Q3 2020 Arcturus Therapeutics Holdings Inc Earnings Call

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At this time all participants are in a listen only mode.

Operator: 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, 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. You may begin.

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, this conference is being recorded.

It's now my pleasure to introduce your host now that so far so head of Investor Relations public relations and marketing. Thank you you may begin.

Thank you operator, and good afternoon, everyone. We are joined today by Joseph <unk>, President and CEO and he says <unk> CFO Dr. spatulas, Philadelphia, So I feel and Dr., Steve Hughes, our Chief Development Officer.

Neda Safarzadeh: 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, and Dr. Steve Hughes, our Chief Development Officer. Before we begin, I would like to remind everyone that, except for statements of historical facts, the statements made by management and any responses to questions on this conference call constitute forward-looking statements that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. 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 company's 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 the success of the companies, the coronavirus, the COVID-19 vaccine candidate, or other candidates, and the company's current and future cash and financial position are

Before we begin I would like to remind everyone.

Except for statements of historical facts, the statements made by management and responses to questions. On 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 99.

Before any.

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 companys future manufacturing and other alterations the status and results of clinical development programs.

The planned initiation design completion of clinical trials, the likelihood off the success of the company's current a virus COVID-19 Bucks is a candidate or other candidates and the companys current and future cash and financial position or 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 and ability to develop and market product candidates unexpected clinical results and general market conditions that may prevent such that she has met or Perry.

Neda Safarzadeh: 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. Such statements are based on management's current expectations and involve risks and uncertainties, including those discussed under the heading Risk Factors in Arcturus's annual report on Form 10-K for the fiscal year ended December 31, 2019, filed with the SEC on March 16, 2020, and in subsequent filings with our submissions or the SEC. Except as otherwise required by law, we disclaim any intention or obligation to update or revise any forward-looking statements, which speak only as of the date they were made, whether as a result of new information, future events, or circumstances, or otherwise. Now, it is my pleasure to pass the ball to Joe Payne, President and CEO. Joe, please go ahead.

Such statements are based on managements current expectations and involve risks and uncertainties, including those discussed under the heading risk factors in our <unk> annual report on form 10-K for the fiscal year ended December 31st 2019, probably with the FCC on March 16, two.

Many 20 and in subsequent filings with our [laughter], a submission or the FCC.

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 today, Dave or maybe better as a result of new information future events or circumstances or otherwise.

Now it is my pleasure so passionate about the job site.

As CEO Joe. Please go ahead.

Hey, Thank you know good afternoon to all thank you for joining Arcturus this quarterly call today.

Joseph E. Payne: Thank you, Neda. Good afternoon to all. Thank you for joining Arcturus' quarterly call today. To begin, and right off the bat, I'd like to congratulate Pfizer and BioNTech on the significant milestone announced earlier today. Congratulations to them, their scientists, and their team for this accomplishment. We believe this is exceptional validation of messenger RNA therapeutics and vaccines, and Arcturus is very fortunate to be part of this messenger RNA therapeutics community, especially since we're all working together in this global effort to vaccinate and protect just each of us from COVID-19. Thanks to our partners in Israel and Singapore for supporting us.

To begin right off the bat I'd like to congratulate Pfizer and biotech.

For the significant milestone announced earlier today congrats.

Congratulations to them their scientists and their team for this.

Accomplishment. We believe this is exceptional validation of messenger Arnie therapeutics and vaccines.

And Arcturus is very fortunate to be part of this messenger Arnie therapeutics community.

Especially since we're all working together in this global effort to vaccinate.

In fact, I just each of us from Cove at 19.

Thanks to our partners in Israel in Singapore, and supporting Us.

Well Arcturus has made substantial recent pipeline progress highlighted by our two most advanced clinical programs Youre CTO 21 is our COVID-19, self transcribing and replicating ornate or star M&A vaccine candidate and Air Sea T 810.

Joseph E. Payne: Well, Arcturus has made substantial recent pipeline progress, highlighted by our two most advanced clinical programs. ARCT021 is our COVID-19 self-transcribing and replicating RNA (or star mRNA) vaccine candidate. And ARCT810, our therapeutic candidate for OTC deficiency or ornithine transcarbamylase deficiency. We're very pleased today to announce encouraging initial clinical results from both of these programs. And we've also made strong progress advancing our earlier stage pipelines, including our CF program, or Cystic Fibrosis. I'll begin with ARCT021, which is also known as Lunar-COV19 or COVID-19.

Our therapeutic candidate for old T.C. deficiency or aren't the same trends carbamazepine deficiency.

How were.

Very pleased today to an.

Now it's encouraging initial clinical results from both of these programs.

And we've also made strong progress advancing our earlier stage pipelines, including our CF program for cystic fibrosis I'll begin with a our CTO 21, which is also known as lunar Dash C. O V 19, or cold 19 to remind you weigh our CTO 21 is being developed in collaboration.

Joseph E. Payne: To remind you, ARCT021 is being developed in collaboration with the Duke-NUS Medical School, and development activities are being performed in Singapore. Today, we're excited to report for the first time preliminary clinical results from our ongoing Phase I-II clinical study. The objectives of this study are to evaluate safety and tolerability and the humoral and cellular immune responses and to determine the dose and administration regimens to be evaluated in further clinical development. Our encouraging Phase I-II results, to which Steve will detail in a few minutes, our Chief Development Officer. They provide further support to suggest that our self-replicating mRNA-based investigational vaccine, this approach using our proprietary star mRNA technology may produce protective immunity at low mRNA doses and potentially with only a single administration.

And with the Duke and U.S. Medical School and development activities are being performed in Singapore.

Today, we're excited to report for the first time preliminary clinical results from our ongoing phase one two clinical study.

The objectives of this study are to evaluate safety and Tolerability and the moral in cellular immune response and to determine the dose administration regimens to be evaluated in further clinical development.

Our encouraging phase one slash two results to which Steve will detail in a few minutes, our chief development officer. They provide further support to suggest that are self replicating it marinade based investigational vaccine.

That this approach using our proprietary story Marni technology may produce protective immunity at low Emerald eight doses.

And potentially with only a single administration.

Now based on our interim clinical data.

Joseph E. Payne: Based on our interim clinical data, we plan to advance a low single dose of 7.5 micrograms along with a prime boost regimen. We saw 100% seroconversion of IgG-binding antibodies in younger adults. However, one out of five older adult participants has not yet seroconverted. The observed geometric mean titers in all of these cohorts exceeded 2,500. Thus, the 7.5-microgram dose level that's been selected. Focusing in on that specific dose, our GMT or geometric mean titer for this group or the GMT exceeded 15,000 for younger adults and exceeded 2,000 in older adults at this dose. IgG binding antibodies continue to increase over time in humans. This is similar in a similar manner to what we observed in preclinical animal models.

We plan to advance a low single dose of 7.5 micrograms, along with prime boost regimens.

We saw 100% zero conversion of AI jie binding anti bodies in the younger adults.

One out of five older adult participants has not yet sheryl converted.

He observed geometric mean titers and all of these cohorts exceeded 2500.

So the 7.5 microgram dose level that's been selected.

Focusing in on that specific dose, our G.M.T. or geometric mean tighter for this.

Group or the G.M.T. was exceeded 15000 for younger adults and exceeded a 2000 and older adults at this dose.

The I.G. binding antibodies continue to increase over time in humans. This is similar or in a similar manner to what we observed in preclinical animal models.

We consider that encouraging.

Joseph E. Payne: We consider that encouraging because the data is still evolving. We remind everyone that the time course for star mRNA technology is extended and different from conventional messenger RNA, which is one of the reasons why we're seeing activity at such low dose levels. The data that we've collected will be published at the time of study completion. We believe that ARCTO21 could be an important addition to the global fight against COVID-19, and we look forward to advancing ARCTO21 into later stage clinical studies as quickly as possible. In parallel with our clinical development activities, we've also made progress with our manufacturing activities for our vaccines. With the support of Catalant and Resifarm and other manufacturing partners, Arcturus remains on track to manufacture substantial numbers of doses. Arcturus announced earlier today an agreement with the Singapore Economic Development Board to support our manufacturing efforts.

The data is still evolving we remind all that the time course first start Marni technology is extended and different from conventional messenger Arnie, which is one of the reasons.

Why were seeing activity at such low dose levels.

The data that we've collected will be published at the time of study completion.

We believe that our CTO 21 could be an important addition in the global fight against COVID-19.

We look forward to advancing a our CTO 21 into later stage clinical studies as quickly as possible.

In parallel with our clinical development activities Weve also made progress with our manufacturing activities of our vaccine.

With the support of Catalent and rest of farm another manufacturing partners Arcturus remains on track.

Manufacture substantial numbers of doses.

Arcturus announced earlier today on that an agreement with the Singapore Economic development Board.

To support our manufacturing efforts and Andy is going to be providing more details on that in a few minutes.

Joseph E. Payne: And Andy is going to be providing more details on that in a few minutes. In August, we signed a binding terms sheet with the Israeli Ministry of Health to supply ARCTO21. We consider this a core or an important part of the country's vaccination strategy. Israel is the second country, in addition to Singapore, to reserve a supply of Arcturus' COVID-19 vaccine, and we also continue to have constructive discussions with additional countries pertaining to stockpiles and supply agreements. Now shifting focus to ARCT 810 for OTC deficiencies, but we continue to make great progress with our Lunar OTC program. We've completed dose escalation of all cohorts, 0.1, 0.2, 0.3, and now including the top dose of 0.4 milligrams per kilogram in our phase one study.

In August we signed a binding term sheet with the Israeli Ministry of health to supply a our CTO 21 if.

We consider this a core are an important part of the country's vaccination strategy.

Israel is the second country. In addition to Singapore to preserve supply of Arcturus has a coke at 19 vaccine and we also continue to have constructive discussions with additional countries pertaining to stockpiling and supply agreements.

Now shifting focus to the New York City, a 10 for LTC deficiency, we continue to make great progress with our lunar Otcs program.

We've completed dose escalation of all cohorts 0.1, 0.2, 0.3, and now including the top dose of 0.4 milligrams per kilogram in our phase one study.

We're pleased to report that steroids pretreatment was not necessary even for the top dose cohort.

Joseph E. Payne: We're pleased to report that steroid pretreatment was not necessary, even for the top dose cohort. And we've commenced enrollment in a Phase 1B study here in the United States in OTC-deficient patients, and our first subject is Initiated Sclerosis. So there's a lot there to report in one quarter for... I now pass the call to Steve to review and provide more detail pertaining to the ARCTO 21 Phase 1-2 study results, as well as new Phase 1 data from our ARCT 8-10. Ornithine Transcarbamylase Deficiency Program. Steve.

And Weve commenced enrollment of a phase one b study here in the United States and no Tc deficient patients and our first subject was initiated screening.

So there's a lot there to reporting in one quarter for.

Arcturus I now pass the call to Steve to review and provide more detailed pertaining to a our CTO 21 phase one slash two study results as well as new phase one data from our air C.T., a 10 or 15 Trans Carbamazepine deficiency program Steve.

Thanks Jay.

Steve Hughes: Thanks Joe. I'm pleased to report that the ARC021 Phase 1-2 study is now fully enrolled with 106 adult subjects, including cohorts of older participants. Before discussing the data, I'd like to go over the study design in some detail. The study is evaluating both a single injection of ARC021 and a prime boost regimen. The subjects received either placebo or ARC021 in a double-blind, randomized fashion. In this study, we have single-dose cohorts at 1, 5, 7.5, and 10 micrograms in younger adults and a 7.5 microgram single-dose cohort in older adults. We are also testing two-dose priming regimens of 3 micrograms and 5 micrograms in both younger and older adults. Younger adults are in the range of 21 to 55 years, and older adults are greater than 55 years of age.

I'm pleased to report that the zeolite to one phase one two study is now fully enrolled with 106 adult subjects, including cohorts of all the participants.

Before discussing the data I'd like to go over the studies on in some detail.

The study is evaluating both a single injection of obviously about two one and fun based regimens.

Subjects received either placebo or obviously led to one and a double blind randomized fashion.

In this study we have single dose cohorts at 157.5, and 10 micrograms and younger adults and the 7.5 like single dose cohort in older adults.

We're also testing to dice priming regimens of three micrograms, and five micrograms and both younger and older adults.

Younger adults in the range of 21 to 55 years and older adults are greater than 55 years of age.

To date 78 subjects have received at least one injection of zero to one.

Steve Hughes: To date, 78 subjects have received at least one injection of ARC-021, 36 subjects have received two injections, and 28 subjects have received placebo. Our interim analysis includes preliminary results from all single-dose cohorts, including the older adult cohort. For the two-dose cohorts, although all subjects have now received at least one dose of vaccine, data are currently only available for the younger adult cohort at the 5-microgram dose. These results include safety up to at least 28 days after vaccination and immunogenicity up to the day 43 time point. Although not all subjects have immunogenicity data at the later time points, and for the single dose cohorts, the neutralizing antibody data only goes up to day 29 at this point in time, and further data is anticipated. Based on the study results, A robust anti-spike protein IgG immune response was observed with 100% seroconversion at all doses evaluated in the younger adult cohort and only one subject that has not yet siroconverted in the older adult cohort.

[noise] 36 subjects have received two injections and 28 subjects have received placebo.

The interim analysis includes preliminary results from all single dose cohorts, including the older adult cohort.

For the two dose cohorts, although all subjects have now received at least one dose of vaccine data currently only available for the young adult cohort at the five microgram dose.

These results include safety up to at least 28 days after vaccination.

And Immunogenicity up to the day 43 towing point, although not all subjects have immunogenicity data at a later time points and for the single dose cohorts. The neutralizing antibody data I know you guys out today 29 at this point in time and further data is anticipated.

Based on the study results.

A bust anti spiked protein Gigi immune response was observed with 100% say about combustion at all doses evaluated in the young adult cohort.

Only one subject has not yet converted in the older adult cohort.

GMT titles for the G. antibodies are greater than 22300 in old cohorts.

Steve Hughes: GMT titers for IgG antibodies were greater than 2,300 in all cohorts. We have selected the 7.5 microgram single-dose and 5 microgram two-dose regimens to take forward into further study. At the 7.5 microgram single dose, the geometric mean titer was greater than 15,000 in younger adults and greater than 2,300 in older adults. In the 5-microgram, 2-dose cohort, the GMT was greater than 16,500. The GMT for neutralizing antibodies in the PRNT50 assay was within the range of titers observed in COVID-19 patient convalescent plasma tested in the same laboratory.

We have selected 7.5 microgram single dose and felt like my could go out and two dose regimens to take forward into further studies.

At the 7.5 microgram single dose the Gen. Geometric mean tighter was greater than 15000, and young adults and greater than 2300 in older adults in the five microgram two dose cohort the GMT was greater than 16500.

The G.M.T. for neutralizing antibodies in the pale in T. 50, I say was within the range of types as observed in the COVID-19 patient convalescent plasma tested in the same level a tree. However, as this is an ongoing study the data is still evolving and not all subjects in the cohorts evaluated have complete result.

Steve Hughes: However, as this is an ongoing study, the data are still evolving, and not all subjects in the cohorts evaluated have complete results for this assay at later time points as it has to be performed in a BSL-3 lab and therefore takes a few weeks to get the samples processed. For example, the single-dose cohorts only have neutralizing antibody data up to day 29, and the IgG results indicate that titers continue to rise through day 43. So these later time points are important.

But as I say at a later time points as it has to be performed in the B S. L. Three lab and therefore takes a few weeks to get the samples processed for example, the single dose cohorts only have neutralizing antibody data up to the dates when she knows after day 29, and the LNG GE was always indicate that taught us continue to rise through day 14th week. So these days.

The time point so important.

Additionally, we do not yet have the neutralizing antibody results from the much what microneutralization tests that we believe that we will be using for our phase. Three study. This will be performed over the next few weeks, we will therefore shammo dice when the neutralizing antibody titers in the coming weeks as these data mature.

Steve Hughes: Additionally, we do not yet have the neutralizing antibody results from the micro-neutralization test that we will be using for our Phase 3 study. This will be performed in the next few weeks. We will therefore share more data on the neutralizing antibody titers in the coming weeks as these data mature. Turning now to T Cell Lisbo, Cytokine staining and ELISBOT tests showed that T cell responses existed to multiple peptide pools spanning the full length of the SARS-CoV-2 spike protein.

Turning now to T cell responses starts.

It's always a kind standing and at least what tests showed that T cell responses existed to multiple peptide pools spanning the full length of the sellers could it be to spike protein. The C.D. for response was T.H., one dominant and the C.D. eight responses were seen to peptide pools include that as from the receptor binding domain.

Steve Hughes: The CD4 response was Th1 dominant, and the CD8 responses were seen to peptide pools that included those from the receptor binding site. Part 021 was generally well tolerated and had a favorable local and systemic adverse event profile. The majority of adverse events have been mild, and there have been no severe injection site reactions or fever at the doses that we plan to take forward to later stage clinical trials. Additionally, no subjects have withdrawn from the study, and there have been no serious adverse events deemed to be treatment-related. There has been one serious adverse event observed. This was an event of cellulitis from an insect bite and was judged by the investigator to be unrelated to the study drugs.

Oh from zero to one was generally well tolerated and had a favorable local and systemic adverse event profile. The majority of adverse events. The mild I've never been noticed the pay of injection site reactions or FEIBA at the doses that we plan to take forward into later stage clinical trials noticed.

No subjects have withdrawn from the study and that would be no serious adverse events deemed to be treatment relate to.

There has been one serious adverse event observed this was an event of cellulitis from an insect bites I'm as judged by the investigates it to be unrelated to study drug.

We continue to collect and analyze data from this study and we intend to discuss the data with regulatory authorities in the coming weeks as we move towards pivotal trials.

Steve Hughes: We continue to collect and analyze data from this study, and we intend to discuss the data with regulatory authorities in the coming weeks as we move toward pivotal trials. Moving now to our ARC-810 program. Part 8.10 is being developed for ornithine transcarbamylase deficiency, a serious disease with limited treatment options. ARC810 utilizes Arcturus' Lunar Lipid-Mediated Delivery Platform to deliver OTC messenger RNA to the liver. The expression of ornithine transcarbamylase enzyme in the liver of patients with OTC deficiency is expected to restore normal urea cycle activity and potentially prevent neurological damage and the need for liver transplantation in these patients.

Moving now to our all 810 program.

On page 10 is being developed for on the theme trends called families deficiency, a serious disease, but limited treatment options out pay 10 utilizes all choices Luna lifted mediated delivery platform to deliver LTC messenger holiday to the liver express.

Especially on the only thing trends called analyzer enzyme in the lives of patients with LTC deficiency is expected to restore normal U.S. talk of activity potentially prevent neurological damage and the need for liver transplantation. In these patients. We have recently completed a 10 phase one study a double blind placebo controlled dose.

Steve Hughes: We have recently completed our ARC-810 Phase 1 study, a double-blind placebo-controlled dose escalation trial in healthy volunteers. The study included four cohorts in total, with dosages tested between 0.1 mg per kilogram and 0.4 mg per kilogram. Subjects were randomized 2 to 1, active to placebo, and all doses were in the anticipated therapeutic range. All subjects have completed all doses and all study visits. The study is designed to evaluate safety and tolerability, as well as pharmacokinetics as primary and secondary endpoints, respectively. In this study, ALT-810 was generally safe and well tolerated. Most adverse events were mild in severity, and there were no severe adverse effects. No subjects moved too early from the study, and there were no essays.

Escalation trial in healthy volunteers.

The study included full cohorts in total with doses tested between <unk> 0.1 milligram per kilogram no 0.4 milligrams per kilogram subjects were randomized two to one active to placebo at an all doses, but when the anticipated future wage boost.

Oh subjects have completed dosing and we'll study visits the study is designed to evaluate safety and tolerability as well as public <unk> pharmacokinetics as primary and secondary end points respectively.

In this study out a 10 was generally safe and well tolerated most adverse events were mild in severity and there were no severe adverse events.

Subjects, because from the study and I would not say he's out.

I'll pay 10 has also demonstrated a favorable pharmacokinetic profile and our preliminary data has shown that no alt a 10 lippitt with detectable in the plasma beyond 48 hours following drug administration.

Steve Hughes: Arct-A10 has also demonstrated a favorable pharmacokinetic profile, and our preliminary data have shown that no Arct-A10 lipid was detectable in the plasma beyond 48 hours following drug administration. Finally, the Phase 1-2 study of ARC810 in OTC-deficient patients, which is being conducted in the United States under an IND, has commenced enrollment, and the first patient is currently in screening. I'll now pass the call on to Anne.

Finally, the phase one two study of out page 10 in the TC deficient patients, which is being conducted in the United States on the R&D has commenced enrollment and the first patient as kind of being screening.

I'll now pass the call on to Andy.

Thank you, Steve and good afternoon, everyone.

Andrew H. Sassine: Thank you, Steve, and good afternoon, everyone. The press release issued earlier today includes financial statements for the third quarter of fiscal year 2020, which I will briefly summarize. Arcturus' primary source of revenues is currently from licensees and collaborative revenue received from research and development arrangements with our pharmaceutical and biotech partners. In the third quarter, the company reported revenues of $2.3 million compared with $3.3 million in the third quarter of 2019. The decline in collaboration revenues primarily relates to a decrease in reimbursements from cure-back associated with the OTC collaboration that ended in the third quarter of 2019. Total operating expenses in Q3 were $23.3 million compared with $10.9 million for the same period of 2019.

This release issued earlier today include financial statement for the third quarter of fiscal year, 2020, which I will briefly summarize.

Our true primary source of revenue is currently from license fees and collaborative.

We see from research and development arrangement with a pharmaceutical and biotech partner.

The third quarter. The company reported revenues of 2.3 million compared to 3.3 million in the third quarter and 29 to that.

The decline in collaboration revenue primarily relates to a decrease in reimbursement from pure back associated with the Otcs collaboration that ended in the third quarter of 2019.

Total operating expenses in Q3 were 23.3 million compared with 10.9 million for the same period of 2019.

The current quarter operating expenses were partially offset with 3.7 million of fund earned under the Singapore vaccine Grant.

Andrew H. Sassine: The current quarter operating expenses were partially offset with $3.7 million of funds earned under the Singapore Vaccine Grant and $0.7 million in funds awarded by the Cystic Fibrosis Foundation. Research and development expenses increased approximately $10 million sequentially from the June 30, 2020 quarter, driven primarily by an approximate increase of $4 million in each of our lunar OTC, ARCT810, and Lunar Code 19 ARCT 021 programs, mostly due to clinical and manufacturing expenses. The remaining $2 million was driven by increased personnel expenses and the cost of our two new pipeline programs, Lunar Flu and Lunar Cardiovascular. Earlier today, Arcturus announced an important manufacturing and vaccine supply agreement with the Singapore Economic Development Board for up to $220 million in additional financial commitment. The EDB will provide a limited recourse loan of $45 million within 60 days, contingent on the delivery of certain documentation.

0.7 billion in fund awarded by the Cystic Fibrosis Foundation.

Research and development expenses increased approximately $10 million sequentially from the June Thirtyth 2020 quarter.

Driven primarily by an approximate increase of $4 million in each of our lunar otcs. They RCT a 10.

And Luna code 19, they always CTO 21 program most.

Mostly due to clinical and manufacturing expenses.

The remaining 2 million was driven by increased personnel expenses and cost of our two new pipeline program lunar flu and lunar cardiovascular.

Earlier today, our troops announced that important manufacturing and vaccine supply agreement with the Singapore Economic development Board for up to 220 million in additional financial commitment.

The EDI be will provide a limited recourse loan or $45 million within 60 days contingent on the delivery of certain documentation.

The proceeds will be used for the purchase of equipment material and services related to the manufacturer of our vaccine.

Andrew H. Sassine: The funds will be used for the purchase of equipment, materials, and services related to the manufacture of our vaccine. Under the terms of the agreement, the loan will be repaid through royalties on future ARCT 21 commercial sales. If ARCT 21 development does not succeed or obtain regulatory approval, the loan will be forgiven. Additionally, Arcturus and EDB have entered into a supply agreement for the right to purchase up to $175 million of ARCT 21 vaccine at pre-negotiated prices, with shipment expected in the first quarter of 2021. These funds provide the company with additional resources to support our effort to continue to rapidly scale up ARCTO21 manufacturing to support our existing Israeli and Singapore agreements, as well as other potential supply deals in 2021.

Under the terms of the agreement the loan will be repaid through royalties on future. They are C.G. 21 commercial sales.

Yes. They are C. T 21 development does not succeed or obtained regulatory approval the loan will be forgiven.

Additionally, a RC truthfully MDB ive entered into a supply agreement for the right to purchase up to $175 million or they are few 21 vaccine.

Pre negotiated prices with shipments expected in the first quarter of 2021.

These fun provide the company with additional resources to support our effort to continue to rapidly scale up.

Our CTO 21 manufacturing to support our existing Israeli and Singapore agreement.

As well as other potential supply deal than 2021.

Along with our global manufacturing partner, we have laid the foundation to.

Andrew H. Sassine: Along with our global manufacturing partners, we have laid the foundation to produce hundreds of millions of doses of ARCT21 over the next 18 months, and we believe the company has an opportunity to positively impact the global COVID-19 pandemic. Our cash balance totaled $307.1 million as of the end of Q3, compared to cash and cash equivalents of $71.5 million at December 31st, 2019.

Produce hundreds of millions of doses.

They are C. T 21 over the next 18 months and we believe the company has an opportunity to positively impact.

The global Cold in 19 pandemic.

Our cash balance totaled 307.1 million as of the end of Q3 compared to cash and cash equivalents.

71.5 million at December 30, Onest 2019.

The increase in cash and cash equivalents and investments is primarily due to successfully raising approximately.

Andrew H. Sassine: The increase in cash and cash equivalents in investments is primarily due to successfully raising approximately $262 million in net proceeds through two public equity offerings in 2020. Based on our current pipeline, the company's cash position is expected to be sufficient and support operations for more than two years. I'll now pass the call back to Joe. Thanks, Andy.

$262 million. The net proceed through two public equity offering in 2020.

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

I'll now pass the call back to Joe.

Thanks, Andy that's certainly been a period of a strong clinical development progress for Arcturus.

Joseph E. Payne: It's certainly been a period of strong clinical development progress for Arcturus. Looking ahead, we anticipate an eventful period of further clinical progress updates. We're highly encouraged by the ARCTO21 data that we've obtained.

Looking ahead, we anticipate an eventful period, a further clinical progress updates we're highly encouraged with the A. Our CTO 21 data that we've obtained we believe the program has.

Joseph E. Payne: We believe the program has enormous potential to play an important role in the global COVID-19 vaccine response. In the coming weeks, we anticipate to obtain additional ARCT-021 Phase 1-2 study data, and, together with the regulatory authorities, we will finalize our plans for further clinical development. Advancing this program forward as quickly as possible is our top corporate priority.

Enormous potential to play an important role in the global COVID-19 vaccine response.

In the coming weeks, we anticipate to obtain additional air CTO 21 phase one slash two study data and together with the regulatory authorities, we will finalize our plans for further clinical development advance.

Advancing this program forward as quickly as possible is our top corporate priority.

With respect to the HR C.T., a 10 program. We also anticipate obtaining initial clinical results and Otcs patient.

Operator: With respect to the ARCT 810 program, we also anticipate obtaining initial clinical results in OTC patients. In addition to our clinical development stage programs, we're making steady progress applying our powerful mRNA platform to develop medicines in a number of promising earlier stage programs, and we look forward to providing you with updates on those in the next year. At this point, we can go ahead and open the line for questions. Operator, please proceed.

Patients.

In addition to our clinical development stage programs were making steady progress applying our our powerful M&A platform to develop medicines in a number of promising earlier stage programs and we look forward to providing you.

You with updates on those in the next year 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. You would like to ask a question. Please press star one on your telephone keypad copper.

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Seamus Christopher Fernandez: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. We ask that you please limit yourself to one question and one follow-up question. One moment, please, while we poll for your questions. Our first questions come from the line of Seamus Fernandez with Guggenheim. Please proceed with your question. Great, thanks for the question. So a few here just trying to get a little bit more specific, and thanks for the additional specifics that you guys provided on the call. Just in terms of the convalescent plasma levels, can you just give us a sense of the titers that you saw with the convalescent plasma for, you know, neutralizing antibodies and IgG? And also, you know, the types of patients that, you know, made up the convalescent plasma were these, you know, predominantly hospitalized patients, just trying to get a better sense of how the convalescent plasma comparison metrics compared against the different data that you've provided.

We ask that you please limit yourself to one question and one follow up question. One moment. Please while we call for your questions.

Our first question will come from the line of Seamus Fernandez with Guggenheim. Please proceed with your questions.

Oh, great. Thanks for the question. So a few here just trying to get a little bit more specifics and thanks for the additional specifics.

You guys provided on the call.

Just in terms of the convalescent plasma levels.

Levels can can you just give us a sense of.

The the tighter stat that you saw with the convalescent plasma or you know neutralizing antibodies energy and also you know the types of patients that no made up the convalescent plasma you know where these predominantly hospitalized patients I'm just trying to get a better.

A sense of how these how the convalescent plasma.

Comparison metrics up against the different data that you provided.

The second question is on just the young adult patient population again relative to the convalescent serum.

Seamus Christopher Fernandez: The second question is on just the young adult patient population, again, relative to the convalescent serum. Can you give us a sense of the percentage of the young adult population that, you know, exceeded the neutralizing antibody titers for convalescent serum, as well as the IgG titers? And then finally, just in terms of the older adults, if you could provide us with that same information, that would be great. Sure, Steve, go ahead.

Can you give us a sense of the percentage of the young adult population.

That you know exceeded the neutralizing antibody titers.

For convalescent children as well as the I'd UGI Titers and then finally just in terms of the older. Adults. If you could provide us that same information that would be great. Thank you.

Sure Steve go ahead.

Okay. Thank you for the question.

Steve Hughes: OK, thank you for the question. I can address some parts of the question, but not all of the parts at this point in time. So for the convalescent plasma that we got, it had a geometric mean titer for neutralizing antibodies of 147, and those ranged from around 10 to 20 up into several hundreds from the graph that we have. We don't have, at this point, the IgG-finding antibodies for those convalescent plasmas. We need to process those.

I can address so some part of the question, but not all of the parts that at this point in time, so for the the convalescent plasma that'd be gault. It had a a geometric mean tighter for neutralizing antibodies of 147.

Those ranged from around 10 to 20 up into several hundreds.

Hey, a fun from the Gulf that we have.

We don't have at this point the I.G. binding antibodies for those side convalescent plasma what we need to process those.

It was the neutralizing antibodies that we felt were most important for that comparison within the convalescent plasma. It includes both younger and older subjects subjects range in age from 24 to 80 383 years of age.

Steve Hughes: It was the neutralizing antibodies that we felt were most important for that comparison. In the convalescent plasma, it includes both younger and older subjects. Subjects range in age from 24 to 83 years of age, and there's a range of collection time from a couple of weeks to several weeks after the onset of the illness. The convalescent plasma includes subjects that have both mild, moderate, and severe disease, with the majority of subjects actually in the mild to moderate category. Would you mind just repeating the last part of the question that you had?

And there's a range of collection time from.

From a a couple of weeks to several weeks after the onset of the illness.

We have the convalescent plasma includes subjects that have.

Both mild.

Moderate and severe disease.

With the majority of subjects actually in the mall to motivate category.

As characterization.

But would you mind just repeating the last part of the question that you had.

Seamus Christopher Fernandez: Yeah, if it's possible to share the percentage of young adults and older adults that exceeded or at least met or exceeded the convalescent sera levels. I think in your press release this morning, there was some commentary in that regard, but it wasn't specific. So at this point, the data that we have is still maturing, so this is an interim analysis cut of an ongoing study. And it's primarily to inform our regulatory submissions.

Yes, if it's possible to share or the percentage of a young adults and older adults that exceeded the or at least met or exceeded the convalescent Sera levels I think in your press release this morning.

There was some commentary in that regard, but it wasn't it wasn't specific.

Yeah. So at this point the that the data that we have is still maturing. So this is an interim analysis kind of an ongoing study the and it's primarily to inform all regulatory submissions. So our purpose for doing this type of car is set up we kind of bonds by rapidly from this study to the next study.

Steve Hughes: So our purpose for doing this data cut is so that we can advance very rapidly from this study to the next study. Not all subjects have completed the later analysis time points for the neutralizing antibody assay, just because it takes some time to actually get those tests processed. We're in a queue with other people, and it has to be performed in a BSL-3 lab.

No all subjects have completed the lights of analysis time points for for the for the neutralizing antibody I say just because it takes some time to actually get those tests processed to the you know where were in acute without attack without the people in it has to be performed and the bass L. Three lab. So it from actually taking the sample to.

Steve Hughes: So from actually taking the sample to getting the test results, the process takes several weeks. So for that reason, we don't have full data yet on the neutralizing antibody titers. And the other thing to consider is that for our technology, the later time points are actually quite important because what we see is our antibody titers continuing to rise over time. So we're not really in a position to provide further color on the neutralizing antibody titers at this point. We should be sharing that information over the coming week. Got it.

Get the test process takes several weeks.

So for that reason, we don't have full data yet on the neutralizing antibody titers and the other thing to consider is that for all technology. The lights of talking points that actually quite important because what we see is though antibody titers to continuing to rise over that over time. So we're not really in a position to provide further color on the neutralizing antibody titers.

At this point, we should be sharing that information over the coming weeks.

Got it and then if I can or ask a separate question obviously, the Pfizer biotech data came and delivered certainly an impressive result.

Seamus Christopher Fernandez: And if I can ask a separate question, obviously, the Pfizer-BioNTech data came in and delivered certainly an impressive result. I think you guys know what their data looks like. You know what the threshold might likely be to sort of predict the, you know, single dose type efficacy. I was just hoping you might give us a general sense of what you think is achievable in that context with a single dose vaccination. In part because, you know, I think there is a little bit of concern from investors that the single dose vaccination won't have exactly the same threshold of data, you know, what the, what the bar is going to be from the agency. So should the Pfizer-BioNTech data, should it shift the bar upward from the 50 to 60% threshold to 70 to 80%? What's your confidence that you could meet, if that were a moving bar, that you could meet that with a single-dose vaccination? And when will we see the data to support that? Well, I have one comment, and if the team wants to add anything, feel free to do so.

I think you guys know what their data looks like you know what the threshold.

You know might likely be to sort of predict the you know a single dose type Africa see I was just hoping you might give us a general sense of what you think is achievable in that context with a single dose vaccination in part because.

I think there is a little bit of concern from investors that the single dose vaccination. If it doesn't have exactly the same threshold of data you know what what the what the what the bar is going to be from the agency. So does the Pfizer biotech data.

Sure to ship the bar upward from the 50% to 60% threshold to 70% to 80%, what's your confidence that that you could meet Uh huh.

If that were a moving bar.

You can beat that with a single dose vaccination and and you know when will we see the data to support that.

Well I've one comment that if you if the team wants to add.

Add to feel free to do so.

I think to rephrase. Your question is what's the likelihood of a regulatory agency, allowing us to proceed in advance this therapeutic given the data that we've collected so far and I think that that's reasonably high and I think that's fair to say in there and so we're.

Joseph E. Payne: I think, to rephrase your question, is what's the likelihood of a regulatory agency allowing us to proceed and advance this therapy, given the data that we've collected so far? And I think that that's reasonably high. And I think that's fair to say.

Steve Hughes: And so we're going to continue to be able to evaluate this technology and mature it, and I think that will be the metric that I'd like to refer to. And I think the likelihood of us succeeding in advancing this is high to very high.

We're going to continue to be able to evaluate this technology and mature it.

And and.

And I think that will be the metric that I would like to to refer to and I think the likelihood of us succeeding in advancing this is high the very high.

Yeah, I just like to also add that at this point in time, there isn't a call a protection that's actually established.

Steve Hughes: I'd also like to add that at this point in time, there isn't a correlate of protection that's actually established. It's important to consider that subjects with mild disease that have recovered... universally, for the most part, have considerably lower antibody titers than subjects with severe disease. But we're not seeing subjects with mild disease falling over with COVID reinfection over and over again. There have only been a handful of cases of COVID reinfection around the world.

It's important to consider that subjects with mild disease that have recovered.

Universally for the most part have considerably lower antibody titers and subjects with severe disease, but we're not seeing subjects with mild disease falling over with kindred, we infection overnight, but again, there's only been a handful of cases of cocodrie infection of around the world. So I think what is clear is that sky high levels of neutralizing antibody titers.

Steve Hughes: So I think what is clear is that sky-high levels of neutralizing antibody titers aren't required for protection. The other important point to bear in mind is T cells. And nobody knows whether, for this disease, T cells are more important than antibody titers as a correlate of protection against disease.

Liquide fall protection.

The other important point to bear in mind is T cells.

And nobody knows whether for this disease T cells are more important than antibody titers than as I call protection of disease, and so I think it's premature to speculate what's the most important.

Steve Hughes: And so I think it's premature to speculate what the most important characteristic to see in terms of protection from the vaccine. The experts that we've talked to are very confident moving forward that our data looks exciting and looks promising as a single dose, and we're going to be in conversations with regulatory authorities this week to discuss our data in more detail and about moving forward with a single dose measurement into the next stages of clinical development. So we remain very confident and very excited about our program and confident that we'll be advancing single doses further in clinical development. Okay, great. I'll jump back in the queue.

Got it to mistake to say in terms of protection from the vaccine the experts that we've talked about I confident moving forward that our data.

Looks exciting it looks promising as a single dose.

And were going to be in conversations with regulatory authorities this week to.

To discuss our data in more detail and about moving forward with a with a single dose.

Women into the next stages of clinical development. So we remain very confident and excited about our program and confident that we will be advancing single dose is spot on in clinical development.

Okay, Great I'll jump back in the queue. Thank you guys.

Seamus Christopher Fernandez: Thank you, guys. Thank you. Our next question has come from the line of Madhu Kumar of Baird.

Thank you.

Thank you. Our next question does come from the line of Matthew Kumar of Baird. Please proceed with your questions.

Madhu Kumar: Please proceed with your question. Hey everyone, thanks for taking our questions. So our first one kind of relates to ARC-21 as well. So is there additional data that the Singapore Economic Development Board has related to the ARC-21 Space 1-2 trial that influenced their decision to set up the arrangement you guys announced today? Or is the data you've put out both this morning and this afternoon kind of the basis set for their decision? Yeah, well, I think the short answer is yes, the Singapore Duke-NUS Medical School is very well aware of our data. They're running the study and managing and overseeing many of the development activities, and that's where a lot of the positive energy that we get and the feedback we get as this continues to develop.

Hey, everyone. Thanks for taking our questions. So our first one kind of relates our 21 as well. So is there additional data that Singapore economic development Board had really dark 21 states went to trial that influence their decision to said it'd be arrangement you guys announce today or is the data you put out this morning. This afternoon.

The basis after their decision making.

Yeah, well I think the short answer is yes, the Singapore, Duke and U.S. Medical school is very well aware of our data they are running the study and and managing and overseeing many of the development activities.

And and that's where a lot of the positive energy that we get and the feedback we get asked this continues to develop but.

Steve Hughes: But to what extent that information is shared outside of Duke-NUS, I can't comment on. Okay, and also, as you're aware, there was a news article that came out overnight suggesting a phase 3 trial for you could start as early as by year-end. Does that seem like it is consistent with your perspective on things, or how are you dealing with the timing for pivotal studies for ARC-21? So we're in discussions at the moment with the Singapore regulators, and we've had discussions with the FDA as part of a pre-IMD package. Both of those discussions have included the overall design for a Phase 3 program. We're continuing our discussions with the regulators.

To what extent that information is shared outside of Duke and U.S.I. I can't comment on that.

Okay, and although you are aware there was a news article that came out overnight, suggesting <unk> a phase three trial for you all could start as early as by year end does that seem like a consistent with your perspective on things or how are you getting the timing for pivotal studies for our 21.

So what we have been in discussions at the moment with the Singapore regulates isn't a up we've had a discussion already with <unk> with the FDIC as part of a pre R&D package.

Both of those discussions have included <unk>, Oh vote design for a phase three program, we're continuing our discussions with the regulators will be having a conversation with Singapore Mega later this week and very shortly will also be reengaging with FDIC to discuss all phase three program so until we've actually.

Steve Hughes: We'll be having a conversation with the Singapore regulator this week, and very shortly, we'll also be re-engaging with FDA to discuss our Phase 3 program. So until we've actually concluded those discussions, I don't think we can really make any further comment on what comes next or the timing. Okay, one last one on A10 and OTC deficiency. Given that you've been able to dose escalate with no kind of obvious safety concerns, is there a reason not to want to look to dose higher? Does the PK you've seen so far, the exposure you've seen so far, feel like you kind of hit the sweet spot in terms of how much OTC you can get in there? Or do you think that there's potential to expand further given the kind of relatively mild conditions you seem to have seen so far?

Hey.

Concluded those discussions I don't think we can really make any further comment on on what comes next door to timing.

Okay, and one last one on 810 and ODC deficiency, given that you've been able to dose escalate with no no kind of hobbies safety concerns is there a reason to not why not look to dose hired as the PK you've seen so far the exposure you have seen so far.

You kind of hit the sweet spot in terms of how much ODC you can get in there or do you think that there's potential to expand further given the kind of relatively mild conditions you seem to have seen so far.

So that the study that that has completed its a healthy volunteer study. So we've really dose as high and the healthy volunteers as we think that we need to go.

Steve Hughes: So the study that has completed is a healthy volunteer study, so we've really dosed as high in the healthy volunteers as we think that we need to go. We also have the patient study ongoing, and we can dose higher in the patients, and we will be using the data from the healthy volunteer study to enable subsequent multiple dose studies as well, where we can evaluate these things in more detail. So the short answer is really we didn't feel that we needed to dose higher in healthy volunteers; it's better to now advance the program as quickly as we can in patients to include more doses and higher doses. And just to help convert the units for people on the call, 0.4 mg per kilogram is tens of thousands of micrograms of dosing.

He also had the patient study ongoing thing we can do is high and the patients.

And we will be using the data from the healthy volunteer study to enable subsequent multiple dose studies as well, where we can evaluate these things in more detail. So the show on surveys really we didn't feel that we needed to start it does however in healthy volunteers, it's better now advance the program as quickly as we can.

In patients to include more doses and higher doses and just drew just to help convert the units for people on the call point for mix per kilogram is tens of thousands of micrograms of dosing. This is but you know Uh huh.

Steve Hughes: This is a, you know, a substantial amount of messenger RNA that we've administered systemically or through intravenous application of mRNA. One thing based on what Steve just said, is there a reason to think you would need to go to higher doses in OTC patients relative to healthy volunteers? Is there any kind of mechanistic rationale why you would need to dose higher? No, not at all.

A substantial amount of messenger arnie that weve administered systemically or through intravenous application of MRV.

The one thing based on what Steve Just said is there reason to think you would need to go do higher doses and Oki C patients relative to healthy volunteers is there any kind of like mechanistic rationale why you would need to dose higher.

No noted total sales based upon all animal data weve seen great efficacy and they any animals that dose is great to them 0.1 milligram per kilogram.

Joseph E. Payne: Based upon our animal data, we've seen great efficacy in animals at doses greater than 0.1 milligram per kilogram. Therefore, our doses in healthy volunteers are well within the therapeutic range. And we've looked at multiple different biomarker endpoints and also looked at mortality in animal models, and we see efficacy at doses of 0.1 milligram per kilogram or greater in the animals. So we're very confident that the dose range that we've tested already in healthy volunteers is well into the therapeutic range that we'll need to test in patients. Excellent. Thank you so much, everyone. Thanks, Matt.

So oh doses in the <unk> in healthy volunteers are well within in the therapeutic range and we've looked at multiple different biomarker endpoints and also I looked at mortality in any animal models and we see at doses of 1.1 milligram per kilogram or greater and the animals.

Efficacy side, we're very confident that the dose range that we've tested already in healthy volunteers is well into the therapeutic range that we will need to testing in patients.

Excellent. Thank you so much everyone.

Thanks, Matt.

Thank you. Our next question does come from the line of Yasmeen Rahimi of Piper Sandler. Please proceed with your questions.

Madhu Kumar: Thank you. Our next question has come from the line of Yasmeen Rahimi from Piper Sandler. Please proceed with your question. Hi team.

Hi team congrats on the great progress that you're making a number of questions I'm not all of them are quick clarification question. So the first one is.

Yasmeen Rahimi: Congratulations on the great progress that you're making. A number of questions, all of them are quick clarification questions. So the first one, is the percentage of zero conversion that you just put out in your 4 o'clock press release referred to as single, or is this a combination of single and boost? And then I have a number of other little questions.

I'm worried that percentage of their conversion did you just put out in your four o'clock press release referred to a single or is it a combination of single and boost and then I have a number of other little questions.

So Steve fab they the sales combustion data that we just speculation that we just discussed.

Steve Hughes: So Steve here, the seroconversion data that we just released and that we just discussed relates to all doses and all cohorts. So for the binding antibody titers, and for the binding antibody titers, we have pretty much full data now, what we see is 100% seroconversion in the two-dose cohorts, which were in younger adults, and we also see 100% seroconversion in all of the younger adult single-dose cohort In the older adult single-dose cohort, we've seen seroconversion in all except one subject, but for the older adult cohorts, we don't yet have the later time points, and we know that as time goes on, we see more and more seroconversions, so we're confident that the seroconversions will continue to increase in that older adult cohort. Thank you, Steve.

The lights to all doses and all cohorts so for the binding antibody titers and for the bonding anybody touches we have pretty much full daytona.

What we see is 100% say about conversion in the two dose cohorts.

Which was in younger adults and we also see a 100% sales conversion in all of the young all of the young adult single dose cohorts in the older adult singled out a single dose cohort, we've seen see what conversion all except one subject but.

For the older adult cohorts, we don't yet have the later time points and we know that as time goes on we see more and more sales conversion. So we're confident that the sales services will continue to increase in the older adult cohort.

Thank you, Steve and then a second question and thank you for giving Oh Gee I'm. Keith also in the four o'clock press release and thank you for pointing out that it's over 15000 for the younger at all and 2300 for the older can you give us another time point for that single 7.5 microgram dose.

Yasmeen Rahimi: And then a second question is, thank you for giving us the GMT also in the 4 o'clock press release. And thank you for pointing out that it's over 15,000 for the younger adults and 2,300 for the older. Can you give us another time point for that single 7.5 microgram dose group so that our investors just feel comfortable that we're continuing to see an increased response over time? Can I phrase that question for Steve?

Its growth so that our investors just felt comfortable that we're continuing to see an increase or a spike over time.

Can I rephrase the question for Steve I are you asking that if.

Steve Hughes: Are you asking if the IGG antibody GMTs increased going from day 29 to day 43, for example? I can only refer to what we've already mentioned. I can refer to the script, and while Steve collects maybe his thoughts as well, but we're very comfortable in saying that the... I'm just reviewing my script that... that the IgG binding antibodies continue to increase over time in humans in a similar manner to what we observed in preclinical animal models. And to refresh your memory, when we were with animal models, this particular data continued to increase to approximately day 50. Now we did not take a day 50 time point in humans, but we mentioned day 43, so that's why we use the approximate, and it's still continuing on.

The.

The Ige antibody GMT is if those increased going from day 29. Today 43 for example, I can only refer to the to what Weve already mentioned I can.

I refer to the script, while Steve Clecs, maybe his thoughts as well but.

You know, we're very comfortable in saying that the.

That.

I'm just reviewing my in my script that that the I. Gigi binding antibodies continue to increase over time in humans in a similar manner to what we observed in preclinical animal models.

And to refresh your memory, where we were with animal models [noise].

This particular data or continue to increase to approximately day 50, now we did not take a day 50 time point in humans, but we mentioned day 43, so thats why we use approximate and that still continuing on but yes that we.

Yasmeen Rahimi: But yes, we can assure people that, with respect to IgG binding antibodies, they continue to increase. And we don't have the date or time point yet, and for some of these cohorts, as Steve mentioned, we don't have the date or time point yet. So this data continues to evolve. Thank you, Joe. I guess I was just thinking if you have something from day 15 or earlier and you could share that, that way we could actually compare it to the time point that you just referenced. So that was the thought process.

We can assure people that.

With respect to IGBT antibodies that they continue to increase in humans overtime I mean doesn't have the data to one point, yet food and alcohol and for some of these cohorts as Steve mentioned, we don't have the complete.

Data package. So this data continues to evolve.

Thank you Joe I guess I was just thinking if you have something at day 15, or earlier and you could share that though actually compared to the time point that you just referenced so that was that was thought process.

So with that I'd add day 15, the geometric mean titles for the older adults was.

Steve Hughes: So at day 15, the geometric mean titer for the older adults was about 20 to 25% of the geometric mean titer of what we saw at day 29. And at day 8, it was about one-third of what it was at day 15. So from day 8 to day 15, it increased about threefold. From day 15 to day 36, it increased in the range of... of two-to-three-fold, yeah, so it is continuing to rise. Thank you. And then I have one last question.

It was about 20% to 25% of the geometric retained <unk>, meaning how much of what we saw at day 29.

Yeah, and I ate it was about one third of what it was at day 15 sales from day to day 15 to increased about threefold from day 15 today 30 today 20, no sorry today 36 increased in the range of of.

Of.

Two to three fold yeah. So it is continuing to rise.

Thank you and then one last question I know that as you pointed out 36 at the patient receive two doses. So can you maybe comment on moving forward you know Toyota.

Yasmeen Rahimi: I know that, as you pointed out, 36 of the patients received two doses. So can you maybe comment on moving forward, sort of which percentage of the population may require a boost shot in two doses to the extent that you can comment on based on the data that you've seen so far? And then, thank you again for taking my questions. Right, so what populations respond to the single administration versus the double administration? Some people have speculated that the elderly population will have weakened immune responses.

Which what percentage of the population may require a big shot in two doses to the extent you can comment on based on that data that you have seen so far and then thank you again for taking my questions.

Right. So you're you know what what populations respond to the single administration versus the double administration.

You know some people have speculated that that.

The elderly population there will be a you know have weakened immune responses. So that may end up being the case with arcturus, but we don't have that data yet.

Steve Hughes: So that may end up being the case with Arcturus, but we don't have that data yet. Based upon the single-shot data, we've seen very robust binding antibody data across all of the cohorts. The older adult cohorts, like with all of the other vaccines, have a slightly lower geometric mean titer than the younger adult cohorts, but even for the older adult cohorts, we've seen that the geometric mean titer is over 2,300. So they're robust binding antibody titers that we're seeing across all age groups and all cohorts. For the neutralizing antibody titers, we don't have the later time points yet, so that data is still evolving, and we'll be able to provide more color as time goes on.

Steve I think.

So based upon the single shot data, we've seen very robust but.

Ponting antibody data across all of the cohorts the older adult cohorts like with all of the other vaccines.

Had a slightly lower.

Jim It would mean tighter than the younger adult cohorts, but even for the older adult cohorts weve seen that the geometric mean tighter is over 2300. So the robust binding antibody titers that were saying across all age groups and all cohorts for the neutralizing antibody titers, we don't have that like to time points, yet and so that data is still.

Evolving them, we'll be able to provide more color as time goes on but the data that we do have showed that mean tides as are within the range of what we see for subjects that have had coated nineteena I know in the convalescent ties and therefore, not if there is a sub population that doesn't respond as well as others are we utilize a non viral delivery check.

Steve Hughes: But the data that we do have show that mean titers are within the range of what we see for subjects that have had COVID-19 and are in the convalescent phase. And if we're not, if there is a subpopulation that doesn't respond as well as others, we utilize a non-viral delivery technology that is multi-dose. So that.

Knowledge that is multi dosable. So that that's one of the features of this product.

Thank you team for taking my question and thank you for the answer.

Yasmeen Rahimi: Thank you, team, for taking my questions and thank you for the answers. Thanks, Yasmeen. Thank you. Our next question has come from Jaigal Nachamovitz of Citigroup. Please proceed with your question. Yes, hi, thanks for taking the question. Just another one on the single-dose versus the prime-boost. You've talked about both.

Thanks, Yes. Thank you.

Our next question is come from Uganda, Chama bits of Citigroup. Please proceed with your questions.

Yeah, Hi, Thanks for taking the question I'm just another one on the single dose versus the prime boost you've talked about Oh could you just give us a little bit more understanding as to how you going to take.

Jaigal Nachamovitz: Could you just give us a little bit more understanding as to how you're going to take... Are you going to take both of those forward, or are you going to make a decision to only take one forward? Could you just provide a little bit more context as far as whether you're going to commercialize both the single dose and the prime boost or make a decision to only go forward with one of them? So at this point in time, this is Steve again. At this point in time, we're advancing both single dose and prime boost regimens forward into the next stage of clinical development, where we'll evaluate them further in several hundred subjects, and then we'll rapidly advance one of those regimens into late stage or into a registration study.

We're going to take both of those forward are you going to make a decision to only take one forward <unk>.

Could you just provide a little bit more context as far as as far as whether whether you're going to commercialize both single dose and the prime boost or make a decision to only go forward with one of them.

At this point in time. This is Steve again that at this point in time, when we're advancing both single dose and time boost regimens forward into the next stage of clinical development well evaluate further in several hundred subjects and then we'll rapidly advance one of those regimens into late stage owing to enter.

And so a registration study so registration study, we'll we'll just take one forward, we still have confidence in the single dose regimen, which is why we are advancing that to the next stage of development, but we're also testing two doses in that next study and nimble value rapidly move to phase three with with just a single regimen.

Jaigal Nachamovitz: So in our registration study, we'll just take one step forward. We still have confidence in the single dose regimen, which is why we're advancing that to the next stage of development, but we're also testing two doses in that next study, and then we'll very rapidly move to phase three with just a single regimen, and at this point, we can't say that it will definitely be a single dose regimen, although we're confident that the single dose has adequate immunogenicity to be protective in humans. Okay, thanks. And do you plan on publishing the results of this study in the near future? As Joe indicated a little while ago, we're planning to publish the results of the study when the study is complete, which the study will complete in the first quarter of next year, and then we'll summarise the results and publish them thereafter. The issue that we have at the moment is that this is an ongoing study, so the data is evolving, so trying to publish the data based upon data that could shift is a little premature.

And at this point, it's we can't say that it will definitely be a single dose regimen, although were confident that the single dose has adequate immunogenicity to be protective engines.

Okay. Thanks, and do you plan on publishing the results of this study in the near future.

Yeah, as Joe indicated a little while ago were planning to publish it was also the study when the study is complete which the study should we study will complete in the first quarter of next year and then we will publish will summarize the results and publish them that after the issue that we have at the moment is that this is an ongoing studies at the date is evolving so trying to.

Publish the data based upon data that could could shift he said as a little premature.

Steve Hughes: Got it, thank you. Thank you. Our next question has come from the line of Gina Wang with Barclays. Please proceed with your question. Thank you for taking my questions. I have a few.

Got it thank you.

Thank you. Our next question is from from line of Gena Wang with Barclays. Please proceed with your questions.

Thank you for taking my questions I have a few first you know just wanted to come from.

Boran Wang: First, you know, just wanted to confirm that Steve mentioned that GMT of 147 for convalescent sealer. Just want to confirm that those are the print 50, and the 147 is the geometric mean, which is what's usually used for these down here.

You mentioned that you have a 147 for convalescent ceiling, just want to confirm those had to pre <unk>.

On a 147 is a more media.

So the it is the print 50 on the 147 is a geometric mean, which is whats usually used oh get these done is I say, okay perfect.

Steve Hughes: Okay, perfect. So then, what is the upper end of those pre-to-50s for convalescent serum? What is the highest number?

So then what is the aim of those.

<unk> well convalescence yeah.

What about the I guess the number.

So the the upper end that goes all the way a that the up the affluent just for subjects with that have severe disease and that I don't have the numbers right in front of me, but it's several hundred at least.

Boran Wang: So the upper end, that goes all the way, the upper end is for subjects that have severe disease and that, I don't have the numbers right in front of me, but it's several hundred at least. Okay, so when you come and, you know, print a 50 GMT within the range of the titers in the convalescent sealant, are you referring to the top end, overlapping with the top end of the convalescent sealant from both your single dose and two dose cohort? Now we're referring to the range.

Okay. So when you Oh man Prima facie, Jim Scheel were being dangerous hydrants lessons are you referring to the topline overlapping with a couple on the convalescence.

But once you have single dose and bad two doses coupons.

Now we have a filing to the range.

Okay, and then any differences between single dose 7.5, Michael Glen versus about 25 microgram intensive upfront.

Steve Hughes: Okay, and then any differences between single-dose 7.5 micrograms versus the pre-induced 5 micrograms in terms of a print 50? It's not possible for us to make that determination at the moment, just because we don't have the full data set from the single doses, as I mentioned. We don't have the latest time points.

No it's not possible for us to make that determination at the moment just because we don't have the full dataset from the single dose is as I mentioned, we don't have the lights time points and fall vaccine technology. The antigen levels. It continue to increase over time, so we see increasing levels of increasing taxes over time, so it's going to be a few.

Boran Wang: And for our vaccine technology, the antigen levels continue to increase over time. So we see increasing levels of and increasing titers over time. So it's going to be a few weeks before we're able to make the comparison between the single dose and the two dose regimens for any of the doses. However, we do see very robust antibody titers in the five microgram single dose cohort, as we do in the five microgram two dose cohort. Okay.

Weeks, yet before were able to make the comparison between the single dose and the two dose regimens for.

Any of the doses. However, we do see very robust antibody titers and and the five microgram single dose cohort as we do in the five microgram two dose cohorts.

Okay. So I mean, just a comment on others Yep Yep.

Steve Hughes: So, I mean, just to comment, all the others, you know, they are print 50 or neutralizing antibody actually reported 14 days after boost. So, just wondering, based on day 29, what data could be looked like compared to, you know, any differences do you see between single dose versus boost? And then a related question is, since you move forward, step 7.5 microgram, boost, single dose, and then two doses, just want to confirm those two doses are 7.5 microgram prime boost, and then what makes you decide to choose 7.5 microgram over 5 microgram you did so far? So, yes, we'll be taking, actually, in the next study, we'll be taking 7.5 single dose, 5 microgram 2 dose, So we're evaluating three different dose regimens in both younger and older adult cohorts.

They all come from neutralizing antibody actually the point a fortune goes the opposite.

So just wondering based on that the 29, what data could look like compared to any differences.

Between single dose versus <unk>.

And then a related question as soon as you move forward next step 7.5, Michael Glen Bose, a single dose and a two dose. It's just want to confirm those two dose is 7.5 microgram prime boost and a woman who decided to choose 7.5 microgram over like Michael when Ted.

So far.

So yes.

Yes, well, we'll be taking actually end up in the in the next study will be taking 7.5 single dose five microgram to dust and 7.52 dose regimens for whatsoever evaluating three different dose regimens.

And both younger and Ida and older adult cohorts.

The reason for selecting 7.5 to move forward is that 7.5 microgram dose was as equally well tolerated to the five microgram dose and so it made sense to move forward with with the higher dose than the lower dose given that at this point, we're not able to make a determination as to whether a single dose or two doses.

Boran Wang: The reason for selecting 7.5 to move forward is that the 7.5 microgram dose was equally well tolerated as the 5 microgram dose. And so it made sense to move forward with the higher dose than the lower dose, given that at this point we're not able to make a determination as to whether a single dose or two doses. Both effective, but we don't have the later time points for the single doses, but in order to advance the program quickly, we need to make decisions with incomplete information. So we're taking 7.5 forward. That was very well tolerated.

Despite the fact, if we don't we don't have the lights are talking points for the single doses, but in order to advance. The program quickly. We made we need to make decisions with incomplete information. So we're taking 7.5 forward that was very well tolerated. It was as well tolerated if not better tolerated than the five microgram dose and and we're also taking.

Steve Hughes: It was as well tolerated, if not better tolerated, than the 5 microgram dose, and we're also taking 5 and 7.5 forward as a two-dose regimen. Okay, thank you. Thank you. Our next question will come from the line of Steve Seedhouse with Raymond James. Please proceed with your question.

Five and 7.45 forward as a as a two dose regimen.

Okay.

Okay. Thank you.

Thank you. Our next question was how can rely that Steve seat House with Raymond James. Please proceed with your question.

Hi, good afternoon. Thanks for taking the question I guess I'm just confused to this conversation did you end up actually dosing people 10 micrograms and the.

Steve Seedhouse: Thanks for taking my question. I guess I'm just confused through this conversation. Did you end up actually dosing people with 10 micrograms in this— You did what went into the decision ultimately to advance 7.5 in both the single and double-dose regimens. So we did dose at 10 micrograms. We dosed a single-dose cohort at 10 micrograms. At the 10-microgram dose, we saw some grade 3 tolerability events. And so we chose to move forward with a 7.5 dose, as opposed to 10 micrograms, because 7.5 was extremely well-tolerated with zero grade 3 events. And we don't believe that we're going to see any trade-off based upon the immunogenicity results that we're seeing by going with the slightly lower dose. Got it, makes sense. Could you maybe just elaborate, were those things like fever, chills, muscle aches, muscle pain, that have been seen with other COVID vaccines, or what were those? So we haven't seen any fevers that are grade 3. In fact, we haven't seen any fevers that are more than mild at any dose level in the study.

You did.

What went into the decision ultimately to advance 7.5 in both single and double.

Dose regiments.

Sure. So we did does that 10 micrograms, we dosed on a single <unk> single dose cohort 10 micrograms at the 10 microgram dose we saw some greatly tolerability events and and so we we chose to move forward with a 7.5 dose as oppose.

10, micrograms, because 7.5 was extremely well tolerated.

With zero grade three events and we don't believe that we are going to see any trade off based upon the immunogenicity results that were seeing by going with a slightly lower dose.

Got it makes sense could you, maybe just elaborate where those things like fever, chills Muslims muscle pain that have been seen with other coven vaccines are what were those.

So we haven't seen any favors that a great play in fact, all any fever, we haven't seen any any features that are more of a mild and I need those levels in the study I can't honestly remember off top of my head was what the grade three events were.

Steve Hughes: I can't honestly remember off the top of my head what the grade 3 events were in the study, so I can't really comment specifically. They just were grade three tolerability events that were, you know, within the vaccine grading scale for those events. Okay, fair enough. And then maybe on manufacturing, last question, at what scale on a dose basis, and maybe this is an unfair question, it could be too early, but I know others, particularly with mRNA vaccines, threw out some estimates pretty early. So at what scale do you think you can manufacture the vaccine in, let's just say 2021?

And in the study.

So I can't really comment specifically, they just weren't great three tolerability of items that were within the vaccine grading scale for those events.

Okay.

Fair enough and then maybe on manufacturing last question, what's still on a dose basis.

And maybe this is an unfair question what could be too early but I know others.

Particularly with Emory vaccines throughout some estimates pretty early so what scale do you think you can manufacture the vaccine and let's just say 2021.

Oh and 2021, I think Andy mentioned, some you know provided some guidance there that we have the foundation to do you know very large.

Steve Seedhouse: Oh, in 2021, I think Andy mentioned some, you know, provided some guidance there that we have the foundation to do, you know, very large manufacturing campaigns. But, you know, we're at the scale right now that's sufficient to supply Israel and Singapore. And we have a process that's scalable for both the process to make the messenger RNA construct, and to formulate it, and to finish and lyophilize it. So, we have partners that help us with this capacity, like we mentioned Catalan and the rest of the farm. So and others that are helping us here. So we're at our manufacturing horizon is very promising. Our technology is validated, and the tech transfer is completed. And we're in good shape there.

Manufacturing campaigns, but you.

You know we're in the scale right now that's sufficient to supply for Israel in Singapore, and we have a process that scalable for both the process to make the messenger R&D construct and to formulate it.

And to fill finish in lyophilized. It so and we have the partners that help us with this capacity like we mentioned Catalent and rest of farm, so and others that are helping us here. So we're <unk> our manufacturing horizon is very promising our technology is validated in tech transferred and we're in good shape there.

Pat do you have an extra comment yeah. Just one other comment you know as Andy mentioned Neal we did receive a that.

Joseph E. Payne: And Pat, do you have an extra comment? Yeah, just one other comment. You know, as Andy mentioned, we did receive that additional $45 million for procurement of raw materials for our manufacturing efforts. So with that additional funding, we're getting ready to get a lot of the key raw materials up to a kilogram scale and get that ordered so that we can be very nimble in manufacturing for next year.

Additional $45 million for procurement of raw materials for our manufacturing effort. So what would that a additional fund.

We're getting ready to will gets a lot of the key raw materials up to a kilogram skill.

And get that order so that we can be very nimble in manufacturing for next year.

Joseph E. Payne: Yeah, thank you. That is all the time we have for questions today. I would like to turn the floor back over to President and CEO Joe Payne for any closing comments. Hey, thanks everyone for listening. At this point, we're going to close the call, but feel free to reach out as always. If you have any follow-up questions, we will be as efficient as we can in our responses. Bye for now. Thank you. This does conclude tonight's call. You may disconnect your lines at this time. Thank you for your participation, and have a great day.

No. Thank you.

That is all the time, we have for questions today, I would like to turn the floor back over to President and CEO, Joe Payne for any closing comments.

Hey, thanks, everyone for listening it looks at this point, we're going to close the call, but feel free to reach out as always if you have any follow up questions. We will be as efficient as we can in our responses bye for now.

Thank you. This does conclude tonight's call you may disconnect. Your lines at this time. Thank you for your participation.

Have a great that.