This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk06: Good day and thank you for standing by. Welcome to the Q1 2022 Regenexx Bioincorporated Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. If you require any further assistance, please press star 0. I would now like to hand the conference over to our speaker today, Mr. Patrick Christmas, Chief Legal Officer. Please go ahead.
spk07: Good afternoon, and thank you for joining us today. With us are Ken Mills, Regenexx Bio's President and Chief Executive Officer, Dr. Steve Piccola, our Chief Medical Officer, and Vid Vasista, our Chief Financial Officer. Earlier this afternoon, Regenexx Bio released financial and operating results for the first quarter ended March 31, 2022. The press release reporting our financial results is available on our website at www.regenexxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, and other words of similar meaning. Any such forward-looking statements are not guarantees of and involves 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, 2021, and the comparable risk factors sections of Regenexx Bio's quarterly reports on Form 10-Q, which will be 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, May 4, 2022, 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. 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. Actual results may differ materially. I would now like to turn the call over to Ken Mills. Ken?
spk04: Thank you, Patrick. Good afternoon, everyone, and 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. Steve will then provide an update on our clinical programs, and VIT will provide an overview of financial results for the first quarter ended March 31, 2022. At the end of the call, we will open up the line for questions. Before Steve gets into the pipeline progress in detail, I would like to provide some context on the gene therapy industry. Despite the recent market performance of the sector, I cannot help but be optimistic for the future of gene therapy. Over the years, we've seen a high level of investment in people, quality, and safety monitoring, and have developed a deeper understanding of the science across the industry. The recent challenges experienced across the industry are not, as history tells us, as a guide uncommon for novel modalities like gene therapy. Challenges create opportunities. In a relatively new field like gene therapy, the recent challenges have led to greater collaboration and involvement with key leaders, including regulatory agencies, that I believe will better define the path towards getting gene therapies to patients with unmet needs as efficiently as possible. While this past year has led to a difficult decision for a number of gene therapy companies, I'm encouraged as Regenexx Bio and the field of gene therapy head deeper into 2022 and beyond. To this end, I'm incredibly proud of how our company has been advancing our pipeline during these times, and I believe our fundamentals have never been stronger. This is why we felt this past quarter was the right time to announce our 5x25 strategy to progress five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. The goal of the 5 by 25 strategy was to lay out a clear and definable plan to advance key programs that have the potential to treat very high unmet need in areas where we and our partners can use our NAV technology platform to develop and potentially commercialize AAV therapeutics as soon as possible. One of the leading candidates to meet our 5x25 strategy is RGX314 for the treatment of wet AMD and diabetic retinopathy. As you know, we have a global partnership with AbbVie to bring RGX314 to market, for which we have received a $370 million upfront payment and are eligible to receive up to $1.3 billion in additional milestones. We believe this deal not only validates Regenexx Bio as a leading player in the gene therapy space, but also validates RGX314 and its broad opportunity in ophthalmology. While the landscape for therapies being developed in both wet AMD and in diabetic retinopathies has changed over the past few months, With the new product launches and also high-profile setbacks in the field, we believe the opportunity for RGX314 has improved based on the encouraging interim safety and efficacy data presented for both wet AMD and diabetic retinopathy. Overall, we plan to take full advantage of AbbVie's leadership in eye care and its commercial strength as we work together to advance RGX314 for both the treatment of wet age-related macular degeneration and diabetic retinopathy. In our 5 by 25 strategy, we also expect to include candidates from our other internal programs, such as RGX202 for the treatment of Duchenne and RGX121 for the treatment of Hunter syndrome. This quarter, we presented positive interim data at the World Symposium for our neurodegenerative lysosomal storage disorder program, RGX121 for the treatment of Hunter syndrome, and RGX111 for the treatment of Hurler syndrome. We believe the data updates highlight the potential of both programs to alter the course of these debilitating diseases and deliver improved patient outcomes. Moving to RGX202, today we announced that we made a difficult decision to delay dosing of patients in our first in-human Duchenne clinical trial. This was a proactive step we elected to take in consideration of patient safety. This decision was due to an unexpected and isolated observation in the final vial-filling stage of the manufacturing process. It didn't meet our quality criteria. We've informed all key stakeholders and are investigating this situation. Based on this update, our current expectation is to be able to dose patients in the first half of 2023. Work preparing for trial initiation continues, including readying clinical trial sites, and manufacturing additional clinical supply. Importantly, this recent and unexpected event highlights the importance of having our own in-house manufacturing capabilities. I view this as a key to our longer-term success. While this will delay our current development plan, it certainly does not impact our strong commitment to developing our GX202 for patients with Duchenne, which continues to be a key element of our 5x25 strategy. Beyond our internal programs, 5x25 may also include programs developed by our NAV technology licensees. Our NAV technology platform is driving the field of AAV gene therapy forward, with over 60 clinical trials utilizing NAV vectors registered in the National Institutes of Health Clinical Trials Database since 2015. Our NAV technology is also the basis for Zolgensma, one of two FDA-approved gene therapies in the United States today. With a number of additional AAV therapeutics being developed over a broad range of therapeutic areas and disease indications by our NAV technology licensees, we believe these programs will also contribute key gene therapy products to meet our 5x25 strategy. With that, I'd like to turn the call over to Steve now to talk in greater detail about the internal programs.
spk05: Thanks, Ken. I'll begin with an update on RJX314, which is being developed in collaboration with AbbVie to treat multiple ocular indications, including wet AMD and diabetic retinopathy. RJX314 uses the NAV-AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor, or VEGF. Wet AMD is the leading cause of vision loss in people over 60, affecting more than 2 million patients in the U.S., Europe, and Japan. The current standard of care for wet AMD patients are anti-VEGF treatments, which require patients to receive injections into the eye every 4 to 12 weeks. Real-world evidence shows that patients with wet AMD are severely undertreated due to the unsustainable treatment burden of these frequent injections. over time. RGX314 is being developed as a one-time treatment for wet AMD that has the potential to reduce the frequency of anti-VEGF treatments and preserve vision loss for patients with wet AMD. Data presented to date for our Phase I-II clinical trial of RGX314 for the treatment of wet AMD using the subretinal delivery approach has demonstrated a durable treatment effect over three years now, including mean improvement in vision and stable retinal thickness and reduction in anti-VEGF treatment burden. We believe RGX314 represents a significant potential We continue to enroll patients in Atmosphere and Ascent, our two pivotal clinical trials evaluating the efficacy and safety of RGX314 in patients with wet AMD using the subretinal delivery approach. Ascent is the first trial to be initiated under our eye care collaboration agreement with AbbVie. These two trials are expected to support a BLA submission for RGX314 in 2024. We are also advancing two additional programs that are part of our collaboration with AbbVie, RGX314 and WET-AMD, and RGX314 and diabetic retinopathy, that are both being developed using an in-office supracoroidal delivery approach. In WET-AMD, we have presented six-month data for the first two cohorts in our Phase II ABA trial, demonstrating evidence of the emerging clinical profile of RGX314 using supracoroidal delivery and and retinal thickness, as well as a 72% reduction in anti-VEGF treatment burden compared to the mean annualized injection rate during the 12 months prior to receiving RGX314. Looking at the safety profile across all cohorts as of November 4th of last year, RGX314 was reported to be well-tolerated in 50 patients with no drug-related serious adverse events. Mild intraocular inflammation was observed on slit-lamp examination at similar incidence across both dose levels, that is, in 4 out of 15 patients in cohort 1 and 3 out of 15 patients in cohort 2, and resolved quickly with topical corticosteroids. We expect to complete enrollment in AV8 in the first half of 2022. Patients in this trial do not receive prophylactic steroids before or after administration of RGX314. Moving to RGX 314 for the treatment of DR. DR is a complication of diabetes and is the leading cause of blindness in adults between the ages of 24 and 75. An estimated 27 million patients are affected by this debilitating disease worldwide. DR is a slowly progressing disease that in a large proportion of DR patients leads to vision-threatening complications, including diabetic macular edema, or DME, and neovascularization that can lead to blindness. However, many with this condition do not receive anti-VEGF treatments, a proven therapy to reduce the risk of developing these vision-threatening complications due to the unsustainable treatment burden. RGX314 could potentially overcome this hurdle and provide an important therapy for patients to significantly alter their disease progressions. We recently presented six-month data from our phase two altitude trial at the angiogenesis conference in February that demonstrated a clinically meaningful two-step improvement from baseline on the DRSS scale after a single superchoroidal RGX314 administration in 47% of the 15 treated patients in cohort one compared to 0% in the observational control. Importantly, this was an increase from the 33% observed at three months. We are encouraged by what we are seeing at this stage. Furthermore, as of January 18th, RGX314 was reported to be well-tolerated in the 15 patients dosed in cohort one with no drug-related SAEs and no intraocular inflammation. Enrollment is complete in the altitude trial. and patients in this trial did not receive prophylactic steroids before or after administration of RGX314. Shifting now to our rare disease portfolio in RGX202, our potential one-time gene therapy for the treatment of Duchenne. We are developing RGX202 to be a highly differentiated product and have designed it to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-terminal, or CT, domain found in naturally occurring dystrophin. 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 include codon optimization and reduced CPG content which has the potential to improve gene expression, increase translational efficiency, and reduce immunogenicity. RGX202 is designed to support delivery and targeted gene expression throughout skeletal and heart muscle using our NAVAVA vector and a well-characterized muscle-specific promoter. As Ken discussed earlier, we continue to prepare for trial initiation, including readying clinical trial site and manufacturing additional supply. We remain fully committed to initiating this trial as soon as possible. Earlier this year, at the World Symposium, we presented data from the ongoing trials for both RGX121 for the treatment of MPS II or Hunter syndrome, and RGX111 for the treatment of severe MPS1 or Hurler syndrome, demonstrating emerging evidence of CSF biomarker activity, along with neurodevelopmental assessments indicating an encouraging potential CNS profile for both clinical candidates. As of December 20th of last year, RGX121 and RGX111 were both well-tolerated with no drug-related SAEs. We continue plans for enrolling patients in the expansion arm of both trials. Overall, we have already made significant progress in 2022, and we look forward to providing further updates throughout the year. Now, I turn the call back to Ken.
spk04: Thanks, Steve, for the good updates and to the team for the progress we've made over this past quarter and in the first part of this year. Before turning the call over to Vit, I would like to highlight our progress that we've mentioned about manufacturing. As you know, we've begun utilizing our new headquarters in Rockville, Maryland, that houses our new CGMP manufacturing facility. I'm excited to share that this facility is now operational, allowing for high-yield production of NAV vectors at scales up to 2,000 liters using our platform suspension cell culture process. With the new headquarters in GMP manufacturing facility, we are continuing to expand our capabilities from basic research and development to commercial scale infrastructure. We have over 21,000 square feet of our corporate headquarters dedicated to our in-house GLP pilot plant, advanced analytics lab, multiple 2,000 liter bioreactor suites for GMP manufacturing of bulk drug substance, and flexible state-of-the-art fill finish suite to support multiple programs. This capability remains a key differentiator for Regenexx Bio and a key element of our strategy. Our facility is cutting edge. It allows us to move quickly from candidate selection to the production of clinical-grade material, which supports accelerating the early development of our AAV therapeutics. Additionally, we believe our approach focuses on early product quality and process control, which lessens the need for changes during clinical development to enable efficient transition from clinical trials to commercial readiness. Furthermore, our manufacturing team has formulated AAV Therapeutics to be used with a number of innovative delivery device solutions and techniques, including pioneering the clinical use of the superchoroidal technique and the intracisternal intervention that Steve alluded to. We believe being a leader in innovative device delivery of AAV Therapeutics is a distinguishing competency for Regenexx Bio. So at this stage, I'm going to turn the call over to Vit for a review of our financial guidance.
spk03: Thank you, Ken. RegenX Bio ended the quarter on March 31st, 2022 with cash, cash equivalents, and marketable securities totaling $764.8 million compared to $849.3 million as of December 31st, 2021. The decrease was primarily the result of cash used to fund operating activities and capital expenditures as well as temporary unrealized losses on marketable debt securities during the quarter ended March 31st, 2022. R&D expenses were $55.6 million for the quarter ended March 31st, 2022 compared to $39.7 million for the quarter ended March 31st, 2021. The increase was primarily attributable of personal cost and costs associated with clinical trials and manufacturing-related activities for our lead product candidates. It was partially offset by Regenexx 314 development costs reimbursable by AbbVie under our iCare collaboration. In accordance with the collaboration agreement, Regenexx Bio will continue to fund certain ongoing clinical trials for RGX 314 through the end of 2022. while other 314 development costs are shared with AbbVie. Beginning in 2023, AbbVie will be responsible for funding the majority of all RGX 314 development expenses. Based on our current operating plan, we expect a balance in cash, cash equivalents, and marketable securities of $764.8 million as of March 31st, 2022, to fund our operations into 2025. With that, I will turn the call back to Ken to provide final thoughts.
spk04: Thank you, Ben. Overall, Regenexx Bio continues to perform at a very high level, and I would like to take this time to thank our Regenexx Bio team, our investigators, and patient communities for their commitment to the development of our innovative AAV therapeutics. Taking just one moment to circle back on RGX202, I want to reiterate our strong commitment to the Duchenne community. This unexpected delay reinforces the importance of our in-house GMP manufacturing facility. We plan for the first runs in this facility to support our clinical supply for our RGX202 and RGX314 programs. we're also able to begin to install new process improvements that we plan to use in our facility that will be expected to produce, for example, in the case of RGX202, approximately five times improvements in vector yield per batch than previously used processes. So to summarize what you've heard from us today and my views on the overall status of our progress so far this year, we continue to be a leader in the field of AAV therapeutics. There are over 2,000 patients dosed with AAV therapeutics derived from our NAV technology platform. Our global eye care collaboration with AbbVie continues to advance and is on track for the first BLA filing in 2024. Emerging clinical trial data and expanded trial enrollment mentioned by Steve supports excellent progress in our suprachoroidal delivery programs to unlock additional value. We have strong science and clinical data behind our rare disease pipeline of AAV therapeutics, where we look to take advantage of accelerated pathways to address high unmet needs. Our internal GMP capability is operational, supporting the high-yield manufacture of quality AAV therapeutics across a diverse range of programs and at the scales necessary to support clinical development and commercialization. We also 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 the potential to generate new, innovative AAV therapeutics. In fact, on that point, this week we announced a summary of around 15 1-5 presentations at the ASGCT conference next week. which reflects leadership in areas such as evaluating our NAV vectors to identify and characterize more clinically relevant features and benefits, engineering novel capsids, enhancing AAV therapeutic tissue and cell type specificity and expression, including optimizations of enhancers and promoter combinations, expertise in designing delivery device systems for use with AAV therapeutics, proof of concept research that informs the next step in our pipeline strategy, and innovative manufacturing process development and analytical capabilities. And all of this stands on the foundation of the capital to fund our mission and operations into 2025. We believe that we remain on track to execute on our five by 25 strategy to advance five AAV therapeutics to late stage development and commercialization by 2025. We're more confident than ever in our science, our people, and our capabilities to support developing AAV therapeutics for diseases that have the potential to significantly impact patients' lives. And with that, this portion of the call is over. I will turn it over to the operator for questions.
spk06: Certainly. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Our first question comes from Alex Tranahan of Bank of America. Your line is open.
spk02: Hey, everyone. This is John. I'm on for Alex. Thank you for taking our questions. Just a couple from us. I think the first question, could you just elaborate a little bit more on the decision to delay the 202 program? You know, what exactly was the issue that you ran into? And how do you think this delay will affect kind of the overall competitiveness of the 202 in the field of DMD. So that's the first question. Second question is also on DMD. So how do you, with recent news on the obviously safety issues run into by other companies, how do you wish to kind of learn from all of that and kind of approach and eliminate the concerns of those issues in your study? That's the second question. Third question, just a short one on manufacturing. Obviously, in-house manufacturing is very promising, but what do you think are the challenges going forward with regards to that? Thank you.
spk04: Okay, John, thanks for the questions. I'll start and let Steve comment on the clinical trial comparisons and also circle back on in-house manufacturing. So, as I reported, we had this unexpected isolated observation in the very final stages of a manufacturing process for our RGX202 clinical supply. And, you know, the unexpected nature of this and the late-stage nature of this caused us to have to report this delay and re-guide first patient dose to the first half of 2023, which is, you know, I think, telegraphing that we have a six to 12-month delay. This was something that was reported at a third-party contract manufacturer of ours, and that didn't meet our quality criteria. So that relates to your third question, John, which is that we've been looking at the landscape for a while. We've been communicating with all of you about how important we think it is to bring the quality and availability of clinical supply and commercial supply for our pipeline in-house. We started that investment pre-COVID with the build-out of our headquarter facility and the intent to bring online the GMP facility, and we announced today that the GMP facility is operational. So for us, a key element of the 5x25 strategy to be able to be a company with five programs in pivotal phase or commercialized by 2025, it was imperative for us to bring those in-house capabilities for GMP manufacturing here to Rockville and enable our team that level of support. With respect to the 202 comparisons to other trials and our approach, I'll turn it over to Steve.
spk05: Hey, John. Thanks for the good questions. On the historical data sets that we can look at in the AEV field, we do have the benefit of all of our licensees and all of our collective understanding in the field, both in Duchenne but also other programs. And I think we get to take advantage of all of this, and I think it's been very collaborative in the field of late, appropriately so, where we get to take advantage of what's been learned. I think each program is specific, though, and you can't really carry too much forward from one program to another because of all the different aspects. So, for example, AAV8 versus AAV9. So some of the programs have seen complement activation, for example, with AAV9 at higher doses, and the other finding of We've taken advantage of the learnings from that. In our AAV8 program, where clinically complement activation hasn't been a real issue in the same way that it's been seen with high-dose AAV9, nevertheless, out of an abundance of caution for a first-in-human study, we're being very robust in how we look at this initially, including complement inhibition with ecolizumab, just a short course, as well as other typical immune suppression regimens to really cover for that aspect. So we feel very excited both based on that as well as our preclinical package where we've seen very good safety at doses, including the very first dose that we're looking at clinically, by the way. We see very good clinical and pathophysiologic proof of concept in our model. So all of this ties together to make us feel very good about our innovative transgene promoter within AAV8 as really an exciting program to advance on.
spk02: Thanks for the call, Eric. Thank you. Thank you.
spk06: And our next question comes from Vikram Pirahit of Morgan Stanley. Your line's open.
spk10: Good day, everyone. This is for Vikram. So we have two questions. The first one is once building has begun for the IGX202 program, how many patients, what of data, and how much follow-up do you think you would need prior to sharing an initial outlook at the data? And then for the initial data set that is initially generated, what do you aim to see to establish that 202 has a competitive safety and efficacy profile?
spk04: Thanks, Gospel. This is Ken. I'll start and let Steve provide some more color if necessary. So we've reported that the trial design at this stage includes two dose levels with a basic 3 plus 3 design, 1E14, moving up to 2E14. and each one of those cohorts has the potential for expansion as well. When it comes to the profile of RGX202 and the execution of the design, we'd be looking to complete the initial cohorts of three patients look at some of the primary safety evidence as well as the secondary endpoints that we'll be measuring, such as microdystrophin expression at about 90 days, as well as intermediate measures of things like functional outcomes and imaging on the order of three months, six months, and beyond. You know, we'll be looking for there to be, you know, similarity, parity, if you will, to existing treatments that are microdystrophin-AV gene therapy-based candidates being studied clinically and look for a safety profile that is similar to improved, micro dystrophin levels that are similar to improved to continue to support evidence that we see a place for RGX202 in the treatment paradigm I think the points to emphasize about, you know, differentiating aspects that we think are key in addition are we're using a different capsid. And to the extent that we see the same types of evidence that I think others have demonstrated or can continue to demonstrate with microdystrophin-based AAV gene therapy, We believe that there could be a place in the market for patients who couldn't access because of pre-existing immune status other types of products using AAV9 or other capsids that would be able to access RGX202, for instance, because of its differentiating immunological profile with AAV8. In addition, we think the C-terminal domain is likely to provide opportunities for us to look for longer-term functional outcome improvements, things that may be gospel we wouldn't pick up in the first 90 days or six months, but at a year, at 18 months, at two years, would start to show a longer-term differentiating profile, and that would be meaningful not only for our continued long-term follow-up in clinical development, but also in the marketplace. And then finally, on the manufacturing side, the emphasis today, you know, a sort of lesson learned on the importance of having control over the quality as well as the control of the process itself here at our manufacturing facilities of paramount importance. And having control over that supply, being able to advance with our people, our processes, And with improvements to those processes that we plan to bring to our new facility as well, we think that being a major contributor to supplying the market and with higher-yield processes potentially have an advantage on cost of goods will be things that, in addition to those early looks, are meaningful long-term contributions to helping patients with Duchenne and having a differentiated profile.
spk10: Got it. Thank you very much.
spk06: Thank you. And our next question comes from Gina Wang of Barclays.
spk08: Your line is open. Thank you. We have three. This is Tom for Gina. We have three questions. The first one is about the 314. So as you're completing the remodeling of two suprachloride trials, I'm thinking when can we expect to see the protein level data? And second is regarding to the CGMP facility. Just to clarify, beyond the analytical rounds that you mentioned, are there any other or what are the other steps to go through to get fully ready for clinical supply? And for the Duchenne program, the last question is, I saw the ASGCT abstract. You showed the higher AAV-mediated transgene expression in the skeletal muscle in the disease model versus the normal mice. driven by downregulation of view factors. Just wondering how relevant is defining to human and how does this help you to refine the dose escalating strategy and also dose selection strategy in the clinical study?
spk04: Thanks for the question. Do you want to grab 314? Sure.
spk05: On 314, as you mentioned, we have the two suprachoroidal in-office delivery studies, one in wet AMD, the other in diabetic retinopathy, where we have the clinical proof of concept in both studies, and we continue to evaluate dose response in both indications. We have very good non-invasive ways to assess clinical response. Your question on aqueous humor protein, we did choose to include measurement of aqueous humor protein with this new route of administration, as these were the first studies ever done with supracroidal delivery, just to include that for assessment. We haven't given any guidance on when we'd have data for that in these ongoing studies. Our focus, particularly now that we actually have clinical signal and even clinically meaningful signal and even a signal on, in the case of diabetic retinopathy, on the end point, related to bioreactor clinical supply, where fortunately that's not on the critical path as far as how we'd advance there. So as Ken mentioned, we continue to be on track with our plan to have a BLA submission in 2024, and that's really driven on completing the two pivotal studies.
spk04: Right, and with respect to the question relating to the preclinical work done and around candidates for Duchenne, including RGX202, there's a totality of evidence that obviously went in to support our IND for the purposes of selecting doses and for FDA granting it safe to proceed. We certainly looked at disease models as well as different types of background models with respect to evaluating things like transaction efficiency and safety and biodistribution. I think it's, you know, People in our research and development organization as well as people in the space have learned that there are differences across animal models with respect to a disease model and what you may see in terms of transduction and what you might find in, you know, black six mikes or other types of models. So, you know, we reconciled all of those things, built the appropriate package to be able to inform the doses that Steve alluded to today, starting at 1E14, planning for dose escalation to 2E14. This, we're continuing to roll out. over time, different parts of the package that went into the IND. But, you know, the totality of evidence has been there since we filed the IND at the end of last year. Thanks for the questions. Operator?
spk06: And our next question comes from Manny Forhar of SVP Security. Your line's open.
spk00: Hey, good afternoon. This is Rick on for Manny. Thanks for taking our questions. So given there's roughly a 6 to 12 month delay in the dosing of RGX202, could you just walk us through some of the steps that need to take place before you can initiate dosing? Is it simply that you have to produce a new batch of clinical product from your in-house facility, or would you potentially have to revise manufacturing protocols, seek a new third party manufacturer, or any other potential steps?
spk04: So I think the essence of the 6- to 12-month delay is that we have to reestablish our clinical supply, and the primary plan for doing so is using the new GMP capabilities here in Rockville. I think we will have strategies like we always do to sort of mitigate different potential outcomes from that, but I think the essence of us hitting that re-guided point is going to be relying on the great capabilities we have here to make that bulk drug supply available get it filled and get it prepared for patients. That will be done, you know, under and sort of as part of the IND that was filed at the end of last year and then we announced was safe to proceed early this year. As we continue to make progress on that and get closer to that next milestone, we'll update, you know, something in addition to that first half of the year guidance. But, you know, this is a recent and unexpected event for us at this stage, so this is where we are guiding right now.
spk00: All right. That's it from us. Thanks for taking the question. Thanks.
spk06: Certainly. Ladies and gentlemen, if you do have a question, please press star, then 1. If you'd like to remove yourself from the queue, please press the pound key. Our next question comes from Andreas Argarides of Bedwish Securities. Your line's open.
spk09: Yeah, good afternoon, and thanks for taking your question. We've also got one on 202. You guys have an abstract at ASGCT that talks about the recruitment of NNOS. So just a quick question as to how 202 may differentiate from other competitors on targeting NNOS binding domain. Thanks.
spk04: Yeah, thanks, Andres. I'm glad you raised that. We should have brought the R&D team to this call, apparently, but I'll try to field these. We've talked about the fact that we think that the C-terminal domain and other elements of the RGX202 construct, which, again, was selected from sort of a multi-year effort on the part of our scientists to select a candidate that was differentiated based on science, based on manufacturability, based on safety. But as we got closer and closer to selecting the final candidate that became RGX202, we We were looking at the entirety of things that contributed to improvements in the structural integrity of the truncated dystrophin and its function, as well as the ability of the biology to recruit things, including NNOS, but not limited to, I think, in that abstract and in other circumstances. published data that showed that there are other aspects of the dystrophin-associated protein complex that we view are being recruited or essential to have the C-terminal domain as part of the expressed protein in order to recruit and stabilize that complex. And so we think that N-NOS among them, which we know has been something that has been talked about as part of, for instance, the construct that we know Solid Biosciences has brought into the clinic, Our view is that that is a good direction to go. It always has been making improvements to the science, the biology of the C-terminal domain component of dystrophin has been a key component for us of evaluation and candidate selection.
spk09: Great, and congrats on going live at Roxo. Very cool. Thanks.
spk04: Thank you.
spk06: Our next question comes from Danielle Godelin of Chardon. Your line is open.
spk01: Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open. Daniel Godelin of Chardon. Your line is open.
spk04: And a third-party manufacturer for this program is not a group that we use for any of the other programs that Regenexx Bio is part of our pipeline.
spk01: Okay, thank you.
spk06: I'm showing no further questions at this time. I would now like to turn the conference back to Mr. Ken Mills for closing remarks.
spk04: Thanks, Operator. Again, just want to reiterate, thanks, everyone, for the time today. Continue to be excited for the field of gene therapy, for the progress we're making here at Regenexx Bio and the capabilities we have to help as many patients as possible. So thanks for everyone's questions and support, and we'll look forward to seeing you all soon. Have a good day.
spk06: This concludes today's conference. Thank you for participating. You may now disconnect.
Disclaimer