Q4 2022 Inovio Pharmaceuticals Inc Earnings Call
In our efforts to develop our DNA medicines platform.
Following prepared remarks, we will conduct a question and answer segment.
During the call, we will be making forward looking statements regarding future events and the future performance of the company.
These events relate to our business plans to develop <unk> DNA medicines platform, which include clinical and regulatory developments and timing of clinical data readouts, along with capital resources and strategic matters.
All of these statements are based on the beliefs and expectations of management as of today.
Actual events or results could differ materially.
We refer you to the documents we file from time to time with the SEC.
Which under the heading risk factors identify important factors that could cause actual results to differ materially from those expressed by the company verbally as well as statements made within this afternoon's press release.
This call is being webcast live and a link can be found on our website.
<unk> dot com and a replay will be made available shortly after this call has concluded.
I'll now turn the call over to <unk>, President and CEO , Dr. Jackie Shay.
Thank you Thomas good afternoon, and thank you to everyone for joining today's call.
In the past year, <unk> taken measured and at times difficult steps to prioritize our pipeline to focus on our programs with the highest probability of clinical and regulatory success and strongest commercial potential.
Guided by our commitment to operational excellence and financial discipline, we are positioning <unk> to best advance our key clinical programs and realize the potential of DNA medicines for patients.
In our press release today, we announced the topline results from our reveal two trial of <unk> 3100 <unk>.
Later in the call our Chief Medical Officer, Dr. Mike <unk> will provide a detailed summary of our clinical programs.
But I'd like to take this opportunity to highlight some key points about the <unk> trial as well as <unk> 31, a seven as a potential treatment for recurrent respiratory papillomatosis.
Our op.
Both of which are HPV related diseases.
As you may recall in.
In April last year, we changed the primary endpoints of Raphael too from an all participants population to an investigational biomarker selected population.
We made this decision based on our analysis of data from reveal one from which we have defined an investigational biomarker signature.
That may have the potential to identify those women more likely to respond to treatment with <unk> 3100.
And reveal two <unk> 3100 did not achieve statistical significance in the primary biomarker selective population for the endpoints ablation regression and viral clearance.
However.
<unk> steady 100 did achieve statistical significance and the all participants population.
The original primary population for the trial.
The endpoints of lesion regression and viral clearance.
Furthermore, the <unk>, all participants data and the combined data across reveal one and reveal two trials.
Built upon the considerable data package that we've now obtained at multiple clinical trials that indicate DNA medicines are potentially able to clear the HPV virus and regress HPV related completion.
It also strengthens our confidence and our other HPV related programs, including <unk> 31, a seven for RFP, where we recently reported encouraging data from the first and second cohorts from the phase one two trial.
Our ERP is a truly devastating disease that can be overwhelming and patient slides and.
And we believe INR 30, 107 has the potential to help alleviate this burden and improve the quality of life for those suffering from this terrible disease.
We are focused on advancing INR 31, 7%. The next stage of development and I look forward to sharing updates on our progress with you in the coming months.
Moving onto our infectious disease portfolio last month, we announced positive results from our phase <unk> clinical trial evaluating <unk> hundred one as a <unk> candidate in healthy adult participants who have previously received a single injection of repo and FDA.
Approved vaccine for Ebola.
We believe this data supports our position that DNA medicines could be an important part of global medical countermeasures against infectious diseases.
Either as primary vaccine or has boosted to existing vaccines.
Infectious diseases like Ebola remain an ever present threat globally.
We are currently in discussions with our collaborators and also potential partners.
Guarding the next development steps.
I know 40 to everyone.
In addition to the progress on the clinical front, we have been working to strengthen our financial position.
Peter will provide the details.
But our emphasis on pipeline prioritization operational excellence and financial discipline.
Has allowed us to reduce our cash burn substantially since last year.
Given these efforts our cash runway is expected to take us into the first quarter of 2025.
Financial Prudence will continue to be an area of high importance as in OPM and underpinned our.
Our decision making process going forward.
With that I'd like to turn the call over to Mike.
To provide a more detailed update on our clinical pipeline and recent highlights Mike.
Thank you very much Jackie and greetings everyone.
I'd like to start today by talking about VTS 3100, and sharing some more detailed insights on the reveal two results, we announced today and our financial press release.
Our phase III program for <unk> 100 includes reveal one and reveal two two trials evaluating the efficacy safety Tolerability and Immunogenicity of <unk> 3100 to treat HPV 16 18 associated service.
Coal high grade squamous intra epithelium lesions or <unk>.
Both trials included a three dose treatment regimen and used regression of cervical lesions along with clearance of the virus as the primary endpoint.
In reveal one the endpoint was evaluated against all participants in the clinical trial with.
But in the second quarter of 2022, we amended the reveal two trial to focus on investigational biomarker selected population.
As Jackie described we made this decision based on our analysis of data from reveal one.
In which we have defined an investigational biomarker signature that may have the potential to identify those women more likely to respond to treatment with <unk> thousand 100.
Due to that amendment, we publicly announced that reveal two was no longer deemed to be a pivotal trial and would not lead to a biologics license application for a biomarker selected population.
Since the U S food and drug administration had indicated that an additional trial or trials would be required.
As the next slide shows the results from reveal one and the old participant intent to treat population did not achieve statistical significance.
A modified intent to treat population did indeed reach significance.
Following the change of primary endpoint and reveal two.
The result in the biomarker population was also not statistically significant.
The percentage of participants meeting the primary endpoint was 28, 6% or six out of the 21 participants in the treatment group.
This is zero out of the four in the placebo group.
The next slide shows the two studies in two populations side by side in more detail.
We just discussed the reveal two biomarker results you can see in the bottom right quadrant.
However, the all participants group in reveal two shown in green in the top right quadrant did achieve statistical significance.
The percentage of patients.
Meeting the endpoint was 27, 6% in the treatment group.
Versus eight 7% in the placebo group in.
In addition, the treatment effect, we saw was hired them observed in reveal one.
While not shown on the slide we also achieved statistical significance in the all participants population of reveal two four viral clearance with 37, 3% in the treated group achieving viral clearance versus eight 7% in the placebo group.
Given the importance of viral clearance and removing the underlying cause of the HPV related diseases.
This data may have positive implications for our other HPV related programs.
Next we can look at the integrated results from both reveal one and two.
Since these trials utilize the same endpoint, we performed an AD hoc integrated efficacy analysis of the results.
This analysis showed that we achieved statistical significance in both the biomarker and in the old participant populations.
For the combined biomarker population, which consisted of 92 participants 68 of which were in the treatment group and 24 in the placebo group the.
The percentage of participants meeting the endpoint was 54, 4% in the treatment group versus 12, 5% in the placebo group.
For the combined all participants population of 404 participants 272 of which were in the treatment group and 132 in the placebo group the.
The percentage of participants meeting the endpoint was 25% in the treatment group versus nine 8% in the placebo group.
With respect to safety in the reveal two trial there were no treatment related serious adverse events and most adverse events were considered to be mild to moderate.
These results were consistent with what was observed in reveal one.
<unk> will continue to evaluate the results to determine the path forward for <unk> 30, 3100 in cervical Hcl and this combined dataset will be supportive in future regulatory interactions.
We also plan to submit the data for publication in a peer reviewed journal later this year.
While disappointed that we did not meet the primary endpoint for reveal two in the biomarker population I am encouraged by the data as it further indicates that DNA medicines may be particularly well suited to treat HPV related diseases. These.
These results also give us additional confidence as we advance INR $31 seven a candidate for the treatment of RFP into the next stage of development.
Which brings me to the recently announced data for INR 31, 7%.
As a reminder, INR 30, 107 is a DNA immunotherapy.
Those are two placements one encoding for HPV, six and 11 E six and seven.
And the second INR $91 12, a plasmid encoding for human interleukin 12, as an adjuvant to boost the immune response.
This DNA medicine candidate was evaluated in an open label Multicenter trial to assess its safety Tolerability immunogenicity and efficacy in patients with HPV six <unk> HPV 11 associated RFP.
There were two cohorts for this trial enrollment.
Enrollment into the trial required a minimum of two surgeries in the year prior to treatment in.
In both cohorts patients received four doses of INR 30, 107 on day zero and weeks three six and nine.
Surgery was performed once in the two weeks prior to the first dose in order to establish a disease baseline, but any surgery performed following day zero, including during the dosing window was counted against efficacy.
Yes.
Last month, we reported positive preliminary results from the second cohort of 11 patients.
Who were administered INR 30, 107, using the exploratory side port needle.
The data from the second cohort achieved statistical significance based on the clinical endpoint of a reduction in the number of surgical interventions echoing data from the first cohort announced in October of 2022.
In particular in the second cohort we saw a median decrease of three surgical interventions.
10 of the 11 patients or 91% saw a reduction in surgical interventions in the year following treatment.
Of those 10 patients for required no surgical intervention during the 52 week trial period.
In the year prior to treatment. These 11 patients had between two and eight surgical interventions with a median of five.
Treatment induced cellular responses against both HPV, six and HPV 11, inducing both activated CD four and activated lytic CDA T cells.
T cell responses were also observed at week 52.
Which was 43 weeks after final treatment with INR 30 107.
Indicating a persistent cellular memory response.
As we mentioned previously we believe this memory response could be a key factor in the treatment of chronic viral diseases, such as our ERP.
As we have seen.
With that other DNA medicines, INR 30, 107 was well tolerated in both the first and second cohorts with all participants completing the treatment course.
Treatment emergent adverse events observed in the trial with January low grade with injection site pain and fatigue being the most commonly reported aes.
When the data from both cohorts as combined it shows that 81% or 26 of the 32 participants saw a reduction in the number of surgical interventions compared to the previous year.
We found these results incredibly important not just because they show the potential of our platform, but more importantly, because of the potential impact INR 30, 107 can have on patients suffering from RFP.
For instance, the two photos on this slide show the change in the way of one of the patients in that trial from before and after treatment.
This patient had required frequent surgeries in the year prior to the trial, but as you can see on the right. There was marked improvement in the disease, which meant from a clinical management perspective that this patient required no surgeries following treatment.
In this next slide you can see the impact of INR 31, seven on a patient with much more significant disease the.
The improvement here is tremendous.
And while some residual disease is visible on the right side of the OE. This patient did not need any surgery off today's era through the completion of the 52 week trial.
We have heard from patients and investigators that any reduction in surgery, even one less surgery would be life changing for patients who often have to schedule their entire lives around surgical procedures to control their disease.
Our phase two results are an indication of the positive impact.
30, 107 could potentially have for the RFP community.
We are currently in discussions with the regulatory agencies to discuss the next steps for this program.
And determine the most expeditious path to bring the potential benefits of this treatment to RFP patients in need.
We continue to have discussions with kols in the U S and Europe as we plan to advance to the next clinical development stage with the goal of recruiting globally for the next trial.
We are also excited to be presenting our phase II trial data at the American Bronco Esophageal Association at Carson in May of this year.
We look forward to providing additional details about that data at this important conference.
Now I'd like to turn to updates on a few other product candidates mentioned in today's press release.
INR 31, 12 is a candidate for the treatment of HPV related cancers.
As you May recall, the asset was returned to us in 2021 from Astrazeneca.
Updated results have recently been published in clinical cancer Research, which include included an overall improved overall response rate or <unk> from.
From a phase one b to a trial evaluating the safety and Tolerability.
Antitumor activity and the Immunogenicity of INR 3100 12.
When used in combination with <unk>, a PD L. One checkpoint inhibitor.
<unk> was updated from 22, 2% to 27, 6%, which meant the number of both complete responses and partial responses increased from three to four.
We believe the results from our HPV HPV program to date supports the reevaluation of INR 31, 12. Therefore, we are currently evaluating the next development steps and also potential collaborators to move iron ore 31 12 forward.
Turning to INR 50 401.
Last year at <unk>, we announced additional overall survival data from our trial of evaluating INR 50, 401 in combination with the PD one inhibitor lift here.
We are in discussions with regeneron regarding the next steps for this program.
Given the Tolerability and Immunogenicity profile when combined with the survival data. We believe this asset should continue to be investigated and we plan to provide additional updates in the coming months.
On the infectious disease from we also announced positive results from our early phase clinical trial evaluating <unk> 40 to <unk> as a booster vaccine candidate in healthy adult participants who had previously received a single injection of <unk>.
The only FDA approved vaccine for Ebola.
As you heard from Jacky earlier, we believe DNA medicines have an important role to play as part of global medical countermeasures against infectious diseases.
We are currently in discussions with collaborators and potential partners and we will seek regulatory input regarding what next steps we need to take to move this product forward.
We will hopefully be able to provide a further update in the second half of this year.
As you can see we've been busy and we have a lot of exciting work ahead.
We believe our DNA medicines are well suited as therapeutics for chronic viral conditions.
Attributes of DNA medicines, such as <unk> T cell responses.
Well tolerated profile ability to re administer and the lack of anti vector response could play an important role in the treatment for HPV related diseases. We are truly excited about taking our pipeline to the next stage of development.
I'll now turn the call over to our CFO <unk> for 2022 fourth quarter and full year financial summary, Peter.
Thank you Michael we finished the fourth quarter of 2022 with 253 million in cash cash equivalents and short term investments compared to $401 3 million as of December 31, 2021.
As of December 31, 2022, and <unk> had $253 1 million common shares outstanding and 271 million common shares outstanding on a fully diluted basis.
Our total revenue was $125010 3 million for the quarter and year ended December 31, 2022, compared to $839001 8 million for the same period in 2021, respectively. The year over year.
Increase in revenue resulted from the fulfillment of our obligations under our contract with the U S Department of defense.
Total operating expenses were $56 1 million and $277 8 million for the quarter and year ended December 31, 2022, compared to $106 3 million and $303 million for the same period in 2021, our net loss for.
Quarter and year ended December 31, 2022 was $54 5 million or <unk> 22 per share basic and dilutive and $279 8 million or $1 17 per share basic and dilutive respectively compared to a net loss of 106.
<unk> 9 million or <unk> 50 per share basic and dilutive and 303 7 million or $1 45 per share basic and dilutive for the quarter and year ended December 31 2021.
Research and development expenses for the quarter and year end December 31, 2022 were $42 1 million and $187 7 million compared to $92 3 million and $249 2 million respectively for the same period in <unk>.
'twenty one.
The year over year decrease in R&D expenses was primarily related to lower drug manufacturing outside services and clinical expenses related to INR 4800, and <unk> 3100, and also non reoccurring expenses related to the acquisition and installation of manufacturer.
Equipment for INR 4800 during 2021, as well as lower engineering services and expenses related to our selected three PSP device array automation project. These decreases were offset by $29 2 million lower Contra research and development.
<unk> recorded from grant agreements Jenna.
General and administrative expenses were $14 million and $90 2 million for the quarter and year ended December 31, 2022 versus $14 million and $53 8 million respectively for the same periods in 2021, the year over year increase in G&A expense.
This was primarily due to a $14 million noncash expense related to the settlement of <unk> Securities Class action litigation.
Including issuance of common stock as part of the settlement and other related litigation costs as well as $6 9 million in one time severance expenses.
Looking forward our projected cash runway into first quarter 2025 includes a cash burn estimate of approximately $32 million for the first quarter of 2023. These projections do not include any funds that may be raised through our existing at the market program.
Or other capital raising activities.
As a reminder, you can find our full financial statements in this afternoon's press release as well as in our 10 Form 10-K filed with the SEC and with that I'll turn it back to Jackie.
Thanks, Peter I'd now like to open up the call to answer any questions you might have operator.
We will now begin the question and answer session to.
To ask a question you May press Star then one on your telephone keypad.
If youre using a speakerphone please pick up your handset before pressing the keys to withdraw your question. Please press Star then two.
Our first question today comes from <unk> Singh with Oppenheimer. Please go ahead.
Great. Thank you and thanks for a couple of a couple of questions just quick ones.
<unk>.
You had mentioned that you had launched the law.
<unk>.
The trial will be <unk> and the various biomarkers in multiple patient populations.
No you won't even more going forward as you look at that data can you just help us understand how that helps you.
Each fall, although trial that youre looking out with other projects.
Number one how we can help you with all commerce and patient population and then I just want a quick follow up.
Thanks, <unk> nice to hear from you.
I'll kick off incentive provide some top level comments, and then I'm going to hand over to Mike to comment in more detail.
I think the really encouraging thing that we've seen from prevail one in reveal two and from the earlier phase II trial for <unk> study of 100, and we've also seen across the annual indication for <unk> thousand 100, and now with our ERP.
It's our ability really to.
Be able to.
C viral clearance and lesion regression and I think I think not the common factor that we're seeing across all of those different indications.
And.
While we did not reach statistical significance in the biomarker selected population, we did reach statistical significance against.
Tissue against tissue regression and viral clearance in the all comers population and Raphael too.
This is really important data and I think it really strengthens our belief in our conviction that DNA medicines that really particularly well suited to addressing HPV related diseases.
And with that I'll hand, it over to Mike to make some more specific comments, Mike. Thank you Jackie and.
Nice to speak to you again.
I think obviously Jackie hit on all the main points I think.
And as you rightly said at the start we obviously do have.
More work to understand the biomarker population.
We only really got the data in our hands about a week ago. So.
It's very early for us to start examining that.
I think.
For me personally I mean as Jake Jeremy. The fact, we are able with a three treatment regimen to clear 36% of patients of their virus, which really is the foundation of the disease in these HPV related disorders.
Is particularly promising and I think also when you think about our <unk> product. We also include IL 12 is an adjuvant. So we were hoping and actually as you saw we actually do have greater efficacy, we were able to get 81% of subjects.
Have less surgeries in the previous year. So I think you just put all the entirety of the data we've seen across our programs.
We just confident I think now that we can treat HPV related diseases.
Yes. Thank you for the commentary and then just the home on that which is that.
Answering.
You've got your lead program.
Our RFP.
And with Regeneron.
What other preclinical targets that you're looking at.
These learnings are kind of.
Coming to effect in mobile.
Are you getting sort.
So better abled better visibility into the time of the preclinical targets you want to go after bringing into the clinics. So that you have greater certainty.
Kind of a platform technology to help it be any medicine. Thank you for the question.
Thanks <unk>.
That's a really interesting question and I would say.
We remain focused on advancing our DNA medicine candidates that have the greatest scientific promise clear regulatory path and strongest commercial potential and that's really underpinned by our desire to bring to market innovative lifesaving DNA medicines for the benefit of patients globally as quickly as Pos.
<unk>.
With our platform, we're able to do many different things I mean, we have candidates across infectious disease HPV related to see immuno oncology.
We also have.
Programs in early clinical development in terms of.
DNA to liberate monoclonal antibodies and then some.
Further earlier preclinical work, but I think what we're really seeing now without DNA medicines is our ability to potentially treat HPV related diseases. I think it's going to be very interesting to see how that may translate to other chronic viral diseases and I think we're also.
We're excited to see what we can do in the immuno oncology space.
Based in HPV related cancers, but also in some other <unk> more broadly.
I think the past few years, we've had a lot of data readouts a lot of encouraging data and we're really digging down in analyzing that data to see what it tells us and to really narrow down and focus on where do we really think the best opportunity to sell the DNA medicines.
It gets potentially lifesaving products to patients more quickly.
So I hope that it thank you.
No. Thank you so much that great really nice update on thanks for the questions. Thank you Jackie.
The next question is from Gregory <unk> with RBC capital markets. Please go ahead.
Hi, guys its a niche on for Greg. Thanks for taking my question just a quick one for me here.
How should we think about the prioritization of your pipeline programs and the relative investment in each thanks, so much.
Thanks.
So first of all this as I mentioned in my previous response, we're really focused on advancing our DNA medicine candidates, where we think we have the greatest scientific promise the strongest commercial potential and a clear regulatory pathway going forward as well.
So that's really what we're looking at as we assess and evaluate these different opportunities.
Quite a lot of data our effort in recent months, we're in the process at the moment as I said with really sitting down and going through that data and.
Really prioritizing how we can move on.
Candidates forwards and in Mato OTA, and we will be providing some further updates on that over the coming months.
Great. Thanks, and just to just a follow up.
The second part of my question. There is there a sort of a difference in the relative investment.
Time and capital into each of your programs just given the.
Prudent approach you've been taking to resource allocation.
Yeah. So when we're looking at cross sell pipeline up USD, considering what the regulatory path so what.
The next steps are likely costs timelines et cetera, and we're really allocating our resources across the different programs.
It depends on top of that.
So I think as Mike mentioned, we are going to be sitting down.
And figuring out the path forward for RFP.
Currently in discussions with the regulator sets. The next steps staff and then we will make banking announcements about that program over the coming months.
The <unk> 3100 as well as he mentioned this is very recent data, we really need to dig down into the biomarker.
Figure out what we can learn from this and how we how we might want to proceed going forward.
We also have other indications for this product.
Canada This model that we need to take into consideration.
Great. Thanks really appreciate it.
The next question is from Geoff Meacham with Bank of America. Please go ahead.
Hi, This is Charlie on for Jeff.
So I guess I have two parts.
Questions first is.
So I'm wondering whether you could provide some details in terms of the while the biomarkers have been tested in this trial.
I will reveal how too.
And maybe.
One is <unk>.
Is the reason why we're not seeing stuff like here.
Due to the fact that the pulp.
The number of patient that road.
Relatively small so is the trial on the power and Thats. The reason why we didn't see a stat sig in the biomarker selected patients.
And I'll have Paul follow up to this.
Okay. Thanks, Jeff I think Thats very interesting questions. So as you may recollect from Nicole.
The biomarker selected population with select <unk>, our investigational biomarker.
I'm going to hand, it over to Mike not provide some further details as to how we how we selected that biomarker and the potential implications might be going forward, Mike yes. So at.
At present, we have not disclosed what our biomarker signals.
And.
We'll do that I think in context of our full analysis of both what we saw in reveal one as well as what we saw in.
And reveal two.
Without the sort of full details of the population and the other impacts that can can affect treatment efficacy I think it would just be a little premature for us to talk about that at the moment.
To your comment around <unk>.
Our.
Obviously, we did expect a.
Higher number of subjects to have the biomarker based on what we saw in reveal one but.
But really it wasn't a powering issue with the study I mean, we we genuinely saw a lower.
Efficacy rate if from the biomarker selected population. So that's what really makes us want to dig into the data and understand.
What went on in that biomarker population. So that we can we can come back in.
And tell people, what what really happened and we're just not at the stage to do that at the moment.
But we will be doing that work.
And if I can just add to that Mike.
Remember that these.
Trials.
Not in mode on the basis of the biomarker the biomarker was applied retrospectively.
<unk>.
We have developed or to find the biomarker signature based on what we had seen in <unk>, one and I think this was part of the reason why.
In discussions with the FDA it became clear that <unk> would need to be exploratory biomarker selected population.
Okay.
Thanks, and maybe just a follow up.
On the other question can you. So you mentioned in the press release that the cash from raising tool.
Into first quarter of 2025.
Can you just provide housekeepers on the assumptions.
In terms of your program and how it would be I guess the next.
Next steps in terms of development for RP.
And maybe the GPM will impact that Castro way. Thank you.
Jackie I will take that.
Thanks Peter.
So what youre seeing is the <unk>.
Wind down there'll be a few wind down costs from our Covid program, but you're seeing the expenses shifting over into the RSP programs and the slight increase in the GBM programs.
We still have money going into our annual programs.
And then.
An increase in <unk>, <unk> and <unk> developments to get those to commercial ready.
Right now probably one of the lead programs as ERP and that does anticipate that we get the phase III trial started.
Upon regulatory approval from the FDA.
To be able to move forward towards the end of the year third quarter, beginning of fourth quarter, and we will cover the majority of those phase III costs.
Great. Thank you.
The next question is from Roger song with Jefferies. Please go ahead.
Great. Thank you for taking the question maybe a few.
A few ones for the detail.
For the reveal trial I think you mentioned the biomarker patients.
To be lower the number of the patients.
The lower than expected.
So just curious what is the expected percentage of the biomarker driven population well.
It looked like general population and also given you now have the datasets from both trial.
Any thoughts around how to improve upon the biomarker strategy I have a follow up after that thank you.
Okay. Thanks structure I'm going to hand, those questions over to Mike Mike, Yes, So as we presented during the presentation.
When you look at the reveal one population.
Biomarker from an efficacy level was at 65, 9%.
And in terms of frequency within the 201.
Patients in the trial it actually accounted for 33% of those.
Patients. So obviously when you when you come on to the reveal two population that there was a difference that we need to.
Investigate there.
And.
There was a second so yes, so in terms of how to improve maintenance I think that goes back to my previous answer we need to dig into this data and see what's going on in the reveal two dataset.
But when you when you think about I mean, as Jackie mentioned it was an investigational biomarker.
The team only had the reveal one population to work on they now have double the amount of data to look for the appropriate signature. So I think there's a lot more.
Team can do to really delve into a biomarker signature and see where that leads us once we've got our hands on more data.
Got it.
Nick.
And then.
Can you just remind us what is the <unk> patient to use.
Given that for one of the key endpoint Houghton.
The criteria.
An investigation.
Wanted to a global cloud for the later stage development. Thank you.
So that's a really good question Roger if you recollect Farrar.
<unk> PON two study we were actually using multiple sites across the U S and now we've been working and talking closely with Kols and other investigators as to how we might expand the study to Europe .
Im going to ask Mike to comment on the criteria for surgery.
And how variable the disease can be.
Yes, so when you look at the sort of surgical.
<unk>.
In the current trial.
We didn't really specify win.
And how the patients could receive surgery. It was ultimately a decision between the patient and the treating clinic.
Clinician as you can imagine.
<unk>.
One of the things because.
Surgery is a key indicator of efficacy.
We will need to try and standardize that as we move towards a registration trial and that is going to be one of the discussions that we have with the regulatory bodies.
At present, we are not in a position that we can disclose what criteria.
Thinking about.
But it is.
It is.
Important aspect of how we design the next trial.
And if I can just add in here and what we're hearing from patients what we're hearing from investigators as they really are looking for an improvement and a reduction in number of surgeries.
A major impact on patients' lives and that's really the that's.
That will move the needle for patients.
So mobile today more discussions to be had but we really are focused on surgery.
Thank you.
The appraisal.
The next question is from <unk> Chen with H C. Wainwright. Please go ahead.
Thank you for taking my questions. First question is the biomarker, you're utilizing a review to and review one is that the only biomarker available or there are some other candidates biomarkers.
Hi, Yes, that's a really important question, so I'm going to hand over to Mike to talk a bit about our biomarker strategy.
I always feel bad because I can't give too much information about this.
Biomarker signature that we used as the primary biomarker to select the population was not the only biomarker that.
Looked at so we will actually have more and more data in the database but.
Again, we haven't disclosed that level of detail at the moment I'm afraid.
I think we can play.
We're working with our partner Qiagen to develop these biomarkers and this data is very near its very recent for us and we can and need to tick down in Switzerland, hopefully come back to you with some further updates at the coming months.
Got it.
The FDA say future trials.
To use a biomarker.
I don't believe they stipulated that that was a decision. After we saw the data from reveal one in terms of.
Proposal to them I mean, what they did.
Say that.
By switching to the biomarker population it became a more exploratory study and we would have had to do while we will have to do.
One or two more trials before we could file for a BLA and that investigator in the biomarker investigational population.
Okay got it.
Good.
Does the fact that.
Combined dataset for bulk biomarker selected population in the participation population.
Boat show.
Statistical significance does that mean.
Okay.
The bulk of the biomarker really does.
Add much to the final results.
I guess it depends what you mean by it doesn't add much but I mean, clearly the efficacy rate in the biomarker selected population in the combined group.
Was I believe 54%.
There was a significantly increased.
Efficacy seen in that that population.
So I mean, there was clearly.
Any indication of a predictive nature of that biomarker.
Okay alright, thank you.
Okay.
This concludes our question and answer session I would like to turn the conference back over to Jacky shave for any closing remarks.
Thank you for your questions and to everyone joining us today.
To summarize as <unk>.
On the call today, and the past year, we've taken measured steps to prioritize our pipeline and focus our efforts on the programs with the highest probability of clinical and regulatory success and strongest commercial potential.
Steps are underpinned by our commitment to operational excellence and financial discipline and our belief in the potential of DNA medicines to improve the lives of patients.
We're excited about our plans to advance our key programs such as the <unk> seven to the next stage of clinical development and look forward to providing you with updates on our progress in the coming quarters.
Thank you again for your attention and have a great evening everyone.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.