come. RNA coronaviruses are well known to mutate rapidly, and while we're not surprised with the emergence of viral variants during this global pandemic, we are carefully monitoring the situation.

When we consider the COVID-19 pandemic at a macro level our expectation is that it will be of prolonged global issue that will require the vaccination of billions of individuals for years to come.

RNA Corona viruses are well known to mutate rapidly and while we're not surprised with the emergence of viral variance. During this global pandemic. We are carefully monitoring the situation were carefully evaluating these variance as they arise we believe that because of the specific type of cellular immunogenicity that <unk>.

Joseph E. Payne: We're carefully evaluating these variants as they arise, and we believe that because of the specific type of cellular immunogenicity that ARCT 021 promotes, our vaccine candidate may provide broad protection against many of the SARS-CoV-2 variants in circulation. It is also possible that these variants may require periodic adaptation of vaccines administered, as is already done with vaccines for influenza. One of the benefits of an mRNA approach is that our vaccines are easily and rapidly able to be modified as needed.

T O 21 promotes that our vaccine candidate may provide broad protection to many of the Sars COVID-19 two variance in circulation.

It is also possible debt. These variants may require periodic adaptation of vaccines administered as is already done with vaccines for influenza.

One of the benefits of an mrna approach is that our vaccines are easily and rapidly able to be modified as needed.

Furthermore, we believe that a our CTO of 'twenty, one could have a differentiated and highly attractive profile of vaccine product that is not of frozen liquid one that is lyophilize and requiring only a single administration. Our CTO of 'twenty. One has the potential over time to become a favorite vaccine option for many countries we.

Joseph E. Payne: Furthermore, we believe that ARCTO21 could have a differentiated and highly attractive profile, a vaccine product that is not a frozen liquid, one that is lyophilized and requiring only a single administration. ARCTO21 has the potential, over time, to become a favored vaccine option for many countries. We continue to rapidly advance our clinical development program for ARCTO21, and based on the highly promising clinical and preclinical data that we've obtained to date, we have recently made the decision to move forward with a single administration regimen in Phase 3 development.

<unk> to rapidly advance our clinical development program for <unk>, our CTO of 'twenty, one and based on the highly promising clinical and preclinical data that we've obtained to date.

We have recently made the decision to move forward with a single administration regimen in phase III development, our decision to advance the single administration regimen is based on our phase one slash two study data that show favorable tolerability and both substantial moral and cellular immunity observed after a single.

Joseph E. Payne: Our decision to advance the single administration regimen is based on our Phase 1-2 study data that show favorable tolerability and both substantial humoral and cellular immunity observed after a single injection. In addition to our clinical data, we have supportive data from both primate and human ACE-2 transgenic mouse challenge models that demonstrate robust protection with a single dose regimen. We are particularly encouraged by the robust cellular immune response seen in Phase 1-2 study subjects that were administered our vaccine. A growing body of clinical data provides support for the important role of CD8 cells in providing protection against COVID-19, and our data gives us additional confidence in the potential efficacy of our vaccine.

<unk> in addition to our clinical data we have supportive data from both primate and human Ace two transgenic mouse challenge models that demonstrate robust protection with the single dose regimen.

We are particularly encouraged by the robust cellular immune response seen in phase one slash II study subjects that were administered our vaccine.

A growing body of clinical data provides support for the important role of CD eight cells and providing protection against COVID-19, and our data gives us additional confidence in the potential efficacy of our vaccine. We are currently conducting final analysis on the results of the phase one slash two study.

Joseph E. Payne: We are currently conducting final analysis on the results of the Phase 1-2 study, and we plan to submit the results for publication in the second quarter. I also want to mention new data that has been submitted for publication based on work from Dr. Uy and his colleagues. We've been seeing several reports emerging that conventional mRNA vaccines may be highly effective after the first shot. So it begs the question, how does ARCT021, a self-amplifying mRNA vaccine, compare to the single shot of an approved conventional mRNA vaccine?

And we plan to submit the results for publication in the second quarter.

I also want to mention new data that has been submitted for publication based on work from Doctor OUI and his colleagues we have been.

We've been seeing several reports emerging that conventional mrna vaccines may be highly effective after the first shot. So it begs the question how does a R. C T O 21 of <unk>.

Self amplifying mrna vaccine compare to the single shot of unapproved conventional mrna vaccine day.

Correct me comparing vaccines has been challenging for investors and the scientific community because everyone uses different methods and assays to measure immunogenicity, but to help us all had to help all of US with this challenge the Duke and U S Medical school and their colleagues have recently collected immunogenicity data from participants.

Joseph E. Payne: Directly comparing vaccines has been challenging for investors and the scientific community because everyone uses different methods and assays to measure immunogenicity. But to help us all, to help all of us with this challenge, the Duke-NUS Medical School and their colleagues have recently collected immunogenicity data from participants receiving a single injection of an approved conventional mRNA vaccine, and the data collected utilized the same assays, methods that we used for determining the immunological profile of ARCTO21.

Receiving a single injection of an approved conventional mrna vaccine.

And the data collected utilize the same assays the methods that we used for determining the immunological profile of a our CTO of 'twenty one.

The research examined the adaptive immune responses following administration of the approved conventional of mrna vaccine based on the cohort of 12 of 20 health care workers the.

Joseph E. Payne: The research examined the adaptive immune responses following administration of the approved conventional mRNA vaccine based on a cohort of 20 healthcare workers. The key results from this study are included in our press release issued just recently this afternoon. The data suggest that following a single administration of an mRNA vaccine, binding antibodies and cellular immunity or T cells are associated with protection against COVID-19 at early time points. However, interestingly, at these same time points where clinical protection is observed, neutralizing antibodies, or antibody levels have been found to be negligible. Suggesting that these are not necessarily required for clinical efficacy.

The key results from the study are included in our press release issued just recently this afternoon.

The data suggest that following a single administration of an mrna vaccine.

Binding antibodies and cellular immunity or T cells are associated with protection against COVID-19 at early time points Interestingly at these type of at the same time points, where clinical protection as observed neutralizing antibodies.

All of our antibody levels have been found to be negligible.

Suggesting that these are not necessarily required for clinical efficacy.

The findings from our CTO of 'twenty, one single shot Immunogenicity based on our phase one slash two study results compares favorably with the findings from Doctor, who we study examining the correlates of protection based on conventional mrna vaccines. We believe these data provide additional.

Joseph E. Payne: The findings from our ARCTO21 single shot immunogenicity based on our phase one slash two study results compare favorably with the findings from Dr. Uy's study examining the correlates of protection based on conventional mRNA vaccines. We believe these data provide additional support for the potential efficacy of the ARCTO21 factor. Following our phase 1 slash 2 study, we have now dosed over 500 subjects in our ongoing phase 2 This is a multi-center, randomized, observer-blind study designed to evaluate the safety and immunogenicity of the study vaccine in younger and older adult participants.

It'll support for the potential efficacy of the a our CTO of 'twenty one vaccine.

Following our phase one slash two study we have now dosed over 500 subjects in our ongoing phase. Two study. This is the multicenter randomized observer Blind study, which is designed to evaluate the safety and Immunogenicity of the study vaccine and younger and older adults participants.

The studies being conducted in both of the United States and Singapore is evaluating two dose levels five micrograms and seven in the half micrograms.

Joseph E. Payne: The study is being conducted in both the United States and Singapore and is evaluating two dose levels, 5 micrograms and 7.5 micrograms. We are also evaluating a prime boost regimen. By evaluating a prime boost regimen, we'll be studying the redosability of our approach. We believe that a redosable vaccine that utilizes the novel lunar non-viral vector delivery system is important, and that a single-shot mRNA vaccine that is more easily distributed, like lyophilized or non-frozen liquid, would be a valuable option for many countries.

We are also evaluating prime boost regimens.

Evaluating of prime boost regimen will be studying the re dose ability of our approach. We believe that of re dosing for vaccine that utilizes the novel lunar non viral vector delivery system is important and that of single shot mrna vaccine that is more easily distributable like lyophilize or non frozen liquid would be of.

Valuable option for many countries.

We plan to finalize the specific a our CTO of 'twenty, one dose for our phase III study to be confirmed by the pending interim analysis data from this ongoing phase II study, which we expect to get during the second quarter.

Joseph E. Payne: We plan to finalize the specific ARCTO21 dose for our Phase 3 study to be confirmed by the pending interim analysis data from this ongoing Phase 2 study, which we expect to get during the second quarter. Meanwhile, our clinical team is already preparing to advance a 5-microgram single-dose regimen for phase 3 development, and we continue to track towards the Q2 study start. We believe that we have the potential to obtain data in the second half of the year and could obtain ARCTO 21 EUA or Emergency Use Authorization in at least one jurisdiction in the second half of this year or H2 2021.

Our clinical team in parallel as the whole ready preparing to advance of five microgram single dose regimen for phase III for phase III development, and we continue to track towards Q2 studies start.

We believe that we have the potential to obtain data in the second half of the year and could obtain a R. C. T O 21, EUA or emergency use authorization and at least one jurisdiction.

In the second half of this year for each to 2021.

Well, we are fortunate to have doctor OUI, the professor of emerging infectious diseases at Duke <unk> Medical school. He's here on the call today to present the recent data.

Joseph E. Payne: We are fortunate to have Dr. Uy, the Professor of Emerging Infectious Diseases at Duke-NUS Medical School. He's here on the call today to present the recent data. Dr. Uy, the time is now yours, and we here in San Diego will advance the slides at your direction. Thanks very much, Joe.

The Doctor OUI all the time is now yours.

And we hear on San Diego will advance the slides for your direction.

Thanks, very much Joe on next slide please.

As you may recall in the address.

At the Investor Conference call. The we had I show on the slide on the Phase III trial data the N T. One six to be too.

Professor Ouyang Inyong: As you may recall, on the last investor conference call that we had, I showed a slide on the Phase 3 trial data of BNT166. And the onset of vaccine efficacy of this RNA vaccine, the conventional RNA vaccine, was at day 12 after the first... As you can see on the red line, the curve for the vaccinated arm pretty much flattens from that point. The adaptive immune responses that coincide with this onset of efficacy could be very informative, therefore, on the necessary elements of immunity against COVID-19. Next slide.

And the onset of the vaccine efficacy of this Arnie convention of irony of vaccine was indeed 12. After the first dose share as you can see on the Red line income for the vaccinated I'm pretty much flat then from that point on wings.

Yes, that's what the immune responses that coincides with the onset of efficacy could be very informative for on the necessary elements of immunity against COVID-19.

The next slide please.

So we took advantage of the rollout of this conventional R&D vaccine in Singapore to defined what components of the adaptive immune responses to develop coincidentally with vaccine efficacy on set.

Professor Ouyang Inyong: So we took advantage of the rollout of this conventional RNA vaccine in Singapore to define what components of the adaptive immune responses develop coincidentally with vaccine adaptation. We found that BNT162b2 vaccination produced binding IgG responses. Interestingly, there were very few antibodies that were neutralizing or even blocking the SARS-CoV-2 and the ACE2 interaction, and 15% were positive on the SARS-CoV-2 PRN. In contrast, 85% were positive for virus-specific T-cells in our Alice spot; the median number of spots per 1 million cells was 28 and 13 on days 10 and 21, respectively. These data suggest that virus-binding antibodies in virus-specific T-cells are sufficient to protect against COVID-19.

We found at the end he wants it to be to vaccination produced to finding the IGT responses 80 per cent of the participants at this time.

Interestingly this new and very few of antibodies neutralize the call.

Even a binding blocking the sacirbey too.

And the H two interaction.

And 15% with all the positives on the task will be to be R&D.

In contrast, 85% with possibly for virus specific T cells are now out of the spot actually median number of spots for 1 million songs for 28 and 13 on the spend in 'twenty one respectively. After the first dose.

These data suggest the virus binding antibodies and various specific T cells are sufficient to protect against COVID-19.

The findings are also consistent with many other studies that show that neutralizing antibodies are not actually would be required for protection.

Professor Ouyang Inyong: These findings are also consistent with many other studies that show that neutralizing antibodies are not absolutely required. Our findings with the conventional RNA vaccine provide a context for us to compare what we have found in our Phase 1-2 trial with Arcturus. High Serial Conversion Rate at Day 4, which, by the way, was actually done using a more astringent serial dilution which we used for the conventional R&D. Moreover, its serial conversion was 100% by date 36.

The findings of the conventional RNA vaccine provided context for us to compare what we have found in our phase one the slash two trial with optical or two one.

The fact, you know also produces high sort of conversion rate of day 14. After the first dose anyone per se.

Which by the way, what's actually done using of mall and stringent zero dilution series rather than the optical density readings, we should be used for the conventional army vaccination of vaccine analysis.

Moreover, the Seroconversion was 100 per cent by 36, so the.

The and Humira of antibody are spot on humoral response.

Very encouraging all.

The other participants developed the very specific T cell responses on the same as it's got the assay. Although there is the for the defense the comes from the self replicating RNA vaccine.

Professor Ouyang Inyong: All of our participants developed virus-specific T-cell responses on the same ELISBOT as we did, although there is a four-day difference that comes from the self-replicating RNA vaccine, ten times greater than conventional R&D. These results again demonstrate the strong potential of ARC.

10 times greater than conventional RNA vaccine.

These results again demonstrate the strong potential of E. R. C T zero to one being a single shot vaccine against COVID-19.

The data.

Data is being on under review right now and should be available are innocent preprinted on line soon.

Stephen L. Eck: This data is being under review right now. It should be available... I'll hand this time over to Dr. Steve Hughes, Chief Medical Officer. I'll begin with Arct810, our therapeutic candidate for ornithine transcarbamylase (OCT) deficiency. ARC810 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 ornithine transcarbamylase enzyme in the liver of patients with OTC deficiency has the potential to restore normal urea cycle activity, preventing neurological damage and the need for liver transplantation.

At this time over the Don Steve use our Chief Medical officer of factors. Thanks.

I'll begin with up to 810, all therapeutic candidate for ornithine trends Cob analyze OTC deficiency.

On a 10 utilizes out to us as lunar lipid mediated delivery platform to deliver OTC messenger RNA to the liver the preliminary target tissue in OTC deficiency.

Expression of the normal one of the same trends call of analyze the enzyme in the level of of patients with OTC deficiency has the potential to restore normal U S cycle activity, preventing neurological damage and the need for liver transplantation.

I O C. T 810 of program is supported by preclinical data of an OTC deficient murine models, demonstrating the dosing of lunar OTC results of my bus ornithine <unk> called out on a nice protein expression and activity, resulting in improvements in UAE of Genesis plasma ammonia and increased survival.

Stephen L. Eck: Our ARCT810 program is supported by preclinical data in OTC-deficient murine models, demonstrating that dosing of lunar OTC results in robust ornithine transcarbamylase protein expression and activity, resulting in improvements in ureogenesis, plasma ammonia, and increased survival. We have already completed a Phase 1 dose escalation study in healthy volunteers. That study demonstrated that administration of ART810 was associated with favorable tolerability and an attractive pharmacokinetic profile, going up to the top dose of 0.4 mg per kg, which is well within the anticipated therapeutic range based on data from our animal studies. Importantly, the lipid was not detectable beyond 48 hours after dosing.

We have already completed the phase one dose escalation study in healthy volunteers that study demonstrated the administration of 810 was associated with favorable total, but lets say and then the attractive pharmacokinetic profile going up to the top dose of <unk> four milligrams per kilogram, which is well within the anticipated therapeutic range.

Based on data from one of animal studies.

Importantly, the lipid was not detectable before beyond the 48 hours after dosing.

We could actually still detect the messenger RNA and the last time point that we assessed which was two weeks after dosing the <unk>.

Stephen L. Eck: But we could actually still detect messenger RNA at the last time point that we assessed, which was two weeks after dose three. The persistence of messenger RNA gives us optimism that we can potentially extend the dose interval beyond a few weeks. We have also initiated a phase 1 dose escalation study evaluating ARC810 for the first time in patients with an OTC deficiency. We've been enrolling this study in the US, but we have recently received approval from Health Canada to also enroll subjects in Canada as well.

Assistance of Messenger RNA gives us optimism that we can potentially extend the dose into will be on the few weeks.

We have also initiated the phase one dose escalation study evaluating <unk>.

<unk> 10 for the first time in patients with the OTC deficiency.

We've been enrolling the study in the U S. But of recently received approval from health, Canada to also on most subjects in Canada as well, we look forward to the tightening of initial results from this study during the coming year.

Stephen L. Eck: We look forward to obtaining initial results from this study during the coming year. We are on track to submit a clinical trial application for a multiple dose phase 2 study in OTC deficiency patients in Q2 of 2021. Turning now to ARCT 032, our therapeutic candidate for cystic fibrosis, ARCT 032 is designed to result in the expression of a functional copy of messenger RNA encoding the transmembrane conductance regulator, or CFTR, in the lungs of CF patients. CFTR is a membrane protein and chloride channel that is deficient in CF patients, causing severe pathology, including lung dysfunction.

We are on track to submit the clinical trial application for a multiple dose phase two study in OTC deficiency patients in Q2 of 2021.

Turning now to I O C T zero of three to all of the therapeutic candidate for cystic fibrosis.

M. A C T zero of three two is designed to result in the expression of a functional copy of messenger RNA encoding the transmembrane conductance regulator or C. F. T O in the lungs of CF patients.

C. F. T O is the membrane protein employed channel that is deficient in CF patients, causing severe pathology, including lung dysfunction.

The C T zero of three to utilize this out to us as lunar lipid mediated lipid mediated aerosolized platform to deliver C. F. T O of messenger RNA to the lungs. We believe that this platform has the potential to restore normal lungs C. F T O activity, thereby correcting the underlying defect, causing the disease.

Stephen L. Eck: ARCT032 utilizes Arcturus' lunar lipid-mediated aerosolized platform to deliver CFTR messenger RNA to the lungs. We believe that this platform has the potential to restore normal lung CFTR activity, thereby correcting the underlying defect causing the disease. The ARCT032 program is supported by preclinical data from a variety of models, including human and ferret bronchial epithelial air-liquid interface cell cultures, ferrets, non-human primates, and a CFTR deficient murine model. These studies have demonstrated the ability to efficiently deliver our lunar mRNA technology to airway epithelial cells following tropical and aerosol administration.

The I O C T zoo at the B. Two program is supported by preclinical data from a variety of models, including human and for it from kill empathy the liquid interface cell cultures.

So it's non human primates and the C. S. T O of deficient viewing Muslim. These studies have demonstrated the ability to efficiently deliver on Luna mrna technology to the airway epithelium cells. Following topical I never saw the administration. Additionally.

Additionally, intranasal administration has demonstrated the ability to the store chloride channel activity and the nasal epithelial cells and the so-called nasal potential different studies and the Saf T O of deficient mess and suggest that our approach has the potential to fundamentally address the underlying deficit associated with <unk> lung disease.

Stephen L. Eck: Additionally, intranasal administration has demonstrated the ability to restore chloride channel activity in the nasal epithelial cells in the so-called nasal potential difference studies in the CFTR deficient mass and suggests that our approach has the potential to fundamentally address the underlying deficit associated with CF lung disease.

We recently successfully completed play on D. We had interactions with FDA to enable the advancement of the ALC Teasdale of three two program into the clinic of expectation is to submit the Cta for the ALC T zero of three two per Gram in Q4 2021.

Andrew H. Sassine: We recently successfully completed pre-R&D interactions with FDA to enable advancement of the ARCT 032 program into the clinic. Our expectation is to submit a CTA for the ARCT 032 program in Q4 2021. We are excited about the potential of this program to benefit patients regardless of the underlying specific genetic abnormality causing their disease, and we are very much looking forward to moving ARCT 032 forward to the clinic. I will now pass the call on to Andy, our CFO.

We are excited about the potential of this program to benefit patients regardless of the underlying specific genetic abnormality, causing the disease and we are very much looking forward to moving the T zero to three to forward to the clinic.

I will now pass the call on for Andy our CFO.

Andrew H. Sassine: Thank you, Steve, and good afternoon, everyone. The press release issued earlier today includes financial statements for the fourth quarter of fiscal year 2020, which I will briefly summarize. Arcturus' primary source of revenue is currently from license fees and collaborative payments received from research and development arrangements with our pharmaceutical and biotech partners. For the year ended December 2020, the company reported revenues of $9.5 million, which is down from $20.8 million for the prior year. The decline in collaboration revenues primarily relates to three factors.

Thank you, Steve and good afternoon, everyone. The <unk>.

Press release issued earlier today includes financial statement for the fourth quarter of fiscal year, 2020, which I will briefly summarize on.

The truth of the primary source of revenue is currently from license fees and the collaborative payments received from research and development of arrangement with our pharmaceutical and biotech partners for the.

The year ended December 2020 of the company reported revenue of $9 $5 million, which was down from $28 million for the prior year.

The decline in collaboration revenue was primarily rate relate to three factors.

First of the five $6 million decrease in reimbursement from cure back associated with the OTC collaboration that ended in the third quarter of 2019.

Andrew H. Sassine: First, a $5.6 million decrease in reimbursements from CureVac associated with the OTC collaboration that ended in the third quarter of 2019. Second, we received a one-time license revenue of $3.3 million from Synthetic Genomics in 2019. And finally, we had slightly lower activity with other collaboration partners. On a quarterly basis, total revenue for the fourth quarter was $2.2 million, which was relatively flat when compared to the $2.3 million in the third quarter.

Second we received the onetime license revenue of $3 3 million from synthetic genomics in 2019.

And finally, we had slightly lower activity with other collaboration partners.

On a quarterly basis total revenue for the fourth quarter was $2 2 million, which was relatively flat when compared to the $2 3 million in the third quarter.

Total operating expense for the year ended December 31 2020.

Andrew H. Sassine: Total operating expenses for the year ended December 31, 2020 were $81.1 million, compared to $46.3 million for the prior year. The current year operating expenses were partially offset with $15.2 million of funds earned under the Singapore Vaccine Grant and funds awarded by the CF Foundation. The increase in net expenditures for the year ended December 31st, 2020, as compared to the prior year, was due primarily to increased activity in clinical and manufacturing expenditures related to the company's COVID-19 and OTC programs, as well as increased personnel costs and other facility costs related to the organizational growth of the company. On a quarterly basis, total operating expenses for the fourth quarter were $33.3 million compared to $23.3 million for the third quarter and $13.8 million for the same period of 2019.

For $81 $1 million compared to $46 $3 million for the prior year the.

The current your operating expenses were partially offset with $15 2 million all of the funds earned under the Singapore vaccine Grant and bonds awarded by the CF Foundation.

The increase of net expenditures for the year ended December 31, 2020 of compared to the prior of year with due primarily to the increased activity in the clinical and manufacturing expenditures related to the company's COVID-19, and OTC program as well as the increased personnel cost.

Off and other facility costs related to the organizational growth of the company.

On a quarterly basis total operating expenses for the fourth quarter with $33 $3 million compared to $23 $3 million for the third quarter.

The $13 $8 million in the same period of 2019.

Approximately $8 million of the sequential increase in operating expenses was due to the ramp in the COVID-19 program related expenses, which included additional personnel manufacturing and clinical trial expenses the <unk>.

Andrew H. Sassine: Approximately $8 million of the sequential increase in operating expenses was due to the ramp in the COVID-19 program-related expenses, which included additional personnel, manufacturing, and clinical trial expenses. The current quarter operating expenses were partially offset by $2.7 million of funds awarded under the Singapore Vaccine Grant and funds awarded by the Cystic Fibrosis Foundation. Our cash balance totaled $463 million as of December 31, 2020, compared to cash and cash equivalents of $301.1 million on September 30, 2020.

Current quarter operating expenses were partially offset with the $2 $7 million of funds awarded under the Singapore vaccine grants and funds awarded by the cystic Fibrosis Foundation.

Our cash balance totaled 463 million as of December 31, 2020, compared to cash and cash equivalent of $301 1 million on September 32020.

The increase in cash and cash equivalents compared to the September quarter was primarily due to the receipt of approximately $162 million of net proceeds from our December 2020 public offering.

Andrew H. Sassine: The increase in cash and cash equivalents compared to the September quarter is primarily due to the receipt of approximately $162 million in net proceeds from our December 2020 public offering. Additionally, subsequent to the end of the year, we received a $46 million loan from Singapore EDB to help fund the manufacturing of our COVID-19 vaccine program. Based on our current pipeline, the company's cash position is expected to be sufficient to support operations for more than two years.

Subsequent to the end of the year, we received a $46 million alone from Singapore ETB to help fund the manufacturing of our of COVID-19 vaccine program.

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

Our strong cash position enables us to fund the phase II and III clinical trial for ARX <unk> 'twenty, one as well as advanced or additional promising pipeline candidate.

Andrew H. Sassine: A strong cash position enables us to fund our Phase 2 and 3 clinical trials for ARC-21, as well as advance our additional promising pipeline candidates. We hope that ARC-21 will receive emergency use authorization later this year in one or more countries. Along with our global manufacturing partners, we have laid the foundation to produce hundreds of millions of doses of ARC-21 annually, and we have ongoing manufacturing campaigns to both meet clinical needs and to stockpile lyophilized ARC-21 for potential commercial use. Hey, thanks Andy.

We hope that our 'twenty, one will receive the emergency use authorization later this year and one of more countries.

Along with our global manufacturing partners, we have laid the foundation to produce hundreds of millions of doses of arc 21 annually and.

And we have ongoing manufacturing campaigns the.

Total meet clinical needs and the stockpile lyophilize of 21 put the potential commercial use.

I'll now pass the call back to Joe.

Hey, Thanks, Andy Arcturus has continued to make progress with our mrna based therapeutic platform in development stage pipeline.

Joseph E. Payne: Arcturus has continued to make progress with our mRNA-based therapeutic platform and development stage pipeline. We believe we are on track to rapidly progress ARCTO21 into a Phase 3 study and potentially gain emergency use authorization this year. We believe that ARCTO21 as a single administration investigational vaccine could have a differentiated profile compared to other available vaccines, positioning the product for potential widespread uptake in the years to come. We're also aggressively moving forward with our broader pipeline and anticipate reporting important clinical milestones from our other programs.

We believe we are on track to rapidly progress our CTO of 'twenty, one and two of phase III study and potentially gain the emergency use authorization. This year, we believe that our CTO of 'twenty one as a single administration investigational vaccine could have a differentiated profile to other available vaccines positioning the product.

For potential widespread uptake in the years to come.

We're also aggressively moving forward with our broader pipeline and anticipate report the reporting important clinical milestones from our other programs. We expect that later this year, we will obtain initial safety PK and biomarker activity data from our <unk> eight.

Joseph E. Payne: We expect that later this year we will obtain initial safety, PK, and biomarker activity data from our ARCT 810 clinical study being conducted in patients with OTC, and we look forward to starting a Phase II multiple dose study later this year. I've also been very pleased with the progress our R&D team has made in advancing ARCTO32 for cystic fibrosis. This program utilizing an aerosolized administration of our lunar lipid-mediated mRNA technology demonstrates the breadth of potential application of our platform.

10 clinical study being conducted in patients with OTC and we look forward to starting a phase two multiple dose study later this year.

I've also been very pleased with the progress our R&D team has made in advancing our CTO of <unk> 32 for cystic fibrosis. This program utilizing an aerosolized administration of our lunar lipid mediated mrna technology demonstrates the breadth of potential application of our platform. Our aspiration with this program is to correct.

For the core underlying deficiency seen in cystic fibrosis and to provide a meaningful new treatment approach for.

Joseph E. Payne: Our aspiration with this program is to correct the core underlying deficiency seen in cystic fibrosis and to provide a meaningful new treatment approach for the tens of thousands of individuals living with cystic fibrosis. In addition to these advanced programs, our team is also working hard to apply our mRNA platform to develop vaccines and therapeutics for many other life-threatening diseases, and we look forward to providing further updates on additional programs at a later date. At this point, we can go ahead and open the line for questions. Operator, please proceed.

The tens of thousands of individuals living with cystic fibrosis. In addition to these advanced programs. Our team is also working hard to apply our mrna platform to develop vaccines and therapeutics for many other life threatening diseases and we look forward to providing further updates on additional programs.

At a later time.

At this point, we can go ahead and open the line for 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 one on your telephone keypad. The confirmation tone will indicate that your line is on the question queue you bid for.

Operator: 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 that your line is in the question queue.

Press Star two if you would like to remove your question from the queue for participants using speaker equipment and may be necessary to pick up of your handset before pressing the star keys.

Operator: You may press star 2 if you would like to remove your question. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the start button. One moment, please, while we poll for questions. Our first question comes from Yasmeen Rahimi with Piper Sandler. Please proceed with your question. Hi, team.

One moment, please while we poll for question.

Our first question comes from Jack Meehan Rahimi with Piper Sandler. Please proceed with your question.

Hi team. Thank you so much for all of the great updates number of questions for you. The first one is direct with the Doctor.

Yasmeen Rahimi: Thank you so much for all the great updates. A number of questions for you. The first one is directed to Dr. Uy. Dr. Uy, thank you for sharing the new data with us. Can you comment on whether you looked at T cell responses post-day 28, specifically maybe at least at day 60, and how those compare to BNT162b2. And then the second question is for Joe.

That's really thank you for sharing the new data with on can you comment on if you looked at T cell responses post day 28 mm specifically, maybe at least the day 60, and how those compare to be N T. One six to be too.

And then the second question is for Joe Joe can you maybe comment on if our choice is equipped and ready to go to incorporate new construct to provide coverage of the bay area and in phase three and then the third question is to you will we be seeing the phase two data before you.

Yasmeen Rahimi: Joe, can you maybe comment on if Arcturus is equipped and ready to go to incorporate new constructs to provide coverage of the variance in phase 3? And then my third question to you, will we be seeing the phase 2 data before you start commencing phase 3? And thank you for taking my questions. Great. Thanks, Yaz.

Derek commencing phase III.

And thank you for taking my questions.

Great. Thanks, Yaz Professor Louis the first one's yours.

Okay. Thanks, Thanks very much at the.

Professor Ouyang Inyong: Professor Uy, the first one's yours. Okay, thanks very much. Those are great questions. Yes, we have looked at longer time points for ARCT021. Day 28 and beyond. I forget the actual exact time points, but it actually works.

Lots of great questions, Yes, we have looked at that.

Longer time points for the RCT sort of two one.

On a day 28 and be on.

Up to I forget the actual exact time points back to the world.

Actually in progress I mean, the high levels of some reason you do see some level of contraction, which is normal for T.

Professor Ouyang Inyong: I mean, the high-level summary is that you do see some level of contraction, which is normal for... [inaudible] But that will be something that we're also going to examine further in an open label long-term follow-up to look at how well this memory responds to be elicited upon re-exposure. What is clear, though, is that the levels both at... the cube stage as well as at the contraction stage, and in this case for B and D, quite a lot lower.

T cells has the switching to memory.

But that that would be something that we're also going to go and ex.

I mean for the in the open label long term follow up look at how well these memory responses school.

Be elicited.

Upon the exposure to the antigen.

What what is true.

The clear, though is that the levels both at the acute stage as well as that of contraction stage and in this case for BMT once used to be two weeks at day 21, the idea all.

Quite a lot lower than what we've seen with the guarantee.

On.

Professor Ouyang Inyong: Thanks. Did you have a follow-up question for Professor Uy-Yas, or would you like me to address your second question? I guess, just as he has, if I may, can you elaborate on the contraction that he was referring to? So, yeah, the contraction actually happens when you have this acute exposure, you get a lot of...

Thank you.

Hey, Thanks, Ed did you have a follow up question for Professor OUI Yours or would you like me to address your second question.

I guess just two of S. He has maybe and if I may can you elaborate on the contraction that he was referring to on.

So yeah, that's the contraction actually when you when you have this acute exposure you get a lot of them.

Expansion of the T cells and then so that's the acute response and then over time then.

Professor Ouyang Inyong: So that's the acute response, and then over time, a portion of which will switch over to the acute response, lymphoid tissues, or possibly even where the exposure of the antigen occurs, and in this case, it could well be the skin. So, at that point, when you measure the T-cells in the blood, you see a contraction. But the important thing is that as long as these T-cells can be rapidly recalled upon

Some of the always here on Washington, which was the cyclical glad to become.

The memory T cells, and then the horn into the lymphoid tissues, or possibly even where the exposure.

Antigen on kind of in this case could well be the skin in the muscles and all of that and of course that so.

The point when you measure the T cells in the blood you see a contraction.

But the important thing is that you know that these T cells can be rapidly because of the Barnett antigen exposure on it.

It looks like that will be protection.

I hope that answers the question I'm not sure whether it's the scientific question, you're asking price and the amount of yourself.

Professor Ouyang Inyong: It looks like they will be protected. I hope that answers the question. I'm not sure whether it's a scientific question you're asking, and Aung San Suu Kyi. Thank you. That was helpful. I'll move on to Joe. Yeah, if you want to.

Thank you that was helpful I'll move on or to a total yeah yeah.

Yeah, Yeah net now with respect of variant coverage I mentioned earlier that we're closely monitoring and closely.

Joseph E. Payne: Yeah. Now, with respect to variant coverage, I mentioned earlier that we're closely monitoring and closely evaluating the COVID variants that are potentially escaping or evading neutralizing antibodies. That is in the literature, and there are reports on those, right? But cellular immunity may provide broader variant coverage; cellular immunity may actually be very important for resistant variants that evade these neutralizing antibody titers. I would refer you to Dan Barouch's work at Harvard Medical School.

Evaluating the COVID-19 variance that are potentially escaping revealing neutralizing antibodies that is in the literature Theres getting reports on those right.

But cellular immunity may provide broader variant coverage.

On the.

Cellular immunity may actually be very important for resistant variance that evade these neutralizing antibody titers.

I refer you to Dan Barros as work at Harvard Medical School, you know he was quoted to say I'm just looking at my notes here, but he was quoted to say that vaccine induced T cell responses are important for COVID-19 vaccines particular, particularly for resistant variance that might partially evade neutralizing antibodies.

Joseph E. Payne: You know, he was quoted to say, I'm just looking at my notes here, but he was quoted to say that vaccine-induced T cell responses are important for COVID vaccines, particularly for resistant variants that might partially evade neutralizing antibodies. So this is becoming a more well-understood and accepted principle that cellular immunity is important for resistant variants. So that's point number one. Now, having said that, even though ARCTO21, as just shown by Professor Uy, generates a robust T cell response that may be broadly protective, if there is any variant that happens to escape our vaccine, then we're still a messenger RNA vaccine, and it's a readily updatable technology, and we can move quickly if needed. Thank you, Joe.

So this.

This is becoming a more well understood and accepted principle debt cellular immunity is important for resistant variance.

So that's point number one.

Having said that even though our CTO of 'twenty. One is just with shown by professor OUI generates a robust T cell response that may be broadly protective if there is any variance that happens to escape our vaccine.

And we're still of messenger RNA vaccine and its a readily update of both technology and we can move quickly if needed.

Thank you Joe.

And will we be seeing the phase two data for phase III.

Joseph E. Payne: And will we be seeing the Phase 2 data before Phase 3? Yes, so Steve, do you want to address that question? So we'll definitely be seeing the Phase 2 data before Phase 3. We've got some interim analyses that are going to be conducted fairly quickly, and they'll go to our Data Safety Monitoring Board for review prior to the finalization of our Phase 3 dose. Depending on the nature of the evaluation, it will depend on whether it's worthwhile sharing as an update at any level of detail because we're conducting more than one interim analysis, and they're looking at different things.

Yes, so Steve do you want to address that question.

So we'll definitely be saying the phase II data before the phase III. We've got some interim analyses that are going to be conducted fairly quickly and they'll go to a data safety monitoring board for review towards the Finalization of our of our phase III dose.

Depending on the on the nature of the evaluation of both depending on whether it's worthwhile sharing is an update and any level of detail because we are conducting more than one interim analysis in the they're looking at different things. Some of the just looking at early safety responses and then others are looking at Immunogenicity responses. So.

Stephen L. Eck: Some are just looking at early safety responses, and then others are looking at immunogenicity responses. So it's quite likely that we'll issue something brief about the safety and something more detailed about the immunogenicity as that data reads out. Thank you, Steve.

Quite likely that the group.

Do something brief.

How about the safety and something more detailed about the immunogenicity as that day.

Data reads out.

Thank you Steve.

Okay.

Yeah.

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

Seamus Christopher Fernandez: Thank you. Our next question comes from Seamus Fernandez with Guggenheim. Please proceed with your question. Thanks for the question. So, I have a few questions here.

Well thanks for the question so.

Few questions here.

First off can you guys. Please talk about your solution to variance in and how you are approaching that in the context of correlates of.

Seamus Christopher Fernandez: First off, can you guys please talk about your solution to variants and how you're approaching that in the context of correlative protection that is emerging, you know, with FDA guidance, the EU's guidance, and then, you know, some folks are implying that the WHO may come up with a standardized correlative protection that crosses vaccines. So, I was just hoping that you would comment on, you know, your approach to variants and then the correlative protection.

Protection.

<unk> are emerging.

With the Fda's guidance the.

You used guidance from them.

Some folks are implying that the W. H O.

<unk> come up with the standardized correlate of protection that crosses vaccines. So just hoping that you would comment on.

Youre approached the variance.

And then the quality of protection.

The second question is on your Phase III trial design plan.

Seamus Christopher Fernandez: The second question is about your phase three trial design plan. Can you just give us a sense of the size of the study and how you're planning to execute it? Would this be a head-to-head type study, a crossover study? And just give us a general sense of the size.

Can you just give us a sense of the size of the study.

And how you're planning to execute it.

Would this be had the head type study of crossover study.

And just give us a general sense of of the size and.

And then I have a couple of additional questions.

Seamus Christopher Fernandez: And then I have a couple of additional questions. It's good to talk to you. This is Joe.

Sure Seamus it's good to talk to you this is Joe.

Thanks.

The planet with respect to variance it just to reiterate is that our present vaccine because of the cellular immunity profile is sufficient to capture of cover the any any variance that are out there.

Joseph E. Payne: Plan A, with respect to variants, just to reiterate, is that our present vaccine, because of its cellular immunity profile, is sufficient to capture or cover any variants that are out there. If there are variants that are challenging or escape or evade protection with our vaccine, we're preparing. We mentioned we're not only monitoring but evaluating the variants that are escaping these neutralizing antibodies, and we'll be well positioned to swap out any manufacturing run with an upgraded variant if needed. Does that address your question? I guess the question is, is it sufficient to cover it in what way, though, Joey?

If there are variance that are challenging or escape of of aid protection with our vaccine.

We're preparing we mentioned we're not only monitoring but evaluating the variants that are that are escaping. These neutralizing antibodies and we will be well positioned to to to swap out any manufacturing run with an upgraded variant if needed.

Does that address your question.

I guess the question is the question.

Yeah, I guess, the sufficient to cover and in what way, though Joey Theres a number of different approaches that we talked about the.

Seamus Christopher Fernandez: There's a number of different approaches that we're talking about, disease prevention, prevention of severe disease, there's a lot of different ways to define that. Right, I understand. Steve, do you want to give the first crack at that?

The <unk> prevention prevention of severe disease.

There's a lot of different ways to define that.

Right understand Steve.

Steve do you want to give the first crack at that yeah. So I think the.

There's a couple of parts in an answer to the question one of the FDA very recently I think within the past week of given updated guidance guidance that.

Stephen L. Eck: Yes, I think the... There's a couple of parts to this answer. One is the FDA has recently, I think within the past week, given updated guidance that includes specific appendixes on how to bring forward new vaccines or variations on existing vaccines for emerging variants. And then the second piece is the effectiveness of the current vaccine against emerging variants. So maybe we just deal with the second piece first, which is really you need to conduct a clinical trial with efficacy-based outcomes in order to address that.

And that includes the specific appendix on how to.

Bringing forward, new vaccines or variations on existing vaccines for them.

For the emerging variants.

And then the second piece is effectiveness of the back of the current vaccine against the emerging variants. So maybe just starting with the second piece first which is.

Really you need to conduct the clinical trial with efficacy based outcomes in order to address that and then people that have been vaccinated.

Stephen L. Eck: And then people that have been vaccinated that end up contracting COVID, then actually sequencing the virus they've got to see whether it's a variant or not. And that can give you an idea of whether you have active or adequate coverage for all of the variants or whether there's one or more particular variants that are escaping your vaccine. And we intend to do that.

The end up contracting COVID-19.

Then actually sequencing that the.

Volume is that they've got to see whether it's the varian or not and that can give you an idea of whether you have active.

Adequate coverage for all of the variants of whether it is one of more particular variance that of escaping the go vaccine and we intend to do that.

The second piece is.

Being able to rapidly pivot with you of vaccine platform to a couple of new variance of where we're seeing some of this was that with the other my mom and I vaccines at the moment, where the where theyre rapidly retooling manufacturing.

Stephen L. Eck: The second piece is being able to rapidly pivot with your vaccine platform to cover new variants. And we're seeing some of this with the other mRNA vaccines at the moment where they're rapidly retooling, manufacturing a vaccine with a slightly different sequence, and then taking that forward into early phase clinical trials to generate immunogenicity data, which then hopefully can be used to show activity against the variant. In order to really go down that road, which is the road that's been put forward by the FDA, you require efficacy data from your vaccine platform.

The vaccine with a slightly different sequence and then taking that forward into the early phase clinical trials.

The generate immunogenicity data.

Then hopefully can be used to to show activity against the against the variant in order to really go down that route which is the way the same pool by the FDA.

Of acquire.

Efficacy data from your vaccine platform. So we're moving aggressively forward with our phase III clinical trial that will generate the the body of the efficacy data that we need to the entity to be able to then very very rapidly pivot to utilize that data to fast track subsequent vaccines if the unnecessary.

Stephen L. Eck: So we're moving aggressively forward with our phase three clinical trial that will generate the body of efficacy data that we need to then very, very rapidly pivot to utilize that data to fast-track subsequent vaccines if they're necessary. And at this point, we don't know whether we're going to need different vaccines for at least the variants that are out there at the moment.

And at this point, we don't know whether we're the way we're going to need different vaccines for at least the vegas out of that.

Moment.

We believe that the T cell coverage that we're seeing with all of vaccine positions us well for.

Stephen L. Eck: We believe that the T cell coverage that we're seeing with our vaccine positions us well for coverage against all of the variants. But if it turns out that we do need additional coverage, then we can leverage the clinical data that we'll have from our Phase 3 program, which we're about to kick off, to very rapidly bring forward new variants based upon immunological correlates of protection as they emerge.

For coverage again against all of the valence, but.

If it turns out that we do need additional coverage then we can leverage the clinical data that we'll have from our phase III program that we're about to kick off two of IRA.

Rapidly bring forward new guidance based upon the immunological corners of protection as they emerge.

Great.

As we look at the design of the Phase III can you just help us understand.

Seamus Christopher Fernandez: And as we look at the design of the Phase 3, can you just help us understand that there are different points in time from where you can start counting events. A number of the, you know, sort of two-dose companies certainly seem to benefit from that quite a bit in terms of the disclosed and sort of trumpeted efficacy. As we think about the design of Phase 3 and the endpoints and your discussions with the agencies in the countries that you're going to pursue, can you just give us a sense of how you're going to execute your Phase 3 study? Yeah, sure.

There are different points in time from where you can start counting events a number of the sort.

The two dose company certainly seem to benefit from that quite a bit in terms of the disclosed them.

And sort of trumpeted efficacy.

As we think about design of phase III and the endpoints in your discussions.

With the agencies in.

In the countries that you're going to pursue can you just give us a sense of of how youre going to execute your phase III study.

Yeah sure so.

It's gonna be a randomized placebo controlled study of comparator or placebo.

Stephen L. Eck: So it's going to be a randomized placebo-controlled study, so I've compared it to placebo. It will be a one-to-one randomization, the same as the other studies, or most of the other studies, at least, that have moved forward and got emergency use authorization or conditional approval. At the moment, there are going to be several thousand participants in the region of 10,000 to 15,000, and they're going to be from several

It will be of one to one randomization of the same as the other studies of most of the other studies at least that of move forward and got emergency use authorization of conditional approval at the moment.

He is going to be several thousand participants.

In the region of 10% to 15000.

And there's going to be several different countries, we're not disclosing the actual countries at the moment, because we are going through the process of discussing with the regulators and doing feasibility individual sites to choose from our short list of the countries that are.

Seamus Christopher Fernandez: We're not disclosing the actual countries at the moment because we're going through the process of discussing with the regulators and doing feasibility at individual sites to choose from our short list the countries that are most tractable for a rapid study startup. But in general terms, we're looking at countries that have a high incidence of COVID at the moment so that we can collect events quickly, that have a very short regulatory approval process in terms of approving the start of the clinical trial, and also countries that have a low vaccine penetrance and are predicted to continue to have a low vaccine penetrance at least through the first four to six months of the study.

The most tractable for a rapid study startup, but in general terms. We are looking at countries that have a high incidence of COVID-19 at the moment. So that we can collect events quickly.

That of a very short regulatory approval process in terms of approving the clinical trial startup and also countries that they.

I have a low vaccine penetrance of predicted to continue to have a low vaccine penetrance of at least through the first for six months of the study.

That allows us to.

The collect all of our events that are needed and the safety follow up that we require to get to get registration.

Seamus Christopher Fernandez: That allows us to collect all of our events that are needed and the safety follow-up that we require to get registration. I think it's inevitable that after a period of time, participants that have been vaccinated with placebo are going to have to cross over, and we've seen that in the studies where they've already got emergency use authorization, they're now allowing crossover, but the important thing is that we don't cross over until we've collected all of our events, and that's what we're planning at the moment.

I think it's inevitable that after a period of time.

Participants that have been vaccinated with placebo are going to have to of course, either when we've seen that with the.

The study is that of what I've already got emergency use authorization and then on allowing cost side of it by the important thing is that we the crossover until we've collected all of our events and that's what we're planning at the moment.

Great.

Maybe just as the.

Seamus Christopher Fernandez: Great. And maybe just as a follow-up question, in terms of just the phase two study data that you guys know so far, can you just give us an update on, you know, how many patients have been dosed? You know, is the safety actually known to the team? And is it unblinded?

One follow up question in terms of the just the phase II study data that you guys know so far.

Can you just give us an update on how many patients have been dosed.

On the safety actually known to the team and is it on blinded.

And is there anything that you would comment on with regard to the phase II study.

Stephen L. Eck: And is there anything that you would comment on with regard to the phase two study? Thanks. I can tackle that question as well. So we've vaccinated over 500 people at the moment. I don't have the most up-to-date figures from today, but it was definitely over 500 as of Saturday. No dosing was performed on Sunday.

So sorry for that question as well so we've vaccinated over 500 people at the moment.

I don't have the the.

Most up to date figures from from today, but it was definitely it was out of over 500 as of Saturday No dosing was performed on Sunday.

Where we don't we haven't unblinded the data at the moment, but we do have of safety Review Committee that is actively looking at the day to on an ongoing fashion.

Stephen L. Eck: We haven't unblinded the data at the moment, but we do have a safety review committee that is actively looking at the data in an ongoing fashion, in a blinded fashion. In broad terms, we haven't seen anything in the Phase II data that is markedly different from what we've seen in our Phase I-II study. Although, of course, we're blinded to dose, so we don't know what's happening at the different doses.

In a blinded fashion in broad terms, we haven't seen anything in the phase II data that is that is markedly different from what we've seen in our phase one two study.

Although of course, we're blinded to dose the we don't know what's happening at the different doses, but at a very high level. The data looks very similar to what we've seen in the phase one two study.

Stephen L. Eck: But at a very high level, the data looks very similar to what we've seen in the Phase I-II study. Okay, great. And this will be my last question. Any second doses? Have any of the second doses been executed in the study as yet? Or is it still too early?

Okay great.

This will be my last question any second doses of.

Have any of the second dose has been executed in the study.

Yes.

Is it still too early.

Yeah. So a number of people of the state the second dose already I don't have that the that number to hand at the moment.

Stephen L. Eck: Yeah, so a number of people have already received a second dose already. I don't have that number on hand at the moment, but it's more than a few. And even with the second dose, we're not seeing anything remarkable. Okay, great. I'll jump back in the queue. Thanks. Thanks, Seamus.

But it's more than a few and even with the second dose way of where we're not seeing anything remarkable.

Okay, great I'll jump back in the queue. Thanks.

Thanks Seamus.

Thank you. Our next question comes from Nick Abbott with Wells Fargo Securities. Please proceed with your question.

Nick Abbott: Thank you. Our next question comes from Nick Abbott with Wells Fargo Securities. Please proceed with your question. Hi guys, it's Joe on behalf of Nick. Congratulations on all the progress and I appreciate you taking the questions. Two from us, you know, maybe just further on the phase three design, without disclosing specific countries, you know, how do you think about site distribution in terms of major geographies?

Hey, Nick Hi, guys, it's Joe on for Nick Congrats on all of the progress and I. Appreciate you taking the questions.

Two from us.

Maybe just further on the phase III design without disclosing specific countries. How do you think about site distribution in terms of major geographies I'm I'm, assuming it's primarily ex U S.

Nick Abbott: I'm assuming it's primarily ex-US and, you know, what consideration will be given to, you know, the prevalence of variant strains within the countries you select? And then, you know, beyond that in the phase 3 design, to what extent do you intend to characterize the T-cell immunity component of the story? And secondly, on the recent licensing deal with Olexion, is there any additional detail you can provide in terms of the specific technology that was licensed and, you know, if and when you expect the technology to be transferred to your manufacturing partners? And could this technology potentially accelerate your prior guidance of, you know, hundreds of millions of doses annually? Great questions. The first one will be addressed by Steve, and then I can handle the Alexion question.

What consideration will be given to the prevalence of Ah variant strains within the countries you select.

And then beyond that of the phase III design to what extent do you intend to characterize.

The T cell immunity component to the story.

And then secondly on the recent licensing deal with Alexia on is there any additional detail you can provide in terms of the specific technology that was licensed.

If and when you expect the technology will be transferred to your manufacturing partners and could this technology potentially accelerate your prior guidance of of.

Hundreds of millions of doses annually.

Great questions the.

The first of all of it will be addressed by Steve and then I can handle the alexia on the question.

Okay.

Thanks for all great questions.

Joseph E. Payne: Okay, so thanks, all great questions. With regard to the phase three study, we're focusing on geographies where we can do placebo-controlled clinical trials and where the COVID incidence rate is high. We're not focusing so heavily on emerging variants because it's difficult to predict and stay ahead of that. So, for instance, the UK variant has a relatively low prevalence in the United States at the moment but is predicted to be a dominant strain by the end of March based on some models, and that time frame would obviously be within the time frame for recruiting a clinical trial.

With regards to the phase III study, we are focusing on geographies, where we can do placebo controlled clinical trials on where the COVID-19 incidence rate is high we're not focusing so heavily on the emerging variants because it's difficult to predict and stay ahead of that so for instance, the UK Varian has a relatively low prevalence in the United States at the moment, but is predicted to be.

The dominant strain by the end of March based upon some models in that timeframe, but obviously be within the timeframe for recruiting of clinical trials. So I'm trying to stay ahead of the variance I think is ASP, Utah. So we'll just have to manage that within the clinical trial and as we said we are confident that because of the strong T cell responses that we're saying that we.

Stephen L. Eck: So trying to stay ahead of the variants is futile, so we'll just have to manage that within the clinical trial. And as we said, we're confident that because of the strong T cell responses that we're seeing, we are going to actually have good coverage against the variants. In terms of the last part of the phase 3 clinical trial question, would you mind just repeating it? Yeah, just in terms of, you know, to what extent will you measure and characterize the T cell immunity component of the story?

The all going to actually have good coverage again against the variance.

In terms of.

On the last part of the of the Phase III clinical trial question would you mind just repeating it.

Yeah, just in terms of you know to what extent will you measure and characterize the T cell immunity components of the story.

So I think in the phase III study that is more challenging and we are doing more T cell working on our phase II study.

Stephen L. Eck: Yeah, so I think in the Phase 3 study that's more challenging, and we are doing more T-cell work in our Phase 2 study, so additional T-cell data is going to be coming out. Our partner that's conducting the lab work is just in the process of validating those assays at the moment, so we'll be able to provide the results of that in due course. In the Phase 3 study, we're not currently planning to conduct any more T-cell analysis because I don't think it helps us very much to get beyond the body of T-cell work that we'll have by then.

So the additional.

The T cell data kind of be coming out.

Our partner <unk>.

The lab work is just in the process of validating those assays at the moment, so we'll be able to provide.

On the results of that in due course.

The phase III study, but not currently planning to conduct any any more T cell analysis that I think it helps us very much to get.

Beyond the.

The body of T cell that we'll have by the end.

Great and with respect to the second question.

On the.

The.

Stephen L. Eck: Great, and with respect to the second question, the exclusive license that we acquired from Elexion helps us with the technology to support our highly efficient processes to manufacture high purity mRNA vaccines. Arcturus has three franchises, not just the vaccine franchise, but also a liver and a lung franchise. And these liver and lung areas are systemically or inhaled administrations of messenger RNA, which require a higher barrier of purity, and it's of extreme importance to have high purity messenger RNA to support those programs. But having said that, we've applied this Elexion IP to ongoing programs, including our vaccine program. Will this provide advantages?

Excuse of the exclusive license that we acquired from <unk>.

For the Alexia on helps us with the technology to support.

Our highly efficient processes to manufacture high purity mrna vaccines.

Arcturus has three franchises not just the vaccine franchise, but also of liver and lung franchise and these liver and lung areas of systemically or inhaled administrations of messenger, RNA, which require a higher barrier of purity.

Of extreme importance step high purity of messenger RNA to support those programs, but having said that we've applied the selection of on IP to the the ongoing programs, including.

Our vaccine program and we will just provide advantages absolutely with respect to.

The more efficient processes and higher purity, which is applicable not only to our liver and lung programs, but of course also of importance to the.

Joseph E. Payne: Absolutely, with respect to more efficient processes and higher purities which are applicable not only to our liver and lung programs but, of course, also to the vaccine program as well. Great, thank you. And, you know, in terms of whether this technology has already been implemented? Or at what point do you expect it to be transferred to manufacturing partners? I mean, is it conceivable to think that it will be involved in the manufacturing runs for phase three? Or is it more down the line to look at commercial supply?

Of the vaccine program as well.

Great. Thank you.

In terms of has this technology already been implemented or at what point do you expect it to be transferred to manufacturing partners. I mean is it conceivable to think that it will be involved in the manufacturing runs for phase three or is it more down the line looking at commercial supply.

I just had one of your share.

Nick Abbott: Yeah, Pad, why don't you... Yeah, no, thanks for that question. Yeah, so we're obviously, we've been in discussions with Alexian for quite a while to evaluate the specific technology. And we've evaluated that in-house, and we believe these processes can be adapted for our future batches. So that is correct. And these can, as Joe mentioned, these will be implemented for our protein replacement applications. But these can definitely be used for our commercial batches of COVID as well. Great, very helpful guys, thank you and congrats again on the progress.

Yeah no. Thanks for that question, yes. So we're obviously we've been in discussions with the election for quite a while to evaluate the specific technology and we've evaluated that in house and we believe.

These processes can be adapted for our future batches. So that is correct and these kind of as Joe mentioned these will be implemented for our.

The protein replacement applications, but this can definitely be used for commercial batches of COVID-19 as well.

Great very helpful guys. Thank you and the congrats again on the progress.

Thanks.

Yigal Nuchomavitz: Thank you. Our next question comes from Yigal Nuchomavitz with Citigroup. Please proceed with your question. Hi, thanks. I have two questions.

Thank you. Our next question comes from Yigal <unk> with Citigroup. Please proceed with your questions Alright.

Alright. Thanks.

Two questions. The first one with respect to the phase two data what do you need to see in that data that will provide additional confidence.

Yigal Nuchomavitz: The first one, with respect to this pending Phase 2 data, what do you need to see in that data that will provide additional confidence that you selected the 5-microgram single-dose regimen? And conversely, what data from phase 2 would make you revert to the two-dose regimen, as well as potentially the 7.5-microgram dose? And then separately, could you just comment on what's different about your technology that allows for lyophilization, in contrast to the other mRNA vaccines already commercialized that have the liquid formulation? Steve, do you want to address the first? Okay, sure.

On your selected the five microgram some of those regimen on Conversely, what data from the phase two would make you revert to the two dose regimen.

As well as potentially the southern of half from like.

Mike.

And then separately could you just comment on what's different about the technology that allows for layoffs of elimination in contrast to the other mrna vaccines already commercialized but have the.

The liquid formulation. Thank you.

Steve do you want the just the first okay.

So primarily we are just looking for confirmation of the safety data readout from the phase II study we are collecting.

Stephen L. Eck: So primarily, we're just looking for confirmation of the safety data readout from the Phase 2 study. We are collecting immunogenicity data as well, but our first readout as we move towards Phase 3 is going to be based on safety. Since we disclosed data back in November and again in December, we've had subsequent internal reads on the data that give us a lot of confidence that the 5 microgram dose is really a sweet spot for us.

<unk> the data as well, but our first read out as we move towards phase III is going to be based upon safety.

Since.

We disclosed data back in November and again in December we've had subsequent.

Internal rates on the data that gives us a lot of confidence in the five that the five microgram doses, where the sweet spot for US and also is that dose is the one for which at least in the phase. One two study we have most exposures in most information. So we think we have sufficient data from the immunogenicity perspective to confidently.

Stephen L. Eck: And also, that dose is the one for which, at least in the Phase 1-2 study, we have the most exposures and the most information. So we think we have sufficient data from the immunogenicity perspective to confidently select that dose. So we're primarily looking at safety data readouts in the first instance. We're also going to have a later immunogenicity interim analysis that allows us to rapidly switch tack if we need to down the

Select that dose.

So the primarily looking at safety data Readouts in the first instance, we're also going to have a later immunogenicity interim analysis that allows us to rapidly.

Switch tack.

If we need to debt.

The mode.

Stephen L. Eck: And just if I can interject, Steve, the likelihood of us proceeding with the 2-shot vaccine is very low. Like I mentioned in the introductory comments, that in the endemic phase of COVID, we believe that it's all going to be single administrations. Whether these are unvaccinated people, whether they're COVID survivors, whether they're viral vector recipients or messenger RNA vaccine recipients, they're all just going to want a single administration, whether it's a boost or a single injection format.

And just if I can interject, Steve the likelihood of us proceeding with the two shop vaccine is very low.

Like I mentioned in the in the introductory comments debt in the endemic phase of the Covid.

Covid, we believe that it's all going to be single administrations, whether these are on vaccinated people, whether they're COVID-19 survivors, whether their viral vector recipients or messenger RNA vaccine recipients. There I'll just kind of want a single administration, whether it's a booster of single injection format. So we're gonna be it were fully <unk>.

Ending or planning on collecting our phase III data as a single shot and we're very encouraged by professor who is the recent data to show that our vaccine favors.

Stephen L. Eck: So we're fully intending or planning on collecting our Phase 3 data as a single shot, and we're very encouraged by Professor Uy's recent data to show that our vaccine favors combined, or it compares favorably. Oh, and then with respect to the second question, Padmanabh.

Our income compares favorably.

Oh, and then with respect to the second question Pat.

Sure.

Yeah.

We've been working on whereas the last players the messenger RNA for for quite a few years.

Padmanabh Chivukula: Sure. You know, we've been working on lipolyzed messenger RNA for quite a few years. We first introduced that for our protein replacement applications, and since we had the platform already working for our protein replacement applications, we decided to implement that for the COVID-19 vaccine. There's some specific know-how that goes into the lipolyzation of nanoparticles containing especially large messenger RNA, but because we started our program a few months after some of the other leaders, during that interim time, we were able to develop a live program and implement that into phase three.

We first introduced debt for our putting the placement applications and since we had the platform already all are already working for for our protein replacement applications, we decided to implement that for all of the COVID-19 vaccine.

Some specific know how that goes into law the localization of nanoparticles containing the.

These especially these last months of the messenger RNA.

But the because we started our program for two months after some of the other leaders.

During that interim time, we were able to develop on the Io program and implement that into our phase III.

Yes, so the phase III study will be evaluating our <unk>.

Padmanabh Chivukula: Yeah, so the phase three study will be evaluating our lyophilized version of our vaccine, and we think this will be very important because we have challenges with respect to just distributing something that once it's melted, it has to be utilized, in the case of a freeze-dried product, you don't incur those challenges of distribution. Thank you. Thank you. Thank you. Our next question comes from Wang Qilin on behalf of Leidenberg.

Version of our <unk>.

Of our vaccine and we think this will be very important for.

Especially for countries that have challenges with respect to just distributing frozen liquids forget about the cold chain just the challenges associated with something that once it's melted it has to be utilized.

On the case of of freeze dried product that you don't incur those challenges of distributions.

Got it thank you.

Thank you.

Thank you. Our next question comes from Wang Julin with Ladenburg. Please proceed with your question.

Boran Wang: Please proceed with my question. Hi. Thanks for taking my question. Maybe just first to follow up on the localization, could you further clarify how you've done any region studies at this moment? Or will you do a region study, and compare the current version before the start of phase three? Will we need any bridging studies, Steve?

Yes.

Alright, Thanks for taking my question, maybe just first of all of the of localization.

Could you further clarify have you done any study of this moment or you do a bridging study compare the current version before the start of phase III.

Well, we need any bridging studies, Steve maybe you can comment is that what your question is when.

Boran Wang: Maybe you can comment. Is that what your question is? So, I can touch on that. So, Wang Zi, one of the things that we, when we started to develop the LIO formulation is we wanted to first look at analytical comparability, of course.

<unk> does that yes.

Okay.

So when the so one of the things that we when we started the developed the law.

Io formulation as we wanted the first look at analytical comparability of course.

We wanted to ensure that pre and post the reconstitution of the particle size of the characteristics were similar between our frozen liquid formulation in the line of product that was one of the key parameters that we evaluated first.

Padmanabh Chivukula: We wanted to ensure that, pre and post reconstitution, the particle size, and the characteristics were similar between our frozen liquid formulation and the LIO product. That was one of the key parameters that we evaluated first. And then the second piece was looking at immunogenicity. We wanted to ensure that we were seeing similar immunogenicity in our preclinical studies for our frozen product as well as our, you know, LIO product. And we've collected that data set, and now we're comfortable with moving forward with our phase three based on that data. Okay.

And then the second piece was looking at Immunogenicity, we wanted to ensure that we were seeing similar immunogenicity in our preclinical studies.

For our frozen product as well as a lot of product and we've collected that data set and now we're comfortable with moving forward with our phase III and based on all of that data.

Okay got it thank you.

And then maybe also a question for Doug.

Boran Wang: And then maybe also a question for Dr. Oe, just a clarifying question about the new data, very encouraging. In the press release, it was also mentioned that the PRNT increased to 100% by day 36 and on day 28 to 59%. So maybe just a clarifying question: how do you compare this with the PRNT50?

Just a clarifying question about the new data we are very encouraging.

In the press release also mentioned that the.

<unk> increased to 100% by day, so to speak and the.

On day two of the age of 59% So maybe just.

Clarifying question, how to compare the squeeze the pier and the 50 I mean, the definition of 50 I guess.

The neutralizing neutralizing for 50% of the.

Professor Ouyang Inyong: I mean, the definition of 50, I guess it's neutralizing 50% of the virus, right? 59% doesn't mean neutralizing 59% of the virus on day 28. How, maybe if we convert this into PRNT50 so that we can compare it with the previous data, can you help me with that? How do we, you know, compare this with prior data? Yep, that's a very good technical question, actually. So the 59% is the prevalence of the proportion that tests positive.

Virus right, 59% doesn't mean neutralizing for 69% the.

Where's the on the tune the E mail.

If we convert this into Pan Pim.

<unk> 50.

So.

Compared with the previous of data can you help me with that.

That.

The comparable.

Credit data.

Yes.

Very good technical cash it actually so the 59 percentage the prevalence of how the proportion of the test positive.

This is sort of the way we did it Noah slightly different so for ICT.

Professor Ouyang Inyong: The way we did it, though, was slightly different. For example, for ARCT021, our minimum dilution was 1 in 20. So we started at a 1 in 20 dilution, whereas for BNT162B2, we started at a 1 in 10 dilution, giving it a little bit more opportunity to detect these antibodies. So that's one difference there, but you're right that actually the... Another important number is the titer itself, the amount of antibody as measured by this thing called PRNT.

Zero to one on.

On them.

The minimum dilution was the one in 'twenty. So we started at the one in 'twenty dilution, whereas for BNP 160, <unk> to restocking ahead of what a one in 10 dilution, so because you're giving it a little bit more opportunity to detect these antibodies because it's how much of eylea.

So that's the one difference there but the.

Youre right that actually the.

The important number and other important number is the the Titans itself the amount of antibody as measured by just didn't comp the R&D <unk>.

And that basically just means that the.

Professor Ouyang Inyong: And that basically just means that the amount of, or it's the dilution. The highest dilution you can go to where 50% of the virus that you put in will be neutralized. The reason why we use 50% is simply because if you do this from 0 to 100%, then the curve appears as a sigmoidal curve, and 50% is the linear part.

Amount of the dilution.

The highest that you shouldn't you can go with 50% of the virus that you've put in will be neutralized.

The reason why we use 50% as simply because of it.

If you do this from zero to 100% then to kind of appears as the sigmoid sigmoidal cash and 50% is the linear patent on that cost. So if you go down or equal higher than years past when do you start to reduce the linearity.

Professor Ouyang Inyong: So if you go down or you go higher up, then you start to lose that linearity, and then it becomes less centric. So that's the reason. But I just want to add one more point. Right now, it's difficult to interpret the titer because we still lack a correlate of protection. We don't know if it's 1 in 10, it's 1 in 20, or it's higher.

Then it becomes less sensitive so so that's the reason for using 50%, but you know.

So I just wanted to add one more point of that.

Right now it's difficult to interpret the Titan because we still that could correlate of protection.

Don't know if it's why the intended when an <unk> is higher.

But that's why we thought it was important for us to look at the.

Professor Ouyang Inyong: But that's why we thought it was important for us to look at the onset of efficacy from the BNT1 Chow to understand what actually started that protection and which, and our findings actually are very consistent with the phase one data where Pfizer and BioNTech could not detect neutralizing antibodies as such. So, I think everything is all coming together to suggest that they can get protection from other elements of the adaptive immune response beyond neutralization.

Onset of efficacy from the <unk> two trial.

So I understand what actually started the protection.

And which and our findings actually I'm very consistent with the phase one data where even now.

Items.

Okay.

I could not on you.

Charging anybody on Sachin on your point.

So I think everything's all coming together to suggest that you can get protection from other elements of the adaptive immune response beyond neutralizing antibodies.

Great Thanks for that.

Boran Wang: My last question is maybe also on the new variants, Ron. Have you done any preclinical evaluation just in terms of T cell response? You maybe discussed this earlier. It's challenging, but so far, do you have any data or preclinical work on the T cell response against any of the new variants with the current vaccine?

We're hopeful on my last question on either maybe also on the new variant from.

And how you'd think of any preclinical evaluation.

Just in terms of T cell response that you may be discuss is the earlier, it's challenging but any.

For any of data of weakening of America.

The T cell responses against the new where any of the new reference with the.

Current vaccine.

Yes preclinical evaluation.

<unk> why don't you go on.

Padmanabh Chivukula: Yeah, pre-clinical evaluation. Pad, why don't you go and address that question? Sure. Of course, as Joe mentioned, that's something that we're actively evaluating, and we hope to share the data in the near future. But that's something that we're definitely considering and collecting.

Sure.

Of course, as Joe mentioned, that's something that we're actively evaluating and we hope to share the data in the near future, but that's something that we're definitely considering it and collecting.

Okay, great. Thanks for taking my question.

Boran Wang: Okay, great. Thanks for taking my question and congratulations on all the progress. Thank you, Wangzi. Thank you. There are no further questions at this time. I would like to turn the floor back over to Joseph Payne for any closing comments. Hey, thanks everyone. It looks like our time's up, and we're going to be closing the call, but feel free to reach out to our team as always if you have any follow-up questions. We will be as efficient as we can in our responses, and bye for now. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation, and have a great day.

So on the address.

<unk>.

Yeah.

Thank you Ramzi.

Thank you there are no further questions at this time I would like to turn the floor back over to Joseph Payne for any closing comments.

Hey, thanks, everyone. It looks like our time's up.

We're gonna be closing the call, but feel free to reach out to our team as always if you of any follow up questions. We will be as efficient as we can in our responses and bye for now.

Yeah.

This concludes today's conference you may disconnect. Your lines at this time. Thank you for your participation and have a great day.

Okay.