Q3 2023 PDS Biotechnology Corp Earnings Call
Greetings and welcome to the P. D S. Biotechnologies third quarter 2023 earnings call and webcast. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference. Please press star zero.
On your telephone keypad as a reminder, this conference is being recorded I would now like to turn the conference over to your host Nicole Jones Investor Relations for P. D. S. Biotechnology. Thank you you may begin.
Good morning, and welcome to P. D F Biotechnologies third quarter 2023 earnings conference call and webcast on the call from the company or a doctor Frank body Rado, Chief Executive Officer.
Hill, Chief Financial Officer, and Dr. Joe <unk>, Chief Medical Officer.
Here. This morning P. D S biotech issued a press release announcing financial results for the quarter ended September 30 of 2023.
We encourage everyone to read the press release as well as P. D. S. Biotechs report on Form 10-Q, which will be filed with the SEC shortly.
Company's press release is available on the P. D. S website at P. D F. Biotech Dot Com. In addition, this conference call is being webcast and will be archived on the company website for future reference.
Before we begin we need to remind everyone that on today's call. The company will be making forward looking statements regarding regulatory and clinical candidate development plans as well as research activities.
Certain information in this presentation may include forward looking statements, including within the meaning of section 21 E. United States Securities Exchange Act of 1934 as amended and section 27 out of the United States Securities Act 1933 as amended.
Concerning P D F Biotechnology Corporation and other matters. These statements may discuss goals intentions and expectations as to future plans trends events results of operations or financial condition or otherwise based on current beliefs about the company's management as well as assumptions made by and information currently available to management.
These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.
Friction of these risks can be found on P. D. S. Biotechs. Most recent filings with the SEC you are cautioned not to place undue reliance on these forward looking statements, which speak only as of the date of this conference call except to the extent required by applicable law or regulation P. D. S. Biotech undertakes no obligation to.
Update the forward looking statements included today to reflect subsequent events or circumstances I will now hand, the call over to Dr. Frank <unk> Frank.
Thank you Nicole.
Welcome to everyone to our third quarter 2023 conference call.
We are excited about the stripes, we are making.
By our commitment to developing groundbreaking therapies that revolutionize cancer treatment based on.
On our proprietary platform and IL 12 fused antibody drug conjugate P. B S O one a D C.
Only known as P. D S O three or one four and 92, what you want.
The clinical data stemming from the P. D F O one ADC assets, which we acquired nearly a year ago from Merck K G. A a dumpster Germany.
Teams to advance and mature reinforcing our belief that this innovative a D C could potentially address the safety and efficacy limitations that havent been observed with cytokine therapy to date.
The combination of verse immune based approaches and our IL 12, ADC has demonstrated the potential to overcome the limitations of effectively treating advanced cancer and extending patients' lives with immunotherapy.
Currently we have safety data with over 250 patients who have been treated with P. D. S O one ADC.
Supporting the early data, suggesting that this innovative ADC.
To meet the reps the IL 12 into the tumor therefore, reducing its presence in the circulating blood.
Subsequently limiting the adverse events that have been reported with other cytokines.
In addition, the increased and sustained presence of IL 12 in the tumor has been shown in our ongoing trials to enhance the clinical activity.
This novel modification of IL 12.
Therefore presents us with a unique opportunity.
The address a broad range of cancers.
We continue to move this ADC forward with various promising approaches.
It is being developed as a monotherapy.
Also being developed in combination with first immune based approaches and also in combination with other standards of care.
I will talk more about these updates on P. D. S O. One ADC later on the call.
Yeah.
We are pleased with our current progress driven by our mission to develop ground breaking therapies that transform cancer treatment.
Our immediate objective revolves around progressing our primary clinical candidates P. D. S. A one to one to the market.
P. D. S 0101 represents a novel investigational HPV 16 targeted immunotherapy.
That triggered a potent and precise T cell response against HPV 16 positive cancers.
This quarter, we made significant progress on olive Hersman platform.
Typically with our phase two versus style diversity with two trial.
We hosted a positive key opinion leader.
Okay. Oh L event that included included key opinion leaders, who have been part of the first stelzer with you with two trial.
And others, who have not been part of the trial and all lead us in the head and neck cancer field.
Okay.
It was important to understand how head and neck cancer expert oncologists view the trial results and the potential of P. D. S 0101 in Keytruda to become the standard of care for recurrent or metastatic head and neck cancer.
Overall the experts we're enthusiastic about the updated first the towels. There was there were two data and the planned initiation of the phase three whereas the towels. There was there were three trial.
Yeah.
At this event, we presented data from both the immune checkpoint inhibitor naive Oh, I see I O naive.
And I see I was assistant patient cohorts, both of which demonstrated impressive patient overall survival.
For today's discussion on diversity policy with you with two trial, we will focus on the ICI naive group.
With this population we reported a 24 month overall survival rate of 74%.
Which means that on the combination of P. D S 0101 and Keytruda.
The probability that the patient will lift at least two years is 74%.
To put this number into perspective.
Published 24 months overall survival rates for approved I see is it's less than 30%.
Meaning that on today's approved therapies, the probability that the patient will lift for at least two years, it's only about 30%.
The first the towels. There was there were two data suggest that patients are living longer when treated with the P. D. S 0101, plus keytruda combination.
Yeah.
It is important to note that disease control, which includes stable disease and tumor shrinkage was seen in 81% of patients.
Tumor shrinkage was reported in 60% of patients.
And a confirmed objective response rate of 27% what's reported based on investigator assessment.
With respect to safety the combination continues to be well tolerated.
With 13% of patients having grade three treatment related toxicities.
No patients having any grateful.
All great five treatment related events.
To put this in context.
And Keno 048.
It is reported that 17% of patients on Keytruda monotherapy.
The wins, great three to five treatment related toxicities.
And 72% of patients on Keytruda plus chemotherapy.
B rents grade three to grade five treatment related toxicities.
With this data we believe that we are on track to revolutionize the treatment of head and neck cancer with improved clinical outcomes and better tolerability.
Furthermore.
In October 2023.
Preliminary biomarker data from the birth of the towels. There was there were two trial was presented at the European Society for medical oncology or ESMO Congress 2023.
The combination of PD is a 101 intruder appear.
Appears to be promoting a pretty dominant th one immunological profile that is associated with enhanced C. D. H killer T cell induction and activity.
The combination also led to subsequent decreases in the population of C. D. H killer T cells in the circulating blood.
We are encouraged that these observations align with other phase two studies reporting that P. D. S 0101 induced Polyfunctional C. D H killer T cells do not reside in the blood.
But rather traffic to tumors.
These data support the two year, 74% overall survival rates reported in burst of houses they want to see what too.
Beyond diverse styles. There was there were two trial. Our focus has remained on steadily advancing preparations for our phase III burst tells you what to do with three trial.
In October 2023, we announced feedback from the FDA regarding the amended investigational new drug application.
And thereafter feedback on the final clinical trial protocol.
We currently have up to 60 sites selected globally.
And all going through the qualifying process.
As anticipated the FDA reviewed phase III clinical trial design has been pivotal to our business development discussions.
Which has yielded positive insights from prospective partners.
Our clinical and medical teams are assessing final details of the trial and therefore, we anticipate burst LLC residual three will now start in the first quarter of 2024.
We will keep you updated on our next steps as we progress towards trial initiation.
Now turning to immunotherapy.
In October 2023 data from the Phase II clinical trial were featured in an oral presentation at the American Society for radiation oncology annual meeting.
S Astro.
These data demonstrated that PD is a 101 in combination with standard of care chemo radiotherapy was associated with a rapid decline in HPV positive circulating tumor DNA.
At five weeks of treatment D. T D N a clearance of 92% plus reported with P. D. S 0101.
Whereas 50% clearance what's observed in patients receiving standard of care chemo radiotherapy alone.
These biomarker data support the 100% response rate in patients receiving P. D. S 0101, and standard of care, which was reported at S. ITC 2022.
This trial continues to progress we will provide further updates.
Now shifting to our IL 12 fused antibody drug conjugates known as pdfs or one a D C.
P. D. S O. One ADC is a novel ADC or antibody drug conjugates that enhances the proliferation potency and longevity of T cells.
And IL 12 in the tumor.
Let's begin by discussing the compelling updated data from the National Cancer Institute led Triple combination trial that was reported on November nine.
This study is the phase II trial of P. D. S 0101.
Pdfs of one ADC and an investigational ICI.
This combination has undergone evaluation across multiple HPV positive cancers encompassing ano.
The cool head and neck vaginal involve a cancerous in two groups of advanced cancer patients.
The ICI and our youth group constituted patients unresponsive to standard of care treatments that have not yet received ICI therapy.
The ICI resistant group included individuals who have shown no response to multiple prior treatments, including ICI therapy.
Regarding the ICI naive group.
The chart shows the confirmed objective responses reported universe styles diversity with too.
And the Triple combination based on investigator assessment, both shown in green.
As well as published keynotes here for eight data.
Notable is the objective response rate of 75% with the Triple combination.
And 27% with the dual combination.
With Keytruda monotherapy and Keytruda plus chemotherapy. The published objective response rates were 19% and 36% respectively.
The next figure contains updated survival data from birth tells the rest of it too and the Triple combination trial in Green.
As well as published data from keynote 048.
What is notable here is.
It's the fact that despite the lower objective response rate with P. D. S 0101, plus keytruda.
The survival benefit seen with a P. D S 0101, plus keytruda combination.
As well as the Triple combination appears to be similar.
With 24 months survival rates of 74 and.
75% respectively.
The Triple combination also shows the compelling three year survival.
75%.
These data suggest that P. D. S 0101 may play a significant flow and extended survival in the ICI naive population independent of objective response rate.
While P D. S O. One ADC appears to promote strong objective responses in this population.
The median overall survival has not yet been reached in either the first styles seriously with too.
Oh, the Triple combination study.
To contextualize published data on standard of care immune checkpoint inhibitor, so ICI ripped.
I report that a 12 months only 30% to 50% of these patients with typically be expect it to remain alive.
And less than 30% of the patients could be expected to remain alive at 24 months.
Therefore survival associated with a P. D. S 0101 combination regimen of two years over styles. There was there were two and.
And three years for the Triple combination is notable.
Now looking at the IC I resistance group, where there's a significant unmet medical need and no F D. A approved products.
These are the patients who have failed all treatment options, including IC ice.
In these ICI resistant patients with HPV positive cancers. They reported median overall survival is only about three to four months.
In the ICI resistant patients.
This slide shows that the published objective response rate with systemic therapies, including high dose chemotherapy is 42%.
The objective response rate was zero percent with P. D. S 0101, plus Keytruda inverse tells you what to do with too.
5% in patients who received the PD is a one to one with low doses of P. D. S O, one ADC and or ICI therapy.
And 63% in patients who received PD is a 101 with initial high doses of tedious, one ADC and ICI therapy.
Again these data appear to demonstrate the role of PD is Oh, one a D C and promoting strong and compelling objective response rates even in late stage ICI resistant cancer patients.
Let's now take a look at the overall survival rate in IC I resistant patients.
On this slide we will see that the irrespective of objective response rate.
The P D S 0101 containing therapy as shown by the green bars.
Provide durable survival results.
Despite the lack of confirmed objective responses with P. D S 0101, plus keytruda.
The 12 month overall survival rate was 56% for breast cells, there was zero two and 72%.
And the Triple combination.
With systemic therapy, the published 12 month overall survival rate is 36%.
This data provides compelling evidence regarding the role of PD is a 101 in the survival of IC I naive and ICI refractory HPV 16 positive patients.
And the potential role of Pds, Oh, one ADC and further extending survival and also promoting objective responses in this population.
This study provides compelling evidence that supports the potential synergy between our first immune based targeted T cell immunotherapies and our IL 12 fused antibody drug conjugates that provides the sustained presence of IL 12 in the tumor.
Thus, providing further expansion and activation of diverse immune induced multi functional killer T cells within the patients tumor.
We believe that this data supports broader application of this combination beyond HPV positive cancer.
And provides the unique potential.
To effectively address multiple advanced cancers in our development pipeline.
As a reminder.
Safety update for this trial was announced in late December 2022, and a 50 patients.
48% of patients experienced grade three related.
Three treatment related adverse events or aes and 4% of patients experienced grade four related adverse events.
To put the safety profile in context.
And the key note 048 study.
It is reported that the combination of Keytruda and chemotherapy resulted in 72% of patients having great three through great five treatment related adverse events.
We are therefore pleased with the Tolerability profile that is emerging for P. D. S O one ADC, even when administered in combination with either oncology agents.
As I mentioned earlier to date, we have safety data from over 250 patients dosed with P. D. S O one ADC.
This provides further evidence that this <unk> modification of IL 12 may be effective in mitigating previously observed cytokine side effects, while promoting improved clinical benefit.
Further justifies its continued development by P. D S biotech.
P. D. S. O. One ADC is also being studied independently of diverse immune immunotherapies.
The National Cancer Institute recently presented data for the ongoing phase II clinical trial of P. D. S. O. One ADC in combination with Docetaxel chemotherapy in advanced metastatic castration sensitive in castration resistant prostate cancer patients.
At the cytokines 2023 annual meeting.
This trial is the first clinical study of an immune a cytokine with docetaxel in prostate cancer.
The study is investigating the safety.
<unk> responses and preliminary clinical activity of the combination in advanced prostate cancer patients.
The trial evaluating three doses of P. D. S O one ADC in combination with Docetaxel.
And showed that the combination was well tolerated at all tested doses with less than 10% of patients having a grateful toxicity.
Most importantly.
Over 60% of patients had a prostate specific antigen or Psa level reduction of greater than 60%.
With some patients having a 90 to 100 Psa reduction.
As shown with PSA levels were documented in all 18 patients.
P D S O one ADC activates T cells.
Natural killer cells, and natural killer T cells, while reducing the presence of immune suppressive regulatory T cells.
As a result, we believe that we now also have an opportunity to apply <unk> ADC for advanced and difficult to treat tumors by combining PD, one ADC with standard of care chemotherapy and radiation therapy.
<unk> Oh, one ADC is also being investigated by the National Cancer Institute in a phase one two study in patients with intermediate and high risk locally advanced prostate cancer in combination with radiation therapy.
As mentioned previously.
<unk> ADC is also being studied as a monotherapy by the National Cancer Institute in an ongoing phase two clinical trial in kaposi sarcoma.
Yeah.
P. D. S. Biotech we are highly optimistic about the potential of this novel P. D. S O one ADC assets in cancer therapy.
Yeah.
Switching now to preclinical development studies.
The National Cancer Institute has developed a second novel approach to treating immune.
Immune checkpoint inhibitor resistant cancers by using versus immune based immunotherapy and Pds <unk> ADC in combination with histone deacetylase or HVAC inhibitors, and Napa oncology standard of care.
The preclinical data were presented during the recently concluded 2023 annual meeting of the society for immunotherapy of cancer or S. T C.
Kansas preclinical study.
Theory anti tumor activity was observed in ICI resistant tumor models with diverse immune based immunotherapy.
Tedious, Oh, one ADC and antenna staff a class one <unk> inhibitor.
This novel Triple combination proof of concept study is under consideration as a potential approach for initial clinical studies of <unk> or 103 to treat Mach one specific cancers.
We are encouraged by the potential of this combination.
The National Cancer Institute will lead this clinical trial and our established cooperative research and development agreement and we anticipate that it will begin in the first half of 'twenty 'twenty four.
P. D S. Biotech has had a fruitful quarter.
And we are preparing to finish out the year strong as we move into 2024.
To summarize.
We hosted a cake successful kols event, where we announced positive updated overall survival and safety data from diverse styles. There was there were two trial.
And gained important insights from head and neck oncology meters above the potential of PD is a one to one in the treatment of HPV positive head and neck cancer.
Preliminary biomarker data presented at ESMO from the burst out 002 trial supports the reported overall survival results.
The biomarker data from the immunotherapy trial presented at Astro demonstrates the role of P. D. S 0101, and eliminating circulating tumor HPV DNA.
The updated triple combination data demonstrates the role of the P. D. S O one ADC and promoting durable overall survival and objective responses.
Even in difficult to treat ICI resistance patients.
Data from the PD is Oh, one ADC and Docetaxel trial presented at cytokines.
Demonstrated tolerability of the combination and the encouraging PSA biomarker results and immune responses.
With that.
I'd now like to turn the call over to Matt to discuss the financial summary, much.
Now turning to our financial results for the three months ended September 30 went through 'twenty three.
Net loss for the period was approximately 10 $8 million were 35 cents per basic and diluted share compared to a net loss of approximately $7 4 million or 26 cents per basic and diluted share for the three months ended September 32022.
The higher net loss this quarter was primarily due to costs incurred in connection with our research and development and clinical programs.
Research and development costs, which includes clinical and manufacturing expenses for the quarter ended September 32023 increased to approximately $6 $4 million.
Compared to $4 $3 million for the same period of 2022.
Kris.
<unk> dollars is primarily attributable to an increase of $1.3 million in clinical trial costs.
And point $7 million in personnel costs, which includes.
$3 million in noncash stock based compensation.
General and administrative expenses for the second quarter of 2023 <unk>.
Greece to approximately $4 $1 million compared to $2 $9 million for the same period of 2022.
The increase of $1 $2 million is primarily attributable to an increase of $27 million in personal costs, including $5 million in noncash stock based compensation and.
And $45 million Investor relations costs.
Our cash and cash equivalents as of September 32023 totaled approximately $54 $3 million, we continue to be prudent with our cash expenditures and we believe that initiating reverse styles as usually with three phase III clinical trial in the first quarter of 2024 are available.
Cash resources will sustain our operational and research and development endeavors into the third quarter of 2024.
We expect to execute our current operational and research and development endeavors by obtaining additional capital principally to learning into collaborations and strategic alliances license agreements with third parties and are public or private debt and equity financings. We've had and continue to provide what we believe to be favorable development milestone to the market.
And have upcoming development milestones, we believe may provide additional catalysts to investors at this time. This completes my financial discussion I would like to hand, the call back over to the operator for the Q&A session operator.
Thank you at this time, we'll be conducting a question and answer session. If you'd like to ask a question. Please press star one on your telephone keypad.
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Our first question comes from the line of Louise Chen with Cantor Fitzgerald. Please proceed with your question.
Hi, congratulations on all the progress this quarter and thank you for taking my question. So I had a few questions for you as you think about 2024 and we table set for next year what are the key milestone catalysts Readouts that you think we should have on our radar.
How do you think about Opex for fourth quarter and 23 in 2024 in light of the fact that you're going to start this versatile 003 phase III and the last question is when do you think we'll see data on first of all how Oh, great. Thank you.
Luis Thank you very much for your questions I'll answer two and I'll hand over the Opex to Matt.
But in terms of the key milestones and catalysts as we move into 2024.
Mentioned key will be guessing burst out there is there are three up and running.
We also have announced and stated that we do anticipate and expect the final data readout from Bristol. Bristol is there is there were two sometime in the second quarter of 'twenty 'twenty four.
So I also just mentioned we do expect to initiate the P. D. S 0103 clinical trial in a mock one related cancers early in 2024th and the first half of 2024.
We also are hopeful that we will have preliminary data from our neo adjuvant trial ongoing at the Mayo clinic in early stage oral cancer HPV positive oral cancer, where were looking at P. D. S 0101, both as a monotherapy and also in combination with Keytruda, we have not had any readouts from our study yet and were hopeful that we will.
I'll get back in sometime in the first half of 'twenty 'twenty four based upon what we've been informed by the Pi and there be a goal of preventing at an upcoming conference.
And also we do expect to have additional data readouts on the immunotherapy cervical cancer trial.
And so we do have a number of potential milestones coming up as well its readout sport and we as you know we.
We don't talk too much about the trials going on also at the National Cancer Institute, We had the readout from the Docetaxel as well as the M. P. S. O. One ADC. We also have those studies ongoing in earlier stage prostate cancer locally advanced prostate cancer. We are hopeful that we will see some data from that trial in 2024, we have the monotherapy.
[noise] trial going in a couple of sarcoma, hopefully we will see some data from that trial in 2024.
And and so I think I think we will have hopefully a pretty busy 'twenty 'twenty four and hopefully we'll be able to provide quite a number of data readouts as we go through the year.
In terms of the birth towels. There was there were three trial.
I think we will have much more clarity on when we will have the data readouts as you know the one when we will be able to provide the data readout will be at our first interim data readout now when we get to the first interim data readout depends on the number of sites that we have open at the start as well as the enrollment rates that we will encounter all with that we will be able to act.
Steve as the trial goes.
Initiative and progressive what we're currently doing as I mentioned, we have 60 sites that have been identified so far.
Goal is to get to 100 sites and what we are trying to understand now is how rapidly each site will come on board and as we understand better how we will open the site and the sequence of opening sites and how many sites will be open at any particular time, we will then able to provide a much more and much more we're back more confident in the timelines, we will be able to provide.
You have to when we will get to that interim data readout, but we are working aggressively on that now and hopefully should be able to provide that information very soon.
Mike I'll hand over to you for the operating costs.
Thank you Frank.
Louise Thanks for your question I want to let you know that.
Yeah. It's a good question we've been.
I would say we've been extremely prudent with the use of the company's cash and capital when you look over the last probably seven quarters or so we burned about.
Little north of $6 million per quarter, and with the significant number of studies that we have ongoing not only the burst hausers. Your two trial, but also trials with the NCI.
He's with MD Anderson as well as Mayo, we've been extremely frugal in our opinion and how we manage these costs, but as we prepare to move forward into a phase III clinical trial, obviously those costs are going to increase.
Now.
From a perspective of op ex the administrative costs will grow slightly but you can expect that the company will incur costs.
In R&D.
Somewhere around.
The overall cost I'm, sorry will be somewhere around between 12.
$12 million to $15 million once the study start up with some of that be frontloaded for the normal deposits that are need to be made to get the consultants euros into like setup.
Which is why we under the current circumstances of US looking at a trial beginning in Q1, we've got cash into Q3 of.
24, which also gives us additional time to go out and look for business development deals. We have the first data came out we've had reverse the NCI triple data come out we've had the docetaxel data come out without the K O. L. Meeting. So there has been a significant number of data readouts and we're hopeful that that will.
Be a catalyst for a potential business development deals as well.
Thank you can I just ask you one follow up question. So for fourth quarter or 23, then you would expect opex to be similar to third quarter or would there be some ramp up when he started it will be there will be some ramp up in AR in.
In Q.
In Q4 of this year. So we spent about 10.
And a half million in total in Q3.
So my expectation would be around there were a little higher.
Okay. Thank you.
Youre welcome.
Thank you. Our next question comes from the line of my Henk, Montana with B Riley Securities. Please proceed with your question.
Good morning, and thanks for taking my questions and appreciate the comprehensive pipeline updates. So maybe a high level question quickly for you guys, given or 101, prolong survival and and the higher <unk>.
You seem to have the driven by or one ADC invested one and this is Emily wondering if perhaps it makes sense to also evaluate the blending whilst line.
Or should we think of trip led to be more than the ICI. It has since patients are maybe even being HCV agnostic could could you just clarify how you're thinking you know that is the positioning of these two.
Programs.
And then I have a couple of follow ups.
Frank if you're speaking you may be on mute.
Thank you very much.
Yes.
I think youre, absolutely right, we have seen highly encouraging survival data with P. D. S 0101, as well as PD, one ADC as well it's extremely encouraging.
Or with the P. D S O one ADC.
We have certainly considered the application of the P. D. S O one ADC in the earlier line ICI naive.
However, after talking to key opinion leaders in the field.
As well as the regulatory experts, it's evident that the survival and safety data generated with the doublets Chris.
Presents the most straightforward regulatory pathway.
As well as the robust uptake if and when it becomes standard of care.
With the doublet will also enable a more rapid potential approval path for early even early use now.
Now when we look at the Triple and the ICI resistant population. It also presents the quickest path to approval and potentially application in multiple HPV cancer indications as you mentioned.
And secondly tumor agnostic.
This triple combination made then also subsequently find its way to an approval for use in ICI naive patients. So this is something we are actually seriously considered but after talking to the experts in the field.
The two auctions were taking now appear to provide the quickest path to rapid approvals.
And uptake.
Understood. Thank you for that clarification, and then maybe drilling down on the doublet trial protocol.
Are there any details on the S&P that you're able to share in terms of the target or as a differential.
Going forward again standard of care.
Yeah.
Talking about sites right now a specific patient numbers, but just sort of.
It would be helpful to understand what sort of hazard ratio and sort of.
Data on the last yeah, you're aiming for and this is a related question. Your ethanol translational biomarker data was actually quite novel in context of demonstrating CBA.
Cell responses to synthetic tumor cells I was wondering if there are any implications of that inbound.
And rich land, our response assessment strategies that you could deploy in their late stage development.
Okay mind can lots of really good questions. So let me start with the biomarker data so with the biomarker data as you did mention we're looking at a number of novel approaches to really understanding and documenting how P. D. S. A 101, it's working and really documenting and clarify.
And the differentiation of our assets.
So if you look at the data presented at ESMO for example, looking at the Polyfunctional CDA T cells confirming in increase in poly functionality with very important but also understanding the kind of immunological profile. The pds or 101 is promoting for example, going from a th two biased towards.
H, one th one being well documented to be better associated with strong C. D. H T cell responses right and also showing that we have potential exit of the CD eight T cells from the blood to the tumor sites right showing the decline in circulating peripheral blood.
Containing C D C D. A T cells. So we have that approach in that study and in the P. S. 0101 contributor now when you also look at what's been done in terms of Biomarkers in the immune assertive study right very complementary to what we've seen with the M. P. D. S 0101, Keytruda study in the.
In the immunotherapy studied what M D Anderson with looking at circulating tumor DNA.
Circulating tumor DNA is extremely important for a number of reasons right.
If you look at cancer today, most patients don't die from the initial tumor ensure cancer.
Often die from micro metastatic.
Cancer that remains after the initial treatment.
And so being able to essentially eliminate the tumors from the.
Patients body becomes extremely important and how do you know that your technology or product is actually achieving that.
What we have seen now with our circulating tumor DNA in that study if the strong potential for PD is a 101 to actually dramatically.
Nate and reduce and eliminate the circulating tumor DNA right at five weeks, 92% reduction versus 52% reduction with the standard of care.
M. D. Anderson is extremely excited about that because they believe it has direct implications for patient survival and very importantly, recurrence after cancer.
So that isn't that is data that we were hoping to be expecting to see coming up in 2020 for how that elimination of circulating tumor DNA correlates with recurrence of their cancer and survival of the patients now.
Now what they also looked at a very innovative approach using cervical brushing to really quantify and understand the kinds of T cells that are actually accumulating in the patient's tumors.
So we talked about the book CD eight T cells in the blood and exiting the block, but it's also important to understand what's happening in the tumor and what they also showed was a really strong correlation.
Between.
The elimination of circulating tumor DNA and accumulation targeting an accumulation of B C. D E T cells within the patients tumor right. So again very different to date most of our peers have looked at T cells in the circulating blood looking at things like interferon gamma, but what we are showing here is that these T cells generally.
By diversity and technology.
We do target and accumulate in the patient's tumors.
So again, we have very complementary studies, which are in agreement with each other which had given us a really good picture.
How and why we've seen the results we've seen in these patients today now if you go to the Triple combination.
Very similar studies have been performed by the National Cancer Institute in the Triple combination again, showing that very strong correlation between induction of HPV 16 specific T cells.
And the clinical responses and also showing that this triple combination. In addition to <unk> do you think strong tumor specific multifunctional T cell <unk>.
In juices and <unk> and.
In inflammatory and immunological profile.
Which is strongly believed to suppress the tumor stability to hide from the immune system right.
So now were getting all the information that we that helps us better understand how and why we've seen the kinds of results. We've seen today and these patients even in the very difficult to treat patients.
So now coming to your earlier question, which has to do with the design of diverse styles. The residual three trial now.
No we have not made details of the clinical design public yet, but I can give you some some insight into how we're thinking about this.
The Delta today is quite significant when you look at the Delta.
What we've seen at the two year results versus what we see in the published data.
We know that by far exceeds what we will have to achieve four approval.
But as a risk mitigation strategy in terms of our statistical design. What we're also looking at is we also saying well, let's assume P. D. S. O 101 patients in our control arm, taking keytruda will do much better than keynotes, you four eight.
And so in terms of our endpoints for the control arm, we anticipating that there'll be higher than keynotes here for H P.
Oncologists are getting more used to administering keytruda, they're getting better understanding of which patients may respond better and so we have to assume that those patients are going to do better than how it's been published today.
What we are also assuming in that design is that our patients in the study at multiple sites all over the world will not do as well as can be seen in burst how serious you are too.
We are also reducing the target.
That's the risk mitigation allows us to overpower the study based upon what we've seen today and mitigates the risk that we will not get to that clinical end point right. So we've taken those strategies into consideration just based upon the really large delta and we seem to get today allows us to narrow that delta, but also be reasonable in terms of trial size and.
Power of the trial to successfully achieve those primary endpoints of overall survival.
Mike and I hope that answers your question.
Yeah, no very very comprehensive they helpful and lastly for now just quickly on the strategic collaboration discussions.
Are you able to describe qualitatively and drove strong should be the exon Doug black voices to blend and how maybe you know recent.
<unk> data may have informal discussions and.
And also.
There's a full data set from your double unexpected in second quarter, where they wanted to see that mature analysis before.
Transacting or they kind of just lay out some of the variables that are the bad debt impact discussion like that thanks for taking my question.
<unk> got to do your own is going to be able to do I'm not going to be able to go in and take that one frankly.
Yes, I'll take that one yes.
Mike actually not I.
I won't be able to go into very specific details as to what we are discussing how however, the data that we have today has been very helpful. In clarifying certain things. So one of the key things that I mentioned over the last couple of earnings calls has been the fact that we are waiting to see the data from diverse styles the reserve.
Two refractory all.
That data is very important because it was key and given us insights into the specific role of Pds or one to one or the contribution of P. S. O 101, and extending life in head and neck cancer patients and so looking at that combination of P. D S 0101 and Keytruda.
In patients who have failed checkpoint inhibitors, the majority of which we know we're on Keytruda.
And still being able to extend those patients' lives significantly was very important for us to demonstrate and to get to get potential partners also comfortable that okay. P. D. S. 0101 is actually biologically active in this population and even seen this expansion in even a much more difficult to treat population so that that will suffer.
Key.
It was also important for us in the Triple combination trial as I mentioned previously for us to have that understanding of what PD is a 101 is doing it that combination because a lot of the questions. We received from investors and prospective partners as well and the Triple how do we know which of these components is working and what is.
Contributing to what.
So now the role of PD is a 101 becomes very clear, but with the data we have today.
We also now see the critical role of PD, one ADC and so now both components both drugs have very clearly shown their biological activity and what was also a bedroom consistent look at birth styles. There was there were two right refractory.
No IL 12 zero percent confirmed objective response, if you're at a low dose IL 12, 5% confirmed objective response, if you go to a high dose IL 12, 63% confirmed objective response very clear in terms of what's happening with the IL 12, right. So.
All of this is data that's now available provides not just pds, but potential partners with confidence in the biological activity of our of our drugs.
Right intense off.
Discussions.
I will say there are no issues with the current protocol right. As you know we have alignment with the FDA on the path forward.
But what's happening with these discussions it's not at all uncommon and we believe that it is prudent to at least evaluate suggestions that the serious potential partner may have.
Even though there are no guarantees that the partnership will result, when all is said and done right by their number of typical things that we would typically want to evaluate how this case, we would not do this for every prospective partner suggestion we receive however.
Hope that gives you some flavor.
The data we've seen today and how it's impacting discussions that you're having.
It does thank you for taking our questions and look forward to C. J L. Pics.
No problem. Thanks, a lot.
Thank you. Our next question comes from the line of Joe Penn Gene with H C. Wainwright. Please proceed with your question.
Hi, good morning, everybody. Thanks for taking the questions two questions. Please so first for O N O. One wanted to ask about currently what you have ready to go followed by your intermediate near near term needs and intermediate needs with regard to manufacturing.
And then the second question is a little bit of the off the beaten path here.
Nice to hear such the encouraging.
Data updates from an old 10101, but I wanted to ask about O to O two in the universal flu vaccine.
You are sitting on what we consider to be a very strong asset profile and the data that you've accumulated to date. So other than the rhetorical answer financial resources, how what could you envision being a development plan for that asset.
Yeah.
Okay. Thanks, a lot Joe I'll start with the first question in terms of what we have ready to go with P. D. S. L 101, so with PD, one and one we have done all the tech transfer the material has been scaled up to our commercial process and the phase III clinical product has already been successfully manufactured and released so in terms of clinical product.
That has been scaled up to the <unk>.
Final process and has been successfully manufactured we have there today. So the material is ready to go we don't have any additional needs from the perspective of P. D. S 0101 materials in order to run the phase.
To run the phase III clinical trial with either program burst out there was there were two or the triple combination.
With P. D S O to O. Two unless you mentioned this is a program that we're quite excited about them.
Today, our resources financial resources are really focused on the oncology programs. However.
We have made significant progress also with this program as you know the data was presented in September at the European influenza comprehensive data from ferrets right, where its been the gold standard for preclinical studies. So it was very important to be able to demonstrate that we can replicate the data that was generated in the mouth.
It'll in the fair rates, which are closer to humans in influenza.
Again, all of that wasn't that has been done successfully we've shown very similar levels or identical levels of broadly reactive neutralizing antibodies against multiple strains of the flu that was shown successfully and ferrets were also showed successful prevention of viral replication in the lungs when the animals.
Given lethal doses of the H one N one virus.
As well as protection against infection and in the Forex also so we have shown we have shown very good translation now from Pds's perspective.
This is not surprising because again, even in our oncology products. We've shown very good translation from preclinical models to human right and so we expect that this the ni AIB is extremely encouraged by the data that we've seen to date.
And so we have had some discussions we are still hopeful that we will get some notification sooner or later regarding the next steps, but we would ambition of what we would like to see it would be for this to go into at least the phase <unk> human clinical trial.
Time next year and start generating the human data that kind of also replicate the kinds of broadview reactive neutralizing antibodies that were seeing in the animal models and human hopefully and provide very important data on safety as you know with preventive vaccine safety is extremely important and we've seen very good safety.
Profile today with Pds are one of the ones that we do expect to see very similar safety with them the preventive vaccine and then <unk>.
Hopefully pending on when in the year, it's down and get some data on actual prevention against against infection with the flu. So we are where we are really hopeful we still aren't very good discussions with an eye AI D. They've indicated that this is something they would like to move forward and so we are waiting to learn what the next steps will be.
When those next steps will start.
I appreciate the color Frank.
No problem.
Yeah.
Thank you, ladies and gentlemen, as a reminder, if you'd like to join the question queue. Please press star one on your telephone keypad. Our next question comes from the line of Jim Molloy with Alliance Resource Partners. Please proceed with your part with your question.
Hello. This is Laura answer Jan Thank you for taking my questions and congrats on your progress.
So you've mentioned and I'm kind of trials for your preclinical PD I still went up three candidate for you know the first half of next year.
Any other updates that you have for your preclinical P. S. I wanted to and I don't want to fight candidates.
Hi, Laura Thanks for your question.
So with PD, one or three.
And the goal is to start in the third.
Third quarter in the first half of next year.
And so that's it's going to be done under our collaboration with the NIH right. Now we are finalizing the CMC section. We are finalizing the animal studies and looking at the new Triple combination, which is potentially going to be very likely that the path. We go down that's being evaluated now in specific tumor models that we would want to include in that.
IND filing so we are.
We are working towards an IND filing hopefully in Q1 of next year to get this into the clinic hopefully by the second quarter of next year with Pdfs of one or two we are also working now on the tech transfer and the formulation development has been completed preclinical work has been complete with PD, one or two and just to remind just to remind that.
Audience, who may still be on PD, it's a one or two specifically addressing prostate cancer.
I'm sure you can see how that potentially lines up with what we're doing with Docetaxel. There is the potential that we could include that to make a new triple combination, but go here where that program is to get that duo combination as rapidly as possible to commercialization, but there's potential for expansion in terms of even more difficult our latest.
Cancer patients and decline of circulating tumor DNA you'd think that P. D. S 0102 assets in which the target. This talk T. A R. P. T. A R. P has been found in about 90% of prostate cancers at all stages of the disease and about 50% of breast cancers. So that's an asset that we do.
Do anticipate hope.
Hopefully getting into manufacturing some time next year in 2024 to allow us to start to evaluate that asset also probably later later in the year, but we will provide updates regarding what their power. What are we doing with that process program with potential partnerships. How are we going to move that forward, we'll provide some more some more of those.
Later after a year.
It goes by.
'twenty 'twenty four P. S 0104, we have not yet made any additional progress with Pds or 104, we've really concentrated on PD. It's a one to one or one or two in all windows suite at this point as well as PD L. One ADC.
Okay.
Got it. Thank you for the clarity and also to find my question alongside the data presented for immuno Sir I'll figure out there you know investigator initiated trial of Pdf's not one on one with the Mayo clinics do you have any estimates as to when you might get data announced here.
No so with them with the Mayo clinic staffing with a mate with the Mayo clinic.
And that's you mentioned that that's another investigator initiated trial is evaluating the early stage HPV 16 positive oral cancer Neo adjuvant setting we have been informed as I mentioned by the P. I thought would be hope to present preliminary data at a scientific meeting in the first half of 2024, and so we will keep you updated as we learn more.
What conference that would be and what the exact timing would be but we are hopeful that we will see some data with the first preliminary data from that trial hopefully in the first half of 2024 and.
And with immunotherapy.
With immunotherapy.
The investigators extremely encouraged with the data that <unk> seen today.
Based on what we've been told by Dr. Clark of MD Anderson, who leads this trial. She is actually planning on submitting interim results of the study for scientific publication and particularly the recent.
Activating tumor HBV DNA outcomes reported at <unk> I'm. The previously reported tracking an accumulation of multifunctional CDA T cells into tumors.
And she also intends to update clinical response and survival data. So we are hopeful that we will get an additional update on that trial in the near future.
Okay.
Understood. Thank you for taking the question.
Thanks, a lot.
Yeah.
Thank you there are no other questions at this time I'll turn the floor back to Dr bedroom auto for any final comments.
Yeah.
Thank you very much.
So thank you to all for participating in our third quarter earnings conference call today.
The progress made this quarter has been truly exciting we remain enthusiastic about what lies ahead for the rest of this quarter and into 2024.
We have made significant strides towards our objective of developing groundbreaking therapies that transform cancer treatments.
We are confident that our efforts will positively impact these patients with critical unmet medical need.
Leading to longer life and improved quality of life.
We appreciate your continued support and eagerly anticipate updating you on our accomplishments. Thank you very much again and have a wonderful day.
Thank you. This concludes today's conference call you may disconnect. Your lines at this time. Thank you for your participation.