Q2 2022 Selecta Biosciences Inc Earnings Call
Good day and welcome to the Selecta bio second quarter 2022 earnings release conference call.
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I would now like to turn the conference over to Kevin Chen Chief Financial Officer of Selecta Bio. Please go ahead.
Thank you and good morning.
Welcome to our second quarter 2022 financial results and corporate update conference call.
Press release reporting our financial results is available on the investors and media section of <unk> website worldwide web select a bio dot com and our quarterly port on Form 10-Q for the quarter ended June 32022, which we intend to file in the coming days with the Securities and Exchange Commission or SEC.
Joining me today are Carson, Brewin, President and Chief Executive Officer, Peter Traber, Chief Medical Officer.
It keeps your modal chief scientific officer.
During today's call, we will be making certain forward looking statements, including without limitation statements about the potential safety.
<unk> regulatory and clinical progress of our product candidates.
Our financial projections, and our future expectations plans partnerships and prospects.
These statements are subject to various risks that are described in our filings made with the SEC, including our most recent annual report on Form 10-K.
You are cautioned not to place undue reliance on these forward looking statements, which speak only as of today August 4th 2022, and selected disclaims any obligation to update such statements, except as required by law, even if management's views change.
I would now like to turn the call over to Carsten Brunn Carson.
Thank you Kevin Good morning, I appreciate everyone, taking the time to join us today.
In the second quarter of 2022, we've made steady progress across our proprietary pipeline and achieved numerous key milestones most notably on June 29, we completed the enrollment of the resolve II trial triggered a $10 million milestone payment obligation from Tobey.
Our partners continue to progress the Interplast form in combination with their gene therapy candidates and in June <unk> extended their option and license agreement for Duchenne muscular dystrophy, and certain limb girdle muscular dystrophy subtypes by nine months and achieved certain preclinical milestones.
These two events resulted in total payment obligations of $6 million from <unk> that we anticipate receiving in Q3 2022.
Finally on April six we priced an underwritten offering raising approximately $38 7 million, we believe that our existing cash cash equivalents restricted cash and marketable securities as of June 32022 will enable us to fund our operations into mid 2024.
The second half of this year will be an important time for selecta as we anticipate completing the phase III resolve trial in collaboration with our partner <unk> we.
We expect to announce joint topline data from results in Q1, 'twenty two 'twenty three.
We also anticipate advancing <unk> hundred two our proprietary gene therapy candidate to treat metabolic acidosis or MMA into the clinic and we remain on track to commence the phase one clinical trials in the fourth quarter of this year.
Our team continues to advance our preclinical pipeline, most notably our IND, enabling studies and manufacturing scale up for our proprietary ITG protease or to help unlock the power of gene therapies, Iga Proteus candidate selection with our partners Ginkgo bio works and icon Biosciences for the treatment of Iga nephropathy.
And accelerating the development of intra L, which is the evolution of our antigen specific precision immune tolerance platform.
With unexpected financial runway into mid 2024, we believe we are well positioned to re imagine immunotherapy in autoimmune disease unlock the potential of AAV gene therapy, and amplify the efficacy of biologic therapies.
Let me now walk you through some of the key highlights and recent activities across all three pillars of our pipeline.
Over 24 million Americans suffer from autoimmune diseases. The current standards of care utilizing union suppressive drugs, which ultimately if patients are vulnerable to serious infections and malignancies or symptoms masking treatments, which failed to address the underlying cause of the disease.
Our approach re imagines the treatment paradigm by addressing the underlying cause of autoimmune disease.
For our positioning immune tolerance platform, we hope to restore immune system balance by inducing an expanding Anderson Pacific regular T cells or T regs in vivo.
As we've highlighted before we're very excited about our recent preclinical data we've generated showing substantial synergistic activity. When <unk> is combined with engineered IL two molecules that are selective for cubic's and evolution of our platform we call into IL.
A top priority for select in 2022 is accelerating the development of a proprietary engineered IL two to combine with <unk>.
We have partnered with Cyrus biotechnology, a world leading protein engineering company spun out of David Vegas Lab at the University of Washington to facilitate development over the next generation.
Highly differentiate our two new tier to combine with them tour.
Unlike other programs in development using engineered T. Rex selective IL two molecules that focus on generalized expansion of T. Regs in tour and intra L. When combined with Amazon of interest is focused on the reduction and expansion of <unk> specific to those auto <unk> responsible for the pathogenesis of autoimmune diseases.
We believe our technology has the potential to be a truly differentiated first in class and specific treatment for autoimmune diseases.
The first autumn indication industry plan to evaluate our positioning immune tolerance platform is in primary biliary cholangitis or PBC, a T cell mediated liver disease, driven by a well defined Amgen PDC two in.
In PBC, the immune system mistakenly attacks tissue in the liver and damage the small bile ducts.
Treatments to help slow the progression and prevent complications in PBC are available approximately 30% to 40% of patients are intolerant to or do not respond to these treatments, leaving patients with limited alternative treatment options and a significant unmet need.
Putting this during intra L with PDC to the audit Amazon implicated in PVC May result in the expansion of cubic's specific to PDC too and restore immune system balance.
We continue to work toward additional indication selection.
Land to expand into other Automd indications, we expect to provide updates on our strategic development paths for <unk> in the near future.
Now moving on to our gene therapy pipeline in Q4, 2022, we anticipate starting a phase one trial of <unk> hundred two a combination of <unk> with MMA 101 in aviation in AAV gene therapy being developed for the treatment of MMA.
And then there is a rare metabolic disease in which the body cannot breakdown certain proteins and fats.
The phase one trial will evaluate the safety and efficacy of <unk> two in treating MMA and <unk> ability to mitigate neutralizing antibodies against the MMA 101 AAV capsid.
Hope this trial will build on our growing body of evidence pointing towards to potentially multifaceted benefits of <unk> enhancing the efficacy and safety of AAV gene therapies. Additionally.
Additionally development of <unk>, two could provide an important regulatory and clinical blueprint for our current and future gene therapy partners potentially et cetera in the development of safer and reduce the bolt AAV gene therapies for patients suffering from rare genetic diseases.
This past may as the American Society of gene and cell therapy selected showcased six presentations, including three from our partnership with <unk> bio.
Our CSO Caky shoe modal was awarded an outstanding poster presentation award for his abstract titled combination of in tour tolerant genic nanoparticles and out to mid teen Synergistically inhibits the formation of anti AAV antibodies.
This poster showed <unk> has the ability to induce durable immune tolerance to a co administered AAV gene therapy vector in mice and demonstrated complete inhibition of anti AAV antibodies formation after multiple doses of gene therapy through 117 days no.
This effect was observed and would be considered sub therapeutic doses for intra alone.
Building on this to date, we are pleased to report new data.
Preclinical studies in mice using gene therapy vector doses of five <unk> Vg per kit or 10 times the dose of prior studies. This study demonstrated that a single dose of <unk> plus four monthly doses of IL two equipment are set with AAV HCP produce durable mitigation of anti AAV antibodies.
Over 131 days.
When combined with our human proof of concept study, where we observed in towards the ability to inhibit the formation of the dosing antibodies in healthy human volunteers Ultra 30 days. We believe these results suggest that <unk> has the potential to solve the re dosing problem associated with AAV gene therapies and transfer.
The treatment paradigm for one and done too low and slow whereby patients could receive multiple dose of gene therapy to titrate up to a therapeutic benefit and avoid the risks associated with high vector doses of gene therapy needed in the onetime only treatment model.
Another key challenge facing the gene therapy modality is one of accessibility currently 30% to 70% of patient population for gene therapy trials are in eligible for inclusion due to preexisting neutralizing anti AAV antibodies, which are result of natural infections. Thus many patients in need.
Unable to access potentially life altering therapies for which there may be few or no treatment alternatives.
ITG proteases have shown promise as the pre treatment to transit the clear preexisting neutralizing antibodies and create a window during which AAV gene therapies could be administered.
However, IGT proteases are derived from bacteria and are themselves highly immunogenic.
Additionally, some ITG proteases are derived from a common human pathogen and consequently, the vast majority of individuals have preexisting antibodies against these proteases.
<unk>, our proprietary ITG Proteus candidate has been optimized to specifically cleave human ITG, but he is derived from a non human pathogens and we have observed low cross reactivity to preexisting enter ITG produce antibodies, we believe that the combination of absorbed within tour could enabled.
Dosing of this enzyme therapy.
We continue with our IND, enabling studies and manufacturing scale up.
I wanted to take a moment to discuss how important we believe <unk> could be for the gene therapy modality.
So many patients with rare genetic diseases gene therapy could represent the most promising treatment option. Unfortunately, many patients are eligible for gene therapy to a pre existing anti AAV antibodies by using <unk> to open a therapeutic treatment window for these patients we have the potential to bring hope to those who may not have any other effective.
Treatment options.
At the same time by increasingly the eligible patient population, we can help companies maximize the commercial potential of the gene therapy candidates.
We're taking a multi pronged approach protecting the immunogenicity challenges facing AAV gene therapies.
In tour and tour L to mitigate the de Novo formation of neutralizing antibodies and enable re dosing and <unk> to address those patients who do to naturally Avi infections are eligible for treatment by gene therapies.
We continue to progress our gene therapy platform towards the goal of providing in this industry, leading toolbox capable of unlocking the true promise of AAV gene therapies.
To maximize the value of our platform by actively pursuing business development and out licensing opportunities for both <unk> and <unk>.
Lastly, I wanted to provide an update on our biologics pipeline, starting with <unk>, which we believe has served as clinical proof of concept for our precision inventories platform with approximately 450 patients dosed to date.
Many biologics can be highly immunogenic, resulting in sub optimal responses due to the development of antidrug antibodies after multiple treatments pace.
Patients develop an immune response may be forced to discontinue treatment or experience adverse reactions.
We believe the use of <unk> as an adjunct to biologics offers a promising approach to reduce this immune response and improved patient outcomes.
<unk> is comprised of <unk> co administered with a proprietary your case, but get the case with the treatment of chronic refractory gout and was licensed to <unk> in 2020.
Our phase III <unk> clinical program kicked off in the third quarter of 2020 and consist of two double blind placebo controlled trials of <unk>.
In both trials <unk> two is being evaluated at two dose levels of <unk> dollars, one mix per gig and 105 mix per kg single dose level of the gastric case, a point to mixed perfect.
On December one 2021, we announced full enrollment for dissolve one with 112 patients enrolled in the United States and we recently closed enrollment is 153 subjects for resolve II, which is being conducted in four countries across eastern Europe , and the United States.
As a reminder, we increased target enrollment of dissolved two from 120 subjects to mitigate any subject discontinuation due to the ongoing geopolitical events in Russia and Ukraine.
Achievement of full enrollment in these off to triggered a $10 million payment obligation from <unk> and we remain on track to complete both studies in Q4 2022 with joined topline data anticipated in Q1 2023.
We plan to work closely with our partner Sobey, our clinical trial providers and regulatory authorities to advance towards the successful completion of the resolve program.
With the extensive clinical data and <unk> currently in phase III, We believe our biologics pipeline is mechanistically de risked and Celexa is well positioned to leverage these learnings into our second <unk> indications in Iga nephropathy, a kidney disease that occurs when immune complexes of an antibody called immuno glow.
A one four Iga one accumulate in the kidneys current treatments fail to address the Iga protein deposits, which is the underlying pathophysiology of the disease.
We believe our novel approach, which combines <unk> with an Iga one protease has the potential to move injurious Iga from the kidneys improve markers of renal function and have a transformative impact on patients' lives.
We are working with currently working with our external partners to identify and Iga Proteus candidate for this program and hope to finalize clinical candidate selection by year end.
We're extremely excited about the advancements across all three pillars of our pipeline and the value driving milestones in the second half of 2022 and beyond with that I'll turn the call over to Kevin to run through our financial results for the second quarter ended June 32022, Kevin.
Thank you Carsten during the second quarter, we proactively took steps to bolster our balance sheet.
Most notably on April six we successfully priced an underwritten offering raising gross proceeds of approximately $38 7 million and ended Q2 2022 with approximately $143 4 million in cash cash equivalents.
Cash and marketable securities.
It is important to note that this cash balance does not include either the $10 million. We have received in Q3 <unk> or the.
6 million from threats that we anticipate receiving in Q3 2022.
We believe that our existing cash cash equivalents restricted cash and marketable securities as of June .
32022.
<unk> will enable us to fund our operating needs into mid 2024.
We expect multiple clinical readouts within our anticipated cash runway, including.
Including the results from the Phase III <unk> trials in Q1 2023.
Results from a phase one trial of <unk> 302.
Turning to our financial results for the quarter ended June 32022.
Net cash used in operating activities was $24 1 million for the six months ended June 32022, as compared to $18 2 million cash used in operating activities for the same period in 2021.
Collaboration and license revenue recognized was $39 3 million for the second quarter of 2022.
As compared to $19 7 million for the same period in 2021.
Revenue was primarily driven by the shipment of clinical supply and the reimbursement of costs incurred for the phase III <unk> program.
They went to the license agreement with <unk> and the shipment of manufactured supply under the <unk> agreement.
Research and development expenses for the second quarter of 2020 were $19 2 million as compared to $14 5 million for the same period in 2021.
The increase in cost was primarily the result of expenses incurred for the <unk> clinical program stock compensation and salaries.
General and administrative expenses for the second quarter of 2022 were $6 2 million as compared to $4 7 million for the same period in 2021.
The increase in cost was primarily primarily the result of expenses incurred for issuance cost for the 2022 equity offerings and stock compensation.
For the second quarter of 2022.
<unk> reported net income of $8 6 million or basic net income per share of <unk>.
As compared to net income of $4 6 million or basic net income per share for the same period in 2021.
I will now turn it back to Carsten for closing remarks.
Carsten.
Thank you Kevin in summary, we're pleased with our progress in Q2 across all three pillars of our pipeline. We're excited about our plans to enter the clinic with <unk> 302 in Q4 2022, the anticipated completion of the dissolved program with our partner Sobey, the advancement of IND, enabling studies.
Our wholly owned pipeline supporting our numerous collaboration partners and our plans to rapidly advance our next generation positioning immune tolerance technology in trial into the clinic.
We believe <unk> could represent a generational leap forward for the intra platform and we look forward to evaluating its full potential in PBC and beyond.
We remain focused on our commitment to solving the hardest challenges in autoimmune disease, and helping patients overcome autumn unity and immunogenicity through are evolving into a position of immune tolerance platform.
Before we conclude today's call I'd also like to thank the entire select the team our investors and the many people who have been supportive along the way, including our patients and their families with that we're happy to take questions.
Thank you Carsten.
We'll now begin the question 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 before pressing the keys.
If at any time. Your question has been addressed and you would like to withdraw your question. Please press Star then two.
At this time, we will pause momentarily.
To assemble our roster.
Yeah.
Our first question today comes from Joe Schwartz of <unk> Securities. Please go ahead.
Hi, This is Beth on for Joe. Thank you for taking our question today. So horizon Therapeutics noted during their first quarter update this year that KRYSTEXXA has achieved less than 5% penetration in the refractory gout market.
We are wondering what you think could be driving this allow uptake and if you and your partner <unk> have discuss any opportunities that you could pursue to enhance <unk> uptake if correct. Thank you.
Yes, Hi, Ben that's a great question, obviously, we're not giving commercial guidance since.
So b has commercial rights, but we remain extremely excited about the commercial opportunity and in general I think horizon has done a lot of the heavy lifting actually.
<unk> physician awareness.
Patient awareness.
Setting a fairly high price point.
As you can tell with the low penetration at this point there remains a tremendous commercial opportunity.
One of the key differentiator of course, there's always efficacy.
We're extremely excited by the phase two results that we saw but one of the key drivers in this patient population is also compliance and as you know KRYSTEXXA has to be twice.
Twice a month.
With the new.
Approval with methotrexate, even the more complex treatment regimen with daily folic acid and weekly methotrexate, whereas <unk> if approved would be a monthly.
Treatment, which would be tremendous differentiation for those patients who have to come into an infusion center, which usually longer drive somebody has to take them.
Makes a huge difference whether this once or twice a month.
Our next question comes from Christian <unk> of Cantor Fitzgerald Gerald. Please go ahead.
Hi, Good morning, everybody for this <unk> partnership what is the total amount of milestone payments that you remain eligible for at this time and I know that you've guided your cash runway. It doesn't necessarily include any potential for any of these milestone.
But I would imagine that some of these might be tied in with the top line readout in a potential filing and then has so we guided anything in terms of if the data does read out positively about salesforce and steps, they're taking to prepare for a potential commercialization.
Yeah, Hey, Chris Great Great question.
So we have overall guided that we're eligible to receive.
$630 million in milestones, which is breaking down an $80 million and regulatory and development milestones and 550 and commercial milestones.
And as we just announced we are eligible to receive.
$10 million for the full enrollment.
So there are some payments milestones left in there.
In the current.
Development backfill space.
But maybe Kevin if you have the numbers.
Mind so.
Yes.
Okay.
Okay.
We received 15 sorry.
Sorry, Kevin I wasn't able to hear you I don't know if thats my liner.
Sorry to be clear, we've already received $15 million and regulatory and development milestones and we're eligible for that for the balance.
65.
Got it thanks for that and then just on this new data you had for <unk> Alan Gene therapies wondering if you might look to share. Some of these additional findings at an upcoming conference or when we could expect to see the specific detail.
Yes, we'll definitely.
Sure sure this data at an upcoming.
Conference.
We will also.
Included into our corporate deck, which you actually can see on our website. So the data actually is on there already.
Perfect. Thanks.
Thank you.
The next question is from Yun Zhong of BT IAG. Please go ahead.
Great. Thank you very much for taking my question. My question is on the <unk> IL and I believe you indicated in the past that we're now going to use IL in the MMA study and is that because.
The engineered IL two will not be ready by the time you initiate the study given that you the new data that you just talked about <unk> in gene therapy.
Does it make sense to maybe try to introduce IL into the planned MMA study and do you have a plan to look for additional indicate sorry in terms of gene therapy indication to potentially include IL two.
Yes, that's a great question. So you're right. We don't anticipate to include into al at least initially.
MMA trial and.
We're really encouraged by the human proof of concept.
Ah study that read out last year with an empty.
Empty capsid, where.
Where we saw good control and the bodies.
But we can once we have an IL two available and went through the appropriate safety studies, we could potentially always add in into al but at least for this phase one.
It is not planned to include an IL two.
In terms of other indications as you know we have paused, our OTC deficiency indication just to preserve cash.
And we really see the gene therapy modality.
As a partnering play.
We're committed to MMA.
On our own regulatory pathway. So we I think we set a clear precedent for our strategic partners on how to use in towards the clinic.
I don't want to rule out you're going to pursue this program in the future, but for now we're focused on MMA.
Okay.
The autoimmune indications I think that's going to be the major direction going forward and in terms of.
Indication selection do you have any specific criteria in terms of the other antigens.
You would like to.
Develop thank you.
Yes, that's a great question and as you know, we've just released exciting into our L data beginning of this year and we're working through indication selection.
We have guided to PVC.
Which we like.
Initial indications since it has a clearly identified other engine PVC too.
It's also a liver directed disease as well as you know in tour accumulates in the liver. So we think.
Liver based.
Autoimmune disease are our focus.
And we'll give more guidance around us but definitely.
We have a clear focus on automated yourself deliver.
Great. Thank you very much.
The next question comes from Jonathan <unk> of Guggenheim Partners. Please go ahead.
Hey, guys. Thank you for taking my question just a couple from me with regard to the chronic refractory gout data coming up could you maybe just help us understand the expectation from that study and then also if you can just touch on you know how do these days that maybe sort of as a proof of concept for the <unk> program that you have.
So that's the first question I had to hop Tomorrow, which I'll ask I'll finish.
Yes.
So.
As you know the phase three study is a placebo controlled study.
We know from the <unk>.
KRYSTEXXA trials there is no placebo effect, so very confident here that we'll have technical success.
We have run two phase II studies.
Where we saw.
But the key efficacy in the 60% range.
Pretty consistently in a set of things.
The main call over 450 patients dose.
Kind of looking at this data kind of as a baseline in terms of expectations.
I mentioned earlier that we think the monthly dosing will be a key differentiator. So I think thats the expectations around our own efficacy so and we've done in the past extensive market research and feel this is a.
Tractive and differentiated profile in <unk>.
Terms of proof of concept I mean, we actually believe just based on the.
The phase II data, we think we have very clear proof of concept.
In the phase one study actually we dosed 19 patients with the enzyme alone take extra case.
Only three made it two week four which shows you it's a highly immunogenic.
Enzyme here.
Or if you look at the phase II studies to get a response rate.
52% amongst five and six you can clearly see that you induce tolerance and prevent the formation of <unk>. So we definitely feel very strongly that we already have technical proof of concept, which we're obviously planning to use for our second enzyme program, which is an iga.
But of course.
The place we will be additional validation will have additional safety data so.
But overall, we're quite excited about this upcoming readout in Q1.
And then with regard to the <unk> program no first on the PBC side other good biomarker defined could respond to.
Your Ayatollah versus not so that's the first part and then where are you with your own IL two new team without the timeline stand out there particular characteristics of an idea.
<unk> to be combining benign pillar if you can just comment there.
Yes, great question and I'll, let Peter answer the first question around Biomarkers and PVC Peter.
Yes, Thanks Carsten.
In PBC.
Very good and validated well established biomarkers of disease.
The one that's been used most frequently.
Alkaline phosphatase levels.
In fact.
These are regulatory endpoints, which had been used for approval.
Drugs, such as better Cologuard.
So.
A reduction in outbound phosphatase levels.
He is an extremely good biomarker and one that can be easily monitored.
And has a relatively rapid response rate so.
That's what we would be utilizing primarily.
Thank you Peter and regards to IL two so we haven't.
Guide on exact timing, but as you know yet and it's tough for us and we're working with our partner Cyrus.
And we'll definitely give an update.
In the very near future.
And it's a top priority, but I'll, let Keith talk a little bit of what we're trying to achieve here in terms of differentiation with this team.
<unk> selected biopsy okay.
Yes, hi.
Yes so.
If youre familiar with the Iot space.
Yes.
All of those to expand total T regs and.
Our approach is more antigen specific because we believe antigen specific T. Regs are going to be really the key to autoimmune disease, where you have a large pool of antigen specific effector T cells.
We see this profound synergy of IL two.
Inc.
<unk> indicates that.
We're getting both expansion of total T regs, which can provide by standards suppression, but more importantly, we feel we are.
Getting this huge increase antigen specific T regs.
Thanks Kim.
The next question comes from Gil Blum from Needham. Please go ahead.
Hi, This is <unk> 10 for Gil Thank you for taking our questions.
So our first question is about <unk> or <unk>.
Inventory for MMA study, it seems that into or IL.
More doses.
Okay very good.
Inhibition of the antibodies.
So are you planning to include more doses of <unk> or in the MMA study.
The second one is about is there any.
<unk> four.
The combination of <unk>.
Tour.
Work.
So it is now in the R&D, enabling studies are you planning to hopefully start a trial next year.
Thank you.
Yes, great question.
The first one.
Two Peter around the MMA setup.
Yes. This is an excellent question and in the.
In the MMA trial.
Does have our results in the empty capsid trial as well as the preclinical results in nonhuman primates and mice.
We have decided to.
Treat with three monthly doses of <unk> following the <unk>.
Single dose of the AAV vector and this has been approved.
By the FDA and it's going to be part of our clinical trial.
Subjects will receive the AAV gene therapy.
Plus in tour and then 56.
56.
Excuse me.
One month and two months later they will receive.
And third dose of.
Again core and this is a direct result of the findings.
In non human primates that we're able to continue to suppress.
Antibody levels with that regimen.
Thank you Peter.
A question on <unk>, we have not guided to.
R&D filing date.
But I think your assumption is not far off but it's not a top priority that we are pursuing.
Thank you.
Yes.
The next question comes from John Newman from Canaccord. Please go ahead.
Hey, guys. Thanks for taking my question.
For your proprietary IL, two that you're developing in conjunction with Cyrus.
Curious about the initial indication there I think the the.
The initial work with IL two.
We'll be PVC.
But I believe that will be with a different IL two.
Curious as to what Youre thinking for the proprietary version that Youre working on.
Yes, good question, John we actually.
Plan on.
Now.
The proprietary out sewer development series for the PBC indication actually.
I think we have stated in the past that we are open to partnerships with existing iOS with players as we believe we have.
A new.
<unk>.
Unique value add here.
Differentiating by inducing astra's indicated tolerance actually so but the first indication would be with a proprietary IL two in PBC.
Okay.
Great. Thank you.
The next question comes from Rajiv Prasad from William Blair. Please go ahead.
Thanks for taking the question.
Maybe just a little bit more color if you can on the gating events.
We needed to start the phase one trial.
And then the third.
Quick follow up.
About the IGD protease.
And the potential development of that how would you think to kind of initiate the clinical our clinical program for <unk> for that asset.
You kind of put it into the phase one trial or did you kind of study it separately.
Yes, I'll, let Peter comment on the gating.
For the MMA trial as you as you know it's the single Center study.
At the NIH and we're currently going through motions get started I'll, let pierre elaborate in more detail.
Yes, Thank you Carsten.
The gating.
Before starting the trial.
At the NIH are really just.
Some administrative.
Our approvals at the NIH, which are well underway.
<unk>.
The setup of all the.
All the.
In Australia and operational issues.
In collaboration with our <unk>, which is helping to support the trial DNI. So.
There is nothing.
Regulatory or.
CMC or any other issues that are gating through the initiation of that trial. So it's on track for.
Subject.
<unk> treated in the fourth quarter of this year.
And Peter since you're on a roll maybe.
As you know we haven't fully guided on the clinical development plan towards the work.
And obviously it will likely take us into indications as possible, but maybe you can talk a little bit of our thinking around.
Kind of starting to send a phase one study in healthy volunteers.
Sure.
To do that Carsten.
The issue with <unk> is that we're trying to reduce existing.
AAV.
Antibodies.
In patients in order to be able to give them the gene therapy.
For that purpose, we can use healthy volunteers who have.
Existing titers of antibodies.
Sure.
Vectors and as Carson said that can be anywhere from 40% to 70% of patients.
In the general population.
So thats the relevant groups, who are phase first phase one study, we'll be looking at both the safety and Tolerability absorbed.
Alone and in combination with <unk>.
And with the efficacy looking at the reduction of anti a naturally occurring anti AAV.
Antibodies so that's.
The first.
<unk>.
Ah trial and that really serves as a proof of concept for gene therapy trials and so then <unk>.
Following that we would be looking to include that as a pretty treatment before an actual gene therapy.
Thanks Peter.
Again, if you have a question. Please press Star then one.
The next question comes from <unk> <unk> of H C. Wainwright. Please go ahead.
Okay.
Hi can you hear me okay.
Yes, we can.
Alright, great. So a few questions on our PBC. So you guided to is that PBC is the primary indication in the auto you mean does this space.
Can you comment on the market opportunity on Javier differentiated from competitors in this space.
Yes, and since we have the resident expert Greg Peter I'll kind of give that question as well, but maybe just kind of to frame it up.
Obviously, we believe they are really addressing the underlying.
<unk>.
To Amazon, So thats driving the disease pathology actions are really addressing the root cause of the disease mechanistically, but I'll, let I'll, let Peter.
Give me more detail.
Yes <unk>. Thanks.
Thats correct.
All of the.
Drugs that are currently being used in PBC.
Don't get at the root immunologic cause of the disease and that's what we're trying to do now.
The number of patients that respond to the current therapies.
It's about 35% to 40% respond to <unk> DRG code gets it and then.
Another half of those may respond to a better coal to gas at but thats restricted to people without severe liver disease.
So people are still even with the therapies today progressing to cirrhosis and requiring liver transplant and there are approximately 10% to 12% of people.
<unk> liver transplants in the United States for PBC. So.
So I think that there is still an unmet medical need to address the underlying root cause of the immunologic damage and that's what our precision immune tolerance platform is aimed at.
Great. Thanks for the color.
At Rps BBC, mostly affects women than men.
So do you have a reason why that's the case then would you consider enrolling more female patients in your future clinical studies.
Yes, Youre correct that.
Many is 90% to 95% of individuals who have PVC are women.
<unk>.
It is the case for many autoimmune diseases that there is a higher percentage of women in other autoimmune indications in the liver like autoimmune hepatitis, there's 70% of the individuals that are women.
So that is a common theme in autoimmune disease. So in our trials of PVC, we anticipate that.
The vast majority will be will be women that are enrolled in the trial.
In terms of the underlying in terms of your question about the underlying reason why women are more affected.
Don't think that Thats been clearly worked out although the animal models that.
Are used for for PBC are also more much more prevalent in severe in female.
Animals so.
It does seem to be something that's replicated in the animal models of PBC.
Okay. Thanks for the color on one final question from me.
It appears <unk> IL as a versatile molecule with broad therapeutic potential obviously, the first indication is Rob disease are the plans to for sale last market indications within the realm of what do you think this is using <unk>.
Yes, that's a great question and obviously, you've just guided one indication at this point PVC will give more guidance.
And we definitely have patients.
<unk>.
Yes.
Whether you take all of those indications into phase III is a different discussion, but we don't want to limit ourselves to rare diseases only.
Thanks, so much for taking my questions.
This concludes our question and answer session I would like to turn the conference back over to Carsten Brunn for closing remarks.
Thank you operator, and thank you everyone for joining us this morning stay safe and healthy. This concludes today's call. Thank you.
The conference has now concluded. Thank you for attending today's presentation you may now disconnect.