Q2 2022 Chimerix Inc Earnings Call

Good afternoon, ladies and gentlemen.

Good afternoon, ladies and gentlemen, thank you for standing by and welcome to the ocular Therapeutics second quarter 2022 earnings Conference call. At this time, all participants are in a listen only mode.

Thank you for standing by, and welcome to the Ocular Therapeutics Second Quarter 2022 Earnings Conference Call.

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

Later, we will conduct a question and answer session, and instructions will follow at that time.

Later, we will conduct a question and answer session and instructions will follow at that time. It is now my pleasure to turn the call over to Donald.

It is now my pleasure to turn the call over to Donald Knotman, Chief Financial Officer of Ocular Therapeutics.

Chief Financial Officer of ocular Therapeutics. Please go ahead Sir.

Please go ahead, sir.

Thank you operator, good afternoon, everyone and thank you for joining us on our second quarter two sound recording our first Tim Baxter product revenue covered by two international agreements of $35 million in aggregate.

Thank you, operator.

Good afternoon, everyone, and thank you for joining us on our second quarter. Recording our first Tembexa product revenue covered by two international agreements of $35 million in aggregate. This was only possible because we made the decision a couple of years ago to manufacture over 300,000 treatment courses of Tembexa at our own risk without a contract, somewhat atypical in the biodefense space. Because of that decision, we were able to take advantage of this opportunity immediately, completing contracts and shipping products in a matter of days.

This was only possible because we made the decision a couple of years ago to manufacture over 300000 treatment courses of 10 Bucks a at our own risk without a contract somewhat atypical in the Dubai Biodefense space.

Because of that decision, we were able to take advantage of this opportunity.

Opportunity immediately completing contracts and shipping product in a matter of days.

If you're looking to isolate and assess Chimeric's execution as it relates to creating and delivering on contracts, these are great examples.

If youre looking to isolate and necessity America execution as it relates to creating and delivering on contracts. These are great. Examples.

The same decision to manufacture product at risk will also position us to respond immediately to place Tembexa into the U.S. stockpile once the BARDA agreement is in place.

The same decision to manufacture product at risk will also position us to respond immediately.

Placed in <unk> into the U S stockpile once the BARDA agreement is in place. We mentioned previously that the monkey pox outbreak introduced some new considerations for both BARDA and kind of merit. So we are and have been thoughtful to address those urgently in the meantime, the international sales recorded.

We mentioned previously that the monkeypox outbreak introduced some new considerations for both BARDA and Chimeric, so we are and have been thoughtful to address those urgently.

In the meantime, the international sales we've recorded have satisfied our near-term capital needs.

Satisfied our near term capital needs.

You may be aware that while Tembexa was approved for smallpox, preclinical data does support the activity of Tembexa against multiple orthopoxviruses, including monkeypox. The FDA commented on that potential in their post-approval manuscript.

You may be aware that while <unk> was approved for smallpox preclinical data does support the activity has come back against multiple or the pox viruses, including monkey pox.

The FDA commented on that potential in their post approval manuscript and the fact of the matter is no randomized control studies have been performed in humans with monkey pox with either of the FDA approved anti virals for smallpox and there are still a lot of unknowns as the virus spreads and mutates into potentially more.

The fact of the matter is no randomized control studies have been performed in humans with monkeypox with either of the FDA-approved antivirals for smallpox, and there are still a lot of unknowns as the virus spreads and mutates into potentially more resistant strains.

We're working with leading infectious disease physicians on potential options to generate additional data.

Distance strains, we're working with leading infectious disease physicians on potential options to generate additional data.

Let me now turn to ONG-201.

Let me now turn to <unk> 201, we're pleased to announce today. The design details of our phase III action study along with 201. This is the most advanced study in this age three to 827 am population of patients. So I'll, let Allen go into the design details, but let me make a few points upfront.

Pleased to announce today the design details of our Phase III Action Study of ONG-201. This is the most advanced study in this H3K27M population of patients.

I'll let Alan go into the design details, but let me make a few points up front.

We've worked with KOLs across disciplines and geographies to design a trial with a probability of success that's high and multiple ways to achieve this efficiently.

We've worked with kols across disciplines and geographies to design a trial with the probability of success that high and multiple ways to achieve this efficiently.

The Action Study is highly differentiated from the other Phase III studies that have been performed in the broader glioblastoma space.

The action study is highly differentiated from the other phase III studies that have been performed in the broader glioblastoma space. So it really comes down to the phase two data we have in hand, and the circumstance in which it was generated compared to other drugs that really differentiate this drug's likelihood of success.

It really comes down to the Phase II data we have in hand and the circumstance in which it was generated compared to other drugs that really differentiate this drug's likelihood of success.

I should first note that about a third of the studies in this space advance the phase, 3 without phase 2 data.

I should first note that about a third of the studies in this space advance the phase III without phase III data.

For those that did advance based on phase 2 data, it was rare that the patient population, was associated with a targeted genetically specified mutation like H3K27M.

For those that did advance based on phase II data. It was rare that the patient population was associated with a targeted genetically specified mutation like Ace III <unk> 27 a M.

With that target, we can focus on the same homogeneous population of patients in phase, 3 that were the source of the data in phase 2.

With that target we can focus on the same homogeneous population of patients in phase three that were the source of the data in phase II. We can also identify those patients with the same tools used in phase II, which are reliable diagnostic methods already nearly universally used.

We can also identify those patients with the same tools used in phase 2, which are, reliable diagnostic methods already nearly universally used.

The isolation of single agent activity is also critical. Many previous phase 2 studies have been conducted with drug combinations or have failed to have, adequate washout periods to distinguish drug effects.

The isolation of single agent activity is also critical many previous phase two studies have been conducted with drug combinations or have failed to have adequate washout periods to distinguish drug effect.

They then relied on time point endpoints like PFS compared to historical benchmarks.

Then relied on time point endpoint like PFS compared to historical benchmarks. In contrast, we've carefully isolated the single agent activity of <unk> 201 in our phase II data.

And in contrast, we've carefully isolated the single agent activity of ONC201 in our, phase 2 data.

Importantly, we've measured tumor response using Raynaud criteria, the most rigorous, standard. This method was developed to address some of the shortcomings of prior response rate, measures such as the Levin and McDonald criteria. Our overall response rate of 20 to 30% in the relapse setting using Raynaud complemented, by the durability of those responses evaluated by blinded independent central review also increased our confidence relative to prior studies done using less stringent criteria.

Importantly, we've measured tumor response using rain out criteria. The most rigorous standards. This method was developed to address some of the shortcomings company.

Short comings of prior response rate measures such as <unk> 11, and Mcdonald criteria are overall response rate of 20% to 30% in the relapsed setting using rain now complemented by the durability of those responses evaluated by blinded independent Central review also increase our <unk>.

Confidence relative to prior studies done using less stringent criteria.

It's also critically important that our efficacy data was generated in the absence of anti-angiogenic, drugs like Avastin, which can confound imaging and yield false response and progression assessments, which have historically failed to translate to phase 3 success for other drugs.

It's also critically important that our efficacy data was generated in the absence of anti angiogenic drugs like Avastin, which can confound imaging and yield false response and progression assessments, which have historically failed to translate the phase III success for other drugs.

Finally, the consistency across multiple clinically meaningful endpoints is particularly convincing. The ONC201 data demonstrates a clear association between response and a reduction in steroid, use and an improvement in performance status.

And finally, the consistency across multiple clinically meaningful endpoints as particularly convincing.

<unk> data demonstrates a clear association between response and a reduction in steroid use and an improvement in performance status.

There's also an association with survival as all responders were alive at 2 years or, were alive at the data lock if that was earlier than 2 years. For patients who did not achieve a response, none were alive at 2 years.

There is also an association with survival as all responders were alive at two years or were alive at the data lock if that was earlier than two years for patients who did not achieve a response none were alive two years, the internal consistency of the state is striking.

The internal consistency of this data is striking.

We previously noted the ongoing work related to compiling safety data to strengthen the, risk benefit assessment of ONC201. Last fall, we reported just a summary of safety data from the 50 patient efficacy cohort.

We previously noted the ongoing work related to compiling safety data to strengthen the risk benefit assessment of all 201 last fall. We reported just a summary of safety data from the 50 patient efficacy cohort.

I'm now happy to say we've completed a more robust assessment of over 200 patients, and, the results reveal a very attractive safety profile as expected.

I'm now happy to say, we've completed a more robust assessment of over 200 patients and the results reveal a very attractive safety profile as expected I'll turn the call over to Alan to share more about the details of the phase III <unk> study as well as hit on those findings in the latest safety assessment Allen.

I'll turn the call over to Alan to share more about the details of the phase 3 action study, as well as hit on those findings in the latest safety assessment.

Alan?

Thank you, Mike.

Thank you Mike.

I'm excited to briefly go over the details of our action phase 3 study.

Quite a degree to go over the details of reactions phase III study.

We expect to activate select U.S. sites later this year and continue into international, sites throughout the first half of next year.

We expect to activate select U S sites later this year and continue into international sites throughout the first half of next year.

Action is a randomized, double-blind, placebo-controlled, and multi-centered study in newly diagnosed, diffuse glioma patients whose tumor harbored the H3K7M mutation. Treatment with OCTL-1 will occur following completion of radiation therapy. The study will enroll approximately 450 patients, who will be randomized to receive, 625 mg of OCTL-1 at one of two dosing frequencies, once or twice weekly, or placebo.

Action is a randomized double blind placebo controlled multi center study in newly diagnosed diffuse clear on what patients whose tumors harbor the <unk> mutations.

Even with <unk> hundred one will occur following completion of radiation therapy.

The study will enroll approximately 450 patients who will be randomized to receive 625 milligrams of October one having one of two dosing frequencies once or twice weekly or placebo.

The primary input of the study is overall survival. The study will also evaluate progression-free survival with an alpha control for both OS and PFS. OS will be assessed for efficacy at three alpha control time points, two interim analysis by the, Independent Data Monitoring Committee, followed by a final assessment.

The primary endpoint of overall survival.

We will also that with progression free survival with an alcohol control for OS and PFS.

All of us will be assessed for efficacy of three alpha control time points two interim analysis by the independent data monitoring committee followed by a final assessment.

The final PFS analysis will be performed using real HTG by blind and independent central review. Participants in the study must have a Karnafsky or Lansky performance status, which is a measure, of patients' ability to perform ordinary tasks, of greater than or equal to 70 at the time of randomization.

The final PFS analysis will be for one using rail hcg by blinded independent Central review.

Participants in this study must have a colosky our landscape performance status, which is a measure of patients ability ordinary tasks of greater than 70 at the title randomization.

Key exclusion criteria are the presence of a primary spinal tumor, diffused intrinsic, pontine glioma, evidence of leptomental spread of disease, or cerebral spinal fluid dissemination.

Keith closing criteria or the presence of primary spinal tumor diffuse intrinsic pontine glioma evidence of leptomeningeal spread of disease or cerebral spinal fluid dissemination.

The study will take place at up to 120 sites in North America, Europe, and Asia Pacific.

The second will take place up to 120 sites.

Latin America, Europe , and Asia Pacific.

The first interim analysis is anticipated in early 2025 with sign-in data in 2026. The study has greater than an 80% power with an assumed hazard ratio of 0.65 for overall survival, and 0.60 for progression-free survival.

The first interim analysis is anticipated in early 2025 with final data in 2026.

<unk> has greater than 80% power quite an assumed hazard ratio of <unk> five for survival and 0.60 for progression free survival.

Independent comparison will perform for each ONC1 study group versus control at each time point.

Independent comparison will perform for each out to one tenant group versus control at each time point.

The study design builds on findings from the phase 2 data that should increase the likelihood, that patients will respond to ONC2-1.

The study design and sales and findings from our phase two data has should increase the likelihood that patient will respond talk to one.

These factors include moving to an earlier line, likely including patients with less, bulk disease, increasing the time for patients being on ONC2-1, as well as limiting the study to patients with a KPS of greater than or equal to 70. All of these factors were associated with better response in the phase 2 data set. In addition, the study design has a number of elements which should support rapid enrollment.

These factors include the movie took or is there a line likely including patients with less bulky disease, increasing the time for patients being on October one as well as limiting this payer to patients with the KPN.

<unk> 70.

All of these factors worth us with better response in the phase II dataset.

In addition, the study design has a number of elements, which should support rapid enrollment.

This includes a wider time window to identify patients as there's a natural six-week gap, between initial diagnosis and completion of radiation therapy.

This includes a wider time window to identify patients and there is a natural six week gap between initial diagnosis and completion of radiation therapy.

The presence of an H3K27M mutation will be identified as part of the standard of care, at the time of initial diagnosis with widely available tests.

The <unk> 27, and <unk> mutation will be identified as part of the standard of care at the tenant initial diagnosis of why is it the whole test in addition.

In addition, the study design has a number of elements which should support rapid enrollment.

In addition, patients are twice as likely to receive ONC2-1 as a placebo.

Patients are twice as likely to receive up to one of the placebo.

We received excitement from numerous K-1s globally to participate in the study.

<unk> fabric from numerous kols globally to participate in the study.

Lastly, we've been keenly listening as FDA guidance and expectations for oncology development, programs are evolving.

Lastly, we have been keenly listening is FDA guidance and expectations for oncology development programs are evolving.

In addition to an increased push towards randomized clinical trials and registration, FDA has pushed for evaluation of multiple doses and target indications, which has included discussions about chimerics.

In addition to an increased push towards randomized clinical trials for registration FAA has pushed farther out I wish in a multiple dose within target indications.

Which is included discussions with Pemex.

Noting that ONC2-1's efficacy was mainly based on a single dose and schedule, we incorporated an additional dose in the phase 2 study, with the upside of increasing study enthusiasm and probability of success. This additional schedule has been well tolerated in previous ONC 2.1 trials.

Noting the Hunter I wanted to ask me was mainly based on the single dose and schedule. We incorporate an additional dose in the phase two study with <unk>.

The upside of increasing steady enthusiasm and probability of a successful study.

This additional schedule have been well tolerated in previous <unk> trials.

In the meantime, we've been updating our ONC 2.1 safety data analysis that includes, a robust safety analysis performed on 2 in 11 patients.

In the meantime, we've been updating our arc 201 seem to doubt data analysis that includes a robust safety analysis the script 211 patients.

With this new safety data added to the data we've already reported, we now have a better, characterization of this risk benefit of this drug.

[laughter] newspaper, David added to that the data we've already reported we now have a better characterization of this risk benefit of this drug.

In this analysis, treatment-emergent adverse events that were drug-related were generally, grade 1 and 2. The most common events were headache, fatigue, nausea, and vomiting. The only related adverse event of grade 3 or higher that occurred in more than 2% of, patients was fatigue reported at 2.8%.

In this analysis.

Emergent adverse events that were drug related where generally grade one and two.

Most comment that hence were headache, fatigue, nausea and vomiting.

Only related adverse event of grade three or higher that occurred in more than 2% of patients with <unk>.

<unk> reported that two 8%.

Adverse events reported in the pediatric population were generally similar to those reported in, adults. Only 5 patients, 2.4%, experienced a treatment-related adverse event, leading to cytodrug discontinuation, reduction, or interruption. These events were neutropenia in 3 patients, hypersensitivity in 1 patient, neutrophil, colon cyst decrease in 1 patient, and a pulmonary embolism in 1 patient.

Having this events reported in the pediatric population route generally similar to the other part of my adults.

Only five patients two 4% experienced a treatment related adverse events, leading to cytokine discontinuation reduction or interruption.

These enhancement neutropenia and treat patients hypersensitivity in one patient.

So call it decreased 10, one patient in Oklahoma to analyze them in one patient.

With the Phase 3 trials soon underway and this data in hand, we plan to revisit the, question of accelerated approval based on the Phase 2 data with FDA in the fourth quarter of this year.

With the phase III trial soon underway and this data in hand, we plan to revisit the question of accelerated approval based on the phase two data with FDA in the fourth.

Part of this year.

With that, I turn it over to Mike Edgehill to speak to our financial results.

With that I turn it over to Mike Andriole to speak to our financial results.

Thanks, Allen, and good afternoon, everyone.

Thanks, Alan and good afternoon, everyone.

With Allen's overview of the action study and rationale for why we're optimistic about, its outcome, I wanted to just make a few comments on the potential commercial market for RONC-201.

Alan's overview of the action strategy and rationale for why we're optimistic about its outcome I wanted to just make a few comments on the potential commercial market for a run through of one.

As most of you are aware, diffuse gliomas are a particularly lethal form of brain cancer, and H3K27M mutants are among the worst of what is already a poor prognosis. The unmet need for new therapies in glioma broadly, and H3K27M mutants in particular, is among the highest unmet needs in all of oncology.

As most of you are aware diffuse gliomas are particularly lethal form of brain cancer at age three to 827 nanometers are among the worst of what is already a poor prognosis.

Unmet need for new therapies in glioma broadly and <unk> 27, a mutant <unk> in particular is among the highest unmet needs in all of oncology.

As it relates to RONC-201, our market research indicates that the unaided awareness of this, agent for H3K27M mutants is already high, and following the participation in the action study of up to 120 sites across the major markets, we expect the association of this agent to H3K27M mutations will be nearly ubiquitous among top-prescribing neuro-oncologists.

As it relates to answer of one our market research indicates about the unaided awareness of this agent for <unk> 27, I'm Eaton's is already high and following the participation in the action study of up to 120 sites across the major markets. We expect the association of this agent to age three K twenty-seven mutations will be nearly <unk>.

With this among top prescribing neuro oncologists to be <unk>.

If the action study is successful, we expect this awareness will translate to rapid adoption, of the therapy in major markets.

Action study is successful we expect this awareness will translate to rapid adoption of the therapy and major markets. This is likely adoption should be aided by our competitive landscape that is quite attractive.

This likely adoption should be aided by a competitive landscape that is quite attractive.

Specifically, we're not aware of any other Phase II or Phase III programs in the industry, targeting this mutation.

Specifically, we're not aware of any other phase two or phase III programs in the industry targeting industry. Jason This is John .

These dynamics likely make RONC-201 unique in a market where there have been several, examples of underperforming commercial launches in oncology in recent years.

M. It's likely make onto a one unique in a market where there have been several examples of underperforming commercial launches in oncology in recent years. Consequently, we view the commercial risk here is relatively low and continue continue to view this as a worldwide annual revenue opportunity that should comfortably exceed $500 million.

Consequently, we view the commercial risk here as relatively low and continue to view, this as a worldwide annual revenue opportunity that should comfortably exceed $500 million.

As Mike mentioned earlier, this past July, we announced two international Tembexa procurement, contracts totaling nearly $35 million. We've delivered nearly all of that product recently and will realize at least $32 million, in revenue in the third quarter.

As Mike mentioned earlier.

This past July we announced two international Tim Baxter procurement contracts totaling nearly $35 million, we've delivered nearly all of that product recently and will realize at least $32 million of revenue in the third quarter on a pro forma basis parents at the end of June would have been approximately $70 million when including this additional.

On a pro forma basis, cash at the end of June would have been approximately $70 million, As it relates to the pending transaction for the sale of Tembexa to Emergent, in late July, the HSR waiting period expired. That satisfied one of the key closing conditions. The other two remaining key closing conditions are execution of the procurement contract with BARDA and BARDA's approval of a pre-novation agreement between Chimerix and Emergent.

Our revenue.

As it relates to the pending transaction for the sale of timber extra to emergent in late July of the HSR waiting period expired that satisfied one of the key closing conditions. The other two remaining key closing conditions, our execution of the procurement contract with BARDA and BARDA is approval of a pre novation agreement between <unk> and <unk>.

I know that investors are eager to have a BARDA contract executed, as are we. Certainly, the recent declaration of the monkeypox outbreak as a public health emergency by both the WHO and HHS has influenced how both parties are approaching the final details of this agreement.

Merger.

I know that investors are eager to have a BARDA contract executed Azure, we certainly the recent declaration of the monkey pox outbreak as a public health emergency by both the WHI and HHS has influenced by both parties are approaching the final details of this agreement.

To that end, we'll work expeditiously with our counterparts at BARDA to finalize the contract as soon as reasonably possible.

And well work.

Expeditiously with our counterparts at BARDA to finalize the contract as soon as reasonably possible in the interim we continue to operate the business in the ordinary course, and we'll provide another update to the market on the Finalization of the BARDA agreement when we can.

In the interim, we continue to operate the business in the ordinary course and will provide another update to the market on the finalization of the BARDA agreement when we can. With our current cash position, in addition to the expected cash generated from the sale of Tembexa, Chimerix expects to be well positioned to advance the action study and other pipeline programs without concern of a near-term diluted financing.

With our current cash position. In addition to the expected cash generated from the sale of tobacco to America expects to be well positioned to advance the action study and other pipeline programs without concern about near term dilutive financings.

Now moving to our statement of operations.

Now moving to our statement of operations.

The company reported a net loss of $23.5 million, or $0.27 per basic and diluted share, for the second quarter of 2022, compared with a net loss of $17.8 million, or $0.21 per basic and diluted share, in the second quarter of 2021. Research and development expenses increased to $18 million for the second quarter of 2022, compared to $13.8 million for the same period in 2021. The main driver of this increase is the ongoing development related to ONC-201.

We reported a net loss of 23, and a half million dollars or 27 cents per basic and diluted share for the second quarter of 2022, compared with a net loss of $17 $8 million or 21 cents per.

Basic and diluted share in the second quarter of 2021.

Search and development expenses increased to $18 million for the second quarter of 2022 compared to $13 $8 million for the same periods in 2021. The main driver of this increase was the ongoing development related on 301.

General and administrative expenses increased to $5.8 million for the second quarter of 2022, compared to $4.4 million for the same period in 2021.

General and administrative expenses increased to $5 $8 million for the second quarter of 2022 compared to $4 $4 million for the same period in 2021 and with that overview I'll now turn the call back to Mike Sherman for closing remarks, Mike.

And with that overview, I'll now turn the call back to Mike Sherman for closing remarks.

Mike?

Thanks, Mike before I open it up for questions I'd like to take a minute to welcome Christopher Jordan for the team as our Vice President of regulatory Affairs.

Thanks, Mike.

Christopher comes to us with over 30 years of pharma experience across all stages of product development. Some of our management team Ive had the pleasure of working with Christopher at Endo site, and Novartis, where he recently led the regulatory strategy and execution of the FDA approval and MAA submission of P. SMA <unk>.

Before I open it up for questions, I'd like to take a minute to welcome Christopher Jordan to the team as our Vice President of Regulatory Affairs. Christopher comes to us with over 30 years of pharma experience across all stages of product development. Some of our management team have had the pleasure of working with Christopher at Endocyte and Novartis, where he recently led the regulatory strategy and execution of the FDA approval and EMA submission of PSMA-17, or Puvicto, as it's now known. His knowledge in the oncology field and track record of navigating complicated regulatory processes will be a great addition to the team as we continue the development of our oncology pipeline.

17, or predict though as it's now known.

His knowledge in the oncology field and track record of navigating a complicated regulatory processes.

Be a great addition to the team as we continue the development of our oncology pipeline with that Brianna I'll turn it over to you to open the call for questions.

With that, Brianna, I'll turn it over to you to open the call for questions.

Thank you.

Thank you at this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad. Your first question will come from Maury Raycroft with Jefferies. Your line is now open.

At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad.

Your first question will come from Maury Raycroft with Jeffreys.

Your line is now open.

Hi, Thanks for taking my questions and congrats on getting the phase III design.

Hi.

Thanks for taking my questions, and congrats on getting the Phase 3 design.

For the Phase III you have two interim OS assessments by independent data monitoring Committee Committee at 164 events, and then 246 events and then the final at 327 events if successful could either of the initial interim assessments at 164 or $2 46 be enough to file for approval.

For the Phase 3, you have two interim OS assessments by independent data monitoring committee at 164 events and then 246 events, and then the final at 327 events.

If successful, could either of the initial interim assessments at 164 or 246 be enough to file for approval?

Yes, those are designed such that.

With with statistical significance at those at those endpoints.

Yeah, those are designed such that with statistical significance at those endpoints, you'll have, PFS in hand, response rate data in hand, and overall survival at those early endpoints.

Got you will have PFS in hand.

Sponsored data in hand, and overall survival.

With those early endpoint is pretty significant advantages.

Pretty significant advantages.

We would expect those to be the basis of a regulatory submission and approval.

We would expect those to be the basis of a regulatory submission and approval.

Got it.

Got it and then.

Also, can you talk more about the twice-a-week dosing and what you've seen in prior clinical, data that supports the rationale for moving the twice-per-week dosing into the Phase III?

Also can you talk more about the twice a week dosing and what you've seen in prior clinical data that supports the rationale for moving the twice per week dosing into the phase III.

Yeah, I might just turn that directly over to Allen and Dosh to share both the rationale, for including it as well as some of the experience we've had with it in prior trials.

Just turn that directly over to Alan <unk>.

Both.

The rationale for including that as well as some of the experience we've had with it in prior trials.

Yeah, this is Allen.

Yes. This is Alan I'll start.

I'll start.

We have evaluated twice-weekly dosing and have been shown that this has been a safe, regimen in several studies.

We have evaluated twice weekly dosing and have been shown that this has been and will affect our safe regimen.

In several studies.

One of the reasons we want to move this forward is we wanted to have the opportunity to have, even a more intense dose.

One of the reason we wanted to move this forward as we wanted to have the opportunity to have even a more intense talent suite.

We know that we want to try to maximize the effect we've seen, and we really haven't seen, any challenge so far with safety from the current dosing regimen.

Know that we want to try to maximize the effect, we have seen and we really haven't seen any challenge so far with <unk>.

Safety from the current dosing regimen.

This also is addressed in part for what you've seen from the FDA regarding optimization of, dose, and we think that this helps also address the situation where you have two shots on goal, and essentially you have two places for a patient to get on study with OP2-1.

This also.

Yes.

What you've seen from the FDA regarding optimization with dose and we think that does help.

Also.

The address to situationally into half two shots on goal and essentially you have two places for a patient to get on study with our tier one.

I'll pass this on to Josh in additional comments.

I'll pass on to Josh in District Court.

Sure.

This is just speaking to the rationale really comes from preclinical in vitro findings showing, that the efficacy of OP2-1 can be increased with prolonged exposure to the same concentration, a little bit of a sweet spot towards 48 hours of an intubation time, really leading to that maximal effect.

Sure. This is just speaking to the rationale really comes from preclinical in vitro findings showing that the efficacy of about 201 can be increased with prolonged exposure because the same concentration a little bit of a sweet spot towards 48 hours with an incubation time really leading to that maximal effects. So.

The thinking is that we're getting into these brain tumors with the current dose, achieving, therapeutic concentrations, and if we can just prolong that duration for an extra day by giving a second dose on a consecutive day there, that might be the key to unlocking an increase in efficacy based on those models.

The thinking is that we're getting into these brain tumors with the current dose achieving therapeutic concentrations and if we can just prolonged debt duration for an extra day by giving a second dose.

To date, there that might be the key to unlocking it.

I can see based on this model so that in combination with the safety experience in the clinic that al spoke to us what pieces to incorporate that.

So that in combination with the safety experience in the clinic that Alex spoke to is what leads, us to incorporate that.

Got it.

Let me- I'll add one other thing, Maury.

Got it.

I'll add one other thing maury that the notion that that too.

The notion that to encourage enrollment in this trial, you would need to go to a two-to-one, randomization anyway if it were a single schedule.

Encourage and enrollment in this trial you would need to go to a two to one randomization anyway. If it were a single.

Schedule and so you kind of get that two to one benefit here with just a little bit.

And so you kind of get that two-to-one benefit here with just a little bit higher in aggregate.

And in aggregate. So it's it's I think a good use of.

So it's, I think, a good use of the statistical power in order to get another shot on goal, for success and still encourage patients to enroll.

Of.

The statistical power in order to get another.

Another shot on goal for success and still encourage patients to enroll.

Got it.

Got it yeah. That's all helpful. And then maybe last question for me just wondering if in communications with FDA.

Yeah, it's all helpful.

Great question for me.

Just wondering if in communications with FDA, if they communicated on whether an accelerated, approval path based on the phase two data and additional supporting data, if that's still on the table.

If they communicated on whether an accelerated approval path based on the phase II data and additional supporting data if that's still on the table.

Now, as we discussed at our last call, we essentially delayed that conversation after, their feedback earlier this spring with a focus on getting moving with the Phase 3 trial and knowing that without this additional safety data in hand, we were a little bit limited in our ability to make a strong case for the risk-benefit assessment.

Yeah, we as we discussed.

At our last call, we essentially delayed that conversation after their feedback. This earlier this spring with a focus on getting.

Moving with the phase III trial, and knowing that without this additional safety data in hand, we were a little bit limited in our ability to make a strong case for the risk benefit assessment. So now that we have.

So now that we have this additional safety data set, which really plays out exactly as, we expected, we'll be able to go back to them.

This additional safety dataset, which really plays out exactly as we expected we will be able to go back to them. So in the meantime, we really haven't pushed that conversation beyond the phase III trial, we'll revisit that here of.

So in the meantime, we really haven't pushed that conversation beyond the Phase 3 trial.

We'll revisit that here later this year.

Later this year.

Got it.

Okay.

Got it okay. Thanks for taking my questions. Thanks, Good morning.

Thanks for taking my questions.

Thanks, Maury.

Your next question comes from Joseph Tomei with Cowen.

Your next question comes from Joseph <unk> with Cowen. Your line is now open.

Your line is now open.

Hi there.

Good afternoon.

Hi, there good afternoon, and thank you for taking my questions. Many of the first one just on <unk> hundred one.

And thank you for taking our questions.

Maybe the first one, just on OCT-201, with the Phase 3 you're administrating shortly, after completion of radiation, is there a timeframe that's mandated in the study?

With the phase III, you're administrating shortly after completion of radiation is there a timeframe that's.

That's mandated in the study and maybe can you can compare this to.

And maybe you can compare this to the timeframe post-radiation that patients saw OCT-201 in, the Phase 2 analysis population.

The timeframe post radiation that patients on 201 in the phase two analysis population that would be helpful.

That would be helpful.

Sure.

I'll let Alan answer that one.

Sure I'll, let I'll, let Alan answer that one.

So there's a couple of ways you're looking at this.

So.

There's a couple ways you are looking at that as one of the reasons. We've done this way we are allowing patients to start the screening process. When they are initially diagnosed and then starting the radiation therapy. So you have plenty of time when you can actually grab the patients.

One of the reasons we've done this way, we're allowing patients to start the screening process, when they are initially diagnosed, and then starting the radiation therapy, so you have plenty of time you can actually grab the patient.

There's a specific timeframe which should be randomized, which I believe, and I'll have, Josh correct this, I think it's six to eight weeks post-radiation. I'm sorry, not post-radiation, post-initial diagnosis.

The specific timeframe, which you should be granted in mind, which I believe Josh practice.

16 weeks post radiation I'm, sorry that correlation post.

But I want Josh to clarify the exact time, I don't really have that in front of me.

Initial diagnosis.

Just to clarify the exact timing I don't have that in my family.

Yeah, sure.

Sure, we'll enroll in the range of two to six weeks post radiation sickness study.

We'll enroll in the range of two to six weeks post-radiation for this study, and that contrasts, to the prior efficacy analysis in the relapse setting was more than three months, that washout period there.

That contrasts to the primary efficacy analysis in the relapsed setting was but was more than three months that washout period. There. So this study is substantially moving paces up closer to radio therapy, which we think will give them a better shot at having prolonged duration of therapy.

So this study is substantially moving patients up closer to radiotherapy, which we think, will give them a better shot at having prolonged duration of therapy, and perhaps better response response.

Perhaps that are required at this point.

Okay, perfect.

Thank you.

Okay perfect. Thank you and then maybe jumping over to <unk>.

And then maybe jumping over to Tim Bexa, is there a time limit associated with the EBS, deal closing on when the BARDA contract needs to be finalized?

Is there a time limit associated with the UBS deal closing on when the BARDA contract needs to be finalized like does that have to be a 2022 events and then the second part of that should we anticipate any substantial additional ex U S revenues going forward or have you kind of hit the key markets.

Like you said, it has to be a 2022 event.

And then second part of that, should we anticipate any substantial additional ex-US revenues, going forward, or have you kind of hit the key markets?

Thank you very much.

I'll let Mike hit those two questions.

So much.

I'll, let Mike hit hit those two questions.

Yeah, there's a outside date in that agreement that's available there for both parties, Joe. It's September 30th in that agreement.

Yes, there is.

There is a outside data in that agreement that's available there for both parties Joe.

September 30 in that agreement.

And then as it relates to the international opportunity, we continue to have discussions, with parties internationally.

And then as it relates to the international opportunity we continue to have a.

Discussions with parties internationally I think the.

I think the declaration of the public health emergency, certainly by the WHO, continues, to sort of activate interest in those conversations.

The declaration of public.

Public health emergencies, certainly by the WHI.

<unk> continues to.

Sort of activate interest in those conversations so.

So the contracts that we entered into at the end of June were certainly, ones that we were able to turn around very quickly we'll continue to have those conversations and you know in the weeks ahead.

Yeah.

The contracts that we entered into at the end of June were certainly.

The ones that we were able to turn around very quickly we will continue to have those conversations.

Thank you very much.

In the weeks ahead.

Perfect. Thank you very much.

Okay.

Your next question comes from Ed White with H.C. Wainwright.

Your next question comes from Ed White with H C. Wainwright. Your line is now open.

Good evening, Thanks for taking my questions just circling back to the potential for accelerated approval.

Have you set a meeting date with the FDA yet.

Regarding accelerated approval and does using the two different dosing schedules in the phase III study.

Somewhat tampered the expectations for accelerated approval.

Yes, I'll, let others add so that's where we're preparing the.

The materials that would be the basis for for that that meeting now is the safety data set is.

Is just has just been completed.

I would suggest that having that study.

In in place and up and running and.

And really well advanced at the time.

An action from the regulators would be taken on an accelerated approval is a big part of what the FDA wants and needs to see and considering.

An accelerated approval. So I think that would would that actually provides some comfort.

We were exploring lower doses.

I think that could be potentially problematic.

In their review, but because we're actually exploring the potential of a more efficacious higher dose.

<unk>.

Obviously, if its not more effective or its or its insufficient safety then.

And then that that would not impact for an accelerated approval relative to the lower dose that actually also simplifies some potential commercial issues that might arise fewer.

Lowering your does from an accelerated approval.

Regimen.

I don't think it impacts.

In a negative way their consideration in fact, I think having a robust design with <unk>.

With certainty around having overall survival to confirm.

Full approval really was going to be required anyway.

And that's just gets them a much more robust assessment of that and frankly consistent with their guidance as it relates to.

For dose optimization that I think would be supportive of that conversation.

Hey, Mike can I ask you this is Alan.

I think part of this goes back to the feedback received actually August received from FTA years back So Jos optimization really wasn't.

In the.

Situation back then things are involved in FDA. So again, if you go according to what they said.

The authorization is often focused on the phase III aspect of that so I do think I agree with Mike that we still have.

The reason to discuss it.

This is also very high unmet need a high unmet need population with significant need.

Yeah.

Okay. Thanks, and then just on.

<unk>.

Regarding monkey pox.

Have you been approached by.

Any governments.

Outside the U S.

Regarding.

Potential purchases due to monkey pox, and perhaps if you could just.

Review in a little bit more detail the preclinical data for monkey pox.

And your thoughts on <unk>.

Neither you or a merchant pursuing studies in monkey Tox.

Maybe.

I think Ed as it relates to the conversations with parties outside the U S.

Those were likely accelerated as a result of monkey pox ill, although maybe never directly.

Referenced in that context, given the approval in smallpox.

As Mike said those those conversations are ongoing maybe I'll turn it over to Randall just to make a couple of comments knowing that there there are a lot of.

Loans in terms of the treatments for Monkey pox, there is some pretty compelling basis too.

To believe that that's come back to that.

Be inactive.

And safe agent for use in this population.

Sure Mike.

So I'll start I guess with in vitro and just say that monkey pox is the second most sensitive orthopoxvirus we've ever tested.

It's about twice as sensitive to turn back.

As <unk>.

About four times more sensitive than.

Then the.

And then the Mousepox virus that we used for approval.

About 14 times more sensitive than the rabbit pox virus that we use for approval. So from an in vitro standpoint, Theres every reason to believe that that monkey pox would be highly responsive to attend back. So we also have two animal models.

One of them in mice, which showed 100% protection from monkey pox virus infection with <unk>.

And then one in our Prairie dogs.

It was it was sort of intermediate protection, but it turned out that prairie dogs.

Monkeys actually.

I know the lives come back so much faster so the exposure within Prairie dogs of Tim back to is about 15% that of human.

And Thats the reason that we saw kind of intermediate responses there.

With respect to to humans.

Obviously, there's the published cases three.

Monkey pox virus cases in the U K.

We're all three patients responded very well to come back.

And the paper was actually fairly negative on the drug for reasons that we don't fully understand that.

The patients receiving <unk>.

<unk> did all fully recover there was clear virological effects.

They did have transient elevations.

Elevations.

That were that caused <unk> to be discontinued.

But the patients all responded slowly and I should just add that with regard to the L. T elevations the manuscript ignored all of the FDA data.

Each was incentives III patients was 392 Brent.

<unk> recipients versus 208, placebo recipients, where the LTE elevations were 7% and the <unk>.

Thats arm and 5% in the placebo arm.

All of the data suggests that this drug should work quite well for monkey pox.

Okay, great. Thanks for taking my questions.

Thanks, Ed.

Your next question comes from Sumit Roy with <unk> Research. Your line is now open.

Your line is now, open.

Good evening, thanks for taking my questions.

Hi, everyone and congratulations on all the progress a quick question on the action trial.

Just circling back to the potential for accelerated approval, have you set a meeting date with the FDA yet regarding accelerated approval and does using the two different dosing schedules in the phase three study somewhat hamper the expectations for accelerated approval?

Yeah, I'll let others add to this.

We're preparing the materials that would, be the basis for that meeting now.

Possibly I wonder if you can remind us some the relapsed refractory glaucoma phase II.

The safety data set has just been completed.

I would suggest that having that study in place and up and running and really well advanced at the time an action from the regulators would be taken on an accelerated approval is a big part of what the FDA wants and needs to see in considering an accelerated approval.

The immediate prior.

So, I think that would actually provide some comfort.

If we were exploring, lower doses, I think that could be potentially problematic in their review, but because we're actually exploring the potential of a more efficacious higher dose that, you know, obviously if it's not more effective or it's insufficient safety, then that would not impact an accelerated approval relative to the to the lower dose.

It actually also simplifies some potential commercial issues that might arise if you were lowering your dose from an accelerated approval regimen.

Right.

So, I don't think it impacts in a negative way their consideration.

Our treatment regimen for those patients was it mostly radiation and <unk>.

In fact, I think having a robust design with certainty around having overall survival to confirm a full approval really was going to be required anyway and this just gets them a much more robust assessment of that and frankly consistent with their guidance as it relates to for dose optimization that I think would be supportive of that conversation.

Hey Mike, can I add here?

This is Alan.

I think part of this goes back to the feedback we received and actually all the students received from FDA years back.

Also the Tim was optimized chemo.

So, dose optimization really wasn't in the situation back then.

And the second is on action.

Things have, evolved in FDA, so again, if you go according to what they've said, dose optimization is often more focused on the phase three aspect of that.

It would have been better to have a physician's choice as a control arm rather than a placebo just any thoughts.

So, I do think I agree with Mike that we have still have the reasons to discuss it.

Yes, so I'm going to first quarter, the choice of the control arm and I think the.

And I think it's important to note in your control in the phase III trial post radiation therapy there.

This is also very high in the population with significant, Okay, thanks.

Really no standard of care patients typically receive the radiation therapy and then they wait until progressive disease. So this is an ideal time to study. This it also builds on some of the factors we saw in the phase two trial, and we think will actually increase the probability of success.

And then just on Canbex, regarding monkeypox, have you been approached by any governments outside the U.S. regarding potential purchases due to monkeypox?

And perhaps if you could just review in a little bit more detail the preclinical data for monkeypox and your thoughts on either you or emergent pursuing studies in monkeypox.

Maybe I'll, I think, Ed, as it relates to the conversations with parties outside the, U.S., those were likely accelerated as a result of monkeypox, although maybe never directly referenced in that context, given the approval in smallpox.

Typically in this tenant youre going to have a little smaller disease youre going to be on therapy longer.

And.

We're gonna included lower Kps core.

Included 16, so we do think these factors increase of probability.

<unk> SaaS and this population I'm going to ask Josh to kind of go through following the prior he was the one who initially doing these trials.

As Mike said, those conversations are ongoing.

Two studies.

Yes.

Hi, there yeah with regards to the prior therapies and that recurrent experience. Obviously all of these patients had radiation recurred.

Weighted more than 90 days as I noted on our earlier comments in terms of additional therapies. These patients thought prior to getting on tier one and it's particularly in the adult population to include <unk>, even though that that chemotherapy is known to not have benefit within subsets of <unk> 27, a decently almac, we still saw a closer.

Or did that just given the paucity of other agents.

Other therapies included Bevacizumab for symptomatic relief with the DMR. In addition to the bankruptcy court Rusty so really just a mixture of chemotherapy.

We're hopeful that moving earlier as we've made a couple of times earlier in line with the prior exposure to both chemotherapy.

Increase the likelihood of our patient.

Colin.

Got it thank you for that and one last question on <unk>.

200, <unk> just curious on the timeline what are you thinking of to bring this drug.

And we are in the clinic.

Yes, we mentioned that the drug is being evaluated in two studies one of our pediatric.

And another on the adult.

Adult study is.

Is being sponsored by the.

The NIH and.

To be fair, our focus has really been on accelerating on 201.

And so we.

We are escalating that that dose through that that program I would expect too.

Be able to get into sort of.

The therapeutic window here into next year, but we'll report separately as we get closer to what we would expect it would be a data readout on on that endless selection for an indication.

That we would pursue that one of the things we've talked about in the past is that even.

Though there's the <unk>.

Targets for all.

The same is October one that that drug opens up different opportunities in terms of development within oncology and so we would expect to pursue.

Non overlapping indications initially with <unk> hundred one.

Got it. Thank you so much for taking the questions.

Thank you.

There are no further questions at this time I will now turn the call back over to Mike Sherman.

Thanks, Brandon and thanks again, everyone for joining the call. We look forward to the next updates, particularly on the progress of the BARDA contract. Thank you have a good evening.

Yes.

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

[music].

[music].

[music].

Maybe I'll turn it over to Randall just to make a couple of comments, knowing that there are a lot of unknowns in terms of the treatments for monkeypox.

Good afternoon, ladies and gentlemen, and welcome to the <unk> second quarter 2022 earnings Conference call.

There is some pretty compelling basis to believe that Canbex be an active and safe, agent for use in this population.

I'd now like to introduce you to your host for today's call Michelle <unk>, Vice President of strategic planning and Investor Relations at Cognex. Please proceed.

Sure, Mike.

Thank you and good afternoon, everyone. This afternoon, we issued a press release on our second quarter operating update you can access this press release and our Investor section of our website.

With me on today's call are President and Chief Executive Officer, Mike Sherman, Chief Medical Officer, Ellen Melamed, Chief Financial and business Officer, Mike Andriole, Chief Science Officer, Randall linear and our Chief Technology Officer.

Josh Allen.

Let me begin I would like to remind you that the statements made on today's call include forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties and other factors.

And uncertainties and other factors could cause actual results to differ materially from those referred to in the forward looking statements. Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties at this time I would like to turn the call over to our President and Chief Executive Officer, Mike Sherman.

So, I'll start, I guess, with in vitro and just say that monkeypox is the, second most sensitive orthopoxvirus we've ever tested. It's about twice as sensitive to Canbexa as variola, about four times more sensitive than the mousepox virus that we use for approval, and about 14 times more sensitive than the rabbitpox virus that we use for approval. So, from an in vitro standpoint, there's every reason to believe that monkeypox would be highly responsive to Canbexa.

We also have two animal models, one of them in mice, which showed 100% protection from monkeypox virus infection with Canbexa, and then one in prairie dogs, where it was sort of intermediate protection, but it turned out that prairie dogs, like monkeys, actually anabolize Canbexa much faster.

So, the exposure within prairie dogs of Canbexa is about 15% that of human, and that's the reason that we saw kind of intermediate responses there.

Good afternoon, everyone. Thanks for joining us today and we've been busy the past few months. So let me get right to the details of the progress we've made and I'll start with <unk>.

With respect to humans, obviously, there's the published cases of three monkeypox virus, cases in the U.K., where all three patients responded very well to Canbexa, and the paper was actually fairly negative on the drug for reasons that we don't fully understand, but the patients receiving Canbexa did all fully recover. There was clear virologic effect.

They did have transient ALT elevations that caused Tembexa to be discontinued.

But the patients all responded fully.

In July we marked a significant milestone recording our first <unk> product revenue covered by two international agreements.

And I should just add that with regard to the ALT elevations, the manuscript ignored, all of the FDA data, which was, instead of three patients, was 392 Tembexa recipients versus 208 placebo recipients, where the ALT elevations were 7% in the Tembexa arm and 5% in the placebo arm.

$35 million in aggregate. This was only possible because we made the decision a couple of years ago to manufacture over 300000 treatment courses of <unk> <unk>.

So, all of the data suggests that this drug should work quite well for monkeypox.

At our own risk without a contract somewhat atypical in the Dubai Biodefense space.

Okay, great.

Because of that decision, we were able to take advantage of this opportunity immediately completing contracts and shipping product in a matter of days.

Thanks for taking my questions.

If youre looking to isolate and SaaS <unk> execution as it relates to creating and delivering on contracts. These are great. Examples.

That's it.

The same decision to manufacture product at risk will also position us to respond immediately.

Placed in Baxter into the U S stockpile once the BARDA agreement is in place. We mentioned previously that the monkey pox outbreak introduced some new considerations for both BARDA and chimeric so.

Your next question comes from Soumit Roy with Jones Research.

Our and have been thoughtful to address those urgently in the meantime, the international sales Rerecorded have.

Despite our near term capital needs.

You may be aware that while <unk> was approved for smallpox preclinical data does support the activity has come back against multiple or the pox viruses, including monkey pox.

You commented on that potential in their post approval manuscript and the fact of the matter is no randomized control studies have been performed in humans with monkey pox with either of the FDA approved anti virals for smallpox and there are still a lot of unknowns as the virus spreads and mutates into potentially more resistant.

Strange, we're working with leading infectious disease physicians on potential options to generate additional data.

Your line is now open.

Let me now turn to <unk> hundred one.

Hi, everyone, and congratulations on all the progress.

To announce today the design details of our phase III action study of Arc 201. This is the most advanced study in this <unk> 27, a M population of patients. So I'll, let Allen go into the design details, but let me make a few points upfront.

A quick question on the ACTION trial.

Possibly, Allen, if you can remind us, from the relapsed refractory glioma phase two, what were the immediate prior line or treatment regimen for those patients? Was it mostly radiation and also the temozolomide chemo?

And the second is on ACTION.

We've worked with kols across disciplines and geographies to design a trial with a probability of success that high and multiple ways to achieve this efficiently.

Would it have been better to have a physician's choice as a control arm rather than a placebo?

The action study is highly differentiated from the other phase III studies that have been performed in the broader glioblastoma space. So it really comes down to the phase II data, we have in hand, and the circumstance in which it was generated compared to other drugs that really differentiate this drug's likelihood of success.

Just any thoughts?

Yeah, so, I'm going to first go to the choice of the control arm, and I think it's important, to note in the control arm in the phase three trial, post-radiation therapy, there really is no standard of care.

I should first note that about a third of the studies in this space advance the phase III without phase two data for.

For those that did advance based on phase II data. It was rare that the patient population was associated with a targeted genetically specified mutation like H <unk> 27 a M.

With that target we can focus on the same homogeneous population of patients in phase three that were the source of the data in phase two we can also identify those patients with the same tools used in phase II, which are reliable diagnostic methods already nearly universally used.

The isolation of single agent activity is also critical many previous phase II studies have been conducted with drug combinations or have failed to have adequate washout periods to distinguish drug effect.

Then relied on time point endpoint like PFS compared to historical benchmarks. In contrast, we've carefully isolated the single agent activity of <unk> 201 in our phase II data.

Importantly, we've measured tumor response using rain out criteria. The most rigorous standard. This method was developed to address some of the shortcomings company.

Short comings of prior response rate measures such as 11 and Mcdonald criteria are overall response rate of 20% to 30% in the relapsed setting using right now are complemented by the durability of those responses evaluated by blinded independent Central review also increase our <unk>.

Conference relative to prior studies done using less stringent criteria.

It's also critically important that our efficacy data was generated in the absence of anti angiogenic drugs like Avastin, which can confound imaging and yield false response and progression of assessments, which have historically failed to translate the phase III success for other drugs.

And finally, the consistency across multiple clinically meaningful endpoints as particularly convincing.

<unk> data demonstrates a clear association between response and a reduction in steroid use and an improvement in performance status.

Also in association with survival as all responders were alive at two years or were alive at the data lock it.

That was earlier than two years for patients who did not achieve a response none were alive at two years, the internal consistency of the state is striking.

We previously noted the ongoing work related to compiling safety data to strengthen the risk benefit assessment of all 201 last fall. We reported just a summary of safety data from the 50 patient efficacy cohort.

I'm now happy to say, we've completed a more robust assessment of over 200 patients and the results reveal a very attractive safety profile as expected I'll turn the call over to Alan to share more about the details of the phase III <unk> study as well as hit on those findings in the latest safety assessment Allen.

Thank you Mike.

Quite a degree to go over the details of our actions phase III study.

We expect to activate flex U S sites later this year and continue into international sites throughout the first half of next year.

Action is a randomized double blind placebo controlled multi center study in newly diagnosed <unk> patients, whose tumors harbor, the <unk> III <unk>, Kevin and mutations.

Patients typically receive the radiation therapy, and then they wade into progressive disease.

We even went off to align with current following completion of radiation therapy.

So, this is an ideal time to study this. It also builds on some of the factors we saw in the phase two trial that we think will, actually increase the probability of the success.

The study will enroll approximately 450 patients who will be randomized to receive 625 milligrams of October one had one of two dosing frequencies once or twice weekly or placebo.

Typically, in this study, you're going to have a little smaller disease, you're going, to be on therapy longer, and we're going to include a lower PPS score than we did in the, 60s.

So, we do think these factors increase our probability of technical success in this population.

The primary endpoint of overall survival.

I'm going to ask Josh to kind of go through what he found in the prior, since he was the, one who was initially doing these trials from the phase two studies.

Josh?

Well also that with progression free survival with an alcohol control for both <unk> and PFS.

Hi there.

Yeah, with regards to the prior therapies and that recurrent experience, obviously, all of these patients have radiation recurred and waited more than 90 days, as I noted on a later comment.

We still saw exposure to that, just given the paucity of other agents.

In terms of additional therapies, these patients saw prior to getting Osteo-1 tended, particularly, in the adult population, to include Kemozolomide, even though that chemotherapy is known to not have benefit within subsets of H3227 and buprenorphine.

Other therapies included Bevacizumab for symptomatic relief of edema, in addition to nitrosourea, and glycolamustine.

All of us will be assessed for efficacy of three out of our control time points two interim analysis by the.

So, really, just a mixture of chemotherapies, and we're hopeful that moving earlier, as, we've noted a couple times here, moving earlier in line with therapy prior to exposure to those chemotherapies will increase the likelihood of our patients benefiting from H3227.

Independent data monitoring committee, followed by a final assessment.

The final PFS analysis looking for one railroad hcg by blinded independent Central review.

Participants in the study must have a colonoscopy or landscape performance status, which is a measure patients' ability to farm ordinary tasks of greater than 70 at the title randomization.

Keith there's a criteria in the presence of a primary spinal tumor diffuse intrinsic pontine glioma evidence of leptomeningeal spread of disease or shrieval spinal dissemination.

The second will take place up to 120 sites in North America, Europe and Asia Pacific.

The first interim analysis is anticipated in early 2025, it's time of day all day.

In 2026.

Cutting is greater than 80% power assumed hazard ratio of <unk> five for survival <unk> six zero for progression free survival.

Independent comparison will perform for each pump to one tenant group versus control at each time point.

The study design and findings from the phase two data has should increase the likelihood that patients will respond to October one.

These factors include the move we took care of their line likely including patients with less bulky disease.

From the time for patients being on October one.

As well as limiting this payer to patients with KPN.

70.

All of these factors worth us with better response in the phase II dataset.

In addition, the study design has a number of elements, which should support the rapid enrollment.

The wider time window to identify patients and there is a natural six week cap between initial diagnosis and completion of radiation therapy.

The presence of in HEK 270, <unk> mutation will be identified as part of understanding of care at the tenant initial diagnosis of wireless test in.

In addition patients are twice as likely receive off to a wonderful placebo.

<unk> cyber from numerous kols globally to participate in the study.

Lastly, we have been keenly listening is FDA guidance and expectations for oncology development programs are evolving.

In addition to an increased push towards randomized clinical trials or registration FAA has pushed further out I wish it on multiple dose and then target indications.

Which is included discussions with Pemex.

Noting that hump to one's efficacy was mainly based on the single dose and schedule, we incorporate an additional dose in the phase II study.

With the upside of increasing spend enthusiasm and probability of a successful study.

This additional schedule have been well tolerated in previous <unk> trials.

In the meantime, we've been updating our all tier one safety data analysis that includes a robust safety analysis per script 211 patient.

With this new safety data added to that the data we've already reported we now have a better characterization of this risk benefit of this drug.

And this analysis treatment emergent adverse events that were drug related where generally creating one and two.

The most common events for headache.

Nausea and vomiting.

The only related adverse event of grade three or higher that occurred in more than 2% of patients.

<unk> reported that two 8%.

Having these events reported in the pediatric population will be generally similar to the other part of that adults.

Only five patients two 4%.

Appearance of treatment related adverse events, leading to tighter drug discontinuation reduction or interruption.

These events were neutropenia and treat patients hypersensitivity in one patient.

Do you feel call just decreased 10, one patient and the Palmer amaranth mineral and patient.

With the phase III trial soon underway and this data in hand, we plan to revisit the question on accelerated approval based on the phase II data with FDA in the fourth quarter of this year.

Got it.

With that I'll turn it over to Mike <unk> to speak to our financial results.

Thank you for that.

Thanks, Alan and good afternoon, everyone.

And one last question on ONC-206.

With Alan's overview of the action strategy and rationale for why we're optimistic about its outcome I wanted to just make a few comments on the potential commercial market for on 301.

Just curious on the timeline, what are you thinking of to bring this drug pre-IND or in the clinic?

Have you are aware diffuse gliomas are particularly lethal form of brain cancer, and <unk> 27, and maintenance are among the worst of what is already a poor prognosis the unmet.

Unmet need for new therapies in glioma broadly and <unk> 27 in particular is among the highest unmet needs in all of oncology.

Yeah, as was mentioned, that drug is being evaluated in two studies, one a pediatric, and another an adult.

As it relates to onto our one our market research indicates about the unaided awareness of this agent for <unk>, 27% is already high and following the participation in the action study of up to 120 sites across the major markets. We expect the association of this agent to <unk> 27, and mutations will be nearly <unk>.

The adult study is being sponsored by the NIH.

And to be fair, our focus has really been on accelerating ONC-201.

And so we are escalating that dose through that program.

I would expect to be able to get into sort of the therapeutic window here next year.

But we'll report separately as we get closer to what we expect to be a data readout on that and a selection for an indication that we would pursue that.

One of the things we've talked about in the past is that even though the targets for ONC-206 are the same as ONC-201, that drug opens up different opportunities in terms of development within oncology.

Equities among top prescribing neuro oncologists to be <unk>.

<unk> study is successful we expect this awareness will translate to rapid adoption of the therapy and major markets. This is likely adoption should be aided by our competitive landscape that is quite attractive.

Specifically, we're not aware of any other phase two or phase III programs in the industry targeting industry rotation.

And so we would expect to pursue non-overlapping indications initially with ONC-201.

These dynamics likely make onto a one unique in a market where there have been several examples of underperforming commercial launches in oncology in recent years. Consequently, we view the commercial risk here is relatively low and continue to view this as a worldwide animal revenue opportunity that should comfortably exceed $500 million.

Got it.

As Mike mentioned earlier.

This past July we announced two international Tim Baxter procurement contracts totaling nearly $35 million, we've delivered nearly all of that product recently and will realize at least $32 million in revenue in the third quarter on a pro forma basis parents at the end of June would have been approximately $70 million when including this additional.

Thank you so much for taking the question.

Thank you.

Revenue.

As it relates to the pennant transaction for the sale of <unk> to emergent in late July of the HSR waiting period expired that satisfied one of the key closing conditions. The other two remaining key closing conditions, our execution of the procurement contract with BARDA and BARDA is approval of a pre novation agreement between <unk> and <unk>.

Sure Jim.

I know that investors are eager to have a BARDA contract executed as are we certainly the recent declaration of the monkey pox outbreak as a public health emergency by both the <unk> and HHS has influenced how both parties are approaching the final details of this agreement to that and will work.

Expeditiously with our counterparts at BARDA to finalize the contract as soon as reasonably possible in the interim we continue to operate the business in the ordinary course, and we'll provide another update to the market on the Finalization of the Bard agreement when we can.

With our current cash position. In addition to the expected cash generated from the sale of tobacco <unk> expects to be well positioned to advance the action study and other pipeline programs without concern of a near term dilutive financing.

Moving to our statement of operations.

Company reported a net loss of $23 $5 million or 27 per basic and diluted share for the second quarter of 2022, compared with a net loss of $17 $8 million or 21.

Basic and diluted share in the second quarter of 2021.

Research and development expenses increased to $18 million for the second quarter of 2022 compared to $13 $8 million for the same periods in 2021. The main driver of this increase is the ongoing developments related to <unk> hundred one.

General and administrative expenses increased to $5 8 million for the second quarter of 2022 compared to $4 $4 million for the same period in 2021 and with that overview I'll now turn the call back to Mike Sherman for closing remarks, Mike.

There are no further questions at this time.

I will now turn the call back over to Mike Sherman.

Thanks, Mike before I open it up for questions I'd like to take a minute to welcome Christopher Jordan for the team as our Vice President of regulatory Affairs.

Thanks, Rihanna.

Christopher comes to us with over 30 years of pharma experience across all stages of product development. Some of our management team Ive had the pleasure of working with Christopher at Endo site, and Novartis, where he recently led the regulatory strategy and execution of the FDA approval and EMA submission of <unk> <unk>.

And thanks again, everyone, for joining the call.

17, or predict though as it's now known.

We look forward to, the next updates, particularly on the progress of the BARDA contract.

His knowledge in the oncology field and track record of navigating a complicated regulatory processes.

I'll be a great addition to the team as we continue the development of our oncology pipeline with that Brianna I'll turn it over to you to open the call for questions.

Thank you.

Have a good evening.

Thank you at this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad. Your first question will come from Maury Raycroft with Jefferies. Your line is now open.

This concludes today's conference call. You may now disconnect.

Thank you.

🪻 📸 106 m, 📸 going to be a nice little thing.

Music, Good afternoon, ladies and gentlemen, and welcome to the Chimerix Second Quarter 2022 Earnings Conference Call.

Hi, Thanks for taking my questions and congrats on getting the phase III design.

I would now like to introduce you to your host for today's call, Michelle LaSpaluto, Vice President of Strategic Planning and Investor Relations at Chimerix.

For the Phase III, you have two interim OS assessments by the independent data monitoring Committee Committee at 164 events in the 246 events and then the final at 327 events if successful could either of the initial interim assessments at 164 or $2 46 be enough to file for approval.

Please proceed.

Thank you, and good afternoon, everyone.

This afternoon, we issued a press release on our second quarter operating update. You can access this press release in our investor section of our website.

With me on today's call are President and Chief Executive Officer Mike Sherman, Chief Medical Officer Ellen Melemed, Chief Financial and Business Officer Mike Andriole, Chief Science Officer Randall Lanier, and our Chief Technology Officer of Omniprotones, Josh Allen.

Before we begin, I'd like to remind you that the statements made on today's call include forward-looking statements within the meaning of the Private Security Litigation Reform Act of 1995 and are subject to risks and uncertainties and other factors. These risks and uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements.

Please refer to our filings with the SEC for a more complete disclosure of these risks and uncertainties.

At this time, I would like to turn the call over to our President and Chief Executive Officer Mike Sherman.

Good afternoon, everyone.

Yes, those are designed such that.

Thanks for joining us today.

With with statistical significance at those at those endpoints.

Youll have PFS in hand.

Sponsored data in hand, and overall survival.

With those early endpoints pretty significant advantages.

We would expect those to be the basis of a regulatory submission and approval.

Got it and then.

Also can you talk more about the twice a week dosing and what you've seen in prior clinical data that supports the rationale for moving the twice per week dosing into the phase III.

Just turn that directly over to Alan Doss Jr.

Both.

The rationale for including that as well as some of the experience we've had with it in prior trials.

Yes. This is Alan I'll start.

We have evaluated twice weekly dosing and have been shown that this has the effect of safe Congratulant.

In several studies.

One of the reason we wanted to move this forward as we wanted to have the opportunity to have even a more intense suite.

Know that we want to try to maximize the effect, we've seen and we really haven't seen any challenge so far with <unk>.

Safety from the current dosing regimen.

It's also the trust.

And part of what you've seen from the FDA regarding optimization of dose and we think that does help.

Also.

Dresser situationally into half two shots on goal and essentially you have two places for a patient to get on study with <unk> hundred one.

I'll pass on to Josh and industrial costs.

Sure. This is just speaking to the rationale really comes from preclinical in vitro findings showing that the efficacy about tier one can be increased with prolonged exposure because the same concentration a little bit of a sweet spot towards 48 hours with an incubation time really leading to that maximal effect. So.

The thinking is that we are getting into these brain tumors with the current dose achieving therapeutic concentrations and if we can just prolonged duration for an extra day by giving a second dose on a consecutive day there that might be the key to unlocking efficacy based on those models so that in combination with the safety.

The experience in the clinic that al spoke to us.

Just to incorporate that.

Got it.

I'll add one other thing Maury.

The notion that that too.

Encourage enrollment in this trial you would need to go to a two to one randomization anyway. If it were a single <unk>.

Schedule and so you kind of get that two to one benefit here with just a little bit higher and in aggregate. So.

I think a good use of.

The.

The statistical power in order to get.

Another shot on goal for success and still encourage patients to enroll.

Got it Okay. That's all helpful. And then maybe last question for me just wondering if in communications with FDA.

If they communicated on whether an accelerated approval path based on the phase II data and additional supporting data if thats still on the table.

Yes.

<unk> discussed.

On our last call, we essentially delayed that conversation after their feedback.

Earlier, this spring with a focus on getting.

Moving with the phase III trial, and knowing that without this additional safety data in hand, we were a little bit limited in our ability to make a strong case for the risk benefit assessment. So now that we have.

This additional safety data set which really plays out exactly as we expected we will be able to go back to them. So in the meantime, we really haven't pushed that conversation beyond the phase III trial, we'll revisit that here of late.

This year.

Got it okay. Thanks for taking my questions. Thanks Marty.

Your next question comes from Joseph <unk> with Cowen. Your line is now open.

Hi, there good afternoon, and thank you for taking my questions. Many of the first one.

On October one with.

With the phase III, you're administrating shortly after completion of radiation is there a timeframe.

<unk> in this study and maybe can you can compare this to.

The timeframe post radiation that patients on 201, and the phase two analysis population that would be helpful.

Sure I'll, let I'll, let Alan answer that one.

So.

There's a couple of ways, you're looking at that as one of the reasons. We have done in this way we are allowing patients to start the screening process. When they are initially diagnosed and then starting the radiation therapy. So you have plenty of time and you can actually grab the patient.

There's a specific timeframe, which you should be granted in mind, which I believe are not Josh practice at six to eight weeks post radiation.

That presentation post.

Initial diagnosis and I wanted to ask to clarify the exact timing I don't want to have that in Manhattan.

Sure, we'll enroll in the range of 2% to six weeks post for aviation for the study.

That contrasts to the primary efficacy analysis in the relapsed setting was.

More than three months that washout period. There. So this study substantially moving patients are closer to radiotherapy, which we think will give them a better shot at having prolonged duration of therapy.

We've been busy the past few months, so let me get right to the details of the progress we've made, and I'll start with Tembexa. In July, we marked a significant milestone recording our first Tembexa product revenue covered by two international agreements of $35 million in aggregate. This was only possible because we made the decision a couple of years ago to manufacture over 300,000 treatment courses of Tembexa at our own risk without a contract, somewhat atypical in the biodefense space. Because of that decision, we were able to take advantage of this opportunity immediately, completing contracts and shipping products in a matter of days.

Perhaps better.

Yeah.

Okay perfect. Thank you and then maybe jumping over to <unk> is there a time limit associated with the UBS deal closing on when the BARDA contract needs to be finalized like I said have to be a 2022 events and then second part of that should we anticipate any substantial additional ex U S revenues going forward.

If you're looking to isolate and assess Chimeric's execution as it relates to creating and delivering on contracts, these are great examples.

The same decision to manufacture a product at risk will also position us to respond immediately to place Tembexa into the U.S. stockpile once the BARDA agreement is in place.

Or have you kind of hit the key markets. Thank you very much.

I'll, let Mike hit hit those two questions.

Yes, there is.

There is a outside date in that agreement.

Available there for both part as Joe.

At September 30 and that agreement.

And then as it relates to the international opportunity, we continue to have disk.

Discussions with parties internationally I think.

We mentioned previously that the monkeypox outbreak introduced some new considerations for both BARDA and Chimeric, so we are and have been thoughtful to address those urgently.

The declaration of the.

Public health emergencies, certainly by the <unk>.

Continues to.

Sort of activate interest in those conversations so.

In the meantime, the international sales we've recorded have satisfied our near-term capital needs.

The contracts that we entered into at the end of June were certainly.

Ones that we were able to turn around very quickly we will continue to have those conversations.

In the weeks ahead.

Thank you very much.

Okay.

Your next.

Question comes from Ed White with H C. Wainwright. Your line is now open.

You may be aware that while Tembexa was approved for smallpox, preclinical data does support the activity of Tembexa against multiple orthopoxviruses, including monkeypox. The FDA commented on that potential in their post-approval manuscript.

Good evening, Thanks for taking my questions.

Just circling back to the potential for accelerated approval.

Have you set a meeting date with the FDA yet.

Regarding accelerated approval and does using the two different dosing schedules in the phase III study somewhat hampered the expectations for accelerated approval.

Yes, I'll, let others add so that's where we're preparing.

The materials that would be the basis for for that that meeting now is the safety data set is.

Just has just been completed I would I would suggest that.

Having that study.

In in place and up and running.

And really well advanced at the time.

An action from the regulators would be taken on an accelerated approval is a big part of what the FDA wants and needs to see in considering.

Accelerated approval, so I think that would would that actually provides some comfort.

If we were exploring lower doses.

I think that could be potentially problematic.

In their review, but because we're actually exploring the potential of a more efficacious higher dose.

That.

Obviously, if its not more effective or its or its.

Insufficient safety, then then that that would not impact and accelerated approval relative to the lower dose that actually also simplifies some potential commercial issues that might arise fewer.

Lower in your dose from an accelerated approval.

Regimen, so I don't think it impacts in.

In a negative way their consideration in fact, I think having a robust design with with certainty around having overall survival to confirm.

A full approval really was going to be required anyway.

And Thats just gets them a much more robust assessment of that and frankly consistent with their guidance as it relates to.

For dose optimization that I think would be supportive of that conversation.

Hey, Mike can I ask you this is Alan.

I think part of this goes back to the feedback received actually all Conservatives received come FTA ears back so dose optimization really wasn't.

In the situation back then things are involved in FDA. So again, if you go according to what to expect.

Sales organization is often focused on the phase III aspect of that so I do think I agree with Mike we still see the reason to discuss it.

This is also very high unmet need a high unmet need population with significant need.

The fact of the matter is no randomized controlled studies have been performed in humans with monkeypox with either of the FDA-approved antivirals for smallpox, and there are still a lot of unknowns as the virus spreads and mutates into potentially more resistant strains.

Okay. Thanks, and then just on.

<unk>.

Regarding monkey pox.

Have you been approached by.

Any.

<unk>.

Outside the U S.

Regarding.

Potential purchases due to monkey pox, and perhaps if you could just.

We're working with leading infectious disease physicians on potential options to generate additional data.

Review in a little bit more detail the preclinical data for monkey pox.

Let me now turn to ONG 2.0.1.

And your thoughts on.

Either you or a merchant pursuing studies and monkey Tox.

Pleased to announce today the design details of our Phase 3 Action Study of ONG 2.0.1. This is the most advanced study in this H3K27M population of patients.

Maybe.

Ill.

I think as it relates to the conversations with parties outside the U S.

Those were likely accelerated as a result of monkey pox ill, although maybe never directly.

Referenced in that context, given the approval in smallpox.

As Mike said those those conversations are ongoing maybe I'll turn it over to Randall just to make a couple of comments knowing that there are a lot of.

In terms of the treatments for Monkey pox, there is some pretty compelling basis too.

To believe that that tobacco.

It'd be inactive.

And safe agent for use in this population.

I'll let Allen go into the design details, but let me make a few points up front.

We've worked with KOLs across disciplines and geographies to design a trial with a probability, of success that's high and multiple ways to achieve this efficiently.

Sure Mike.

So I'll start I guess with in vitro and just say that monkey pox is the second most sensitive orthopoxvirus we've ever tested.

It's about twice as sensitive to turn back.

As <unk>.

About four times more sensitive.

Then the.

And then the Mousepox virus that we used for approval and about 14 times more sensitive than the rabbit pox virus that we use for approval. So from an in vitro standpoint, Theres every reason to believe that that monkey pox would be highly responsive to <unk>. We also have two animal models.

One of them in mice, which showed 100% protection from monkey pox virus infection with <unk>.

And then one in our Prairie dogs.

It was it was sort of intermediate protection, but it turned out that prairie dogs.

Monkeys actually.

Now the lives come back so much faster so the exposure within Prairie dogs have come back to is about 15% that of human.

And Thats the reason that we saw kind of intermediate responses there.

With respect to to humans.

Obviously, there's the published cases three.

Monkey pox virus cases in the U K.

We're all three patients responded very well to come back.

And the paper was actually fairly negative on the drug for reasons that we don't fully understand.

But the patients receiving <unk> did all fully recover there was clear virological effects.

They did have transient.

Elevations.

That were that caused <unk> to be discontinued.

But the patients all responded slowly and I should just add that with regard to the aot elevations. The manuscript ignored all of the FDA data.

Each was instead of three patients was 392 Brent.

<unk> recipients versus 208, placebo recipients, where the LTE elevations were 7% and the <unk>.

Thats arm and 5% in the placebo arm.

No.

All of the data suggests that this drug should work quite well for a monkey pox.

Okay, great. Thanks for taking my questions.

Et cetera.

Your next question comes from Sumit Roy with <unk> Research. Your line is now open.

Hi, everyone and congratulations on all the progress a quick question on the action trial.

The Action Study is highly differentiated from the other Phase 3 studies that have been, performed in the broader glioblastoma space.

It really comes down to the Phase 2 data we have in hand and the circumstance in which, it was generated compared to other drugs that really differentiate this drug's likelihood of success.

Possibly I wonder if you can remind us some of the relapsed refractory glaucoma phase II.

The immediate prior.

<unk>.

A treatment regimen for those patients was it mostly radiation and <unk>.

Also the <unk> chemo.

And the second is on action.

It would have been better to have a physician's choice as a control arm rather than a placebo just any thoughts.

Yes, so I'm going to first quarter, the choice of the control arm and I think the.

I think it's important to note and you control in the phase III trial post radiation therapy there.

Really no standard of care patients typically receive the radiation therapy and then they wait until progressive disease. So this is an ideal time to study this and it also builds on some of the factors. These towns a phase II trial, and we think will actually increase the probability of success.

I should first note that about a third of the studies in this space advance the Phase, 3 without Phase 2 data.

For those that did advance based on Phase 2 data, it was rare that the patient population, was associated with a targeted genetically specified mutation like H3K27M.

Typically in this tenant youre going to have a little smaller disease youre going to be on therapy longer.

And.

We're going to include the lower Kps core.

<unk> 16, so we do think these factors increase our profitability.

<unk> SaaS and this population.

With that target, we can focus on the same homogeneous population of patients in Phase, 3 that were the source of the data in Phase 2.

We can also identify those patients with the same tools used in Phase 2, which are, reliable diagnostic methods already nearly universally used.

Just to kind of go through following the prior has he was the one who initially doing these trials.

The isolation of single-agent activity is also critical. Many previous Phase 2 studies have been conducted with drug combinations or have failed to have, adequate washout periods to distinguish drug effects.

They then relied on time point endpoints like PFS compared to historical benchmarks.

In contrast, we've carefully isolated the single-agent activity of ONC-201 in our Phase, 2 data. Importantly, we've measured tumor response using RANO criteria, the most rigorous standard. This method was developed to address some of the shortcomings of prior response rate, measures such as the Levin and McDonald criteria. Our overall response rate of 20% to 30% in the relapse setting using RANO complemented, by the durability of those responses evaluated by blinded independent central review also increased our confidence relative to prior studies done using less stringent criteria.

There's also an association with survival as all responders were alive at two years, or were alive at the data lock if that was earlier than two years.

It's also critically important that our efficacy data was generated in the absence of anti-angiogenic, drugs like Avastin, which can confound imaging and yield false response and progression assessments, which have historically failed to translate to Phase 3 success for other drugs.

For patients who did not achieve a response, none were alive at two years.

Finally, the consistency across multiple clinically meaningful endpoints is particularly convincing. The ONC-201 data demonstrates a clear association between response and a reduction in steroid, use and an improvement in performance status.

<unk>.

The phase two studies.

The internal consistency of this data is striking.

Yes.

We previously noted the ongoing work related to compiling safety data to strengthen the, risk-benefit assessment of ONC 201. Last fall, we reported just a summary of safety data from the 50-patient efficacy cohort.

Allen?

Hi, there yeah with regards to the prior therapies and that recurring experience obviously all of the patients had radiation recurring.

I'm now happy to say we've completed a more robust assessment of over 200 patients, and, the results reveal a very attractive safety profile, as expected.

Thank you, Mike.

I'm excited to briefly go over the details of our Action Phase III study.

I'll turn the call over to Allen to share more about the details of the Phase III action, study, as well as hit on those findings in the latest safety assessment.

We expect to activate select U.S. sites later this year and continue into international, sites throughout the first half of next year.

Action is a randomized, double-blind, placebo-controlled, and multi-center study in newly diagnosed, diffuse glioma patients whose tumor harbored the H3K7M mutation.

Treatment with ONC 201 will occur following completion of radiation therapy. The study will enroll approximately 450 patients who will be randomized to receive 625 mg of, ONC 201 at one of two dosing frequencies, once or twice weekly, or placebo.

The primary input of the study is overall survival. The study will also evaluate progression-free survival with an alpha control for both OS, and PFS. OS will be assessed for efficacy at three alpha control time points, two interim analysis, by the Independent Data Monitoring Committee, followed by a final assessment.

The final PFS analysis will be performed using real HTG by blinded independent central review. Patients in the study must have a Karnofsky or Lansky performance status, which is a measure, of a patient's ability to perform ordinary tasks of greater than or equal to 70 at the time of randomization.

Key exclusion criteria are the presence of a primary spinal tumor, diffused intrinsic, pycine glioma, evidence of leptomental spread of disease, or cerebral spinal fluid dissemination.

The study will take place at up to 120 sites in North America, Europe, and Asia Pacific.

Weighted more than 90 days as I noted on the earlier comment in terms of additional therapies. These patients thoughts prior to getting off till one tended, particularly in the adult population to include <unk>, even though that that chemotherapy is known to not have benefit with that subset.

The first interim analysis is anticipated in early 2025 with sign-in data in 2026. The study has greater than an 80% power with an assumed hazard ratio of 0.65 for overall, survival and 0.60 for progression-free survival.

The PFS comparison will perform for each OCTL-1 study group versus control at each time point.

The study design builds on findings from the phase two data that should increase the likelihood, that patients will respond to OCTL-1.

When we cover them differently, we still saw a closer to that just given the coffee with other agents. Other therapies included Bevacizumab for symptomatic relief with the DMR. In addition to the bankruptcy related flight Rusty so really just a mixture of chemotherapy.

These factors include moving to an earlier line, likely including patients with less, bulk disease, increasing the time for patients being on OCTL-1, as well as limiting the study to patients with a KPS of greater than or equal to 70. All of these factors were associated with better response in the phase two data set. In addition, the study design has a number of elements which should support RAP-N1.

We're hopeful that moving earlier as we've made it a couple times earlier in life.

This includes a wider time window to identify patients, as there is a natural six-week gap, between initial diagnosis and completion of radiation therapy.

The presence of an H3K27N mutation will be identified as part of the standard of care, at the time of initial diagnosis with widely available tests.

In addition, patients are twice as likely to receive option 1 of a placebo.

We received excitement from numerous K-1s globally to participate in the study.

Lastly, we've been keenly listening as FDA guidance and expectations for oncology development, programs are evolving.

Prior exposure to both chemotherapy.

In addition to an increased push towards randomized clinical trials and registration, FDA has, pushed for the evaluation of multiple doses and target indications, which has included discussions with Chimerix.

Noting that ONC21's efficacy was mainly based on a single dose and schedule, we incorporated, an additional dose in the phase 2 study, with the upside of increasing study enthusiasm and probability of a successful study. This additional schedule has been well tolerated in previous ONC21 trials.

In the meantime, we've been updating our ONC21 safety data analysis that includes a, robust safety analysis performed on 211 patients. With this new safety data added to the data we've already reported, we now have a better, characterization of this risk benefit of this drug. In this analysis, treatment emergent adverse events that were drug-related were generally, grade 1 and 2. Most common events were headache, fatigue, nausea, and vomiting. The only related adverse event of grade 3 or higher that occurred in more than 2% of, patients was fatigue, reported at 2.8%.

Increase the likelihood of our patient portal.

Adverse events reported in the pediatric population were generally similar to those reported in, adults. Only 5 patients, 2.4%, experienced a treatment-related adverse event, leading to cytodrug discontinuation, reduction, or interruption. These events were neutropenia in 3 patients, hypersensitivity in 1 patient, neutrophil, called disc decrease in 1 patient, and a POMOD embolism in 1 patient.

With the Phase 3 trials soon underway and this data in hand, we plan to revisit the, question of accelerated approval based on the Phase 2 data with the FDA in the fourth quarter of this year.

<unk>.

Got it thank you for that and one last question on <unk>.

200, <unk> <unk> curious on the timeline what are you thinking of.

To bring this drug.

And we are in the clinic.

Yes, we mentioned that the drug is being evaluated in two studies one of our pediatric.

And another on the adult.

Adult study is.

<unk> is being sponsored by <unk>.

The NIH.

Sure.

Fair, our focus has really been on accelerating on 201.

So.

We are escalating that that dose through that program I would expect too.

Be able to get into.

The therapeutic window here into next year, but we'll report separately as we get closer to what we would expect it would be a data readout on on that end of selection for an indication.

We would pursue that one of the things we've talked about in the past is that.

Even though there is.

The targets for our two objectives are the same as <unk> 201 that that drug opens up different opportunities in terms of development within oncology and so we would expect to pursue.

So non overlapping indications initially without 201.

Got it. Thank you so much for taking the questions.

Thank you.

Yeah.

With that, I turn it over to Mike Angiol to speak to our financial results.

There are no further questions at this time I will now turn the call back over to Mike Sherman.

Thanks, Allen, and good afternoon, everyone.

With Allen's overview of the action study and rationale for why we're optimistic about, its outcome, I wanted to just make a few comments on the potential commercial market for RONC-201.

As most of you are aware, diffuse gliomas are a particularly lethal form of brain cancer, and H3K27M mutants are among the worst of what is already a poor prognosis. The unmet need for new therapies in glioma broadly, and H3K27M mutants in particular, is among the highest unmet needs in all of oncology.

Thanks, Brandon and thanks again, everyone for joining the call. We look forward to the next updates, particularly on the progress of the BARDA contract. Thank you have a good evening.

As it relates to RONC-201, our market research indicates that the unaided awareness of this, agent for H3K27M mutants is already high, and following the participation in the action study of up to 120 sites across the major markets, we expect the association of this agent to H3K27M mutations will be nearly ubiquitous among top-prescribing neuro-oncologists. If the action study is successful, we expect this awareness will translate to rapid adoption of the, therapy in major markets.

Your next question comes from Soumit Roy with Jones Research.

This likely adoption should be aided by a competitive landscape that is quite attractive.

Your line is now open.

Specifically, we're not aware of any other Phase II or Phase III programs in the industry targeting this mutation.

Hi, everyone, and congratulations on all the progress.

These dynamics likely make ONC-201 unique in a market where there have been several examples of underperforming commercial launches in oncology in recent years.

A quick question on the ACTION trial.

Consequently, we view the commercial risk here as relatively low and continue to view this as a worldwide annual revenue opportunity that should comfortably exceed $500 million.

Possibly, Allen, if you can remind us, from the relapsed refractory glioma phase two, what were the immediate prior treatment regimen for those patients? Was it mostly radiation and also the temozolomide chemo?

As Mike mentioned earlier, this past July, we announced two international tembexit procurement contracts totaling nearly $35 million. We've delivered nearly all of that product recently and will realize at least $32 million in revenue in the third quarter. On a pro forma basis, cash at the end of June would have been approximately $70 million, when including this additional revenue. As it relates to the pending transaction for the sale of tembexit to Emergent, in late July, the HSR waiting period expired. That satisfied one of the key closing conditions.

And the second is on ACTION, would it have been better to have a physician's choice, as a control arm rather than a placebo?

The other two remaining key closing conditions are execution of the procurement contract with BARDA and BARDA's approval of a pre-novation agreement between Chimerics and Emergent. I know that investors are eager to have a BARDA contract executed, as are we.

Just any thoughts?

Certainly, the recent declaration of the monkeypox outbreak as a public health emergency by both the WHO and HHS has influenced how both parties are approaching the final details of this agreement.

Yeah, so I'm going to first go to the choice of the control arm.

To that end, we'll work expeditiously with our counterparts at BARDA to finalize the contract as soon as reasonably possible.

And I think it's important to note in the control in the phase three trial, post-radiation, therapy, there really is no standard of care.

In the interim, we continue to operate the business in the ordinary course and will provide another update to the market on the finalization of the BARDA agreement when we can.

Patients typically receive the radiation therapy, and then they wade into progressive, disease.

Okay.

With our current cash position, in addition to the expected cash, generated from the sale of tembexit, Chimerics expects to be well positioned to advance the action study and other pipeline programs without concern of a near-term diluted financing.

So this is an ideal time to study this. It also builds on some of the factors we saw in the phase two trial that we think will, actually increase the probability of the success.

Now, moving to our statement of operations, the company reported a net loss of $23.5 million, or, $0.27 per basic and diluted share for the second quarter of 2022, compared with a net loss of $17.8 million, or $0.21 per basic and diluted share in the second quarter of 2021. Research and development expenses increased to $18 million for the second quarter of 2022, compared to $13.8 million for the same period in 2021. The main driver of this increase is the ongoing development related to ONC 201.

Typically in this setting, you're going to have a little smaller disease, you're going, to be on therapy longer, and we're going to include a lower PPS score than we did in the, 60s.

General and administrative expenses increased to $5.8 million for the second quarter, of 2022, compared to $4.4 million for the same period in 2021.

And so I think these factors increase our probability of technical success in this population.

And with that overview, I'll now turn the call back to Mike Sherman for closing remarks.

This concludes today's conference call. You may now disconnect.

I'm going to ask Josh to kind of go through what he found in the prior since he was the, one who was initially doing these trials from the phase two studies.

Mike?

Josh?

Thanks, Mike.

Hi there.

Before I open it up for questions, I'd like to take a minute to welcome Christopher Jordan to the team as our Vice President of Regulatory Affairs. Christopher comes to us with over 30 years of pharma experience, across all stages of product development. Some of our management team have had the pleasure of working with Christopher at Endocyte and Novartis, where he recently led the regulatory strategy and execution of the FDA approval and EMA submission of PSMA-17, or Puvicto, as it's now known. His knowledge in the oncology field and track record of navigating complicated regulatory, processes will be a great addition to the team as we continue the development of our oncology pipeline.

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

Yeah.

With that, Brianna, I'll turn it over to you to open the call for questions.

With regards to the prior therapies and that recurrent experience, obviously all of these, patients have radiation recurred and waited more than 90 days, as I noted on an earlier comment.

Thank you.

Some of the additional therapies these patients saw prior to getting Osteo-1 tended particularly, in the adult population to include Kemozolomide, even though that chemotherapy is known to not have benefit within subsets of H3227 and hemoglobin.

At this time, I would like to remind everyone, in order to ask a question, press star then, the number one on your telephone keypad.

We still saw exposure to that, just given the paucity of other agents.

Your first question will come from Maurice Raycroft with Jeffreys.

Other therapies included Bevacizumab for symptomatic relief of edema, in addition to nitrosylurea, glycolamide.

Your line is now open.

So really just a mixture of chemotherapy and we're hopeful that moving earlier, as we've, noted a couple of times here, moving earlier in line with therapy prior to exposure to those chemotherapies will increase the likelihood of our patients benefiting from T201.

Hi.

Got it.

Thanks for taking my questions and congrats on getting the Phase 3 design.

Thank you for that.

For the Phase 3, you have two interim OS assessments by independent data monitoring committee at, 164 events and then 246 events, and then the final at 327 events.

And one last question on ONC-206.

If successful, could either of the initial interim assessments at 164 or 246 be enough, to file for approval?

Just curious on the timeline, what are you thinking of to bring this drug pre-IND or in the clinic?

Yeah.

Yeah, as was mentioned, that drug is being evaluated in two studies, one a pediatric, and another an adult.

Those are designed such that with statistical significance at those endpoints, you'll have, PFS in hand, response rate data in hand, and overall survival at those early endpoints. Pretty significant advantages.

The adult study is being sponsored by the NIH.

We would expect those to be the basis of a regulatory submission and approval.

And to be fair, our focus has really been on accelerating ONC-201.

Got it.

And so we are escalating that dose through that program.

And then also, can you talk more about the twice-a-week dosing and what you've seen in, prior clinical data that supports the rationale for moving the twice-per-week dosing into the Phase 3?

I would expect to be able to get into sort of the therapeutic window here into next year.

Yeah.

But we'll report separately as we get closer to what we expect to be a data readout on that and a selection for an indication that we would pursue that.

I might just turn that directly over to Alan and Dosh to share both the rationale for including, it as well as some of the experience we've had with it in prior trials.

One of the things we've talked about in the past is that even though the targets for ONC-206 are the same as ONC-201, that drug opens up different opportunities in terms of development within oncology.

Yeah.

And so we would expect to pursue non-overlapping indications initially with ONC-201.

This is Alan.

Got it.

I'll start.

Thank you so much for taking the question.

We have evaluated twice-weekly dosing and have been shown that this has been, in effect, a safe regimen in several studies.

Thank you.

One of the reasons we want to move this forward is we wanted to have the opportunity to have, even a more intense dose.

There are no further questions at this time.

We know that we want to try to maximize the effect we've seen, and we really haven't seen, any challenge so far with safety from the current dosing regimen.

I will now turn the call back over to Mike, Sherman.

This also is addressed in part by what you've seen from the FDA regarding optimization of, dose, and we think that this helps also address the situation where you do have two shots on goal, and essentially you have two places for a patient to get on study with OCTL-1.

Thanks, Rihanna.

I'll pass it on to Josh for an additional comment.

And thanks again, everyone, for joining the call.

Sure.

We look forward to the next updates, particularly on the progress of the BARDA contract.

This is just speaking to the rationale.

Thank you.

It really comes from preclinical in vitro findings showing that the efficacy of OCTL-1, can be increased with prolonged exposure to the same concentration, a little bit of a sweet spot towards 48 hours of an incubation time, really leading to that maximal effect.

Have a good evening.

The thinking is that we're getting into these brain tumors with the current dose, achieving, therapeutic concentrations, and if we can just prolong that duration for an extra day by giving a second dose on a consecutive day there, that might be the key to unlocking an increase in efficacy based on those models.

That in combination with the safety experience in the clinic that Alex spoke to is what leads, to incorporate that.

Got it.

Let me...

I'll add one other thing, Maury.

The notion that to encourage enrollment in this trial, you would need to go to a two-to-one, randomization anyway if it were a single schedule, and so you kind of get that two-to-one benefit here with just a little bit higher end in aggregate.

So it's, I think, a good use of the statistical power in order to get another shot on goal, for success and still encourage patients to enroll.

Got it.

Yeah, it's all helpful.

And maybe last question for me, just wondering if, in communications with FDA, if they communicated on whether an accelerated approval path based on the phase two data and additional supporting data, if that's still on the table?

Yeah, we, as we discussed at our last call, we essentially delayed that conversation after their feedback this earlier this spring with a focus on getting moving with the phase three trial and knowing that without this additional safety data in hand, we were a little bit limited in our ability to make a strong case for the risk-benefit assessment. So now that we have this additional safety data set, which really plays out exactly as we expected, we'll be able to go back to them.

So in the meantime, we really haven't pushed that conversation beyond the phase three trial.

We'll revisit that here later this year.

Got it.

Okay, thanks for taking my questions.

Thanks, Maury.

Your next question comes from Joseph Tomei with Cowen.

Your line is now open.

Hi there, good afternoon, and thank you for taking our questions.

Maybe the first, one, just on OCT-201, with the phase three you're administrating shortly after completion of radiation, is there a time frame that's mandated in the study, and maybe can you can compare this to the time frame post-radiation that patients saw OCT-201 in the phase two analysis population?

That would be helpful.

Sure, I'll let Alan answer that one.

So there's a couple ways you're, looking at this.

One of the reasons we've done this way, we're allowing patients to start the screening process when they are initially diagnosed, and then starting the radiation therapy, so you have plenty of time you can actually grab the patient.

There's a specific time frame which you should be randomized, which I believe, and I'll have Josh correct this, I think it's six to eight weeks post-radiation.

I'm sorry, not post-radiation, post-initial diagnosis.

But I want, Josh to clarify the exact timing.

I don't have that in front of me.

Yeah, sure.

We'll enroll in the range of two to six weeks post-radiation for this, study, and that contrasts to the prior efficacy analysis in the relapse setting was more than three months, that washout period there.

So this study is substantially moving patients up closer to radiotherapy, which we think will give them a better shot at having a long duration of therapy, and perhaps better response response.

Okay, perfect.

Thank you.

And then maybe jumping over to Tim Bexa, is there a time limit associated with the EBS deal closing on when the, BARDA contract needs to be finalized?

Like you said, it has to be a 2022 event.

And then second part of that, should we anticipate any substantial additional ex-US revenues going forward, or have you kind of hit the key markets?

Thank you very much.

I'll let Mike hit those two questions.

Yeah, there's a outside date in that agreement that's available there for both parties, Joe. It's September 30th in that agreement.

And then as it relates to the international opportunity, we continue to have discussions with parties internationally.

I think the declaration of the public health emergency, certainly by the WHO, continues to sort of activate interest in those conversations.

So, you know, the contracts that we entered into at the end of June were certainly...

Once we were able to turn around very quickly, we'll continue to have those conversations in the weeks ahead.

Thank you very much.

Your next question comes from Ed White with H.C. Wainwright.

Your line is now open.

Good evening.

Thanks for taking my questions.

Just circling back to the potential for accelerated approval, have you set a meeting date with the FDA yet regarding accelerated approval?

And does using the two different dosing schedules in the Phase 3 study somewhat hamper the expectations for accelerated approval?

Yeah, I'll let others add to this.

We're preparing the materials that would be the basis for that meeting now.

The safety data set has just been completed.

I would suggest that having that study in place and up and running and really well advanced at the time an action from the regulators would be taken on an accelerated approval is a big part of what the FDA wants and needs to see in considering an accelerated approval.

So I think that would actually provide some comfort.

If we were exploring lower doses, I think that could be potentially problematic in their review.

But because we're actually exploring the potential of a more efficacious higher dose, that obviously if it's not more effective or it's insufficient safety, then that would not impact an accelerated approval relative to the lower dose.

It actually also simplifies some potential commercial issues that might arise if you were lowering your dose from an accelerated approval regimen.

So I don't think it impacts in a negative way their consideration.

In fact, I think having a robust design with certainty around having overall survival to confirm a full approval really was going to be required anyway.

And this just gets them a much more robust assessment of that and, frankly, consistent with their guidance as it relates to for dose optimization that I think would be supportive of that conversation.

Hey, Mike, can I add here?

This is Alan.

I think part of this goes back to the feedback that we received, and actually also received from FDA years back.

So dose optimization really wasn't in the situation back then.

Things have evolved in FDA.

So, again, if you go according to what they've said, dose optimization is often more focused on the phase three aspect of that.

So I do think I agree with Mike that we still have the reasons to discuss it.

This is also a high-inventory population with significant need.

Okay, thanks.

And then just on ChemBEX, regarding monkeypox, have you been approached by any, governments outside the U.S. regarding potential purchases due to monkeypox?

And perhaps if you could just review in a little bit more detail the preclinical data for monkeypox and your thoughts on either you or a merchant pursuing studies in monkeypox.

Maybe I'll, I think, Ed, as it relates to the conversations with parties outside the, U.S., those were likely accelerated as a result of monkeypox, although maybe never directly referenced in that context, given the approval in smallpox.

As Mike said, those conversations are ongoing.

Maybe I'll turn it over to Randall just to make a couple of comments, knowing that there are a lot of unknowns in terms of the treatments for monkeypox.

But there is some pretty compelling basis to believe that ChemBEX be an active and safe, agent for use in this population.

Sure, Mike.

So, I'll start, I guess, with in vitro and just say that monkeypox is the, second most sensitive orthopoxvirus we've ever tested. It's about twice as sensitive to ChemBEX as variola, about four times more sensitive than the mousepox virus that we use for approval, and about 14 times more sensitive than the rabbitpox virus that we use for approval. So, from an in vitro standpoint, there's every reason to believe that monkeypox would be highly responsive to ChemBEX.

We also have two animal models, one of them in mice, which showed 100% protection from monkeypox virus infection with ChemBEX, and then one in prairie dogs, where it was sort of intermediate protection, but it turned out that prairie dogs, like monkeys, actually anabolize ChemBEX a much faster. So, the exposure within prairie dogs of ChemBEX is about 15% that of human, and that's the reason that we saw kind of intermediate responses there.

With respect to humans, obviously, there's the published cases of three monkeypox virus, cases in the U.K., where all three patients responded very well to ChemBEX, and the paper was actually fairly negative on the drug for reasons that we don't fully understand, but the patients receiving ChemBEX did all fully recover. There was clear virologic effect.

They did have transient ALT elevations that caused Tembexa to be discontinued.

But the patients all responded fully.

And I should just add that with regard to the ALT elevations, the manuscript ignored, all of the FDA data, which was, instead of three patients, was 392 Tembexa recipients versus 208 placebo recipients, where the ALT elevations were 7% in the Tembexa arm and 5% in the placebo arm.

So all of the data suggests that this drug should work quite well for monkeypox.

Okay, great.

Thanks for taking my questions.

That's it.