Q3 2022 Regenxbio Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Hello, and thank you for standing by.
Welcome to the Q3 2022, Eugenics Baidu, Inc earnings call and update on altitude.
At this time all participants are in a listen only mode.
After the speaker presentation, there will be a question and answer session.
To ask a question. During this session you will need to press star one one on your telephone.
It is now my pleasure to introduce Chief legal Officer, Patrick Christmas.
Good morning, and thank you for joining us today.
Earlier this morning, <unk> released financial and operating results for the third quarter ended September 32022, as well as new data from our Alpha two trial.
The press releases and data presentation are available on our website at www Dot <unk> Dot com.
Today's conference call will include forward looking statements regarding our financial outlook and our development of <unk> hundred one four 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 believes should intended and other words of similar meaning.
Any such forward looking statements are not guarantees of future performance and involve certain risks and uncertainties.
These risks are described in the risk factors and management's discussion and analysis sections of <unk> annual report on Form 10-K for the full year ended December 31 2021.
And comparable risk factors section of <unk> quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's Web site.
Any information we provide on this conference call is provided only as of the only as of the date of this call November three 2022, 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.
Please be advised that today's call is being recorded and webcast. In addition, any unaudited or 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 CEO of <unk> bio.
Thank you Patrick good morning, everyone. Thanks for joining us I'm pleased to begin today's call with a recap of the recent business highlights as well as an update on our corporate goals.
This assist our chief financial Officer will provide an overview of financial results for the third quarter ended September 32022.
Whereby coastal today, Steve for Cole, our Chief Medical Officer on the West Coast recently attending Retina Society Hill.
We'll provide an in depth overview of the data that was presented yesterday at the retina Society meeting from our phase II altitude trial evaluating <unk> 314 for the treatment of diabetic retinopathy or Dr. Using super Cradle delivery towards the end of the call we'll be joined by altitude investigator Laila Vaskevitch from Duke University.
An independent retina expert Dr. Peter Kaiser from the Cleveland Clinic.
Taylor and Peter will stay on with US as we open up the line for questions.
At <unk>, our mission is to improve lives through the curative potential of gene therapy focused on developing therapies for diseases that have significant unmet need we continue to be a leader in gene therapy. There are thousands of patients who have been dosed with AAV therapeutics derived from our NAV technology platform and hundreds more are receiving treatment.
Every quarter.
I'm very proud of how our company has been advancing our internal pipeline and I believe our fundamentals have never been stronger we put into place are five by 'twenty five strategy to progress five AAV therapeutics from our internal pipeline and licensed program into pivotal stage or commercial products by 2025.
I'm now going to summarize some of the program highlights and operational updates from our announcements this morning.
Our global eye care collaboration with Abbvie to develop and commercialize <unk> hundred one for for retinal disease continues to advance and is on track for our first BLA filing in 2024.
Progress in trial enrollment and emerging clinical trial data also supports excellent progress in our Super Choroidal delivery program.
And our <unk> hundred one for sub retinal delivery for the treatment of wet AMD was reported to be well tolerated with long term durable treatment effects now observed up to four years.
We expect this trial along with the two ongoing pivotal trials atmosphere in a sense to support our planned BLA submission in 2024.
In October we also announced positive interim data from the phase II trial of Rdx 314 for the treatment of wet AMD using super choroidal delivery.
These data showed rdx 314 was well tolerated with stable <unk> CVA and a meaningful reduction in anti VEGF treatment burden at all dose levels out to six months.
We announced the expansion of this trial to further explore the third dose level in our sixth cohort with a short course of prophylactic ocular steroid following <unk> hundred one for administration in order to potentially prevent the observed incidence of mild to moderate ocular intra ocular inflammation.
Yesterday as I mentioned at the Retina Society meeting new positive interim data was presented from our phase II <unk> trial of <unk> hundred one four for the treatment of Dr. Using Super Choroidal delivery and Steve will lead a review and discussion of these data in greater detail shortly.
We've been working diligently to prepare on the initiation of our first in human trial of <unk> for the treatment of Duchenne and continue to expect to dose. The first patient in the affinity Duchenne trial in the first half 2023, <unk> hundred two as a potential onetime gene therapy for the treatment of Duchenne and being <unk>.
Improvements in Neurodevelopmental function and caregiver reported outcomes demonstrated CNS activity up to two years after Rgs 121 administration.
The expanded pivotal phase of this program is expected to enroll up to 10 M. P. S. Two patients using commercial scale GMP material to support a BLA filing in 2002 thousand for using the accelerated approval pathway.
With the potential to enroll additional patients.
This is our second active pivotal program and another opportunity for a BLA filing by 2000 2004.
Our ongoing phase two trial of Argy X 111 for the treatment of severe MTS, one or Hurlers syndrome continues with plans to enroll additional patients and cohort two expansion are.
Our manufacturing innovation center in GNP capacity capability remains a key differentiator for <unk> and a key element of our strategy. Our in house facility is cutting edge and allows us to move quickly from candidate selection to production of clinical grade material, which supports accelerating the early <unk>.
Element of AAV therapeutics.
Additionally, we believe our approach focuses early on product quality and process control, which lessens the need for changes during clinical development to enable efficient transition from clinical trials to commercial readiness.
I will now just like to take this time to thank our entire <unk> bio team all of our investigators in their site support staff and the patient communities for their commitment to the continued development of our AAV therapeutics.
We certainly believe that one time gene therapy can address.
Whole range of unmet needs and both chronic and rare diseases and we remain dedicated to these patients and their families.
Overall, reflecting on this quarter at this point in the year very proud of the progress we've made to advance our five by 25 strategy.
And with that I will now turn the call over to visit for review of our third quarter results in financial guidance. Thank.
Thank you can return next bio ended the quarter on September 30th 2022, with cash cash equivalents and marketable securities totaling $617 million compared to $849.3 million as of December 31.
2021, the decrease was primarily as a result of cash used to fund operating activities and capital expenditures as well as temporary unrealized losses.
The bulb debt securities during the nine months ended September 30th 2022.
R&D expenses were $63.3 million for the quarter ended September 30th 2022, compared to $47.9 million for the quarter ended September 30th 2021 <unk>.
The increase was primarily attributable to personnel costs and expenses associated with the clinical trials and manufacturing related activities for our lead private candidates and was partially offset by.
<unk> forward development cost reimburse all all I add the under our eyecare collaboration in accordance with the collaboration agreement <unk> will continue to fund certain ongoing clinical trials for Rgs 314 through the end of 2022, while other three one <unk>.
Costs are shared with Abby.
Beginning in 2023, <unk> will be responsible for funding the majority of all <unk> development.
The expenses based on our current operating plan, we expect the balance in cash cash equivalents and marketable securities of $617 million as of September 30th 2022 to fund our operations into 2025.
And now we would like to return the call over to Steve for an in depth discussion of the recently announced altitude data.
Thank you guys.
As Ken shared we recently presented NRM data updates for Archie X 314 trials for the treatment of wet AMD using sub retinol and Super Choroidal delivery.
R. G X 314 is also being developed for the treatment of D. R. And we're pleased to be sharing new interim data from our phase two altitude trial of <unk> 314, using super quarterly choroidal delivery.
It was presented yesterday at the Redness Society meeting.
Slides from that presentation can be found in the media presentations and publications section on our website.
Joining me. This morning, we have Dr. Layla voice of Itch Associate Professor of Ophthalmology and director of the Juke Vitreoretinal Fellowship program and the lead investigator who presented the altitude David yesterday.
We're also joined by Dr. Peter Kaiser Director of the center for ocular research and evaluation at the <unk> Institute at the Cleveland Clinic.
Dr. As a complication of diabetes and is the leading cause of blindness in adults between the ages of 24 and 75 and.
An estimated 27 million patients are affected by this debilitating disease worldwide.
<unk> slowly progressing disease that can lead to fish and threatening complications.
Including diabetic macular edema 40 at me and Neovascularization that can lead to blindness.
Like in wet AMD patients with Dr treated with anti VEGF therapy, which is proven to reduce the risk of developing efficient threatening complications. However.
However, due to the unsustainable treatment burden using anti that Jeff therapies.
Primarily the result of that frequent <unk> injections required.
Many patients with this condition put off receiving any treatment until symptoms become unavoidable.
We believe a gene therapy like Archie X 314 could potentially overcome this hurdle and provide an important therapy for DDR patients to significantly altered their disease progression.
Altitude is a multi center open label randomized controlled.
Does escalation phase two trials evaluating the efficacy safety and Tolerability of Super Choroidal delivery of <unk> 314, using the Ses microinjector in patients with a Dr diagnosis of moderately severe or severe nonproliferation diabetic retinopathy and PDR.
Or or mild proliferative diabetic retinopathy PDR.
Patients in cohort one received our check 314 of it dose level of 2.5, 11 genome copies Fry, which we refer to as there was one while patients and cohorts two and three received <unk> 314 at an increased dose level of 511 Chi C Fry, which.
We refer to as goes to pay.
Patients and cohorts one through three did not receive prophylactic corticosteroid therapy before or after our tier 314 administration.
As of October 17th 2022, or 314 was reported to be well tolerated and cohorts 1335.
Five serious adverse events were reported.
Which were considered drug related.
For the total group of cohorts, one through three receiving Archie X 314, 50 patients in total common ocular adverse events in the study I 306 months, we're predominantly mild and included Contra title hemorrhage content title Hyperaemia inept spy writers.
In addition, three patients experiencing trochlear inflammation iwai, all of the which were filed and resolved on topical corticosteroids.
There were no meaningful differences in safety outcomes observe for patients who were nap positive best.
Best corrected visual acuity remained stable and cohorts one through three 306 months.
At six months patients treated with Archie has 314 demonstrated clinically meaningful improvements and disease severity versus observational control as measured by the diabetic retinopathy severity scale or D. Rss.
Specifically 20 per cent of patients representing 40 per cent of patients and dose, one and 11% of patients and dose to achieve two step or greater improvement in crf's escort.
Versus 10% and observation control.
Additionally, 54% of patients representing 60 per cent of patients and dose level one.
And 51% of patients and dose level to achieve any level of drs improvement versus 20% and control.
And it's important to note that zero out of <unk> 314 treated patients had at least two step worsening indyref sat score while 20 per cent of patients in the control arm experienced at least that two step worsening.
So with that.
I will now turn the call over to Doctor Layla both of their too is sitting next to me and a lovely Pasadena, where laid out Layla we were really excited to hear.
Hear your presentation yesterday at the restaurant Society meeting here. So now it's really a great opportunity for us to hear your political.
Clinical perspective as lead investigators in the trial on the interim results that that you presented.
It's a pleasure to be here today.
Very exciting fashion term data.
Cause that's disgusting.
Discussing this morning.
It's been nicely highlight Clinton apathy.
That's the problem.
Which probably helped prominent globally and that really teen ink theory, uhm, Gary busy clinics, a diabetic retinopathy patients Unfortunately, because of their status and working on each cannot keep up with the treatment pardon.
Injection.
Did that results typically my clinic about 90% of my patients are being watched and not treat it often.
Often not eating coming for the appointment.
There is a tremendous need for better treatment.
Unsustainable treatment.
Having a one time treatment offered me providing a solution that.
I'm excited to see the internal I'm dangerous.
First of all.
He looks very promising with improvements in cohort.
Alright, and coke, including premium right.
Right now.
Any score.
No disease listening that we signed it even though like even more importantly, 18 thoughts looks panicked.
We're seeing.
With minimal evidence inflammation.
Encouraging to me.
This translates to me.
Totally Wendy having a treatment option for 90% of my patient that currently being embarrassed.
Who are potentially going to we have E ink visual declined in the future and it's option me provide a solution to the.
I think.
Great. Thanks, so much layla for that perspective as the audience can can hear we're very excited about.
This interim data.
That layla presented in the potential of our G X 314 for patients with Dr.
As we continue to build upon a drug profile of our Jeff 314, and Dr. We've made the decision to expand the altitude trial to include a higher a third dose level of <unk> and Layla outline that as well yesterday at the presentation to trial is currently enrolling too new.
New cohorts cohorts 45 at this third dose level cohorts four and five are enrolling patients stratified by Dr. Abscess levels with patients and cohort for having moderately severe disappear N. P. R, which is D. Rss levels of 47 to 53 and patients and cohort five.
Have mild to moderate PDR, which is D. Rss levels of 61 to 65. So we're excited at that ability to Ah evaluated and Ah expanded Drs range.
Patience and these cohorts will receive a short course of prophylactic ocular steroids following Archie X 314 to evaluate the ability to prevent or reduce the.
The incidents of the mild and troxler implementation seen to date and Ah setting up no prophylactic steroids.
Patients will be enrolled in these cohorts, regardless of baseline aviate naff status.
So now we also have sitting here with us in Pasadena. This morning, Dr. Peter Kaiser.
Who are in in addition to being an expert clinician in clinical triallist and.
Expert across the restaurant space is also a very experienced central reading center.
Greater an expert an overseer.
Including assessment of diabetic retinopathy and use of the standard Drs theft scale.
So Peter really.
Perfect opportunity to really blend your your expertise both clinically but also how you think of.
And points when it comes to diabetic retinopathy and use of the Vrs that scale. So we'd love to hear your your key takeaways from this interim data updates sure.
[laughter]. Thanks for inviting me Layla really outline of great, which is we have two products that are F. D. A approved for the treatment diabetic retinopathy regulatory endpoint that we use as diabetic retinopathy severity score, which really is something that we we do it a reading center level and in general at a critical level later on I won't be counting microlenders.
I'm looking at it as closely as we do in a clinical studies.
It's important to understand that the deer assess was developed a long topic almost 30 35 years ago now for the early triggered diabetic retinopathy studying is one of the first randomized studies done crossing medicine.
And the importance of a two step change is that's a very significant change in the level of retinopathy and that's why the F. D. A F E M a use that for regulatory approval.
Whoever in clinical practice, where we want to see is overall, our patients getting better and it's layla correctly pointed out. The reason we don't use the F. D. A approved products both I Leah and we expect us that often you know there are.
There are a few patients we do use it off but but in general we do is because it requires very frequent injections. So it means working each patient simply can't take the time off from work to get these injections or there for about you know they they just don't Wanna do it most of these patients actually have very little changes ambition. So I don't really see it.
<unk> with these injections book, but as physicians, we can see the improvement.
Really brings out the point of objects three one for this this is to me is a killer app for gene therapy. The idea of doing it in office procedure to allow these patients to have improved making a diabetic retinopathy.
Scores, which we saw very nicely with the presentation by later like yesterday of the altitude interim study results. This is very exciting for all of us in the retina field.
Wonderful. Thanks, Thanks, so much Peter <unk>.
And with that we are ready to turn the call over for questions.
Operator.
Thank you.
As a reminder to ask a question you will need to press star one one on your telephone once again to ask a question. Please press star one one.
And our first question comes from the line of Gino Wang with Barclays.
Hello, Thank you very much for taking our questions and she also like Gina I have two questions. The first question about the inflammation. So that information wait at all 511 dose cohort seemed to be pretty similar to the web M D.
At the same dose can can you just give them more colors like the onsite unset duration and house like information wants resolved like what's still rolling it and how long it's used and how long I could take two days off.
I have a follow up question on the.
Ah New Profi cohort, so Cancun will Congress down the short course steeled alright.
Even though we're same as the avs full wet M D such as an estimation like do you can you can choose both topical.
And one time steps.
Oh injection and once once a year ago.
We haven't used and what will be the dose Megan Thank you very much.
I think those questions are best directed to you in the experts there.
Great.
Thanks for for the questions all all give.
Initial comment.
And pass it over to Layla to give her perspective of what she experienced within the trial Ah firsthand. So in terms of inflammation and you're exactly right. We saw we didn't see anything not anticipated.
So we were quite pleased with the low rates of <unk>.
Mild <unk> inflammation in the characteristics, where what we've seen previously nothing.
Concerning and that we we see it come on and.
Generally within two to six weeks of our tier 314 am very easily managed with a short course of of topical corticosteroids.
Investigators will here Layla perspective, and I'm very happy with the profile that we're seeing that's consistent with what we've seen previously but if we also have this great opportunity to.
Evaluate and further characterized in a setting a prophylactic steroids.
Where that allows the clinicians to assess how these patients due and potentially mitigate even further the risk of inflammation.
And we're doing that with topical.
Ocular steroids in the expansion of the altitude study and it'll just be a standard short course with typical paper over weeks, which are investigators in our thought leaders are very comfortable with that type of prophylactic.
Prophylactic Regiment.
But we have layla here, who actually goes patients in the trial and.
It is very aware of the data we saw across the trial, what what what was your perspective as you think of your own experience and your colleagues experience in the trial as far as inflammation.
Yeah, exactly like you highlighted mm.
We.
Having had patients in this trial.
Watching them very carefully dynamic antiphon Asia I would say it was really mild.
It prevented present in exactly two to four weeks.
After the injection potentially have to take and immediately theory, where to maybe a little more frequent in that entire segment south cause that's what does that translate.
Eastern kinetic for the patient.
Something because these patient clinical trial, setting where closely watching and noting and if we did see any attention to it because of my sensitivity to inflammation gene therapy child, we were proactive in training and so I think the treatment like he mentioned, it's very simple.
Active as well and topical steroid format and it was at short short on paper penalties for patients with gay and I'll point out in this cohort is about 6% of patients overall across actually all three coins that had the inclination very manageable like topical areas I think like I translate to my clinical study.
I think the safety profile is chronic ink and very manageable right now actually.
Great. Thanks, Layla Ah next question.
Thank you.
And our next question comes from the line of Vic room for heat with Morgan Stanley .
Good morning. This is some gospel on some <unk> we.
We have two questions. So the first one is I don't when doctors treat patients with.
Holliday measuring progress I did generally looking at the two step improvement in D. S. S. All for any level of improvement.
And then also too no how do you believe the addition of a dose of prophylactic steroid what impact the commercial opportunity for objects to own fault, if if at all.
Thanks for <unk>.
Right right at you.
Great. Thanks, Gospel and I'm Gonna directed right away to Peter because I think both these questions fit very well for getting Ah Ah.
Clinical perspective independently of how how Dr. Patients are managed and also how to think about Ah.
Topical steroids [laughter].
So I'll I'll handle the second question first you know so when you when you look at any new treatment as around the specialist with heightened sensitivity trochlear.
<unk> information and you know that term.
Term as a catch all phrase obviously it includes anything that we could possibly see what I look at the results of the Super corridor treatment both in a M D and diabetic retinopathy of Archie 314. This is mild iwai I served on a safety review committee for Novartis and this is not the same thing there's no red reclusion.
Renovate occlusion rental vasculitis, it is very mild and trucker information that's treated with a short course of steroids.
To me that that is not a big deal. So I'm not concerned about that certainly you'd have to we have to see more patients, but but so far none of the data concerns me in any way.
In terms of the first part of your question Dr assess.
We do that at a reading federal level.
This requires really carefully counting migraineur isms being a speeding et cetera.
In clinical practice the average Joe Ratliff specialist is absolutely not going to do that but what we are going to do is look at these patients over time to make sure that they are improving so in other words, if they have early neovascularization. So like levels 61, which was enrolled in a clinical study we're gonna be watching that neovascularization very closely with any of our treatments for that ma'am.
Matter to make sure that that area is resolving so in other words, we would expect with our treatment they've got neovascularization with disappear.
Because that Neovascularization is what leads to future vision problems tracks readily attachments, which is haemorrhage.
And that's what causes eventually blindness untreated. So that's what we are most worried about.
Over time, we'd watch to make sure they disappear, but we also like to see the the hemorrhages in a microorganisms disappear also this is something we could very easily deal with the clinical exam. So most rather specialist are not doing it almost drs evaluation. We're just looking at the patient through a dilated funded success.
Got it thank you very much.
Thank you.
And our next question comes from the line of Alex Stranahan with Bank of America.
Hey, guys. Thanks for taking our questions a couple from US also on D. R. First maybe you could talk about the the rationale for adding the higher dose level, an altitude is there a certain bar on Bureau S or some other metrics that you'd ideally like to hit them that you are not already just trying to.
I understand how you're thinking of the data thus far given it looks like there was actually a step down and B R. F. S improvement from dose one that those two but maybe there's the bulletin one step improvers and cohort three.
And secondly could you talking about the observational controlling the study.
Is this an appropriate comparator arm through your discussions would be F. B, a I guess looking at a pivotal study do you think you would need to run a head to head similar.
Took to what you're doing in the wet M D program.
Thanks, Alex.
So in terms of rationale for the higher dose.
These are both the aviate studying altitude. These are the first two studies ever evaluating super crowed or delivery of gene therapy for these indications. So this is really an exciting time for the field and for us to really characterize Rgs 314 via this route.
Administration.
And we actually have.
Interim data that we've presented with dose level three in the wet AMD setting from the Aviate study. So we in fact have a head start of evaluating this so it made perfect sense for us in our strategic partner Abby to continue to evaluate in this study.
Regarding dose level, one dose level too.
As Peter mentioned there there are various.
Cuts in and ways to look at a change in in D. R. S. S and the reality is when we look at the totality of of this data we see what we what we want to see in terms of both dose level, one and dose level too.
That <unk>.
<unk> as far as what we would need to do in a pivotal study. There. We are very confident in a observation control for the reasons that Layla and Peter both nicely elucidated that even though we know available repeated injections work quote unquote.
Terms of.
Improving Dr ISS and improving Dr. In preventing vision threatening complications those treatments are simply not used.
Only in a rare proportion of patients as as late as I mentioned, so standard of care is really still watchful waiting. So an observation control is ideal for the setting and one of the nice things about Dr development.
And it's nice that we have the concurrent control in this trial, where we see what you'd expect to see and I think either.
Layla or theater it'd be great D. When you look at our observation control and you think of.
Precedence canoe.
Control in the literature and your own clinical experience.
What do you expect to see if you don't treat pace.
Patients.
Yeah, I know exactly what you're pilot.
I would expect to see a progression overtrain them too.
Two fish in worsening.
And complications and I find out the team.
Actually I think observational arm is very acceptable cause status in a real world setting currently we are not.
Not treating T N word I frequent injections and tell them from my personal opinion, and and really experience in the clinical cockpit for it and it's quite acceptable.
Yeah, I totally agree.
Current clinical standards from a regulatory standpoint is not to do a headset study against a intravitreal Antevert Jasmine Jackson said would not be required.
A sham control.
This disease is not only regulatory a reasonable.
Also a very doable study.
Like patients the opposite if you put the anti veg efforts to control would be very hard for me to get a patient study. So so it's the opposite of what you would think but from a regulatory standpoint, absolutely totally fine.
Find to do it like a Champ control and.
And in terms of numbers you know I think this is the beauty of this data set is is that there is a control group. So you can kind of see what happens over time, it and what's happening to this control group at a six month interim that is sort of what would expect about 20 per cent or so or having a pretty significant worsening a few patients get better at it if you.
At the control groups.
David Vista ride ride et cetera, some panorama somebody's other studies that have been done it's about 10% to 15% will actually improve a little bit and largely that's not due to the fact that the disease is getting better in general that.
Is is that the patient enough studies suddenly realized wait a minute I actually need to do better control my sugars better control my blood pressure because I'm in this study.
That's what leads to that improvement it's nothing to deal with like in General is late upset. These pages are gonna go downhill, but I'll improve but if you do improve the sugar is a blood pressure that will improve fixed and we've seen that in the UK Pds in the D. C. T studies in the past.
Thank you.
Thank you.
Our next question comes from the line of Elie Moreau with you B S.
Hi, This is Sarah alley. Thanks, so much for taking a question I guess looking at the change in D. R. S. S score that you see at non sex.
Differences across cohorts between no worsening or no change in a greater than two stopped breathing one step improvement I guess do you look at this as an effect.
The new trying antibody status.
And thoughts about that moving forward into a potential thief.
Three are aren't labeling and then I got that second question as any detail or color that you can provide on five I think he needs that occurred during treatment would be great. Thanks, so much.
Great. Thanks, Thanks, Sarah Ah So on your your first question about that.
The the different cohorts in the different dose levels and the Nab status.
Very similar to what we see in the Aviate study, we've not seen an impact.
As we look at this data of course with.
15 to 20 patients per cohort you're gonna have some very.
Very ability that you would anticipate and also thinking of baseline.
Dr assets, how severe you are at baseline is a variable that can impact whether you can improve two steps.
Or not I think that's actually would be a good question.
Turn it over to Peter to talk about that nuance of.
Of grading and how to think of data based on baseline characteristics, but certainly if you take that into account we find.
And again looking at the totality of the data that in each of the dose levels in each of the cohorts that patients are moving in the right direction. Unlike the control arm. If you really take into account all the variables of not worsening by a lot like a couple of the control subjects and having improve.
<unk> on average.
And the other so.
And again, we in a after you get to not only look at these results, but also are 88.
Study to really assess how did naps matter.
Or not and that's why we chose in the expansion to enroll patients independent of their nap status will still measure it it will still be able to assess that checking to see if we continue to see.
Impact there.
Think before I go to the next question all.
I think Peter you're I think that's a nice question to really get your sense. When you tease her into the data how how do you <unk>.
Look across cohorts based on that.
The baseline characteristics for example for yeah. So I think you know whenever you're looking at him that especially in phase two.
Relatively small numbers of patients you'd want to read too much into it you want to look at totality of that data and to me. If you look at all the cohorts.
Their training in the right direction, there's right shifts and every single cohort, whereas in the control group you don't see a shift at all which is what he expected maybe even a slight left.
Left shifts, which which eventually untreated you'd expect to occur.
Over time.
But if you look at say cohort one versus two or three there's actually a very large imbalance at baseline.
<unk> scores in it's a very important balance so so in court one yourself more patients, but early PDR. So level of 61 and level 61 is a really minimal amount of neovascularization at the desk.
So it's two to move that two steps forward.
Is actually very easy with just a little bit of after you've got Jeff like Eddie after you've got Jeff given to a patient with mild NBD that mvd's disappear and they quickly go to 57, a M. And then drop even further thereafter, whereas you take somebody who say severe M PDR and try to improve them two steps that's a much.
Change in terms of what needs to be done to the eyes. So.
You know if you have a lot of Pdr's early PDR. This can be easier to show it to step change.
But that's that's not what we care about we care about the overall population of patients and to me that's what I said at the beginning the right shift of all of these patients is what's more exciting they're really looking.
Gradually at a few patients who just kind of went one way or the other way right. After six months time point.
Great and Sarah your other question on essay is.
Ah so here none of.
Of the five essays were considered drug related.
They're really the types of things that happen to patients Ah diabetic patients.
Who on average or are older not quite as old as the wedding M. D patients, but just to give you. An example, broken femur other unrelated aspects and in fact, the only ocular.
S. A E happened and a fellow I Ah for the patients who had the worsening vitreous hemorrhage. So overall very very clean Ah from a safety standpoint.
Alright, thanks, so much.
Thank you.
And our next question comes from the line of Luka with RBC capital markets.
Okay. Thanks for taking my question this is Lisa.
<unk> just a few questions and I am wondering if you can elaborate more on the decision to include prophylactic steroids.
With redfin can be diabetic retinopathy data allowance or that says how the other day that between the the diabetic retinopathy and what Andy program.
And as well you know on the baseline characteristics I noticed that the <unk> three patient had no prior anti bad Japanese action, but the cohort one based on bad and I can't get a sound a little bit better.
Just wondering <unk> well you enrolled patients who are empty bed bath experienced nurses that definitely.
Thanks, Thanks, Lisa Ah so ah to elaborate more on the decision to expand.
You know again, we take advantage of all the data we have so that's one of the the nice aspects of having both a wet AMD aviate study ongoing as well as this altitude study and Dr. Patients. So it really gives us a chance to look at safety and Tolerability and also <unk>.
Take effect for these fetch after it in red.
<unk>.
And we're very pleased with our our partner Abbey and we look in concert at.
At these interim data and I think it was very natural.
A decision to to go up on dose dose level three as we did with the same exact dose.
[noise] aviate.
I see the second question Lisa on pre.
Previous treatment yes.
Yes. There is as you mentioned there were some patients in one of the cohort who had previous treatment. What we do in these types of studies is we make sure there's a certain wash out window. So even if that patient is not quote unquote treatment naive.
They at least have not had an anti that Jeff injection in at least six months to two.
Minimize the risk of a confounding factor there and there were actually some interesting presentations yesterday getting into and from other programs thinking about treatment naive versus not so will follow with that same approach going forward. So we have an amended that part of the protocol, where a patient can have had prior anti bad.
But not within a recent timeframe.
Alright, Thank you for taking my question.
Thank you.
Our next question comes from the line of Andrea's with Wedbush.
Good morning, Thank you for taking our questions.
For us so on on the bottom of slide nine it says that a couple of patients received and tivo jokes therapy you're.
Could you tell us how how we determine <unk> what's the criteria.
I have a follow up.
Sure. So in patients with this disease of course, we look for complications in the the investigators looked for compensations and.
At the end of the day the investigator.
Of course that sponsor agree if it's indicated to to treat a patient that they should proceed with with treatment and it certainly with the longer we follow these patients. So that's one of the key potential benefits of a sustained anti that Jeff treatment has the ability to prevent patients from <unk>.
Developing vision threatening complications so we have the one patient in the control group, who did need treatment that we elaborate on and.
A footnote who even with treatment wound up with four step were sitting at the end and we had alone patient in the 50 <unk>.
<unk> 3314 treated is.
That had a single anti that Jeff injection early in the course and you see how that patient did so did you look at the totality of this data that also directionally goes in the same.
A shift in terms of outcomes.
Peter discussed in terms of how we look also at the imaging basis of of how severe the the diabetic retinopathy as <unk>.
Layla as you presented this data you have a perspective on on thinking of recruitment and the realities of that aspect. When you think of this kind of patient population that goes up to 61, and then 65, where we're including those patients because they are at very high risk of.
Advancing how do you think of that in terms of the.
The risk of billing.
Billing to DMV.
And high risk PDR and needing treatment.
It seems like you pointed out.
Are there any historic and a friend apathy of trials have not typically included mouths PDR moderate PDR and he like aimed at his trial and we that we gotta conclusion, although maybe you know significant gains to have there's also risk of progression, especially early on in their treatment protocol.
I'm still at any point out the one patient that it received anti injection, what's really quite soon after angel only the one wonders whether there was any response to student achievement that earlene enrollment period and.
And he was also a higher diabetic retinopathy severity towards the miles pediatric patients. So we are right. They are set up for unfortunately holiday progressing too complication.
I think that could be very well explained by now.
Okay, Great and then.
<unk> previous questions here, but just so so thinking about observing the decrease in going to step improvement observed from cover it once it <unk> how are you thinking about or.
Or what are your expectations.
For the for the higher dose.
Thank you.
Andres well, we'll have to see of course.
So.
That's why we do.
The trial, we are encouraged that with those level, one dose level to where we're seeing what we want to see.
And now to have this opportunity to look at a higher dose level and as as Layla mentioned, we're also expanding to include not only the mile PDR, but also the moderate PDR, so and Stratifying based on that so we're gonna have a lot more patience and a lot more data.
To really assess.
This response here as well as how we can.
Assess it in.
In a wet AMD and really learn from from both.
So thank you.
Thank you.
As a reminder to ask a question. Please press star one one.
Our next question comes from the line of Daneel Gatlin.
Charted.
Good morning, Thank you for taking the question.
I have one on essentially pulling from six to 12 months since the previous ensure the data on improvement from three to six months and compare that to the standard of care one per cent and rendered unusable.
Wanted to see what if if if you can if you know.
Continues to progress beyond six months and what would be your expectations for 314.
So in the existing cohorts and then going forward, we care about these time points that we've.
Presented to data and we certainly look forward to.
Compiling and cleaning and and being able to report in the future on longer term follow up time points for these cohorts, including the one year time point as.
As far as expectations I think.
One aspect is for illustrative reasons one can.
Think of what's been done before how repeat injection with existing therapies impacts.
Diabetic retinopathy severity and the realities of as.
Treatment frequency decreases in patients falloff use that the diabetic retinopathy severity returned.
And.
I think is.
As our guests have have highlighted we know without treatment, which would be the observation control in a future study that patients in general do not get better and it's just that small percentage of patients that.
Get better due to other factors that Peter highlighted so it really puts us in a good position in terms of a regulatory standpoint, if we think a bigger studies that are powered and take out the risk of of imbalances in terms of hitting a regulatory.
Bar, while also hitting what ultimately matters to the investigators in the patient's which is shifting the severity to the right into the favourable direction and keeping patients from getting worse in developing the blinding complications that that Peter highlighted.
Nothing better thank you very much.
Thank you and I'm showing no further questions so with that I'll hand, the call back over to C. E O Ken meals for any closing remarks.
Thanks, operator, I appreciate that Steve Thanks for walking us through that overview and.
Really grateful to doctors face of itch and Kaiser for both their time early this morning their perspectives on treatment paradigms in D R and perspectives and weighing in on the new interim data from the altitude trial.
Just want to reiterate that Progenics bio continues to perform at a very high level. We have an amazing team one that's dedicated to expanding the understanding and the applications of the vectors.
Developing in generating new innovative EEV therapeutics that have the potential to significantly impact patients lives. We've had several data updates over the past months from both our eyecare collaboration with Abby as well as a rare disease portfolio. We have a foundation of capital over $600 million to fund our mission in operations into.
2025, and through multiple filings in other anticipated data milestone so.
Truly believe we have a clear and definable path to achieve our five by twenty-five vision to advance 580 therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025, we look forward to keeping you all updated on our progress as we finished the year begin to look ahead of 2023.
Again, thanks, very much to our guests in the entire team and have a great rest of the day.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating and you may now disconnect.
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