Q2 2021 Regenxbio Inc Earnings Call
[music].
Good afternoon, and welcome to the region ex value second quarter 2021 earnings conference call.
At this time all participants are in a listen only mode.
Later, we will conduct a question and answer session and instructions will be given at that time as a reminder, this conference call is being recorded.
I would now like to turn the call over to Mr. Patrick Christmas Chief Legal officer for region ex value you may begin true.
Good afternoon, and thank you for joining us today with US are Ken Mills for Genesis, <unk>, President and Chief Executive Executive Officer, Dr. Steve Nicola, Our Chief Medical Officer, and Vince <unk>, Our Chief Financial Officer.
Earlier this afternoon and rejected by a released financial and operating results for the second quarter ended June 32021.
Press release reporting our financial results is available on our website at www dot for Phenix bio Dot Com <unk>.
Today's conference.
Conference call will include forward looking statements regarding our financial outlook. In addition to regulatory and product development plans. These.
Forward looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words, such as expect plan will may anticipate believe should intend and other words of similar meaning and.
Any such forward looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described and the risk factors and the management's discussion and analysis sections of <unk> annual report on form 10-K for the full year ended December 31, 2020 and.
And comparable risk factors sections of regenerative items and quarterly reports on form 10-Q, which are on file with the securities and Exchange Commission and available on the SEC's website and.
The information we provide on this conference call is provided only as of the date of this call August 9.2021, and we undertake no obligation to update any forward looking statements. We may make on this call on account of new information future events or otherwise.
Be advised that today's call is being recorded and webcast. In addition, any unaudited pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company.
Actual results may differ materially.
I would now like to turn the call over to Ken Mills Kenneth.
Thank you Patrick good afternoon, everyone. Thanks for joining us and I hope you're all having.
Safe and nice summer on today's call will begin with a recap of recent business highlights Steve.
Steve will provide an update on our clinical programs and it will provide an overview of financial results for the second quarter of 2021.
At the end of the call will open the line for questions.
I am pleased to report that 2021 has been productive for <unk> bio and we've made important progress across our clinical development program and.
And anticipate a busy second half of 2021.
Our dedicated team remains focused on bringing the therapeutic potential of our pipeline programs for patients in need and we look forward to continuing our leadership and AAV.
And <unk> gene therapy development and manufacturing.
Our focus this year continues to be on execution across our pipeline program.
Clinical programs evaluating RG ex 31 for for the treatment of wet AMD and diabetic retinopathy and expanded and continue to be on track. The first trial and our pivotal program evaluating sub retinal delivery of Rdx <unk> 4 and patients with wet AMD atmosphere continues to enroll patients and our second pivotal trial.
Expected to initiate and the fourth quarter of 2021.
In addition, we continue to advance our 2 phase III trials evaluating the Super Choroidal delivery of <unk>, 3.1 and for using the SCS micro injector.
The first interim data from cohort 1 of H.
Our phase II trial in wet AMD will be presented at the retina Society, 54th annual scientific meeting that begins in September and Chicago, Illinois.
We're on track to report initial data and diabetic retinopathy later this year and the fourth quarter.
For Rgs when Q1 are 1 time gene therapy for the treatment of NPS to or Hunter syndrome. We were pleased to share additional positive interim data from our clinical program and <unk> in May we continue to drive this program forward enrolling additional patients at a higher dose and enrolling pediatric patients over the age of.
5 years old.
And finally, our work on RG ex Q O. Q also continues we now expect to file an IND for the treatment of Duchenne muscular dystrophy by the end of this year.
I will now turn the call over to Steve for and even more detailed clinical and regulatory update.
Thanks, Ken.
As Ken mentioned, our pivotal program evaluating the sub retinal delivery of <unk> $3.14 for the treatment of wet AMD continues to be on track.
We are enrolling patients and the atmosphere. The first day 2 planned pivotal trials expected to support a BLA in 2024.
As a reminder, atmosphere is expected to enroll approximately 300 patients and evaluates RJ and $3.14, compared to repeated ranibizumab and <unk> injections of standard treatment option for patients with wet AMD.
We also expect to initiate the second of 2 randomized well controlled clinical trials as part of for a pivotal program and the fourth quarter of 2021, and we look forward to sharing additional details.
Beyond our pivotal program for <unk> hundred 2014, we've made progress in our 2 phase III trials evaluating <unk> 314, when delivered to the Super Choroidal space.
We have completed dosing of patients and the third cohort of our phase II trial for the treatment of wet AMD known as aviate.
This is the cohort of patients that received the same dose of <unk> $3.14 as patients and the second cohort that is 511 genome copies per eye, but the patients and the third cohort are neutralizing antibody or Nab positive at entry.
This may provide us additional information about the effects of <unk> 314, and Nab positive patients potentially broadening the patient population that could be treated with this in office delivery approach.
I am also pleased to announce that we plan to present initial data from cohort 1 at the lower dose of 2.5 years <unk> and GC per eye at the Retina Society, 54th annual scientific meeting, which runs from September $29 for October 2nd.
Additionally, we plan to reported initial data from cohort 2 and the fourth cohort.
Sorry for the fourth quarter of 2021.
For altitude, our phase II trial to evaluate RG ex $3.14, Super choroidal delivery and patients with diabetic retinopathy, we have completed enrollment of cohort 1 and we expect to report initial data and the fourth quarter of 2021.
We have also begun enrolling patients in cohort 2 at a higher dose and are pleased to announce that we will be expanding into a third cohort of patients and this trial as with 88 cohort 3 of altitude will evaluate efficacy safety and Tolerability and up to 20 patients who are now positive.
And the same dose evaluated and cohort 2 will be evaluated and cohort 3.
As in previous cohorts patients will not receive prophylactic immune suppressive corticosteroid therapy before or after administration of <unk> 314.
In addition, we are making great strides and our rare disease portfolio and are well positioned to provide key clinical updates and the second half of 2021 and beyond.
From our ongoing phase 1.2 trial of <unk> hundred 21 in MPS II patients up to 5 years old we were pleased to share additional positive interim data from cohorts, 1 and 2 <unk> and mid may.
As reported <unk> 121 continued to be well tolerated with no drug related serious adverse events.
Biomarkers and measures of neuro developmental function indicated CNS activity. Following our Gx 121 administration with continued evidence of systemic enzyme expression and biomarker activity observed.
We also began dosing patients in cohort 3 and an increased dose level of <unk> 11, GC per Gram brain math and the second quarter of 2021, we.
We continue to enroll patients and this cohort.
Our phase 1.2 trial, if Archie ex 121 for the treatment of NPS to in pediatric patients over the age of 5 years old also continues to enroll patients and we look forward to keeping you updated across both of our <unk> 121 phase 1.2 trials.
Enrollment is ongoing and cohort 2 of our phase <unk> trial of <unk> 111 for the treatment of NPS 1 at a dose of 5 E 10, GC per Gram brain mass.
As we are focused on realizing the therapeutic potential of our <unk> 111 for NPS 1 patients in need.
Our team is preparing to submit the IND for RG ex 200 to a potential onetime gene therapy for the treatment of Duchenne.
And we plan to submit the C and D package by the end of 2021.
Lastly, we remain on track to provide program updates for RJ ex 181 for the treatment of CL and to disease.
And <unk> $183.81 for the treatment of ocular and manifestations of CL and 2 disease by the end of 2021.
Our team has made significant progress and the first half of this year and.
And we look forward to driving this momentum throughout the second half of 2021.
With that I'll turn the call back over to Ken.
Thanks for the Great overview, Steve I'm excited to share just a few more of our business update.
In July we officially moved into our new headquarters and Rockville, Maryland, It's been tremendous to watch this lab and office space come online and I'm glad to have our team and move into this space.
And the headquarters includes a GMP facility, which is expected to allow for production of NAV vectors that scales up to 2000 liters and we're focused on integrating our capabilities to ensure adequate supply and is available across all of our program.
And we anticipate that the manufacturing facility and this space will be fully operational starting in the first half of 2022.
Our proprietary NAV technology platform also continues to be the foundation for development of gene therapies outside of the walls of <unk> bio our licensee partners have made significant advancements and their respective programs utilizing NAV AAV delivery with several and late stages of development.
Partners that Novartis have reported the treated more than 4500 patients with IV intravenous <unk>, which uses the NAV <unk> 93 for the treatment of SMA. We've also increased for TV initiation of Novartis as new pivotal study of interest equal delivery and patients with type 2 SMA.
In addition, ultra <unk> recently reported plans to begin dosing patients and 2 pivotal studies for <unk> 301 for the treatment of OTC deficiency and Gtx for 1 for the treatment of GST and <unk> were.
We also note the re initiation by Astellas of the pivotal trial for <unk> for the treatment of X linked <unk> myopathy.
All of these candidates use our NAV <unk> vector.
Currently therapeutics as a company that we helped form in 2020 and in June 2021, currently Ive announced definitive agreement for unit cure to acquire core leave and its lead program for the treatment of temporal lobe epilepsy now known as <unk>.
This utilizes <unk> AAV 9 NAV <unk> vector <unk>.
This transaction closed in July of 2021 under the license and collaboration agreement <unk> received equity and core leave and is eligible to receive milestone as well as royalties on net sales and $2.16.
As a result of the acquisition <unk> bio received a portion of the $46.3 million euros and upfront cash unicare paid to acquire core and leave and is eligible to receive a portion of the over 200 million and additional milestones.
And 200 million euros of additional milestones that may be paid to <unk> shareholders high unit share.
We look forward for the continued collaboration with all of our licensee partners to bring EDG and therapy forward using our proprietary NAV technology platform to patients in need.
With that I'd like to turn the call over to debt for a review of our financials.
Thank you Ken <unk> ended the quarter on June 32021, with cash cash equivalents and marketable securities totaling $593 million compared to $522.5 million as of December 31, 2020.
And the increase was primarily due to the $216.1 million of aggregate net proceeds received from our follow on public offering of common stock completed and in January 2021, including the full exercise of the underwriters option to purchase additional shares in connection with offering.
Great. Thanks was partially offset by net cash used in operating activities of $71 million cash used to purchase property and equipment.
$50.9 million and <unk> royalties paid.
Healthcare royalty management of $22 million during.
During the 6 months ended June 32021 based on our current operating plan, we expect the balance and cash cash equivalents and marketable securities of $593 million as of June 32021 to fund our operations, including the completion of our inter.
Manufacturing capabilities and clinical advancement of our profit candidates into the second half of 2023 with that I will turn the call back to Ken and Rob Powerbar from Anthony Rizzo and with <unk>.
Thanks, Nick.
Our hard work experience and commitment of our entire team has enabled significant progress the costs are and across our entire gene therapy portfolio. We're focused on building on our momentum from the first half for 2021 to execute on clinical and preclinical development for the remainder of this year and beyond.
With that.
We will open up the call operator for questions.
As a reminder to ask a question you will need to pass car, 1 and <unk>.
Your phone and we'd tell you your question press the pound key please turn by while we compile the Q&A roster.
Your first question comes from the line of Geoff Meacham from Barclays. Your line is now open.
Hey, guys. This is alec on for Jeff.
And thanks for taking our question just a few from us.
Since cohort 1 from the <unk> study it comparable in terms of the dose level for cohort 5 from the sub retinal study.
Could you just remind me the thought process behind starting at this dose and whether sort of.
For the bioavailability is expected to be comparable between the 2 administrative techniques.
Or could it maybe be a little bit less just in terms of expectations for the data and then as a follow up to that and I'm just trying to frame the update at the conference in terms of the length of follow up is it safe to say that it could be somewhere and the 6 month range given the study opened about a year ago.
Obviously, maybe not enough to reach the 40 week BCD day and client and then just lastly, a quick 1 do you think it would be appropriate to apply a read through.
To what we might see and the Dr update and <unk>, given it's obviously different patient populations.
Thanks, Alex Steve would you like to handle that.
Sure Great.
Thanks, Alec for for those questions.
So why start.
Oh for 1 dose level with Super Choroidal.
With the same GC per is that we had in our phase 1 to cohort 5.
Basically.
We had the benefit of a full dose range that we had gone through with the sub retinal delivery.
The overall preclinical package, including GOP Tox studies, where we had the ability to start that high and also to be able to go higher. So we felt it was important to already right out of the gate start with the dose where there could be aqua pose of actually.
Being able to look for some type of Pharmacodynamic signal.
To your second question of how might we think of that.
Translating.
The reality is these are and we've always said that these are different routes of administration.
Fortunately, we chose Super choroidal because.
Like sub retinol it allows us to administer locally where unlike with interim vitriol administration, we can give that dose where it spreads close to the target retinal tissue, but it is a different route where you get a broader spread than say the more intense.
Transduction.
Smaller area that you expect with sub retinal delivery so.
It's really hard Alex to say more than that and Thats why we do the dose ranging with a different route of administration, but here we have the benefit because of all the experience we have to be able to start a little higher.
As far as the data that we're going to be able to look at.
At Retina Society, and what we're going to be able to come out again very consistent with what we've said.
From the beginning where in the wet AMD disease setting.
<unk> always felt even and our sub retinal phase <unk> study and we.
Signaled the same in our Super Choroidal wet AMD study aviate that 6 months is a.
And more fulsome time point to really evaluate the key biomarkers that we care about include.
Including functional outcome. So the typical outcome measures that that we've talked about and the path and that we have experienced looking at at 6 months are well, we're going to look for and what we will be able to present.
And at Retina Society.
Your question on diabetic retinopathy.
Yes, you're spot on that to a different patient population.
However, we do have the body of evidence across many different anti VEGF repeated injection.
Programs that have looked at true.
And then of different patient populations, including diabetic retinopathy as well as wet AMD, where.
There.
Is the general belief of.
A range of doses that has affected and 1 disease setting.
And of a bet, Jeff driven retinopathy that by targeting anti <unk> targeting bet, Jeff with.
A similar doses in other VEGF driven retinopathy that you have the potential to detect a signal. It's just in that patient population, where the signals is something different.
Albeit just as important it is just that and diabetic retinopathy, we have the ability to look at the severity of the underlying diabetic retinopathy and actually great that and actually see can we improve.
And the diabetic retinopathy severity with onetime administration in the office with our <unk> hundred 1 for us.
Operator.
Uh-huh next question comes from the line of Gena Wang from Barclays. Your line is now open.
Thank you.
1 question with 3 parts <unk>.
1 for <unk>.
Simple client programs and first 1 clarifying question.
Across all other cohort in avs and aptitude trials.
Volume net sales.
For each injection.
And my second question is a full AVN.
And 1 data and the retinal society.
Should we expect meaningful information for act from the extremities and also for the full presentation. We do include the protein level. In addition to visual acuity rationale for taking this and the injection frequency data.
And.
Hi.
The last part of the question is you started cohort 3 for both avian and attitude and.
Any concerns on safety since you increased the concentration and all for any concern.
Efficacy. Thank you enroll the patients with existing neutralizing antibody.
Hi, Tito this is Ken.
And then maybe Steve can provide more color if needed in terms of their volume and question and thanks for your questions by the way, especially in August.
The.
100 micro leaders as the standard volume this injected with our Super critical device that we've selected for delivery of <unk> 3.1 for and Thats been the.
Dose volume that we've used in the initial cohorts of both of the studies.
When we dose escalated in the 88 study.
The first transition was with.
Going from 2.511 to 511 was go from 1 single injection of 100 microliters of volume.
2 separate injections and the same visit so in that case, we were using 2 different injection site tutor for and injectors. So we were technically injecting 200 microliters into those patients.
As we continue to move forward with altitude, we've standardized so on the 100 microliter volume for a higher concentration now and we would expect to continue to do that in cohort 3 and cohorts that we would plan to move forward for further study.
And the data I think I heard the backend of your question, maybe not the front and so we're approaching.
For a month or so away from bringing together data with investigator on podium at <unk>.
Retina Society meeting our approach here is <unk>.
Similar to if not identical to our approaches that we've had on.
Our study of the sub retinal data, which is too.
And bringing the full package of information that we're collecting from the study forward and I think Steve mentioned in response to Alexs question that we've always used the cutoff.
6 months is the time point, that's been important to us and collect all the different measures and the thing.
And we're measuring are the same as what we've measured and the path.
And when it comes to these outcomes, including safety of course, and the functional outcome, Steve referred to and protein levels.
Haven't done the data current right now will be transitioning into that and the next.
30 to 60 days to prepare for that announcement and.
And we're bringing as much data as we tend to that podium presentation based on what we have.
And from the clinical study.
And the final question was about.
Cohort 3.
And I have to do with yes.
And efficacy fever.
Okay.
Good.
Yes, I can.
Jump in there.
Hi, Gena.
Yes, so the aspect of.
Increased concentration by being able to go to a single 100 microliter injection that Ken referred to that we're able to do and <unk> 3 of 88.
And also and <unk> and <unk>.
<unk> 3 cohort 2 and cohort 3 of altitude, whether we have any safety concerns there.
And we felt.
Comfortable to advance to using that higher concentration in both net negative. But then also net positive patients based on the data we have and also the higher concentration data that we have from our preclinical package that was included in our and D.
And all of that was what made us feel comfortable to go there.
<unk>.
Related question was what about efficacy issues of evaluating and net positive patients as we're doing now and both aviate.
And.
And we'll be doing in altitude.
And here. This is why we do these cohorts here again from the beginning even before starting the initial cohorts and that negative patients. Our plan had always been and we'd always communicated that we were going stepwise first.
Looking at net negative patients and fees were the first ever studies looking at Super Choroidal gene therapy.
But now that we have done that at 2 different doses.
And the wet AMD population and that's what gave us the comfort to advance there and this is this is why we're so excited to make these.
Net against milestones for for this space to not only be able to assess <unk> negative patients, but also to look at both safety and efficacy and patient 2 are net positive.
Okay. Your next question comes from the line of Dane Leone from Raymond James Your line is now open.
Alright, Thank you for taking the question.
I guess first question for me.
When do you think you would consider getting a bilateral study for RG <unk> III for.
Either Super cried all R R and sub.
The sub retinal.
Procedure.
And then secondly.
Can you maybe give some color in terms of.
The.
And year on DMD and if there is.
And.
Originally you had that.
Slated to begin in the mid part of the year.
Back towards the latter part of the year any color there would be.
I appreciate it as well thank you.
Sure, Dan and I will take the second part of that question, which is for 200 to the IMD deliverables and the process for sort of finalizing and starting to author and prepare the IMD is what's ongoing right now within the company and I think we had given guidance at the beginning of.
For the year that we thought we could have that all prepared by mid year and what we're seeing is a little bit of change to that into the fourth quarter of this year, but nothing in terms of the process internally that has changed materially for us in terms of getting that IND filed and this study up and running just been a little bit.
Adjustments to the original plan based on the work that needed to be done and has been done.
Maybe with respect to the bilateral consideration I'll ask Steve to weigh in there.
Sure Hi, Dan.
It's a good question, it's actually 1 we'd get anecdotally not surprising Lee from for example patients.
And our phase 1.2 sub retinal study who have had good success with treatment and 1 eye and interest and.
Wouldn't it be great if I could have both my eyes treated.
So I'll take each route separately.
And for sub retinal.
Delivery.
The benefit of all the experience that we have here both in terms of the relative immune privileged status of the sub retinal space and also the precedent and up lets turn to <unk>.
Bilateral administration.
It does make sense that.
Going forward, we would consider.
The potential to treat the fellow eye of patients who had 1 eye treated as a steady eye in our our trials so we haven't and.
<unk> <unk>.
Plants, there, but that is something that we think makes a lot of sense from a clinical development standpoint and also.
Of course, and the real world going forward to fully realize the value proposition for.
<unk> 3.1 for.
Gene therapy treatment.
For Super Choroidal delivery as we've often said that's been much earlier innings in terms of evaluation.
So first things first we evaluate how steady eye treatment goes in terms of.
Safety and an efficacy.
And overall Tolerability and based on the results that we see there and the accumulated data also that we have from sub retinal as of that time point, we'd also be and are better positioned to evaluate treatment of the LOI of steady patients.
Okay. Next question comes from the line of Manny for <unk> from SBB Leerink. Your line is now open.
Hey, Good afternoon. This is Rick on the line for Mani Congrats on all the progress and just 2 questions from us.
First.
And so the data and the Hunter program has been pretty impressive to date.
And I was hoping you could just share some of your most recent thoughts on the pathway to approval here and if you can comment specifically on.
Approvable endpoints and Hunter syndrome, and expectations for a single arm registrational trial versus placebo controlled.
And then the second question is just around financials.
I know the cgmp facility is expected to be fully operational during the first half of 2022. If you could just elaborate on some of the expected changes and distribution of Capex versus Opex and the facility is completed and Inc.
We should.
And any meaningful increases in spend as projector manufacturing sales up.
Thanks, Rick.
Start with the first 1 on Hunter we've.
Also as you mentioned and been very encouraged by some of the outcomes that we've seen from day.
The initial study.
And the first 2 doses in particular have.
Shown evidence of changes in.
Biochemistry that represent that the gene therapy is.
Working the way that it is designed and is tracking towards having a meaningful effect. In these kids were always wanting to reconcile that with other functional data and clinical assessment data, which we know historically can take longer to reconcile for baseline, but we like and we are enable now.
To collect from cohorts, 1 and cohorts 2 and what we think are meaningful understandings and relationships between some of those early biochemical changes and some other longer term progress and.
Of the assessments and so I think Thats our plan as we continue to steer. This program forward is to bring that evidence forward with all the stakeholders, including regulators show evidence of the connection between early biochemical changes and long term changes in clinical outcomes.
And we're also going to a higher dose, which we think should even further power and amplify that strategy because I think we.
And are expecting and have seen evidence of increased dose effect and while we maintain a good safety profile. So.
And for us and any rare disease program.
Were patient enough to want and taken all of the data, but our team is really focused on halfway towards acceleration, where there's this great unmet need. So we will look at this program going forward as leaning as heavily as we can on early evidence of biomarker changes to justify the clinical changes that.
We want for these kids and their families and that I think regulators should fairly expect as well.
On the financial side I'll start and if you have any more color I think we have.
The Capex investment as you mentioned has been ongoing across the spectrum of this year when we finish and.
And have the manufacturing suite operational and we'll complete that phase of investment.
We'll also be bringing additional programs online over the next several months and into the middle of next year, including our Rdx 202 program and as we talk about expanding our <unk> hundred 1 for program with additional dose levels and and an additional study and the requirements are still there operationally for.
Increased utilization of of any GMP space overall, I think that more and what we're going to see is some reduction of capex and the transition from 'twenty, 1 'twenty 2 and beyond at least as it relates to the GMP facility, but probably a steady continued increase in.
The operational expenses associated with and expanding platform of clinical studies, including and especially DMD later stages of Rdx 3.1 for with more patients coming on to the second pivotal and potentially new programs as well.
And Adnan.
Yes, Thanks, Rick Yes, we expect that for.
From a capex perspective.
No.
Continuing spending just to get to.
Final completion.
Manufacturing suite, and then in 2020.2 a lot of other work will be more focused on just standard.
And for suite and a lot less focus on additional capex.
And then and Tyco Ken's point.
There will be a change in opex per day, a change in opex.
A shift from using external Cmos once our facility is up online.
Bringing more debt in house.
With the expanded programs and expanded need for drug product and.
And the clinical stages.
We assume that it's going to be a little bit higher than we.
What we currently see.
Okay. Next question comes from the line of Matthew Harrison from Morgan Stanley. Your line is now open.
Hey, great good afternoon.
I guess 2 follow up questions 1 on 3.1 for and 1 on 1 on the Hunter.
So on.
And.
I guess my question here is can you just.
Let us think about a little bit how you compare and contrast, your program, which obviously is a gene therapy versus some of the antibodies that are and development, especially the ones that seem to cross the blood brain barrier better and and how you think about the relative gag reductions.
And those 2 treatments and.
And just the competitiveness.
Development, there and then.
And Leon on 3.1 for.
I know theres been a lot of questions people have asked about that I guess, what I was really hoping for was.
You have a couple of cohorts here, we're only going to see the first dose.
And what as you think about developing Super Choroidal do we need to wait for all 3 cohorts or if you see data that you think is good enough from this first cohort could you move that forward quickly maybe you could just give us sort of the scenarios on how you might develop that.
And given that first set of data with Tennessee.
Yes, Matthew Thanks for the question.
And we've always I think.
Establish that we're disciplined and we're focused on building good pharmacological understanding.
And of Prana candidates and product candidates include.
A treatment candidate with the new route of administration, and we tested 5 different doses with our sub retinal route of administration working through and understanding of safety and pharmacology functional clinical responses and protein level and made a very educated and I think thoughtful decision about how to move that into pivotal phase and we will take the same.
Type of disciplined approach with respect to.
Super Choroidal, except and an important exception here, we're starting obviously already with a baseline of pharmacological understanding that we can relate and correlate to sub retinal, especially on safety. We've had evidence already we've talked about with all of you that were starting and higher dose level and we're able to continue to dose.
Escalate based on the preclinical data and our clinical understanding overall.
The true answer is we we will know when we're able to accelerate and we see the entirety of our data from the cohorts that we choose to start to enroll and escalate too and.
And I think that when we certainly want to have a dose curve perform moving onto a later stage of development with any round and administration and any pharmacological Kennedy profile.
Typically when we have conversations with regulators and groups like FCA.
More and better, especially when you are moving into a patient population and that's about hundreds of thousands if not millions of patients and it can be a very different conversation when you're talking about a rare disease or an ultra rare disease with unmet.
The unmet need that is so severe that werent different type of thinking.
And that's why we've been so encouraged overall so far this year.
And on track with enrollment we've been on track with including expansion of our phase III studies, the higher doses into Nab positive patients.
We're on track to report that first data at 6 month time points for cohort, 1 and indeed, I think as important and we're on track because of that enrollment and expansion for relatively fast follow on with respect to those additional cohorts as well. So that's going to be our approach will keep sharing the data at the time points that we think are important and meaningful.
To all of you and all of the stakeholders here as we get it and make sure that we have the right amount of data to make decisions about where the program to go next which we have always wanted our programs to move as quickly as possible and into late stages of development, especially with wet AMD and Dr.
And let's say on the Hunter program side of it.
I think we were very conscious and excited about the landscape of interest that people have in lysosomal storage diseases like hunter to bring something especially for these diseases that have enzyme replacement therapy to treat systemic or peripheral symptoms, but nothing that is addressing a central nervous system disease here.
That exist and these kids that we all know exist.
And what's unique for us about gene therapy, and our approach is and I kind of characterize it often is and.
Inside out approach right. So when we see changes in Biomarkers, when we see evidence and biochemistry changing and the CSS of kids.
And it symbolizes represents the symbolized it tells us the scientific story that we have true.
<unk> transcribed and express protein intracellular and Thats, where the problem is and so when we see that change happening with something like a substrate of the enzyme in the CSF and we've seen that correlation and animal to those intracellular changes for us.
But that's very meaningful and very important and why we've done a lot of characterization of the substrate and they're a direct correlation to those gene therapy changes and interest cellular changes that could only occur if our treatment is transitioning and transcribing <unk> sales and transcribing protein.
Other treatments other mechanisms of action.
So and have shown changes in biochemistry and they.
They have different mechanisms of how they operate they are often outside and approaches using proteins that are.
Bound to the enzyme, whereas you mentioned antibodies or antibody fragments are things that can help those proteins those enzymes transport across other broadband barrier et cetera.
And that's not our area of expertise and I don't want to speak beyond what we focus on and where our science is taking us.
And I think that we view that 1 time treatment for gene therapy that is showing changes at pre clinically and clinically are meaningful and correlate to the fact that the June has gotten into the brain cells and design is about as meaningful a data set as we can show and these important diseases and.
And now we need to back it up with the clinical evidence as well. So that's what gets US excited about onetime gene therapy for things like Hunter syndrome.
Okay. Your next question comes from the line of Aston and Raj <unk> from UBS. Your line is now open.
Sir Your line is now open.
And there is novelis bonding silhouettes.
Open the lines 5 and Luca easy.
From RBC capital your line is net ruble.
Alright, thanks, so much.
I appreciate you taking my question and congrats on the progress maybe just a few here.
And given the phase III for wet AMD.
Thank you mentioned in the past and be a rescue injection criteria was going to be more stringent and the phase III versus prior trial wondering if that is still the case and maybe if you can expand a little more on it.
And then the second on the bridging study and do you have any update there I know you are pivoting from a deer and cell lines suspect. It's aligned so I'm wondering if you have started debt trial and probably most importantly for debt trial gating to start the second phase III or any other trial and then any update on the clinical whole for bat and.
Disease that would be great. Thanks, so much.
Thanks, Luca and I'll start back to front there.
Don't have any updates on to Matt and study, we're expecting to provide more updates on that program between now and the end of the year.
Overall for the <unk> 31 for a pivotal program.
We announced that we are initiating the second pivotal study that we expect that to start in the fourth quarter of this year we have.
Now that we have continue.
Continued to enroll in the.
Atmosphere study and that overall enrollment is occurring across all of the studies, including the bridging study. So we are on track with respect to atmosphere and the bridging study and the plans that we have for initiation of the second pivotal study and there.
And there is not an interrelationship between the staging of the bridging study and the start of the second pivotal those were things that we had planned already and are and are happening. According to the timeline and are on track I guess with respect to the first part of your question and I'll put this back and fees court to talk about the.
And criteria for re treatment.
And atmosphere.
Yes, thanks, and thanks Luca yes.
You're exactly right.
We.
I have taken advantage of the learnings from the phase 1.2 study, which was a first in human study where.
We had a very low bar for re treatment, where investigators could retreat based on any amount of fluid without any requirement for increase and fluid or a decrease and visual acuity and as we presented before.
We were still able to show a dramatic reduction and treatment burden and those patients.
Though a lot of the injections that were even given where we are given for very little fluid or even in some cases, no increase and fluid.
So for our pivotal study.
Studies.
We are incorporating a stricter rescue or re treatment criteria, where we use objective data that is requiring either a reduction and best corrected visual acuity and or a certain amount of.
Increase in the central retinal thickness and these criteria are very much in line with debt.
And the precedent of what's out there in terms of other studies that are looking at increasing the treatment.
Interval or treatment duration.
So where we are in that same.
Basic range, it's just that and our case, we're looking at a potential 1 time.
Treatment and these trials.
Thanks Luca.
Once again to ask a question you will need to press star 1 on your telephone.
Your next question comes from the line of Dana Liang from Raymond James Your line is open.
Hi, Thanks for taking a follow up question.
And 1 specifically we have gotten questions and.
My question is given the.
Issues with a peer company.
And patients.
And experiencing severe reactions and the.
Diabetic macular edema.
To their gene therapy.
Just wanted to give you guys a chance to comment in terms of having the.
First cohort that you expect to report out and diabetic retinopathy, which is a different indications.
And the fourth quarter, just maybe compare and contrast, your expectations for the biology of the diabetic retinopathy patients.
Versus diabetic macular edema patients and then.
And specific points of interest.
And may be able to make around.
Around how you view the safety of your program. Thank you.
Thanks Dean.
Relating me back in again.
You bet.
Steve do you want to answer that.
Yes.
Yes glad to have the follow up question.
From you Dane.
Yes, similar to how Ken.
Talked about.
Other programs and and other space.
And we're really not in a position to go into.
And any pontificating of what could be going on and another setting.
We are obviously aware of that.
Findings.
And that's.
And I totally that the different program with a different vector different transgene and importantly different route of administration, where.
They are.
And is obviously known the.
Risk of inflammation and that exist with with that routed administration.
And why we've been excited about and.
Selected sub retinal initially and then Super Choroidal, where unlike with Intraventricular administration of any vectors.
Including.
AAV, 2 or modified AAV 2 vectors and.
Nab vectors wherewith interim vitriol, you can get inflammation with Super Choroidal, and both small animal models and also a large animal models, including.
Multiple non human Primate studies, we have not seen inflammation. So that's why we were excited to go into both wet AMD and diabetic retinopathy.
And dose ranging studies and both those indications without.
Prophylactic steroids.
And why we're excited based on initial data.
From the initial cohort and both studies to be able to go up and dose and both wet AMD and also Dr. And also importantly felt comfortable to advance also and now positive patients in both settings with that higher dose so.
And we go where.
The science leads and the data.
So we are.
Again, we can speak to our data we're aware of the context.
And the whole field.
But each program is specific.
Based on Inspector Transgene, and other factors and importantly route of administration.
Thanks, Steve.
Your next question comes from the line of <unk> <unk> from UBS. Your line is now open.
Hey, Thank you for taking my question and I apologize for missing for Q4.
Jumping between calls but just.
And a touching again on the Super Choroidal delivery can you help us understand how widely used right now.
And and what context. Thank you the net.
And how much.
And what the economics could be.
And correlated below average for.
Covid shale.
Molly jet.
And then I have 1 other follow up.
Yes.
Yes.
Question for you.
Okay.
Alright.
I'll take the front and of that asset so.
So super choroidal space or delivery to that space more broadly than just gene therapy. The most extensive experiences with clear side.
And they're at CFS, micro injector, where they've dosed well over 1000 eyes.
Mostly with a steroid.
<unk> triamcinolone and preparation for treatment of non infectious uveitis.
It's also been used and other treatment settings, and based on the safety and Tolerability and feasibility of administration there continuing to advance.
Also in partnership with.
Other companies such as Bausch for their their lead program.
So that's actually 1 of the reasons, we chose to partner with clear sight to used and most validated clinically.
Device for delivering.
And infusion to the Super Choroidal space.
For our 1 time in office gene therapy approach.
And why we are excited to advance on that we like clear side and their partners have seen very good feasibility.
In terms of administration of <unk> 3.1 for utilizing.
And the SCS micro injector.
<unk>.
This is a different route of administration with the benefit that.
Hi.
You don't have to go to the operating room to perform and.
And these are a retinal surgeon and specialists. So this is a very simple and.
Straightforward and office.
Approach debt that we've seen so we're very pleased and excited to continue advance.
And with Supercoil delivery.
And aspect, we still need to see is whether neutralizing antibody status.
And is important or not in terms of.
The potential expansion of debt.
And the use of the Super Choroidal injection route.
And did you have any anything else to add on the back end of that question.
No Steve just that we're not prognosticating on pricing of Super growth right. Now we are initiating our first in human and investigation of what we think is exciting rather the administration and approach and.
And have the opportunity to evaluate that and take inventory of it look.
And more to the future to talk about next steps for the program and ultimately happy to have conversations about commercialization of this high potential approach.
Okay. There are no further question at this time I will turn it over back to Mr categories for any closing remarks.
Thanks, operator, and thanks, everyone for participating today for those of you who are still hanging on.
Today, we had an exciting quarter, we have <unk>.
Free data updates that we've communicated between now and the end of the year, starting with retina society than cohort 2 wet AMD and diabetic retinopathy cohort run between now and the end of the year for Rdx 3.1 for an IND filing for our DMD program and more updates on <unk>, 1 looking to continue to charter.
Of course for how that program moves forward. So thanks for the great questions and we touched on a lot of these topics emphasized that the first half of this year has been a great period of execution at the company and looking forward to more updates for the rest of the year and have a good afternoon.
This concludes today's conference call. Thank you for participating you may now disconnect.
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