Q2 2021 INmune Bio Inc Earnings Call

Welcome to the Viva Conference Center. The next available come from specialist will be with you momentarily.

[music].

Conference on or May I have your name.

David Brown.

Hi, I'm, sorry can you repeat that.

David Brown.

Oh right.

And which conference on your joining.

In modal bio.

Okay and.

And are you with immune bio or another company.

No I'm from IRR.

From IRA.

Okay.

Is it M y R a or huh.

A I E R. A.

Yeah I'm sorry.

Oh, no problem I'll place you into the immune bio call.

Thank you.

Youre welcome.

[music].

Greetings and welcome to the immune by our second quarter 2021 earnings call.

After today's presentation there'll be an opportunity to ask question to ask a question you May Press Star then 1 on your telephone keypad to withdraw your question. Please press Star then 2.

And I know that this conference is being recorded a transcript will follow within 24 hours on this conference call.

Replay is available the instructions on the press release announcing the second quarter call.

At this time, it's my pleasure to introduce Mr. David My co founder and C. S. R. L mean by David the floor is yours.

Thank you Rachel and good evening or good afternoon, everybody. We thank you for joining us for the call for IMMU Bio's second quarter 2021 financial results.

With me on the call is Doctor RJ, <unk>, CEO and co founder of <unk> bio who will provide a business update.

Before we begin I remind everyone that except for statements of historical facts. The statements made by management and responses to questions on the conference call are forward looking statements under the Safe Harbor provisions of the private Securities Litigation Reform Act of 1985.

These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward looking statements.

Please see the forward looking statements disclaimer on the company's earning press release as well as risk factors in the company's SEC filings, including our most recent quarterly filing with the SEC.

There's no assurance of any specific outcome undue reliance should not be placed on forward looking statements, which speak only as of the day. They are made as of the facts and circumstances underlying these forward looking statements may change.

As required by law EMU bio disclaims any obligation to update these forward looking statements to reflect future information events or circumstances.

We had a busy quarter as we continue to make progress on our E&P on an DN TNF platforms and now I'd like to turn the call over to Dr. Jay <unk> co founder CEO of IMMU bio to discuss these developments RJ.

Thank you David and thank you everyone for joining the call as is our practice I will arrange my remarks to highlight the key takeaways for the second quarter on subsequent period and provide updates to our platform programs before I pass it back to David to discuss our financial results and upcoming milestones and then we'll move to <unk>.

Good day.

And a little bit of a change I'll begin with our proprietary natural killer cell priming.

Priming platform, which we have turned a termed a suitor con what as a suite of kind of in vitro and commune gives NK cells increase tumor binding that's all call. So called the EBITDA increased proliferative capacity.

And increase tumor killing capacity. This combination of features have previously been seen and NK cells cultured with a cocktail of cytokines IL 12.

<unk> and 18.

The NK cells produce with income in our termed memory like NK cells. It has a phenotype that has been shown to be most effective in killing cancer cells.

So certainly in vitro improves anti tumor NK responses and we believe in patients. It will do this in a simple cost effective manner. There are no cytokines anywhere involved in either the manufacturer of the cells or the of the of income in or the treatment of the patients.

And we believe this product will have therapeutic potential in both solid and liquid tumors.

And commune is manufactured in bulk and available off the shelf.

On a month ago, we announced the first patient had been treated in the phase 1 trial evaluating <unk> in patients with high risk Myelodysplastic syndrome, or Mds and high risk Mds is a pre leukemia.

Patients often what is called blast off.

<unk> developed a very severe form of AML.

The station has received 3 doses of bank NIM by intravenous infusion with absolutely no problems biomarker data shows the presence of activated NK cells in the patient's blood that were not there before thank me on therapy.

And there is evidence of NK cell proliferation, which is exactly what you want and patients that have bone marrow dysfunction.

We expect to provide more detailed biomarker response data in the near future. This is the first of 3 patients in the lowest dose cohort, we expect to enroll the second patients soon.

Why don't we start with M. D S. A serious hematopoietic stem cell disorder.

As our first indication Mds patients have functionally defective NK cells that do not have strong avidity to their cancer cells and I remind you low avidity means low tumor killing.

This level of dysfunction is actually predictive of overall survival the worst the avidity the shorter the survival.

In vitro study of their NK cells shows that they respond to income in private with increased avidity and increased killing of tumor blasts in vitro a response that may predict improved tumor killing in the patient.

The biomarker panel used to monitor these patients we will provide detailed data on the patients immune response to therapy.

Patients are eligible for enrollment in this phase 1 trial are not eligible for high dose chemotherapy.

Or stem cell transplant, often based on frailty or age.

And we believe a safe effective well tolerated immunotherapy may be their only option.

We hope that income you may be a solution to a difficult problem.

We plan to enroll 9 patients with high risk Mds in the dose escalation protocol.

The primary endpoint is safety and Tolerability of Intravenously administered Inc.

Secondary endpoints are biomarkers of NK function in the peripheral blood overall response rate using the W. H O criteria for M. D S and duration of that response I remind you. This is a typical open label phase 1 dose escalation trial in patients with cancers cancer. There is no placebo group.

We will release day to periodically as we have done with the X Pro Alzheimer's disease trial.

Based on extensive preclinical data we believe income they have clinical may have utility in solid tumors as well, we hope to initiate a phase 1 trial in ovarian cancer in the coming months.

We understand the mechanism of action of income that's unique and different than existing encase cell therapies, including acts like a cytokine cocktail, even though there are no cytokines, hence the pseudo kind name and can makes the patient's own NK cells better we are not.

Giving the patient NK cells from some other source.

And we understand that <unk> mechanism of action may be confusing we have created a short video that explains how anything on works.

The video can be found on our website on the therapies, including videos or on our Youtube channel. We hope you have Europe and contact us if you have any questions.

On to EXPAREL as part of our DN TNF platform to our knowledge. This is the only selective TNF inhibitor targeting inflammation without causing demyelination or immuno suppression.

X pro is completely different from the currently approved TNF inhibitors.

By neutralizing the bad form of TNF called soluble TNF, we eliminate inflammation everywhere, including the brain.

By protection the function of the good TNF called transmembrane TNF extra improves the immune response to tumors and infection promotes re myelination.

Nerve cell survival and signaling.

These differences are wide DNF can be used to treat not neurologic diseases. While currently approved nonselective TNF inhibitors are contraindicated in patients with neuro a logic disease.

We repeat this message frequently in an effort to educate investors the academic community and the clinical community.

Because of this difference we are not competing with currently approved anti TNF drugs or biosimilars.

So has many unique therapeutic opportunities to pursue.

Have them to ourself as far as it relates to targeting soluble TNF.

We have announced programs using extra to treat Alzheimer's disease treatment resistant depression.

Performing preclinical studies in models of a L. S.

The vs diseases or the tip of a very large iceberg extra can be used to treat CNS indications, where neuro inflammation plays an important goal.

That list is long.

We encourage you to remove the more than 60 publications found on our website for an understanding of the breadth of the X pro therapeutic opportunity and CNS.

We try not to complicate the cause of cognitive decline in Alzheimer's disease and related dementia. Our hypothesis is simple neuro inflammation results and synaptic dysfunction in there on the loss that results in debilitating and progressive cognitive dysfunction in our opinion, if a drug therapy does not reverse either or.

Both problems it has little hope of changing the course of the disease.

Based on data from our phase 1 trial in patients with Alzheimer's disease X Pro fulfills this requirement.

Friedman with Expo for 3 months actually in more than a handful of patients for almost a year [noise] decreases neuro inflammation improves synaptic function and decreases nerve degeneration.

Can we say that decreasing neuro inflammation, improving synaptic function and decreasing neuro degeneration improved cognition not.

Not yet we got a hint from several of the patients that had quite remarkable responses, including 1 patient who went back to work but.

But to properly measure cognitive improvement a blinded randomized placebo controlled trial is needed.

That is the design of our phase 2 trial, which is designed to answer this question.

I will not go into details on the warrant to detail into the results of the phase 1 trial here, We've released day to 3 times in the past year on that data will be available on our website at.

Final data releases planned for the third quarter.

I will highlight the successes of the phase <unk> trial phase 1 trial not only have we've shown that extra decreases neuro inflammation using multiple biomarkers. We've showed a dose effect and have provided insights into the impact of Expo on the CSF proteome white and gray matter structure and function.

We now believe that the novel Noninvasive White matter analytics of white matter free water on a parent's fiber density developed by our partner in Macau are very useful in the development of X pro for Alzheimer's disease.

D and the many other CNS indications that we hope to attack on the future put bluntly. We believe the Golden era of CNS drug development has arrived and will be driven by thoughtful use of biomarkers to help us understand the disease, the biology to drugs and therapies immune bio is on the leading edge of.

This revolution.

Last week, we released the design of the blinded randomized phase 2 trial planned in patients with mild a D. The dose duration on the design of the trial was informed by our successful phase 1 program and the phase III trial, we plan to enroll 160 patients with mild a D who are biomarkers of inflammation in the 2 to 1 ratio.

That is due to active drug 1 placebo patients who will receive 1 milligram per kilogram once a week as a subcutaneous injection for 6 months. The patients have must have mild a D is defined by a C. D. R. O 0.5, or 1 point O and at least 2 of the peripheral biomarkers of inflammation use.

And the phase 1 study.

The primary cognition endpoint is the.

Early Alzheimer's disease M C I alzheimer cognitive composite or E. Mac, a very sensitive composite of validated neuro cognitive tests ideally suited to measure the effects of treatments.

On cognitive decline in patients with mild a D.

There are many secondary endpoints in cognition function in CNS biology, the patients that complete the 6 months study will be eligible for 12 months of X Pro and an open label extension trial.

We've been asked how we can do a small short trial with confidence.

Clinical design is at its heart a statistical exercise statistical significance is influenced by variability and the patient responses, the less variable and patient less variability in patient responses. The smaller the trial can be we have applied every 1 of the many insights from the phase 1 trial to design the phase <unk>.

2.

Trial by.

By using the enrichment and biomarker strategies perfected in the phase 1 study we have modeled the rate of cognitive decline in the untreated patients the impact of extra on those patients untreated on on cognition, Hence 168 patients treated for 6 months is what is needed.

To be clear competition for these patients will be fierce because of commercialization.

Can't imagine based on news today, maybe even though on on me Nab from Lilly and by the many trials sponsored by companies in the field and earlier stages of development.

Because of our biomarker of inclusion criteria, we expect a 50% screen.

The screen failure rate.

We plan to open as many 50 as many as 50 centers in the United States, Canada, and Australia to enroll these patients.

Despite being a 6 month trial, we do not expect to report top line data.

Until the second half of 2023, just think if we were doing a larger longer trial.

Wait could be frustrating.

We believe the ability of Expo to decrease neuro inflammation may have clinical utility across a range of neurodegenerative and psychiatric diseases once that indication as treatment resistant depression or T. I D.

A man on track to initiate a phase II trial in T. R. D by the end of the year.

As with Alzheimer's disease, and P. O D will we use biomarkers of inflammation to confirmed diagnosis enroll patients and determine the response to therapy.

So like he ethic trials rarely use biomarkers in development. We believe the use of Biomarkers will make development in the field less risky and more efficient.

The trials and funded in part by $2.9 million S. P. I R. A grant from the NIH.

The market opportunity in <unk> is significant in the U S. An estimated 7 million people are suffering from CRD. Currently there is no way to predict which therapy will work in which patient.

Contemporary medical practice involves a trial and error are cycling through patients through therapies.

Which 1 works in that particular patient once a patient sales 2 therapies. They are declared treatment resistant.

20% of patients are treatment resistant about a third of those have biomarkers to suggest neuro inflammation is a course of their treatment resistant.

Our hypothesis is once again, a simple neuro inflammation contributes both to the symptoms of depression and resistance to therapy treating neuro inflammation may provide both symptomatic and their product therapeutic loose relief.

Just to give you an idea of how big the problem is the cost of T. R. D to the health care system is estimated to be $64 billion per year.

That should be the cost to the economy, because not only are there direct cost of therapy, but cost to lost wages et cetera.

The trial will be formed a collaboration with 2 of the world's pioneers in the field Professor Andy Miller, and associate Professor John cells or both of Emory University.

A 6 week double blind placebo controlled study of EXPAREL versus placebo with 45 patients in each arm.

In addition to psychiatric symptoms the patients must have elevated blood CRP, a peripheral biomarker of information to be enrolled the primary end point isn't to prove functional connectivity as measured by MRI secondary endpoints include reduction in biomarkers of inflammation and improvement in clinical measures.

Turning to Queller, our program, our phase II program treating the cytokines storm in hospitalized patients with COVID-19.

In November we enrolled the first patient in the phase 2 trial for treatment of pulmonary complications of COVID-19, the double blinded randomized placebo controlled trial set to enroll 366 high risk COVID-19 patients in 2 equal sized cohort.

1 cohort is placebo plus standard of care, while the others Queller plus standard of care. The primary endpoint was the need from mechanical ventilation during the 28 days following enrollment in the study.

COVID-19 has changed our lives on has presented a challenging clinical development landscape. The disease has changed since March 2020, when we started mortality rates have decreased tenfold.

Pudic strategies have been in continual flux with standard of care evolving over time.

Personally I thought the incredible success of the vaccination programs would stop the pandemic and its track.

I did not anticipated anticipate that so many would put their health and the health of their loved ones at risk by not getting vaccinated.

And then bio will report topline data in about 5 weeks and the pit in patients that can be evaluated this.

Report replaces the go no go decision we had previously planned.

76 patients have reached that 28 day endpoint and are going to be part of this analysis data validation is under way.

This change of plan was driven by 3 factors first the FDA has signaled they will no longer grant E waste for treatment of COVID-19 that mean that is the phase 2 trial that we had originally planned which was going to be eligible for an EUA is no longer eligible for an EUA.

We will have to do a phase III trial this means that.

That debt.

We you know the 366 patients were not going to be enough.

Patient enrollment is geographically challenging the patient comes to the pandemic comes in waves that appear to be geographically based if you have sites opened in that geography great.

If not not so great.

Finally clinical teams have been cautious about enrolling patients in the <unk> trial, because we do not have preclinical data or clinical data, although the medical or biologic rationale for the trial are sound without data in man clinical teams are careful.

Yeah.

The strategy that is converting this to a phase II trial with a formal analysis will provide clinical teams the company and investors and the FDA with the information they need to evaluate the program that is we will all get to see the data.

On.

So what are the next steps we plan on end of Phase 2 trial, a trial meeting with the FDA when the database has been locked and analyzed.

We will discuss the next steps with the H D. F D. A based on the data from the trial. Our goal is for the FDA to give us a clear direction on the approval pathway.

Once we have data from that trial in a conversation with the FDA, we will make a decision on what the next steps are and we will communicate them to you.

I'd go back to my original statement drug development for the treatment of COVID-19 is a unique challenging and frustrating task. We asked for your patience as we analyze the data and negotiate with the SBA.

Finally, as we indicated last quarter there have been no change in the M. D O 3 program, our DNF oncology program.

We hope to initiate a phase II.

You know trial and much more positive cancer once the pandemic is better controlled although this program is clinically dormant laboratory research continues.

On the combination of M. D O 3 with tyrosine kinase inhibitors and mark for expressing tumors.

Dressers show Archie is submitting an abstract at the San Antonio breast cancer Symposium.

For November.

Yeah.

At this time, we have no plans to revisit the Nash program.

Now pass the floor over to David to review the Q2 financials.

Thank you RJ I'll provide a brief overview on financial results for the busy quarter and upcoming milestones.

Net loss attributable to common stockholders for the quarter ended June 30th 2021 was approximately $6.7 million compared to approximately $2.1 million for the comparable period in 2020.

Research and development expenses totaled approximately $4.5 million for the quarter ended June 30 of 2021 compared to approximately <unk> 9 million for the comparable period in 2020.

Primary reason for the increase in expenses was an increase in R&D activities related to our clinical programs and costs associated with manufacturing additional drug supply.

General and administrative expenses was approximately $2.1 million for the quarter ended June 30 of 2021 compared to $1.2 million for the comparable period of 2020.

At June 30th 2021 on the company had cash and cash equivalents of approximately $39.5 million.

Subsequent to the end of the second quarter. The company raised gross proceeds of approximately 40 million through a registered direct offering.

The proceeds of $15.5 million from the ATM.

Based on our current operating plan. We believe we are cash is sufficient to fund our operations and achieve potentially evaluating value, creating milestone into late 2023.

As of August 4.2021, the company had approximately $17.7 million shares of common stock outstanding.

Now I'd like to move on enlist our upcoming milestones before we get to Q&A.

In the fourth quarter as RJ stated, we plan to initiate our phase II program for all timers disease with expert on patients with neuro inflammation.

Also in the fourth quarter, we plan to initiate a phase II trial for expropriation patients with treatment resistant depression is partially funded by a $2.9 million and I am the age grant.

The week of September 6 we will be hosting a webinar to discuss data from our phase 1 b trial of <unk> in patients with Alzheimer's disease and neuro inflammation.

This month, our data from Queller should be in the hands of the data safety monitoring board.

And we will have a phase 2 meeting with the FDA to determine next steps.

After that after day D. S M Dias had their review.

Finally, we plan to report additional data you need me in before year's end.

We'll also plan to launch a second study in ovarian cancer likely by the end of the year or early next year.

I will note that these trials on phase, 1 small and they're not and they're running the U K and are not tremendously expensive.

In addition, assuming the clinical landscape has not changed we are planning trials in our other programs. Once COVID-19 pandemic has been controls on our trial sites give us. The go ahead. These include ambulatory and potentially other CNS indications.

So in summary, we're pleased with our progress during the second quarter as we continue to advance our pipeline towards potentially evaluating value creating milestones this year.

At this point I'd like to thank you for your time and attention and certainly your support as shareholders and I would like to turn it back to the operator for Q&A.

Rachel would you please poll for questions.

Hi.

Thank you at this time.

We'll be conducting a question and answer session. If you would like to ask a question. Please press star 1 on your telephone keypad.

We will indicate your line is it in the question queue. You May press star 2 if he would like to remove your question from the queue.

I think I said that.

Please pick up the handset before pressing the star.

Yes.

Your first question is from Jonathan Aschoff from Roth Capital Partners.

Please go ahead. Thanks.

Hi, RJ and David I was wondering given that there is you know a ton of a D out there.

And only about 3 patients required per site is second half 'twenty 3 guidance for the phase 2 data.

Pretty conservative and if not why not.

So I hope, it's conservative, but if you look at the.

Current clinical trial activity out there sites can enroll 0.3 patients.

Her site.

Per months per trial, so in fact.

No.

You know our.

Basically we are using that metric to set our enrollment criteria. Yeah. You can bet that I had been beating up our clinical team, saying, it's gotta be shorter than that but through them and their experts or the people that are working within the CRO people are saying man its a jungle.

Out there and remember you're talking.

About we're talking about mild a D mile day D is probably about 40% of a D. So that's around you know about 2 million patients total so we have actually design the clinical trial in a way to incentivize patients to join what.

Are those incentives I mentioned them in the park 1 of them is it's 2 to 1 randomization. So they have a 2 thirds chance of getting drug versus only a 50.50 chance if someone's doing a.

You know a typical 1 to 1 randomization.

There's also private companies out there that are doing open label trials with where everybody gets drug now that's great for the patients because they know they're getting enrollment it's difficult.

To understand what's happening with the.

The therapy. The second thing is because it's only 6 months. We then give them. Another 12 months of therapy, whether they are on the placebo group or not so we think that and we've been told by our clinical sites with that as a very attractive.

Aspect because you remember the average age of an Alzheimer's patients 71, so that means the primary Perry payers Medicare Medicare for all practical purposes has a 20% co pay I don't know what Biogen is going to be doing with that 20% co pay you know theres lots of strategies that companies use to man.

Co pays but the fact is at $56000 a year plus MRI scans plus 12 infusions.

The cost of therapy is going to be more than 56000, and so you know the patients are gonna have to come up with somewhere between 10 and 20000, we're hoping that between our with our incentives with the fact that you know they get a different approach. The fact that we are educating clinical teams about why the draw.

<unk> is a attractive strategy. That's why we were at a I see it was all about clinical team education.

We hope on enrollment is faster, but 1 thing I've learned in this business if I promise you enrollment in 6 months and it takes 6 months in 2 weeks.

I get called on the carpet so my clinical teams our CRO says, it's going to take a year I hope it's less.

But that's what I'm presenting I hope to surprise you.

With a shorter trial.

Thank you.

I'm on my last question is will your primary and planned and inflammation biomarkers of interest.

Potentially change from phase II to phase III or certain at this point that you're focusing on the correct ones second part is what do you expect for your efficacy endpoint for that subsequent trial.

Okay. So I I predicted you would have 3 questions and you didn't you didn't you didn't let me down Jonathan but they're both very good questions. So we as you know we love Biomarkers and we really love. These imaging biomarkers of white matter at SAIC, we presented apparent fiber density parents fiber dense.

City is goes up very quickly in patients with Alzheimer's disease and went up very quickly in those patients and all patients and in patients with mild day D. Those patients got better I believe personally. This is a personal statement we have to prove it that ASD is going to be the most potent biomarker of efficacy.

Okay don't know that until we actually connected to clinical outcome.

But to me I think we have a batch of biomarkers that we need to run this trial, but it doesn't but if we you know we are we have a lot of shall we say hum exploratory endpoint for instance, we're using we're going to be studying some patients with E. G endpoints on the phase 2 trial, we're experimenting with that we are.

Always looking because at the end of the day.

The cognitive endpoints that are currently used for Alzheimer's disease.

They are awful they were developed for patients with moderate to severe disease a D. S Cog 13.

Is is insensitive and patients with Mci and mild disease.

But what people have been stuck with them, we've gone under the influence of Judy Yeager Who's 1 of the the.

Experts in neuropsychiatric neurocognitive testing.

We are using something called E. Mach E. Mac is a composite of it think of 6.

Our neuro cognitive tests.

And it is recognized by the clinical community is being very good for measuring changes in Mci and mild a D. We are also measuring a D. S. Cogs you know all the other ones. So we're gonna have those results, but we believe you need.

Need to actually.

Taylor the endpoint for the stage of the disease to use an endpoint that has you know poor utility.

In mild day D to as a primary endpoint, we think is not a good strategy. So we're using E Mac.

And we think it gives us a very good way to see exactly what the drug is doing.

We're measuring all the other stuff and in fact, we're actually Pat we're powered off a descanso team.

But it's.

It's not a very those those are old fashion, not very useful endpoints.

And where we hope to leave the field into the future.

Okay.

Thanks Marcia.

Thanks, Gary.

Your next question is from Mikael Kazan from D. P. I G. Please go ahead.

Thank you RJ for the additional details on ink noon, just maybe 1 from me on the kind of NK proliferation that you mentioned from the first patient at high risk Mds patients can you maybe give us a sense of what kind of memory NK cells, you're seeing and how do you think that can contribute in terms of persist.

Since and the response thank you.

Yeah, so you've kind of jumbled together 3 components here you know the memory like NK cell is a phenotypic type debt is actually a cancer killing.

The and that really correlates with avidity and the ability to produce both porphyrin cytokines.

<unk> proliferation is kind of a different story and persistence is actually the third story so.

Let's start with the first.

I think the.

N K community now agrees that memory like NK phenotype is the desired phenotype for killing cancer cells. You know I mean, you know as you know the job of NK cells is either killing cancer, killing a viral virally infected cells. So you know you don't want to.

Do you have a lot of cytokines for instance, and end up with a lot of cells that have the anti viral phenotype that doesn't do you any good and killing cancer itself. It turns out that the NK the memory like NK phenotype now starting in about just really only 3 or 4 years ago is pretty well defined.

Bifurcation is I think 1 of the more interesting aspects, particularly when you're dealing with patients with hematologic malignancies. It turns out that many because many of them have marrow bone marrow dysfunction.

In fact, they're NK cells levels are low so stimulating proliferation.

Particularly of a tumor type of a NK cell, there's polarized towards memory like phenotype should just improve your cancer, killing.

Abilities.

The final thing is persistence and by the way you'll see on the slide deck, there's actually a figure that shows in this first patient Midlands, 1 patient first patient the the the proliferation over the first.

<unk> I think it's 15 days.

I can't comment on persistence at this point because we just haven't followed the patient out long enough. We believe from the you know from the X from the from the you know ex vivo NK infusion data that we had using a similar strategy that we should get at least 30 days of cover.

Ridge from the last dose and so on.

So last doses day 15, it should be somewhere around 45 days of of killing what's interesting is that the.

<unk> been at the NK cell activated are primed by and commune.

1 of his jobs, besides killing cancer cells is it.

Calls on the calorie and what I mean by that it actually well.

Prime another NK cell. So your prime 1 NK cell and you may end up with 10 Prime day NK cells, and that's not necessarily proliferation that is actually recruitment of wrestling NK cells bottom line is so far everything that we would've predicted that's happening in V.

Throw it in the laboratory.

It has happened in the patients that we can measure so far we've got a measure persistence and we got a measure of tumor, killing and that's information you'll get over the next couple of weeks. So far so good and we're delighted at the end of the day, we just need to treat more patients and we will do that.

Thank you for that.

Okay.

Thank you. Your next question is from Paul.

On the straight up from D. G. I say please go ahead.

Yes.

Hey, guys. This is from blending and for Tom actually thank for taking my questions I've 2 questions actually.

So in terms of imaging modality to measure.

Free water on our fiber.

For density like how adaptable for like different hospital to implement and then second question is could you just speak for it on like what are the data out there that shows the correlation between the improvement in cognition and changes in ASD.

There are studies that have looked at this are you guys are hoping to be like a pioneer in this topic. Thank you. Okay. So the great thing about both all of these white mother analytics as they can every hospital.

That has a standard MRI scanner unless it's a first generation anything 3 to 3 T..3 Tesla scanners are the standard. These days can do these they need to add about 5 minutes of of of scan time to capture the sequences that are necessary theres no injection of die.

There is nothing special it's all our software computer kind of strategy. So in the case of the phase 1 trial.

<unk>, our partner basically communicated with the clinical sites and they basically went through the process to make it so they're there scanners could scan so theres nothing special here and that's 1 of the great utilities as an aside it's a noninvasive study also.

Line of data, we're getting out of out of the scans correlates with the kind of great data, we get out of CSF, both whether you're looking at inflammatory cytokines of the protium.

Problem is you know getting on L. P is complicated it's expensive and patients alike as physicians may not like it. So so the bottom line is almost all patients who are in CNS trials, where Hep C. N S diagnoses.

Have scans.

And they can get in these data points can be.

Obtain whether you're in London, whether youre in Iowa city, or whether you're in Scranton, Pennsylvania, Okay.

Do you know or Scranton, Pennsylvania so.

The second question is the clinical data that shows an improvement of Asti.

Correlates with clinical response, well, we're the first ones to use this.

The first 1 to have a drug that shows that you can improve a S T and as I mentioned in the patients with mild day DNR trial in those 2 patients they had improvement in ASD and they both had an improved had a had a fairly impressive clinical response.

But you know.

Yeah, we are the leading edge here do I think we're going to be the only 1 using this no because as you know in drug development when people find a good biomarker others adopt it and we're fine with that at the end of the day. We're we're excited about it we think I think as he is going to be very.

As ultimately a a surrogate biomarker of efficacy, but that's me talking and we have a lot of work to do before we get there.

Yes.

I see great. Thank you.

Thank you your net.

Income from bank Tani on beef.

<unk> Securities. Please go ahead.

Oh good afternoon, congrats on the progress on thanks for taking my question. So maybe just following up on the you know the biomarker data from patient number 1 that you have in the slide here.

Great to see the <unk> 69 active have you looked at the 67.

You know both D and both NK and T cell like how how are you doing and I understand you from low doors, but obviously you don't see I see something of interest. So I'm just curious if.

If you looked at the impact on T cells it on it yet.

Well, we have not in the patient because we have studied the impact of income in on T cells extensively in the past now I will say the focus this was all in vitro, but we also have some data from the first generation program. The fear you know the fear was was where you're going to get some kind of cytokine storm right. When you started.

You know.

The problem with giving many cytokines as you get T cell activation when what Youre trying to do is get NK cell activation NK cells don't causes cytokine storm. They just kill cancer cells T cells can cause pathology when they get activated so 1 of the things. We did very early on was to determine whether we were at risk for cytokine storm.

And although this is a question better answered by Mark with Dell Who's in the inventor of <unk>.

The processing and the CSO, who it was.

Running this trial in fact, we have no evidence that inked activates.

T cells now the next question well is if you you know prime NK cells and they start doing the kinds of things that where they kill landscape, we kill tumors, which some of which includes making cytokines do you get recruitment of T cells on.

I'm going to let Mark answer that question Professor Lidell answer that question for you because it's a little beyond the insight I have into the product, but our focus is purely at this point on N. K function do we make the right NK cell, which is the memory like NK cell does it does.

It proliferate.

Does it kill tumor.

The patients tumor and does how long is the persistence.

And then ultimately you know it's kind of just like in our Alzheimer's program, you know decreasing neuro inflammation, improving synaptic function and decreasing nerve regeneration is great but at the end of the day you have to improve cognitive function.

The thing with the NK program, we can do all this great stuff, but ultimately the proof is in the pudding. When we ended up seeing tumor responses.

At the beginning of that journey, but so far everything we predicted in the lab is happening in the patient or at least that we've measured so far we're pretty excited about that.

But it's it's an N of 1.

And just just to clarify on the on the clinical responses.

At Oh gosh.

Sounds right like an MBA.

And your understanding is going on higher dose, it's nice that you're going to feed those head.

So it's on the clinical responses you just have to go higher doses than maybe the street longer and motivation is that so that's what the that's what the higher dose does their thinking is.

You know, we don't know if how much of this stuff you have to give to get maximal.

You know, there's 2 issues you get maximum killing right maximal avidity and killing and then how what is the duration of that math.

Maximum killing and and our feeling is there's a day is going to be a dose response, we don't know that you'll see you know the dose response is an increased number of doses of the same drugs. So we go from 3 to 4 to 5 doses over a.

Up to a 21 day period I think is what it is but the bottom line is the longer you give it you should get a lot bigger umbrella of coverage and we think although we have yet to prove it because we've only.

Using the logos, we are intrigued about whether we actually get a more aggressive NK cell now I remember you always worry about aggressive immune cells. Because you may end up with a safety signal.

But this patient has sailed through this so far I mean, he's not a youngster you know patients with Mds that are candidates for chemotherapy or bone marrow transplant tend to be on the 17th right. I mean, you know where we're like a geriatric medicine company right, we treat elderly patients with Alzheimer's, we treat elderly patients with cancer.

Even the C E O is elderly for Brian on that.

So.

I'd tell you a day D. So yeah.

Right. Thank you that's very kind of you.

Quick follow up on the on the evacuation.

Question for the Alzheimer's endpoint.

Appreciate the color on.

The rationale on how it might be different than the more conventional endpoints could you just comment on what your assumptions are for the placebo at month, 6 and and and just under 50% screen failure rate.

How should we think about.

They're different enrichment idea on the floor markers you have versus you know the more intangible things like availability.

Availability of a beta antibodies like how how are you getting to that 50, plus what's the incremental contribution of so I think.

You, obviously have the new slide set up because you asked.

In this in the Alzheimer's section, there's a there's a slide that talks about how we came up with that and basically what we did and this is no. We hear this is CJ Barnum, who you know and as his team.

And the guys at Amoco, we looked at the AD need database and we looked at how patients with how fast patients with Alzheimer's disease progressed in that day database using you know the various metrics cognitive metrics that is in the add any database all of those patients had mris and many of them.

The patients had the biomarkers that we had measured or enough of the biomarkers that we could get a component and so what we did is we looked at the rate of progression in the patients that were hot had poor fall inflammation by our definition.

Whether they had increases in white matter free water I E. R. M. R. I differ each and have no inflammation and then how quickly those patients progressing in their disease. It turns out that our peripheral biomarkers. As you were just a reminder, there was CRP greater than 1.5 milligram per liter.

Hemoglobin, a 1 C greater than 6%.

Fed rate of greater than 10 seconds, Okay Bowie for so EBITDA before is really a genetic biomarker, but patients had to have 1 most patients had too.

Those patients actually had <unk>.

Significantly higher white matter free water, so our biomarkers.

Signaled really picked out a group of patients that were hot right that was the goal of the Biomarkers and it turns out those patients that are hot in the AD in the group progress much more quickly in their cognitive decline compared to patients who aren't hot.

So using that data and you see some of that in that slide not only do they.

Go more quickly, but the variability decreases that's what we use the power of the trial. So we're very comfortable that if you get the heart patients they.

They progressed quickly and so we we're very comfortable we're going to be able to separate based on what we see in our phase 1 trial from those patients who are on placebo now so.

Remember, though that the consequence of our and the official SBA term is an enrichment criteria is that we have about a 50% enrollment rate for every 2 patients that get referred to the trial only 1 makes it into the trial. So you know that's kind of the price you pay for an enrichment.

Strategy.

But when you have an enrichment strategy you can do 168 patient trial. If you don't have an enrichment strategy you have to do a 450 or 600 patient trial right.

Thank you what about the placebo rate.

Enoch endpoint IC in the in your slide you have the Adas 13, but.

So yeah, we're measuring all the other stuff and actually we powered it on Adi Adas 13, because that's what what Adney had but the EMA is much more sensitive and and you know like I said earlier, Judy Jaeger as really the expert here. She was actually 1 of the key persons that helped develop it.

It was developed by a bunch of academics I think that debt I mean, you can see somewhere you've seen the 6 scales that are in the <unk> I think if you want a detailed discussion about how <unk> was developed and why it is better for mild and Mci patients. The best thing I can do.

Get you on the phone with Judy.

Professor Dr. Jaeger, because she first of all she is articulate she knows the stuff inside out and she can explain it whereas I can only just tell you what I told you so far.

That sounds great. Thanks, so much for taking my questions.

Thank you. Your next question is from Daniel Carlson from Kw Research. Please go ahead.

Hey, guys congrats on the progress and thanks for taking my questions.

Yeah.

First thing just on X pro.

On the literature I've been reading is kind of equating law on Covid with.

In terms of the symptoms and I'm wondering if you're intending to do anything in that disease and also other trials you might be planning for EXPAREL.

Yeah, so thanks for that.

We became interested in neuro inflammation in COVID-19 are at the very beginning.

It took until probably may of this year for the literature to begin to express the observation that there seems to be.

Behavioral and CNS manifestations that might be related to neuro inflammation.

Since in the last month, Dan I mean, it's become a tsunami of of commentary a lot. Some of it's in the press on somewhat of the literature, we actually engage the SDA several months ago on this issue and I can tell you. It was a little bit of a shock or what happened the FDA ruling was.

Not supportive of a clinical trial in law on Covid, because they said a constellation of symptoms has not been defined.

So if you don't have symptoms you don't have something to treat I have to say we were a little stunned by that now I remember this was a couple of months ago.

There was just a big NIH FTA or actually it was NIH panel 2 day meeting on long Covid July I think it was 14th 15th.

We were hoping that our guidance would come out of that to help the FDA, but none did everybody said everybody said Oh, it's a terrible problem, they're wringing their hands, we need to do something about it.

So we're actually actively involved with you and talking to the FDA now coming up with the strategy I can I won't want to guarantee it but what I can say that we believe like you do.

That many of the neuro side.

Psychiatric and cognitive problems associated with long Covid argued in neuro inflammation, obviously X pro neuro inflammation is what we do we think it's a match made in heaven.

But obviously, we can't move forward until the FDA and us agree on something but I think we'll get there.

But don't hold me to that but I can tell you. There is active there was an effort within the company to get to an agreement with the FDA. So we can move because I think we've got the perfect drug you know.

Yeah.

That's.

I agree so.

Love to see what happens.

I'm just.

Not trying to front run your alzheimers data, but in the past you've mentioned that the high dose patients were still on drug I was wondering if that was still the case with the people on the phase 1 trial so.

So if we start on that a year.

And and and.

But part of it is because we're trying to model. It after our our U S trial I have to say Theres a lot of pressure from those patients and their clinicians to get him back on.

On drugs. So we're looking into what that process looks like because I don't want to have to do it under a clinical trial. They have in Australia like they do in the U S kind of a compassionate use program. So we're exploring that but you know it's always it's always heartening went on when a patient you know wants to stay on a drug.

It means they think they've benefited you know which at the end of the day, that's an important criteria for for success right. They think that they think the juice to squeeze ratio was positive that as they got more benefit from problems from the drugs. So so we'll probably get them back on drug, but we've got to work through the regulatory.

And and a process for that so.

Got you and then and this 1 last question I'm just wondering now that you got it.

Coppers.

Our staffing plans are and where you are yeah.

Yeah, well as you can imagine there's a lot of focus on getting enough people to run these clinical programs. So clinical operations is growing no question about that.

You know, we we still lean very heavily on our on our our vendors and partners and as I like to tell everybody that joined the company I said, if you're coming here to do 1 job youre coming to the wrong company everybody is aware at least 2 hats and.

And we work hard and but we're growing most of the growth is on the clinical operations side as you can imagine as David mentioned, you know, we're manufacturing drug right now and so David and I kind of worked closely with our manufacturing consultant obviously on the manufacturing is done by a third party.

Regulatory is we have a regulatory group we've been working with for 3 years. So we have these vendors that we keep close to the vest.

And you know, it's kind of a funny problem because now they know the programs so well, it's almost better to keep them involved than to bring on our own regulatory department.

But at some point you know we'll work through that right now our main focus is getting the rubber to meet the road that as the clinical programs have to get up and running and they've got to be running well and they've got to be running.

Fast right I mean, we've actually hired 2 people 2 whose main job is to focus on improving the rate of Alzheimer's disease patient enrolment I need to go back to I don't know if Jonathan still on the phone, but you know John is it Didnt drew original question was something could you could do already.

About it was going to take 12 months to enroll 168 patient trial competition is fierce I hope to do better we're putting the resources behind it but at the end of the day I cant manufacturer patients we have to get them from the clinical teams. They are the gatekeepers.

Alright, well thanks I appreciate it.

Thank you ladies and gentlemen.

We have reached an all day.

Question and answer session.

Like to turn the call back to talk to all day.

Thanks.

Mark.

Yeah. So thank you I mean I have to say the price.

First of all we love all our programs, we love all our children were great great parents, but I mean, it is really exciting to really introduce intermune to the clinical world I mean, we've been keen on this program for a long time, it's been.

Hard to get to the clinic for a combination of read it reasons, including COVID-19.

But we think this is a unique NK immuno oncology program and like inhibiting inflammation neuro inflammation.

When you make when you prime or somehow do NK therapeutics, it's not only that you'd do it. It's what you end up with what kind of NK cell you end up with giving someone a resting NK cell doesn't do anybody any good giving somebody on anti viral NK cell doesn't do anybody on.

On a good.

At least with cancer, what they need is an NK cell that has 1 mission in life and that's to kill cancer cells and that appears to be what inkerman is doing we're pretty excited about that.

I mean, we talk all the time about our export program in Alzheimer's disease, we like what we've got we like where we're going and we believe now it's up to us and them.

Prove that it works in a blinded randomized placebo controlled trial.

I have to say.

The landscape is changing you know the CEO of literally just said today that he was confident they were going to get there Don on me Mab proved with a single phase III trial, which was 268 patients 1 to 1 randomization, which I find remarkable.

I think there must be something up their sleeves that we don't know, but I think the FDA has developed a very open mind.

2 Alzheimer's disease therapies.

It's going to be pretty exciting for the next few years.

But anyway. Thank you all for your support you know where to find us David and I love to talk to investors call US, We'll walk you through the new debt because theres a lot of new data in there.

And have a good day. Thank you.

Yeah.

Thank you that does conclude I'll come back once a day.

Thank you for participating you may now disconnect.

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