Q3 2024 REGENXBIO Inc Earnings Call
Welcome everyone to the Q3 2024 Regenix Bio Ernest Conference call. At this time, I'll participate on a listening mode.
After the speaker's presentation there will be a questioning and succession.
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Speaker Change: Please be advised that today's conference is being recorded. At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer, a regional expio. Please go ahead.
Speaker Change: 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 uncertainty that may cause actual results to differ from those forecasted.
Speaker Change: and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, in other words, of similar meaning.
These such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties.
These risks are described in the risk factors.
Speaker Change: In the Management's Discussion and Analysis section, Regenexx Bio's annual report on Form 10-K for the full year ended December 31st, 2023, and Comparable Risk Factor sections of Regenexx Bio's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.
Speaker Change: Any information we provide on this conference call is provided only as of the date of this call, November 6, 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.
Speaker Change: Please be advised that today's call is being recorded and webcast. In addition, any unaudited or proforma financial information that may be provided is preliminary and does not afford to project financial positions or operating results of the company. Actual results may differ materially.
Speaker Change: I will now turn the call over to Curran Simpson, President and CEO of Regenexx.com
Curran Simpson: Thank you, Patrick, and thank you everyone for joining us today. On the call with me today are Mitchell Chan, our newly appointed Chief Financial Officer, and Dr. Steve Pakola, our Chief Medical Officer.
Speaker Change: I will begin by recapping our business highlights and key upcoming milestones.
Speaker Change: Steve will then provide an update on our clinical programs before passing to Mitch, who will review our financial results for the quarter.
Speaker Change: I'll then provide some closing remarks and open the call for Q&A.
Speaker Change: This is a very exciting time for Regenexx Bio as we continue to generate positive clinical data and prepare to commercialize multiple potential first and best-in-class gene therapies.
Speaker Change: We've had another productive quarter and have several important milestones expected before year-end.
Speaker Change: These include the first functional data from our Duchenne program, which is expected in the coming weeks.
Christmas: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Christmas: We're also very excited to have initiated the BLA filing in MPS 2.
Speaker Change: also known as Hunter Syndrome.
Speaker Change: and for the end of phase two meeting coming up later this month for RGX 314 in diabetic retinopathy, which we'll refer to as DR.
Speaker Change: Recall that this meeting was accelerated from first quarter 2025 to fourth quarter 2024 by AbbVie, our partner for the Retino franchise.
Speaker Change: You'll hear more from Steve about the great progress being made in 3.14 including continued progress in DR and wet AMD.
Speaker Change: Diving into our programs, I'll start with RGX202, our next generation potential best-in-class gene therapy for Duchenne.
Speaker Change: We expect to initiate the pivotal phase of the ongoing Affinity Duchenne study imminently.
Speaker Change: Once that has begun, RGX202 will be the only next-generation gene therapy in phase 3 study for this devastating disease.
Speaker Change: We've had productive discussions with the FDA as we have advanced RGX202 to pivotal phase.
Speaker Change: and have confirmed that the Accelerated Approval Pathway remains open to us.
Speaker Change: RGX202 continues to demonstrate the potential to drive increased benefit to patients compared to available therapies and our clinical data to date are checking all the boxes to demonstrate this differentiation.
Speaker Change: Thus far we have seen a favorable safety profile, no SAEs, and consistent robust microdystrophin expression.
Speaker Change: The last box to check is Functional Outcomes, which, as I mentioned, we will begin sharing this month.
Speaker Change: Earlier this year we shared encouraging early functional observations from clinic and caregiver videos.
Speaker Change: We're excited to share the first functional results, which will include data on some of these patients from dose level 1 and 2 at later, more meaningful time points very soon.
Speaker Change: Another key element of differentiation, we believe, is the fact that we are commercial ready when it comes to manufacturing RGX-202 today, which can be a key driver of an effective commercial launch.
Speaker Change: Our manufacturing uses a modern, suspension-based bioreactor process.
Speaker Change: that is highly productive.
Speaker Change: Needless to say, we are very excited about RGF202 as a potential best-in-class gene therapy in Duchenne and continue to aggressively accelerate development to potentially be second to market.
Speaker Change: Let's now pivot to RGX 121, the program furthest in development.
Speaker Change: RGX 121 is on track to be the first gene therapy and one-time treatment for MPS2 or Hunter syndrome.
Speaker Change: Today, as we announced, the first module of a rolling BLA for RGX 121 was submitted as planned in Q3 2024.
Speaker Change: and we expect to complete filing the BLA in the first quarter of 2025.
Speaker Change: Like Duchenne, MPS2 occurs in boys and is a progressive devastating disorder.
Speaker Change: Also like Duchenne, we are pursuing a BLA under the Accelerated Approval Pathway and would receive a PRV upon regulatory approval.
Speaker Change: The initiation of our BLA marks a major milestone for patients, for whom there is currently no cure and no treatments to address the significant neurocognitive decline.
Speaker Change: It also marks a major milestone for Regenexx Bio as RGX-121 represents both our first potential commercial product and an opportunity to build commercial infrastructure that will benefit our other programs, those in line for commercialization.
Speaker Change: Lastly, I will make a few comments on RGX 314, the late-stage retinal franchise we are developing with our partner AbbVie.
Speaker Change: As you'll hear from Steve, we continue making great strides across multiple indications.
Speaker Change: The recent positive news from our fellow eye study offer an opportunity to expand the addressable patient population for 314 in wet AMD where the majority of patients eventually develop bilateral disease.
Speaker Change: and the data and progress we are making in DR, another large commercial opportunity is highly encouraging.
Speaker Change: In D.R. we expect to initiate a global pivotal trial in the first half of 2025.
Speaker Change: We are excited that we will soon have both programs, WET-AMD and DR.
Speaker Change: in Phase 3 studies.
Speaker Change: We look forward to continuing to work with AbbVie to tap the potential of 314 to prevent vision loss for millions worldwide.
Speaker Change: In summary, we are making excellent progress and look forward to sharing several important catalysts in the coming weeks.
Speaker Change: and continue to see clinical results supporting the immense potential of these novel programs.
Speaker Change: With that, I would like now to turn the call over to Steve for an update on our clinical programs.
Steve Pakola: Thank you, Curran.
Steve Pakola: I'll start with RGX202, a potential one-time gene therapy for the treatment of Duchenne.
Speaker Change: Today, we announce exciting progress in the Phase 1-2 affinity Duchenne trial.
Speaker Change: This is a multi-center dose escalation and dose expansion clinical study to evaluate the safety, tolerability, and clinical efficacy of a one-time dose of RGX202 in patients with Duchenne H1211.
Speaker Change: As we approach pivotal phase, I'm pleased to share that we have dosed the last patient in the expansion cohort of dose level 2, which is the pivotal dose level.
Speaker Change: On the continued strength of our data, we expanded the Affinity Duchenne trial to include a new cohort of patients aged 1 to 3 years.
Speaker Change: and today we announce that the first patient has been dosed in this cohort. The 1 to 3 age group represents a significant portion of the prevalent population. Yet this group has no access to approved or investigational gene therapy.
Speaker Change: In the U.S., Regenexx Bio is the only company recruiting patients under 4 years old.
Speaker Change: We look forward to initiating the pivotal study and sharing the first functional data from this program in the coming weeks.
Speaker Change: Now on to updates from our retina franchise, RGX314, which is being developed in collaboration with AbbVie to treat wet AMD and DR via subretinal and supracaroidal routes of administration.
Speaker Change: I'll start with 314 for DR being evaluated in the Phase 2 Altitude Trial using in-office supracoroidal delivery.
Speaker Change: Like what AMD, DR is a progressive disease that causes vision loss and ultimately blindness if not treated appropriately.
Speaker Change: It is a leading cause of blindness in working age adults.
Speaker Change: As we've shared with our partner AbbVie, we have accelerated the end of Phase 2 meeting with the FDA to this quarter.
Speaker Change: We look forward to completing this meeting and sharing our proposed pivotal trial program soon.
Speaker Change: As you may recall, we previously expanded the broad multi-indication global potential
Speaker Change: of 314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema or DME, a vision-threatening complication of diabetic eye disease that impacts more than 30 million patients worldwide.
Speaker Change: 314 is already well positioned to potentially become the standard of care to treat diabetic retinopathy. Broadening the altitude trial to include patients with DME further expands the global potential to benefit more patients.
Speaker Change: In WET-AMD, we are evaluating 314 via two different routes of delivery, subretinal and supracaroidal. Within subretinal, we have two ongoing pitheral trials, atmosphere and ascent.
Speaker Change: in North America, Europe, and Japan.
Speaker Change: These trials continue to progress well, and global regulatory submissions remain planned for the first half of 2026.
Speaker Change: We recently announced exciting news from our Phase 2 fellow eye study of subretinal 314 in patients with bilateral wet AMD.
Speaker Change: This study is the first of its kind evaluating a potential one-time gene therapy as a treatment for patients with bilateral disease.
Speaker Change: The positive data demonstrated 3.14 at the same dose being evaluated in the pivotal program was well tolerated with no cases of intraocular inflammation.
Speaker Change: We also see continued impressive efficacy, including a 97% reduction in treatment burden at 9 months. 100% of patients needed 0 or 1 supplemental injections.
Speaker Change: and 78% of patients were completely injection-free while demonstrating sustained vision stability and disease control.
Speaker Change: Notably, these positive results were seen in difficult-to-treat patients with high treatment burden prior to 314.
Speaker Change: The fellow eye study supports plans for a label inclusive of bilateral use representing a meaningful option for the significant number of patients with wet AMD in both eyes.
Speaker Change: Overall, we continue to be encouraged by the progress on our RITML programs.
Speaker Change: I'd like to particularly highlight the safety profile observed, including in our supracaroidal programs.
Speaker Change: We are confident in advancing the pivotal phase because of this safety profile, particularly in the setting of short-course, seven-week prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials.
Speaker Change: In more than 180 patients treated in office, we're seeing a differentiated safety profile representing a meaningful potential treatment option for patients and physicians.
Speaker Change: Finally, on RGX 121 being developed for the treatment of NPS 2.
Speaker Change: Earlier this year we announced that the Campsite Pivotal trial met its primary endpoint with high statistical significance.
Speaker Change: Patients treated with RDX-121 achieved decreased CSF levels of heparin sulfate D2S6, a key biomarker of brain disease activity, to below maximum attenuated disease levels.
Speaker Change: Our BLA uses the accelerated approval pathway and is based on D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit.
Speaker Change: We also previously reported that 80% of patients who received the pivotal dose discontinued enzyme replacement therapy or remained treatment-naive.
Speaker Change: This is a meaningful update for patients and families whose only option today is weekly enzyme replacement therapy that does not address the neurocognitive decline of this disease.
Speaker Change: RJX121 is well positioned to be the first gene therapy and one-time treatment for Hunter syndrome that can directly address neurocognitive decline.
Speaker Change: To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline.
Speaker Change: Lastly, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who have been involved in and supported all of these trials.
Speaker Change: And with that, I'll turn the call over to Mitch to review our financial guidance. Mitch.
Mitch: Thank you, Steve. RegenixFile ended the quarter on September 30th, 2024 with cash, cash equivalents, and marketable securities of $279 million compared to $314 million as of December 31st, 2023.
Speaker Change: during a nine-month-ended September 30th.
Speaker Change: 2024, partially offset by $131 million.
Speaker Change: and Net Proceeds received from an upsized public offering, a common stock and pre-funded warrant completed in March 2024.
Speaker Change: R&D expenses were $54 million for the third quarter of 2024 compared to $58 million
Speaker Change: for the third quarter of 2023. The decrease was primarily due to decreases in headcount and preclinical activities. Returning SPIO expects this cash balance, cash equivalents and marketable securities of $279 million.
Speaker Change: as of September 30th, 2024 to fund his operation into 2026.
Speaker Change: This cash runway guidance is based on the company's current operational plans and excludes the impact of any payment that may be received from AVI upon the achievement of development or commercial milestones under our RTX 314 collaboration.
Speaker Change: Additionally, our runway guidance excludes the potential monetization of a priority review voucher that may be received for RGX 121.
Speaker Change: With that, I will turn the call back to Curran.
Speaker Change: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Curran Simpson: Thanks Mitch. As you heard, we are making significant progress advancing each of our late-stage programs in multiple large commercial opportunities.
Curran Simpson: and are heading into year-end with strong momentum and multiple de-risking events.
Curran Simpson: To recap, in Q4 of this year, we plan on initiating a pivotal trial for RGX-202 under an accelerated approval pathway and look forward to sharing both the trial design and our first functional data.
Speaker Change: Also in Q4 of this year, we will complete our End of Phase II meeting with the FDA for 314 in DR.
Speaker Change: This will pave the way for initiation of the first global pivotal trial in the first half of 2025 and trigger milestones in our collaboration with AbbVie.
Speaker Change: Finally, we will continue the progress of the rolling BLA submission for RGX-121 and expect to complete the submission in Q1 2025.
Speaker Change: If approved, this would become the first approved gene therapy for treatment of Hunter Syndrome, a very meaningful development for the patients and families living with this devastating disorder, and would receive a PRV upon regulatory approval.
Speaker Change: It has been a turning point year for us.
Speaker Change: As we look toward the next 12 months and beyond, we see a company that is positioned to deliver on multiple late-stage opportunities.
Speaker Change: The groundbreaking science that underlies our programs is demonstrating differentiation against standard of care and available treatments.
Speaker Change: Each of our programs represent one-time treatments with the potential to transform the trajectory and management of disease for patients in need of new and better options.
Speaker Change: and we look forward to continued momentum in achieving the important milestones in the last quarter of this year and beyond.
Speaker Change: With that, thanks to everyone for your time today. I'll turn the call over for questions. Operator?
Speaker Change: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced.
Speaker Change: To withdraw your question, please press star 11 again. We ask that you please limit yourself to one question and one follow-up. Please stand by while we compile the Q&A roster.
Speaker Change: Our first question comes from the line of Gina Wang with Barclays. Your line is now open.
Speaker Change: Hi, it's Tony on for Gina. Quick questions on DMV for the age 1-3 year old cohort. Are there any concerns there on durability given the patients are
Speaker Change: still young and may be growing additional muscle tissue. And then if you all do receive biomarker approval.
Speaker Change: color approval. Would multiple time points be needed for a biopsy versus just one time point at three months? And then also for the data at the year end, how should we think about the magnitude of functional change?
Speaker Change: Hi, Tony. Steve here. Thanks for the questions. So I'll start with your question about the one- to three-year-olds. Yeah, it is a topic that comes up in the field of how young can you go in terms of
Speaker Change: the issue of replicating cells.
Speaker Change: We're actually quite
Speaker Change: excited about the opportunity here when we think of AV8, our vector, because we we have a proxy for considering the potential dilution effect of dividing cells and durability because we know AV8
Speaker Change: for liver-directed hemophilia treatment. We actually have durability now out beyond 12 years for a lot of
Speaker Change: These kids where we see very sustained activity and of course liver cells divide So that gives us a lot of confidence here as well
Speaker Change: and certainly there's a major unmet need here because there are no gene therapies currently available for this age group.
Speaker Change: Hi Tony, to your other question around biomarker, we don't have any requests for additional biomarker data beyond what's included in the protocol.
Speaker Change: So I wouldn't expect anything additional to be requested there. And I think to answer your question about magnitude of effect...
Speaker Change: There are benchmarks for what people consider magnitude of effect to be adequate for consideration for approval, including the benchmarks we can pull from even Peter Marx's assessment of Leviticus.
Speaker Change: And so I think that sets a good precedent for our data that will be coming shortly and how we're thinking about the program. And I think just to reiterate, we're super excited by the biomarker data that we've got in terms of the levels of microdystrophin we're seeing.
Speaker Change: especially in the eight and older patient population that up front looks considerably higher than other programs. So thanks for your question.
Speaker Change: Thank you so much.
Speaker Change: Thank you. Our next question comes from the line of Vikram Purwitt with Morgan Stanley. Your line is now open.
Gaspo: Hi, everyone. This is Gaspo for FICM. We have one question on RGX202. Could you recap for us your latest view on how best to gauge the functional data we are expecting later this month? Thank you.
Speaker Change: Hi, Gospel. Thanks for the question. We're very excited to.
Speaker Change: who will soon be
Speaker Change: able to present our functional data is something we've been looking forward to. I think we come with the benefit of a lot of precedent and a lot of learnings in the space.
Speaker Change: where we get to look at the totality of the data. So, a lot of the usual suspects that you'll be aware of, certainly the time function tests,
Speaker Change: such as 10-meter walk run or time to stand, which are measures that we know are valid, clinically meaningful. We'll also look at NSAA, which historically has been looked at.
Speaker Change: and we have the opportunity as well to look at caregiver reported outcomes. So it's really a unique chance for us to look at a lot of different ways to see how these boys are doing to really assess clinical benefit.
Speaker Change: and Gospel, I would also point to our ability to look at external controls as we think about individual patient data. We can mine pretty substantial databases to look at what the natural history is and expect to include that as part of our analysis, but thanks for the question.
Speaker Change: Thank you very much.
Speaker Change: Thank you. Our next question comes from the line of Manny Farouhar with Leverink Partners. Your line is now open.
Manny Farouhar: Thanks for taking my question. I guess a little more detailed question. So when you think about the data we're going to see from this initial group of patients, is it reasonable to expect that their experience
Speaker Change: and follow-up and data will be rolled into a larger pool of data collectively per a pivotal data set or will a future pivotal data set include the inpatient recruited in the future not including these first-hand full of patients and I have a quick follow-up.
Speaker Change: Thanks for the question, Lonnie. Yes, we certainly do expect to use data that was is being accumulated in our phase 1-2 study, particularly for patients that were dosed.
Speaker Change: at Dose Level 2. I'd say most of the functional assessments that we're doing for those patients will be the same as what we're doing in Pivotal. And I think one area I would point out that we're really excited about in terms of transitioning
Speaker Change: from Phase 1-2 to Pivotal is that the process and product quality will be the same through Phase 1-2 development and Pivotal development. And so if you were to think back to the ADCOM or Sarepta, they made a major process change.
Speaker Change: in the middle of their Pivotal program.
Speaker Change: and you could see comparisons of process A and process B.
Speaker Change: We won't have any of that and I think that will work well in terms of including
Speaker Change: those patients in our safety database because the product profile is the same throughout the study. So we do intend to leverage them as part of that, and that will obviously help us with
Speaker Change: recruitment, and we'll talk further, very near term, about the details of the pivotal study. I'll turn it over to Steve to comment as well. Yeah, I just wanted to elaborate on one aspect that further supports the ability to use the patients.
Speaker Change: already dosed in phase 1-2 is...
Steve Pakola: The primary endpoint for accelerated approval is microdystrophin. So, it makes perfect sense that the data that we have, particularly with dose level 2, that it's quite natural that we'd be able to use that data in addition to the patients we enroll in the future in the pivotal.
Speaker Change: That's helpful. I'm going to hop over to Ophthalmology for a follow-up, if that's okay. You guys have disclosed...
Speaker Change: for achievement of first-patient dose in a pivotal superchoroidal delivery treatment of DR. Can you walk us through on what timeline we might see milestones following your end-of-phase-II meeting and how those would be recognized, i.e., how they would flow through the financial statements, when they'd show up on the balance sheet for his income statement, etc., just to clear that up for our own modeling?
Speaker Change: Sure, Monty. I'll turn that question over to Mitch.
Mitch: Yeah, so for modeling purposes, the protection milestone payment could actually show up in the balance sheet. That's where you can actually account for that. And for P&L, this will be recognized as a one-time, non-recurring for obvious reasons, one-time payment there.
Speaker Change: Hopefully that helps from that standpoint.
Speaker Change: https://www.kennethmills.com
Speaker Change: So the recognition will all be recognized in the same quarter it is received, or is this something that will be recognized radically over time?
Speaker Change: No, it's going to be upon receival. Okay, thanks guys. I'll hop off. I know you've got a lot of analysts waiting in line.
Speaker Change: Thank you. Our next question comes from the line of Annabelle Samimi with Stiefel. Your line is now open.
Speaker Change: https://www.kennethmills.com Christmas is coming.
Speaker Change: Hi, this is Jack on for Annabelle. Thanks for taking our questions.
Speaker Change: So, for 202, I believe you've mentioned previously that you were considering imposing a minimum threshold of microdystrophin expression on yourselves in the pivotal trial, even though that might not be something that the agency would necessarily require. I think the number was something maybe like 10% expression for approval. Is that something that you still feel confident in doing, and have you ever discussed that with the FDA?
Speaker Change: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Stephen Pakola,
Speaker Change: Wife
Speaker Change: in the future, in the very near future. What I can say now is that concept of a 10% threshold is something that in the field has roughly been considered something to think about as.
Speaker Change: What would relate potentially to a clinically meaningful amount? Fortunately, we're seeing microdystrophin levels that are
Speaker Change: much higher than that level. So that really gives us a lot of flexibility when we think of designing a study and empowering a study. So we look forward to giving more details on that in the coming weeks.
Speaker Change: Got it. And then if I may just ask one more, one of the biggest pushbacks that we hear from investors is not necessarily around 202 microdystrophin expression or its safety, but rather just that we have a pretty small sample size to work with at the moment.
Speaker Change: So, how meaningful do you think the functional data, the upcoming functional data will be in kind of defining that profile, given it's only from a couple patients, or in other words, how well might it translate into a more general population?
Speaker Change: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Speaker Change: I think Jack that's a good question and we do have a relatively limited data set but I think
Speaker Change: What we're looking for primarily in this data set is conviction that a pivotal trial is highly likely to succeed and that we have a demonstration of efficacy. And I think that I would sort of reiterate that
Speaker Change: The fact that we have a differentiated product, we're almost threefold higher in microdystrophin levels than other programs for patients at a similar age. All of those factors...
Speaker Change: I think will come together, even with limited functional data, to, I think, especially in the patient community,
Speaker Change: bring a really strong interest in the program and allow us to enroll quickly. And so we're really excited about where we are and I think we're eagerly anticipating being able to share our results just in a few weeks around the functional data.
Speaker Change: Great, looking forward to it. Thanks guys.
Speaker Change: Christmas, Stephen Pakola, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Speaker Change: Thank you. Our next question comes from the line of Alex Stranahan of Bank of America. Your line is now open.
Speaker Change: Hi, Matthew on for Alec. Thanks for taking our questions. Two quick ones from us. For DMD, are you concerned at all about the durability of impact, especially going into younger patients? And are you at all thinking about re-dosing? And then for WET-AMD, can you provide some color on how you think about the ILEA biosimilars from Amgen and potential market impact?
Speaker Change: I'll let Steve take that. Thanks for the question.
Steve Pakola: So, the durability aspect in the younger patients was something we touched on earlier in the call.
Steve Pakola: We have evidence particularly with our serotype that there is not a dilution of
Steve Pakola: effect over time that you have good durability.
Steve Pakola: even in organs where you have dividing cells. So that's one of the aspects that...
Steve Pakola: made us excited to go after this unmet need age group of one to three, so also excited that we announced today the dosing of the first patient in that cohort. Redosing, that's
Steve Pakola: something that the field I think is going to
Steve Pakola: be evaluating over time. Right now, our focus is on first-time treatment with one-time gene therapy for
Speaker Change: the very large patient population that's out there that isn't going to be able to get treatment.
Speaker Change: for some time, even with available treatment options. We expect to have good durability, as I just mentioned, but certainly there's the opportunity for us to explore ways that we could go after redosing.
Speaker Change: that we're...
Speaker Change: We're very excited in our our pivotal programs with Subretinal in collaboration with AbbVie
Speaker Change: and also in collaboration with AbbVie, the supracroidal advancement where as just discussed we have diabetic retinopathy that we look forward to finishing our end of phase two meeting and being able to advance into pivotal development there.
Speaker Change: out.
Speaker Change: What was the other, if I could ask, what was the other aspect about the WET AMD program?
Speaker Change: Yeah, I just started thinking about Aaliyah bio-similars from... Oh, yeah.
Speaker Change: that's been around over time, and we're starting to see more biosimilars come in. We're actually seeing no impact of biosimilars on
Speaker Change: for example, some of the branded longer durability.
Speaker Change: products, you know, so if you think of
Speaker Change: incremental benefits in terms of durability of high-dose ilea or faricimab. We're not seeing those impacted which really shows
Speaker Change: the value proposition that clinicians and patients are seeing, and so we would expect no impact for an even bigger paradigm shift of a one-time treatment that would not only decrease injection burden, but potentially even prevent the need for injections.
Speaker Change: Thank you.
Speaker Change: Our next question comes from the line of Luca Issi with RBC Capital Markets. Your line is now open.
Luca Issi: Oh, great. Thanks so much for taking my question and congrats on the progress. Maybe, Steve, bigger picture, what was your reaction to the Phase 3 data presented by Pfizer a few weeks back at World? Looks to me that they show pretty impressive evidence of expression there.
Speaker Change: But still, there was no functional benefit whatsoever there.
Luca Issi: So is there a scenario where the FDA here changes the kind of regulatory standard going forward in light of that data and maybe decides to put a little more emphasis on function versus expression here?
Luca Issi: Again, any thoughts there? Much appreciated. And then maybe, Mitch, I believe this is your first time that you're joining the earnings call. Can you just maybe talk about why you decided to join the team? As you were doing diligence on Regenexx, what do you find particularly attractive about it? Thanks so much.
Speaker Change: Thanks, Luca. I'll take the first part before we hand it over to Mitch. So.
Speaker Change: the Pfizer results. So as you mentioned, there's a micro dystrophin expression, but not a clear signal of efficacy from their trial.
Speaker Change: As far as we're concerned, this actually is exactly why we, right from the beginning of our program, focused on designing the best construct that we could.
Speaker Change: and part of what that means is reconstituting as closely as we can the native dystrophin molecule in terms of the key functional elements.
Speaker Change: So that's a key reason why
Speaker Change: We and our team took the time to develop a second generation
Speaker Change: construct that, for example, includes the important C-terminal.
Speaker Change: domain elements, and some other improvements. So really the overarching aspect is not all constructs are created equal.
Speaker Change: So, the farther you are away from a native dystrophin, the less confidence that you can have that you're going to translate expression into clinical benefit.
Speaker Change: and the FDA acknowledged that as well in the Adcom for Levitas, for example, where they raised the importance of C-derminal domain elements and the fact that those being absent in some constructs
Speaker Change: For those reasons we think the differentiation that we have with our product and how close we are in terms of the key elements
Speaker Change: preserves are reasonably likely to predict benefit.
Speaker Change: aspect for our program. And certainly we've seen no change in our discussions with the FDA as recently as our end of phase two meeting. So we're aligned on how to proceed with the PIVDRL program.
Curran Simpson: and Luca, this is Curran. I guess I would add one thing to Steve's comment that I mean if you look at the accelerated approval for Elevitas
Speaker Change: They utilized the functional data in that assessment So it won't surprise us at all that FDA would want to see maybe not as a primary end point But supportive data on the functional side, so we're
Speaker Change: well-prepared to address those questions at the time of filing for accelerated approval and and we're planning for that eventuality and obviously I think for you know we see good uptake now in the market I think I think in general
Speaker Change: What we're looking for is that, with functional data being demonstrated, that a lot of patients are going to be interested in our program, and certainly around the differentiation aspect, given the levels of microdrosophin we're showing.
Speaker Change: and many more. Thank you. Merry Christmas. Merry Christmas.
Speaker Change: I'll turn it over to Mitch.
Mitch: Yes, thanks Luca for the question as well too, and I must say I've been here for almost two months and one of the major reasons why I joined is really the scientific excellence at the company and during my brief time here that has translated to be very much true.
Mitch: And I think the other aspect is, over the next 18 to 24 months, there are potentially several BLAs that could happen at our company. And entering this commercial phase is actually very exciting, to say the least.
Speaker Change: and these aren't just simple BLAs, these are great opportunities to deliver great medicines to patients.
Speaker Change: So these are potential best-in-class, if not even blockbuster, opportunities for this company. So with that, I would say the value proposition is too great to pass, and hence why I'm here. And I'm surrounded by great teammates here, which could actually deliver and execute towards these pivotal moments at the company.
Speaker Change: Thanks so much, guys.
Speaker Change: Thank you. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is now open.
Paul Choi: Hi, thanks. Good afternoon and thank you for taking our questions. I want to switch gears maybe to RGX 121.
Paul Choi: and I want to see what your latest thoughts are on a potential adcom following the filing. And then secondly, what are the latest, I guess, bit of feedback you're hearing relative to the Denali asset and maybe just how doctors and the physician community are thinking about potentially sequencing these drugs. Thank you very much.
Speaker Change: Go to Beadaholique.com for all of your beading supply needs!
Speaker Change: Thanks, Paul. Thanks for joining the call. I think on the first question, we're preparing as if there will be an outcome. That's something that normally
Speaker Change: You're not notified by FDA until the filing is accepted and and they map out their plan for review But on our end, we're certainly Planning that an ad come could be required, but we have no Information to say that it's it's required at this point
Speaker Change: I think to your second question, I think, you know, there's a huge difference between our approach and Denali's. I think our approach is...
Speaker Change: require a patient to go in for a weekly IV would be incredibly valuable, and that's how we're thinking about the program. In addition, the data that we released early in the year that showed that
Speaker Change: The majority of patients that were on enzyme replacement therapy
Speaker Change: then even the initial product profile that we had developed.
Speaker Change: We feel like we're in a really strong position with the MPS community as we get closer and closer to a potential commercial approval.
Speaker Change: and feel like we'll be able to position our product as a first choice for patients based on the data that we have in hand.
Christmas: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Speaker Change: Great, thank you.
Speaker Change: Thank you. Our next question comes from the line of Brian Scorney of Baird. Your line is now open.
Brian Scorney: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson, Stephen Pakola,
Speaker Change: Hey guys, thanks for taking our question. This is Charlie on for Brian. So yeah, I just want to revisit the youngest cohort of DMD patients. Just, you know, knowing that in general they're not diagnosed until they're about four to five.
Speaker Change: years old, are you having any issues identifying these patients relative to the older cohorts, and do you think there are any efforts there you could make for the potential future market in terms of moving that average age of diagnosis up? Thanks.
Speaker Change: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson,
Speaker Change: Thanks. I'll turn that over to Steve. Thanks, Charlie, for the questions.
Steve Pakola: So I think one aspect is although that's traditionally been the the time point of diagnosis We are seeing newborn screening pick up
Speaker Change: and I think we're going to progressively, over the next few years, see more and more states.
Speaker Change: take on newborn screening. So that's going to move things earlier.
Speaker Change: We announced today that we actually dosed our first patient in that age group, so that gives you an early anecdotal, albeit sense, that these patients are there and we feel confident we're going to be able to...
Speaker Change: find these patients with the investigators that that we have. And we think once these patients are found and the families consider the options
Speaker Change: consider a second-generation potential best-in-class product that has the differentiating aspects that we've been describing is going to be really a compelling
Speaker Change: plays an important part in the considerations of the actual families when they're seeing our investigators.
Speaker Change: and Stephen Pakola. Merry Christmas. Merry Christmas. Merry Christmas.
Speaker Change: Great, thank you so much.
Speaker Change: Thank you. Our next question comes from the line of Danielle Gutterlin with Chardon. Your line is now open.
Danielle Gutterlin: Hey guys, thank you for taking the question and congrats on the progress.
Speaker Change: I have a couple of questions. One in the 202 program, I saw in your press release that you got an approval or authorization to start clinical trial in Canada, which you plan on doing in First Health. Can you share some of the details of that trial and whether the data from the trial will be part of the pilot data package?
Speaker Change: And then a question on 314.
Speaker Change: Given, you know, recent data from the bilateral study, what are your plans for the parallelized data for supercovertile program both for DM, both for wet AMD and DR? Thank you.
Speaker Change: Thanks, Neal.
Speaker Change: We're excited that we've expanded.
Speaker Change: for inclusion with Canada in in the program. So we're going to be able to open up multiple sites there and we'll give more details when we give the overall details on the design but we had no issues getting approval in Canada which I think
Speaker Change: supports the quality that we see with our product and the overall design of our plan and consistency with feedback that we've heard from the FDA.
Speaker Change: Similar to what we discussed before, any of the data that we see
Speaker Change: in the program from whatever region.
Speaker Change: is going to be relevant both for the pivotal end point for accelerated approval, microdystrophin, but also the functional data that Curran mentioned would also be looked at, but not really be the primary focus for the initial approval.
Speaker Change: 314, the bilateral study.
Speaker Change: We started with the subretinal program as far as evaluating bilateral treatment.
Speaker Change: since we had a lot more exposures, a lot more data, so it made sense to...
Speaker Change: have the first step be looking at bilateral dosing with that route of administration.
Speaker Change: Since we're advancing rapidly along with AbbVie, the DR into Pivotal, it's a great question you're raising that we'll want to also evaluate bilateral treatment with supracroidal.
Speaker Change: So we'll be planning that. We haven't announced any specific details yet, but certainly it makes sense that that's what we would want to do. We're excited at that opportunity because we've seen...
Speaker Change: If you have significant inflammation in a first eye, the immune response...
Speaker Change: seen there, if there's any spillover to the systemic circulation, then...
Speaker Change: You would wonder, will that affect the safety and efficacy in the fellow eye?
Speaker Change: So, that's why we're excited that...
Speaker Change: subretinal with the compartmentalized delivery. We didn't expect to see any issues in fellow eye and we haven't. And supracroidal also because it's a compartmentalized delivery where we're not seeing significant immune mediated responses in the first eye. That also gives us confidence that we'll be able to dose in the fellow eye.
Speaker Change: Thank you.
Speaker Change: Our next question comes from the line of Yi Chen with H.C. Wainwriting Company. Your line is now open.
Yi Chen: Hi, thank you for taking my question. With respect to the pivotal program in diabetic retinopathy, can you comment...
Yi Chen: Whether you plan to enroll a lot of patients without symptoms, and if so, what would you measure as the primary efficacy endpoint?
Yi Chen: Thank you.
Yi Chen: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Stephen Pakola,
Speaker Change: Sorry, it was a little bit difficult to hear you. Was this referring to the 202 pivotal plan? No, for 314 for the diabetic retinopathy pivotal program, do you expect to enroll a lot of patients without symptoms? And if so, what would you measure?
Speaker Change: as the primary efficacy endpoint.
Speaker Change: and Stephen Pakola. Merry Christmas.
Speaker Change: Okay, so I think this, correct me if I'm wrong, but this would relate to the diabetic retinopathy indication in our pivotal program. It's an excellent point in that
Speaker Change: In diabetic retinopathy, these patients are often asymptomatic until they develop the blinding
Speaker Change: complications like diabetic macular edema and proliferative diabetic retinopathy.
Speaker Change: But yet
Speaker Change: they're at significant risk of developing these conditions. So what's needed is a treatment that could prevent patients from ever developing these blinding complications.
Speaker Change: and the existing therapies, repeated injections.
Speaker Change: are just not sustainable because patients are asymptomatic. So clinicians and patients are choosing to not be treated because the treatment burden is just too much. So the whole reason, or one of the significant reasons
Speaker Change: We in AbbVie see this as such a major opportunity as it's a one-time in-office treatment.
Speaker Change: So that really does allow this to be a compelling case for a clinician and their patient that
Speaker Change: one-time in-office treatment can help prevent
Speaker Change: them from developing the symptoms and the need for repeated treatment. So, yes, we would include asymptomatic patients.
Speaker Change: We
Speaker Change: measures of whether their severity of their diabetic retinopathy is getting worse.
Speaker Change: And also, we can look at those hard outcome measures of...
Speaker Change: vision-threatening complications, where we saw already in our Phase 2 study close to a 90% reduction in vision-threatening complications of DME and PDR. So that's what has us in the community so excited about being able to
Speaker Change: move forward with the end of phase two meeting and then into federal development next year.
Speaker Change: Christmas, Kenneth Mills, Vittal Vasista, Curran Simpson, Stephen Pakola, Curran Simpson,
Speaker Change: Thank you.
Speaker Change: Thank you. I would now like to turn the call back over to Curran Simpson, President and CEO, for closing remarks.
Speaker Change: I'd like to thank everybody for joining us for the call. We have a lot of really important and exciting milestones to report through the rest of the year and really excited to to reach out to you as each of those are realized and have a great evening. Look forward to following up with several of you. Thank you.