Q2 2023 Precigen Inc Earnings Call
Good morning, and welcome to the prestige in second quarter, and first half 'twenty to 'twenty, three financial results and business update call.
Please note this event is being recorded.
I would like to turn the conference over to Steve Harrison Vice President of Investor Relations.
Yes.
Thank you operator, and thank you for joining US today with me are Dr. Helen <unk>, President and CEO , presaging and Harry to May see and our CFO .
Helen will provide details on today's releases and an update on our portfolio after which Harry will review, our second quarter and first half 2023 financial results.
Our prepared remarks, we'll open the call to Q&A.
Before we begin let me briefly review our forward looking statements.
During today's call we will make various forward looking statements investors are cautioned that our forward looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results or outcomes to differ materially from those indicated by our forward looking statements.
Please read the safe Harbor statements contained in this presentation as well as risk factors contained impressive <unk>. Most recent SEC filings for a more complete discussion of these risks and uncertainties.
I will now turn the call over to Dr. Thompson Mary Helen.
Thank you, Steve and thanks to all of you for joining us today.
<unk> today is a very exciting day for precedent and I like to provide you with the significant progress that we have made in the first half of this year.
I will discuss two major topics today, one is the positive regulatory developments, which we announced this morning for our lead program <unk> 2012, and an orphan rare disease setting in the RFP and secondly, the portfolio prioritization to focus on effort.
To accelerate the development of Pier G N 2012 towards commercialization, while we continue advancement of our other key programs and extend our cash runway to 2025.
With that in mind, let's go to slide number four.
We have been as you know active in discussions with the FDA to align on a rapid regulatory path for <unk> 2012, given the high unmet need in order to patient.
But there is no approved drugs.
The treatment options remains is recurring surgeries that are a major burden for these patients.
With physically how well economically.
We are pleased to announce that the FDA has confirmed.
The ongoing single arm phase one two study will serve as the pivotal study to support BLA submission for an accelerated approval.
At the same time.
There is no additional randomized control study will be required to support accelerated approval.
And we have that agreement with the FDA on the endpoints from the ongoing phase one two study to support the BLA submission, which includes the complete response rate, which is the percentage of patients with no surgical intervention required during the 12 months following the truth.
Meant.
On an immunological surrogate marker for HPV specific T cell responses, which by the way has been already implemented both in phase one and phase two.
<unk> also has reached an agreement with FDA that a single on confirmatory study needs to be initiated but not complete it and that's very important prior to the submission of the BLA.
At the same token we.
We are very thankful to the FDA and they have even encourage that.
Too hard and evaluate the inclusion of exploratory arm to the confirmatory study for repeat dosing for the non complete responders to potentially expand the label and we are very excited about that.
The ability of the ongoing phase one two to serve as a pivotal for accelerated approval can significantly reduce the developmental time to licensed chart and you can imagine what that does that mean for our patients because now it did randomized phase threes.
It requires yet and we can move much faster that especially as I will go through the part for the license check for us.
To further expedite the development of T. Our Gen 2012, we are preparing precedence in house gene therapy manufacturing facility to produce drug substance for commercial launch.
Yeah, we do eat that simply this allows us to maintain control of manufacturing in house, we leverage our internal expertise.
And we would reduce the cost and time lines due to reduce reliance on a contract manufacturer.
Okay.
If we look at.
What has happened and it take a moment to recognize the current status of the ongoing single arm phase one two study it as you have seen and we have reported the data the phase one has been completed and the enrollment and dosing in the.
Phase two portion of this study is also complete it.
Phase II patient follow up data collection and the completion is anticipated that by the second quarter of 'twenty 'twenty four.
The phase one data that we presented in January has shown 50% of our patients.
Patients that they were treated at dose level two.
Have a complete response.
And then that means that you need that no further surgery in the follow up of 12 months.
Today, we are pleased to report that all complete responders from the phase one they remain surgery free with a minimum follow up 18 months and the responses are still ongoing.
We are very pleased and excited about the promise of the P. O Jan 2012 for RP patients who received numerous surgical procedures in the absence of therapeutic in their lifetime that can be very harmful financially burdensome to the patients and over all the health care.
Getting this therapy as quickly as possible to the patients who need relief is our highest priority obviously.
I'd like to acknowledge at this point the tremendous effort of <unk>.
Surgeon team and all the investigators and collaborators to move the T O N 2012, some discovery phase.
And two our recognition as a pivotal trial on a path for an accelerated approval in about three years.
Including the pandemic, yes.
With that in mind, if we look at the slide number five.
But I would like to highlight is what differentiates pier G. In 2012, and I didn't know worst platform from the rest.
And we see.
The debt market and the C O L research and we have listened to what all the kols have been telling us that what is unique and differentiated about this molecule in this platform.
As you can see in this slide one thing that really stands out is the mechanism of action that has been seen as very promising.
The physicians describe the pier G. N 2012 mechanism of action is promising.
Particularly they are impressed with this molecule to generate the T cell responses that specifically targets HPV, six and HPV 11 wireless pipe Todd.
Which is the root cause of our RP and this is what is important about this therapy because it goes to the root of.
The problem, which is the infection in the patients that allows this recurrence of their pops alone months in a very very dangerous regions on vocal cords and trachea and even in the lungs.
Secondly, there is a very favorable safety data, we have shown some of the safety data from phase one and as you can see and it was mentioned the safety is.
The grade one and grade two its flu like vaccination and this is extremely favorable obviously for the patients and their physicians. They appreciate that tremendously and especially that some of the patients in the future would it be pediatrics and this clearly its end.
Important factors.
So and finally debt reduction in the number of surgery I think we have heard from our patients continuously that even reduction in one less surgery, it's fundamental to that.
Now, having complete responders that over 12 months and ongoing they do not require any surgery and by the way we have been in the most severe patient population, which they require more of them three surgeries per year.
Being able to accomplish that so this is quite exciting and we are really happy for the patients.
And finally this is a plus.
Platform that we the very attractive route of administration, what does that meet these vaccines have been given subcutaneously two the patients you can imagine now the patients that they have to go continuously under surgery now they can go to their physician basically office and rich.
<unk> has sub Q injection very similar to our flu injection and this is quite the accomplishment and that differentiation.
So with that in mind, if we look at the slide number six and on top of this the slot.
What you see is the scenario that we are describing in regard to the patient.
We are looking at their normal basically vocal cord throat, often normal individual and then on the right hand side you are looking at what the RP patients suffers.
And these patients are dependent on the surgery only continuously to remove this benign tumors just to be able to talk or just to be able to breathe can you imagine having a child that you have to do these continuously on a month.
The basis takes them for this kind of surgery.
Yeah.
Obviously, there are no approved therapeutics for the RFP and this is the importance of the decision of F. D. A that are allowing us to go for accelerated approval, which I'm thankful to the F. D. A in general for recognizing the need of the patients.
And also the innovative studies that can be addressing that need.
As we have said.
The current standard of care is repeated surgeries.
And this does not.
But the underlying root of this.
Indication.
It would be.
Due to the chronic nature of the disease RP patients can undergo hundreds of surgery done.
Their lifestyle.
This repeat that surgeries as I mentioned before it can worsen the condition of our RFP as it can increase their spreads of HPV virus and can result in a significant comorbidity, including lots of work all functions.
There is a significant economic and the quality of life burden of this disease throughout the lifetime of our RP patients.
And as you can see on the slide there are and these are approximate numbers that in the U S. There are 10000 at least cases adult and six thousands of doing them and then ex U S. There is a much larger population upwards of 60 and we.
We really don't know the exact number of juveniles and these are part of the research of studies.
Well, we wouldn't be doing as part of the project at market for the U S and ex U S.
So with the potential now to accelerate to work at becoming a commercial stage company and considering the challenging capital markets at this time.
We believe that we should be laser focused on expediting that 2012 path to commercialization.
By doing this we believe that we can best position precedent for near term success in this current environment.
On slide number seven we are highlighting some of the actions that we're taking to realign our resources and pipeline to realize a substantial savings, especially with respect to external C are always spending and SG&A costs compared to the original budget.
Harry will further expand on the cost saving measures, we are taking over the past years and the colleran to yes.
But just to mention what we are now focused it's not only to accelerate the path for P. O Jan 2012 without damaging the very important other programs that we have but also extending our cash.
One way, which allows us to get to the Readouts.
The surface and beyond by various means so let's go through some of these actions.
First of all.
Reducing the cost of the clinical C. All rose four outside reducing the number of the sites that will be involved in various programs as I will go through them and definitely we have been reducing our SG&A costs and continue to do so.
And Harry will highlight that.
At the same token we are re directing our R&D team to focus on CMC and translational clinical research activity.
We have a highly productive and cross trained teams, which currently as we speak are involved in shifting focus in order to address the CMC and translational clinical translational work required to support P. R. J N 2012 time to approval.
What does this do for US first of all there is no reduction in our R&D force.
Secondly, this allows us to hold on to our talent.
Without any again I stress that head count reduction.
Furthermore, we will save time and money and trying to adjust the path and this is very very important for the very agile timelines that we have for the submission of the BLA.
In regard to our PR Gen 3000 sex Ultra car T program. This remains a high priority for US as you know we have shown positive data at ash.
Almost 30% objective response rate in the AML patients that they have no other therapy in front of them.
And we have received a fast track designation from FDA is that in view. This is extremely important program.
We plan to maintain our two very productive.
Active sites Muffin and mail for the ongoing phase one study for now.
We plan to present interim phase one data in 'twenty 'twenty four.
There will be no initiation of new sites in the remaining part of the 2023.
And we provide further updates in upcoming quarterly calls.
We also have a plan to get additional collateral tea on the plant site expansion in 2024.
In regard to PR Jan 3005, Similarly, we continue our phase one B study enrollment that's fret Hodge.
And as part of the cost saving measures, we plan to activate our second site under our credo with NCI to continued advancement of the program without major clinical or C. R O cost to us and that's very very important for our patients.
As well as for this program, which is very unique.
And with regard to PRT on 3007, obviously that program is an investigator initiated phase one at MOSFET, which is ongoing and continues to move.
Now in regard to what we mentioned a four P O Jan 2009, especially in our cervical cancer, which is by the way on the same platform I didn't know worst platform.
In 2012.
We are.
In.
I'm excited to announce that the plan is to activate the NCI side first and we leverage our crave out for the phase II study to reduce the clinical cost for this year and we will be giving update in early 'twenty 'twenty four in regards.
To the other sites.
And.
Also.
And very important that we have been in discussions.
With a number of parties Ford and non dilutive funding opportunities, which can even further extend.
Our runway from 'twenty to 'twenty five.
We have begun first of all the process of Divesting example luck.
And that is important.
And I know that Harry will speak to as we divest that the trends all wall and that has allowed us to completely pay off our convertible notes. We are also in discussion and very exciting discussion in regard to our age.
0194 T. One D program with number of parties and we are planning to give our.
Our investors an update in the upcoming quarter lease. Furthermore, there are ongoing discussions on our ultra car T program for partnerships and we will be addressing that.
And all of this are the means all non diluted funding opportunities that we have along with the cash runway that currently we have to up to 2025, and we believe that these non dilutive funding Kent.
Extend that pass along by much for that so with that exciting update I'm going to now turn the call over to our CFO Harry to discuss the financial updates on our strategy.
Thank you Helen and also thank you to those participating on the call today.
Speak from the notes or the information on slide eight just to focus a little more.
Call.
This is a momentous day for press agenda as Alan has said earlier.
Behind with the announced regulatory path for <unk> in 2012, we've positioned our balance sheet to provide us the cash runway to successfully transition toward a commercial commercial stage company.
As you'll see in our financial statements included in our 10-Q, which was filed with the SEC earlier. This morning. We have now retired all of our convertible notes. The retirement of these notes will save us $7 million per year in cash interest costs going forward.
In addition through the efficient early retirement of a significant portion of our convertible notes, we were able to save approximately $8 $4 million in cash over the past 10 months.
Turning now to a discussion around SG&A since I last or since I started with press agenda and in October of 2021, we've been laser focused on right sizing our SG&A cost for the company. We are today and I am pleased to announce that on a year to date basis compared to.
The first six months of 2022, our SG&A costs have decreased $5 $4 million or 21%.
Just looking at the second quarter of 2023 compared to the same period last year SG&A costs decreased $3 4 million or 27% showing a positive trend over the first quarter.
A portion of these savings were due to past head count reductions, which are now being realized.
We finished the quarter with $95 $6 million in cash cash equivalents and short and long term investments, providing a basis for a strong forward looking cash runway to it.
King into account the re prioritization of our pipeline selling has laid out.
Elimination of our convertible notes and continued focus on reducing SG&A expenses. We are now providing guidance on our cash runway into 2025 selling as previously mentioned.
This extended cash runway is important for our shareholders as it gives us a runway well beyond the pivotal phase two data read out of <unk> in 2012 in 2024 and provides us with substantial amount of time to obtain additional funding via non dilutive methods.
<unk>.
I will now turn the call over to the operator for Q&A Steve.
Yes. Thank you.
At this time, we will begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone.
If youre using a speakerphone. Please pick up your handset first before pressing the keys to withdraw your question. Please press Star then two.
At this time, we will pause momentarily to assemble the roster.
And the first question comes from Jason Butler with JMP Securities.
Alright, Thanks for taking my question and congrats on the progress.
Couple on Pier G N 2012.
Was there any discussion with FDA about the magnitude of benefit and a complete response rate you would need to show in the phase II portion to support accelerated approval and then can you just remind us what the patient population.
Baseline characteristics in the phase II portion look like versus phase one and then I have a follow up thank you.
Sure. Thank you. Thank you Jason So in regard obviously, we have had discussions in regard a Wednesday complete responses and we are happy that the FDA has agreed with our endpoints as I mentioned as far as the complete responders with the follow up of 12 months.
A N and our then current design of a combination of a phase one phase two <unk> data.
Sure.
Being considered at pivotal I'll add for the accelerated approval one of the things that we are very very thankful and grateful to the FDA leadership and is it.
The fact that recognition that our phase two is the exact same design as all of our phase one in the same patient population with our basically minimum of three surgery, and our bombs and bullets all phases, one and two have enrolled patients.
With the same characteristics, we have the same endpoint and this is part of the reason that the F. D. A also has.
Confirm that we can combine them.
<unk> pharma and.
Dose level two of phase one and the phase two wishes all dose levels to to get that also what is also very exciting.
And part of the discussions that we have had with the FDA and the possibility to have additional on done and those are not.
Not necessarily part of the confirmatory <unk> it can be additional and that we can expand the label well I'm going to first of all the patients that they have less than three surgeries are obviously.
Little as one surgery, even for you.
And also for repeat dosing one thing that we clearly showed in arc <unk> data presentation. In January we have the overall, 83% response rate in this patient population, 50% about patients had a complete responses and 33.
Some of our patients reduce the number of surgeries and F. D. A definitely recognizes the mechanism of action here and the value of the immunological enhancement of the T cell against HPV and has actually.
Encourage us to.
To have another arm added that we can address those partial responders by repeat dosing, which we are very thankful for that and I think it's a excellent for their future expansion of the label updates at drug product. So yes, we have had discussion on yes, we have that agreement.
And and by the way as I mentioned and I will mention again, the end points for phase, one and phase two and what we have confirmed with the FDA at the same endpoint.
Great. Thanks, and then how should we think about repeat dosing in terms of how far out you know the timing after the first dose.
Would you wait as long as 12 months or could you actually give a second dose earlier, given the and some of your complete responses at least you were seeing it within the six to 12 week timeframe.
Yeah excellent question definitely this is something that currently we are discussing with all of our investigators for this as you can imagine there are ones that they are depending on the number of the surgery.
Then if patients are not complete responders, obviously, they might after theyre, finishing the course, which by the way the course of their treatment here is for vaccination for treatment and once that is finished you can imagine if the patient requests.
Liars or surgery two months later or so then this is something that we can obviously, it's not a complete responder and it wouldn't be at at this point is considered a partial responder or non responder and with that we can design various aspects and then we can also look at that.
A number of different patient population. This is all in discussions with our investigators and obviously as we design. Those arms are we won't be going back to the FDA and also seek further guiding a true breakthrough designation, which is extremely valuable.
And important to us because it allows us to have a continuous dialogue in a very rapid fashion with the FDA a number of things and this would be part of it. So we are looking forward to that but then again I want to stress. This is not part of the confirmatory. This is optional for us and it's actually it's encouraging.
The F D. A sees the positive a result of this that would like us to and encourages us to even go for that extend that repeat dosing.
Yeah.
Thank you and congrats again.
Thank you.
Thank you and the next question comes from Jennifer <unk> with Cantor Fitzgerald.
Hey, good morning, Thanks for taking my call.
And congrats on a lot of good progress this quarter, especially with 2012, maybe to start off on 2012.
Yeah.
Is there a way we should think about the timeline between the positive phase or if theres positive safety data in the second quarter.
The confirmatory study and then BLA submission.
And I know you just said that the exploratory arms aren't required for BLA submission, but would you want to submit something on that point in conjunction with the submission or where you know what is your thinking currently and I have a few more after thanks.
Yeah.
Obviously, we are laser focused first on getting Agra.
All of their ducks in a row and are moving towards the BLA submission as you know.
And we have mentioned and that's why it's one of the exciting part.
One too they are single arm is the open label is not randomized and as the data comes in we have the data and are clearly a weekend and thought a preparation.
Also have a plan through our.
The breakthrough designation.
To move and I asked for a rolling BLA and this is part of our strategy. So for fact that rabbit and finally the last is.
Mentioned, our phase II follow up will be done by the second quarter of 2024. So we have all the intention to be prepared and move as fast as we can for the submission of our BLA in regard to the confirmatory trial clearly our confirmatory trial.
And as part of that agreement is going to be again, a single arm trial very similar to what we have done and that has to be just initiated and we are already in the process of that and you can imagine there is really not that much a discussion around the design of this.
What needs to be done as far as the arm for the extension of the label and inclusion of their patients with the lower burden of the disease or for the repeat dosing. This is something that.
Currently we are discussing and after designed clearly we will see how that can be done, but the first priority for us is to put their confirmatory in initiate that ads b submit the BLA because it's every inch of intention for us.
To submit the BLA at as soon as possible as we know is that these patients have no other options and we're looking forward to get this to the commercial taught us on this call.
Got it.
Okay wonderful and as you look at the 18 month follow up data in this complete responders and you're considering you know the ability for re dosing how does all of that play into your current thinking about pricing.
Yeah. So.
So yes, we are receiving that data and we see the data as it goes number one since they are still complete responders and they are in response they have not require any read dosing. So obviously, that's very exciting and we're very very happy for the patient.
In regard to debt patients that.
Are partial responders and we are designing their arm to address.
That repeat dosing. This is something that we will be addressing and we will report on what the design would be in the upcoming months and we will be further discuss about the market and the pricing at that point.
Okay, Great and then my last question just on your discussions with.
Parties for non dilutive opportunities I think to that you are two focuses that you mentioned was where AG or one nine and then the ultra car T platform.
I guess when you're talking about the discussion.
What type of framework are you working under is this more like a research and development collaboration or is it something where we're at.
Just trying to understand what the upfront in terms might be to you guys.
Absolutely so in regard to the edges of the one nine as you know we have had their phase two data are positive phase two data and.
Google pad also prepare for the phase three and our manufacturing.
Rochelle manufacturing however, we had refrain from entering to the phase III because of the prioritization of the program on the cash requirement that the program had a in the past year and a half it has become very clear in the field.
And that especially with the approval of some of the antibodies for the antibody and capitalism up for T. N type one D and actually put an injunction with the data that we have shown both as a monotherapy and in combination that it actually superior.
To that treatment. The age is that a one nine has become a center of attention.
We're in discussion with number of parties and this discussion is not about the research development I would say on the level of it is at a 109 for sure and it's a required is talking about partnerships and in regards to the ultra car T. Similarly in view of the some of the day.
Especially on the AML that we have shown and the potential in the solid tumors.
We are in discussion with a number of parties that it's taken into consideration.
Various type of but collaboration or partnership.
That.
Addresses our research and clinical and we won't be reporting hopefully in the near future on dose and finally, I think maybe I can add this even though you didn't ask it Jennifer we are also very excited about nowadays.
We have thought that the progress on Divesture of our subsidiary exemplar and I think this will be also very important in providing non dilutive cash to extend our runway from 2025 to five.
So those are all the means that up by <unk>.
Now extending our cash runway to 2025, not only we get our data readout, but also it allows defloration off these discussions that we have with various partners to.
To come to hopefully a reality and that will even further extend our cash runway.
Okay very helpful. Thanks, again, guys and congrats.
Sure.
Thank you and the next question comes from Arthur He with H C. Wainwright.
Yeah.
Hey, good morning.
Thanks for taking hi.
Thanks for taking my question, just a technical difficulty.
Thank you for the question had been asked before.
So.
So regarding the <unk> program.
I'm just curious.
Your perspective.
The efficacy data.
And the point of what is kind of efficacy you think used a critical threshold and what kind of data do you think is more commercially favorable.
I think from a perspective of commercially favorable and you can see there is nothing that there's no other therapeutic I'm from <unk>.
That currently exist for these patients except number of surgeries over and over and over again in the lifetime of this and if you can imagine that if you have this at least from a childhood it means a lifetime.
Surgeries and challenges.
So in that regard, we hope to be the first therapeutic on the market for this disease patient population in regard to the efficacy as well we have said.
We have.
Our ramp in these shown what as far as 50% of our patients from phase one and it is they are a complete responders.
And one thing that we have discussed with FDA and it's very clear that surgeries alone doesn't lead to the regression of the.
These patients and because if it was then all the years that these patients had the surgeries. They should've been cured by now, which unfortunately that is not the case and therefore, we have the.
Yeah automatically correction, it's not there, but even if you consider that it's gonna be above 10% you will be benefiting this patient population, but we are currently standing at 50% response rate.
So we are very excited and by the way. This is a very deep response, not only we have completed our 12 months of a response, but as I mentioned.
From a phase one odd patients responses to complete responses are ongoing and none of them have required answered.
Yes. Thank you for that answer and just go a little bit deeper.
The study.
During our conversation with the FDA did they put any hello for the pre existing level of the antibody to the factor.
As a screening.
Climate for the patient and also did they make a requirement for a morning.
Good.
Are we seeing the body uphold their treatment.
We already had them actually.
In our design, we already had the immunological readout, which included both neutralizing antibodies as well as H P. B a specific T cells.
And actually F D. A very much appreciated that and recognize the importance of these readouts in conjunction with the mechanism of action that we are showing and one thing I should remind everyone in regards to the other in the worst platform again.
As we have shown in previous Ah They eat out both in regards to pier G. In 2012, but P O Jan 2009.
And even in healthy volunteers, there is no prior or very little.
Pre immunity to the Gorilla Adenoviruses and this is the uniqueness.
All this platform one other things that in the data with Pier G. N 2012, we showed in January is that upon repeat dosing.
You would not see increases in neutralizing antibody or if there is a slight increase then it comes down and therefore, you will not have the issues that you're having with AB five and other viruses, which basically limits you, giving this only once.
That you can give twice and we have shown now that data.
Extensively for various drug products that tells us that other than the west platform. Both Piazza in 2012, and 2009 and similar I would remind everyone that we have shown and HPV as specific T cells from our phase one pier G N 2012.
As well as phase one and in <unk> 2009, which in those setting their patients that they had HPV cancers for instance, upon repeat dosing.
Monthly basis.
We have shown that you can keep enhancing the T cell responses.
Over the years for instance that the patients have been on treatment and again. This is part of the differentiation of the mechanism of action of this platform versus all the other at five Threatful viruses.
And other platform that existed.
Oh, that's great.
If I may I guess, if I may.
Squeezebox question, so regarding the market outside the U S. What's your kind of strategy for that thanks.
As we just have.
Confirmed with the FDA, we are moving rapidly with the discussions with the MAA at the same token with the U K and also the Japan currently and to basically position PST in 2012, as a drug products and also on a path for a license there.
Oh. Thank you. Thanks for thanks for taking my question and congrats on the progress.
Thank you.
Thank you and our next question comes from Ben Burnett with Stifel.
Hey, Thank you very much and I walked through in my congrats on the progress this quarter.
Thank you Ben.
Sticking with Pier G in 2012.
You in the past you provided efficacy on a number of different endpoints. In addition to the 12 month CR rates I guess, what's kind of the totality of the data that the FDA is going to look at it or are they are they focus on there's other endpoint.
Good points that you've shown in and I guess, maybe how focused are they on durability versus response rate.
I think a very good question, but first of all the parts of the endpoints that we put forward, which was a very meaningful was it.
We didn't go for reduction in the number of surgeries.
We went for upfront and we provided it was that no surgeries required and we made that for 12 months, which is quite a long period of time it was not for certain.
Three months or six months and one other thing that we did Ah, which I believe it was a scene.
Seen as a very positive point was we went to a very severe patient population.
Which they required three surgeries and Hyatt.
So all those elements together.
Not only shows the durability of the immune response, especially now that we continue obviously following all of our patients and are especially with the responders. We are showing they are well past 12 months and they continue to be in full response.
So that speaks to the durability of that response at 12 months follow up and beyond now.
On the other hand, the fact that we showed and mechanism of action associated with it.
And I think this is again was appreciated by the FDA leadership, because clearly we have clinical data from the patients that are in full response.
They have generated.
Perfect HPV, six and 11 responses.
And that obviously this is due to that treatment as these patients did not have these responses prior to entering into the trial. So I think that has become very very important and the fact that.
<unk> mechanism of action it relates to the ability to re dose with the I didn't know where its platform again, that's a huge differentiation and difference between us and others. Because we did you allow now too.
Number of in this case is of course, a floor at over 85 days.
And by the way subcutaneously, given and it allows obviously.
Having increase neutralizing antibodies are tremendous increase.
That neutralizing antibodies, which will hinder that usually the T cells and we don't see that at all I'll pause there.
It allowed all of that to.
To be considered as the uniqueness of disrupt product and also the SBA.
Confirmation for accepting the endpoints that we had plus the immunological markers that we have.
Currently <unk> has.
Put in the trials and the us.
Okay excellent that's that's very helpful.
I would also like to ask a question around this repeat dosing, which I think is really interesting I guess do you have a sense at this point like how many patients would kind of constitute a relevant database to adjudicate efficacy of repeat dosing in it and I'm, assuming with repeat dosing just be.
The four dose course.
It is or would you maybe modify that course.
You re dosing.
Yeah, I think that that's a discussion that we have with our investigators are clearly you can think of various scenario for repeat dosing Ah that patients or 40 cents. After a period of when if they require surgery and <unk>.
Comes albeit that they are not fooled responders then they can receive and.
Another course or are you can imagine also a situation that these patients received a single doses throughout.
Because again because of uniqueness of this platform and the fact that you can give it in their repeated fashion as we have done for <unk> 2009 on a monthly basis and we have had patients on the trial that they received this over two years and we had complete responders that are similar.
They went to very deep responses.
For over a year after receiving that.
Vaccination with PR. Gen 2009. This also can become another scenario that you can be doing.
On a monthly basis or.
Every three months and this is the discussions that we have based on the immunological readout and we will be designing appropriate arms to address exactly that factor.
For repeat dosing.
To address the full population and you can imagine also this is M. P. O. Jan 2012, clearly is extremely important in this RFP and for US it's very very important to address.
The whole patient population, if we can and we will do that as we also will go into the pediatric population.
Okay Fantastic and if I could just maybe squeeze one more just clarification question sure.
Cash runway, which by the way great to hear.
About the cash runway and obviously congrats on that fully.
The remaining debt.
Does the updated cash runway include costs associated with this this expansion repeat dosing cohort and the confirmatory study or is that separate.
Yeah.
It does include than it does include some of that.
To the specificity as Helena said, we were still needing to design that book, but there is contemplation of those costs. Yeah. Then I can also say that it doesn't include the confirmatory because again, our confirmatory is a single arm I want to remind everyone. It's not a randomized.
Control phase III will be a single arm with the similar exact design as we have done with the phase one or phase two.
<unk> debt extended arms is something that we will be discussed but that does not have to be initiated prior.
Prior to BLA and we can initiate those arms at a later point after the design so for the purposes of the costs and a runway we have consider.
Part of our manufacturing as you can see that we are switching our own manufacturing by re prioritizing.
Own manufacturing facility to address some of the costs are.
And is it does take two of talent there.
Initiation of the confirmatory trials.
Trials.
Wonderful. Thank you so much.
Sure.
Thank you and the next question comes from Brian Chin with J P. Morgan.
Hi team. Thanks for taking my question this morning.
For a discussion with the FDA.
They talk about how long of a safety follow up do you need to in.
In the ongoing study before filing and then on the preparation work for filing can.
Can you talk about you know whether there are any additional preclinical work that you need to tee up between now and filing that you have.
To work on and then I have a couple of follow up thank you.
Sure.
So in regard to the safety profile is similar to the endpoints that we have for the efficacy of one year safety follow I'll follow ups of course, and we have a we will be following these patients regardless.
They move on them. So those are part of the endpoints and as we have mentioned and I will repeat at this product drug product has a very favorable.
Safety profile in all of the patients that we have created a very very similar and very favorable.
As far as.
In regard to their preclinical the discussions obviously the preclinical work that.
It has been already taken place prior to us going to a phase one phase two but obviously and his.
As part of any.
Uh huh.
BLA submission, we have to meet all the criteria that the F D. A.
Is asking for this is part of a typical of a submission for the BLA, which includes obviously the phase II data.
It has to be similar and.
And two what we have seen that up to this point and it has to meet the clinical endpoints. We also are in discussion with FDA for and manufacturing compatibility and using our commercial material and manufacturing.
Manufacturing in the confirmatory trial. So those discussions are ongoing and when we submit our BLA of course it has to have all those components in.
For the rapid review and approval.
We're hoping that we will move.
Moving towards that way.
Okay, and then on the manufacturing front.
Can you elaborate on your commercial readiness.
You know what's needed specifically to prepare on the CMC side and at.
At the time of your anticipated launch.
What is the capacity that we should anticipate.
Okay.
So we have.
Evaluated our own manufacturing facility, which by the way provided all of the GMP material that was used.
And these trials are even during the pandemic time as you can imagine because we have started the trial.
<unk> 2012 on April <unk>.
I believe of 2021, so you can imagine our manufacturing had prepared that during.
The ongoing.
Pandemic, which was very important because at that point all of the external manufacturing they were shut down.
And that no one could prepare anything so that's one of the importance as I mentioned, why we have decided to move the commercial manufacturing to our own facility and make our facility commercially and basically are ready.
For.
Towards this path and for the licensed sure Pat we will be moving on to our materials for the commercial material is at risk.
Speak our teams are working on various aspects of comparability and also production.
Since we have produced our GMP material it ourselves.
The processes are minimally switched we hope that we have a very good compatibility profile for manufacturing, which will be obviously are presented to the F. D. A.
And we anticipate that we will be ready.
To launch from our commercial facility here and after the approval of our BLA I should mentioned that especially within their patient population and that is in the U S. A we believe our commercial facility has.
The capability.
To produce enough doses for that and also obviously after the approval and during this process. We are also looking at further expansion.
So with that we believe that we can be.
Our facility will be sufficient for production of the doses that it's needed.
Great if I can.
Can I squeeze in a last one that'd be great.
Just one on.
Your overall thinking around the entire R&D portfolio.
As you mentioned that there are multiple potential partnerships and.
Divesting opportunities that you currently have on the table.
And given that you have a cash runway out to 2025.
Can you talk about you know how should we think of how the R&D portfolio will evolve.
Over the next 12 months and.
What are the what are the factors that that you that you will take them. When you think about what to prioritize and what to partner off and thank you.
Okay.
Two things.
So I'm very clear.
Thank you I for US immediate partnership is very clear that and we had announced this previously on AG is of the one nine because I. We believe that this is something that I have it's very exciting however, presage and it does not have the cash requirements to go to extend that phase III.
With this asset and this is why we have they're very.
Very active discussions with a number of parties around age is there one night in regards to our ultra cars as I mentioned, especially the peer Gen. Three five because it's much more advanced and from their objective responses are.
It has that fast track and talk to.
Perhaps a rapid regulatory and our.
Our strategy for the AML patient staff, we anticipate that the two sides, the mustard and Mayo clinic.
<unk> done an excellent job in recruiting and they will continue to do that especially in this half of the year.
So we will be having their data for the phase one be in a minimum the interim data for the 2024 again this position us and not only from a regulatory path and the decision has to be made for perhaps.
And rapid move in that direction, but also in our discussions with the groups that are.
Right now are interested in the program and.
In advancement of the program towards commercialization.
The priority of that portfolio I want to stress this and I know Harry has a stress.
<unk> has now really minimize their costs.
<unk> SG&A.
We have minimized to limit a dig.
Ex extraneous CRO costs are by.
By not opening some of the sites as we all know in develop drugs in development one of the heaviest cost. These are sites that you're initiating as it requires a large.
Cash.
By not doing that in an immediate fashion, we are saving to get to the readout of our PRT in 2012, which is as I mentioned at the decision of the SBA why it's so important to us is because it eliminated requirement of the phase III.
Which you can imagine and appreciate it would've taken another 30 or 40 years just to get to the point of.
Data and right now we are basically.
First of all we are seeing our data from phase II as we speak because these are open.
Price.
And secondly, we will finish the complete follow up which is the endpoint of 12 months that the FDA has agreed with <unk> by the second quarter of 2024, so our cash runway well beyond that and it allows us to have a readout and move with our BLA submission.
From a non dilutive fashion definitely there's discussions that we have is very productive and ongoing and our hope is that we'll extend.
Our cash runway beyond 2025.
One other thing that I have to say and I'm grateful to the teams at precedents.
At four <unk>.
Dedication that they have shown and what we have done which is not typical to a lot of other companies is our R&D because of their knowledge and especially in on a fight of assay development immuno logical immunology and clinical.
They have pivoted that they have taken a lot of their responsibilities on that side.
Which we do not need to know hire a tremendous force retrained booth time.
In order to move rapidly towards the commercialization and I think that's another.
Trent that presage and has and obviously be able to utilize it.
Hello, Thank you.
Sure. Thank you thank.
Thank you and this concludes our question and answer session I would like to turn afford doctors have the very for any closing comments.
Thank you.
First of all I would like to thank you for joining us today.
I want to extend our thanks to the patients for participating in clinical trials, our investigators for their dedication and commitment working on studying new therapies for unmet needs and to the team at depressed surgeon, who have worked so hard over the last several years.
As we have discussed today, we believe the pier G. In 2012 has a paradigm changing potential and with today's announcement of the F. D. A alignment on a path to an accelerated approval request for our ongoing phase. One two study. This is an important milestones that brings us a step.
Closer in our transition to a commercial stage company and in realizing our vision of bringing life changing therapies to patients with unmet medical need given that the phase one two is fully enrolled and serve as a pivotal this sets us up to potentially to bring in.
Life, changing first therapeutic option for RP patients, who have been waiting for decades for such an option. Thank you again and now I will send it to operator.
Yes. Thank you.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.
Okay.
Hum.