Q3 2023 REGENXBIO Inc Earnings Call
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Good day, and thank you for standing by.
I'll come to <unk> Bio's third quarter 2023 earnings conference call.
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I would now like to hand, the conference over to your host today, Patrick Christmas Chief Legal Officer. Please go ahead.
Good afternoon, and thank you for joining us today.
Earlier this afternoon, <unk> released financial and operating results for the third quarter ended September 32023 press.
Press release is available on our website at Www Dot <unk> Dot com.
Today's 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.
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 the management's discussion and analysis section of <unk> annual report.
And on Form 10-K for the full year ended December 31, 2022, a comparable risk factors sections of <unk> quarterly reports on Form 10-Q, which are on file with Securities and Exchange Commission and available on the Sec's website.
The information we provide on this conference call is being provided only as of the date of this call November eight 2023.
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.
Any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions, where 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 afternoon, everyone and thanks for joining us.
I'm pleased to begin today's call with an explanation of our updated strategic plan.
Dr. Steve Mccall, our Chief Medical Officer will then provide an update on our clinical programs.
Our Chief Financial Officer will provide an overview of financial results for the third quarter ended September 32023.
At the end of the call we will be opening up the line for questions.
At <unk>, our mission is to improve lives through the curative potential of gene therapy.
Earlier today, we began work on a pipeline prioritization and corporate restructuring plan that will enable <unk> to focus our capabilities and resources on large commercial opportunities where product candidates are differentiated can be expedited and.
And support meaningful value generation soon and for the long term.
I wanted to be clear about what this sharpened focus means moving forward.
Our highest priority programs are.
Our Adv RG X three one for a program for the treatment of wet age related macular degeneration, and diabetic retinopathy being developed in collaboration with Abbvie.
<unk> for the treatment of Duchenne.
<unk> one for the treatment of MTS SKU or Hunter syndrome.
Okay.
Now in the last few months, we've experienced exciting progress for each of these programs.
We've reported positive clinical data from investigational treatments from diabetic retinopathy and Duchenne.
And we've held a very encouraging armies meeting with the FDA about expediting the BLA for the treatment for <unk>.
These milestones demonstrate how our science is supporting avenues to accelerate the development of new gene therapies.
And today, we're following that encouraging data and announcing updated strategic plans for <unk> bio.
We believe that there is a multibillion dollar potential for <unk> 314, as a single injection treatment to.
To become the first in class gene therapy for wet AMD and the standard of care to treat and prevent the progression of diabetic retinopathy.
Initial efficacy data from patients treated with <unk> with <unk>, enabling us to accelerate this program.
<unk> is a market where there is a large unmet need for new therapies.
And that is capable of supporting multiple gene therapies, and we believe <unk> has unique differentiating features that support its potential to be a best in class product.
During a very constructive arm at meeting with the FDA. Just recently in October we received encouraging feedback and confirmed alignment with the FDA on key elements of an expedited BLA.
So we remain on track to support a BLA filing in 2020 for using the accelerated approval pathway.
Once you one would be the first gene therapy treatment for MPS II.
In today's challenging market the ability to create value quickly and efficiently is critical.
Importantly.
These restructuring decisions extends our cash runway much deeper into 2025.
Allowing us to progress our pipeline to a number of key inflection points.
These would include initiating in dosing the first pivotal trials for three one for using Super Choroidal delivery.
Enrolling the pivotal program for our RG <unk> program.
And completing performance qualification lots to support our planned BLA for RG <unk>.
And also achieving the BLA approval for Rgs once you want an mpls too.
Now, it's worth noting that successfully achieving certain of these milestones between now and then would also trigger hundreds of millions of additional funds.
Such as milestone payments from our collaboration partner Abbvie for initiating Super Corrado pivotal trials.
These milestones represent a meaningful portion of the over $560 million in development milestones eligible through this partnership for us.
And the potential receipt of a pediatric review voucher for approval of our Gx. Once you won generally we've been observing priv sales are resulting in nearly $100 million to BLA sponsors at the time of receipt.
So our updated strategic plans are intended to generate significant value for shareholders. As we ensure resources are allocated to our most valuable assets.
To be able to accelerate the development of these assets.
And to extend our operational runway in order to achieve even more milestones that can unlock value.
These additional non dilutive sources that I just highlighted for instance are not in our current runway guidance and if received will allow us to bridge two additional value, creating milestones such as more product approvals and potentially to profitability.
Now I'll turn the call over to Steve. So he can review some of our clinical progress and guidance for the prioritized programs in greater detail Keith.
Thank you Ken.
I'll begin with $3 14, which is being developed in collaboration with Abbvie to treat wet AMD and diabetic retinopathy, we had sub retinal and Super Choroidal routes of administration.
314 utilizes our NAV <unk> vector to deliver a gene encoding a therapeutic antibody fragment to inhibit VEGF.
The anti VEGF market opportunity is poised to grow significantly as the population ages.
314 for the treatment of wet AMD <unk> sub retinal delivery is being evaluated in two ongoing pivotal trials atmosphere in ascent.
Each are expected to enroll a total of 200 patients in the U S Europe, and Japan supporting the global development of the program with anticipated global regulatory submissions in late 2025 through the first half of 2026.
We also have two ongoing phase II trials that fall under our collaboration with Abbvie.
In office supercritical delivery of $3 14 for treatment of wet AMD and the Aviate study.
And diabetic retinopathy or Dr and the altitude steady.
Aviate as an active control dose escalation trial evaluating $3 14 for the treatment of wet AMD we.
We most recently presented safety data in July from cohort six evaluating the dose level III that included short course prophylactic ocular steroids following administration of $3 14.
The initial data presented continues to support the safety profile of $3 14, and highlighted the inclusion of short course, prophylactic steroid eyedrops, which resulted in zero cases of intraocular inflammation.
We plan to present full six month results from cohort five and six at Hawaiian eye and retina meeting in the beginning of 2024.
Altitude is an observation controlled dose escalation study of $3 14, supercritical delivery for the treatment of Dr.
We're very excited about the opportunity and Dr. Given the size of the market, which exceeds that of even wet AMD and because we believe this patient population can benefit the most from a potential onetime gene therapy.
At <unk> this past weekend and on a call with retina physicians on Monday, we presented positive data from dose levels, one and two cohorts at one year.
Patients at dose dose levels did not receive prophylactic steroids before or after 314 administration.
3014 was reported to be well tolerated at both dose levels.
One time in office $3 14 injection demonstrated clinically meaningful improvements in disease severity with reductions in vision threatening events.
Importantly, 100% of the patients with baseline MPR treated with dose level to achieve stable to improve disease severity.
Moreover, dose level, two and these patients reduce the risk of vision threatening events by 89%.
We are encouraged by this data and the potential of a one time in office injection for patients with diabetic retinopathy.
Moving now to <unk> 202 for the treatment of Duchenne.
<unk> as a potential onetime gene therapy for the treatment of Duchenne being developed as a highly differentiated product designed to deliver a transgene for a novel micro dystrophin that includes the functional elements of the <unk> terminal.
Rounded naturally occurring.
Rgs <unk> two is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV AAV vector and a well characterized muscle specific promoter.
Our AAV eight.
Capsid also represents an alternative for boys, who may not be eligible for other AAV mediated micro dystrophin therapies do.
Due to the presence of preexisting neutralizing antibodies.
At World muscle held in October we shared interim clinical data from the phase one two affinity Duchenne trial.
Initial results from the first two patients for whom results were available showed robust micro dystrophin expression and appropriate localization to muscle cell membrane.
In the $4 four year old patient micro dystrophin expression was measured to be 38, 8% compared to control.
A reduction from baseline in serum creatinine kinase or CK levels of 43% was observed.
<unk> evidence of clinical improvement.
The $10 six year old patient.
Had micro dystrophin expression measurements of 11, 1% compared to control and a reduction from baseline in serum CK levels of 44%.
Micro dystrophin expression was measured by western blot with comparable results observed when measured by the <unk> method.
Overall, the data showed that <unk> was well tolerated with no drug related serious adverse events and all three patients treated as of the time the data were presented.
As Ken shared earlier, we recently held an <unk> meeting with the FDA for <unk> hundred 21 for treatment of NPS too.
I'm pleased to share that this was a very positive and constructive discussion.
We were able to align with the FDA on our manufacturing strategy the adequacy of our safety database and confirmatory study design.
Patients treated with <unk> 121 continue to do well on follow up and we expect to share top line data from the phase 123, <unk> trial in the first quarter of 2024.
While we are no longer moving forward with our <unk> 111, 181, and 381 rare neuro degenerative programs. We believe in the potential of these therapies and are committed to finding strategic alternatives for them.
Including potential partners or leveraging public private partnerships.
So to conclude we have made significant progress with data updates in trial progression across all programs in our pipeline as we continue working to advance our prioritized programs.
Lastly, I'd like to thank the patients families clinicians and patient advocacy representatives, who have been involved in and supported all of these trials.
And with that I'll turn the call over to Beth to review our financial guidance.
Thank you Steve returning spinal ended the quarter.
September 32023, with cash cash equivalents, and marketable securities totaling $365 million compared to $565 million.
December 31 2022.
The decrease was primarily driven by cash used to fund operating activities. During the nine months ended September 32023.
R&D expenses were $58 million for the third quarter of 2023 compared to $63 million for the third quarter of 2022.
The decrease was primarily attributable to an increase in development cost reimbursement from Abbvie under our care collaboration.
With the strategic re prioritization plan and 15% workforce reduction announced earlier today, we expect to save at least $100 million over the next two years, we now expect the balance in cash cash equivalents and marketable securities of <unk>.
$365 million as of September 32023 to fund our operations into the second half of 2025.
This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from abbvie. Upon the achievement of development or commercial milestones under our three one for collaboration.
With that I will turn the call back to Ken to provide final thoughts Ken.
Thanks for that.
As we look ahead, our extended cash runway will now enable us to reach additional meaningful value driving milestones for our programs, which I've outlined.
We also want to bring focus to the fact that we have a lot of important near term value driving catalysts expected.
Medical conferences upcoming in the first half of 2024. This would include new six months data from recently dose cohorts of the trial for wet AMD Super Choroidal.
Additional dose level, one and initial dose level II data from the Infinity Duchenne trial.
Topline data from the pivotal phase III campsite trial.
I wanted to reiterate that our updated strategic plans are intended to generate significant value for our shareholders. As we ensure resources are allocated to our most valuable assets.
Two accelerating the development of these assets.
Extending our operational runway until we achieve more milestones that can unlock additional value.
Including access to non dilutive capital that we've talked about from the Abbvie partnership or other sources like the anticipated sale of our PRT that could.
All of which extend our runway even further.
With a renewed sense of focus I expect that we will continue to perform at a high level as we execute on our mission.
And as a result of these updated strategic plans announced and implemented today, we believe <unk> is well positioned for long term success.
With that I think we can now turn the call over for questions operator.
As a reminder, if you'd like to ask a question at this time. Please press star one one on your Touchtone telephone and wait for your name to be announced soon.
Draw. Your question. Please press star one again.
In the interest of time, we ask that you limit yourself to one question and rejoin the queue for any additional questions.
Our first question will come from the line of Gena Wang with Barclays.
Thank you for taking my questions. Okay, I will follow one question rule.
I know there's tons of a question can ask.
So one question I have is what you can learn from this.
Experience in terms of clinical development for the DMD program and regarding primary endpoints selection and also efficacy bar.
Thanks Gena.
A good question, obviously, we ourselves have been engaged in dialogue with regulators about our <unk> and <unk>.
Especially as we've been able to emerge with our own clinical data. It's been an important focus for us since world muscle Society to think about how to accelerate the program and we've given guidance next year that we believe we have the ability to both do select and start a pivotal phase program.
I think what we're seeing in the landscape of micro dystrophin continues to be encouraging that it's clearly helping boys I think it's something that we viewed since we entered this space is beyond sort of increments, but something that in certain plays certainly is having.
More response than in others.
We believe that the C terminal domain hypothesis for Rgs to two is a meaningful differentiator and I think where it can be an important differentiator is on clinical function and the long term clinical function. So.
We're very much engaged about how do you design trials to accelerate and still continue to borrow the endorsement in the use of micro dystrophin as a surrogate endpoint to support accelerated approval think about how to further support that in a pivotal setting and even in a commercial setting with respect to looking at long term.
Function, so I think that.
The domains that are part of the.
Scoring that's used in Duchenne boys and I think some people are starting to recognize both at the regulator level and at the clinical level that some of these domains are more reliable in terms of prognostic indicators for improvement.
We're very much dialed into that and think that having an opportunity to have our own direct dialogue about our data and seeing the evolution of what's happening on the regulatory landscape actually puts us in the best position to start executing next year on a really great package.
Thank you.
Our next question comes from the line of Dane Leone with Raymond James.
Thanks for taking my question.
One for me.
It'd have to be the DMD person.
There is hope that obviously altitude and Eva.
Support moving into.
Pivotal studies during 2024.
Could you comment on the potential for that.
There's been a lot of debate and the shifting regulatory landscape.
Whether the way.
Hi, Ryan.
The sub retinal study can actually be used.
For further study of the gene therapies.
It seems like the FDA sighing away from an ability to use a sham control.
And that may cause problems or longer acting therapies.
Therapies.
Okay controlled studies going forward.
Thank you.
Thanks, Dana I'll, probably let Steve address the comment about the regulatory landscape I guess with respect to altitude and <unk> I think what's been an important part of the update today with respect to the strategic plan is that the.
The extension of the runway for <unk> I think.
For us increases the likelihood of.
Current capital supporting the transition of Super choroidal into pivotal phase in achieving some of the milestone value.
Hence that can be unlocked, we have half a billion dollars of potential development milestones.
Over and large proportion of that is associated with transition of.
Super Choroidal delivery for wet AMD and Dr occur.
Occurring and patient dosing beginning there so.
We view that the data that's starting to come off that we're particularly excited about right now with respect to diabetic retinopathy is really <unk>.
Keeping up for supportive decisions for that transition and we have additional data coming up just early in 2024 with respect to the 88 study so I think.
I think as confident as we've ever been about.
The science that we're seeing and the likelihood of these events occurring in the future for US I think our improved particularly with respect to the updated strategic plan and the extension of the runway that we have to focus on those events.
Steve do you want to pick up the regulatory parts.
Sure Hi, Dan. Thanks, Thanks for the question yes.
Interestingly, maybe not surprisingly this was.
A discussion point at.
This past weekend and also some of the ancillary.
Meetings that were held there the issue of Sham control.
And I think Theres, a couple of key points here that.
A big component of.
The Fda's view on the challenges of masking with a sham control.
Late to Intrepid trio injection and Thats due to the fact that there is a general belief.
Within the FDA in particular that getting an <unk> injection the patient can actually.
They're getting a real intra ocular injection and may even be able to see something in the visual access to suggest that theres actually been.
Fluid injection, so for our Super <unk> programs, that's not an issue because we're not actually injected into the eye and we've had regulatory interactions.
We're aligned on an approach for giving a quote unquote sham injection that preserves masking.
The other aspect.
Come up from the Fda's discussion of this or there's other ways to address the such as considering having to active.
Arms of different dose level of of your given drug that at least then preserve the masking between.
Active arms.
So there's several approaches that companies can considered but fortunately for us. The fact that we're not an <unk> injection really shields us from from this issue.
Thanks for the question, Dan I guess the level of detail that Steve is giving about thought that's going into the.
The application of Super final delivery in later stage trials as I think additional evidence of.
The work that's going on inside the company and in the partnerships to support these types of things.
Our next question comes from the line of Vikram <unk> with Morgan Stanley.
Hi, everyone.
Staff will unfold.
I have one question.
For potential partnerships for <unk> one.
One on 301.
You have a timeline in mind for establishing a partnership what would you be looking for partnerships outside of capital.
Okay.
Cost for the strategic update plans today are really focused on.
Assuring in sourcing capital for Rdx, three one for RG <unk> in <unk> Q1, two.
What we think is the strongest potential value that we have in the pipeline today, so with respect to 111 and other things that's going to be discontinuation of any clinical development work and an exercise that will result in.
Looking for opportunities in the short term for partnering but it won't become something that will be.
Viewed as a meaningful contribution to the operating plans going forward.
Thank you very much.
Thanks.
Our next question comes from the line of Alec Stranahan with Bank of America.
Hey, guys. Thanks for taking my questions just one for me could.
Could you maybe expand upon the positive FDA interactions you've had after the update for two dose level, one and did you get any input on the pivotal study design as well.
Particularly as it relates to that.
Current age cohort thanks.
Yes. Thanks for the question, Alex I think that it's been a very dynamic process for us with respect to contact with the FDA on our <unk> and that's because of the landscape of whats happening in micro dystrophin in general.
We want to understand.
How FDA is for thinking about our data and other data sets.
The evolution of things with respect to micro dystrophin as a class.
I think for us incredible.
The opportunity to.
Early on at dose level one.
Talk about safety and micro dystrophin expression in sort of the <unk>.
Pathway too.
Making a dose selection.
I think there's also a lot of interplay that we see on let's say for instance, manufacturing Alec right.
We're working through basically DLA readiness for our manufacturing facility and a manufacturing process with one Q1.
That is also something that is the path for us with respect to two O too and so.
Sure.
For us between RMS eating and interaction around once you won and between the opportunity to sort of update.
Leadership and people at FDA with additional information and data about <unk> two.
And also get feedback about what is going on with respect to the landscape of micro dystrophin in general it's a really rich time, I think that where its setting us up well for.
Thinking about strategy and operational plans that are about acceleration and I think the best example of that was.
Just being able to modify the clinical protocol to reduce the number of patients from three to two.
<unk> moving into parallel enrollment scenario with.
The dose levels that we're at I think.
Was something that was informed by data and was informed by safety. It was informed by ups.
<unk> two our dossier with respect to the IND.
And having alignment with FDA on that I think was a meaningful signal.
Great. Thanks, guys very helpful.
Okay.
Our next question comes from the line of Ellie Merle with UBS.
Hi, This is Sarah on for Elliot. Thanks, So much for taking our question.
Just quickly on Patel.
Potential milestones from Abbvie I know, they're not currently in your guidance can you remind us what the milestone would be for moving into pivotal studies with Super Great. All and then any color around the timing of other near term milestones there that we should be thinking about thanks.
Okay.
Sure Sir Thanks for the question, Yes, we disclosed that we have over $560 million of eligible development milestones associated with the partnership and a large proportion of those milestones are associated with the super choroidal programs transitioning into pivotal phase.
So I think those are things that we deal with this changing in guidance and runway guidance are.
Increasing likelihood for them to occur across the operational runway that we have now.
Obviously, they've been answering questions already about.
Specific timing or things that have been going into how that decision is made what I can say about.
Some of the updates that we've given recently like with respect to the exciting data that we've seen from diabetic retinopathy and some of the thinking that has been going on within the partnership is that we really think that the datasets are starting to mature now to a point where those types of decisions can be made soon so.
The Hawaiian eye data update coming also in the beginning of next year.
These are things that now with a.
Runway guidance into the second half of 2025, I think are achievable and again I tried to frame. This in the overview I think these are opportunities to sort of bridge to obviously, we're talking about hundreds of millions of dollars in milestones here that can occur that can bridge the company even further in Q years 'twenty.
Six 2007 for instance, and those start to the year is now where we're talking about BLA.
BLA filing the sub retinal program in potential if you think about acceleration for our Duchenne program additional product launches. So we really like how the strategic update plan here and the interplay of some of these milestones are coming together to think about.
Effectively having opportunities to capitalize ourselves with things that are currently assets of the company all the way to whole role of product approvals and potentially even profitability.
Great. Thanks.
Thank you Sir.
Our next question comes from the line of Luca <unk> with RBC capital markets.
Oh, good thanks for taking our questions.
Just maybe one this is Lisa on for Luka, just maybe one on DMD.
We know the <unk>.
The trial is enrolling patients up to 11 years of age however from the Embarq data it appeared harder to discern a benefit in older children versus younger children.
Just wondering what gives you confidence that Q2 will show a benefit in older children.
Especially when it appeared that the western blot suggested that there was higher expression in the younger patients any color there would be helpful. Thanks.
Thanks Lisa.
We have an older patient enrolled already and so on.
I certainly acknowledge the remark about the differences that we've seen in micro dystrophin expression, but we're going to be able to see sort of unfold in front of us and continue to be able to update on the progress of that patient and I think the.
The meaningful differentiator here is the C terminal domain design of our expression cassette, we just think that scientifically from a biological plausibility perspective.
Amounts of micro dystrophin that are expressed with the C terminal domain are going to translate into improved function.
And I think that gives rdx two two.
A better and as good as any other treatment, but really better than any other treatment that spring forward.
To date to show improvement in older Boys. So we continue to view that the opportunity to enroll in that age range is something that's going to be important for our profile clinically and ultimately commercially and we do think that there is strong validation in the four to five in the.
The emergence of more data and 6% to seven is also sort of helping inform the benefits there, but we really feel strongly that the C terminal domain the functionality associated with it what we're seeing from our preclinical data and the early evidence that we've reported on and we will continue to update on an older patient I think is.
The thing that we're excited about for that age range.
Thanks Lisa.
Our next question comes from the line of Brian <unk> with Baird.
Hey, good afternoon, everyone and thanks for taking my question.
It sounds like Youre getting near a decision point on pivotal programs with the Super Choroidal administration. So I'm just wondering what's sort of the rate limiting factor here in terms of aviation.
And altitude to kind of make a decision and you really need.
Like one year data from cohort six in cohorts four and five.
Further to that point and you've been talking very enthusiastically about diabetic retinopathy.
Do you see sort of a pivotal program moving forward in the Dr. In wet AMD at the same time or one of these indications potentially.
Third earlier than the other.
Yes. Thanks for the question, Brian I think again like we have a lot of enthusiasm about the recent data update.
The effect there of course.
Just a few days ago, and I think the new Dr data.
Now been communicated and there has been a focus for us in terms of communication in the last few days.
With respect and then we have 88 update coming only in January.
I think our vision has been from the beginning that.
Wet AMD sub retinal wet AMD Super Cradle, wet AMD diabetic retinopathy, but they are they're obviously all interrelated because the same pharmacological agent, but each one of them because of the difference in delivery or in the last case and the difference with respect to the potential market and.
The sort of evidenced this needed clinically to think about how to transition into pivotal.
They're all they're all slightly different path, but that they derived from the same consideration and variables that we would look at for any kind of advancement of a program like this.
Almost independent of modality into pivotal phase I always like to point out that.
We are the company that is the first you have transitioned into a pivotal phase program with respect to an AAV gene therapy in a large market indication in wet AMD.
And now we also have the strength in sort of the robust.
Decision, making to sort of bring additional variables into the equation with us with with Abbvie.
Yes, the decisions that are going to be different and separate between.
The Super <unk> wet AMD in the supercritical diabetic retinopathy.
Rely on different datasets and different inputs. So it's certainly possible that.
They could happen at the same time, but it is likely that.
Those decisions are independent variables and would come forward, but I think.
The message today is.
How strongly we feel about reinforcing our excitement about the value of <unk> 314, and the opportunity to continue to realize that value.
We're continuing to make that focused investment with an extended runway here I think really improves the probability of success of meeting some of these milestones.
In terms of transitioning the pivotal therefore, realizing some of these.
Monetary milestones that are associated with the partnership.
In a way that is improved right just with that.
Extended runway alone, but at the same time. We've also started to become really encouraged about the newer and longer term data that's been coming out of the investments that have been made in things like aviate an altitude. So.
Im excited for things to come here.
Moving into 2024.
Thanks, Tim.
Thanks, Mike.
As a reminder, that is star one one to ask a question.
Our next question comes from the line of Annabel <unk> with Stifel.
Hi, This is Jack on for Annabel, Thanks for taking my question.
So for the sub retinal formulation of <unk> hundred one core in wet AMD, what's the right amount of follow up time FDA is looking for to establish safety and durability, there and what might the value proposition would be here for the payer is when you think of pricing that's considering that many of these patients are elderly and may not see.
The maximum benefit of a long term treatment.
Steve you want to take the regulatory part here.
Sure.
Jack.
So taking the first part of your question the duration from.
Regulatory standpoint, as far as follow up.
Got it very clear feedback.
Back as far as the end of phase II meeting that allowed us to finalize the pivotal program that.
Really as a class.
Requirement, having one year.
50 and efficacy data.
Which also with somewhat informed by efficacy but.
Imminently by gene therapy aspect.
Also have longer term follow up data from a lot of the patients.
From a pretty sizable safety database and we actually already have from our phase one two.
Data base out three or four years, good safety and also good durability from an efficacy standpoint.
Both based on other programs, even outside the eye that have shown durability out.
Even beyond the dozen years for example in hemophilia with the same AAV.
Zero type AAV eight and then now our own data gives us a lot of confidence on duration of efficacy.
And I think thats, obviously going to inform the value proposition, having durable efficacy evidence.
And the value proposition importantly, as more than just decreasing treatment burden and visit burden.
Really the big unmet need here is by breaking the barrier of the treatment burden. It ensures that these patients are going to have the ongoing sustained anti bet Jack activity that they need to prevent.
Vision threatening complications that they simply arent getting now both in terms of wet AMD and diabetic retinopathy because of the treatment burden. So.
There is various layers the value proposition treatment burden visit burden and actual vision and complication outcome.
Yes, and I would add Jack that I think it's pretty well established by a lot of different sources.
The cost of.
The costs related to blindness, that's associated with wet AMD is on an annual basis, something that can be in excess of $100000 of year.
And that's.
Separated from the cost of drug so when we think about wet AMD patient youre talking about the life expectancy might be on the order of 10 to 15 years, I think and in the real World. There is a need there for.
Recovering division that is being lost because people aren't staying compliant with the existing treatments.
And the cost and the obviously the effect that that's having on a productivity basis with respect to.
The effect that it has on the families of those patients as well as significant and so durability is everything I like Heskey brought up four year evidence, which just continues to grow its there as a backstop for things on a regulatory basis, but I think also important in the commercial setting.
Great. Thanks, so much.
Our next question comes from the line of Manny <unk> with Leerink partners.
Hey, guys. Thanks for taking my question.
Obviously, you've never fun decisions to make but obviously the right thing to do us all in the press release, a little bit of detail around about $100 million savings et cetera. A couple of years could you give us a sense of where that tempo is like when should we expect that to drop in immediately starting in <unk> and be fairly linear on a quarterly.
<unk>.
Or is it something that's a little more frontloaded little more backward over the first couple of years.
Beyond that.
How should we think about post that two years' period, what is the implication on opex.
Longer term.
Do you want to chime in on this one.
Sure. Thanks, Randy I think that.
As youre thinking about that 100 million it would be not 100% linear as much as it slowly gets bled into our operating plan going forward.
Some of it will be a little bit lumpy as we start to discontinued programs and obviously with that 15% head count reduction.
Little bit more front end loaded.
And then as we think about Opex.
Sir.
Looking at the models and search.
To determine what's the appropriate kind of run rate.
<unk> seen looking at different analysts vials as their estimates for opex seem to be.
Higher than what we're tracking against and I think coming.
Coming out of this quarter into next year.
We'll have a better idea of what the run rate is on Opex.
And then on the other side of 2025, obviously with non dilutive capital that we're talking about and.
Yes, the opportunity, possibly the market's wall Mark finally.
I think post 2025.
We're going to still maintain our discipline as it relates opex, but will also have to certain.
Yes, moving programs forward as they become commercial opportunities and then also.
Start to think about our pipeline going forward.
That's helpful. Thanks, I'll hop off.
Thank you.
This concludes today's conference call. Thank you for participating you may now disconnect.
Okay.
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