Q4 2021 Regenxbio Inc Earnings Call
Thank you for joining Q4 2021 with Gen X Bio Inc. Earnings Conference call at this time your lines have been placed.
On the later in the call there will be a Q&A session and instructions will be given at that time, if you need operator assistance. Please press star Zero as a reminder, today's call is being recorded and if you wish to ask a question. Please press star one I'll now turn the call over to your host today, Patrick Christmas Chief.
Legal I'll start with Jan next Tayo, Sir Please go ahead.
Good afternoon, and thank you for joining us today with US today are Ken Mills, <unk>, Brady that expires, President and Chief Executive Officer.
Dr. Steve Nicola, our Chief Medical Officer, and Mr system, Our Chief Financial Officer.
Earlier this afternoon, <unk> released financial and operating results for the fourth quarter and full year ended December 31 2021.
Press release reporting our financial results 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 and can be identified by words, such as expect plan will may anticipate believe should intend 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 sections of <unk> annual report on Form 10-K for the full year ended December 31, 2021, and comparable risk factors sections.
<unk> quarterly reports on Form 10-Q , which are on file with the Securities Exchange Commission and available on the SEC's website.
Any information we provide on this conference call is provided only as of the date of this call March one 2022, and we undertake no obligation to update any forward looking statements. We 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 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'd now like to turn the call over to Ken Ken.
Thank you Patrick good afternoon, everyone and thanks again for joining us I'm pleased to begin today's call with <unk>.
Quick recap of business highlights as well as an update on our corporate goals.
Steve will then provide an update on our clinical programs and will provide an overview of financial results for the fourth quarter and year ended 2021.
At the end of the call we will open up the line for questions.
I wanted to start off by saying, how pleased I am with our performance as an organization over this past quarter and this past year.
Against the challenging backdrop in 2021 <unk> has continued to perform at a very high level and.
And I really like to take this time to thank our <unk> bio team, our investigators and the patient communities for their commitment to the development of our innovative <unk> therapeutics.
One of the more important events for our company. This past year was the signing and recent closing of our eye care collaboration agreement with Abbvie for the development and commercialization of <unk> hundred one four.
We're really pleased to be working with Abbvie and industry leader in eye care as we advance our <unk> 31 for a potential onetime treatment in clinical trials for the treatment of wet AMD and diabetic retinopathy and consider development in other chronic eye disorders.
Aside from Abbvie significant financial investment that we believe validates our innovative gene therapies and provides significant cash runway. The collaboration allows us to leverage add these leading development and commercial expertise.
We plan to take full advantage of this collaboration as we work together to advance <unk> hundred one floor and multiple billion dollar eyecare markets.
Yesterday, <unk> bio we recognized rare disease day as we brought focus to this event and thought to generate change for the more than 300 million people worldwide living with a rare disease their families and caregivers by participating in a number of awareness and stakeholder engagement exercises.
Our 2021 momentum has continued in this new year with a number of recent announcements that we believe raise the profile of our pipeline of <unk> therapeutics for rare diseases.
For instance, we made significant progress advancing RG X two zero to our gene therapy for the treatment of Duchenne.
Importantly, RG X 202 is our first homegrown program, leveraging our proprietary NAV <unk> vector to deliver a transgene for novel Micro dystrophin that includes the functional elements of the <unk> terminal domain of dystrophin.
We believe that <unk> has the potential to address the limitations of other treatment approaches for patient suffering from the severe degenerative disease.
With the recent clearance of our investigational new drug application, we're excited to get our clinical trial started which we expect to take place in the first half of this year.
Today, we also announced that the FDA has granted rare pediatric disease designation for RG <unk>, which makes this program eligible for obtaining a priority review voucher in the future.
Last month, we presented positive interim data at the World Symposium for RG <unk>, one being developed for the treatment of Hunter syndrome, and <unk> 111 for the treatment of Hurler syndrome. We believe the data updates highlighted the potential of both programs to alter the course of these debilitating neurodegenerative diseases and deliver <unk>.
<unk> patient outcomes.
As you May know.
We have moved into and began utilizing our new headquarters building in Rockville, Maryland that has our internal GMP facility located within our headquarters there.
This facility is on track to be fully operational in the first half of 2022 and is expected to allow for the production of NAV vectors that scales up to 2000 liters.
Importantly, with the new headquarters and Cgmp manufacturing facility, we are continuing to expand our capabilities from basic research and development to commercial scale infrastructure.
As a result of this and all of our achievements were excited to be introducing a new arm of the <unk> buyout strategy called five by 'twenty five.
That will be a clear and definable plan to advance <unk> therapeutics.
With a number of license and collaboration agreements in place as well as the growing internal pipeline. The purpose of five by 'twenty five is to identify the key programs that treat very high unmet needs in areas, where we are partners and licensees can use our NAV technology platform to develop and potentially commercialize <unk> therapeutics.
As possible.
We believe this will help us focus as an organization on key value, creating assets, where we have the expertise to develop and enable the development of these programs in an efficient way.
Specifically, we intend to progress Fyvie therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025.
A leading candidates to meet our five by 'twenty five strategy include our internal programs such as Rdx 314 for the treatment of wet AMD and diabetic retinopathy RG <unk> for the treatment of Duchenne and <unk> one for the treatment of Hunter syndrome, but in addition, we will draw from other programs that we plan to advance internally into development.
And programs being developed through our NAV technology licensees to achieve this strategical.
What this signifies for me is that we're stealing <unk> bio and the direction of supporting more late stage development and commercialization of <unk> therapeutics.
This is a natural evolution for the company that has been foundational and the progress in the field of <unk> Therapeutics and has made over 10 plus years of foundational commitment.
With that I'd.
I'd like to turn the call over to Steve He is going to go into greater detail about our internal programs Steve.
Thanks, Ken.
I'll begin with an update on our Gx $3 14, which is being developed in collaboration with Abbvie to treat multiple ocular indications, including wet AMD and diabetic retinopathy.
<unk> 314 uses the NAV <unk> vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor or is that Jeff.
Wet AMD is the leading cause of vision loss in people over 60 affecting more than 2 million patients in the U S Europe and Japan.
The current standard of care for wet AMD as the anti VEGF treatments, which required patients to receive injections into the eye every four to 12 weeks for the duration of the disease.
Real World evidence shows that patients with wet AMD are severely under treated due to the unsustainable treatment burden of these frequent injections required with currently approved anti VEGF therapies.
As a result, the majority of wet AMD patients experienced significant vision loss over time.
<unk> hundred 14 is being developed as a onetime treatment for wet AMD that has the potential to reduce the frequency of anti VEGF treatments and preserve vision for wet AMD patients.
In our phase one two clinical trial of <unk> 314 for the treatment of wet AMD using the sub retinal delivery approach and.
It's long term follow up study, we have observed a durable treatment effect over three years, including mean improvement in vision and stable retinal thickness and reduction in anti VEGF treatment burden.
We believe <unk> 314 represents a significant potential advancement for the treatment of wet AMD.
We continue to enroll patients in the atmosphere trial. The first of two pivotal trials to evaluate the efficacy and safety of <unk> 314 in patients with wet AMD using the sub retinal delivery approach.
We also recently announced in January the initiation of the assent trial, our second of two pivotal trials evaluating the efficacy and safety of sub retinal delivery of <unk> 314 in patients with wet AMD.
Importantly, the central is the first trial to be initiated under our eye care collaboration agreement with Abbvie.
These two trials are expected to support BLA submission for <unk> 314 in 2024.
We are also developing <unk> 314, using an in office Super Choroidal delivery approach.
In November 2021, we presented interim six month data from cohort two of the phase II trial at the American Academy of Ophthalmology meeting.
The data presented continues to demonstrate evidence of the emerging clinical profile of <unk> hundred 2014 with patients in cohort two showing stable visual acuity and retinal thickness as well as a 72% reduction in anti VEGF treatment burden compared to the mean annualized injection rate during the.
12 months prior to receiving <unk> 314.
Looking at the safety profile across all cohorts as of November four 2021, <unk>. Three 2014 was reported to be well tolerated and 50 patients from cohorts one to three with no drug related serious adverse events.
Mild intraocular inflammation was observed on slit lamp examination at similar incidents across both levels.
Those levels in cohorts, one and two with four out of 15 patients in cohort one and three out of 15 patients in cohort two and resolve quickly with topical corticosteroids.
We're also pleased to announce the completion of enrollment in cohort four and the expected completion of cohort five in the first half of 2022.
Cohorts four and five are evaluating Archie at $3 14 at a third dose level of 112 genome copies per eye and we look forward to sharing additional data from these cohorts.
Moving to <unk> $3 14 for the treatment of diabetic retinopathy or Dr.
Dr is a complication of diabetes and is the leading cause of blindness in adults between the age of 24 to <unk> 75 worldwide.
An estimated 27 million patients are affected by this debilitating disease worldwide.
Looking at a large opportunity for <unk> bio.
Unlike what AMD, Dr does not present itself to caregivers with a set of acute morbidities early on.
Instead, it is a progressive disease, and while a large proportion of Dr patients develop vision, threatening complications, including diabetic macular edema or <unk>.
And Neil Vascularization that can lead to blindness.
Many with this condition do not receive anti VEGF treatment.
A proven therapy to reduce the risk of developing these vision threatening complications.
And thats because of the unsustainable treatment burden required with today's available treatments.
Product profile like <unk> three one fours.
That has the potential to be a one time in office treatment could potentially overcome this hurdle and provide an important therapy for patients with diabetic retinopathy.
We recently presented six month data from our phase two <unk> trial at the Angiogenesis conference.
February that demonstrated a clinically meaningful that is in at least two step improvement from baseline on the diabetic retinopathy severity scale or Drs SaaS. After a single <unk> three one for administration.
47%.
The 15 patients treated in cohort one compared to zero percent of patients in the observational control.
Importantly, this was an increase from the 33% observed at three months.
We're encouraged by what we're seeing at this stage.
The data demonstrate comparability as well using the same endpoint to the outcomes seen in the other trials that were the basis of approval for the current approved anti VEGF treatments for Dr. <unk>.
Furthermore, as of January 2022, <unk> hundred one forward was reported to be well tolerated in the 15 patients.
With Archie at $3 14 in cohort one.
With no drug related <unk> and no intra ocular inflammation observed.
Shifting to our rare disease portfolio. Our team has made significant progress advancing our gx to owe to our potential onetime gene therapy for the treatment of Duchenne.
We are developing <unk> 202 to be a highly differentiated product and have designed it to deliver a transgene for novel Micro dystrophin that includes the functional elements of the C terminal or Cte domain founded naturally occurring dystrophin.
In preclinical studies, the president presence of the <unk> domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction induced muscle damage and dystrophic mice models.
Additional design features including codon optimization and reduced CPG content have the potential to improve gene expression increased translational efficiency and reduce immunogenicity.
<unk> two is designed to support the delivery and targeted expression of genes throughout the skeletal and heart muscle using our NAV <unk> vector.
Well characterized muscle specific promoter SPC $5 12.
This product has now received both orphan and rare pediatric disease designation, which marked important milestones and acknowledgment of the need for new treatment options for patients with Duchenne.
In January we announced our IND was cleared by the FDA and we are now on track to initiate our phase one two affinity Duchenne trial in the first half of the year.
We provided other key updates to our rare genetic disease portfolio at this year's World Symposium highlighting phase two data for both <unk> hundred 21.
And <unk> 111 are onetime gene therapies for the treatment of NPS to or Hunter syndrome.
And severe mpls Wan or Hurler syndrome.
For <unk> hundred 21, we presented updated data from all three cohorts imports.
Importantly, we observed dose dependent reductions in CSF biomarkers with cohort three patients approaching normal levels of the <unk> biomarker, along with demonstration of meaningful improvements in neuro developmental function and caregiver reported outcomes observed up to two <unk>.
Years after <unk> hundred 21 administration.
For our <unk> hundred 11 data World was our first reveal and while the patient numbers are small we did observe emerging evidence of CSF biomarker activity, along with neuro developmental assessments, indicating an encouraging potential CNS profile.
We plan to enroll additional patients in cohort two and.
And in both updates as of December 22021, <unk> 121, and <unk> 111 were well tolerated with no drug related aes.
Overall, we have already made significant progress in 2022, and we look forward to providing further updates throughout the year.
Now I'll turn the call back over to Ken.
Thanks, Steve for the really good updates and especially to the team for the progress over the past quarter and this past year.
Let's see before turning the call over to hit.
Wanted to circle back to discuss our manufacturing a bit more in its importance to our overall strategy.
We have over.
21000 square feet of our corporate headquarters that's dedicated to our in house <unk> pilot plant advanced analytic labs, multiple 2000 liter bioreactor suites for cgmp manufacturing of bulk drug substance then.
New flexible and state of the art fill finish suite to support all of our multiple programs focus and we've been talking about our investment.
And in in House GMP facility is an important next step to have better control over our manufacturing process and supply, but specifically I wanted to highlight that there is a real close alignment that exists between our research team and our manufacturing team. We believe that this is a key differentiator for <unk> in two ways.
First it allows for us to move quickly from candidate selection to production of clinical grade material, which supports accelerating the early development of our AAV therapeutics and.
And second we believe that 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 into that commercial readiness.
And another piece to add is that our manufacturing team is also formulated <unk> therapeutics to be used in a number of different innovative delivery device solutions and techniques, including the pioneering work in clinical use of Super Choroidal, an intracisternal intervention.
So we believe being a leader in innovative device delivery of AAV therapeutics distinguishing competency <unk> bio as we progress our new five by 'twenty five strategy.
With that I will turn the call over to <unk> to review our financial guidance.
Thank you Mr. President regenerative bio ended the quarter and year on December 31st 2021, with cash cash equivalents and marketable securities totaling $849 3 million.
Compared to $522 5 million as of December 31, 2020.
The increase was primarily the result of the $370 million upfront payment recognized upon the closing of the Abbvie eye care collaboration and $216 1 million of aggregate net proceeds received from our follow on public offering of common stock completed in January .
2021, the increase was partially offset by cash used to fund operating activities and capital expenditures during the year ended December 31 2021.
Based on our current operating plan, we expect the balancing cash cash equivalents and marketable securities of $849 3 million as of December 31, 2021 to fund our operations, including the completion of our internal manufacturing capabilities.
And clinical advancement of our product candidates into 2025.
With that I will turn to the state of Virginia, <unk> address back to precedent mills to provide final thoughts.
Much appreciate it as always and thanks for the highlights of the financial position of the company.
So as you've heard from Stephens.
And our update today, we've had important progress across our pipeline of <unk> therapeutics.
Furthermore, we look forward to steering in the direction of supporting more late stage development and commercialization of <unk> therapeutics through our five by 'twenty five strategy and.
And utilizing our internal GMP facility to support the acceleration and the development of our AAV therapeutics.
We're confident that we have the right team in place across all key business levels, including science manufacturing and commercial we believe that our science has been validated both by our own growing body of clinical data as well as key collaborations like our <unk> collaboration with Abbvie and the numerous other license agreements with leading biotechnology companies, who use our <unk>.
Technology.
We believe truly that we have the end to end capabilities in place to support our plans to efficiently and successfully advanced our exciting pipeline.
And as noted we have capital and our balance sheet to support our strategy.
I am more confident than ever in our science and our people to support our ability to develop AAV therapeutics for diseases that have the potential to significantly impact patients lives.
We look forward to continued progress in the coming year.
I am, particularly excited about advancing our new five by 'twenty five strategy within the company and progressing our high care collaboration with Abbvie in dosing. The first participants in our <unk> clinical trial for the treatment of Duchenne.
For now I will turn the call over to the operator for questions.
Thank you at this time, if you will.
Ask a question. Please press star one on your telephone keypad again to ask a question simply press star one on your telephone keypad.
Your first question is from the line of Gena Wang from Barclays. Your line is now open.
Alright, okay. Thanks.
Thanks.
Question on for Gena.
Thanks for the update as well we have three question.
First question is about the study following your comment on the manufacturing.
More color on our current study.
Study and estimated time of completion.
So if you plan to present data sometime later this year.
Second one is for <unk>.
And the study cohorts right.
We know the total dose was the same as cohort two but delivered only by one injection versus two injections in cohort two.
Any reason to expect potentially lead to a better visual acuity or better safety and lastly for the <unk> trial.
Trial design.
How should we think about patient baseline.
H.
A score.
What would be the initial dose.
Thanks, Tom for the question.
Steve I'll start with the bridging study and maybe you can follow up on the two additional questions I think.
Hung with respect to the bridging study, it's part of our overall pivotal program, which we announced last year with respect to.
Providing guidance on our BLA date.
Date of 2024, we're right now operating all three studies in parallel and enrollment is ongoing in all of the studies atmosphere ascent as well as the bridging study.
We don't have any additional guidance beyond that all of this is on track and we continue to.
Including on.
Other side of that announced collaboration with Abbvie Abbvie with respect to the eyecare collaborations continue to support the 2024 planned for BLA for the sub retinal approach so.
That's our answer to that question with respect to Super Choroidal <unk>, one for Steve do you want to take that one.
Sure.
So as you pointed out.
Cohort three is a single injection of 100 microliters.
The same total dose, though in terms of GC per eye as cohort two.
Cohort two had two separate injections of each 100 micro leaders our plan is.
That one injection is better than two from an overall feasibility and patient and doctor.
Delivery standpoint.
We have no reason to expect one approach would be better than another though on our safety.
Tolerability standpoint, certainly a single injection is much preferred.
And I will take that opportunity to say all of our other cohorts are.
Going forward, our with the single injection with 100 micro leaders in both our <unk> study and our altitude Supercoil delivery study.
Regarding.
<unk>.
And then you also asked about when we could have.
How does or when we could have results.
We're excited about the agreement we have with the FDA from the end of phase II from our.
Overall bridging plan.
As Ken mentioned, we're very excited about our.
Global partnership with Abbvie, so where.
Very excited with collaborating closely with Abbvie on talking about our future plans for for other disclosures, but we don't have any other updates to give in terms of of that program in terms of.
What we have already.
<unk> discussed youre.
Third question on our affinity Duchenne.
So as as we've disclosed we're starting with <unk> <unk> GC per keg and this is a dose that we're.
Excited about based on our overall preclinical package and the findings that we have there we're of course in onetime gene therapy.
For Duchenne.
It's important to start at a dose that you believe you will see some effect and.
Potential for benefit so we're excited about.
Starting that study the first half of this year.
Yes, Steve I think the question was to do with inclusion criteria Tong we.
As we're starting up the study we have disclosed that we're going to be focused on.
Males in the age range of I think it's four to 11 with ambulatory function.
Including.
Mutations in the DMD gene that are between certain Exxon and we will be excluding patients on the basis of.
Anti AAV antibodies. So that's some flavor for the inclusion and demographic criteria for this study.
Thanks for the question.
Okay.
Thank you and your next question comes from the line of.
Alex <unk> from Bank of America. Your line is now open.
Hey, guys. Thanks for taking my questions.
A couple from us.
First in the Supercoil Dr patients.
Sustained four step improvement.
Are there any characteristics unique to that patient that you can point to the outsized response.
Given the anticipated pace of enrollment.
For a couple of the higher dose cohorts in the first half of this year is it safe to assume we could see three months data.
From both the wet AMD and Dr. Sucrose studies, maybe later this year with you.
<unk> to wait for a more mature six months.
Data update.
And then just on your 525 plan and use of cash.
Going forward.
The runway.
Into 2025, I guess would you consider maybe bringing into any external technologies to supplement that platform is or is the plan really to support. The later stage development that may be.
Add to it de Novo banks.
Thanks, Alex Steve do you want to jump on the 301 for Dr question.
Sure.
So Alex you pointed out.
The first step improver.
That we included in our presentation from cohort one.
And.
The nice aspect of the diabetic retinopathy severity score is the ability to actually see the evidence of.
Disease, and what ultimately progresses and eventually leads to better outcomes for these patients.
So we don't go into the granularity of the specific.
Changes, but.
The consistency that we see across the data set in terms of being able to see.
Significant.
A meaningful proportion of patients able to achieve at least two step improvement and also have some cases, where you get more than two step the more step changes you have the more evidenced the stronger.
The improvements are in the underlying evidence of disease. When you actually look at at the retinal disease. So.
We're excited that we have.
Cohort one.
We have a six month data and that we can continue to follow those patients longer.
Similar to the answer to the prior question, we're not in a position to give specifics on.
When we have data coming out from later cohorts, but we and our partner happier excited about advancing not only with longer term follow up for cohort one but also.
Being able to do the same at a higher dose in cohort two and three where we also get to look at Nab negative as well as nap net positive.
Patients.
And on the five by 'twenty five questions Alec I think yes.
I hope that this strategy emphasizes several points one is absolutely our focus on our medical and our operational including our GMP capabilities to enable the development of current and emerging late stage programs towards commercialization is absolutely a focus.
I think it also places emphasis on our research and early development team to bring forward new innovations and connect with the types of things, we've evidenced that we can do in the past, bringing forward new biology bring forward new focus for <unk> therapeutics on targets.
<unk> made that up potentially either organically or in partnership with new devices and new routes of administration. So I think the next few years are for us about getting into later stages of development and establishing the company having capabilities for late stage development as well as commercialization.
But bringing forward that continued innovation that's that's been there all along in my view and.
As you alluded to and I think we feel that we're in a strong financial position to be able to make those types of investments on an end to end basis through 2025, and with evidence of a BLA in 2024 and other things emerging I feel really.
Encouraged that we're in a really good place for shareholders and stakeholders.
Thank you.
Thank you. Your next question comes from the line of the crop.
From.
Morgan Stanley Your line is now open.
Thanks for taking I'll call. This as gospel on forward Vikram. So we have one question. So Ford is several corrado delivery of <unk> hundred one for you have observed some intra ocular inflammation in wet AMD.
And Dr.
Do you have a current hypothesis as to what could be driving this difference.
Thanks Gospel, Steve would you like to.
I'd answer here.
Yes.
Can address that thanks for the question.
Keeping in mind, it's relatively small numbers across the different groups, but as you pointed out we haven't seen any intra ocular inflammation in cohort one in the Dr patient population and.
And we see low rates.
And easily managed rates in the data that we've presented for the wet AMD population. So we do.
Conjecture that there is directionally, a greater likelihood to have an inflammatory response.
Some have wondered could dr patients be more prone to an inflammatory response.
There is no evidence of that from our historical EFT.
The <unk> and all the interventions that exist with biologics that have been used to treat both wet AMD and Dr.
Certainly from our data.
There continues to be no suggestion of of an increased risk so.
We're just very glad to see.
Across both platforms that are wet AMD patient population.
Dr population.
We don't see any signs of concerning inflammation and thats, particularly key since this is in the backdrop of no prophylactic steroids. Unlike other programs out there. So we're very pleased with the overall safety and Tolerability that we're seeing to date in Supercoil in office delivery for both.
Wet AMD and Dr.
Thanks possible.
Thank you.
Thank you. Your next question comes from the line of Daily on from Raymond James Your line is now open.
Hi, Thanks for taking the questions just two simple ones from me.
Regarding.
The 88 study.
And.
Next follow up on the clinical data.
Is it possible that we're going to get the 12 month data from cohort one during the back half of 'twenty two.
And would it be possible to get six month data on cohorts, two or three before year end and.
And then the second question I have is could you just remind us of how the economics.
Work now that you have the sense study open.
With 301, four and when some of the costs of the trial program per.
Atmosphere and.
Transfer to Abbvie from European now thanks.
Thanks Dean.
I think as we've talked about with everyone since the <unk>.
Announcements, including of the Abbvie collaboration.
We have a partner here and Abbvie and we've been aligning with them and sort of setting in place a lot of important structures for us to continue to leverage one another's experience and expertise to.
To accelerate as quickly as possible all the work that's going on around <unk> 31 for in terms of plans for updates while we don't have any specific guidance right. Now what we are saying is that we continue to use the intervals that we have been updating on with respect to the program. So in the case of wet.
<unk>, we view that things at the six month and 12 month time points for cohorts are.
Meaningful contributory in terms of making decisions about programs as well on the diabetic retinopathy side, we've seen evidence of intervals on the order of three months and six months.
We plan to continue to use those as mileposts to establish communication with all stakeholders, including investors and we plan to continue to do that.
At major medical conferences with investigators who are involved in our studies, making presentations, so I think that what.
We're able to do right now is show everyone, where we are with respect to enrollment and talk about the fact that we look forward to in the future being at medical conferences with similar intervals of updates as we have in the past and as we get closer to those dates like we did with respect to angiogenesis just I think a few weeks ago, then we're able.
To get more clarity when things are actually accepted by these submit.
Submissions of these investigators for these presentations and.
With respect to the economics, thanks for bringing that up because it's.
Something that starts this year with respect to transition of costs and I think we said out of the gate that.
This was a partnership particularly in the U S. We have economics of sort of 50 50 profit share and.
We are going to continue to be involved in the execution of clinical trials as well as things like clinical supply and ultimately commercial supply, especially in the U S. But this is also a year in 2022, where we start to see the impact of ex U S costs as well as transition overall in cost sharing.
With respect to Regenesis and Abbvie, So I would say.
And I think it's even evidenced in the financials for 2021, we were still bearing of course most of the costs, because we announced the closing of the deal in in November Although obviously, our balance sheet was strengthened by the one time upfront payment of $370 million. This is a year where transition of costs certainly begin to.
Where the cost sharing starts to set in and I think what I remember about the deal on the <unk>.
Initial side as that continues all the way through 2023 until we get to a steady state that I think is fair.
Fairly representative of where geographically Abbvie has a responsibility and also the fact that we have sort of 50% of the.
Profit in commercialization involvement on the US side. So I think we're going from paying for mostly everything in 2021, two by the time, we get to 2023, something Thats more representative of the sort of global geographic share in terms of commercial control.
Thanks, Chris Thanks for the question well.
Thank you. Your next question comes from the line of Manny through heart from SBB Leerink. Your line is now open.
Hey, guys. Thanks for taking the question regarding five by 'twenty five.
Definitely we think about modeling it and timing.
Obviously there is.
Pretty straightforward way to think about what the metrics are to consider in 2025, but can you give us a sense of how to think about ramp of investment.
Specific events that you think we should be focused on in.
In the interim between here and 2025.
In terms of timing of moving certain things about credit in the late stages.
Bold relevantly datasets et cetera.
Yes. Thanks, Thanks for the question and the focus on that strategy I think we've outlined and identified that we view that <unk>. Four is obviously a major contributor to the five by 'twenty five strategy where.
Looking at obviously the continuation of the pivotal program for sub retinal and have given guidance for a BLA in 2024, I think that communicate that.
Is obviously our lead program that we're looking to make that transition into in late stages of development and beyond from 24 into 'twenty five.
Super Corrado.
Our phase III studies that are being run both in wet AMD as well as diabetic retinopathy and we view the kind of runway in front of those programs is having.
The types of experiences and decisions that we had when we were sort of in the phase two.
Stages of.
<unk>.
The sub retinal programs, so seeing those transition into later stages of development would.
It would be considered to be options for sort of a base plan of achieving metrics.
And <unk> is already obviously clinical phase we've talked about that we've leased.
Recently shown data that we believe is supportive of really good outcomes for some of the children that are enrolled in these studies, we've done significant dose ranging in.
The clinical trials, we've seen evidence of biomarker changes that are dose dependent and we've seen correlations to outcomes. When it comes to cognition and other things that are both measurable and important. So we're feeling really good about clinical data, they're putting us on track to make advancements with respect to <unk> and <unk>.
Frankly, <unk> has a program we continue to be really encouraged by the science, we've seen pre clinically the safe to proceed.
And capabilities that we have in place, especially on the quality of product manufacturing.
We are giving guidance to dosing the first patients in the beginning of this year.
And we have in mind that <unk> is going to be a contributor to the $5 25 strategy, which would mean that it would be a program that would be in our view eligible and consistent with getting into that range of pivotal stage.
Commercial through 2025 so.
Those are things that are in focus today I think obviously there are.
A number of partnered programs are licensed programs that are in earlier stages or even heading into later stages of development that we think could become a part of the metrics that meet that and we have things that we think we could be bringing forward science.
Scientifically or through partnership.
That means that well, we're putting forward what we think is important.
Important meaningful straw.
Strategy that also has a sense of urgency about it one that I think is.
Our strategy that as a company I think it's unique capabilities. We have the experience is the position that we're in with respect to different stages of assets to be able to.
Put ourselves on the line for <unk>.
Achieving metrics like that I think is a meaningful and important step for us as a company I hope that.
Touches on a few different elements that we have in mind for achieving that strategy. Although I think there are a number of different ways to compile a positive outcome here and we want to help as many patients as possible.
No.
Really how useful that color.
Thanks, Tony.
Thanks, So much and your next question comes from the line of Luke EC from RBC. Your line is now open.
Oh, great. Thanks for taking my question. This is Lisa on for Luka.
Firstly on the phase III wet AMD pivotal trial.
<unk>.
I believe the phase threes for wet AMD is really one of the largest Alberta, you sub retinal injection as the route of administration.
Given this is the surgical procedure.
I'm just wondering if you can provide us any color on what.
You have employed maintain consistency from site to site in order to help one of any variability.
And my second question has to do with the bridging study.
I know Youre bridging study is powered to show non inferiority on protein concentration as the primary endpoint, but we also see a few secondary endpoints listed including the CVA and just wondering if you could also provide more color on whether or not needing non inferiority on the secondary endpoint will also be required by.
The regulators here.
Thank you.
Thanks, Lisa Steve you want to answer both those questions.
Sure.
Hi, Lisa.
Thanks for for those two questions. So the first one yes, we're really proud of.
The scale.
So to speak in terms of both the size of the trial and overall advancement for the field in terms of sub retinal delivery of gene therapy.
For a big indication like wet AMD.
To your 0.1 issue is scalability in terms of surgeons and actually training on this and this is something that we have a lot of experience on over the years given that we advanced first through our phase one two study and those 42 patients.
And as with that study we carry forward.
What you might expect a surgical.
Trainor, our liaison team that trains new surgeon in.
Performing this procedure and as we talked about during phase one to what we're seeing in action now that we are.
Into two.
Two pivotal studies now atmosphere in ascent as we actually get to see this real time in terms of.
Training additional surgeons and <unk>.
As we anticipated we are seeing that it's fairly straightforward because of these.
These are retina specialist in retina surgeon to have experience doing a lot more complicated procedures then.
This procedure of a standard.
Small gauge vitrectomy and.
<unk> injection of <unk>.
The gene therapy separately.
So.
It's something that we're glad to be actually implementing on and actually executing and we're basically following.
The same process of training new surgeons.
And following these but as anticipated we're not seeing any issues with new surgery, new surgeons coming online for this.
The second question on the bridging study so we reached agreement with the FDA at our end of phase II on our overall plan.
We have a primary endpoint looking at protein to show General comparability.
The reality is as we already know and with that number of patients.
<unk>.
In a active comparison type approach there.
There really isn't a power to differentiate or show non inferiority on those other types of.
Anatomic or functional endpoints, but we do obviously measured them and take advantage of having that to continue to learn more about and gather more data but.
There.
I think you can the main answer to your question is theyre not the study is empowered to really look at those at any kind of definitive way so.
We don't see that as a key aspect.
Thank you very helpful. Thanks for taking my questions.
Thanks Lisa.
Thank you and your next question comes from the line of Andrew Yes argue rise from Wedbush. Your line is now open.
Thanks for taking our question.
A quick one from us and apologies if it was us.
Previously, we had a little connection issue, but so based on the sub retinal three went forward data.
Showing that patients with baseline.
<unk>.
It did not impact transduction can we or how do you expect or is there any read through to cohort three.
The data that we're going to see for me. Thanks.
So with.
Steve you're on it.
Okay, alright, thanks, Ken So for sub retinal as you mentioned, we did not see any impact of preexisting neutralizing antibodies to AAV eight nor did we expect to because there is so much known.
About sub retinal delivery and that's why that's been historically the gold standard.
Including the relative immune privileged status of the sub retinal space, but we still measured.
Baseline Knapp status and confirmed in our phase one two that patients who had preexisting NAV did just as well from a safety and efficacy standpoint as patients who were not negative.
Four Super Choroidal delivery, we're very encouraged that pre clinically we don't see inflammation in any type of.
<unk> response, and Thats, what allowed us to feel confident to go into dose ranging without prophylactic steroids.
We did intentionally set up different cohorts, so that we could answer the question Youre asking.
Whether like sub retinal delivery can we deliver rdx <unk> four to the Super Choroidal space.
And whether neutralizing antibodies matter or not when delivering to that space. So that's why we are excited to be able to look at that in both.
Cohort two compared to cohort three but then also at the third dose level cohort four which we completed dosing in.
Cohort five the map positive corollary of.
Cohort four so we look forward to answering that question.
Great. Thanks for thanks for the color.
Thanks.
No further question at this time I would now like to turn back the call over to Ken Mills to make any closing remarks.
Thanks, Operator, I just wanted to say thanks, everyone again for joining us today and I hope that all of you have a great weekend and we look forward to seeing you all soon.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
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