Q2 2022 Plus Therapeutics Inc Earnings Call
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Good afternoon, ladies and gentlemen, and welcome to the plus Therapeutics second quarter 2022 results call 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 have.
Effect, 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 the plus Therapeutics annual report on Form 10-K, and quarterly report 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 circumstances. After the date. They are made it is now my pleasure to turn the floor over to Dr. Marc Hedrick plus therapy.
<unk>, President and Chief Executive Officer, Sir you may begin.
Yeah.
Thank you Jonathan I appreciate it.
Good afternoon, everyone and thank you for once again, joining us today as we provide an overview of recent business highlights and discuss our 2022 second quarter financial results.
Joining me on the call today is Dr normal of France, Our Chief Medical Officer, and Andrew Sims, Our Chief Financial Officer.
I'll begin the call by reviewing our recent corporate and clinical progress before turning the call over to Andrew to review, our financials and Dr. The France will be joining us for our question and answer period.
Okay.
I can say with a tremendous amount of certainty that 2022 is shaping up to be an outstanding year progress for plus therapeutics across all fronts I continue to be very pleased with our team's performance in critical areas, such as drug manufacturer and clinical development.
Also I'm very excited about the performance of our 186 Arnelle drug in our two active clinical indications glioblastoma and Leptomeningeal metastases while.
Still in the early to mid stage of clinical development 186 are enel is functioning biologically in a manner that is very consistent with its original design objectives, and showing a solid safety profile, coupled with a biologic response.
So let's start with Iridium <unk> six nano light to some development program and specifically our CMC activities.
In July 2022, the company completed the technology transfer and initiation of cgmp manufacturing of the 186, Arnelle drug intermediate with Paramount Pharma solutions. Additionally.
Additionally, the intermediate drug product is.
Testing and we believe it to be compliant with FDA guidance for manufacture of nano life somewhat drug products for use in late stage clinical trials and even commercialization.
We expect to have GMP drug availability in the second half of 2022 on time for ongoing and planned phase III clinical trials in adults with recurrent glioblastoma leptomeningeal metastases and all future disease targets.
In Q2, the company submitted a briefing package to the FDA to seek their opinion on the sufficiency of the <unk>.
Six are in our CMC development plans for GMP drug manufacturer.
The company anticipates, making a summary of those meeting minutes public when finalized.
Regarding the.
GBM program.
This trial is enrolling currently and it is a dual phase <unk> multicenter sequential cohort open label volume a dose escalation study for recurrent glioblastoma.
The trial is currently funded to a significant a significant degree by the U S NIH and the National Cancer Institute.
In July of 2022 at the society for nuclear Medicine, and molecular imaging.
Annual meeting Dr. Bill Phillips presented positive interim data on our lead investigational drug 186, Arnelle for the respect GBM trial in patients with recurrent GBM during.
During the presentation. The company noted that the trial is evaluated 23 adult patients with recurrent GBM across seven cohorts of.
With increasing dose to date after a single administration there have been no dose limiting toxicities.
And promising efficacy signals have been observed in patients receiving an average absorbed dose of radiation of greater than 100 Gray.
As presented in Q2, the most recent data shows a two year improvement in median overall survival in patients receiving greater than 100 gray versus those receiving less than 100 gray.
Furthermore, in the greater than 100 gray subset of patients. The median overall survival of 130 weeks compares favorably with real world data and a recent meta analysis of similar patients receiving monotherapy bevacizumab and that was about 38 32 weeks median overall survival.
And this data is referenced in detail on our website.
As planned we submitted a second briefing package to the FDA for the purpose of defining the clinical development plan for <unk>.
This is the company's first formal detailed clinical correspondence and interaction with the agency since the in license of <unk> in mid 2020.
Based on the positive safety profile and promising efficacy signals observed thus far and what is a very poorly met medical need wed like to determine the agencies opinion of the best next steps for ongoing clinical development.
This we intend to craft a collaborative longer term plan, leading to a potential new drug approval for what is a very unique and novel combination of a radiopharmaceutical and novel delivery methodology.
The company anticipates, making a summary of those meeting minutes as well public when finalized.
Big picture based on the data observed thus far we believe the best overall clinical development path forward would incorporate at least a three pronged approach.
First to continue the current phase one two trial to explore further dose escalation as we have yet to observe dose limiting toxicities and also continue to work to further optimize the delivery and dosing parameters.
Second.
We intend to explore serial of dosing.
And in Q2, the FDA allowed the company to proceed to a multi dose extension trial to go after tumors.
Again, either either if they recur or if in key areas of the tumor where incompletely treated with a single administration. This is going to allow us to potentially treat larger tumors are those with significant morphologic geometric complexity that may be difficult to completely treat in a single administration.
Finally, we feel the cohort dose and.
And volume is likely appropriate to move forward as a recommended phase II dose.
To treat patients with small to medium sized tumors.
Whether that's in the current phase II NIH sponsored trial, that's ongoing or combined phase two or phase III trial design sponsored by the company that will be up to our discussions with the FDA.
Taking a step back and putting this in the big picture the.
The combination of studies I, just mentioned allows us to begin to explore.
And solve for a big Dream, which is to transform brain cancer from a death sentence says it's today to a chronic disease managed by serial arnelle treatments as needed for each patient throughout their disease course.
This fall the trial's principal investigator Dr. Andrew Brenner, who will provide a full data update on the phase one to respect GBM trial at the European Society of medical oncology.
Paris, France, and that's going to be September 19 to 13th we don't have the exact date and time, but that will be a podium presentation.
As to our Leptomeningeal metastases, our <unk> development program. This trial as a reminder, is a multicenter phase <unk> dose escalation study to determine the maximum tolerated dose safety and efficacy of <unk> hundred 86, Arnelle an L M.
To remind you <unk> is an end stage typically fatal complication associated with advanced cancers that infiltrate the fluid line structures of the central nervous system or <unk>.
The incidence of <unk> is growing with better local cancer care.
Median survival.
With current aggressive treatment is about three to eight months, depending on which primary tumor actually caused the LTM.
The one and two year survival rates are about 7% and 3%, respectively and survival without treatment is about four to six weeks.
The most common tumors, giving rise to <unk>.
Center gastrointestinal malignancies in melanoma.
There are no approved therapies and standard treatment includes a grab bag of things such as external beam radiation therapy to the affected sites.
Followed potentially by chemotherapy that can be given orally intravenously or commonly administered twice weekly directly into the cerebral spinal fluid space until the patient can no no longer tolerate the therapy or passes away.
In Q2, the company completed enrollment on time of cohort one of the respect <unk> phase <unk> dose escalation trial of 106 Arnelle.
186, Arnelle was successfully delivered without dose limiting toxicities and this initial cohort.
And the independents that respect LMS trial data safety monitoring Board has approved the plan to move ahead with cohort two which we are in the process of doing.
Also in Q2, the company announced that we had entered into a multi year agreement with <unk> incorporated to employ it's cerebral spinal fluid assay system and their respect Lf trial by.
<unk> assay provides a highly sensitive method to assess and quantify tumor cell burden and.
The central nervous system and also allows us to look at specific tumor cell markers and indicators of radiation damage assay results will be used to evaluate biologic response to the treatment and treatment efficacy and ultimately potential the termination of the time.
And your cadence of re treatment in patients enrolled in the trial.
Finally regarding our novel recently in licensed radio Embolic micro particle technology called 188, Arnelle Bam or just Bam.
We have completed the technology transfer phase and are on track to complete key CMC feasibility activities and certain IND, enabling preclinical studies by the end of the year and we're on track for that.
In addition, we are planning to meet with the FDA for a pre R&D meeting this year as well.
With this resorbable biomaterial embolic technology, coupled with our highly potent radiotherapy pudic isotope. We believe we can target almost any solid organ tumor in the body using standard interventional radiological means and leverage the breadth of the human vascular.
System to selectively reach only the tumor.
Without having to incur a cyst.
Stimac lease circulating radiotherapeutic that could harm the bone marrow or other organs of the body.
<unk> 188, analyte percent biodegradable alginate microspheres as a next generation fully resorbable technology that solves many of the existing problems with current radio embark technology.
Been out there for many decades for the treatment of liver cancer.
And our plan is to initially focus developing the band technology as a next generation <unk> radio embolization therapy for non operable liver cancer, which has a very low five year survival rate of about only 20%.
And the drugs that are out there by a resorbable they're permanent.
So with that I'll turn the floor over to Andrew our CFO , who will review the financials Andrew.
Mark Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the 2022 second quarter ended June 32022.
As of June 32022, cash and cash equivalents were $18 1 million compared to $18 4 million as of December 31, 2021.
This represents 18% to 20 months of cash on hand.
Cash used in operations for the second.
In <unk> 2022 was $6 5 million compared to $5 4 million in the same period for the previous year.
The main changes between the second quarters of 2022 and 2021 are as follows.
Total operating expenses for the second quarter of 2022 were five $5 1 million compared to $2 6 million for the second quarter of 2021 the.
The increase is due primarily to the following.
Increased onetime development expenditures on CMC related activities to develop and produce GMP quality arnelle drug material.
The overall cost of this development program is in line with our original forecast of approximately $5 5 million.
<unk> expenditures are scheduled to be completed in late Q3, 2022 with only minimal additional stability testing expenses required on a go forward basis thereafter.
$1 million related to a combination of third party professional services and consulting and preparation for our planned FDA meetings as Mark mentioned.
The clinical trial planning activities to support the ongoing and future Glioblastoma development program.
The expenditures will be completed as planned in Q3 2022.
And to a lesser extent, an increase in legal IP and other general corporate expenses.
Interest expense decreased from 229000 in the second quarter of 2021 to a 181000 in the second quarter of 2022.
This decrease reflects the continued principal paydown that commenced in November 2021 on the company's Oxford debt.
Net loss for the second quarter of 2022 was $5 3 million or <unk> 24 per share compared to a net loss of $2 8 million or 25 per share for the second quarter of 2021, now I'll turn it back to Mark.
Great. Thank you Andrew before we move on to Q&A, Let me just summarize key milestones anticipated for the remainder of 2022.
So besides of course, continuing to work to meet our clinical enrollment goals.
We intend to present respect LTM cohort one data at the society of neuro oncology.
Brain Mets meeting August 12 to 13th in Toronto.
We also intend to present the respect GBM phase one data at the European Society of medical oncology and.
In September in Paris, we intend to report on our two planned FDA meeting minutes in Q3, one for CMC and one for the respect GBM ongoing clinical program.
We anticipate achievement of our GMP <unk> hundred 86 are now manufacturing capability goal.
Soon and we'll make that public we also will communicate our planning process in an ongoing manner and the beginning of execution of phase III activities for respect GBM.
We intend to submit as mentioned.
A.
A protocol for respect pediatric brain cancer. The respect PBC trial later in the year, we will announce that and then finally, we'll announce a 188 Bam pre IND submission for planned clinical introduction in liver cancer and that will be right around the end of the year.
So at this point, Jonathan let me turn it back over to you and we'll take some Q&A.
Certainly ladies and gentlemen, if you have a question at this time. Please press Star then one.
One moment for our first question.
And our first question comes from the line.
Mccarthy from Maxim Group your question please.
Hey, guys. Thank you for taking the question is Michael <unk> on the line for Jason.
I'd like to see is.
You could provide a bit more on the mechanism behind the band program and how it behaves.
Differently in the body to enable that targeted use in solid organ cancers.
Hey, Michael.
Yes so.
Right now.
The data we have is preclinical only.
And.
But the idea is that unlike the two products on the market that are permanent glass or polymeric.
They are used for radio embolization this product would be bio resorbable and so we're still in the process of defining the.
The curve that the timing of that by a reserve ability, but but as I mentioned the idea is that you would identify the tumor.
You would.
Embolize the.
The area around the tumor to incorporate the tumor and the radiation delivery area and.
And then.
After some time after the radiation has been fully delivered and theres been full decay.
Then the body roll reserve that and reestablished perfusion, which they would potentially allow you to come back and retreat. If you needed to or there was further recurrent so thats sort of the general idea is that to answer your question.
Okay.
I believe.
Dropped off and then join rejoin the call.
Okay, No worries satisfy me.
Thank you.
One moment for our next question.
And our next question comes from the line of Ed Woo from <unk> capital. Your question. Please.
Yes.
Cohort one of the respect.
Trial.
How many patients was that and do you and enrollment go according to plan and what do you think would be the challenges to new cohorts number two.
Hey, Thank you.
Good.
To take a step back the FDA has asked us to.
Have a have a.
A three month period between the first patient in one court three months in.
First patient next cohort so sort of this.
Mandatory weight, we also have a 30 minute.
Excuse me, a 30 day delay between.
The first patient in the new cohort in the second patient, but we can do two and three relatively quickly so.
And best case.
We could get the first nine patients.
Enrolled around the end of the year.
And that's that's kind of going at the maximum rate depending on.
Kind of following that FDA.
Dictated schedule and then the trial.
Design incorporates at that point and this was a great suggestion by the FDA to come back to the FDA and then we will we will amend.
Based on the safety data, we will amend the data.
Collection and.
They provide the opportunity for re treatment to these patients so potentially we could come back and start providing additional treatments as we get increasingly increasingly more comfortable with the safety profile. So the idea is again just.
We'll try to get the first nine patients enrolled quickly assuming there are no safety issues of course, and that's kind of around the end of the year.
And then we'll go to the FDA there'll be a pause while we interact with the FDA and then we plan to come back with quite a bit number of sites.
There's a lot of interest in the trial.
And then we will move to hopefully additional doses in each patient and an expanded.
<unk>.
Profile.
Great and then the next question is you obviously had a lot of interaction with the FC.
And looking forward to putting out the notes that you guys have.
What has been a timetable with interacting with the FDA have things pretty much gone back to normal.
Post COVID-19 or are you still seeing possible delays here and there.
Yes so.
Most of our.
Most of our interaction with the FDA.
That has been more recent.
And.
To answer your question.
Both to myself and to our Chief Medical officer, and our and our regulatory consultants. So I think we've been very happy with the turnaround and the.
And the interaction it's been great.
It seems totally normal.
Alright, thats good to hear it well that's all the questions I have I wish you guys. Good luck. Thank you.
Thank you.
Thank you once again, if you have any questions at this time. Please press Star then one.
And we have a follow up from Jason Mccarthy from Maxim Group one moment.
Sorry about that.
Amped up the call for <unk>.
No.
Problems.
I would like to see if you could discuss a bit further with the collaboration with <unk> that does for your clinical trial in <unk>.
How do regulators view the use of CNS side to guide treatment and cannot be used as a surrogate endpoint for response monitoring or is it more targeted at just collecting additional data to support the development.
Yes, so the <unk>.
Ultimate use of this has yet to be determined we do think there is an opportunity to potentially use it as a surrogate endpoint.
In fact, I am sure it will be now whether it's ultimately it becomes a primary endpoint or secondary endpoint or something else. It's it remains to be seen we will see what the data shows I think that would be <unk>. So that it would be a meaningful.
Follow up endpoint in these patients.
So the way I look at it is that.
This is this is an interesting disease because all of these patients have my reservoirs in them that we use both therapeutically and as I mentioned I think that the current treatment. It's typically important in this patient patients come back twice, a week and half chemotherapy injected into the <unk>.
Port well, there's also the opportunity at any point in time to withdraw CSF.
And measure certain things.
What we've done thus far with <unk> is simply measured tumor cells per ml and report that and I Didnt mentioned this youll see the full data set in August but in.
In all three patients we've treated we've seen dramatic reductions in tumor cells that are persistent out.
With a single administration, so that that these tumor cell data is looking like it is.
It's providing information.
That supports biologic activity of the radio therapeutic in the CSF. We're also looking at.
Other tumor cell markers more an exploratory phase and also intend to look at markers of radiation related damage and do that again as exploratory phase with with <unk>. They have much greater capability beyond just the.
Physical counting of tumor cells. So we think it's.
<unk> has a lot of potential utility and potentially even guiding therapy, I mean, one could imagine that.
Patient gets treated you follow there.
Certain markers, including tumor cell count.
Over a period of time and you make your re dosing decisions based on the data you find from from.
From repeated or serial CSF sampling.
Alright. Thank you very much and then just one last one from me.
I'd like to just ask if there are any unique challenges associated with the treatment of LNG compared to something like Glioblastoma.
Yes.
I would say.
On the downside.
Relative to GBM.
These patients can be very fragile and so we've had.
We've had a couple of patients too.
We had.
We're on track to treat in a D compensated.
They are they are survivals are very low even even with treatment.
Low so but from the time they've had their my reservoir placed.
<unk> had there we do have flow study just to make sure. There's good flow from the <unk> to the rest of the of the CSF space the patient to be compensated and they no longer.
Match, the inclusion exclusion criteria so for us.
The key there is simply to make sure that we compressed the time.
Down and then also we make sure that we.
Ideally have more patients than we have.
We have drug so that we don't.
Nope.
Slowdown in enrollment trial.
You didn't ask about this but on the flip side I'll just volunteer that.
These are much easier patients to enroll in the sense that.
Physicians are very interested in this trial there is a lot of interest in participating the patients deficiency that we talked to see multiple patients a week that would qualify.
I think this trial can enroll very quickly once we get.
At a more mature phase of the development plan.
And Theres a lot of a lot of physician interest in this drug.
Alright, Thank you very much I really appreciate the additional color.
Thanks for the question Michael.
Thank you once again, if you have a question. Please press Star then one.
Okay.
And this does conclude the question and answer session of today's program I'd like to hand, the program back to Dr. Marc Hedrick for any further remarks.
Thank you Jonathan just to close I want to thank everybody that joined us on the call today and provide my appreciation also to stockholders employees.
<unk> and consultants with whom we work in the patients who trust us so as always.
We will work to provide full of frequent updates as we move forward with these various programs. Thank you once again.
Thank you, ladies and gentlemen for your participation in today's conference. This does conclude the program you may now disconnect good day.
The conference will begin shortly to raise your hand during Q&A you can dial stolen.
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