Q4 2022 Plus Therapeutics Inc Earnings Call

February 23, 2023

Good afternoon, ladies and gentlemen, welcome to the plus therapeutics fourth quarter and full year 2022 results conference call before.

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 report on Form 10-K, and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time.

Therapeutics advises you to review these risk factors in considering such statements plus therapeutics assumes no responsibility to update or revise any forward looking statements to reflect events trends or circumstances. After the date they are made.

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

Thank you Andrea good afternoon, everyone and thank you once again for taking the time to join US today as we provide.

Whites and discuss our 2022 fourth quarter financial results.

Joining me for the call today is Dr. Norman with France, our Chief Medical Officer.

And Mr. Andrew Sims, our Chief Financial Officer.

I'll begin the call by reviewing 2022 and then.

Andrew to review, our financials and Dr. The France will be joining us for Q&A.

At a high level I was extremely pleased with our accomplishments in 2022.

Going into the year, we set for ourselves some significant development goals, and we achieved or exceeded almost all of them.

At the same time, we continued a very conservative approach to managing our balance sheet ending the year with a similar cash level to the prior year.

But we materially expanded our availability of cash as Andrew will discuss.

So let me begin by focusing on drug development clinical and regulatory activities and related milestones.

First I ask that you wind the clock back over a year and recall that we ended 2021 with a single drug which was 186 are now active in only a single phase one clinical development program for recurrent glioblastoma funded in large part by the NIH.

That was in essence, the whole of our active clinical development program at that time, it was a year ago.

Fast forward to the end of 2022, we ended the year with two investigational drug candidates <unk> 186, Obits Pomato, formerly called 186 are Enel and rhenium 188, bio absorbable alginate microspheres or 188 are in L band as we call it.

<unk>, our investigational drug <unk> 186, Obispo Meda Iridium Obispo Meda, we have two active clinical programs now ongoing one for recurrent GBM and the other for Leptomeningeal cancer.

In terms of Glioblastoma and 2022, we substantially expanded this program specifically, we advance from phase one to phase two.

We are continuing the dose escalation for larger tumors in higher dose volumes.

We manufactured GMP drug, allowing us to move into phase III.

We enrolled the first patient in the phase III trial.

And we negotiated with FDA to continue the phase one dose expansion for larger tumors and now have an active re treatment protocol with FDA to explore retreating patients that happened to occur after a first treatment.

Leptomeningeal disease, we move this program to essentially a co lead program with GBM.

And specifically, we advance that program successfully from preclinical stage two in enrolling phase one and we obtained $17 6 million in funding for this program that in combination with pluses one third match as required by secret grit of water that should be sufficient to fund this program through <unk>.

<unk>, two and the enrollment of approximately 150 patients.

For pediatric brain cancer.

We did not initiate this trial in the calendar year because of the discussions with the FDA that were acquired for this first in pediatric patient Radiopharmaceutical trial, we did make significant progress specifically after three rounds of FDA interactions on the nature of the IMD for pediatric brain cancers.

Reviewers have accepted our clinical protocol design, but still require and request some additional adult data, which we plan to submit relatively soon.

Our second drug 188, <unk> was in licensed in early 2022 from academia and during the during 2022, we successfully transferred that technology to plus then successfully manufactured that drug internally last year. We then use that drug to successfully.

Human Oregon, ex vivo perfusion model confirming the preclinical feasibility and the manufacturing of that drug and then we submitted a pre IND information package to the FDA.

Big picture in terms of milestones achieved 2022 was a transformative year in the company's development.

Additionally, in 2022, we presented important data readouts in our two lead clinical programs GBM and Leptomeningeal cancer.

First in November 2022 results from the company's phase one respect GBM trial for our current Glioblastoma was presented at snow The society for Neuro oncology meeting in Florida by the trial pie.

And the phase one dose escalation trial at that time 24 patients with recurrent GBM across seven cohorts received a single dose of <unk> administered.

Administered in the dose escalation phase achieving up to 740 <unk>.

Turning to the tumor.

Compared on average to about 35, gray total absorb radiation dose delivered to tumors using external beam radiation.

The data in our trial showed that rhythm of estimate it can be safely administered and there was a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and percent tumor volume and the treated volume.

The strength of the signal is unusually positive for a phase one trial and.

And we found that specifically for every 100, great increase in the absorbed dose correlated.

Every increasingly absorbed dose that correlated with about a 36% decrease in the risk of death.

The more radiation to the tumor the lower the risk of death.

And also in every 1% increase in the tumor volume treated up to a Max of 100%. Obviously that is associated with the four 5% decrease in the risk of death and that was highly statistically significant.

There were no dose limiting toxicities reported and the overall safety profile was very favorable.

The study concluded that a single administration of <unk> by convection enhanced delivery and recurrent glioma patients with poor prognosis is feasible safe and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor.

And then the latter cohorts, we were delivering a therapeutic dose and over 80% of the patients treated.

Based on the data from the Phase one trial in Q4 2022, we initiated a phase II dose expansion trial evaluating <unk> for the treatment of patients with recurrent GBM using our cohort six dose which is $22 three militaries in eight eight <unk>.

Leaders.

Injected for small and medium sized tumors and thats essentially tumors that are about 2000 Ccs or worse.

This phase II will enroll up to an additional 31 patients with small to medium sized tumors in our proxy.

Tend to enroll that trial in approximately 24 months or less.

That trial continues to be supported by an award from the National Cancer Institute.

While we have five sites authorized.

The NIH with the Pi and the NIH, we plan to expand the number of trial sites beyond the authorized five to facilitate faster enrollment.

The primary endpoint.

As a reminder is overall survival following single administration, which is an input we agreed to with the FDA and secondary endpoints will assess the safety Tolerability objective response rate partial response.

Sce's event free survival and progression free survival at six months.

Also as mentioned above key focus areas of ongoing clinical investigation in the GBM development program will be further dose exploration by increasing the dose and also increasing the number of doses.

Two patients who happened to occur after a single administration.

And also to inform the design of future Registrational trial.

As discussed previously the company and the FDA agreed to hold future meetings is facilitated by our orphan and fast track designations on the Registrational Registrational trial design, including the use of external data to augment the control arm and speed of enrollment and a potential pivotal.

Now, let me move on to our Leptomeningeal metastases or <unk> development program.

<unk> trial is a multicenter phase <unk> dose escalation study.

Created dose safety and efficacy of Verenium Obispo Meda.

As you May know.

Complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system also called <unk>.

It so happens that the incidence of <unk> is growing.

With local and.

And improve cancer care and there are no approved FDA therapies and there are about 120000 patients per year that affected with Elliot and is substantially under diagnosed.

Standard treatment includes external beam radiation therapy to the affected sites potentially with chemotherapy given either orally.

Intravenously are often administered twice a week directly into the CSF space.

Systemically administered therapies, almost never work because of the blood brain barrier.

Preventing access to the <unk>.

So going back again to the snow meeting back in November . We also prevented presented the early phase one data from the respect <unk> trial at that meeting that demonstrated that a single administration of <unk>. It was feasible safe and well tolerated across the two dosages study at that time and cohorts.

One and two with patients with patients in that trial.

After treatment showing a decreased.

SaaS tumor cell count by 48 hours following treatment that was between 46% to 90% in terms of reduction of the tumor cell count that was measured in the CSF.

The $17 6 million product development Research funding award.

We received from the cancer Prevention and Research Institute of Texas for Secret began funding in the fourth quarter of 2022 as.

As mentioned this award will cover the majority of the development cost, including funding for up to 150 enrolled patients for the Eliot program over three years.

And that's an important source of non dilutive funding that material strengthens the company's balance sheet.

In early 2023, we completed.

Enrollment in cohort two of the trial and now six patients have been treated.

<unk> next steps with that trial following the SMB the data safety monitoring Board review, which is anticipated to be in March.

We anticipate that we'll complete enrollment in part a of the phase one portion soon perhaps in the next quarter that would be nine patients total.

Thereafter, we plan a meeting with the FDA to determine the exact dose expansion plans for the phase one part B trial, and then we expect to initiate that.

That part B trial in the second half of 2023. We also expect initial data from the phase one part a to be presented also in the second half of 2023.

As I mentioned on our third quarter 'twenty to call in November we have made and are making significant progress in building, a more resilient and robust G&P supply chain through our.

Our strategic partnerships that enable the development manufacture.

And even future potential commercialization of our products.

Our current supply chain and key partners are positioned to supply.

Cgmp Iridium Obispo Mehta for any ongoing and planned phase two three clinical trials in patients with GBM <unk>, our pediatric brain cancer and that is now fully in place as of the end of last year.

Yeah.

And pediatric brain cancer based on expensive extensive.

So obviously, we expect to submit an updated investigational new drug application.

For what will be called the respect PBC phase one safety dose finding an efficacy study.

<unk> made it for pediatric brain tumors. It will be submitted in conjunction with our lead academic institution Lurie Children's hospital at Northwestern University in Chicago.

Finally regarding our novel recently in licensed radio Embolic micro particle technology 188, R&R ban with success.

72 objectives. Furthermore, based on the FDA feedback regarding the most.

Regulatory designation for the investigation of product specifically.

Whether it should be a drug or device in terms of its regulatory path. We are pursuing the request for designation process to define this in parallel to performing required development developmental activities.

Regardless of whatever the ultimate regulatory designation ultimately is it's our view that despite the fact that the competing legacy products that are on the market.

Which are permanently and dwelling radio embolic products that had been in the market for in some cases over two decades.

<unk> bio resorbable nature, our R&R Bam supports its ultimate designation as a drug.

Nonetheless, we will collaborate with the FDA to seek their ultimate guidance on this determination and proceed in parallel with those development activities that we can reasonably do irrespective of the ultimate regulatory determination.

The company plans as mentioned previously on other calls to initially focus on developing the <unk> technology as a next generation <unk> radio embolic therapy for it first liver cancer.

So with that summary, I will turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials Andrew.

Thank you Mark good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2022 fourth quarter and full year ended December 31 2022.

As of December 31, 2022, cash and cash equivalents were $18 1 million compared to $18 4 million as of December 31, 2021.

The company believes the combination of current cash.

<unk> grant funding in conjunction with existing discretionary capital sources secures a cash runway through 2025.

Cash used in operations full year, 2022 was $13 million compared to $10 3 million for full year 2021.

During the fourth quarter of 2022, the company received its first secret grants funds of approximately $1 9 million as planned.

The main year over year changes between full year 'twenty, two and full year 'twenty one are as follows.

Revenue of 224000 was reported related entirely to separate.

Operating expenses for full year, 2022 were $19 9 million compared to $12 5 million for the prior year.

<unk> 2022 total included two main areas of spend that were one off in nature.

The first area of increase was CMC spend related to the development of GMP quality drug and key regulatory consulting activities necessary necessary to advance the phase two GBM clinical trial.

These expenses were over $4 million in 2022.

2023 spend related to these activities is forecast to be less than 500000.

In addition, and to a lesser extent the company had a forecasted increase in litigation and legal spend related to a legal settlement disclosed in Form 10-K.

The net result is that we expect an overall decrease in total burn in 2023 based on our currently disclosed milestones.

Interest expense decreased from 932000 and for full year 2021.

711000 for full year 2022.

This decrease reflects the continued principal paydown the commenced in November 'twenty, one and the company's Oxford debt.

Net loss for full year, 2022 was $20 3 million or <unk> 77 per share compared to a net loss of $13 4 million or $1 11 per share for full year 2021.

Now I'll turn it back to Mark.

Thank you Andrew.

Before we move on to Q&A.

Allow me to provide a very detailed guidance on anticipated milestones for 2023.

First of all we intend to expand the Glioblastoma clinical trial sites and make meaningful enrollment progress with respect GBM phase III trial to support a target completion of enrollment date by the end of the year 2024.

We also plan to publish the respect phase.

PM data.

In a high impact factor peer reviewed journal.

We also plan to present clinical safety and efficacy data of the phase one and phase two respect GBM trials in the second half of 2023.

In terms of LTM meningeal metastases, our plan is to complete enrollment in the phase one part a of the respect <unk> trial and begin enrollment in the phase one part b.

We also intend to respect Lf trial to expand the number of clinical trial sites to support that expansion into part b of that phase one.

Also in the second half of 2023, we will present clinical safety and efficacy data.

Based on the phase one part a of the respect <unk> trial.

As per the secret Grant, we will explore potentially synergistic drug combination studies of locally delivered rhenium obispo meda, coupled with promising systemic therapies in relevant preclinical models of Leptomeningeal disease.

We also will initiate the IND to treat pediatric patients with a pin the Moma and high grade glioma and begin enrollment the first clinical trial site should be northwestern and Lori Children's hospital.

In conjunction with the FDA.

We intend to finalize the regulatory designation for the 188 are in L band technology and complete key developmental activities. This year.

Furthermore, we think in 2023, there are opportunities to execute corporate partnerships to expand the business opportunities for pluses unique CNS oncology platform.

And then finally building on our success with secret we intend to submit multiple grants to raise non dilutive capital to support expansion of the company's drug development pipeline.

So with that behind US, let me turn this back over to Andrea for Q&A session Andrea.

Thank you at this time, we will conduct a question and answer session. As a reminder to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw your question Press Star One again, please standby, while we compile the Q&A roster.

Our first question comes from Justin Walsh with Jones trading. Please go ahead.

Hi, Congrats on the progress thanks for taking the questions to start I was wondering if you could maybe provide some more color on what we can expect in the upcoming data Readouts. You just mentioned so for prospect GBM curious about any patient data, we haven't seen from the phase <unk> portion as well as what we might see from the.

<unk> portion and likewise for respect that lab.

Hey, Justin it's Marc obviously.

Well present, what data we can see.

But I'll, let norm take that question because he is.

He is up to his shoulders and evaluating that data Norman.

Thanks Mark.

Great question, Justin and as you've seen over the past eight years, we've developed progressive.

Statistical evaluation models, starting with the km.

And less than 100, Gray, which was based on the preclinical.

Ill call it point, where there is clear.

Efficacy from that absorbed dose.

No that radiation works in more radiation is better.

Okay.

Those two cohorts.

And by comparison it was roughly a two year OS versus a five month OS for our specific data we.

Added to those evaluations and these were.

Presented at <unk>.

Medical meetings and peer accepted presentations one on the <unk>.

Cox proportional hazard ratio model, which is a.

It's a survival model and the statistics that uses all of the data and instead of the cutoff of 100, Gray, which as I said was supported both by what is known with radiation absorbed dose in general and was supported by our specific pre clinical data instead, we presented the totality of our data with.

Cox model.

And showed.

Which we reported in several meetings of an <unk>.

Proved survival percentage, we use the incremental 100, gray and Mark mentioned that with a greater than 40%.

Closer to 45%.

Prudent in survival for each additional 100 grant absorbed dose and a comparable survival that was.

Three years to 4% for each 1%.

Covered tumor.

Treatment.

We expanded that.

Because of the.

It doesn't correct for all the covariant.

Parametric types of bias you might get with what is call the accelerated failure time model.

That showed.

Consistent and actually better statistically significant the Cox model was.

0.003.

Values for both whereas the AFP model showed a zero point zero zero.

Okay.

So these and these were all on our data without <unk>.

In its totality without any differentiation of cutoff as we did with the initial Lotto meningeal excuse me a Kaplan Meier.

100, great cutoff. So we'll continue to analyze the phase II trial that we started will.

We will build on these data we have analyses that we'll present probably in our publication that is in draft now.

For a major publication on phase one on what this means.

Predictability of phase II.

It will probably present that also future ask or snow ESCO meeting in the summer and certainly for the snow meeting in fourth quarter.

I am very happy in a separate call we can't get into the statistics in great detail, but if theres any interested in really digging into that just let us know what I'll be happy to spend some time with you.

Got it.

Maybe one you mentioned the all the presentations you guys have been going to different scientific meetings I am curious what some of the reception to the <unk>.

Data is that you presented so far obviously the.

Ti is quite yes, you're asking about this but how does the community received.

Yes.

I am glad you asked that because for me to bring it up maybe not as humble as we shouldnt be.

And not to be a wise Guy I think you should ask some of the Kols out there what they think what they tell us on.

Unprompted is that this is surprising data for such an early program and they have not seen it in <unk> and.

And typical.

Therapeutic programs now part of my answer to them. Some of them know me is this is a radiopharmaceutical and it's not uncommon early in a program to get a very good sense.

On how it's going to work because the mechanism of action first of all is well known it's well accepted energy transfer to the tumor is efficacious.

And more is better.

We have the delivery problem solved for both the GBM and <unk>. So thats very effective as has been presented and as you are well aware and we've shown that the increasing doses were.

We have done during the dose escalation remain very well tolerated.

And quite.

In a sense predictable because we're not using exhaust of doses are extremely high doses, they've all been well tolerated without any observed <unk>.

Limiting doses or maximum tolerated doses observed or identified so we're on very solid ground for a very good therapeutic index. The safety margin is.

It's very comforting and robust and people have recognized this and in fact, many times will get unsolicited requests for interest in our programs because they have seen.

<unk> seen our presentations at one of the several meetings we participated in.

And last but not least is what we all know.

For both <unk>, and GBM, but particularly <unk>.

There is nothing out there for these folks there is theres no therapies nothing works there is not really very many investigative programs.

<unk> is really a waistline options for patients. Unfortunately and people are recognizing that this this is something there and then GBM. The data speaks for itself and you really can't you can't ignore that preliminary signal at all and I think when we can report.

Hopefully and acceptance in a major impact journal that Mark mentioned.

There'll be further recognition on this preliminary data. So thanks, thanks for that question.

Got it maybe the tax one for Mark and kind of build builds on what you are saying about some of the interest that you guys have been getting I'm sure you can't speak to specific potential partners, but I'm wondering if you can shed any light on the types of conversations you are having or would like to be having or are they primarily related to potential.

<unk> therapies or other other types of opportunities.

Hey, Justin I would like to.

We've.

We've done three transactions over the last like one transaction a year as we work to expand the pipeline build.

Build it out.

And so.

Yes.

Or is there kind of across the board quite honestly.

We're very promiscuous in terms of discussing and evaluating ways, we can build value for shareholders.

Whether that's out licensing our <unk> licensing so we continue to expand those discussions and as the data gets out there that things that Norman presented.

Those get more and more notoriety.

Increases the number of discussions so it can be really hard to say much about that at this point.

The conversations are increasing not decreasing got.

Got it and one more for me.

Just sort of speaking to the I guess some of the general tones here. It seems to me like we are at.

Another inflection point in the radio therapeutic field with the significant increase in the use of targeted radiopharmaceuticals and prostate cancer. So I am wondering if you guys have seen any change in the tone or content of discussions you've been having as the commercial potential of some of these radio therapeutics has come even more into focus.

Yes.

I may let the Doctor comment.

Scientifically and we've been doing this for a year or two and knows a lot about the space and has seen it evolve probably has more drugs approved under us.

His watch than anybody in the country through the radio therapeutic space, but.

So.

Starting maybe early 2021 and just on the you know this because youre in.

Well we.

We're seeing banks increasingly add.

Analysts that are dedicated to radiotherapeutic. So that's an important.

<unk>.

I think an important milestone there is bank coverage as analyst coverage.

There are as capital flows into the space.

There are there is manufacturing infrastructure thats being funded and built out in anticipation of the market coming.

So.

And then you see major players doing deals in this space. So we'd see a lot of really promising.

Movements in the capital markets.

That are pointing to <unk>.

Years ahead of us of growing value in this space. So we cannot be more.

More excited to be here at the ground floor and one thing that's different about US I think you know Justin is we have real data we have.

There are a lot of companies that.

Have are building infrastructure, but we're.

Where we are building data profile that I think is very exciting and a group of diseases that are.

Don't have good options.

So, yes, we're very optimistic and bullish Dr. Do you want to.

I think what Youre asking.

You are mentioning.

The <unk> space, which is very crowded it's been successful recent approval. There are several out there and as you will know before that was the.

Serotonin receptor Dota Tate approval, which has been successful and quite frankly in the literature and the meetings that.

<unk>.

What's been talked about understandably and they burn they've earned that with some good data and some good results.

And Aldo humility I'd like to add that when we presented at the European Association of nuclear Medicine.

You may notice that they have a highlights presentation at the beginning of the meeting to present, what they with the reviewers and the leadership of that society.

Or the.

The up and comers or the new data things that pay attention to and our.

<unk>.

Data presentation, there, which I did was chosen for the highlights lecture is the first presentation now admittedly there was a PSA MA paper in a.

Dota Tate paper, and so forth, but consistent with what <unk> been doing over the last years and those products are getting getting the attention they should get but it was very I think rewarding and very appreciated by us and in fact, the folks came up to me afterwards and.

A picture for prosperity in the sense of noting that this was.

This is quite in advance that they recognized.

Definite radiopharmaceutical that rather than the classic systemically administered using some elegant biochemistry or targeting mechanism, which is.

Which is elegant and something that's very straightforward and had some very incredible data that they pointed to very carefully so.

We've we've made to highlight lectures and I think this is recognition by the field that there are other.

Other candidates out there looking to make a difference.

Well I look forward to seeing the continued building of this.

Data set and thanks for taking my questions.

Thank you.

Thank you one moment for our next question.

Our next question comes from Ed Woo with <unk> capital. Please go ahead.

Yes, congratulations on the progress in 2022 and that definitely congratulations on the <unk> Grant.

There any possibility of visibility that youll be able to apply for the grants for any other indication.

Hey, Ed. Thank you for the question I think you mean the <unk>.

Secret Grant are we going to be able to apply that to other indications.

No I mean in terms of getting grants for other indications coupled with the new government.

Got it yes, no. Thanks.

I appreciate the question so.

You know we've been we've been successful knock on wood.

And getting third party grant support in terms of the NCI Grant Vascepa Grant one of the reasons, we moved to Texas.

Easy to say now that we have a grant under our.

And our sleep, but was that we thought that $6 billion of capital for cancer funding.

Be able to get some of that to fund our programs and mobile hole that we were we were fortunate to be able to do that.

We know of companies that have.

Up to three separate grants.

So so we do in fact think that some of our programs that arent funded.

Or aspirational programs that we'd like to bring on board, but because of our.

Okay.

Frugality about capital deployment in other words, we don't we don't want to.

Spend it until we raise it that there might be some opportunities there so.

Our plan and that was the milestone this year, so we're going to submit more than one grant clean.

Clean the secret, but also potentially other grants that some of our opportunities that we have available to us.

Fund.

Additional programs to build out the pipeline so that's our goal.

Those can be hard to get but we're going to submit them and we think we sort of cracked the code to a degree on separate and we think there might be some greater opportunities ahead of us there.

What was the timing in terms of when you submitted your application to when you got.

What are the graph.

For separate the LM grant.

Yes.

Yes actually.

It was I think about 18 months. So we submitted a couple of iterations, we got close a couple of times.

With the NIH.

Terrific feedback how you can improve the grant we worked in the background to continue to advance.

The program, while we were continuing those dialogues.

No.

I think that.

Treating a patient really.

Really helped convince them and the data that will help convince them that this is something that's worth funding so.

Yes.

It's like all grants typically sort of iterative key is being persistent.

Having data data helps.

Alright.

Definitely congratulations and definitely looking forward to more good news from you guys. This year. Thank you.

Thank you Ed.

Thank you one moment for our next question.

Our next question comes from Sean Lee with HC Wainwright. Please go ahead.

Good afternoon, guys and thanks for taking my questions.

My first question is on the phase two GBM study can we expect the data readouts from that prior to.

<unk> full patient enrollment expected by the end of 'twenty four.

It's an open label non blinded study so the short answer would be yes.

To give you more details it will be as I I think I was answering justin's question on the <unk>.

Hypes of statistical analysis.

I would expect us to have some reviews of the different types of analyses just because there is.

Lots of ways to utilize those to form the design of the Registrational trial.

I'd like to give you more detail, but the short answer is yes.

It will depend on how the data develops and if we can certainly.

Accelerate the accruals.

Even faster will be in a position to move on that more quickly and part of that will be in our preparation to go to the FDA. So.

We plan to share that I can't give you exact timing however.

No issues, thanks for the additional color.

My second question is on the upcoming on pediatric study.

What are some of the key learnings and takeaways from GBM.

GBM trial that you feel could.

Help you apply to the pediatric study and make it more successful.

Yes.

Great question very.

Very applicable and we actually leverage the pediatrics.

Questions and presentations to the FDA, we leveraged our adult data significantly.

That in fact result in the FDA asking.

Not asking questions, but more clarifications on that data, which is a good thing because it gets them more involved in that data.

The first interactions with FDA was to kind of include all comers in pediatric brain tumors, which is a broad spectrum.

And that in this year and first in pediatric patients for any drug, particularly a radiopharmaceutical.

FDA is careful and conservative.

We got that feedback for example, we are limiting the tumors to super <unk> and the ones with high unmet medical need with terrible prognosis depth pendant moments in the high grade Gliomas.

We have had most recently the FDA agreement by the reviewers for the pediatric protocol and just show them some last.

Clarifications they have on some of the adult data, which is straightforward we have and it's just the re analysis and shows their interest in the adult data, which will be able to leverage for future adult.

Considerations and so Mark do you have anything they all set on this.

Well just.

The thing I would add to that Sean is.

And we mentioned this before in the adult and the.

Adult trial deliveries the key if we can cover the tumor with enough radiation theyre going to kill the tumor period sort of in the discussion.

We translated that data directly into the pediatric population and so I think that really gives us confidence in that trial that we can we can deliver the drug. The other thing is it's very common to put electrodes into the brain and these these kits so.

We have a high degree of confidence that the.

Convection delivery process will be well tolerated, so we're really able to leverage both.

Epilepsy treatment data as well as our adult delivery data to feel confident going into this trial, we were able to convey that successfully I think to the FDA given the fact that.

The clinical protocol.

Thank you for that that was very helpful.

And last question on the.

Pam product I know it might be early but are there specific indications, where you feel the product will be particularly well suited for.

Yes.

Our initial target is going to be for Hepatoma.

There are two drugs on the market that are long in the tooth they're non bio resorbable. They are used to treat epitope, we think it's about one $2 billion.

Opportunity.

But those are permanent and we're providing a drug that has different radiotherapeutic different characteristics that are.

Related to the iridium that make it more attractive.

So its resorbable, so the ideas that you've kind of tune the buyer absorption.

Timing so that by the time the radiation is full.

<unk> fully decayed or near fully decade.

<unk>.

The embolic has been by our Resorbs back.

Vascular patency has resumed and you can go back in and re treat the patient multiple times. That's the idea. So this would be a very differentiated unique novel product and so livers.

First but potentially we could go any any tumor that you can target by <unk>.

Radio.

Amortization or angiographic catheters, potentially tolerate even things like potentially pancreatic cancer and other things sarcomas that are difficult to treat or get to potentially would lend themselves to therapy, but livers.

I think our initial target is there is an existing market.

Great. Thanks, Marc and that's all the questions by half.

Thank you Sean.

Thank you as a reminder to ask a question. Please press star one on your telephone are there any written questions today.

Okay. Andrea we have we have one written question.

The other three other written questions that have been largely answered this question.

Revolves around our <unk> trial and the use of novel.

Cell testing approach to determine biological response was.

How is that important to your trial.

Going forward and.

And your development plans so.

Yes, Youre talking about when you said.

Interesting test called CNS side.

It's manufactured by a California company.

Thus far we are I would say, we're incredibly pleased with that test I think it fills up.

A critical gap in.

The diagnostic and therapeutic approach to these patients.

The.

The current <unk>.

Existing weigh that.

Mmm is diagnosed is by a mix of imaging and imaging is not great.

Clinical findings, which are often very vague and nonspecific.

And then the.

CSF lumbar puncture results, which look at glucose protein and cell count, which is the same thing that Norman and I use when we are medical school.

A year or two ago that is very nonspecific.

And very non sensitive for that so.

I think as I've mentioned in the first four patients where we have data on we have significant reduction tumor cell counts as measured by that assay. So.

We're very we're very pleased with what we've seen thus far but it's very early.

Another relevant piece of information is L. M is significantly under diagnosed so.

Only about 25% of patients with LMR diagnosed we know that based on the autopsy data. So there is an opportunity to increase the total addressable market.

<unk> for our therapeutic by up to four times.

That opens up a pretty significant.

Increased application for the test and.

The other interesting thing is beyond just quantification of tumor cells. So you can actually use that test potentially to tailor therapy, although we don't use it for our trial you can actually put it in.

Groups of antibodies and look at specific.

Epitope expression.

<unk> insight to hybridization and genomic analysis as part of that test too.

Taylor therapy.

In terms of using systemic <unk> immunotherapy and so forth.

Beginning to explore and are Super grant so.

That's a good question and we think it's going to be very important long term to pair the the therapeutic with with diagnostic like this and innovative.

Okay to think about it almost like a companion diagnostic.

And that's the that's the only question.

Unanswered, so andrea anything else.

I'm not showing any further questions right now mark if you'd like to close it out.

Yeah. So thanks to everyone for participating on the call today appreciate your interest in the company.

Once again, thanks to our employees and are collaborating physicians and scientists that we work with on a daily basis, and we're very appreciative also for the patients who enrolled in this trial that need this help.

And trust us to deliver for them in the family. So we're very appreciative to them. So we look forward to continuing the updating process.

And as we move forward and thanks also to our stockholders for their continued support and confidence. Thank you.

Yeah.

Okay.

Thank you for your participation in today's conference. This concludes the program you may now disconnect.

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Good afternoon.

Ladies and gentlemen, welcome to the plus therapeutics fourth quarter and full year 2022 results conference call.

<unk> Therapeutics advises you to review these risk factors in considering such statements plus therapeutics assumes no responsibility to update or revise any forward looking statements to reflect events trends.

Or circumstances after the date they are made.

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

Thank you Andrea good afternoon, everyone and thank you once again for taking the time to join US today as we provide an overview of recent business highlights and discuss our 2022 fourth quarter financial results.

Joining me for the call today is Dr. Norman with France, our Chief Medical Officer.

And Mr. Andrew Sims, our Chief Financial Officer.

I'll begin the call by reviewing 2022 and then.

Andrew to review, our financials and Dr. <unk>, France will be joining us for Q&A.

At a high level I was extremely pleased with our accomplishments in 2022.

Going into the year, we set for ourselves some significant development goals, and we achieved or exceeded almost all of them.

At the same time, we continued a very conservative approach to managing our balance sheet ending the year with a similar cash level to the prior year.

But we materially expanded our availability of cash as Andrew will discuss.

So let me begin by focusing on drug development clinical and regulatory activities and related milestones.

First I ask that you wind the clock back over a year and recall that we ended 2021 with a single drug which was 186 arnelle active in only a single phase one clinical development program for recurrent glioblastoma.

And in large part by the NIH.

That was in essence, the whole of our active clinical development program at that time, it was a year ago.

Fast forward to the end of 2022, we ended the year with two investigational drug candidates.

<unk> 186, Obispo Meda, formerly called <unk> hundred 86 are Enel and rhenium 188, bio absorbable alginate microspheres or 188 are in L band as we call it.

Regarding our investigational drug <unk> 186, Obispo Meda Iridium Obispo Meda, we have two active clinical programs now ongoing one for recurrent GBM and the other for Leptomeningeal cancer.

In terms of Glioblastoma and 2022, we substantially expanded this program.

Specifically, we advance from phase one to phase two.

We are continuing the dose escalation for larger tumors in higher dose volumes.

We manufactured GMP drug, allowing us to move into phase III, we enrolled the first patient in the phase II trial.

We negotiated with FDA to continue the phase one dose expansion for larger tumors and now have an active re treatment protocol with FDA to explore retreating patients that happened to occur after first treatment.

So leptomeningeal disease, we move this program.

So essentially a co lead program with GBM and specifically, we advance that program successfully from preclinical stage two in enrolling phase one and we obtained $17 6 million in funding for this program that in combination with pluses one third match as required by secret.

A water that should be sufficient to fund this program through phase II and the enrollment of approximately 150 patients.

For pediatric brain cancer, while we did not initiate this trial in the calendar year because of the discussions with the FDA that were required for this first in pediatric patient Radiopharmaceutical trial, we did make significant progress specifically after three rounds of FDA interactions on the nature of the IND for <unk>.

Pediatric brain cancers, FDA reviewers have accepted our clinical protocol design, but still require and request some additional adult data, which we plan to submit relatively soon.

Human Oregon ex vivo perfusion model confirming the preclinical feasibility in the manufacturing of that drug and then we submitted a pre IND information package to the FDA.

So big picture in terms of milestones achieved 2022 was a transformative year in the company's development.

Additionally, in 2022, we presented important data readouts in our two lead clinical programs GBM and Leptomeningeal cancer.

First in November 2022 results from the company's phase one respect GBM trial for recurrent Glioblastoma was presented at snow The society for Neuro oncology meeting in Florida by the trial pie.

And the phase one dose escalation trial at that time 24 patients with recurrent GBM across seven cohorts received a single dose of radium Obispo Meda.

Administered in the dose escalation phase achieving up to 740 <unk>.

Turning to the tumor.

On average to about 35, gray total absorb radiation dose delivered to tumors using external beam radiation.

The data in our trial showed that <unk> can be safely administered and there was a statistically significant correlation between overall survival and both absorbed radiation dose to the tumor and percent tumor volume and the treated volume.

The strength of the signal was unusually positive for a phase one trial and.

And we found that specifically for every 100, great increase in the absorbed dose correlated.

Every increasingly absorbed dose that correlated with about a 36% decrease in the risk of death.

The more radiation to the tumor the lower the risk of death.

There were no dose limiting toxicities reported and the overall safety profile was very favorable.

The study concluded that a single administration of <unk> <unk> of estimated by convection enhanced delivery.

<unk> patients with poor prognosis is feasible safe and potentially effective in increasing overall survival when a therapeutic dose of radiation is delivered to the tumor.

And then the latter cohorts, we were delivering a therapeutic dose and over 80% of the patients treated.

Leaders of inject eight for small and medium sized tumors and thats essentially tumors that are about 2000 Ccs or worse.

This phase II will enroll up to an additional 31 patients with small to medium sized tumors in our proxy.

Tend to enroll that trial in approximately 24 months or less.

That trial continues to be supported by an award from the National Cancer Institute.

While we have five sites authorized under the NIH with the Pi and the NIH, we plan to expand the number of trial sites beyond the authorized five to facilitate faster enrollment.

The primary endpoint.

Sce's event free survival and progression free survival at six months.

Two two patients who happened to occur after a single administration.

And also to inform the design of future Registrational trial.

Now, let me move on to our Leptomeningeal metastases or <unk> development program.

<unk> trial is a multicenter phase <unk> dose escalation study.

Created dose safety and efficacy of radium Obispo Meda.

As you May know.

Complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system also called the left them in <unk>.

It so happens that the incidence of <unk> is growing.

With local and.

And improve cancer care and there are no approved FDA therapies and there are about 120000 patients per year that effective with Elliot and is substantially under diagnosed.

Standard treatment includes external beam radiation therapy to the affected sites potentially with chemotherapy given either orally.

Intravenously are often administered twice a week directly into the CSF space.

Systemically administered therapies, almost never work because of the blood brain barrier.

Preventing access to the left them in <unk>.

So going back again to the snow meeting back in November . We also prevented presented the early phase one data from the respect <unk> trial.

Meeting that demonstrated that a single administration of Verenium Obispo Meda was feasible safe and well tolerated across the two dosages study at that time in cohorts, one and two with patients with patients in that trial.

After treatment showing a decreased <unk>.

<unk> tumor cell count by 48 hours following treatment that was between 46% to 90% in terms of reduction of the tumor cell count that was measured in the CSF.

The $17 6 million product development Research funding award.

We received from the cancer Prevention and Research Institute of Texas for Secret began funding in the fourth quarter of 2022 as.

As mentioned this award will cover the majority of the development costs, including funding for up to 150 enrolled patients for the <unk> program over three years.

And that's an important source of non dilutive funding that materially strengthens the company's balance sheet.

In early 2023, we completed <unk>.

Enrollment in cohort two of the trial and now six patients have been treated.

Regarding next steps with that trial following the SMB the data safety monitoring Board review, which is anticipated to be in March.

We anticipate that we will complete enrollment in part a of the phase one portion soon perhaps in the next quarter that would be nine patients total there.

Thereafter, we plan a meeting with the FDA to determine the exact dose expansion plans for the phase one part B trial, and then we expect to initiate that that part B trial in the second half of 2023. We also expect initial data from the phase one part a to be presented also with the SEC.

<unk> half of 2023.

As I mentioned on our third quarter 'twenty to call in November we have made and are making significant progress in building, a more resilient and robust G&P supply chain.

Our strategic partnerships that enable the development manufacture.

And even future potential commercialization of our products.

Our current supply chain and key partners are positioned to supply.

Cgmp Iridium Obispo Mehta for any ongoing and planned phase III clinical trials in patients with GBM <unk>, our pediatric brain cancer and that's now fully in place as of the end of last year.

Sure.

And pediatric brain cancer based on expensive extensive.

Seriously, we expect to submit an updated investigational new drug application.

For what will be called the respect PBC phase one safety dose finding an efficacy study of <unk> for pediatric brain tumors. It will be submitted in conjunction with our lead academic institution Lurie Children's hospital at Northwestern University in Chicago.

Finally regarding our novel recently in licensed radio Embolic micro particle technology 188, R&R Bam we succeed.

72 objectives. Furthermore, based on the FDA feedback regarding the most.

Regulatory designation for the investigation of a product specifically.

Regardless of whatever the ultimate regulatory designation ultimately is it's our view that despite the fact that the competing legacy products that are on the market.

Which are permanently and dwelling radio embolic products that had been in the market for in some cases over two decades.

The bio resorbable nature of our Rns Bam supports its ultimate designation as a drug.

The company plans as mentioned previously on other calls to initially focus on developing the <unk> technology as a next generation <unk> radio embolic therapy for it first liver cancer.

So with that summary, I will turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials Andrew.

As of December 31, 2022, cash and cash equivalents were $18 1 million compared to $18 4 million as of December 31, 2021.

The company believes the combination of current cash committed grant funding in conjunction with existing discretionary capital sources secures our cash runway through 2025.

Cash used in operations full year, 2022 was $13 million compared to $10 3 million for full year 2021.

During the fourth quarter of 2022, the company received its first secret grants funds of approximately $1 9 million as planned.

The main year over year changes between full year 'twenty, two and full year 'twenty one are as follows.

Revenue of 224000 was reported related entirely to separate.

Total operating expenses for full year, 2022, with $19 9 million compared to $12 5 million for the prior year.

The 2022 total included two main areas of spend that were one off in nature.

The first area of increase was CMC spend related to the development of GMP quality drug and key regulatory consulting activities necessary necessary to advance the phase two GBM clinical trial.

These expenses were over $4 million in 2022.

2023 spend related to these activities is forecast to be less than 500000.

In addition, and to a lesser extent the company had a forecasted increase in litigation and legal spend related to a legal settlement disclosed in Form 10-K.

The net result is that we expect an overall decrease in total burn in 2023 based on our currently disclosed milestones.

Interest expense decreased from 932000 and for full year 2021.

711000 for full year 2022. This decrease reflects the continued principal paydown the commenced in November 'twenty, one and the company's Oxford debt.

Net loss for full year, 2022 was $20 3 million or <unk> 77 per share compared to a net loss of $13 4 million or $1 11 per share for full year 2021.

Now I'll turn it back to Mark.

Thank you Andrew.

Before we move on to Q&A.

Allow me to provide a very detailed guidance on anticipated milestones for 2023.

We also plan to publish the respect phase.

GM data.

In a high impact factor peer reviewed journal.

We also plan to present clinical safety and efficacy data of the phase one and phase two respect GBM trials in the second half of 2023.

In terms of El Limn Meningeal metastases, our plan is to complete enrollment in the phase one part a of the respect <unk> trial and begin enrollment in the phase one part b.

We also intend in this respect the Lf trial to expand the number of clinical trial sites to support that expansion into part b of that phase one.

Yeah.

Also in the second half of 2023, we will present clinical safety and efficacy data.

Based on the phase one part a of the respect <unk> trial.

In conjunction with the FDA.

We intend to finalize the regulatory designation for the 188 are in L band technology and complete key developmental activities. This year.

Furthermore, we think in 2023, there are opportunities to execute corporate partnerships to expand the business opportunities for pluses unique CNS oncology platform.

And then finally building on our success with secret we intend to submit multiple grants to raise non dilutive capital to support expansion of the company's drug development pipeline.

So with that behind US, let me turn this back over to Andrea for the Q&A session Andrea.

Our first question comes from Justin Walsh with Jones trading. Please go ahead.

Hi, Congrats on the progress thanks for taking the questions.

To start I was wondering if you could maybe provide some more color on what we can expect in the upcoming data Readouts. You just mentioned so for respect GBM curious about any patient data, we haven't seen from the phase one two a portion as well as what we might see from the phase <unk> portion and likewise for respect that lab.

Hey, Justin it's Marc obviously.

Well present, what data we can.

To you, but I will let norm take that question because he is.

He is up to his shoulders and.

Evaluating that data Norman yes, thanks Mark.

Great question, Justin and as you've seen over the past eight years, we've developed progressive.

Statistical evaluation model, starting with the km.

Gray and less than 100, Gray, which was based on the preclinical.

I'll call it a point, where there is clear.

Efficacy from that absorbed dose and we know that radiation works in more radiation is better.

Okay.

Those two cohorts.

And by comparison it was roughly a two year OS versus a five month OS for our specific data we.

Added to those evaluations and these were.

Presented at <unk>.

At medical meetings and peer accepted presentations one on the <unk>.

Cox proportional hazard ratio model, which is a.

Yes.

It's a survival model and the statistics that uses all of the data and instead as a cutoff of 100 Gray, which as I said was supported both by what is known with radiation absorbed dose in general and it was supported by our specific pre clinical data instead, we presented the totality of our data with that cash.

Model.

And showed.

Which we reported in several meetings of an improved survival percentage, we use the incremental 100, gray and Mark mentioned that with a greater than 40%.

Closer to 45%.

Prudent survival for each additional 100 grant absorbed dose and a comparable survival that was.

3% to 4% for each 1%.

Covered tumor.

Treatment.

We expanded that.

Model because of the.

It doesn't correct for all the covariant.

Parametric types of bias you might get with what is call the accelerated failure time model.

That showed.

Consistent and actually better statistically significant the Cox model was.

0.003.

Values for both whereas the AFP model showed a zero point zero zero.

So these and these are all on our data without.

And its totality without any differentiation of cutoff as we did with the initial Lotto meningeal excuse me a Kaplan Meier.

100, great cutoff. So we'll continue to analyze the phase II trial that we started will will.

We will build on these data we have analyses that we'll present probably in our publication that is in draft now.

For a major publication on phase one.

What this means.

Predictability of phase III.

Present that also.

Future ask or snow ESCO meeting in the summer and certainly for the snow meeting in fourth quarter. So.

Very happy in a separate call we can't get into the statistics in great detail, but if theres any interested in really digging into that just let us know and I'll be happy to spend some time with you.

Got it.

One you mentioned.

All the presentations you guys have been going to a different scientific meetings I am curious what some of the reception to the <unk>.

The data is that you presented so far obviously the.

Ti is quite yes, you're asking about this but how does the community received.

Yes.

I'm glad you asked that because for me to bring it up maybe not as humble as we shouldnt be.

And not to be a wise guy.

I think you should ask some of the Kols out there what they think what they tell us.

Prompted.

Is that this is surprising dataset for such an early program and they have not seen it and al and typical.

Therapeutic programs now part of my answer to them. Some of them know me is this is a radiopharmaceutical and it's not uncommon early in a program to get a very good sense.

On how it's going to work because the mechanism of action first of all.

Well known it's well accepted energy transfer to the tumor is efficacious.

And and more is better.

We have the delivery problem solved for both the GBM and <unk>. So thats very effective as has been presented and as you are well aware and we've shown that the increasing doses where.

We've done during the dose escalation remain very well tolerated.

And quite.

In a sense predictable because we're not using exhaust of doses are extremely high doses, they've all been well tolerated without any observed <unk>.

Limiting doses or maximum tolerated doses observed or identified so we're on very solid ground for a very good therapeutic index. The safety margin is.

It's very comforting and robust and people have recognized this and in fact, many times will get unsolicited request for interest in our programs because they have seen.

<unk> seen our presentations at one of the several meetings we participated in.

And last but not least is what we all know.

For both LMR, GBM, but particularly ILM.

There is nothing out there for these folks there is there is no therapies nothing works there is not really very many investigative programs.

<unk> is really <unk>.

Waistline options for patients. Unfortunately, and people are recognizing that this is something there and then GBM. The data speaks for itself and you really can't you can't ignore that preliminary signal at all and I think when we can report.

Hopefully and acceptance in a major impact journal that Mark mentioned.

There'll be further recognition on this preliminary data. So thanks, thanks for that question.

Got it maybe just one for.

For Mark and kind of build builds on what you are saying about some of the interest that you guys have been getting Im sure you cant speak to specific potential partners, but I'm wondering if you can shed any light on the types of conversations you're having or would like to be having or are they primarily related to potential combination therapies or other.

Those types of opportunities.

Hey, Justin I would like to.

We've.

We've done three transactions over the last one transaction a year as we work to expand the pipeline build.

Build it out.

And so.

Yes.

Is there kind of across the board quite honestly.

We're very promiscuous in terms of discussing and evaluating ways, we can build value for shareholders.

Whether thats out licensing our <unk> licensing so we continue to expand those discussions and as the data gets out there that things that Norman presented.

Those get more and more notoriety.

Increases the number of discussions so it can be really hard to say much about that at this point.

That.

The conversations are increasing not decreasing.

Got it and one more for me.

Just sort of speaking to the I guess some of the general tones here. It seems to me like we're at a.

Yes.

Let the Doctor comment.

Scientifically and we've been doing this for a year or two and knows a lot about the space and has seen it evolve probably has more drugs approved under <unk>.

His watch than anybody in the country radio therapeutic space, but.

So.

Starting maybe early 2021 and then just on the you know this because youre in.

Well.

We're seeing banks increasingly add.

Analysts that are dedicated to radiotherapeutic. So that's an important.

I think an important milestone there is bank coverage as analyst coverage.

There are as capital flows into the space.

There are.

Manufacturing infrastructure, Thats being funded and built out in anticipation of the market coming.

So.

And then you see major players doing deals in this space. So we see a lot of really promising.

Movements in the capital markets.

That are pointing to <unk>.

Years ahead of us of growing value in this space. So we cannot be more.

More excited to be here at the ground floor and one thing that's different about US I think you know Justin is we have real data.

There are a lot of companies that.

Have are building infrastructure, but we are.

Where we're building data profile that I think is very exciting and a group of diseases.

Don't have good options.

So, yes, we're very optimistic and bullish Dirk do you want to collaborate.

Collaborate.

I think what Youre asking.

You are mentioning.

The <unk> space, which is very crowded it's been successful. The recent approval there are several out there and as you will know before that was the.

Serotonin receptor Dota Tate approval, which has been successful and quite frankly in the literature and the meetings. That's that's.

<unk>, what's been talked about understandably and they burn they've earned that with some good data and some good results.

And all due humility I'd like to add that when we presented at the European Association of nuclear Medicine.

You may notice that they have a highlights presentation at the beginning of the meeting to present, what they with the reviewers and the leadership of that society feel are the.

The up and comers or the new data things that pay attention to.

And our.

GBM.

Data presentation, there, which I did was chosen for the highlights lecture is the first presentation now admittedly there was a PSA MA paper in a.

Got a picture for prosperity in the sense of noting that this was.

This is quite in advance that they recognized.

Definite radiopharmaceutical that rather than the classic systemically administered using some elegant biochemistry or targeting mechanism, which is.

Which is elegant and something thats very straightforward and had some very incredible data that they pointed to very carefully so.

We've we've made to highlight lectures and I think this is recognition by the field that there are other.

Other candidates out there aren't going to make a difference.

Well I look forward to seeing the continued building of this.

Data set and thanks for taking my questions.

Okay.

Thank you.

Thank you one moment for our next question.

Our next question comes from Ed Woo with <unk> capital. Please go ahead.

Yes, congratulations on the progress in 2022, and that's definitely congratulations on the <unk> Grant.

Are there any possibility of visibility that youll be able to apply for the grants for any other indication.

Hey, Ed. Thank you for the question I think you mean the <unk>.

Secret Grant are we going to be able to apply that to other indications.

No I mean in terms of getting grants for other indications coupled with a new grow got it.

Got it yes no.

The question so.

You know we've been we've been successful knock on wood.

And getting third party grant support in terms of the NCI Grant Vascepa Grant one of the reasons, we moved to Texas.

Easy to say now that we have a grant under our.

And our sleep, but was that we thought that $6 billion of capital for cancer funding.

Be able to get some of that to fund our programs in <unk> that we were we were fortunate to be able to do that.

We know of companies that have.

Up to three separate grants.

So so we do in fact think that some of our programs that arent funded.

Or aspirational programs that we'd like to bring on board, but because of our.

Internal frugality.

Frugality about capital deployment in other words, we don't we don't want to.

Spend it until we raise it that there might be some opportunities there so.

Our plan and that was the milestone this year, so we're going to submit more than one grant clean.

Including the secret, but also potentially other grants that some of our opportunities that we have available to us.

Fund.

Additional programs to build out the pipeline so that's our goal.

Those can be hard to get but we're going to submit them and we think we've cracked the code to a degree on secret and we think there might be some greater opportunities ahead of us there.

What was the timing in terms of when you submitted your application to when you got.

Awarded the graph.

For the.

L M Grant.

Yes.

Yes actually.

It was I think about 18 months. So we submitted a couple of iterations, we got close a couple of times and like.

Like with the NIH.

We expect feedback how you can improve the grant we worked in the background to continue to advance.

The program, while we were continuing those dialogues.

So.

I think that.

Treating a patient really.

Really helped convince them and the data that will help convince them that this is something that's worth funding so.

Yes.

It's like all the grants typically sort of iterative key is being persistent.

Having data data helps.

Right.

Definitely congratulations and definitely looking forward to more good news from you guys. This year. Thank you.

Thank you Ed.

Thank you one moment for our next question.

Our next question comes from Sean Lee with HC Wainwright. Please go ahead.

Good afternoon, guys and thanks for taking my questions.

My first question is on the Phase II GBM study can we expect the data readouts from that prior to <unk>.

Full patient enrollment expected by the end of 'twenty four.

It's an open label non blinded study so the short answer would be yes.

To give you more details it will be as I I think I was answering justin's question on the <unk>.

<unk> <unk> of statistical analysis.

I would expect us to have some reviews of the different types of analyses just because there is a lot.

Lots of ways to utilize those to form the design of the Registrational trial. So.

I'd like to give you more detail, but the short answer is yes.

It'll depend on how the data develops and if we can certainly accelerate the accruals.

Even faster will be in a position to move on that more quickly and part of that will be in our preparation to go to FDA. So.

We plan to share that I can't give you exact timing however.

No issues, thanks for the additional color.

My second question is on the upcoming pediatric study what are some of the key learnings and takeaways from GBM.

GBM trial that you feel could.

Help you will apply to the pediatric study and make it more successful.

Yes.

Great question very.

Very applicable and we actually leverage the pediatrics.

Questions and presentations to the FDA, we leveraged our adult data significantly.

That in fact result in the FDA asking.

Not asking questions, but more clarifications on that data, which is a good thing because it gets them more involved in that data.

The first interactions with FDA was to kind of include all comers in pediatric brain tumors, which is a broad spectrum.

And that initiative and first in pediatric patients for any drug, particularly a radiopharmaceutical.

FDA is careful and conservative.

We got that feedback for example, we are limiting the tumors to super <unk> and the ones with high unmet medical need with terrible prognosis depth pendant moments in the high grade Gliomas.

We have had most recently the FDA agreement by the reviewers for the pediatric protocol and just show them some last.

Considerations and so Mark do you have anything else said on this.

Well just let's.

The thing I would add to that Sean is.

And we mentioned this before in the adult <unk>.

Adult trial deliveries the key if we can cover the tumor with enough radiation, we're going to kill the tumor period sort of enter into discussion.

We translated that data directly into the pediatric population and so that I think that really gives us confidence going that trial that we can we can deliver the drug. The other thing is it's very common to put electrodes into the brain and these these kits so.

We have high degree of confidence that the.

Convection delivery process will be well tolerated, so we're really able to leverage both.

Epilepsy treatment data as well as our adult delivery data to feel confident going into this trial, we're able to able to convey that successfully I think to the FDA given the fact that.

The clinical protocol.

Thank you for that that was very helpful.

My last question is on the.

Pam product I know it might be a little early but are there specific indications, where you feel the product will be particularly well suited for.

Yes.

Our initial target is going to be for Hepatoma.

There are two drugs on the market that are kind of long in the tooth they're non bio resorbable. They are used to treat up to 12 I think it's about one 2 billion odd.

Opportunity.

But those are permanent and we're providing a drug that has different radiotherapeutic different characteristics that are.

Related to the iridium that make it more attractive.

So lets resorbable. So the idea is you kind of talk.

Tuned the buyer absorption.

Timing so that by the time the radiation is.

Fully decayed or near fully decade.

<unk>.

Embolic has been by our Resorbs.

Vascular potencies resumed and you can go back in and re treat the patient multiple times. That's the idea. So this would be a very differentiated unique novel product and so livers.

First but potentially we could go any any tumor that you can target buyer.

Radio.

I think our initial target is there is an existing market.

Great. Thanks, Marc and that's all the questions behalf.

Thank you Sean.

Thank you as a reminder to ask a question. Please press star one on your telephone are there any written questions today.

Okay. Andrea we have we have one written question.

The other.

Further written questions that have been largely answered this question.

Walls around our <unk> trial and the use of novel.

Cell testing approach to determine biological response was.

How is that important to your trial.

Going forward and in your development plans so.

Yes, Youre talking about what you said.

Interesting test called CNS side.

It's manufactured by a California company.

Thus far we are I would say, we're incredibly pleased with that test and I think it fills.

A critical gap in.

The diagnostic and therapeutic approach to these patients.

The.

The current.

Existing weigh that.

Mmm is diagnosed is by a mix of imaging and imaging is not great.

Clinical findings, which are often very vague and nonspecific.

And then the.

CSF lumbar puncture results, which look at glucose protein and cell count, which is the same thing that Norman and I use when we are in medical school.

A year or two ago that is very nonspecific.

And very non sensitive for that so.

I think as I've mentioned in the first four patients where we have data on <unk>.

Significant reduction tumor cell counts as measured by that assay. So.

We're very we're very pleased with what we've seen thus far but it's very early.

Another relevant piece of information is L. M is significantly under diagnosed so.

Only about 25% of patients with LMR diagnosed we know that based on the autopsy data. So there is an opportunity to increase the total addressable market.

<unk> for our therapeutic by up to four times.

That opens up a pretty significant.

Increase application for the test and.

Groups of antibodies and look at specific.

Epitope expression.

<unk> insight to hybridization and genomic analysis as part of that test too.

Taylor therapy.

In terms of using systemic <unk> immunotherapy and so forth.

Beginning to explore and are Super grant so.

That's a good question and we think it's going to be very important long term to pair the the therapeutic with with diagnostic like this and innovative.

Okay to think about it almost like a companion diagnostic.

And that's the that's the only question that's on.

And answered so Andrea anything else.

I'm not showing any further questions right now.

Mark if you'd like to close it out.

Yeah. So thanks to everyone for participating on the call today appreciate your interest in the company.

Once again, thanks to our employees and are collaborating physicians and scientists that we work with on a daily basis.

We're very appreciative also for the patients who are enrolling this trial that need his help in.

And trust us to deliver for them and their families. So we're very appreciative to them. So we look forward to continuing the updating process.

And as we move forward and thanks also to our stockholders for their continued support and confidence. Thank you.

Okay.

Yeah.

Thank you for your participation in today's conference. This concludes the program you may now disconnect.

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