Q1 2021 Plus Therapeutics Inc Earnings Call

Good afternoon, ladies and gentlemen, and welcome to day, plus Therapeutics first quarter 2021 results call.

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Before we begin we want to advise you that over the course of the call and question and answer session forward looking statements will be made regarding events trends business prospects and financial performance, which may affect plus therapeutics future operating results and financial position.

All such statements are subject to risks and uncertainties, including the risks and uncertainties described under the risk factors section included in plus Therapeutics annual reports on form 10-K, and quarterly reports on form 10-Q filed with the Securities and Exchange Commission from time to time.

Plus therapeutics advises you to review these risk factors in considering such statements plus therapeutics <expletive>umes no responsibility to update or revise any forward looking statements to reflect events trends or circumstances. After the day. They are made it.

It is now my pleasure to turn the floor over to Dr. Marc Hedrick, plus therapeutics, President and Chief Executive Officer, Sir you may begin.

Great. Thank you Catherine good afternoon, everyone and thank you for taking the time to join us today as.

As we provide an overview of recent business highlights and discuss our 2021 first quarter results. Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer.

Before Andrew provides a summary of our financial performance I would like to provide an update on the companys business activities since our last earnings call.

For those of you new to the company plus develops complex innovative therapeutics for rare and difficult to treat cancers, such as cancers of the central nervous system.

Our aspiration from a drug development perspective is to leverage our expertise in drug formulation.

Nanoparticle drug design drug manufacturing and scale up and expertise in novel delivery technologies to provide better tumor targeting and killing a greater safety profile and ultimately better clinical outcomes.

Towards that goal in 2020, we broadened our expertise and technology platform to include the use of radionuclides in our drug formulations.

Our lead drug is our enel radium nano wiper films, which is a proprietary lipid <unk> encapsulated radio nuclei.

The active agent.

Is the Iridium 186, isotope, which is a dual energy emitter, releasing both cancer, killing beta particles and gamma particles, which are useful for imaging.

Our initial indication for R&M as recurrent glioblastoma, which affects approximately 12000 patients annually in the U S and about the same number of patients in the EU.

It is the most common and lethal form of brain cancer in the treatment of this devastating disease remains a significant medical challenge.

Published studies indicate that external beam radiation provides the best incremental improvement in survival of all therapies currently used for Glioblastoma.

And it remains an essential component of multimodal therapy for both Glioblastoma and in fact, many other cancers.

In theory, though.

Leo Blastoma and indeed, any tumor can be fundamentally controlled if a sufficient dose of radiation can be delivered to that tumor.

With Arnelle it may be possible to deliver radiation dose only to the tumor that is perhaps 20 times higher than can be given with external beam radiation therapy.

And despite the Super high doses of radiation delivered by Arnaud.

And precisely because of its inherent tumor targeting capability on.

Wanted radiation exposure to nearby healthy tissue is actually reduced.

This compares favorably to the most commonly used chemotherapy as well as external beam radiation, which is <expletive>ociated with significant side effects.

That occur due to their deleterious effects on normal tissues.

Pre clinically in.

In animals are enel has shown the ability to deliver almost 2000 gray.

Substantially prolonging survival and a bleeding brain tumors, such that cancer sales cannot be observed in the microscope.

So our <unk> product is currently under evaluation in the U S respect trial, which is a dual phase one two multicenter sequential cohort open label volume in dose escalation study of the safety Tolerability and distribution of 186 are enel.

Administered by convection enhanced delivery to patients with recurrent on progressive malignant glioma.

After standard surgical radiation <unk> chemotherapy treatment.

The study uses a modified three plus three fibonacci dose escalation scheme, followed by an expansion at the MTBE or maximum tolerated dose to determine efficacy.

In addition, the trial is funded to a significant degree by the U S National cancer Institutes.

And in short the trial is progressing nicely.

In November 2020, we provided an interim analysis on the first 15 patients enrolled in respect specifically going through the fifth cohort.

And that data set can be found on our website.

In this interim look it showed that intra tumoral RNA <unk> can successfully deliver approximately 15 times he of door absorbed dose of radiation that can be administered by standard external beam radiation therapy without significant toxicity.

Our <unk> was well tolerated.

With no dose limiting toxicity observed.

Despite markedly higher absorb doses of radiation compared to EBIT.

Most recently in March of this year and our bio Europe corporate presentations that can also be found on our website. We provided an interim update through cohort six.

In summary, we found that it's feasible to deliver eight eight ccs of Arnelle loaded with 22.3 militaries of radiation safety safely without treatment related serious adverse events.

In fact, most adverse events were causally unrelated to arnelle, except scalp. This comfort considered related to the surgical procedure itself, but not the drug.

Hi absorbed doses were delivered to the brain.

Nearly 600 gray.

But only with very limited systemic radiation outside the brain in.

In fact, there was about approximately 3000 fold difference between radiation to the brain vs. The body, hence the absence of systemic effects of the radiation.

There were two long term survivors greater than 30 months and in terms of overall survival median and mean survival duration in subjects with tumor coverage greater than 75%.

At the time, eight three months and $12 nine months, respectively with six patients still alive.

Median survival duration with tumor coverage less than 60%, which was largely the bev failure patients was $4 nine months with one patient still alive.

Rather than escalate to cohort seven after cohort six.

Dms B data monitoring safety board elected to treat an additional three patients at the cohort six dose and volume, but increase the convection rate to 20 micro liters per minute.

Based on the physics of conviction the presumption is that enhanced our enel distribution in the brain will be observed and therefore better coverage of the residual non enhancing tumor cells achieved and in theory ultimately better patient outcomes.

Our experience, thus far points to tumor coverage correlating with length of survival, which makes sense, because 90% of recurrences occur within about two centimeters or less of the primary.

Furthermore, the increase convection flow rate will shorten the time to deliver the drug and make it easier on the patient and hospital staff.

Thus far two of the three planned additional patients at 20 micro liters per minute have been successfully treated with others and screening.

Thereafter, the SMB, we'll evaluate the data.

And discuss and make recommendations.

Potential next steps <expletive>uming no emergent dose limiting toxicities are observed include but are not limited to escalating to dosing cohort seven.

Enrolling additional patients at the current levels with further changes in the delivery parameters are simply moving directly to the phase two expansion cohort at the recommended phase two dose.

As an aside and running in parallel to the phase one.

And besides sort of outside the direct clinical objectives of the trial.

Also being developed in conjunction with academic collaborators is a mathematical model to better predict the spatial and temporal distribution of arnelle delivered by conviction.

Data collected by the phase one by imaging when interpreted and analyze will help create a mechanism based model of delivery and hopefully facilitate the.

The increasingly more accurate delivery of our enel in the phase II expansion component of the trial and therefore maximize the clinical outcomes.

Regarding.

Additional clinical development programs for <unk>.

A priority for us in 2021 as we've explained previously has been to begin development clinically with Arnelle in additional indications to that end, we submitted to Arnelle pre IND meeting briefing packages to the FDA one for Leptomeningeal metastases, the other for pediatric brain cancer.

<unk>, including opinion on Mama high grade glioma, and diffuse intrinsic pontine glioma.

We plan to conduct these pre IDE meetings with the FDA for both indications in 2021.

Understand any gaps that may exist in the preclinical data fill those as needed and initiate those trials as soon as 2021.

Both indications represent significant unmet medical needs.

For example, in <unk> and <unk>.

M or leptomeningeal metastases that affects about 110000 patients in the U S. It has no clear standard of care.

And these patients actually die very rapidly. Despite the care that is currently provided to them.

Yeah.

As for pediatric brain cancers, though much rare day.

Carry an equally poor prognosis and the treatment approach, we envision for pediatric brain cancer would mirror our approach in adults with glioblastoma using the direct targeting of the tumor and convection enhanced delivery.

Now regarding our manufacturing and supply chain development, which has been a key focus of our team of late.

In the first quarter. This year, we entered into a master services agreement with peer mall pharma solutions for the development manufacture and supply of RTL immediate drug product essentially they will make the light for some for us for the long term.

We anticipate that this will lead to clinical and commercial supply agreements for the drug product at the appropriate fuse future stage of development and we're working on those and we are on track in terms of our development and CMC timeline.

Now at this point I'll turn the call over to Andrew for a brief review of our first quarter financial results Andrew.

Thank you Marc and good afternoon, everyone.

Please refer to our press release issued earlier today for a summary of our financial results for the first quarter ended March 31 2021.

As of March 31, 2021, cash and cash equivalents were $14 4 million compared to $8 3 million as of December 31, 2020.

Cash used in operations for the first quarter 2021 was approximately $3 million compared to $1 5 million in 2020.

This difference is mainly due to timing differences on when certain accounts payable and accrued expenses were paid in 2020 and be particular relating to BARDA and professional fees.

There were no revenues in the first quarter of 2021 as compared to approximately 119000 in the same period last year.

This decrease was due to the closeout of the BARDA contract as previously disclosed.

Research and development expenses were $1 1 million for the first quarter 2021, as compared to <unk> 9 million for 2020.

The increase was primarily due to the additional <unk> development costs.

G&A expense was $1 4 million for the first quarter 2021, as compared to $1 6 million for 2020. The decrease was primarily driven by a reduction in professional fees and recruiting expenses.

Interest expense decreased for the first quarter 2021 to approximately 247000 from approximately.

On the 349000 for the same period in 2020, reflecting the principal pay down in 2020.

Net loss for the first quarter 2021 was $2 7 million as compared to a net loss of $1 1 million for the first call for 2020.

The net loss was consistent year on year when excluding the book gains on the warrants reported in the first quarter of 2020.

This required bulk transaction was eliminated in the second quarter of 2020, when the series U warrants for amended.

And now I'll turn it back to you Mark.

Great Andrew Thank you.

So let me just summarize our forthcoming milestones and then we'll move to Q&A.

So we intend to complete enrollment of the respect phase one study in recurrent glioblastoma.

As soon as we get to the recommended phase two dose and then proceed with the trial.

We plan to complete the pivotal trial planning with the FDA in parallel for arnel for recurrent Glioblastoma and then complete the key CMC activities as I mentioned before.

We also plan to complete the pre IDE meetings as mentioned with the FDA execute any IND, enabling studies, if needed and move into clinical trials for our follow on R&M indications Leptomeningeal metastases in pediatric brain cancer.

We also plan to continue to develop and evaluate additional external and internal drug development candidates to bolster our pipeline.

And then we continue to explore through our partnership discussions for our three clinical stage injectable drugs Arnelle does surplus on generic Dr. <unk>, plus and with that those are our prepared remarks, I'll turn it back over to you Catherine for Q&A.

The floor is now open for questions. At this time, if you have a question or comment. Please press star one on your Touchtone phone.

If at any point. Your question is answered you may remove yourself from the queue by pressing the pound key.

We do ask that low you pose your question you pick your handset can you provide optimal sound quality.

Yeah.

And your first question is coming from.

Yes.

Sean Lee with H C Wainwright.

Good afternoon, Mark and Andrew.

Jim.

Yeah, Hey, Sean.

Hi, Thanks for taking my questions.

My first question is on the respect studies, so you mentioned that.

DMC has decided to.

<unk> expansion cohort on number six instead of going to of course on it so should we take it that the.

Doses used in cohort six is likely going to be the once you guys using the next space.

Sean.

Could be presented.

Presented what I thought were the most likely outcomes in the script and so.

Where we did not see dose limiting toxicity in the sixth cohort and typically that would be the reason to stop.

They're in and take that dose forward.

But.

We were kind of using the phase one not only to get the recommended phase II, but phase II dose, but also to ensure that we go into the next trial with the appropriate delivery parameters and.

And so I think where we are.

Maybe getting a little bit greedy here, but we're delivering so much radiation.

We can where.

We're essentially.

How many times can you kill the same cancer cell. So part of what we're trying to do is to get that microscopic disease. That's non enhancing on the scans and then and we do that effectively by increasing the flow rate, which correlates to increasing the pressure and pushing the leading edge of the radiation.

Out into that microscopic disease. So.

It may be that this current dose of <unk>.

$22 three militaries at about almost 90 <unk> is what we take forward but.

But I think we'll just have to see we could.

We could conceivably go to cohort seven as well, but with this increased flow rate.

Got it when do you think we'll be able to get the next update on cohort six.

In terms of data, yes, we actually.

The Snowmageddon in Texas at the end of February because all three of our sites are in Texas actually made.

Made in the February and March.

Light light months, so things recovered in April.

There are a lot of patients in screening.

As I mentioned, we've got we've created two out of three patients. So.

I think.

We we may it may be the next earnings call.

Or if we make a decision prior to that we may just put that that news out at that time, so either before or likely the next earnings call.

Thanks for that.

The next question is on the CMC side, so with the tech transfer on the Master services agreement with probable on what's the expected time low timeline on that.

When do you expect you have CMT ready drug.

For the like for example, a pivotal study.

So yeah.

Yes. Good question, where we are on track from a timeline perspective. So we've sort of said we want to have we want to have drug ready for a registrational trial.

By around the end of 2021.

And so we're on track to do that.

Phase two drug supply as we speak.

Contemplate an expansion cohort for the phase one.

That will be ready for that as well, but that's a different.

That'll be a different supply chain. If you will for that so we're on track for both of those with kind of the.

Or the end of 'twenty.

'twenty one early 'twenty two is sort of the timeline to have that drug available.

I see my.

My last question is on the.

Plus the potential for the next for the pivotal study. So what are your thoughts on the design. So for this study would you be looking to go at it with a traditional randomized.

Randomized phase III or on an adaptive phase III with adaptive design or would you put to participating on the.

Other.

On the studies are going on such as GBM agile.

Yes, so let me break that down because virtually.

In terms of the phase one two.

That trial is fairly locked in that's 55 patients estimated 21 to get to the maximum tolerated dose.

Excuse me up to another 34 patients at the recommended phase II dose.

That's fairly well locked in I don't see.

Excuse me, that's likely to make many changes there in terms of phase III.

I think what I'd.

But I think I can say is we're likely to look at overall survival.

As a primary endpoint.

The number of patients is going to be based on what we see in the combination of the <unk>.

The phase one phase two.

At the recommended phase two dose.

Dissipate, we'll use as synthetic <unk>.

Control arm.

And that.

Those will be patients that are very likely.

<unk> had no more than one recurrence.

Bev naive patients as you know those do very poorly.

And they don't they don't come back very well.

So I don't see us.

Kind of randomized one to one against standard of care is using potentially as synthetic control arm or participating in and the agile.

Control.

I see thanks for the additional color.

Uh huh.

Thank you Sean.

Your next question comes from the line.

Ed.

On a Sunday on capital.

Yes.

Yes. Thank you for taking my questions I had a question more on the three sites that you have running I know you mentioned that towards the storm again and kind of delay things but.

It's everything back on track any COVID-19 issues and also have you thought about potentially expanding to sites.

Hey, Ed, Yes, I mean, it was really just.

Maybe for five five week delay, we typically screen patients every week, so just patients couldn't travel.

All of our sites are in Texas, Texas got hit pretty bad So we're back to normal where screening.

Multiple patients a week now so things are going well, we're doing a lot of work to do.

Get the word out about the trial and I think that's that's helping us and we're looking at some other ways to do that and then to your point about trial expansion. So yes, we absolutely are talking two additional sites.

Probably not not thinking as much about the phase one as is an expansion cohort at the recommended phase two dose so that when when that decision is made we'll be ready to.

To get those sites on board and trained and then those sites ultimately well.

Go into a registrational trial, <expletive>uming we get there.

Convection enhanced delivery there.

We know who the high volume sites are and will be going to those sites.

Early on in that process to degree, we havent gone to them already.

Great and then.

<unk>.

Additional indications.

That you have a day.

On the file on IND.

Okay.

Yes.

Okay.

Edward Youre cutting has there been any day.

I'm sorry can you hear me now yeah, I think so yes go ahead.

Alright.

Katherine maybe.

In February or maybe you can call back in a jump back in and that would be great. Maybe if there's somebody else in the queue, we could go to them.

Hello.

And there are no further questions at this time I would like to turn the floor back over to you Dr. Hedrick for any additional or closing remarks.

Okay, great. Thank you Katharine sorry about the technical difficulties I just want to thank everyone that joined us on the call.

And the analysts that participate in the call and also I'd just like to.

Take a moment to say, thank you to our employees, who who worked so hard and so dedicated to trying to find a solution for <unk>.

Glioblastoma and other rare cancers, and then also like to specifically, thank the patients and the doctors and the hospital staff.

Who we spend a lot of time with and they help really support and make our clinical trials happen. So thanks again and please have a good evening.

Yeah.

Thank you. This does conclude today's conference call. Please disconnect. Your line at this time and have a wonderful day.

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