Q3 2022 PDS Biotechnology Corp Earnings Call
[music].
Greetings and welcome to P. D S Biotechs third quarter 2022 earnings conference call and webcast.
At this time, all participants are in listen only mode.
Question and answer session will follow the formal presentation.
If anyone should require operator assistance during the conference. Please press star zero from your telephone keypad.
Please note this call is being recorded.
At this time I'll hand, the conference over to Gabby D. Covina C. G capital Gabby you may now begin.
Good morning, and welcome to TD S. Biotechnologies third quarter 2022 earnings conference call and audio webcast.
With me today from the company are Doctor, Frank, but I do auto Chief Executive Officer, Dr. R&D Wood, Chief Medical Officer, and Dot Hill, Chief Financial Officer.
Earlier this morning P. B S biotech issued a press release announcing financial results for the quarter ended September 32022.
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 S. E C. Shortly.
The company's press release is available on P. D. S website at P. D S biotech dotcom.
In addition, this conference call is being webcast and will be archived on the company web site for future reference.
Before we begin we need to remind everyone that on today's call. The company I'll be making forward looking statements regarding regulatory and product candidate development plans as well as research activities.
Information in this presentation may include forward looking statements, including within the meaning of section 21 E of the United States Securities Exchange Act of 1934 as amended and section 27, a of the United States Securities Act of 1933 as amended.
Turning Pds Biotechnology Corporation and other matters. These.
These statements may discuss goals intentions and expectations as to future plans trends, even results of operations or financial condition or otherwise based on current beliefs of 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 a description of these risks can be found in 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.
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 with that I would now like to turn the call over to Doctor, Frank but I do I do Frank.
Thank you Debbie and thank you to all for joining us on our quarterly call today.
During the third quarter of this year, we achieved some major milestones as we continue to progress the development of our oncology pipeline.
Particularly our lead candidate <unk> hundred one towards Registrational trials.
<unk> <unk> hundred one is an investigational immunotherapy designed to treat human papillomavirus or HPV positive cancers.
Before going through our quarterly and other business updates I want to remind everyone that there are two key obstacles that have limited broader application of immunotherapy in the treatment of cancer.
Despite the revolutionary success of checkpoint inhibitors.
The first challenge has been the limited ability to induce in the body the.
The right type of killer T cells.
With the Reits, killing potency, meaning polyfunctional or multi cytokines inducing killer T cells.
As well as induction of these killer T cells in the right quantities.
We refer to this as the critical three Rs <unk> cell activation.
<unk> type right potency right quantity.
We know today is that the induction of adequate tumor.
Tumor infiltrating killer T cells is crucial for effective and durable all long term immunotherapy.
The second limitation is inability to overcome tumor immune suppression.
Beyond the immune checkpoint specific mechanisms currently addressed by checkpoint inhibitors.
We know today is that you must utilize a variety of mechanisms independent of the immune checkpoints to suppress T cell attack.
The ability to more broadly overcome tumor immune suppression, while also generating potent tumor attacking T cells presents the potential to more effectively treat a broader percentage of cancer patients.
Clothing terminally ill cancer patients as our current data suggests.
Our Pds biotech our technology platforms are designed to specifically address these two critical limitations of immunotherapy.
We believe this proprietary approach to immunotherapy could clearly differentiate pds biotech from our peers.
With regards to in vivo <unk> killer T cell induction at the society for immunotherapy of cancer conference known as S. ITC This past week.
Our collaborators at the National Cancer Institute, and the MD Anderson Cancer Center presented the results of Immunological studies performed as part of their respectively met phase II clinical trials.
These studies were aimed at further documenting the immunological mechanisms by which burst immune anniversarying plus IL 12 work.
They also document the types of immune responses generated and their correlation with clinical efficacy.
The MD Anderson poster reported the induction of Polyfunctional CDA T cells, which were shown to infiltrate the tumor when pdf's <unk> hundred one is administered to locally advanced cervical cancer patients in combination with standard of care chemo radiotherapy.
No increase within the tumor cell killer T cells has been reported by MD Anderson in patients, who only received chemo radiotherapy.
In the M D. Anderson presentation, they reported an increase in the tumor DNA in the blood after chemo radiation.
They also report an increase in the killer T cell population as a result of Pds or 101 dosing.
The studies demonstrate subsequent elimination of the blood circulating tumor DNA.
This increase in tumor infiltrating CDA killer T cells correlates with clinical responses in nine out of nine patients.
Who had greater than 60% tumor shrinkage at midpoint devaluation.
Complete responses with no evidence of disease in <unk>.
Eight of the nine patients was seen by day 170.
One patient due to events not related to treatment only received three of the five <unk> hundred one doses.
This is the only patient whose treatment did not result in a complete response.
The MD Anderson data is especially eliminating because the immune responses are not confounded by the presence of any other immunotherapy.
The observed immune responses are solely attributable to Pds for one one.
The National Cancer Institute also reported immunological data, resulting from the administration of the Pds <unk> based triple combination and checkpoint inhibitor refractory patients.
This study also demonstrated the induction of HPV 16 specific killer T cells in the blood accretive patients.
Firming, the immunological role of Pds <unk>.
A significant increase in ground zone B inducing CD eight T cells was also demonstrated.
<unk> is associated with killer T cells that have the ability to target and kill cancer cells.
We believe the results reported at S. ITC support the potential of <unk> based products to successfully overcome the first critical limitation of immunotherapy by.
By generating the right type write quantity and right potency of tumor infiltrating killer T cell in advanced cancer patients.
The second challenge is.
It's more broadly overcoming mechanisms used by tumors evade detection by the immune system.
As cancer progresses.
Multiple regulatory mechanisms are co opted by the tumors to evade attack by T cells.
Some of these mechanisms are independent of the immune checkpoints that are blocked by checkpoint inhibitors.
For example.
In the difficult to treat HPV positive cancer population.
The response rate with checkpoint inhibitors is reported to be about 13% to 20%.
And diverse hotels, there was zero two study.
We appear to demonstrate in the early data and checkpoint inhibitor naive patients.
Is that by blocking the immune checkpoints with Keytruda.
And promoting HPV specific CD eight T cell induction with Pds, a one to one.
We improved the response rates to over 40%.
In the National Cancer Institute study.
Using diverse immune plus IL 12 platform in the Triple combination study.
In a similar population of HPV prostate cancer patients, who are naive to checkpoint inhibitor therapy.
The National Cancer Institute reported an objective response rate of 88%.
We believe this may be due to the fact that the triple combination is able to more effectively overcome the tumor immune suppression, therefore, making a larger percentage of tumors more susceptible to attack by the Pds or 101 in views killer T cells.
Also we see in this population.
75% survival rate at 25 months.
The key note zero $4 eight study reports on overall survival of 51% at 12 months with the combination of chemotherapy and Keytruda.
Current metastatic head and neck cancer.
Further evidence of this effect is seen in the checkpoint inhibitor refractory arm of the Triple combination study.
In this population.
And the patients who received the optimal dose the National Cancer Institute reported an objective response rate of 63%.
To start with you. This patient group has an objective response of less than 10%.
Also in the full cohort, including those who received both optimal.
Sub optimal dose combinations, the national Cancer Institute reported a 66% survival.
After a median of 16 months of follow up.
The historical median survival for this population is reported to be only three to four months.
These results suggest that the triple combination may be effective in addressing one of the key limitations of immunotherapy, which is broadly overcoming tumor immune suppression beyond what is achievable with checkpoint inhibitors alone.
As you can see in the table.
We have strategically collaborated with some of the most respected cancer centers in the world to perform doesn't broad range of studies to enable us to more quickly understand and which indications the various combinations may work better.
To allow us to select the most promising combinations and indications to rapidly progress into Registrational trials.
As we look ahead to 2023 and beyond.
Our key priority is to advance <unk> hundred one as rapidly as possible to commercialization in as many indications as feasible.
To date, we have reported phase II efficacy data from over 60 patients and safety data from over 100 patients in three trials.
And we are encouraged by the fact that the clinical and immunological results continued to be consistent.
And to demonstrate the potential efficacy and safety of Pds or 101.
The data generated in diverse hotels University with two trials to date for example has allowed us to determine that the dual combination of Pds <unk> and Keytruda.
<unk> be most suitable to address recurrent metastatic checkpoint inhibitor naive.
HPV 16 related head and neck cancer.
However.
In more advanced checkpoint inhibitor refractory disease, the data generated by the National Cancer Institute using diverse Simeon plus IL 12 platform in the Triple combination.
Just that in such advanced disease, the ability to more broadly overcome tumor immune suppression, while generating tumor attacking T cells makes this our preferred combination to further evaluate in this patient population in a registrational trial.
As you are aware <unk> hundred one in combination with Keytruda has been granted fast track designation by the FDA.
We met in the third quarter with the FDA to discuss the potential to progress the combination into a registrational trial.
We announced this quarter that based on a successful FDA meeting Pdfs biotech has begun the process of preparing next steps towards a registrational trial in 2023.
The FDA provided guidance on key elements of the clinical and CMC program that will support the submission of a biologics license application for our lead assets Pds <unk>.
The guidance received from the FDA ahead of completing the phase II trial has the potential to speed up our development timeline by approximately one year.
Similarly, with the NCI National Cancer Institute led Triple combination.
We announced this quarter the Pds biotech and the National Cancer Institute has decided to end recruitment into the trial to focus our initial attention on progressing development of the triple combination in the checkpoint inhibitor refractory population.
To this end, both Pds biotech and the National Cancer Institute are encouraged by the data to date.
And remain hopeful that we will meet with the FDA before the end of the year.
Depending on the FDA meeting schedule and upcoming holidays.
As I alluded to in our last conference call.
We did get the go ahead from the FDA to progress the versatile zero-zero two trial into a registrational trial.
It would take precedence over initiation of PBS or one or three.
As a result, we have moved the preparation date for the <unk> III IND to the first half of 2023.
Clinical manufacturing of the product is progressing as previously stated.
I would now like to turn the call over to Lauren for her to take us through the clinical data recently presented at <unk> by our collaborators at MD Anderson Cancer Center, and the National Cancer Institute Lauren.
Thanks Frank.
Now turning to the data presented at ITC.
Data from the NCI Triple combination were presented on immune responses and the checkpoint inhibitor refractory population.
There are very few treatment options available.
<unk> presented included a more than twofold increase in circulating HPV 16 specific T cells in the blood of 79% or 11 of 14 of the evaluated patients on day 15 after treatment.
Immune responses were associated with increases in natural killer cells soluble grandson D, which is associated with active killer T cells, interferon gamma and TNF Alpha signaling a pro inflammatory response.
Immunogenicity findings highlight the potential role of the combination and altering immune suppressive forces and support previously announced results documenting promising clinical outcomes and as PPI refractory population receiving the triple combination.
And overall early increases in several monitored.
Such as grandson B and interferon Gamma for example, <unk> were associated with a clinical response.
The outcomes that we've seen in the expanded interim data along with the T. C. 2022 presentation continue to demonstrate potential induction of high quality and relevant immune responses that may be associated with clinical efficacy durability and safety in a very challenging.
<unk> patient population with very few available treatment options.
These results confirm the decision made by Pdf's biotech and NCI to focus on the CPI refractory patient population for ongoing clinical development of a triple combination regimen.
Turning now to the MD Anderson phase III immuno search trial, which is investigating Pds <unk> hundred one in combination with standard of care Chemo radiotherapy also known as CRT for the treatment of locally advanced cervical cancer.
Highlights here include the family.
17 patients have been involved in the trial to date.
Seven of the nine patients 78%.
Globally advanced FICO stage, three and stage four surgical cancer nine of the 17 patients have completed a day 170 post treatment positron emission tomography computed tomography or pet scan.
Scan to assess the status of the cancer.
100% for all nine patients treated with the combination of PD 101, and CRT demonstrated an objective response on day 175 C T.
89% or eight of these nine patients treated with the combination of <unk> hundred one CRT demonstrated a complete response or CR with no evidence of disease on day, one Saturday by Cat C T.
One patient who only received three of the five scheduled doses of <unk> hundred one future non treatment related events showed signs of residual disease.
As a result of disease free survival at one year is also 89%.
The one year overall survival is 89% or eight of nine patients as one patient who had a complete response has died as a result of an event unrelated to either the treatment or their underlying disease.
Patients treated with the combination of PDF of 101 in CRT had a 71% increase in multi cytokine in D C.
Also known as highly functional chiller CDA positive T cells within the tumors from baseline to the end of treatment. This increase went from 38% to 65%.
This increase in activated T cells was not seen in a prospective monitoring cohort of patients receiving similar standard care chemo radiation therapy alone.
With respect to safety and Tolerability of Pds are one on one self limited low grade local injection site reactions continued to predominate.
We are pleased by these promising preliminary efficacy and safety results seen to date from the ongoing EMEA surf trial and look forward to its continued progress.
In late October we hosted a key opinion leader round people with presentations by doctors Vod grows from the department of head and neck surgery Division of surgery, The University of Texas, MD Anderson Cancer Center Cats.
Kathryn a price co chair of the head and neck disease group at Mayo Clinic comprehensive cancer Center, and Jared White head and neck cancers section Chi Leinberger comprehensive cancer Center USC school of Medicine.
The well attended events focused on the current treatment of head and neck cancer, and how Pds, a 101 might fit into the treatment paradigm, notably the Pds <unk> Keytruda combination shows the potential to treat patients with extremely debilitating recurrent metastatic head and neck cancer and pre.
Breast oncologist goals of improved clinical outcomes and quality of life.
Now shifting to our preclinical programs.
Data on both Pds <unk> and Pds <unk> three were recently presented at the 2022 American Association for Cancer Research also known as ACR Special conference on tumor immunology and immunotherapy.
Poster presentation highlighted the development diverse immune based drug formulations containing multi epitope peptide antigen sequences of the tumor associated protein TARP, which is known as T cell receptor gamma chain alternate reading frame protein.
And modified sequence of the muck one oncoprotein.
John .
The research presented provided the foundation for the development of Pds, a one or two as a potential treatment for TARP associated acute myeloid leukemia, prostate and breast cancers, and PDL one O three as a potential treatment for mark one associated breast colon lung ovarian and.
Other cancers too.
<unk> findings for PDL, one or two were high levels of CD eight killer T cell responses against multiple target antigens and predominant induction of Polyfunctional potent killer T cells.
Key findings for Pds open on three work similar high levels of CVA killer T cell responses against multiple mock one antigen and effective targeting and killing of Mach one positive target.
In the body in vivo.
We are pleased with the preclinical research to date for these compounds confirming their biologic activity.
Manufacturer of PDL, one or two clinical outages is in progress as is the manufacturer of Pds Oh, one O three clinical product.
With respect to our in fact immune platform data were presented at the American Society of Nephrology meeting in July .
In this study data highlighted that the vaccine in fact immune co delivered with influenza computationally optimized broadly reactive antigens known as Cobra antigens generate T cell and antibody against multiple strains of the flu and importantly.
<unk> provided full protection against lethal infection in animals.
We remain excited by these data, suggesting that Pds O to O. Two has the potential to achieve the goal of providing the broad protection thought in a universal influenza vaccine.
We are in discussions with ni AIG regarding clinical funding for this vaccine and we will keep you informed as decisions are made.
At this time this completes my data presentation and I'll now turn over the call to Matt to review our financial results.
Matt.
Thank you Lauren this quarter was a tremendous one for the company in late August we completed a $35 million financing receiving an initial tranche of $25 million, which immediately strengthened our balance sheet and provided the financial resources necessary to advance the company's clinical pipeline specifically.
Operations for Registrational trial for our lead candidate P. DSO one O one.
Looking at our summary financials for the third quarter ended September 32022.
Research and development expenses increased to $4 4 million for the three months ended September 32022 from $3 7 million for the three months ended September 32021, the increase of $7 million and 22 was primarily attributable to an increase of $2 million of clinical studies and research costs.
$3 million in personnel costs.
And $44 million in manufacturing services, partially offset by a decrease of $42 million in professional fees and facilities.
General and administrative expenses decreased to $2 9 million for the three months ended September 32022 from $3 3 million for the three months ended September 32021.
The decrease of <unk> $4 million is primarily attributable to a decrease of $5 million in personnel costs.
A decrease of $1 million and facilities costs.
Offset by.
An increase of $42 million in professional fees.
We ended the quarter with approximately $71 6 million in cash a strong position as a result of our partnering model and continuous financial discipline with a registrational trial beginning in 2023, we estimate we will fund our operations through mid 2020 for.
That concludes my portion of the call and I'd like to turn the call over to the operator for a question and answer session.
Operator.
Thank you at this time, we'll be conducting a question and answer session.
I'd like to ask a question. Please press star one on your telephone keypad than a confirmation tone will indicate your line is in the question queue.
We first start to feel like to remove your question from the queue.
For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.
One moment. Please so we pull for questions. Once again that is star one thank you.
Yes.
Thank you.
Our first question comes from the line of Louise Chen Cantor Fitzgerald. Please proceed with your questions.
Hi, Good morning, this is carvey on to Luis from charter.
For taking our questions. Our first question is Oh.
On your HPV associated locally advanced cervical cancer.
I wonder how the landscape what your bulk overtime and how does Pds <unk> fit within the treatment paradigm along with other potential treatments second is on your flu vaccine opportunity curious just to know more about how you size or help us understand the opportunity for you and lastly, what was sufficient.
Feedback on your pipeline.
ITC conference. This year. Thank you so much.
Perfect. Thank.
Thank you very much for the questions I'll take the first.
Top of the questions and I will also hand over to Loren to add anything she might want to add to the answer so with cervical cancer.
But the standard of care as you May know is chemo radiotherapy that has really been the standard of care for a few years now for several years now.
And despite the fact that there is there are reasonably compared to other cancers reasonably effective initial responses one of the key.
Key limitations of the CRT approach its recurrence of the cancer.
There is still a significant unmet need in this space you may recall back.
Less than a year ago, probably several months ago. There was announcement by Astrazeneca that they have they have failed their phase three trial in this exact same patient population combining and be a checkpoint inhibitor.
With chemo radiotherapy.
The goal there is really to try to improve their responses and also to prolong the duration of survival of patients. So that is something that oncologist and the cervical cancer space are really aggressively and actively looking for.
One of the key things we did here is we.
The high risk patient population, both patients who have the lowest chance of seeing clinical benefit as well as the highest chance of recurrence of the cancer right. So these were patients with large tumors approximate.
<unk> size or larger.
These are patients who were likely we'd also have.
Metastasis into the lymph nodes.
So with this with these patients these are the difficult to treat patients and the data we've generated to date suggests strong potential of the ability of <unk> 101, with the generation of these killer T cells.
To really be able to attack and treat these counts with what those were.
Interesting in the data would be presented for example, what's the circulating tumor DNA.
Where do you see that the patients have circulating tumor DNA at the time of treatment, but in correlation with extension or expansion of the CDA T cells.
You see the decline in the.
Decline in the circulating tumor DNA to zero right. So this is very encouraging data early data right. So we still have the data currently from nine patients, but highly encouraging so far and this is an area that we will continue to monitor and also opportunity opportunistic just like we've been with versatile once we get a sufficient number.
Patients pending what the data looks like at that time, we may decide to have discussions with the FDA and determine where we go from there with that with that treatment.
So thats still continue with cervical cancer with the universal flu.
Opportunity with Universal flu, we believe is a significant opportunity as you know.
This is <unk>.
<unk> seen that the industry has been trying to develop for.
Several years, probably more than a decade.
Because of the fact that the spring soft flu are very variable and change from year to year and with every year coming we are trying to determine what the predominant spring would be in developed a vaccine hopefully protect us against the dominant strain for that particular flu season.
Right.
Often.
There are.
There are years, where the efficacy of the vaccine is reported to be less than 50%.
And so what the universal flu vaccine approaches trying to address.
Developing a vaccine that will be effective against a broad range of varian move errands, and which would protect potentially protect us against multiple strains of the flu and that could eliminate the need to be developing a new the new flu vaccine every year right. The initial data.
And presented to date has been very encouraging things that we can provide.
Generate neutralizing antibodies against a wide variety of these.
<unk> strength and also provide strong protection against lethal challenge.
The next step for US notes, we are still in discussions with the NIH.
Who are very interested in the data.
So we are now discussing the next options and next steps in terms of where we go from here with the clinical trial design would look like and if we could potentially get funding from the NIH to move this into a into a pivotal trial. So those discussions are ongoing and we will hopefully be able to.
Provide an announcement sometime soon.
And besides that.
Be willing to move this into phase one.
Human clinical trial.
And then the.
The third question you asked could you remind me the third question.
Yes, I'm just curious to know more about this decision feedback when your data is it okay perfect.
Yes, I will at this time to hand over to Lauren Lauren do you have anything to add to what I said and also the physician feedback.
I see.
Yes, I think one of the greatest areas of interest is the fact that we now have clinical outcomes that include imaging outcomes as well as Immunogenicity and importantly, a surrogate biomarker for direct tumor.
Tumor measurement in terms of the circulating tumor DNA. This is particularly important in HPV associated cancers because.
There is emerging in clinical practice, the availability to track circulating tumor DNA in HPV related cancers.
And the fact that we see induction of these polyfunctional potent CDA T cells within the tumor microenvironment of the cervical cancer patients and we see those sales increase and there is a corresponding decrease in circulating tumor DNA has the potential to be very exciting.
I do know that to the NCI is planning on measuring circulating tumor DNA in the Triple combination study, we don't have that data yet, but that is really a key area of interest that we have seen in terms of feedback that we've received.
Great Super helpful. Congrats on the data and progress this quarter. Thank you.
Our next question is from the line of <unk> <unk> with B Riley. Please proceed with your question.
Hey, Good morning. This is Andy on for <unk>. Thank you for taking questions and congratulations on the progress maybe.
Maybe just to kind of build starting on the cervical cancer patients can you set expectations for what chemo radiotherapy would achieve in this patient population in terms of response rate and complete response and are there any large scale randomized trials that you can point to you in this area of that.
Can help us get a better sense of advocacy and then I have a few follow up questions.
Oh sure so I'll start again and hand over to Lauren.
I think in terms of the cervical cancer and the potential of it.
Combination here I think one of the key things that we're looking at as Lori just mentioned is understanding exactly how pds <unk> 101 O versus immune is impacting the treatment regimen and exactly what <unk> hundred one could potentially be doing to improve the therapy for these patients.
As Laura mentioned in these patients who are not treated with <unk> hundred one there was no evidence of increased CDA T cell induction in these patients and you'll see that very clearly with the patients who are treated with Pds <unk> hundred one.
Also in terms of the survival of these patients. So as Ron also mentioned that the vast majority of these patients are stage three and stage four patients for.
So visa late stage cancer patients typically the initial response in these patients I think.
MD Anderson reported earlier in the abstract.
70%.
But what's most debilitating for these patients is then disease recurrence, which is really high at the stage of cancer progresses.
Right. So as you progress to stage three and stage four you see pretty high rates of recurrent starting before even a year.
And so that's really both on the key characteristics and outcomes that we're looking at so we've seen a significant improvement in the clinical response from about 70% to about a 100% and almost 90% complete response, we also see 100% survival of these patients one patient died from a non disease related or treat.
<unk> related events, but really now monitoring these patients to see if we can significantly enhance the overall survival as well as limit the disease recurrence.
In terms of a similar large law trial. The one I'll refer you to is the one I just referred to.
Simply concluded by Astrazeneca worthy.
At this exact same patient population locally advanced cervical cancer, where they combined.
Anti PD, one checkpoint inhibitor with chemo radiotherapy, so very similar to what we are doing a fair, but we are combining hours with Pds <unk> hundred one of course with the checkpoint inhibitor.
And we are hopeful based upon the data we've seen and unfortunately know about the importance of killer T cells. The right type of killer T cell because what <unk> hundred one appears to be doing and so we are very pleased with what we've seen so far in highly encouraged.
And look forward to continuing to monitor these patients to really understand.
The immediate near term outcomes by the long term durability of the combination.
That's helpful and would you and then.
Yeah.
Go ahead.
Yeah, I was just going to ask a follow up on the T cell adoption.
We know that chemo radiotherapy, you don't see an increase in the tumor of these cells can you also confirm that you don't see an increase in blood and then maybe on the increases that you are seeing in the blood.
Do you have a sense of how larger fold increase you believe is sufficient and then also where are you able to kind of monitor the changes in T cells over time or is it really just that 15 day data point that you worked out.
Okay.
So two trials and long as really the expert with circulating tumor DNA, so I'll hand over to Loren shortly.
And we are looking at two trials here, so with the National Cancer Institute trial, They monitor those T cell responses they looked at the <unk>.
Immune correlates before initiation of treatment and 15 days after treatment. So this will limit it to that time period and they focus on the checkpoint inhibitor refractory population and what they showed in that case is very clear induction.
The multi functional HPV 16 specific T cells, and so via T cell characterization was specific to what Pds <unk> hundred one should induce and shoring up what we see some increased significant increase in that specific T cell population that targets HPV 16 cancers in the responding patients.
So they showed a very strong correlation between that and responses as well as things like <unk>, which is specific to active tumor attacking CDA killer T cells.
They also look at things like interferon gamma showing increases in all of those correlate.
It was very informative in terms of the role of PD, one and those immune correlates with AMD with VY <unk> hundred one.
What's very interesting about the MD Anderson study, but did not look only at the circulating T cell responses, but they also look at the T cell, but actually infiltrate the tumor microenvironment, which is very important right. Because we can generate T cells, which may increase in the blood, but may not be effective in targeting and actually infiltrating tumors.
And so what the MD Anderson study tells US and shows US is that we see a strong correlation between what we have observed in the preclinical studies, where we see these T cells effectively infiltrate the tumor meter tumor there we see a very similar thing happening in the humans and this is the first study that we have done to date in humans characterizing.
T cell response within the tumor itself. So very informative study is really confirming what we've seen in our preclinical studies.
What was also very interesting about the MD Anderson study Oxy mentioned, if the circulating tumor DNA.
And so what they show.
And the poster will be presented.
The patients have circulating tumor DNA at the time of treatment startup treatment.
They also showed in again.
We haven't attributed any cost and effect to that but what they showed was that after initiation of treatment. There was a significant increase.
The level of inquiries varies from patient to patient about the significant increase in the circulating tumor DNA. After chemo radiation started but what they also showed was that as the CD eight T cell response buildup in Vale.
T cell response within the tumor.
<unk> zero and then at a number of time points all the way through hundred 70 days right. So therefore, the longer duration evaluation of the T cell response, but what they showed was that <unk> <unk>. Five for example, you could see a very strong CDA T cell response, but by that time, what they also showed was that circulating tumor DNA had gone down to zero right.
Alright, so it appears to suggest that as we generate the T cell CDA T cell response, it's effective in lowering and eliminating the circulating tumor DNA, which is which is very important and what you want to see quite effective T cell immunotherapy, Lauren I'll hand over to you to add to anything you may want to add to that.
Thank you Frank you did highlight the fact that one of the strengths of the MD. Anderson study is is that they're able to examine the time course of both these immune responses and the circulating tumor DNA responses.
At five different time points over the course of standard of care chemo radiation therapy, which has to be completed within a certain.
Time course window.
Other thing that I think is very important to note is is that.
What we're really looking for is not only these early results, but we have preliminary survival at one year and it's going to continue to be very informative as the results in the clinical outcomes on the study matures. The reason is is that surgical cancer is.
Really a disease of disenfranchisement as young women present with locally advanced disease and it is this locally advanced disease that really results in suboptimal responses to initial chemo radiation therapy as well as our predispose risk for earn.
Disease recurrence.
Diminished survival outcomes.
The <unk> trial that trial that Frank had mentioned.
Performed by Astrazeneca with their checkpoint inhibitor failed to demonstrate a benefit in terms of reduction.
The reduction in progression free survival that was not statistically significant so we clearly can see that if we are able to one have these complete responses early on and of course, the standard chemo radiation therapy as well as potential reductions in circulating tumor DNA.
We're looking to see how that will translate not only in terms of short term immediate imaging outcomes, but the longer term outcomes.
<unk> disease recurrence and continued survival.
Yes, Laurence Thanks, a lot and I think one thing to add to that as the management team here, having these studies actually independently performed by some of the world's leading experts in the field. We believe also generates confidence in the reports and very importantly for Pds biotechnology independent expert valid.
<unk> of our science.
Also very important with the steady with the MD Anderson study it highlights the breadth of the potential applications of our <unk> based products. If they are able to significantly improve the efficacy of some of the most used cancer therapies without compounding that toxicity. So to date I think we are highly encouraged by the immune correlate data generated in <unk>.
By both MD Anderson and the National Cancer Institute.
That's helpful. And then maybe one quick final question for Warren.
I think it's impressive and notable that you saw increases in <unk> B and interferon gamma.
Just maybe talking a little bit more about those was there a kind of threshold that was associated with clinical response or any more color you can provide on the correlation there would be helpful.
I wish I could provide more correlation in your question is excellent.
One of the things is that we do know is is that.
Is it the presence or absence of a specific response or is it the magnitude of a specific response as well as its presence and I think that from the data that MD. Anderson has presented we don't have a sense of whether or not theres, a certain minimum threshold that has to be at.
<unk> in terms of the magnitude of these responses, but something that we would definitely want to explore moving forward.
Point that you highlighted that we see both grandson D as well as interferon gamma historically in the past when we had been characterizing immune responses, we always measured interferon gamma and we tend to measure it.
As just a monotherapy response, but we clearly now have an understanding that when you see induction of antigen specific responses that are polyfunctional. So you see our induction of multiple different cytokines, such as interferon gamma but in addition to <unk>.
<unk>, which is specifically characteristic of cytosorb cytotoxic functional T cells as well as TNF Alpha and IL. Two is this polyfunctional potent T cells that really appear to be able to have the anti tumor efficacy that we're looking for.
And Lauren to Aflac is it correct that with these patients every patient is going to have very different kinetics, and so measuring the maximum maximum immune response in each patient is quite tricky because the fact that one patient has the maximum response on day 10 doesn't necessarily.
And that patient two will have the maximum response on day 10. It may be on day 15 for that patient, but maybe on day five right. So taken with the approach that you have to take in human clinical trials, where you look at a specific time point you may be able to monitor increases in that patients immune correlates, but you may not necessarily be able to detect.
And that this is the maximum bet. This patient actually generated just based upon the different kinetics youll see in each patient.
That's absolutely correct, Frank and it's why with given the inherent biologic variability that there is an every patients individuals immune responses when we're able to look at them collectively together and see these trends were across multiple patients. We see increases in these HPV 16 spin.
<unk> grandson be positive CDA T cells over the course of treatment and a corresponding decrease in the observed circulating tumor DNA is suggest to us that the responses that are being induced whenever they are being induced into whatever magnitude there being induced.
Or having an anti tumor effect and again early data, but very very interesting and things that we want to follow.
Excellent we'll keep looking for more there then thank you for taking the questions and congratulations again on progress.
Okay.
Yeah.
Our next question is from the line of Joe Pesci. This with H C. Wainwright. Please proceed with your questions.
Hey, everybody. Good morning, this is Joe for Joe.
So I just wanted to you know what.
Frank and Laura I mean, that's a question about the.
Factorial components of immune.
No therapy in cancer vaccines over the years and I'll link to one of the.
Components of the immuno serve study and feel free to let me know if I'm getting too much into the weeds, but youre sharing today a lot of correlates about the T cell activation, which I think is extremely important and then when you look at even in the background and how this study was conducted theyre talking about targeting tumors that are over five centimeters.
Now if you look at the past by others and other studies five centimeters always has seem to be a.
Sort of a boundary that a lot of cancer vaccine companies for example would want to target under five centimeters. So I'm just curious.
Where previously the bulk of the tumor might have been viewed as a problem.
For cancer vaccine efficacy your T cell activation here really talks to your original thesis from Franks prepared comments regarding the T cell activation data that you have.
Yes, yes.
Okay.
And I was just going to say I think what you said is very true I think one of the key things you mentioned is that there have been lots of failures in the cancer vaccine space.
Both of which we believe is attributed to the inability to induce the right type of killer T cells and the right quantity and I think what is also very important for Pds is different based upon the history in the space.
For us our technology to really show a differentiation.
What's important for us to go to the more difficult to treat cancers, because we have shown in our preclinical studies clear differentiation between.
The induction of the right type of T cell <unk>.
And tumor regression in preclinical studies and so our approach by looking at these patients who have these large high tumor burden was really twofold.
To be able to get a quick read on whether or not this is working.
And also to be able to show differentiation that these T cells are active enough to really treat the difficult to treat cancer patients that most immunotherapies wont address right. If you go all the way from there to what we're looking at with the NCI. We are looking at checkpoint inhibitor refractory patients again. This is the population of patients that almost.
No immunotherapy looks at.
Because of the tumor burden.
The difficulty in treating those patients.
What we are trying to establish here our approach is to really clearly say look this appears to be working we've looked at the most difficult to treat patient populations that no therapy forget immunotherapy, no therapies able to effectively treat.
And it was very important in the early days for US the data has been very encouraging but I think what we now have.
Both the NCI and MD Anderson is now really explaining why these combinations have worked as effectively as we have seen to date and providing some validation.
The clinical data that we have been seen in terms of this is exactly what pds <unk> hundred one is doing this is the kind of immune response is generating and also very importantly, this is exactly what we see in the preclinical studies and that data appears to translate very well based upon the technology its mechanism of action into humans right.
It's really it was a deliberate approach that we've taken in terms of really establishing the potential efficacy of our platform by looking at the more difficult to treat patient populations that not just immunotherapy, but cancer drugs in general really haven't been able to effectively address.
When you when you were going to say something when I started.
The only thing I would echo is is that this difficult to treat cancer population, particularly with cervical cancer that present with locally advanced disease. It is the real world population, where there is incredible unmet medical need. So that's again for all the reasons that Frank has already iterate it but importantly it.
It's where the patients are this is how they present with unfortunately locally advanced disease.
That is very difficult to treat and and.
Allow continued good clinical outcomes.
And those sizes of tumors, if I hear you correctly.
That's correct Yep, perfect and then I guess.
Just looking forward.
Does this immuno serve serve has the.
The beginning of the design here, where you would just do a randomized study plus or minus chemo Rad or is it do.
Do you in.
Have visions towards another type of study based on how difficult. This population is based on the recurrence rates.
I think now we are in the inflammation obtaining information stage right. It's still it's still early we would like to see data from some more patients and I think at that point, just like we've done with versatile zero-zero too. If the data continues to look encouraging us encouraging us today as we will definitely want to sit down with the <unk>.
And discuss how we could move back into a registrational trial and what's the right type of Registrational trial for this patient population would actually look like.
I think it's a little bit early now the data is highly encouraging, but we would like to see a little bit more data from these patients and then make hopefully make the right decision at that point in terms of where we go and how we designed that trial.
Sure. Thanks for the added details.
No problem.
Our next question is from the line of James Molloy with Alliance Global Partners. Please proceed with your question.
Hi, this is where our cereal on frictional I. Thank you for taking my questions. So for the end of Phase II meeting that was recently completed for the rest of the time Oh two trial what are the next steps that you are looking to taking for this trial in particular and what is just an overview of its timeline and also looking forward what might.
The idea of registration trial for this specific indication look like and is it still in line for a mid 2020 for each site. Thank you.
I'll hop Lawrence start and then I'll end up with the timelines and so forth so lowering our Honda Honda with you first.
Great. Thank you Frank so our discussions with the FDA were very helpful.
Of identifying what the.
Elements of our design should be in terms of a pivotal registrational trial, we've initiated feasibility in order to be able to.
Determine.
What needs to happen as far as we know that this is going to be a global trial and that's one of the things that we are in the process of investigating we do look to anticipate having the trial initiated in the first half of 2023.
Again, it would be dependent upon feedback that we're receiving not only from the FDA, but also from European agencies and countries, where we would be conducting the trial.
Frank.
Thanks, Thanks, Lauren Yeah. So relapsed lung said really that we are now in the clinical design stage right in terms of designing what this trial will look like working with the status of patients to understand the population. The population size and then we would definitely want to run that by the FDA again, and just make sure that the FDA.
And the agreement that if we if we run those trials as designed.
The endpoint is that it would be acceptable to the FDA.
When we are at the stage now and hopefully hopefully the goal is to hopefully get this started sometime around the middle of the middle of next year.
Okay.
Thank you for taking my questions.
Thank you.
Our next question is from the line of Robert Leboyer with Noble capital. Please proceed with your question.
Good morning, and Doctor once discussion there was a mention of one or two.
Three.
With I mentioned of the manufacturing process for clinical trials.
Is there any estimate at this point of when you might be able to file and IMT move forward to clinical trials.
Yes, so and between <unk> hundred three we prioritize Pds <unk> III. So PD one to three as I mentioned is in our going through clinical manufacturing.
And and we expect that that would very likely be the next product that goes into human clinical trials, we had initially projected.
We would be filing the IND for that program by the end of this calendar year. However, as I mentioned in the.
Earlier remarks based upon.
The Fda's agree.
The agreement that we moved <unk> into a pivotal trial and the amount of regulatory work that goes towards getting a registrational trial up and running we are prioritizing Pds <unk> 101 at this point and therefore because of that prioritization of Pds <unk>, what we decided to do is to.
I wouldn't I wouldn't want to say de prioritize but it's the <unk> 101 has taken precedent and therefore, we anticipate that the Pds <unk> suite will be ready for IND sometime in the first half of next year, just because of the prioritization now all the regulatory work, we have to do to get a global <unk>.
Global Registrational trial going.
Did that answer your question.
Yes, it did.
One or two.
102 should be following.
103, if that's also in clinical and manufacturing PDL for one of three further with PDL, one or two we have the antigen manufacturing stage PD. One is the reception of the final clinical product manufacturing stage basically a little bit ahead of peak of 103, but obviously as we continue with our business development discussions everything we have.
Discuss here today in terms of our understanding of how this technology is working really helps us with also business development activities and having discussions with other potential and prospective partners and so we keeping all our options open in terms of how quickly or how slowly those programs get into the clinic and also being.
Mystic in terms of what the financial situation of the company and so all of those are being taken into consideration in terms of the timing of both.
Both Pds <unk> hundred three and PD, one or two but the goal right now is to get our product into the commercialization path, where we just registrational trials as quickly as efficiently as possible and again, we also have in that discussion with the FDA regarding the triple combination. So the goal here is to also understand what the regulatory pathway would be.
For the Triple combination and also how quickly we can move back into commercialization. So all of those have been taken into consideration when we determine how quickly we move the pipeline also into clinical trials, but with both of them preclinical studies are complete and we and the clinical manufacturing stage towards IND.
<unk> and progression.
Okay, great. Thank you very much.
Youre welcome.
As a reminder, you May press star one to ask a question at this time.
Thank you.
At this time I will now turn the floor back to your Doctor Frankfurt Auto for closing remarks.
Thank you well. Thank you very much for joining our third quarter earnings and update call.
We've made extraordinary progress in both our clinical and preclinical development programs showing the potential of our verse immune and inspecting and platforms.
We plan to continue the momentum as we move through the fourth quarter and into 2023, and we look forward to updating you as we progress. Thank.
Thank you very much again for your time.
And have a great day.
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Thank you.