Q1 2024 REGENXBIO Inc Earnings Call
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The Star one one again please be advised that today's conference is being recorded I would now like to hand, the conference over to your Speaker today, Patrick Christmas Chief Legal Officer. Please go ahead.
Patrick J. Christmas: Good afternoon, and thank you for joining us today.
Patrick J. Christmas: Earlier this afternoon, <unk> released financial and operating results for the first quarter ended March 31 2024.
Patrick J. Christmas: The press release is available on our website at Www Dot <unk> Dot com.
Patrick J. Christmas: 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 expects plans will may anticipate believe.
Patrick J. Christmas: Sure.
Patrick J. Christmas: Other words of similar meaning.
Patrick J. Christmas: 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, 2023, and comparable risk factors section.
Patrick J. Christmas: Or are just by its quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the Sec's website.
Patrick J. Christmas: Any information we provide on this conference call is provided only as of the date of this call May eight 2020 for 2024, 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.
Patrick J. Christmas: 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.
Patrick J. Christmas: I would now like to turn the call over to Ken Mills CEO of <unk>.
Kenneth T. Mills: Thank you Patrick good afternoon, everyone. Thanks for joining us.
Kenneth T. Mills: Im pleased to begin today's call with a recap of the recent business highlights as well as an update on our corporate goals.
Kenneth T. Mills: Today current Simpson, our Chief operating officer, who will be speaking for Steve Nicola Chief Medical Officer, who is unable to join US today <unk> will provide an update on our clinical programs.
Speaker Change: Assist our Chief Financial Officer, who will provide an overview of the financial results for the quarter ended March 31, 2024 at the end of the call will open up the line for questions.
Curran M. Simpson: We have what I think are some exciting updates today and so I wanted to get right into these topics. We started off the year, making significant progress across our pipeline as we advanced each of our programs towards pivotal stage clinical trials and commercialization in 2024, we've put a focus on large commercial opportunities where our product candidate.
Curran M. Simpson: These are differentiated can be expedited and support meaningful value generation soon and for the long term.
Curran M. Simpson: Our priority programs, our rdx <unk> for the treatment of Duchenne.
Curran M. Simpson: <unk> 314, or 314 for the treatment of wet AMD and diabetic retinopathy or Dr being developed in collaboration with Abbvie.
Curran M. Simpson: <unk> for the treatment of MTS <unk> Hunter syndrome.
Curran M. Simpson: All of our programs remain on track to meet our goals for this year program milestones over the past couple of months further demonstrate how our new plan is supporting the acceleration of the development of our gene therapies and the expansion of value for shareholders.
Curran M. Simpson: We're especially pleased to share new positive data in important updates about acceleration in our programs for Duchenne and Dr. Using in office delivery.
Curran M. Simpson: We are providing some new updated guidance on near term milestones for these programs. So let me explain.
Curran M. Simpson: We're thrilled to see RPX to choose demonstrating strong micro dystrophin expression across a wide range of patients including in older Boys like those ages eight to just under 12 and importantly, we are seeing positive safety signals no SAE as had been reported in patients who've received rdx two two which is highly notable.
Curran M. Simpson: <unk> and <unk> gene therapy trials.
Curran M. Simpson: Today, we announced that we have selected our pivotal dose.
Curran M. Simpson: Also we have already begun a new expansion phase of our clinical development with the pivotal dose. This includes the enrollment of third and fourth Boyds already expansion using the pivotal dose will continue into the third quarter and can enroll up to a total of seven boys and aegis ranging from four to under 12.
Curran M. Simpson: By early Q3, we expect to hold an end of phase II meeting with the FDA, which will support our final pivotal design and pivotal trial initiation is anticipated in late Q3 to early Q4 of this year.
Curran M. Simpson: <unk> is a differentiated product candidate in the landscape for Duchenne, representing the closest thing to natural healthy dystrophin and we believe has the potential to make a meaningful difference for a broad range of patients.
Curran M. Simpson: Given these unique characteristics of <unk> are significant ongoing unmet need in the Duchenne community and conversations with the FDA, we're confident in our plans to file a BLA using the accelerated approval pathway.
Curran M. Simpson: Separately.
Curran M. Simpson: We believe there is a multibillion dollar potential opportunity for ABVD Rdx 314 at the single injection treatment to become a first in class gene therapy for wet AMD and the standard of care to treat and prevent progression for diabetic retinopathy.
Curran M. Simpson: Enrollment remains on track for sub retinal delivery program for wet AMD currently in pivotal trials and today, we announced that based on positive interim results to date from the phase III <unk> trial and Dr. The design and evaluation of two pivotal trials is ongoing which would be the first pivotal trials for our in office superstore.
Curran M. Simpson: <unk> delivery.
Curran M. Simpson: These positive results and activities are in Florida. The planned discussion with the FDA at an end of phase II meeting anticipated in Q1, 2025 that can enable the rapid acceleration toward pivotal development.
Curran M. Simpson: We would expect to initiate the first two pivotal trials for supercritical delivery of diabetic retinopathy in the first half of 2025.
Curran M. Simpson: As a one time treatment, we believe that 314 is well positioned to become the standard of care to treat and prevent prevent progressive.
Curran M. Simpson: The progression of diabetic retinopathy, which is expected to impact over 20 million people globally in the next five years.
Curran M. Simpson: Overall, we're thrilled about the current status and the way that 2024 can achieve meaningful value generation based on what we've seen in these first few months.
Curran M. Simpson: With that I'm going to turn the call over to Chief operating Officer current Simpson, who will take us through a bit more of a detailed update on the duchenne data and our plans for accelerating the pivotal trial initiation for Duchenne in the second half of this year and diabetic retinopathy in the first half of next year current.
Curran M. Simpson: Thank you Ken I'll start with our <unk> 202, a potential onetime gene therapy for the treatment of Duchenne.
Simpson: <unk> represents an alternative for boys, who may not be eligible for other AAV mediated micro dystrophin therapies due to age or presence of preexisting neutralizing antibodies.
Simpson: Today, we reported that new micro dystrophin expression from the second patient aged eight one years, who received <unk> at dose level, two was measured at 29% compared to control at three months.
Curran M. Simpson: A reduction in baseline in serum creatinine kinase CK levels of approximately 90% was observed at 10 weeks.
Curran M. Simpson: We're excited about this data and the robust response seen in this trial, particularly in dose level two and in older Boys.
Curran M. Simpson: We shared previously we used to methods of measuring micro dystrophin protein western blot, EHS and LC Ms. Notably in this case, the micro dystrophin measured using LC Ms. For this patient was approximately 44% higher than the Western Blot result.
Curran M. Simpson: Today's data adds to the totality of evidence demonstrating that all patients who completed three months trial assessments indicate consistent encouraging increases in expression of <unk> 202, micro dystrophin and the reduction from baseline in serum CK levels supporting early evidence.
Curran M. Simpson: <unk> of clinical benefit.
Curran M. Simpson: In addition, early evidence of the strength in motor function improvement were observed via trial clinical assessments and home videos shared would trial investigators by caregivers.
Curran M. Simpson: As of May three 2024, <unk> hundred two continues to be well tolerated in all treated patients with no serious adverse events.
Curran M. Simpson: Given our robust data and positive safety signals, we plan to move forward with dose level two two.
Curran M. Simpson: <unk> per kilogram as our pivotal trial dose.
Curran M. Simpson: We have initiated an accelerated dose level two expansion cohort and it's already dosed two patients we expect to treat up to a total of seven patients at the pivotal dose.
Curran M. Simpson: Looking ahead, we remain on track to share strength and functional data for both dose levels and initiate dosing in the pivotal trial in late Q3 early Q4 this year.
Curran M. Simpson: Moving to $3 14, which is being developed in collaboration with Abbvie to treat wet AMD and diabetic retinopathy via sub retinal and supercritical routes of administration.
Curran M. Simpson: Valuation $3 14 for the treatment of wet AMD, the sub retinal delivery in two ongoing pivotal trials atmosphere and ascent in the U S Europe and Japan.
Curran M. Simpson: We anticipate global regulatory submissions in the first half of 2026.
Curran M. Simpson: We are also evaluating $3 14 in the phase II altitude trial.
Curran M. Simpson: Which is a dose escalation study of 314 using Super Corrado delivery.
Curran M. Simpson: We're very excited about the opportunity and Dr. Given the size of market, which exceeds that of wet AMD.
Curran M. Simpson: One year data from dose levels, one and two showed <unk> to be well tolerated with patients demonstrating clinically meaningful improvements in disease disease severity with reductions in vision threatening events.
Curran M. Simpson: Based on these and other positive interim results from altitude today, we are pleased to share more details about our path to pivotal stage in Dr.
Curran M. Simpson: We are evaluating the design for two pivotal trials in support of an end of phase II meeting with the FDA anticipated in the first quarter of 2025.
Curran M. Simpson: We expect to start the first pivotal trial and Dr. In the first half of 2025.
Curran M. Simpson: We are aligned with our partner Abbvie on this timing and believe there may be opportunities to further accelerate.
Curran M. Simpson: To conclude we continue to make significant progress with data updates in trial progression across all programs in our pipeline.
Curran M. Simpson: Lastly, I'd like to thank the patients families clinicians and patient advocacy representatives, who have been involved and supportive of these trials and.
Curran M. Simpson: And with that I'll turn the call over to Deb to review our financial guidance.
Deb: Thank you Carrie and Karen expire we ended the quarter.
Deb: March 31, 2024, with cash cash equivalents and marketable securities totaling $381 million compared to $314 million as of December 31, 2023.
Deb: The increase was primarily attributable to the $131 million in net proceeds received from an upsized public offering of common stock and pre funded warrants completed in March 2024, partially offset by cash used to fund operating activities in the first quarter.
Deb: <unk> 2024.
Deb: R&D expenses were $55 million for the first quarter of 2024 compared to $59 million for the first quarter of 2023. The decrease was primarily attributable to reduced manufacturing and clinical supply.
Curran M. Simpson: Costs for our lead product candidates and personal related cost as a result of reduced head count it was partially offset by an increase in.
Curran M. Simpson: Clinical trial expenses across our lead product candidates.
Curran M. Simpson: We expect the balance in cash cash equivalents and marketable securities of $381 million as of March 31, 2024 to fund our operations into 2026.
Curran M. Simpson: This cash runway guidance is based on the company's current operational plan.
Curran M. Simpson: The impact of any payments that may be received from abbvie. Upon the achievement of development and commercial milestones under our 301 for collaboration.
Curran M. Simpson: Including a potential milestone payment of $200 million.
Curran M. Simpson: Favorable upon achieving the dosing of the first patient in the pivotal trial for Super Choroidal delivery for the treatment of Dr. Additionally, this cash flow guidance excludes any potential monetization of our priority review voucher that may be received for <unk> 'twenty one.
Curran M. Simpson: With that I will turn the call back to Ken most hobby to provide final thoughts.
Kenneth T. Mills: So to wrap things up so far in 2024, our plans are on track and intended to generate significant value for shareholders. As we are ensuring that resources are allocated to the most valuable assets and to accelerate the development of those assets.
Kenneth T. Mills: As outlined here today and supported by the press release announcements, our motive motivated by expanding that value by addressing important unmet need in patients and focusing on large commercial opportunities, where we think our product candidates are differentiated and have a clear regulatory pathway forward.
Curran M. Simpson: The recent efficacy and safety data has allowed us to determine the planned pivotal dose for rdx too, which is an enabling us to further accelerate this program. So far this drug candidate is exceeding our expectations in the clinic, we've already begun a clinical trial expansion fees to add boys onto our pivotal dose a step that we believe will.
Curran M. Simpson: Contribute meaningfully to our accelerated approval plans.
Curran M. Simpson: Duchenne is a market where there is 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.
Curran M. Simpson: Regardless of today's landscape of Duchenne treatments communication from the FDA continues to support the need for alternative gene therapies for rare diseases, including Duchenne.
Curran M. Simpson: Backed by strong data, we're acting with urgency and in concert with the FDA, taking steps to initiate the pivotal trial for our <unk> as soon as possible this year and focused on serving needs in a broad range of voice.
Curran M. Simpson: We're also continuing to grow value with our eye care partnership with Abbvie.
Curran M. Simpson: It's using our onetime treatments that provide sustaining vision health long term and overcome the clinical challenges of managing retinal diseases.
Curran M. Simpson: The updates today highlight key alignment on important partnership goals in 2024 that are directed at completing trial designs and plans for initiating first pivotal trials for three four using an office super cradle delivery in diabetic retinopathy.
Curran M. Simpson: And completing enrollment of our pivotal trials for three one for using sub retinal delivery to support filing of global regulatory submission.
Curran M. Simpson: And as Curt mentioned, we believe there are opportunities to further accelerate these program.
Curran M. Simpson: <unk> one is meaningfully changing course of disease in boys with MTS II VI, restoring a missing gene and we are on track to file our first BLA as a company in 2020 for using the accelerated approval pathway for <unk> one.
Curran M. Simpson: Our pivotal trial achieved its primary endpoint of reduction of natural substrate in the CSF patients treated with <unk>, one and showed continued improvement and neurodevelopmental skill acquisition up to four years.
Curran M. Simpson: And have discontinued intravenous enzyme replacement therapy.
Curran M. Simpson: Our pivotal trial was designed to enroll believes under the age of Fi a strong proportion of those enrolled in our program are below the age of two and these are key features that are important in assessing neuron empathic Hunter syndrome.
Curran M. Simpson: We're locking our clinical trial databases and our team is busy collecting final pivotal trial data in completing steps for the entire BLA filing process.
Curran M. Simpson: By the end of 2024, our pipeline should be filled with programs that are initiating pivotal stage fully enroll the pivotal stage, we're under a file BLA.
Curran M. Simpson: And as we've mentioned in the fourth quarter, we announced the successful public offering this raise strengthens our balance sheet. It extends our operating runway into 2026 to support the acceleration of our Kennedy through multiple value generating milestones today, but its worth noting and restating that achievement of certain of these milestones would also trigger.
Curran M. Simpson: Hundreds of millions of dollars of additional funds.
Curran M. Simpson: As a result of these recent updates and upcoming milestones announced today, we believe <unk> is well positioned for success.
Speaker Change: Thanks, everyone for.
Speaker Change: <unk> for your time today.
Speaker Change: Finishes our disc.
Speaker Change: A discussion part of the call and now we're going to move over to Q&A.
Speaker Change: Thank you.
Speaker Change: A reminder to ask a question. Please press star one to one on your telephone and wait for your name to be announced toward the Joel. Your question. Please press star one one again, please stand by while we compile the Q&A roster.
Vikram Purohit: Our first question comes from the line of Vikram pool, Rohit <unk> from Morgan Stanley.
Vikram Purohit: Hi, everyone on this as Gospel answer Vic we have one question on the DMD program. So what do you think added trial enrollment a regulatory implication if any.
Vikram Purohit: Pfizer's update yesterday for 202.
Vikram Purohit: Hi Hospital. Thanks for the question I think that.
Speaker Change: As we reflect on what was obviously a sad events reported by Pfizer yesterday.
Hospital: We continue to feel very strongly.
Hospital: As we always do about the importance of safety with gene therapy and in rare diseases in general, especially in pediatric population, which is why we continue to feel very strongly and enthusiastic about the safety profile of <unk> to date being.
Hospital: Really the wind at the back for how partly how we're thinking about being able to progress on a more accelerated basis into pivotal phase. The same way that we had reflection when we made those decisions about our <unk>, one and advancing it into pivotal phase.
Hospital: I do think that from a regulatory perspective.
Vikram Purohit: So has to at a high level would be something that agencies like the FDA take into consideration.
Vikram Purohit: For existing approved products as well as products and development I think it's going to.
Vikram Purohit: This is something that I think people should be cautious about generating data in certain populations. I personally feel is a must when you think about the ability to apply an understanding in certain areas.
Vikram Purohit: In certain ages are certain progressed areas of disease.
Vikram Purohit: I think you also have to think about where those lines and differences are and seeing.
Vikram Purohit: Boy enrolled in a trial.
Vikram Purohit: He will go through an event like that I think.
Vikram Purohit: It's something that we've been emphasizing for a while that it's important to generate data, including in older blades, where we have been doing so.
Vikram Purohit: As you continue to think about how to progress into later stages of development to support.
Vikram Purohit: That clinical understanding and the potential for commercialization there so I imagine that.
Vikram Purohit: Many stakeholders are reflecting on that as well.
Speaker Change: Thank you.
Speaker Change: Thank you one moment far next question.
Speaker Change: Our next question comes from the line of Gena Wang from Barclays.
Gena Wang: Thank you for taking my questions.
Gena Wang: Just wanted to confirm did I hear you correctly that the.
Gena Wang: Fifth patient the mass spec protein level was 44% higher.
Gena Wang: 65% protein level.
Gena Wang: Level.
Gena Wang: Mass spec and also will you pick one methodology for protein level for pivotal study would that be western blot.
Gena Wang: Spak.
Speaker Change: Related question, sorry have you already scheduled the date for end of phase two meeting in Q.
Speaker Change: And also regarding understanding you will still need to finalize the trial with FDA, but can you submit BLA once three months protein data available.
Speaker Change: Hi, Gena.
Speaker Change: We will unpack that thanks for the good questions on the first point about the micro Dystrophin result, recurrent said is that we had.
Gena Wang: Approximately 44% higher L. CMS result, compared to the Western Blot Jeff's result, typically for US we've gotten comparable results in previous assessments between noise. In this case L. CMS was higher but that 44% applied to the result, we reported in the press release.
Gena Wang: Getting to about 30% for the LC Ms results.
Gena Wang: With respect to the plans.
Speaker Change: Can I say I mean, we're just in constant.
Speaker Change: <unk> communication with the FDA on really all of our programs, but in particular Duchenne Theres a lot going on in the space I think hospitals question.
Gena Wang: Can't be ignored as well so we.
Gena Wang: You need to see very close.
Gena Wang: We do have plans for an early Q3 meeting with the FDA on sort of end of phase II pivotal planning and initiation, we have shared with them already during the course of the program.
Gena Wang: Ideas about variables and features that are important to us or that were hearing are important to them in order to be able to design.
Gena Wang: And they think is.
Gena Wang: The most efficient and appropriate trial, we've really been focused on wanting to emphasize gaps in understanding for the community we've talked a lot about.
Gena Wang: The data that we've been able to generate and the focus that we've been able to put on older boys continuing to show.
Gena Wang: Positive micro dystrophin results measurable micro dystrophin results in this case.
Gena Wang: Today and another eight year old we continue to enroll in that age range. The last few patients we enrolled were five year old Anthony <unk>.
Gena Wang: So we feel like the data and the conversations that we have are going to set up for a very constructive discussion with FDA in early Q3, and we've also been open about the fact that we want to have that discussion.
Gena Wang: On what Punitively would be the other side of the potential action date with respect to the existing accelerated approved product. So we feel like everything is really on track and being able to declare the pivotal dose today to bring that into the conversation and discussion.
Gena Wang: <unk> is something that is also important.
Speaker Change: Thank you.
Speaker Change: Thanks Kim.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of Alec Stranahan from Bank of America.
Gena Wang: Hey, guys. This is John I'm on for Alex.
John: So just a quick question from us in terms of the second half data update for DMD program.
Speaker Change: Bill too.
John: A functional assessment data.
John: Kind of what kind of data should we be expecting on what.
Speaker Change: Thank you.
Speaker Change: Can you give us a call.
Speaker Change: It's something to look look too I'd like a standard what would that be if you could shed some light on that thank you.
Speaker Change: Yes, John sure I mean, I think we are.
John: We're collecting.
John: Normal strength and functional assessment, including the full Northstar domain on all of the boys in affinity Duchenne.
John: <unk> some of the activities that were going on in this trial by sharing some.
Dr. The: Dr. <unk> shared some video that he was able to bring forward at the MDA conference just a few months ago.
Speaker Change: So we're going to have the opportunity to you with boys that have achieved timed.
Speaker Change: Time points, some of which will be by the second half of the year, reaching out to 12 months and maybe some a little bit earlier.
Speaker Change: NSA scores as well as.
Speaker Change: Sub domains of Northstar, including.
Speaker Change: Things that have been the focus of other recent duchenne approvals or even discussions around.
Speaker Change: The recent sort of confirmatory.
Speaker Change: Evidence that was presented by the existing approved products sponsor, so things like time to stand and.
Speaker Change: Sort of domains associated with your ability around movement. So.
Speaker Change: These these are the types of things that I think you can expect from us in the second half of the year based on patients that have been enrolled to date.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: One moment for next question.
Speaker Change: Our next question comes from the line of Annabel <unk> from Stifel.
Annabel: Hi, Thanks for taking my question I.
Annabel: I guess on the DMD program I want to sort of understand your view on this you're saying that the micro dystrophin levels are consistent but it doesn't seem like it's specifically linear with age.
Annabel: So I was just wondering if you had any more insight into what's happening there and.
Annabel: Is this maybe going to change what the clinical relevance of is of micro dystrophin, specifically or are there other factors that theyre considering here.
Annabel: And then the second question I have is obviously, Mr. After hasnt updated decision depending on final approval and label expansion and now we're getting a lot of questions about what the various scenarios might be sitting from your perspective.
Annabel: Can you opine on how that might impact you and your opportunity going forward.
Annabel: And how you sort of view the different scenarios that are possibly emerging from that thanks.
Speaker Change: Yes, absolutely anabolic and I think that so.
Speaker Change: Partial answer to the first question just to clarify we're talking about different methods of measure for micro dystrophin today that we generally have viewed as comparable we've been using western blot and CMS I think we're the only company to use both.
Speaker Change: We have been presenting western blot, which is more of an automated western blot Ada in general.
Speaker Change: Community because people are more familiar with it with respect to what is in the.
Speaker Change: Existing approved product label.
Speaker Change: In terms of what we measured in this eight year old today, we previously measured in the 12 year old, let's remind everyone network talking about results that are positive measures of micro dystrophin protein and age ranges that generally have not been reported with other products.
Speaker Change: And in this case between the and a few that we enrolled at dose level II, we're seeing.
Speaker Change: At an average of 50% micro dystrophin level expression.
Speaker Change: Based on that Western blot method so.
Speaker Change: Really encouraged about that based on what we've seen in our preclinical data what we see of the safety profile and what we've seen that has started to emerge from some of the strength in functional assessments, even at dose level, one again, referring back to what Dr. Panda was able to share a bit on podium at MDA. So I think this.
Speaker Change: The safety profile in particular need a dose decision about the pivotal dose rather straightforward one for US we think we're continuing to see high levels of micro dystrophin expression, especially in older Boys and we think that in particular is something thats representative of a really strong stable.
Speaker Change: And durable product candidate.
Speaker Change: When it comes to the.
Speaker Change: Upcoming decision on that.
Speaker Change: The confirmatory evaluation evidence of.
Speaker Change: <unk> in the supplement I think we've been reasonably cautious with all of you all along about what that outcome may be.
Speaker Change: And also what we think the opportunity for <unk> is now.
Speaker Change: Things changed in the last couple of days and we've often talked about.
Speaker Change: Unmet need for Duchenne boys with gene therapy is having.
Speaker Change: <unk>.
Speaker Change: Two or three other candidates in development.
Speaker Change: Yesterday, obviously theres been a bit of a change to the profile of one of them, which I think everyone's still trying to digest.
Speaker Change: We continue to view that <unk> to two with new biology with the C terminal domain with the type of micro dystrophin expression that we've been showing in older boys, but also in four to seven year olds as being robust and significant and unique.
Speaker Change: <unk> is a differentiated product profile and thats without even having reached the time point, yet on strength and function, where we can really exercise and understanding of the benefits of the fee terminal domain. Those are things that are we think coming in front of us. So we.
Speaker Change: We see a differentiated product profile here as being very important.
Speaker Change: As important for the incident population of Duchenne Boys always I think it's important for the prevalent population of voice.
Speaker Change: As they are considering what their options are or will be as families and physicians and we've talked often about the fact that in general <unk> also holds a unique potential position in the market.
Speaker Change: As you know.
Speaker Change: Boys are certainly going to be excluded from access to other treatments due to preexisting immunology, just like they would be for our own.
Speaker Change: And in the case that we've talked about where there would be two products on the market that both were let's say ahead, either on the market or in pivotal phase development ahead of <unk>.
Speaker Change: We've sort of label that is maybe 15% of the market prevalent market that would be able to be uniquely addressed by <unk>. If you change that to <unk> with rgs to Q2 could be second to market and that number could be higher it could be something more like 20% to 30%. So I think for us.
Speaker Change: The work that we're doing to focus on the go forward plan for accelerating <unk> is about the strength of our differentiation and the strength of our data the safety data and efficacy data and addressing what we still think is unmet need with first generation micro dystrophin products.
Speaker Change: But.
Speaker Change: The case of just being as good as other theme.
Speaker Change: Is also something that from an economic perspective is foundational value.
Speaker Change: Valuable, but we think that our gx too of course is much more than that and we think that the data is showing that and we intend to continue to show that through as fast an expansion and acceleration fees as possible working with the FDA.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of Ellie Merle from UBS.
Speaker Change: Hi, This is gavin on for Elliot. Thanks, So much for taking our question Anthony have another word on that strengthen functional measures there'll be getting in the DMD update in the second half. So what do you think would be meaningful to see at that time point that you will share later this year. So at 12 months follow up on earlier relative to what you think could be meaningful.
Speaker Change: In the longer term so in another year or two.
Anthony: Sure. Thanks, Jasmine look I mean, I think we believe that <unk> with the C terminal domain has biological function and structure that translates into improvements in muscle function that we've seen.
Anthony: And its design in animal modeling and.
Speaker Change: Even early evidence of strength and motor function improvement was observed that we reported back.
Speaker Change: With the investigator at the MBA conference in March So we continue to be eager to accumulate.
Speaker Change: Domains of the North star that we can collect on strength and function and be able to show that and show the support for that differentiation coming into the second half of the year.
Speaker Change: That is not impacting though our conversations with the FDA on the approach to the accelerated approval pathway and the regulatory plan that we have.
Speaker Change: If it is it's only enhancing it because any evidence of early strength in motor function improvement is being observed and becoming a contribution to the totality of evidence, but the conversations with the FDA are about continued unmet need in the duchenne population even with existing.
Speaker Change: Seeing none the standard of care.
Speaker Change: Boys, who cannot get access to treatment because of preexisting immunology points, you may not be able to access treatment in certain age ranges because theyre looking for more data are there gaps in data in that understanding.
Speaker Change: Boys you may have certain types of mutations that have not been able to be studied in exploring either due to profiles of other products or simply because they haven't been.
Speaker Change: Done and so that's been our focus is to design something that is both efficient.
Speaker Change: Effective and accelerated in sort of pivotal design, but also something thats answering not just questions that FDA feels like it already has answers too and I think FDA is evidenced pretty strongly that it is supportive of micro dystrophin as a surrogate biomarker predictive of clinical benefit.
Speaker Change: We certainly with RG <unk> are achieving levels of micro dystrophin.
Speaker Change: <unk> or really above what I think is expected in terms of the regulatory process. So where we're going next to moving quickly on micro dystrophin accelerated approval and then focusing on strength and function data that we accumulate over time to further differentiate us in the commercial market and on more of a confirmatory basis.
Speaker Change: Great. Thank you.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of Brian <unk> from Baird.
Brian: Hey, good afternoon, and thank you for taking the question.
Brian: Quick one.
Brian: Thank you previously given the weight dosing.
Brian: Dosing of the underpinnings just wondering if you can provide.
Speaker Change: On page number five here.
Brian: Jumping out to me.
Brian: Based on the data provided so far.
Brian: There is differentiation between dose level, one or two.
Brian: Our CK levels changes so I'm, just wondering what what's kind of informing them. So you can go ahead.
Brian: Those level too.
Brian: Thanks.
Brian: Yes, Brian again, I mean, I think we're looking at a dataset in dose level two right now that is entirely be in Eaton above.
Brian: And the dose level. One data includes one patient from that age range, but the two other patients that are in the four to seven range, which I know to all of you and to most people is a more familiar territory because that's.
Brian: That's what the data is that has been shared.
Brian: Most often and almost entirely with respect to <unk>.
Brian: Existing labeling of the accelerated approved product as well as data.
Brian: From other datasets from other programs for us.
Speaker Change: I think there is several things we.
Brian: We're seeing.
Brian: Ranges of results here that are.
Brian: Consistent with what we've observed in animal models, where we've seen differentiation of those doses.
Brian: In terms of functional outcomes in the animals and the other thing is that we're looking at.
Brian: The range of the results overall, and we're incredibly happy and proud of the fact that everything that we're seeing in reporting it already in double digit micro dystrophin ranges not the case with other datasets as you look at them. So achieving that I think says something to us about the overall stability in the overall.
Brian: All quality of RG <unk> and the Kennedy as designed.
Brian: But secondarily I think we do see rdx <unk> again, having something that is just between those two results.
Brian: Close to 50% micro dystrophin expression and these are employees, one who is 12 in one who's eight and for US those are the types of boys that are more progressed disease with.
Brian: Frankly that are more challenged to be able to get levels of micro dystrophin expression with gene therapy, and I think thats reflective of the evidence that other programs haven't even chosen to progress or shared data in those types of age ranges. So this is what has got us incredibly enthused and excited is that dose level one showed us.
Brian: Yes, we can get great results in four to seven year old and we got a strong result also in.
Brian: I E.
Brian: An older Boy, a 10 year old in that case, but in dose level to the first two kids that we enrolled were older Boys and we got what we think are phenomenal results that in the safety profile was an easy decision along with discussions we've been having with FDA to designate that is our pivotal dose.
Speaker Change: Great and just.
Speaker Change: How about the wait for patient number Bob.
Bob: Yes, sorry, I didn't hear you did you say wheat.
Bob: Yes can you tell us the way to producing number you.
Bob: You provided the other rates.
Speaker Change: Yes, I don't have that off the top of my head off to follow up with you on that.
Speaker Change: Alright. Thanks.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of Danielle Brill from Raymond James.
Speaker Change: Hey, guys. This is Alex on for Danielle Thanks for the question.
Alex: Couple of three one or given the updates today do you still plan to publicly disclose those data updates from altitude later this year and just curious why the large gap between now and the guided end of phase two meeting with FDA and <unk> 25.
Alex: Then looking at wet AMD.
Alex: Sure.
Speaker Change: We think the wet AMD data.
Speaker Change: Got it up a little bit more mature. So we would have guessed that would've been advanced to pivotal as well, so what kind of data or time points to you and have being need to see to convince you to advance.
Speaker Change: Supercoil wet AMD or <unk>.
Speaker Change: Pivotal development.
Speaker Change: Yes, Thanks, Alex.
Speaker Change: You've hit on an important point, we're working in partnership with Abbvie here to ensure successful program, including.
Speaker Change: <unk> commercial and clinical value is achieved we are well aligned with them on this guidance.
Speaker Change: We have been.
Speaker Change: Focused on the fact that when we bring a package forward to the FDA for a pivotal design, which would be the first such pivotal package for supercritical delivery for gene therapy in diabetic retinopathy.
Speaker Change: It's going to be as robust and.
Speaker Change: Sort of important as you could expect for that conversation.
Speaker Change: We don't rule out that things could be done on an accelerated basis to beat that guidance, but right now we sort of felt most confident in the Q1 2025 guidance, which is months away right and so for US also the fact that we view initiation of the pivotal in the first half of 'twenty.
Speaker Change: <unk> I think in sort of emphasize that we think that the sort of time energy and effort that would be put into an end of phase two discussion will be something that we can accelerate off of in terms of pivotal initiation overall.
Speaker Change: With respect to Super Cradle device overall in program plans between diabetic retinopathy in wet AMD. This is actually pretty consistent and predicted for us.
Speaker Change: Talked about back in the end of 2023, that's the diabetic retinopathy data that was presented was maturing and kind of coming into focus in terms of key.
Speaker Change: Key measures of efficacy and safety that was a little bit ahead of where we saw things with respect to wet AMD Super Cradle.
Speaker Change: Updated wet AMD Super Cradle.
Speaker Change: Client <unk> meeting earlier in the year at six months data and said we were encouraged by that but also viewed that it was the decision was potentially frame shifted from diabetic retinopathy by at least a few months and so we continue to.
Speaker Change: <unk>.
Speaker Change: The guide that overall.
Speaker Change: What I would say is eventually one of the indications has to be the first to go into pivotal phase and into that discussion with FDA I think that the view that the first also would be the one that would be <unk> pivotal trial design approach is something that I think is consideration overall and that we feel strongly.
Speaker Change: Regina expiring in alignment with Abbvie about this that the unique nature of the data that we're seeing in diabetic retinopathy in the unique unmet need is also something that is very attractive for bringing that forward as the potential for.
Speaker Change: Application of the supercritical delivery approach, but we have guidance for Q3 update on wet AMD as well and be able to talk more about that program now.
Speaker Change: Alright, thanks, so much.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of Mani <unk> from Leerink.
Mani: Hi. This is early on for money. Thank you for taking my question. So maybe just a quick follow up in terms of the.
Mani: Typical corridor for at $3 14.
Mani: So in terms of the data David can you, maybe just give us a little bit more granularity in terms of six months.
Mani: Follow up timing that we would be seeing and also the potential data point that would that would basically influence your decision. Thank you.
David: Sure I don't think we have any more specific guidance right now on what the next data updates are going to include again our process here working in partnership with Abbvie is right now we're focused on program execution and acceleration based on these positive interim results that we decided for.
David: <unk>.
David: Led us to this updated guidance.
David: <unk>, an initiation of the pivotal but we generally have kept a reasonably steady cadence of updating the community at conferences and when we're able to bring additional data forward usually in settings of medical conferences. We do right now we expect the next program update and data for <unk>.
David: At AMD Super <unk> to be in Q3.
David: But we're especially excited that diabetic retinopathy program now has guidance for the first supercritical program to move into pivotal phase.
Speaker Change: Thank you.
David: As a reminder to ask a question. Please press star one one on your telephone.
David: <unk> for your name to be announced to withdraw your question. Please press star one one again.
David: Our next question comes from the line of Luca <unk> from RBC capital.
Luca: Oh, great. Thanks, so much for taking my question Congrats on the progress maybe a quick one on DMD circling back on the preexisting immunology.
Luca: Obviously trying to differentiate in DMD in multiple ways, including to Sito, Ms domain as well as obviously going after a broader patient population, but what percentage of patients will be eligible for therapy.
David: Because they have neutralizing antibodies against both <unk> and Pfizer just trying to get an America percentage share on just to kind of lowest hanging fruit.
David: And then maybe on the competitive landscape for ocular gene therapy. We recently saw some data for the long acting TGI data was somewhat mix for Dr. Despite actually pretty good data for wet AMD what are your thoughts on.
David: What drives that dichotomy between the two and maybe more broadly what are your thoughts on the long acting <unk> as a potential competitive threat for your program. Thanks, So much.
Speaker Change: Thanks Luca.
Speaker Change: So I think you do a pretty solid job of modeling that concept of the cross reactivity of different serotypes look I think we generally have offered up that to maybe a solution on its own again thats with two other competitive products.
Speaker Change: Let's say <unk> and Pfizer are competitive with our <unk> product in a hypothetical firmware.
David: You'd be looking at cross reactivity to different AAV and say, what's what's last uniquely for <unk> I think that's about 15%.
David: I think you can draw on that from a number of sources of data again, it's generally accepted and known that the prevalence of neutralizing antibodies against any AAV capsid is going to be something on the order of 30, maybe even 40% of subjects.
David: Even even more for some of the earlier <unk> like AED two for instance, but but in general where we are with.
David: 74, <unk> nine or <unk> 88, so I think in the case, where there's two competing products 15% in the case when we are second to market, which I think is a possibility we need to start considering here for our gx too in terms of where we are positioned to continue to execute the safety.
David: Profile the data that we're showing.
David: Can be above that number I can see 20% to 30% in a head to head comparison with <unk>.
David: Another another vector.
David: <unk>.
David: On the comment about Teekay is I mean, good observation I know there was a couple of datasets that had been presented in the last few months both in N PDR.
David: I mean, obviously.
David: AAV gene therapy Rdx, three one for the body of evidence around the clinical data between sub retinal and Super Cradle and its ability in a continuous way with its PK profile to target anti VEGF VEGF.
David: Jeff.
David: Basically a molecule thats, a new approved therapeutic entity I think it is very different than the continuation that people have worked on to try to bring forward broad spectrum chemistry agents like tyrosine kinase inhibitors to affect that.
David: Jeff in the eye.
David: Our view is.
David: Nothing compares to the profile of a onetime treatment expressing an anti VEGF biologic that is part of the known standard of care.
David: For wet AMD and related conditions remember.
David: Treatments like Eylea and Lucentis are actually labeled for Dr. In PDR population Theyre, just not used at all or Theyre not adopted even.
David: Arguably in the 1% cases, so we are bringing forward to the market.
David: As importantly, our profile is something that is already established clinically as showing benefit but just hasnt had the commercial adoption I think I think teekay eyes are coming from a different space I don't think that necessarily the chemistry and the formulations have completely been worked out I don't think that Teekay is have been worked out entirely.
David: We're all across.
David: No diseases, and I think that there is certainly not one time treatments, which is well I think is what a meaningful differentiation for 314 Super crew idle is so.
David: For us at this stage, we think we have a profile that is.
David: A clear commercial leadership profile in our clinical leadership profile.
Speaker Change: Thank you so much.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: Our next question comes from the line of John Neal Good tailwind from Chardan.
John Neal: Hey, guys. Thank you for taking the question I have a follow up on that point and diabetic retinopathy.
John Neal: Does it begin to prepare for the end of phase II discussions what is your current thinking on the primary endpoint of greater than or equal to two step Drs as improvement.
John Neal: Versus the greater than or equal to three step worsening that some other companies are planning or considering to use.
Speaker Change: Thank you.
Speaker Change: Yes, good question, Danielle I think that.
Speaker Change: Okay.
Speaker Change: Most important emphasis for us about the clinical and commercial opportunity in Dr is actually what Corinne mentioned about <unk>.
Speaker Change: <unk> threatening events revision threatening complications we have shown evidence of risk reduction up to almost 90%.
Speaker Change: In vision threatening complications in diabetic retinopathy patients and this is the thing that in the long term is what is affecting their vision.
Speaker Change: And so to longitudinally be able to affect that is the priority and that will be something that we will continue to collect and trial.
Speaker Change: When it comes to the concepts of Drs, scoring two step worsening or two step improvement. These are regulatory outcomes that I think have meaning in terms of how we're going to power studies and I think that we've shown evidence of data previously in our develop.
Speaker Change: <unk>, where we've had really high propensity of patients who overall have achieved improvement in Rss relative to observational control and we've had zero percent of patients worsened relative to high number of patients on a percentage basis, who are worsening in these <unk>.
Speaker Change: Observational controls so I think there is.
Speaker Change: Good options there for us in terms of the regulatory end point, but I want to really emphasize that we think that the focus clinically and commercially for bringing.
Speaker Change: Especially uniquely a onetime treatment forward would be the emphasis on the reduction of vision threatening events and for their I think again, we can point to at least an 89% reduction in data we presented last year.
Speaker Change: As some of the best data and supportive evidence for.
Speaker Change: This type of treatment in diabetic retinopathy.
Speaker Change: Got it thank you.
Speaker Change: Thank you at this time I'm showing no further questions. This concludes today's conference call. Thank you for participating you may now disconnect.
Speaker Change: Okay.
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