Q3 2021 Plus Therapeutics Inc Earnings Call
Good afternoon, ladies and gentlemen, and welcome to the plus Therapeutics third quarter 2021 results call. At this time, all participants have been placed in a listen only mode and the floor will be opened for your questions. Following the presentation.
Even like.
So a question at that time, Please press star one on your telephone keypad. If at any point. Your question has been answered you may remove yourself from the queue by pressing the pound key we ask that you. Please pick up your handset to allow optimal sound quality. If you should require operator assistance. Please press star zero.
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.
Such statements are subject to risks and uncertainties, including the risks and uncertainties described.
And under the risk factors section included in the plus Therapeutics annual reports on Form 10-K, and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time.
<unk> Therapeutics advises you to review these risk factors and 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 that they are made.
It is now my pleasure to turn the floor over to Dr. Marc Hedrick, plus therapeutics, President and Chief Executive Officer, Sir you may begin.
Thank you very much Ashley.
Good afternoon, everyone. Thank you once again for taking the time to join US today as we provide an overview of recent business highlights and discuss our 2021.
Third quarter financial results.
Joining me on the call today is Mr. Andrew Sims, our Chief Financial Officer.
Before Andrew provides a summary.
Murray of our financial performance I would like to provide an update on the companys business activities since our last call.
Big picture in the third quarter, we made good incremental progress toward our mission to become a global leader in developing and delivering precision targeted radio therapeutics for cancer.
Specific.
Clearly we received clearance from the FDA for our investigational new drug application for the use of <unk> 86 in patients with lepton Meningeal metastases we.
We also entered into an agreement for the commercial production of our Radiopharmaceutical Arnelle 186.
And we continue to strengthen our leadership.
Specific team with the appointment of a highly experienced chief Medical officer, Dr. Normal in the France. Finally, we presented data at the <unk> meeting as well as obtained accepted to present data from their respect GBM trial at both Astro and snow.
I'll cover these achievements in more detail in a moment.
<expletive> to that'd be first provide a summary of plus for those new to the company.
Our lead investigational targeted radiotherapeutic as our Enel Iridium near end of life the film.
This is a proprietary lipid somone encapsulated radionuclide that is deliberate local regionally via targeted three dimensional.
But convection enhanced delivery.
It is administered directly to the tumor.
The active agent is rhenium 186, isotope, which is a dual energy emitter, releasing both cancer, killing beta particles, which are high energy electrons and gamma particles, which are useful for imaging and dosimetry.
<unk> is a very unique isotope in part because of its energy profile it.
<unk> energy has a short path link which provides delivery precision.
Our low dose rate, which provides a margin of safety in a high energy density, which is particularly toxic for highly mitotic cells.
Cancer.
<unk>, which can overwhelm the DNA repair mechanisms that could otherwise contributes to radio resistance.
Thus far we've shown that we can successfully deliver.
20 times, the radiation dose one can deliver with traditional external beam radiation.
Our initial indication for arnel as recurrent glioblastoma.
Blastoma, which affects approximately 13000 patients annually in the U S and about the same number of patients in the EU.
It is the most common and lethal form of brain cancer in the treatment of this devastating disease remains a significant unmet medical challenge.
Published studies indicate that.
<unk> beam radiation provides the best incremental improvement in survival of all therapies currently used for Glioblastoma, which is about five months.
And it remains an essential component of multimodal therapy for both Glioblastoma and in fact, many other cancer.
But it is limited by the complications.
Extra them higher dosages.
[noise] Arnelle is currently under evaluation in our U S respect GBM trial, which is a dual phase one and phase II multicenter sequential cohort open label volume in dose escalation study of the safety Tolerability and distribution.
Of 186 Iron out the trial is currently funded to a significant degree by the U S National Cancer Institute.
We are now into an eight dosing cohort following the data and safety monitoring board recommendation to proceed to the next incremental cohort and to date, we have treated 20.
<unk> stroke patients.
We provided interim results during the recent Canaccord Genuity and Wainwright investor meetings and that data can be found on our website.
Notably cohort eight represents a 40% increase in both dose and radiation radiation compared to.
Two seven.
Thus far in the respect trial highly targeted and continuously infused or convicted volumes of up to $12. Three milliliters containing 31, 'twenty militaries of radiation have been well tolerated.
Up to four catheters can be successfully placed for delivery.
The best accommodate a variety of tumor sizes and geometries.
Our analysis been shown thus far to be safe and well tolerated despite delivering up to 740 gray of absorbed radiation to the tumor.
Which again by comparison is 20 times the radiation dose typically do.
Cohort by <unk> in the recurrent setting.
Yeah.
Regarding safety.
And this data is as of August one 2021.
There have been no adverse events or aes with the outcome of deaths or discontinuation due to aes.
<unk> 40 of Aes reported with mild and moderate that's grade, one or two and intensity and non serious.
The adverse events or Aes were the highest incidents were fatigue muscular weakness.
The headache.
And also gait disturbance, most aes were considered causally unrelated to our enel.
The minute one case of scalp discomfort, which was considered related to the surgical procedure in one case of cerebral edema.
He's with grade three or leukocytosis, hyperglycemia muscular weakness seizure brain edema worsening a vascular necrosis of the shoulder basic <unk> cerebral edema and pneumonia.
All of these events were considered unrelated to arnelle by the investigator with the exception of brain edema for one subject, which was considered possibly related to our health.
Serious adverse events or S. Aes were reported for two subjects in cohort two namely seizure invasive cerebral edema.
One subject each in cohort four and five both seizure and two subjects in cohort six pneumonia and worsening a vascular shoulder necrosis and cerebral edema.
All of these events were considered unrelated to our enel by the investigator with the exception of cerebral edema for one subject, which was considered possibly.
It's Arnaud <unk> tapering of oral corticosteroids, none left led to study discontinuation.
There were no meaningful differences are patterns and the incidence of related treatment emergent aes reported across individual treatment groups or cohorts.
Neither the incidence nor severity.
Relatedly of Aes appeared to be appeared to increase with increasing doses of <unk>.
As to the important issue of drug delivery feasibility.
There have been no delivery failures, thus far.
We can safely deliver up to an average absorb.
Severus of 740 Grand radiation to tumors.
The mean absorbed radiation dose to the tumor is 392 great.
Up to four catheters can be used for delivery and the mean percent tumor coverage with the radiation is 90%.
Although the phase one trials.
They're not designed nor powered for efficacy, we see promising signals of biological effect and potential efficacy.
As mentioned previously imaging based measures of progression are challenging.
As the substantial tissue effects of the treatment often show up pseudo progression.
While we analyzed.
Sales in the imaging results in an ongoing manner. We look closely also at the gold standard endpoint survival.
Three of 22 patients have survived up to 30 months or more where average survival for the current GBM with standard of care is only about eight to 10 months.
Many of those.
<unk> chips have been treated relatively recently and at the higher dosing and volume cohorts. It understandably makes.
Definitive efficacy determinations on overall survival challenging.
But as to the issue of overall survival, what I can say.
We have observed that increases in both connect.
Patient volumes and radiation dosage seem to correlate with better tumor coverage and higher tumor absorb doses in this in terms seems to correlate with overall survival and this is what one would expect based on the biology of radiation therapy in these tumors.
And as of August one 2021, eight of 22 patients remained alive.
And the early cohort of 13 patients enrolled between 2015 when the trial started prior to our involvement to 2019, where we had the longest follow up only five or 13.
<unk> had absorbed tumor radiation doses greater than 100, gray and tumor coverage percentage greater than 75%, which in our view our key biological thresholds.
The average survival overall survival in these five patients was 769 days or about 25 months and.
And to pay.
Patients are still alive in this cohort.
In the more recent cohort really since we took over the trial.
Of those nine patients treated.
Enrolled since 2027 of nine had both absorbed tumor radiation doses greater than 100 grade and a tumor coverage percentage of greater than 70.
Per cent, a much better delivery success percentage, because obviously at the higher volumes and radiation doses were administering in these higher dosing cohorts. The average overall survival in these seven patients is 173 days, but six of these patients are still alive.
We.
<unk> provide a full update at the November society for Neuro oncology meeting in Boston.
Later this year.
Furthermore.
Our team continues to make excellent progress in our drug scale up and manufacturing activities and is simultaneously putting in place the essentials for commercial readiness.
We will pacifically during the third quarter 2021, the company entered into an agreement with radio medics incorporated for the commercial production and logistical support of the company's investigational radiopharmaceuticals.
Thus far in 2021, the company has entered into five collaboration agreements to support its process development and analytical.
This three activities as well as to strengthen its supply chain and compliance with good manufacturing practices for the manufacturer of the 186 are enel investigational drug the company remains on track to deliver GMP 186 iron out by mid 2022.
Looking forward.
<unk> the company will present interim data from its respect GBM clinical trial at the 2021 Astro annual meeting scheduled for October 24% to 27% this year and if the 2021 society for neuro oncology annual meeting an education day scheduled for November 18th to 'twenty.
One also of this year.
In addition at four PM Eastern standard time on November 18th this year at snow in Boston.
<unk> will sponsor and in person and virtual scientific round table discussion and Q&A period with respect to trial principal investigators at that time, we will provide.
<unk> actual clinical update on the safety and potential efficacy data as of that time point, including a discussion of potential next steps.
In parallel we expect to continue to enroll patients in cohort eight this year ideally completing this cohort in Q4 of this year.
And based on that timeline, we intend to present.
Present, the clinical data set to the FDA in the first half of next year and determine next steps.
Regarding additional indications.
<unk> is also being developed for.
For other diseases, including let them in.
Sustainment, NGL metastases and pediatric brain cancer.
Leptomeningeal metastases are L. M is an increasingly common secondary cancer complicating.
From other cancers and based on the increasing overall survival rates that we're seeing with better therapies.
For.
Very solid and hematologic tumors.
L M effects over 100000 patients per year in the U S and patients can present with a broad range of signs and symptoms is a simultaneous involvement in multiple areas of the cranial spinal axis.
Earlier this week, we announced clearance of our IND application from the FDA.
Primarily for 1600 <unk> for the treatment of <unk>, we expect to initiate patient accrual in a phase one dose escalation trial in the fourth quarter of 2021, the trial will be called respect L. M.
It'll be a multicenter sequential cohort open label single dose dose escalation phase one study of.
<unk> Tolerability bio distribution dosimetry and anti tumor activity of 186, Arnelle given intraventricular Lee.
We have a standard Amaya reservoir the subjects over 18 years of age with L. M.
The primary endpoints of the study are the incidence and severity of adverse events.
Vince and SaaS and the incidence of dose limiting toxicities the secondary endpoints of the overall response rate duration of response or excuse me duration of response progression free survival and overall survival.
And the planned forthcoming trial really just speaking as a practical.
The <unk> to help you understand what we're doing we intend to administer arnelle via common indwelling catheter as I mentioned, our reservoir called EMI reservoir.
Sits under the skin on the head and communicate directly with the ventricle and the left them in NGL or cerebral spinal fluid space.
As I mentioned this is continental.
<unk> and all of these patients with <unk>.
And really it makes the delivery of very straightforward issue.
Furthermore, the reservoir allows periodic.
Seth our staple spinal fluid sampling to occur and facilitates the use of tumor related biomarkers to follow patient response and enables.
The potential use of related surrogate outcome measures.
Sure.
Additionally, we believe there is an opportunity to help patients with pediatric brain cancer using <unk> now.
Based on our pre IMD meeting feedback received earlier this year, we intend to submit 90 in early 2022 to investigate the use.
The potential in kids with brain cancer.
Finally as mentioned in September the board and I are pleased to welcome Dr normal of France aboard as the Companys Chief Medical Officer Dr.
Dr with France, who will join Andrew and me on our forthcoming earnings calls.
Dr with France bring several deck.
Of arts of unique and highly relevant clinical regulatory and commercial expertise to the plus therapeutics management team.
He is actually a new nuclear engineer a board certified internist and a nuclear medicine physician.
He joined the industry, a while back after leaving his clinical practice at Johns Hopkins in Baltimore.
He has a proven track record and radio Therapeutics and drug development regulatory affairs drug lifecycle management and related commercial experience here.
He has brought numerous radiotherapeutic successfully to market.
And as background will be important to our success as we expand our pipeline.
<unk> key programs.
Decades clinical development and positioning the company for long term regulatory and commercial success.
At this point I'll stop and turn the call over all the gantry appropriate review in the third quarter financial results Andrew.
Mark and good afternoon, everyone.
Please refer to our press release issued earlier today for a summary of our.
<unk> results for the third quarter ended September 32021.
As of September 32021, cash and cash equivalents were $21 3 million compared to $8 3 million as of December 31, 2020.
Cash used in operations for the first nine months of 2021.
Our financing at least $7 6 million compared to $5 2 million in the same period in 2020.
With the key components of the cash used in operations and main changes between 2020 and 2021 as follows.
There was no revenue in the first nine months of 2021 as compared to approximately 303.
Was the pricing in the same period last year.
This decrease was due to the closeout of the legacy government contract as previously disclosed.
Research and development expenses were $3 7 million for the first nine months of 2021 as compared to $1 6 million in the same period of 2020.
The increase of $2 1 million was anticipated and reflects additional arnelle CMC development costs to obtain cgmp drug product for the plans for pivotal Registrational trial.
G&A expense was $4 8 million for the first nine months of 2021 as compared to four.
<unk> 1 million for the same period in 2020. This increase is mainly due to an increase in legal and other professional fees.
Interest expense decreased for the first nine months of 2021.
<unk> 708000 from approximately 854000 for the same period in 2020, reflecting the pay down of debt.
To go to $4 3 million in 2020.
Net loss for the nine months to September 32021 was $9 2 million as compared to a net loss of $4 6 million for the equivalent period in 2020 <unk>.
Excluding the book gains on the warrants of $2 3 million that we reported in the first quarter of 2012.
The change in net loss reflects the incremental R&D and G&A spend as I mentioned earlier.
And now I'll turn it back to you Mark.
Thank you Andrew.
Before we move on to Q&A, Let me just summarize the milestones we anticipate over the next few quarters.
You mentioned many of these already.
But I'll summarize those here.
First of all with respect to that.
With respect to your respect GBM trial, we intend to complete the current cohort presented comprehensive trial update that snow as mentioned.
Upon completion of the current trial and data analysis, we plan a clinical meeting with the FDA in the first half of 2022.
To finalize the ongoing clinical trial plan.
Regarding the CMC activities for our <unk> we are.
Working toward completing key GMP manufacturing activities and remain on track to begin stability testing this year with GMP investigational drug products anticipated to be available.
It will have 2022.
We currently plan to CMC focused FDA meeting for the first quarter of 2022 to clarify and resolve any open CMC issues that may exist at that time.
Regarding the respect <unk> trial for Raptor meningeal disease with the IND approval, we plan beginning accrual as soon as this quarter 2021.
Regarding pediatric brain tumor therapy IND submission is planned for early 2022.
In terms of.
Our business development activities, we continue to be active in assessing in licensing and out licensing opportunities and will provide updates and ongoing matter if and when we have news to report on that front.
So actually I think at this point, we'll move on to Q&A.
Yeah.
Finally, and at this time.
Now open for your questions at this time, if you would like to ask a question. Please press the star and one on your telephone if at any point. Your question has been answered you may have.
Lynn.
So can we queue by pressing the <unk> again, we do that thank you for your question. Please pickup your handset.
Optimal for quality.
And I'm like Wow any question Kim.
And we'll take a quick question from Jason Mccarthy with Maxim Group. Please go ahead.
Thanks.
Thanks for taking the question Brent.
A brief question on northern La France, he looks like he's a very experienced guy and nuclear medicine can you talk to us a little bit about what that recruitment process is like the doctor with France.
Seizing the Arnelle platform and why he is excited to join.
Hey, Jason Thanks, Thanks for the for the.
The question.
So this is a pivotal hire for us.
As you might imagine.
Been functioning in the role as CFO and CEO for for a number of months.
And we knew that.
Putting somebody with.
The right qualifications will be difficult.
<unk>.
Physician Cmo's that havent oncology background are much more common but having somebody a that's that's got relevant nuclear medicine experience.
And then has brought.
Multi.
<unk> products to market or just it's a very small universe of of experienced individuals and so.
Yes, I think we went through we went through.
Our recruiter, who did a great job identify the number of candidates but.
And very good candidates, but Dr La France, who spends a lot of his current.
Hey, it is at his previous employer.
Doing.
This development and due diligence on various assets.
So I'd say two to three months and looking at the data and I think he was impressed with.
First with the technology.
And impressed in there.
Current agents of this field and targeted radio therapeutics and so.
Even at.
At this point in his career.
We've been very good job. He was I think it was highly motivated and where we feel very lucky and fortunate to have him on board and to kill Hill.
B work this way.
Reserve forward on.
Starting on day one.
Great and then going back to the respect GBM study.
Talk a little bit maybe about how high the absorbed dose really could be touch coherent 740.
It goes on when you change the flow rate and the concentration in.
And the volume, you're really getting getting to a significantly high number well over right external beam radiation.
Sure.
Regulators and physicians comfortable with because you've had no D. L. Ts can you just continue.
I don't go higher or do you just stop.
And then go to FDA and see where things are at.
Yeah. So it's a good question and.
The way, we currently analyzed average absorbed dose.
While very good approximation of what we're delivering.
Due to the tumor.
And frankly, we can assess the surrounding brain.
<unk> is a good estimate but we're in the process.
And I can't speak too much about this but we're looking more deeply at the amount of radiation delivered.
On a.
On a much smaller scale.
Livery, then defining what's average absorbed dose to the tumor looking at it in a much more detailed fashion and we think that granular data is going to be very important going forward. It's wanted to make that clear that this is given these doses of radiation.
The dosimetry evaluation.
Radiological feedback.
Scale, but it's going to improve very significantly I think for us in the next 12 months or so, but but having said that you.
This trial escalated relatively slowly it started in 2015 I think there was a concern about potentially delivering well.
Well past the 35 grade that's typical in their current setting.
60.
It would be great and the primary setting for external beam radiation for GBM.
Some nervousness.
With respect to the FDA, but.
But obviously, we've gone way past that the safety profile looks very promising at this point.
The way to think about it.
Is he put this average.
$60 ish absorbed dose number that's that's very high.
Really the question is what's the amount that you need.
To kill the tumor and then also essentially sterilize the.
Transformed cells that are sitting in the periphery of the tumor that you can't visualize but.
Very likely there.
Really the corporate that will cause the recurrence and <unk>.
So it looks like based on the data that.
Yeah.
A average absorbed dose of 100 gray.
It's probably a good threshold does it does it make sense to go up beyond that probably not.
What's.
And that will be important really as the volume and that's why but as you as you increase the volume we keep the radiation.
Percentage.
We deliver currently two five <unk> per cc. So we've maintained that from the last cohort to this course cohort. So we are delivering.
More volume more volume, but also more radiation, but at the same concentration. So the key is to try to not only treat the tumor the treat that surrounding areas. So I know that's a long answer but.
Bottom line is I think where we're near the end of what's feasible in terms of volume and radiation and whats necessary to optimally do the job.
Morning.
This probably.
Probably as the last cohort although.
We'll see what the data looks like.
And then just last question on the on the L. M program, that's coming up are there any.
Different sets of circumstances or challenges in terms.
<unk> and have better placement where.
One can find its way into its very different than <unk> right. You can have some spinal cord involvement or.
Are there different more difficult to reach areas of the brain or is that not not in this year.
Yeah.
Good.
And the deliveries totally different and in GBM and <unk>.
The one.
One of the one of the benefits of studying this disease therapeutically is that almost all of these patients that are diagnosed with <unk> ended up getting in a myer reservoir. So they have a long.
Question built in reservoir that is.
It terminates in the ventricle and allows essentially real time access with a small bore needle.
Directly through the skin into the ventricular system. So on one hand, it allows you to deliver that in an outpatient setting.
Long term in the span of about five minutes delivering this drug.
<unk> could do it's very straightforward.
It also allows for the ability to sample the CSF for cell count protein glucose and other.
The DNA based markers.
To look at a tumor response as biomarkers.
So the delivery.
Sophistication and challenge is much lower in this group of patients than it is with respect to to GBM.
Great Mark Thanks for taking the question.
Thanks, Jason appreciate it.
Well take our next question from Ed Woo with <unk> capital. Please go ahead.
Yes. Thanks for taking my question you mentioned that this is probably the last cohort you guys have how would you be able to say no. When you release the data in November whether Youll go for a ninth cohort or not.
Hey, Chad its mark.
It really just depends on how quickly we enroll these last patients.
It's possible, but but I just I can't predict.
And I can't predict whether we will have a dose limiting toxicity or any safety issues at the at the current dose we've treated.
One patient in this current cohort patient did well.
But it really depends so I.
Can't predict that.
But if we know more about that particular issue will certainly.
Discuss that at the time of the call.
Great.
Congratulations on.
The recent the IMD.
Therefore aren't out for another indication pretty soon it looks like you'll have three indications are you pretty much just focused on those three or are you guys going to be working on other indications at the same time.
Big picture interested.
Building out the targeted radio therapeutics platform, we think that 186 are in L. A.
For these narrowly focused CNS indications are we're just scratching the surface part of the reason to bring Norman.
With France, and the loop as he is.
Probably his experience as anyone and evaluating new technologies in this field. So we continue to kick the tires on on new things that could augment the portfolio, but we want to balance that with being able to to appropriately finance that in a shareholder friendly way so.
We're very.
Three happy here.
Hands are very full with what we have but we're still looking towards the future and building out the portfolio in new and interesting in value creating ways.
Great well, thanks for answering my questions and good luck.
Thanks, Ed.
There are no further questions and I will turn the call back over to Dr. Hedrick for any additional or closing remarks.
Thank you so much Ashley just wanted to say thank you to everybody that joined US on the call are that are listening to call and the recorded version on behalf of the board I'd like to just thank.
Thank our employees and.
And our team members and physicians that we work with and the patients that are trust us to enter into these trials.
Thank you very much for participation and have a good evening.
Sure.
Thank you and this does conclude today's conference call.
Please disconnect. Your line at this time and have a wonderful day.
Hum.
[music].
Uh huh.
[music].