Q4 2022 Regenxbio Inc Earnings Call
Speaker 1: We you.
Speaker 3: Hello, and thank you for standing by. Welcome to the Q4 and full year 2022 GenX Bio Earnings Call. At this time, all participants are in listen-only mode. After the prepared remarks, there will be a question and answer session. Instructions will be given at that time. As a reminder, this call is being recorded.
Speaker 3: It is now my pleasure to introduce Chief Legal Officer Patrick Christmas. You may begin.
Speaker 4: Good afternoon and thank you for joining us today. Earlier this afternoon, Regenexx Bio released financial and operating results for the fourth quarter and full year ended December 31, 2022. The press release is available on our website at www.regenexxbio.com.
Speaker 4: 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, as complementary generate FUND,
Speaker 4: Plan, will, may, anticipate, believe, should, intend.
Speaker 4: In other words, a similar meaning.
Speaker 4: 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 Regenexx Bio's annual report on Form 10-K for the full year ended December 31st, 2022, and comparable risk factors sections of Regenexx Bio's quarterly reports on Form 10-Q .
Speaker 4: which are on file with the Securities and Exchange Commission and available on the SEC's website.
Speaker 4: Any information we provide on this conference call is provided only as of the date of this call, February 28, 2023, 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.
Speaker 4: Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company.
Speaker 4: Actual results may differ materially.
Speaker 4: I would now like to turn the call over to Ken Mills, CEO of Regenexx Bio. Ken maybe you can turn up that kind of virtual intervention with the couple
Speaker 5: Thank you, Patrick. Good afternoon, everyone. Thanks for joining us. I'm pleased to begin today's call with a recap of our recent business highlights as well as an update on our corporate goals. Dr. Steve Ficola, our Chief Medical Officer, will then provide an update on our clinical program, and Visma Sista, our Chief Financial Officer, will provide an overview of financial results.
Speaker 5: therapies for diseases that have significant unmet needs.
Speaker 5: We continue to be a leader in gene therapy with thousands of patients who have been dosed with AAV therapeutics derived from our nav technology platform.
Speaker 5: Today we recognize that we're at the intersection of rare disease day and the final day of February that was part of low vision awareness month. I'm encouraged by the momentum in AAV gene therapy. With recent approvals, upcoming regulatory decisions, encouraging clinical trial outcomes within AAV gene therapy.
Speaker 5: and positive signals and actions from leaders at the FDA about the importance of accelerating gene therapy development, I believe the opportunity for gene therapy, and particularly AAD therapeutics, has never been stronger.
Speaker 5: Additionally, with our expected near-term approval goals and continued efforts from research through clinical development and commercial-ready manufacturing, I'm proud of Regenexx Bio leadership in this field.
Speaker 5: We've continued to make great progress in the fourth quarter and throughout the course of the year advancing our internal pipeline as we execute our 5x25 strategy to advance five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025.
Speaker 5: To summarize some of our program and operational highlights.
Speaker 5: We've made significant progress across our global eye care collaboration with APPE. Enrollment is ongoing in atmosphere and ascent. The two pivotal trials for RGX314 for the treatment of wet AMD using sub retinal delivery. The pivotal trials are expected to support a VLA filing in 2024. Regenexx Bio's NavExpress platform process has been incorporated into these pivotal trials.
Speaker 5: and is expected to be produced at our Manufacturing Innovation Center for future commercialization of RGX314.
Speaker 5: Related to that, earlier this month we presented initial data from a phase two bridging study of RGX314 using subretinal delivery where we evaluated wet AMD patients receiving RGX314 manufactured by our NavExpress platform process.
Speaker 5: at the same dose levels being used in the two pivotal trials. The clinical profile of these pivotal doses of RGX314 using the commercial scale process is encouraging and provides validation for our plans for future commercialization. Now we've also progressed RGX314 this year using supercroyal delivery.
Speaker 5: for both WEDAMD and Diabetic Retinopsy with positive interim data updates in the last quarter of 2022 supporting the emerging clinical profile and the potential of this in-office approach for one-time gene therapy. The AV and altitude trials are ongoing.
Speaker 5: We expect to complete recent enrollment of recently announced new cohorts in these trials in the first half of 2023 and report additional interim data, including initial data from these cohorts in the second half of 2023.
Speaker 5: Quickly moving over to our rare disease pipeline, we announced earlier this year that the Affinity Duchenne trial of RGX202 is active in recruiting patients.
Speaker 5: Duchenne is a key piece of our 5x25 strategy and represents a large patient population with significant unmet needs.
Speaker 5: Our Duchenne program features a highly differentiated product candidate, including an optimized, novel microdistrofen and a unique AAV8 capsid, which has the potential to improve muscle strength, motor function, and increased access to gene therapy for boys with Duchenne.
Speaker 5: We are also starting our trial using our proprietary commercial scale CGNP NavExpress manufacturing process that has demonstrated increased purity and yield and that we believe will support efficient advancement from the clinic to commercial readiness.
Speaker 5: Today we announced that we expect to report initial data from the affinity Duchenne trial in the second half of this year.
Speaker 5: As I mentioned, our NavExpress platform process and the commercial scale manufacturing innovation center represent key differentiators for Regenexx Bile that we're using across our entire clinical trial pipeline to support accelerating the development of AAV therapeutics. Our pivotal program for RGX121 for the treatment of MPS2...
Speaker 5: to support a VLA filing in 2024 using the accelerated approval pathway.
Speaker 5: We had multiple presentations last week at the 2023 World Symposium where we certainly provided positive updates from trials associated with RGX121 as well as RGX111 in severe MPS1 or Herler syndrome. Log1340wind GuardianDaddy Catholic subreddits
Speaker 5: and treatments that we're developing for CLN2, a form of Batten disease, all of which Steve will review in greater detail momentarily.
Speaker 5: We expect to share additional updates on Batten, Hurler, and the Hunter program plans and clinical progress throughout 2023. With that, I'm going to turn the call over to Steve so he can review in more detail our clinical progress.
Speaker 6: Thank you, Ken. I'll begin with an update on RGX-314, which is being developed in collaboration with AbbVie to treat wet AMD and diabetic red toposy.
Speaker 6: RGX314 uses the NAV AAVA vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor, or VEGF.
Speaker 6: WED-AMD is the leading cause of vision loss in people over 60, affecting more than 2 million patients in the US, Europe , and Japan.
Speaker 6: The current standard of care for wet AMD patients are anti-veg f treatments which require patients to receive frequent injections in the eye Real-world evidence shows that patients with wet AMD are severely under treated due to the unsustainable treatment burden of these frequent injections.
Speaker 6: As a result, the majority of wet AMD patients experience significant vision loss over time.
Speaker 6: Last quarter, we presented positive data from the Phase 1-2A long-term follow-up study of RGS314 for the treatment of wet AMD using subretinal delivery at the AAO annual meeting that was held in October . We expect this result, this trial, along with our two ongoing pivotal trials, Atmosphere and Spotify, to happen in September .
Speaker 6: Genesis Conference earlier this month.
Speaker 6: The data demonstrated that RGF 314 produced by the NAV Express platform process exhibited a similar clinical profile to the initial adherence cell culture process used in the Phase 1-2A trial, validating the NAV Express platform process to support the production of RGF 314 for future commercialization.
Speaker 6: RTX 314 has been well tolerated in this ongoing trial.
Speaker 6: Patients in the two high dose cohorts also demonstrated stable to improve BCVA and CRT and meaningful reductions in anti-VegF burden with the majority of subjects in Section 3. The Phase 2 Pharmacogenomics Study is designed to evaluate the same dose levels being used in the two pivotal trials.
Speaker 6: a randomized dose escalation study evaluating RGX314 in subjects with wet AMD.
Speaker 6: We also announced the expansion of this trial to further explore the third dose level in a sixth cohort with a short course of prophylactic ocular steroids following RGX314 administration to potentially prevent the observed incidence of mild to moderate IOI.
Speaker 6: Patients are being enrolled in Cohort 6 regardless of NAP status. Moving to RGX-314 for the treatment of diabetic retinopathy.
Speaker 6: DR is a complication of diabetes and it's a leading cause of blindness in adults between the ages of 24 to 75 and affects an estimated 27 million patients worldwide. DR is a slowly progressing disease that can lead to vision threatening complications including diabetic macular edema and neovascularization.
Speaker 6: that can lead to blindness.
Speaker 6: Like in wet AMD, patients with DR are treated with anti-VEGF therapy, which is proven to reduce the risk of developing vision-threatening complications.
Speaker 6: However, due to the unsustainable treatment burden of frequent anti-VEGF injections, many patients with this condition either elect to forgo treatment or put off receiving any treatment until symptoms become unavoidable.
Speaker 6: We believe a one-time gene therapy like RGS314 could potentially overcome this hurdle and provide an important therapy for DR patients.
Speaker 6: to significantly alter their disease progression. In November , we announced new data from altitude our randomized controlled dose escalation phase 2 trial evaluating supercoronal delivery of RGX314 in patients with DR at the Retina Society annual meeting. We also announced that we expanded that trial to include a higher.
Speaker 6: shifting to our rare disease portfolio, RGX202 is our potential one-time gene therapy for the treatment of Duchenne, being developed as a highly differentiated product designed to deliver a transgene for a novel microdistrofen that includes the functional elements of the CT-2.
Speaker 6: muscle damage and dystrophic mice models. Additional design features, including codon optimization and reduced CPG content, have the potential to improve gene expression, increase translational efficiency, and reduce immunogenicity.
Speaker 6: Our GS202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV-A V8 vector and a well characterized muscle specification.
Speaker 6: specific promoter. In January , we announced that our Phase 1-2 affinity Duchenne trial is active and recruiting and will assess the safety and tolerability of RGS202 as well as microdistrofen protein expression levels, muscle strength and functional measures.
Speaker 6: and muscle MRI in patients with Duchenne. We are on track to dose our first patient in this trial using commercial scale CGMP material from our NavExpress platform process in the first half of this year.
Speaker 6: We are also recruiting patients in the affinity beyond trial an observational screening study with the primary objective to evaluate the presence of AAV8 antibodies in patients with Buchenne to potentially help identify participants for the affinity to send trial.
Speaker 6: and other possible future trials of RGX202. We also continue to progress our two programs for mucopolysaccharide doses.
Speaker 6: RGX 121 for NPS 2 and RGX 111 for NPS 1. Last week we presented positive data from both programs at the 2023 World Symposium.
Speaker 6: Additional positive interim data from the Phase 1, 2, 3 campsite trial of RGX-121 for MPS2 showed patients in cohort 3 using the Pivotal Program dose continue to demonstrate the largest reduction in CSF gagged and these patients continue to approach normal levels at week 48.
Speaker 6: As a reminder, heparin sulfate or HS and D2S6, a component of HS, closely correlated with severe NPS2, are GAGs that are key biomarkers of I2S enzyme activity and are being measured in the CSF at baseline and after administration of RGX121.
Speaker 6: CSF GAGs have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in NPS2 disease under the accelerated approval pathway as buildup of GAGs in the CSF of NPS2 patients correlates with clinical manifestations including neurodevelopmental active deficits.
Speaker 6: Additionally, patients demonstrated continued improvement in neurodevelopmental and daily activity skill acquisition up to three years after RTX 121 Administration.
Speaker 6: As of January 3rd, 2023, RGX-121 was reported to be well tolerated across all cohorts with no drug-related SAEs. At World, we also shared additional positive interim data from the Phase 1-2 trial of RGX-111 for the treatment of severe MPS1.
Speaker 6: As of January 17, 2023, RGX-111 was reported to be well tolerated with no drug-related serious adverse events. Patients demonstrated positive I do A biomarker activity in the CNS and encouraging continued neurodevelopmental skill acquisition.
Speaker 6: as measured by age and developmentally appropriate validated instruments for neurodevelopmental testing. Following these two programs, we are also developing two programs to help treat the manifestations of CLN2. RGS 181 to treat the neurodegenerative manifestations.
Speaker 6: and RGX381 to treat the ocular manifestations.
Speaker 6: As we recently announced, we expect to initiate the Phase 1-2 clinical trial of RGX-381 in the UK in the first half of this year. And late last year, a patient was dosed under a single patient investigator initiated study of RGX-181 in Brazil.
Speaker 6: Awareness Month, and I'd like to take this opportunity to acknowledge the patients, caregivers, investigators, and physician partners who participate in our work.
Speaker 6: Without them, our progress in advancing our programs with the goal of delivering the curative potential of gene therapy simply would not be possible.
Speaker 6: And with that, I would like to turn the call over to VIT to review our financial guidance. VIT? Yes.
Speaker 7: Thank you, Steve. GenX BioN is a quarter in year on December 31, 2022, with cash, cash equivalents, and marketable securities totaling $565 million compared to $849 million as of December 31, 2021.
Speaker 7: The decrease was primarily driven by cash used to fund operating activities and capital expenditures in 2022. R&D expenses were $242 million for the year ended December 31, 2022 compared to $181 million.
Speaker 7: in 2021.
Speaker 7: The increase was primarily attributable to personal costs and expenses associated with clinical trials and manufacturing related activities for relief product candidates. And was partially offset by Vigenics 314 development costs reimbursable by ABB under eye care collaboration.
Speaker 7: In accordance with the collaboration agreement, Virginia Spyler was responsible for the funding of certain ongoing clinical trials for Virginia 314 through the end of 2022, while other RGX314 development costs were shared with ABB.
Speaker 7: Beginning in 2023, ABBE will be responsible for funding the majority of all RGX314 development expenses.
Speaker 7: We expect a balance in cash, cash equivalents, and marketable securities of $565 million as of December 31, 2022 to fund our operations into 2025. This cash runway guidance is based on the
Speaker 7: on the company's current operational plans and excludes the impact of any payments that may be received from Abbe on the achievement of development or commercial milestones under our RGX314 collaboration. With that, I will turn the call back to Ken to provide final thoughts.
Speaker 5: Thanks for that update, Sid. I'd like to reiterate that Regenexx Bio continues to perform at a very high level and is inspired by the patients, families, caregivers, and other stakeholders that we encounter every day in our journey to improve lives through the curative potential of gene therapy. In 2022, we made meaningful progress with our RGX314 trial enrollment objective.
Speaker 5: the latter of which we expect will support a BLA filing using the accelerated approval pathway.
Our history science resources, people and values, combines and make us an industry leader in gene therapy and in the development of potentially groundbreaking therapies.
We have an amazing team of scientists and engineers dedicated to expanding the understanding and the application of AAV vectors, applying the differentiated capabilities of the nav technology platform, and exploring opportunities to generate new innovative AAV therapeutics that have the potential to significantly impact patients' lives.
We look forward to 2023 with a number of important updates on all of our research and clinical stage programs. With a balance sheet to fund our mission and operations into 2025, I believe we have a clear and definable path to achieve 5 by 25, the vision, and continue to lead what's possible in AAV therapeutics.
With that, operator, we will turn the call over for questions.
If you'd like to ask a question, please press star 11. If your question has been answered and you'd like to remove yourself in the queue, please press star 11 again. One moment while we compile the Q&A roster. And our first question comes from Gina Wang with Barclays. Your line is open. Okay.
Hello, can you hear me?
Hi, this is Shiu. I'm from JINA. Thank you so much for taking our question and congratulations on the progress. We have two questions, one on 3.14 Super colloidal web AMD and one question on DMD-202. 1.13 approval, 2.14 approval, 2.14 approval, DMD-202, 2.14 approval.
So for 3.14, the new PROF-E cohort 6, the dose is 1E12. So what type of data would you consider successful and will give you confidence this will be the pivotal dose?
and under what condition you would consider to further escalate the dose.
The second question is about DMD. So what should we expect in your data update in the second half of 2023? How many patients? And in addition to the biomarker data you just mentioned, would you report any functional endpoints?
and what type of benchmark data should we use to evaluate the update. Thank you very much.
Thanks a lot for those questions. I'll take them and then Steve if you want to add any color let me know.
The guidance about second half of the year, we're talking about AV8N altitude updates for the trials. We're ongoing with the enrollment of the cohort that includes the prophylaxis, and I think it's early to predict precisely when the updates will occur, but I think what you can expect from us is...
Sort of the normal structure of updates that we have when we get to six-month time points for cohorts in our wet AMD and diabetic retinopathy studies. I think it's too early to be talking about any interpretation of the data at this point with you because...
We don't have any specific data to talk about. We obviously have a lot of benchmarking when it comes to how we made dose decisions around the subretinal profile in terms of transitioning to pivotal. I think in the second half of this year, when we have additional data to bring forward, we'll be able to talk to that specifically. Thanks for that question. Thank you.
On the 202 side, I think, again, we're in the process of sort of active and recruiting study today, so we're giving guidance for second half of the year data. I think we have outlined in our clinical trial design that in the first, you know, three to six months of assessments, we're going to see things that are more weighted toward early biomarker assessments and...
maybe certain types of imaging outcomes. I think some of the functional outcomes would be things that will be tracked in the studies at time points closer to maybe 9 or 12 months. So I think that's what we have in terms of the trial design. I think as we get into the second half of the year and closer to the point in time where we'll have those data updates, we'll be able to provide more information. I think in terms of benchmarking, we've talked about this.
microdystrophin is being differentiated in the class of microdystrophin. We talked about the C-terminal domain bringing scientific and I think interesting potential clinical opportunities for differentiation. Early on we'll be looking at expression of that microdystrophin construct in biopsies and its effect on
Some of the imaging techniques that are available will certainly be looking at safety in the first in human examination here of RGX202. So those are the things that I think we could expect to compare to in the second half of
that are available and will certainly be looking at safety in the first and human examination here of RGX202. So those are the things that I think we could expect to compare to in the second half of the year. Thank you very much.
Thank you. Our next question comes from Dane Leon with Raymond James. Your line is open. Thanks for taking the questions. Let's ask like probably two most popular ones that have been coming in from investors recently. The first one is...
Do you have a sense when you will have first data from the 202 program of the first patient or patient you treated with the MD? What the password will be from a clinical strategy, obviously right now. There's been discussion that Sir Rept is disclosed tonight that they will not in fact have an marathon.
So, I guess thoughts given how their program worked out, how you would approach your clinical development program. And then the second one is quite popular that whether in your view and your team's view, 9001 infringes on your IP path in this state. Thank you. So, let me present this study or three studies from several
Thanks, Dave. Always appreciate your questions and getting right to the point.
Look, until we have data, we're not going to be leaning in anymore to what exactly are passed in terms of next steps with respect to clinical development of 202R. Right now, we think we've got a great program to assess early safety, set biomarker activity, look at functional outcomes, and I think these things all fit within.
kind of the guidelines of programs that others have run, including the SREPDAs and Pfizer who have advanced with Microdistrophin, Class of Products to later stages of development. We think we've got the benefit of playing from behind and observing some of the scientific clinical and regulatory strategies that have been employed. We think we've got some scientific advantages. We think we have some CMC differentiation.
and we'll be able to start reading that out in the second half of the year. With respect to our intellectual property and how it relates to other programs, I think we have talked about in the past that we have identified patents in our portfolio that we view are part of an action that we have.
taken with respect to Sarepta. And what I can say about that is it's ongoing and that the lawyers are responsible for executing on that and when we have material updates, we'll be able to bring those forward. But at this point, there's nothing else to say. Thank you very much.
to Sarepta. What I can say about that is it's ongoing and that the lawyers are responsible for executing on that and when we have material updates we'll be able to bring those forward. But at this point there's nothing else to say. Thank you very much. Thanks.
Thank you. Our next question comes from Alex Stranahan with Bank of America. Your line is open. Hey guys, this is John . I'm on for Alex. Just a couple of questions from us. So the first one, for your NavX price platform, how long do you expect the transition to the new platform to be and when can we expect current products?
clinical needs to be fully supported by the platform. So that's the first one. Second question on 314. I think the last time we talked, you maybe just give more color on framing the market for 314. I think assuming you're still targeting patients who require frequent injections and would opt in for the one-time treatment. So, like, what percentage of patients would you say
fall into that category. That's it for me. Thanks. Yeah. Great, John . Appreciate the questions. I'll take the first one and let Steve handle the second here. So, NavExpress, we've got to practice the pronunciation because this is a new trademark name for us. It's our platform process that is a bioreactor process that we have.
I've actually been using our CDMOs, but I've also now installed here at Scales in our Rockville facility, our Manufacturing Innovation Center. And we opened that center last year, done, so we've been incorporating and designing plans to incorporate material based on the NavExpress process into our RGX314 programs, both for sub-retinal pivotal, for super-croidal...
in the clinic with that process, and that's been a point of emphasis we've been making, is that we think there's going to be, therefore, an efficient transition through clinic and in that transition from clinic to commercial. And then with other programs that we've guided to, like program updates for RGX 111 in the second half of the year, we've said that we've...
already started the process of making additional RGX-111 material with the NavExpress process. So basically everything is there now. In some cases we're incorporating it into late stage execution. In other cases we're beginning clinical trials and clinical investigation with that process. And we think that this is very important to be at this stage, have a high quality, high purity, high yield process and one that's very reproducible. So thanks for that. I'll let Steve talk about the 314 market. Hi John . Steve here. Yeah, a common question of thinking how to...
segment or think about the spectrum of wet AMD and diabetic retinopathy patients. On the wet AMD side, you raise the point of more, those patients who are more anti-veg epneady and need more frequent injections, and it certainly makes sense that those who need injections every month or every two months or every three months, they have a higher burden, so they may see more value, they and their caregivers may see more value than if very infrequent injections are needed.
But the reality is we know across the spectrum, whether you're getting injections every month or you're getting them every three or every four months, you'd rather have fewer injections into your eyeball and fewer visits to the eye doctor. So we really see a one-time treatment option that can either prevent the need for re-injections or in those who still need re-injections, you can dramatically decrease that treatment burden.
has a value proposition across the spectrum. We do know with, even with agents like for isimab and data coming out on high-dose ILEA, there are incremental benefits there, but still the majority of those patients still need frequent injection. So we really see the opportunity across the spectrum. Certainly with subretinal delivery in that setting, when we talk to clinicians.
There's a subset of patients that they think of that they would approach about this treatment. We're excited about suprachoroidal delivery as an in-office.
administration approach that might expand the proportion of patients that clinicians would think about. And then DR really opens everything up because none of the available treatments or experimental agents where you need to repeat and jack even if very infrequently.
are going to be able to address the massive unmet need of high-risk DR patients the way that a one-time administration could.
I was thinking as you were talking about the conversation you had at Angio with Charlie and Peter Kaiser when they were presenting, I guess, the bridging study data. And I think Charlie had some remark like, I see 25 percent of the patients in my clinic right now that could potentially increase their ability to more highly analyze repearmenal channels than normal path compared to mix filtering, certainly be able to analyze anchor segments
transition over to a one-time gene therapy. And he was talking about it in that moment of having just reported the data from the bridging study, which is doses that we're studying in a pivotal phase with that commercial process. So I think we've heard themes like that from physicians as the program has evolved and emerged overall, which is it's interesting to start to hear people quantifying that now on the basis of sort of day-to-day experience in their clinic and at times when these new treatments are also finding their way to the community.
There you go, John . Thanks for the question. Thanks. Our next question comes from Ellie Murrell with UBS. Your line is open.
Hi, this is Sarah on for Ellie. Thanks so much for taking our question. I have two questions. First on super coroidal wedding D and Dr. Are you thinking that you would wait to start a pivotal program there until you move until you get data from the sub retinal phase three and sort of timelines for entering that and then
Second, for DMD, I just want to confirm if the data update that we're going to get second half is going to include microdistrofen as the biomarker or should we be expecting something else? Thanks. Thanks, Sarah. Okay. Thanks, Sarah.
I appreciate you with your questions. No, I think that we have learnings across both programs with respect to pharmacology and sort of planning for one-time gene therapy with respect to wet AMD in particular, but there's no entanglement between the execution on pivotal phase for subretinal and decisions that
are being made with respect to supercroyd. I think that point in time was at the beginning of the program, not where we are now with respect to supercroyd. Right now, supercroyd decision making is with ABB and Regenix Bio, you know, in a place where it's looking at the data, it's coming out from the doses that are being explored, evaluating that clinical profile against the target product profile, independent of sub-redinal.
Second question for Duchenne, yeah, I mean for us, measures of microdistrofen are the biomarker of choice for initial assessments. And as I alluded to in an earlier question, there may be additional things at earlier time points, like three months and six months, that we may be able to bring forward. But from a biomarker perspective, I think that we view that microdistrofen measured from biopsy collection as something that will be
With the 54% expression level seen from Sireptiv's, you know, commercial manufacturing method, kind of be the bogey here for success. And then maybe one on 314. You know, I was just looking at the bridging study data, and I noticed that one of the patients in the high dose group did not receive.
of full dose at the time of the subretinal procedure. So I was just wondering if you can walk us through what happened there, like why this patient didn't get the full dose and if there's any learnings from this, thank you.
Hi, Lisa. I can take the second one. So we've had very good compliance and success with the surgical procedure across the different studies that we've done.
This was just a one-off case where the full dose wasn't administered. There was no particular need to change anything in terms of this. We're able to pick this up in this kind of a rare instance because we monitor all the cases.
throughout associated with some data that's wrapped abroad for that. I would say that there's going to be different methods. There's going to be different assessments. There's certainly some level of heterogeneity in collection. I think we want to be within the range of what I think is reasonable to have been observed on an individual basis, it's about wanting something as panel of HOW Tribe. That was our
expressing, you have to remember, regentex protein is going to be different, like D diluted, you have got elements of a functional domain that other proteins don't have. And so, you know, that could mean that that function could translate into positive clinical benefit at a different type of concentration, a different type of protein level.
And we still want to be in the range of things that we've observed in vivo interpreclinical work and that is similar to ranges of things that Syrefta and Pfizer and Solid and others who have worked in the space with AABD and Therapy of Scene. So that's where we're heading.
Thanks so much for taking my questions. Thanks a lot. Have a good one. Thank you. Our next question comes from Andreas Argyroz with Wedbush Securities. Your line is open.
Great. Hey, guys. Thanks for taking our question. Just a quick one here. KOLS we've spoken with have expressed enthusiasm around 314's impact on reducing disease worsening in DR. How are you thinking about the upcoming results and how they'll inform the decision to take it forward? And what's the bar for safety and efficacy? Hi, Andres.
Great question. The key consideration for us is we know these patients are not getting treated even though we know anti-veg F can prevent progression to vision-threatening complications So for us a one-time treatment that can decrease progression is the goal basically. Now traditionally
anti-veg apps that require repeated injections into the eye have looked at this from a certain regulatory bar of showing a certain proportion of patients who can have a two-step improvement. And we can certainly look at that, but what we've seen is that...
The overall goal is to take patients who otherwise are going to inacturably get worse over time and change that trajectory. So on average, they're getting better, not worse. So we really have an opportunity to look at this across the spectrum.
of not just the traditional approaches of decreasing the proportion of patients who have at least a two-step worsening and increasing the proportion of patients who have a two-step improvement, we're able to really look across the spectrum and see are we seeing patients improve? And I think that's an opportunity that exists for a one-time treatment where the benefit-risk of such an approach.
can really allow that. So that's what we're gonna be able to look at across now three different dose levels and look at our traditional time points that we look at six months, for example, as Ken mentioned, as an initial look, even at dose level three, to see how do we look on those traditional validated.
FDA-approvable endpoints as well as across the whole spectrum of diabetic retinopathy disease.
and points as well as across the whole spectrum of diabetic rectinopathy disease. Okay, great. Thanks for taking my question.
Thank you. Our next question comes from Manny Feruja with SVB Securities. Your line is open. Hi, good afternoon. Living Songer for Manny on the line. Just a few quick questions. I guess for the decision program, how would you expect potential for approval to impact enrollment timelines? And secondly, ahead of the MPS filing, how would you expect potential
So, you know, I think of it as more akin to hemophilia where there also have been many studies that have been ongoing in hemophilia A and hemophilia B and with different products at different stages of development, there's never been evidence of sort of interference with the ability to enroll. And I think that's been true even as studies have gone on among Sarepta and Pfizer and Solid in the past. So we don't see an impact there. I think we continue to be excited about a differentiated approach.
planning processes are. I would not expect additions to CAPEX materially. I think this would be changes in OPEX that we would observe associated with building out commercial infrastructure by way of people and other infrastructure. But we'll be able to provide more information about that once we complete the process.
Our next question comes from Caroline Palamecki with Barenberg. Your line is open.
Hi, thanks for taking the question. My first question is just asked, but I do want to ask, maybe just staying on the business side, if you can give any more guidance to, as to your expected royalty revenue for 2023, I know there were a lot of, there were several companies out there having positive results using your...
I wonder if you could tell us more about that. Thanks. Sure, Caroline. I think in 2023 we're expecting to continue to see top line royalty recognition from Zolgensma. And we also have some license revenue that's recognized from Zolgensma.
a number of agreements that we have in place that are associated with things like annual fees. But I think this guidance this year has focused on the fact that our operating plan, you know, outside of those revenues, and materially the transition of top-line revenue from the little genza right now is going to pay back the transaction that we entered into with healthcare
Certainly groups like Ultragenics and Rocket are strong performers with respect to either transitioning or in later stages of development, but we're not including any of those in our guidance today.
Thank you. That concludes our question and answer session. Thank you for your participation. You may now disconnect. Everyone have a great day.
Got it, thanks. Thank you. That concludes our question and answer session. Thank you for your participation. You may now disconnect. Everyone have a great day.
The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.
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After the prepared remarks, there'll be a question and answer session. Instructions will be given at that time. As a reminder, this call is being recorded. It is now my pleasure to introduce Chief Legal Officer Patrick Christmas. You may begin. Good afternoon, and thank you for joining us today. Earlier this afternoon, Regenexx Bio released financial and operating results for the fourth quarter of the 2020-2021 fiscal year.
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, in other words, a similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks.
NEX Bios quarterly reports on Form 10Q, which are on file with the Securities and 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, February 28, 2023, and we undertake no obligation to update any forward-looking statements we may make on this call and account new information, future events, or otherwise. Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is polemian.
today's call with a recap of our recent business highlights as well as an update on our corporate goals. Dr. Steve Fakola, our Chief Medical Officer, will then provide an update on our clinical program and business sister, our Chief Financial Officer, will provide an overview of financial results for the 24th quarter ended December 31st, 2022.
At the end of the call, we will open up the line for questions. At Regenexx Bio, our mission is to improve lives through the curative potential of gene therapy, and we are focused on developing therapies for diseases that have significant unmet needs. We continue to be a leader in gene therapy with thousands of patients who have been dosed with AAV therapeutics derived from our nav technology platform. Today we recognize that we're at the intersection of rare disease day and the final day of rare day of February . That was part of Low Vision Awareness Month.
I'm encouraged by the momentum in AAV gene therapy. With recent approvals, upcoming regulatory decisions, encouraging clinical trial outcomes, and positive signals and actions from leaders at the FDA about the importance of accelerating gene therapy development, I believe the opportunity for gene therapy, and particularly AAV therapeutics, has never been stronger.
Additionally, with our expected near-term approval goals and continued efforts from research through clinical development and commercial-ready manufacturing, I'm proud of Regenexx BioLeadership in this field. We continue to make great progress in the fourth quarter and throughout the course of the year advancing our internal pipeline as we execute our 5x25 strategy.
to advance five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. To summarize some of our program and operational highlights, we've made significant progress across our global ICARE collaboration with APPE. Enrollment is ongoing in Atmosphere and Ascent, the two pivotal trials for RGX314 for the treatment of wet AMD using subretinal delivery. The pivotal trials are expected to support a VLA filing in 2024.
Regenexx Bio's NavExpress platform process has been incorporated into these pivotal trials and is expected to be produced at our Manufacturing Innovation Center for future commercialization of RGX314. Related to that, earlier this month we presented initial data from a phase two bridging study of RGX314 using subretinal delivery where we evaluated wet AMD patients receiving RGX314 captured by our NavExpress platform process.
last quarter of 2022, supporting the emerging clinical profile and the potential of this in-office approach for one-time gene therapy. The AVE and altitude trials are ongoing. We expect to complete recent enrollment of recently announced new cohorts in these early trials in the first half of 2023.
and report additional interim data, including initial data from these cohorts, in the second half of 2023. Quickly moving over to our rare disease pipeline, we announced earlier this year that the affinity Duchenne trial of RGX202 is active in recruiting patients. Duchenne is a key piece of our 5 by 25 strategy and represents a large patient population with significant unmet need.
Our Duchenne program features a highly differentiated product candidate, including an optimized novel microdistrophin and a unique AAV8 capsaid, which has the potential to improve muscle strength, motor function, and increase access to gene therapy for boys with Duchenne. We are also starting our trial using our proprietary commercial scale CDMP NavExpress manufacturing process.
that has demonstrated increased security and yield, and that we believe will support efficient advancement from the clinic to commercial readiness. Today we announce that we expect to report initial data from the Affinity Duchenne trial in the second half of this year. And I mentioned there now express prototype form process in the commercial scale, manufacturing innovation center, represent key differentiators for a genx file that we're using across our entire clinical trial pipeline, to support accelerating the development of AAV therapeutics.
Our Pivotal program for RGX-121 for the treatment of MPS-2 or Hunter Syndrome also is expected to incorporate our NAV express drug product manufactured at our Manufacturing Innovation Center to support future commercialization. And today we announce that the campsite trial, the Pivotal trial,
is expected to complete enrollment in the first half of 2023 to support a BLA filing in 2024 using the accelerated approval pathway. We had multiple presentations last week at the 2023 World Symposium where we certainly provided positive updates from trials associated with RGX121 as well as RGX111 in severe MPS1 or Herler syndrome.
and treatments that we're developing for CLN to form a baton disease, all of which Steve will review in greater detail momentarily. We expect to share additional updates on baton, curler, and the Hunter program plans and clinical progress throughout 2023. With that, I'm going to turn the call over to Steve so he can review in more detail our clinical progress. Thank you, Ken. I'll begin with an update on RGX 314, which is being developed in collaboration with AppV to treat wet AMD and diabetic retopathy. RGX 314 uses the Nav AAVA vector to deliver a gene and coating a therapeutic antibody fragment.
to inhibit vascular endothelial growth factor or VEGF. WED-AMD is the leading cause of vision loss in people over 60, affecting more than two million patients in the US, Europe , and Japan. The current standard of care for WED-AMD patients are anti-VEGF treatments, which require patients to receive frequent injections in the eye. Real-world evidence shows that patients with WED-AMD are severely under-treated due to the unsustainable treatment burden of these frequent injections. As a result, the majority of WED-AMD patients experience significant vision loss over time.
Last quarter, we presented positive data from the Phase 1-2a long-term follow-up study of RGS314 for the treatment of wet AMD using subretinal delivery at the AAO annual meeting that was held in October . We expect this trial, along with our two ongoing pivotal trials, Atmosphere and Ascent, to support our planned BLA submission in 2024. As Ken mentioned, we also presented data from the Phase 2 pharmacodynamic bridging study of RGS314 for the treatment of wet AMD using subretinal delivery at the angiogenesis conference earlier this month. The data demonstrated that RGS314 produced by the NavExpress...
levels being used in the two pivotal trials. We also continue to advance to additional RGF 314 programs for the treatment of WEDAMD and diabetic retinopathy using in-office supercroydal delivery. Last quarter we announced new data from the Phase 2-ABA trial.
a randomized dose escalation study evaluating RGX 314 in subjects with WEDA-MD. We also announced the expansion of this trial to further explore the third dose level in a fixed cohort with a short course of prophylactic ocular steroids following RGX 314 administration to potentially prevent the observed incidence of mild to moderate IOI. Patients are being enrolled in cohort 6.
regardless of NAF status. Moving to RGX 314 for the treatment of diabetic retinopathy. DR is a complication of diabetes and is the leading cause of blindness in adults between the ages of 24 to 75 and affects an estimated 27 million patients worldwide. DR is a slowly progressing disease that can lead to vision threatening complications, including diabetic macular or DMA and theovascularization that can lead to blindness. Like in wet AMD patients with DR are treated with anti-VATGF therapy.
which is proven to reduce the risk of developing vision-threatening complications. However, due to the unsustainable treatment burden of frequent anti-bedjet injections, many patients with this condition either elect to forego treatment or put off receiving any treatment until symptoms become unavoidable. We believe a one-time gene therapy like RGS 314 could potentially overcome this hurdle and provide an important therapy for DR patients.
to significantly alter their disease progression. In November , we announced new data from altitude our randomized controlled dose escalation phase 2 trial evaluating supercaroidal delivery of RGS 314 in patients with DR at the Retina Society annual meeting. We also announced that we expanded that trial to include a higher third dose level with patients stratified by DRSF levels.
across cohorts, and all receiving a short course of prophylactic ocular steroids following RGX314 administration to potentially prevent the observed incidents of mild IOI. Shifting to our rare disease portfolio, RGX202 is our potential one-time gene therapy for the treatment of Duchenne, being developed as a highly differentiated product designed to deliver a transgene for a novel microdistrofen that includes the functional elements of the CT terminal or CT domain found in naturally occurring distrofen.
In preclinical studies, the presence of the CT domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice models. Additional design features, including codon optimization and reduced CPG content, have the potential to improve gene expression, increase translational efficiency, and reduce immunogenicity. RGS202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle.
using our NAV AAV8 vector and a well-characterized muscle-specific promoter. In January , we announced that our Phase 1-2 affinity Duchenne trial is active and recruiting and will assess the safety and tolerability of RGX-202 as well as microdistrofen protein expression levels, muscle strength and functional measures, and muscle MRI in patients with Duchenne. We are on track to dose our first patient in this trial using commercial-scale CGMP
are two programs for mucopolysaccharide doses.
RGX-121 for NPS-2 and RGX-111 for NPS-1. Last week, represented positive data from both programs at the 2023 World Symposium.
Additional positive interim data from the Phase 1, 2, 3 campsite trial of RGX-121 for MPS2 showed patients in cohort 3 using the Pivotal Program dose continue to demonstrate the largest reduction in CSF gag and these patients continue to approach normal levels at week 48. As a reminder, Heparin sulfate or HS and D2S6
component of HF closely correlated with severe NPS2 are gags that are key biomarkers of I2F enzyme activity and are being measured in the CSF at baseline and after administration of RGX-121. CSF gags have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in NPS2 disease under the accelerated approval pathway, as builds up of gags in the CSF event, PS2 patients correlates with clinical manifestations, including neurodevelopmental deficits. Additionally, patients demonstrated continued improvement in
Patients demonstrated positive IJWA biomarker activity in the CNS and encouraging continued neurodevelopmental skill acquisition as measured by age and developmentally appropriate validated instruments for neurodevelopmental testing. Following these two programs, we are also developing two programs to help treat the manifestations of...
of this year. And late last year, a patient was dosed under a single patient investigator-initiated study of RGX181 in Brazil. To conclude, we have made significant progress with data updates and trial progression across all of the programs in our pipeline.
as we continue working toward our goal of 5 by 25. As Ken mentioned, today is Rare Disease Day and February is Low Vision Awareness Month. And I'd like to take this opportunity to acknowledge the patients, caregivers, investigators, and physician partners who participate in our work. Without them, our progress in advancing our programs with the goal of delivering the curative potential of gene therapy.
simply would not be possible. And with that, I would like to turn the call over to this to review our financial guidance. This. Thank you, Steve. The Genics BioN of the quarter-year on December 31, 2022, with cash, cash equivalents and marketable securities totaling $565 million.
compared to $849 million as of December 31, 2021. The decrease was primarily driven by cash used to fund operating activities and capital expenditures in 2022. R&D expenses were $242 million for the year ended December 31, 2022 compared to $181 million in 2021. The increase was primarily attributable to personal costs.
and expenses associated with clinical trials and manufacturing related activities for lead private candidates. And with partially offset by Vigenix 314 development costs reimbursable by ABBY under eye care collaboration. In accordance with the collaboration agreement, Vigenix Bio was responsible for the funding of certain ongoing clinical trials for Vigenix 314 through the end of 2022, while other RGX 314 development costs were shared with ABBY.
ABBYY will be responsible for funding the majority of all RGX314 development expenses. We expect a balance in cash, cash equivalents, and marketable securities of $565 million as of December 31, 2022 to fund our operations into 2025. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from ABBYY on the achievement of development or commercial milestones under our current
our RGX314 collaboration. With that, I will turn the call back to Ken to provide final thoughts. Thanks for that update, Sid. I'd like to reiterate that Regenexx Bio continues to perform at a very high level and is inspired by the patients, families, caregivers, and other stakeholders that we encounter every day in our journey to improve lives through the curative potential of gene therapy. In 2022, we made meaningful progress with our RGX314 trial enrollment objectives and geographic expansion planning. We also established in-house manufacturing to meet global clinical and commercial regulatory standards.
We remain committed to developing treatments for rare diseases and made significant advancements with our pipeline of treatments for diseases that we outlined such as Batten, Duchenne, Hurler, and Hunter syndrome, the latter of which we expect will support a BLA filing using the accelerated approval pathway. Our history, science, resources, people, and values combine to make us an industry leader in gene therapy and in the development of potentially groundbreaking therapies. We have an amazing team of scientists and engineers dedicated to expanding the understanding and the application of AAV vectors, applying the differentiated capabilities of the nav technology platform, and exploring opportunities to generate new innovative AAV therapeutics that have the potential to significantly impact patients' lives. We look forward to 2023 with a number of important updates.
on all of our research and clinical stage programs. With a balance sheet to fund our mission and operations into 2025, I believe we have a clear and definable path to achieve 5x25, the vision, and continue to lead what's possible in AAV therapeutics. With that, operator, we will turn the call over for questions. Thank you. If you'd like to ask a question, please press star 11.
If your question has been answered and you'd like to remove yourself in the queue, please press star one one again. One moment while we compile the Q&A roster. And our first question comes from Gina Wang with Barclays. Your line is open. Hello, can you hear me? Yep. Hi, all. This is you on Fongina. Thank you so much for taking our question and congratulations on the progress. We have two questions. One on three 14 supercloid. And with M D and one question on DM D to two. So for on three third on three 14 the new proof vehicle or six on the dose is one 12.
So what type of data would you consider successful and will give you confidence this will be the pivotal dose? And under what condition would you consider to further escalate the dose? The second question is about DMD. So what should we expect in your data update in the second half of 2023? How many patients? And in addition to the biomarker data you just mentioned, would you report any functional endpoints? And what type of benchmark data should we use to evaluate the update? Thank you very much.
I do. Thanks a lot for those questions. I'll take them and then if you want to add me, color, let me know. I think the guidance about second half of the year, we're talking about AVN altitude updates for the trials where we're ongoing with the enrollment of the cohorts that include the prophylaxis and I think it's early to predict precisely when the updates will occur but I think that you can expect from us is sort of the normal structure of updates that we have when we get to six-month time points for cohorts in our WEDAMD and diabetic retinopathy studies. I think it's...
to early to be talking about any interpretation of the data this might do because we don't have any specific data to talk about. We obviously have a lot of benchmarking when it comes to how we made those decisions around the sub-retinal profile in terms of transitioning to pivotal. And I think in the second half of this year, when we have additional data to bring forward, we'll be able to talk to that specifically. Thanks for that question. On the two sides, I think again, we're in the process of active and recruiting study today. So we're giving guidance for second half of the year data. I think we have outlined in our clinical trial design that in the first three to six months of assessments, we're going to see things that are more weighted toward early biomarker assessments.
maybe certain types of imaging outcomes. I think some of the functional outcomes would be things that will be tracked in the studies at time points closer to maybe 9 or 12 months. So I think that's what we have in terms of the trial design. I think as we get into the second half of the year and closer to the point in time where we'll have those data updates, we'll be able to provide more information. I think in terms of benchmarking, we talked about this microdistrofen is being differentiated in the class of microdistrofen. We've talked about the C-terminal domain bringing scientific and I think interesting potential clinical opportunities for differentiation. Early on, we'll be looking at expression of that microdistrofen construct in biopsies and its effect on some of the imaging techniques that are available and we'll certainly be looking at safety.
in the first in-human examination here of RGX202. So those are the things that I think we could expect to compare to in the second half of the year. Thank you very much. Thank you. Our next question comes from Dane Leon with Raymond James. Your line is open. Thanks for taking the questions. Let's ask like probably two most popular ones that have been coming in from investors recently. The first one is...
Do you have a sense when you will have first data from the 202 program of the first patient or patient you treated with the MD? What the password will be from a clinical strategy, obviously right now. There's been discussion that Sir Reptus disclosed that they will not in fact have an ad on. So I guess thought given how their program worked out how you would approach your clinical development program. And then the second one is quite popular that.
whether in your view and your team's view 9001 infringes on your IP path in the States. Thank you. Thanks, Dave. Always appreciate your questions getting right to the point. I think until we have data, we're not going to be leaning in anymore to what exactly are paths in terms of next steps with respect to clinical development of 202R. Right now, we think we've got a great program to assess early safety, assess biomarker activity, look at functional outcomes. I think these things all fit within kind of the guidelines of programs that others have run, including the Sarepta and Pfizer who have advanced with microdistrofen class of products to later stages of development. We think we've got the benefit of playing from behind and observing some of the scientific, clinical and regulatory strategies that have been employed. We think we've got some scientific advantages. We think we have some CMC differentiation.
We've also got a CAFTA that we think addresses market access and clinical access needs. We want to get safety data. We want to get biomarker data. We want to start to see that RGX202 is demonstrating something that we view as a clinically meaningful profile. In order to do that, we'll get patients dosed and we'll be able to start reading that out in the second half of the year. With respect to our intellectual property and how it relates to other programs, I think we have talked about in the past that we have identified patents in our portfolio that we view are part of an action that we have taken with respect to Sarepta. What I can say about that is it's ongoing and that the lawyers are responsible for executing on that. When we have material updates, we'll be able to bring those forward.
But at this point, there's nothing else to say. Thank you very much. Thanks. Thank you. Our next question comes from Alex Trinahan with Bank of America. Your line is open. Hey, guys. This is John and I'm on for Alex. Just a couple of questions from us. So the first one, for your Navvex press platform, how long do you expect the transition to the new platform to be and when can we expect current products and clinical needs to be fully supported by the platform? So that's the first one. The second question on through one four. I think the last time we talked, you may just give more color on framing the market for through one four. Think assuming your targeting patients who require frequent objections and would opt in for the one-time treatment. So like what percentage of patients would you say fall into that category?
That's it for me. Thanks. Yeah, great John , appreciate the questions. I'll take the first one on that Steve Handle, the second here. So now, VIXPRESS, we got to practice the pronunciation because this is a new trademark name for us. Our platform process, that is a bioreactor process that we have actually been using at our CDMOs, but have also now installed here at scale in our rock field facility or manufacturing innovation center. And we opened that center last year, John , so we've been incorporating and designing plans to incorporate material based on the NavIXPRESS process into our RGX314 programs, both for sub-retinal pivotal, for super-croidal. We're incorporating it into RGX121, especially for the pivotal phase programs. It's important to get patient exposures with the commercial process as we complete our pivotal phase programs to support our BLAs.
When it comes to something like RGX 202, we'll actually be starting out of the gate in the clinic with that process, and that's been a point of emphasis we've been making is that we think there's going to be therefore an efficient transition through clinic and in that transition from clinic to commercial. And then with other programs that we've guided to, like program updates for RGX 111 in the second half of the year, we've said that we've already started the process of making additional RGX 111 material with the NavExpress process. So basically everything is there now. In some cases we're incorporating it into late stage execution. In other cases we're beginning clinical trials and clinical investigation with that process, and we think that this is very important to be at this stage, have a high quality, high purity, high yield process, and one that's very reproducible. So thanks for that. I'll let Steve talk about 314 market.
Hi John , Steve here. Yeah, a common question of thinking how to segment or think about the spectrum of WEDA-MD and diabetic retinopathy patients. On the WEDA-MD side, you raise the point of more, those patients who are more anti-fed and by a Jeff Needy and need more frequent injections. And it certainly makes sense that those who need injections every month or every two months or every three months, they have a higher burden so they may see more value. They and their caregivers may see more value than if very infrequent injections are needed. But the reality is we know across this spectrum whether you're getting injections every month or you're getting them every three or every four months.
In that setting, when we talk to clinicians, there's a subset of patients that they think of that they would approach about this treatment. We're excited about supercaroidal delivery as an in-office administration approach that might expand the proportion of patients that clinicians would think about. And then DR really opens everything up because none of the available treatments or
experimental agents where you need to repeat inject even if very infrequently are going to be able to address the massive unmet need of high risk DR patients the way that a one-time administration could. Yes, Steve, I was thinking as you were talking about the conversation you had at Angio with Charlie and Peter Kaiser when they were presenting I guess the bridging study data and I think Charlie has some remark like I see 25% of the patients in my clinic right now that could potentially transition over to a one-time gene therapy and he was talking about it in that moment of having just reported the data from the bridging study which is doses that we're studying in a pivotal phase with that commercial process.
I think we've heard themes like that from physicians as the program has evolved and emerged overall, which is, you know, it's interesting to start to hear people quantifying that now on the basis of sort of day-to-day experience in their clinic and at times when these new treatments are also finding their way to the clinic these days. There you go, John . Thanks very much.
I was deemed like that from physicians as the program has evolved and emerged overall, which is, you know, it's interesting to start here, people quantifying that down on the basis of sort of day-to-day experience in their clinic and at times when these new treatments are also finding their ways to the clinic these days. There you go, John . Hey, thank you. Thank you so much. Thank you. Thank you.
Thank you. Our next question comes from Ellie Murrell with UBS. Your line is open. Hi, this is Sarah on for Ellie. Thanks so much for taking our question. I have two questions. First on supercaroidal wet AMD and DR. Are you thinking that you would wait to start a pivotal program there until you move, until you get data from the subretinal phase three sort of timelines for entering that? And then second for for DMD, I just want to confirm if the data update that we're going to get second half is going to include microdistrofen as the biomarker or should we be expecting something else?
Right now, supercoil decision making is with AbbVie and Regenexx Bio in a place where it's looking at the data that's coming out from the doses that are being explored, evaluating that clinical profile against the target product profile independent of subretinol.
Second question for Duchenne. Yeah, I mean for us, measures of microdistant are the biomarker of choice for our initial assessments. And as I alluded to in an earlier question, there may be additional things that earlier time points that like three months and six months that we may be able to bring forward. But from a biomarker perspective, I think that we view that microdistant measured measuring interested in measurement data. Yet as I discussed this, I believe that if Allies did things within these könnte law ? apert, it was us using internet, but was practically rätt.
thumbs, Luca. Maybe just another one on DMD on the microdictive and biomarker. With the 54% expression level seen from Syrective, you know, commercial manufacturing method, kind of be the bogey here for success.
maybe just another one on D&D on the microdischiv and biomarker. With the 54% expression level seen from Syrective, you know, commercial manufacturing method, kind of be the bogey here for success. And then maybe one on. And uh.
314. You know, I was just looking at the bridging study data and I noticed that one of the patients in the high dose group did not receive a full dose at the time of the sub retinal procedure. So I was just wondering if you can walk us through what happened there, like why this patient didn't get the full dose and if there's any learning from this. Thank you.
Hi, Lisa. I can take the second one. So we've had very good compliance and success with the surgical procedure across the different studies that we've done. This was just a one-off case where the full dose wasn't administered. There was no
particular need to change anything in terms of this. We're able to pick this up in this kind of a rare instance because we monitor all the cases. So we have a trainer at every single surgical case and then also the same for our SES super crow-ito delivery.
And with Lisa, your first question about, I guess, you know, the number that you threw out associated with some data that's wrapped up raw for that, I would say that, you know, there's going to be different methods, there's going to be different assessments.
of seen in animals and the translatability of that because we're getting good responses in the model in human. So I don't know that I go to a specific number though because I also think that when we're talking about the amount of protein that we may be expressing, you have to remember.
Regenexx protein is going to be different, like Steve alluded to. It's got elements of a functional domain that other proteins don't have. And so, you know, that could mean that that function could translate into positive clinical benefit at a different type of concentration, a different type of protein level.
And we still want to be in the range of things that we've observed in vivo, interpreclinical work, and that is similar to ranges of things that Syretta and Pfizer and Solid and others who have worked in the space with AABD and Therapy have seen. So that's where we're heading. Thanks so much for taking my question.
Thanks a lot. Have a good one. Thank you. Our next question comes from Andreas Argorad with Web with Securities. Your line is open. Great. Hey guys, thanks for taking our question. Just a quick one here. K. Wells, we've spoken with, have expressed enthusiasm on around 314's impact on reducing disease worsening in DR. How are you thinking about the upcoming results and how the long form of the decision to take you forward and what's the bar for safety and efficacy? Hi, Andreas.
Great question. The key consideration for us is we know these patients are not getting treated even though we know anti-bed-jap can prevent progression to vision-threatening complications. So for us a one-time treatment that can increase
The progression is the goal, basically. Now traditionally, anti-bed jobs that require repeated injections into the eye have looked at this from a certain regulatory bar of showing a certain proportion of patients who can have a two-step improvement. And we can certainly look at that, but what we've...
seen is that the overall goal is to take patients who otherwise are going to inaxeorably get worse over time and change that trajectory. So on average, they're getting better, not worse. So we really have an opportunity to look at this across the spectrum of not just the traditional approaches of decreasing the proportion of patients who have at least a two-step worsening and increasing the proportion of patients who have a two-step improvement.
we're able to really look across the spectrum and see, are we seeing patients improve? And I think that's an opportunity that exists for a one-time treatment where the benefit-risk of such an approach can really allow that. So that's what we're gonna be able to look at across now three different dose levels and look at our traditional time points that we look at, six months for example, as Ken mentioned, as an initial look, even at dose level three to see how do we look on those traditional validated.
FDA-approvable endpoints as well as across the whole spectrum of diabetic retinopathy disease. Okay, great. Thanks for taking my question. Thank you. Our next question comes from Manny Furuhar with SVB Securities. Your line is open. Hi, good afternoon. Nithin Songho from Annie on the Line.
Just a few quick questions. I guess for the decision program, how would you expect potential for approval to impact enrollment timelines? And secondly, ahead of the MTS filing, how should we think about the build up for the commercial infrastructure in terms of impact on CAPEX and OPEX? Thanks for the questions.
stages of development, there's never been evidence of sort of interference with the ability to enroll. And I think that's been true even as studies have gone on among Syretha and Pfizer and Solid in the past. So we don't see an impact there. I think we continue to be excited about a differentiated profile.
following some of these other medicines in the class into the clinic towards commercialization. With respect to MPS II, I think we'll be in a position to talk in the second half of the year as we update on program plans overall and come into 2024 with that BLA filing in focus about what the pre-commercial and commercial planning processes are. I would not expect additions to CAPEX materially.
changes in OPEX that we would observe associated with building out commercial infrastructure by way of people and other infrastructure. But we'll be able to provide more information about that once we complete the milestones of full enrollment of the pivotal and complete the work that we're doing to prepare for the VLA filing. Thank you. Thanks. Thank you. Our next question. Okay. Thank you. Our next question is from
comes from Caroline Palamecki with Barenberg. Your line is open. Hi. Thanks for taking the question. My first question was just asked, but I do want to ask, maybe just saying on the business side, if you can give any more guidance to as to your expected royalty revenue for 2023. I know there were a lot of, there were several companies out there that were having positive results using your AAB vector. I just wonder if you could tell us more about that. Thanks. Sure, Caroline. I think in 2020,
The transition of top line revenue from the old Genema right now is going to Payback the transaction that we entered into with healthcare royalty partners the $200 million financing we did A couple of years ago, so we don't use that to continue to build out the balance sheet We have that cash on hand already Yeah, I think we do see some other things on the horizon in terms of
potential product approvals. We outlined some of this in the press release today. Certainly groups like Ultragenics and Rocket are strong performers with respect to either transitioning or in later stages of development, but we're not including any of those in our guidance today.
Thank you. That concludes our question and answer session. Thank you for your participation. You may now disconnect. Everyone have a great day.