Q2 2024 REGENXBIO Inc Earnings Call
Speaker Change: Welcome everyone to the Q2 2024 Regenxbio Earnings Conference Call. All lines have been placed on mute to prevent any background noise.
Speaker Change: After the speaker's remarks, there will be a question and answer session.
Speaker Change: If you would like to ask a question, simply press the star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1. At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of Regenxbio. Please go ahead.
Unknown Executive: If you would like to ask a question, simply press the star followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1. Good afternoon, and thank you for joining us today. Earlier this afternoon, Regenxbio released financial and operating results for the second quarter ended June 30, 2024. The press release is available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans.
Patrick Christmas: Good afternoon and thank you for joining us today. Earlier this afternoon, Regenxbio released financial and operating results for the second quarter ended June 30th, 2024. The press release is available on our website at www.regenxbio.com.
Unknown Executive: 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 nature. 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.
Patrick Christmas: Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.
Patrick Christmas: and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend and other words of similar meaning.
Patrick Christmas: Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties.
Patrick Christmas: These risks are described in the Risk Factors in the Management's Discussion and Analysis section.
Speaker Change: of Regenxbio's annual report on Form 10-K for the full year ended December 31st, 2023, and comparable risk factor sections of Regenxbio'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, August 1st, 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 pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results.
Curran Simpson: I will now turn the call over to Curran Simpson, President and CEO of Regenxbio. Dr. Steve Pakola, our Chief Medical Officer, will provide an update on our clinical programs, and then Vittal Vasista, our Chief Financial Officer, will provide an overview of the financial results for the second quarter ended June 30, 2024. At the end of the call, we'll open up the line for questions.
Speaker Change: I will now turn the call over to Curran Simpson, President and CEO of Regenxbio.
Curran Simpson: Thank you, Patrick. Good afternoon, everyone, and thank you for joining us. I'm pleased to be leading today's call, my first one as Regenxbio's Chief Executive Officer.
Speaker Change: Today we'll be sharing a number of exciting positive updates and discuss the momentum happening across our pipeline of differentiated AAV therapeutics. I'll begin with a recap of our business highlights as well as an update of our corporate goals.
Speaker Change: and key milestones that we have achieved.
Speaker Change: Dr. Steve Pakola, our Chief Medical Officer, will provide an update on our clinical programs. And then Vittal Vasista, our Chief Financial Officer, will provide an overview of financial results for the second quarter ended June 30, 2024.
Speaker Change: At the end of the call, we'll open up the line for questions.
Speaker Change: It's been a productive first half of the year for Regenxbio as we make significant progress advancing each of our programs toward pivotal stage clinical trials and future commercialization.
Speaker Change: Our priority programs are RGX202 for the treatment of Duchenne.
Curran Simpson: AbbVie RGX314 program for the treatment of wet AMD and diabetic retinopathy, or DR, being developed in collaboration with AbbVie, and RGX121 for the treatment of MPS2 or Hunter Syndrome. Our LEAD programs, specifically 202 and 314, represent large commercial opportunities where our product candidates are differentiated from current standards of care, can be expedited via accelerated approval due to significant unmet need, Let me begin with RGX202, which represents the next generation of microdystrophin gene therapies and is poised to potentially be the second AAV-based product to reach the market. RGX202 is a differentiated product candidate utilizing an advanced microdystrophin construct with potential for improved functional benefit as shown in our preclinical data.
Speaker Change: AbbVie RGX 314 program for the treatment of wet AMD and diabetic retinopathy or DR being developed in collaboration with AbbVie and RGX 121 for the treatment of MPS2 or Hunter syndrome
Speaker Change: Our lead programs, specifically 202 and 314, represent large commercial opportunities where our product candidates are differentiated from current standard of care.
Speaker Change: can be expedited via accelerated approval due to significant unmet need and support meaningful value generation soon and for the long term.
Curran Simpson: It is the only microdystrophin product that includes the C-terminal domain, a key region of the naturally occurring dystrophin gene, which has been shown in preclinical studies to protect the muscle from contraction-induced stress and improve the ability of the muscle to repair itself. As I mentioned, RGX202 is demonstrating consistently high levels of microdystrophin expression across patients of all ages. But I want to note that it is in older ambulatory boys where we're seeing the highest levels of microdystrophin expression reported in older ambulatory patients, especially compared to other published data.
Speaker Change: Let me begin with RGX202, which represents the next generation of microdystrophin gene therapies and is poised to potentially be the second AAV-based product to reach the market.
Speaker Change: There are a number of exciting developments for RGX202. Steve will share more details about the positive data reported today.
Steve: demonstrating consistent robust micro dystrophin expression across treated patients reflect reflecting a broad range of ages.
Speaker Change: But I first want to highlight the differentiating factors that we believe will make RGX202 a best-in-class product and the excellent progress we are making to both expedite its development and maximize its commercial potential.
Speaker Change: RGX202 is a differentiated product candidate utilizing an advanced microdystrophin construct with potential for improved functional benefit as shown in our preclinical data.
Speaker Change: It is the only microdystrophin product that includes the C-terminal domain, a key region of the naturally occurring dystrophin gene.
Speaker Change: which has been shown in preclinical studies to protect the muscle from contraction-induced stress and improve the ability of the muscle to repair itself.
Speaker Change: As I mentioned, RGX202 is demonstrating consistently high levels of microdystrophin expression across patients of all ages.
Speaker Change: But I want to note that it is in older ambulatory boys where we're seeing the highest levels of microdystrophin expression reported in older ambulatory patients, especially compared to other published data.
Speaker Change: And, RGX202 has been well tolerated and no SAEs have been reported, which is a significant element of the overall risk-benefit analysis for patients
Speaker Change: Caregivers and Regulatory Agencies, and a meaningful differentiator versus other Duchenne gene therapy trials.
Curran Simpson: As I mentioned, our goal is to be the next approved gene therapy in Duchenne, and we are taking all of the necessary steps towards this goal. We recently completed a successful end of phase II meeting with the U.S. FDA, and we walked away from this meeting confident in our plans to file a BLA using microdystrophin as the primary endpoint for accelerated approval. The meeting also involved discussion of our industry-leading NavXpress suspension-based commercial-ready manufacturing process used in this trial. At our in-house manufacturing facility, we have the capacity and yields to produce 2,500 doses of RGX-202 per year.
Speaker Change: As I mentioned, our goal is to be the next approved gene therapy in Duchenne, and we are taking all of the necessary steps towards this goal.
Speaker Change: We recently completed a successful end of Phase II meeting with the U.S. FDA and walked away from this meeting confident in our plans to file a BLA using microdystrophin as the primary endpoint for accelerated approval.
Speaker Change: The meeting also involved discussion of our industry-leading NavXpress suspension-based commercial-ready manufacturing process used in this trial.
Speaker Change: At our in-house manufacturing facility, we have the capacity and yields to produce 2,500 doses of RGX-202 per year.
Curran Simpson: Given the differentiating characteristics of RGX202 and the significant ongoing unmet need in the Duchenne community, plus our manufacturing expertise, we are well positioned to advance this program towards commercialization. For the treatment of DR using supracarotid delivery, we are accelerating plans for our end-to-phase II meeting with the FDA. The new timeline supports the rapid acceleration towards pivotal trials with initiation expected in the first half of 2025. Approval of the Plan BLA could result in receipt of a Priority Review Voucher in 2025.
Speaker Change: Given the differentiating characteristics of RGX202 and the significant ongoing unmet need in the Duchenne community, plus our manufacturing expertise, we are well positioned to advance this program towards commercialization.
Speaker Change: Turning to ADVI-RGX314, our gene therapy being developed in chronic retinal diseases with our partner ADVI, we have made several advancements across the supracoroidal trials in diabetic retinopathy and wet AMD.
Speaker Change: First, with regard to the altitude trial of 314 for the treatment of DR using supercoroidal delivery, we are accelerating plans for our end of phase 2 meeting with the FDA.
Speaker Change: This meeting is now expected to take place in the fourth quarter of this year versus our initial guidance of first quarter 2025.
Speaker Change: The new timeline supports the rapid acceleration towards pivotal trials with initiation expected in the first half of 2025.
Speaker Change: Importantly, Regenxbio will be entitled to a $200 million milestone payment upon successful dosing of the first patient with AVI-RGX314 in DR, which again is anticipated in 2025.
Speaker Change: We are also excited to announce that, working with our partners at AbbVie, we will be expanding the broad, multi-indication, global potential of 314 by initiating a new cohort in the ALTITUDE trial for patients with diabetic macular edema, DME,
Speaker Change: 314 is well positioned to become the standard of care to treat and prevent the progression of diabetic retinopathy.
Speaker Change: Broadening the ALTITUDE trial to include patients with DME further expands the global potential of 314.
Speaker Change: We have also made important progress on our 314 programs for WET-AMD, as well as in our RGX-121 program for MPS2, as we approach potential approval and becoming the first gene therapy for Hunter Syndrome.
Speaker Change: We remain on schedule to initiate a rolling BLA filing in the third quarter of 2024.
Speaker Change: Approval of the Plan BLA could result in receipt of a Priority Review Voucher in 2025.
Speaker Change: Overall, we are making excellent progress and have provided positive updates across all programs with a number of additional catalysts on track to be shared later this year.
Speaker Change: We remain excited by our progress as we continue on the strategic plan. We are accelerating the development of our pipeline and expanding their value for shareholders, while bringing potentially life-changing therapies to patients facing great unmet need.
Speaker Change: With that update, I'd like to now turn the call over to Steve for an update on our clinical programs. Steve?
Steve: Thank you, Curran.
Steve: I'll start with RGX202, a potential one-time gene therapy for the treatment of Duchenne.
Curran Simpson: Today, we reported new microdystrophin expression data from two new patients, age 5.8 and 8.5 years, who received RGX202 at dose level two, the dose we are advancing to the pituitary phase. Microdistribution expression was measured to be 77.2 and 46.5 percent, respectively, compared to control at three months. We are very excited as today's data adds to the totality of evidence demonstrating consistent high micro In addition, early evidence of strength and motor function improvement was observed via trial clinic assessments and home videos shared by caregivers.
Steve: Today we reported new microdystrophin expression data from the two new patients, aged 5.8 and 8.5 years, who received RGX202 at dose level 2, the dose we are advancing to pivotal phase.
Speaker Change: Microdistribution Expression was measured to be 77.2 and 46.5% respectively, compared to control at 3 months.
Speaker Change: As of July 8, 2024, RGX202 continues to be well tolerated with no serious adverse events.
Speaker Change: And all patients who reach three-month trial assessments indicate meaningful increases in expression of RGX202 microdistrophin and reduction from baseline in serum creatinine kinase levels.
Speaker Change: Supporting Evidence of Clinical Improvement. We are very excited as today's data adds to the totality of evidence demonstrating consistent high microdystrophin expression across all treated patients.
Speaker Change: In addition, early evidence of strength and motor function improvement were observed via trial clinic assessments and home videos shared by caregivers.
Steve Pakola: On the continued strength of our data, in June, we announced the expansion of the Affinity2Shen trial to include a new cohort of patients aged 1 to 3 years. This is a group of boys where there remains no approved gene therapy products and a group that represents a significant portion of the untreatable prevalent population of Duchenne boys. As Curran mentioned, with our partner AbbVie, we have accelerated our end-to-phase 2 meeting with the FDA and believe this puts us in an excellent position to initiate our first pivotal trial in DR. Today, we announce that we are now enrolling a new cohort of the ALTITUDE trial to evaluate 314 in patients with center-involved diabetic macular edema, or CIDME.
Speaker Change: On the continued strength of our data, in June , we announced the expansion of the Affinity to Duchenne trial to include a new cohort of patients aged 1 to 3 years.
Speaker Change: This is a cohort of boys where there remains no approved gene therapy products and a cohort that represents a significant portion of the untreatable prevalent population of Duchenne boys.
Speaker Change: As we ultimately seek a broad label for RGX202, we will continue to produce data where limited or no data exists to further establish a differentiated product profile that can enhance RGX202's commercial potential.
Speaker Change: Moving to 314, which is being developed in collaboration with AbbVie to treat wet AMD, DR, and DME 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-Off as suprachoroidal delivery.
Speaker Change: As Curran mentioned, with our partner AbbVie, we have accelerated our end-to-phase 2 meeting with the FDA and believe this puts us in an excellent position to initiate our first pivotal trial in DR.
Speaker Change: Today we announce that we are now enrolling a new cohort of the ALTITUDE trial to evaluate 314 in patients with center-involved diabetic macular edema, or CIDME.
Speaker Change: DME is a vision-threatening complication of diabetic eye disease and impacts more than 30 million patients globally.
Speaker Change: We are also evaluating 314 for the treatment of wet AMD via subretinal delivery in two ongoing pivotal trials, Atmosphere and Ascent, in the US, Europe , and Japan.
Steve Pakola: Our long-term follow-up data from the Phase 1-2 subretinal trial out to four years have set the gold standard in clinical development for wet AMD gene therapy. We have also fully enrolled the Open Label Fellow Eye Study evaluating 314 in patients previously treated with 314 in the other eye. This study is expected to support a label inclusive of bilateral use, representing a meaningful option for the significant number of patients with wet AMD in both eyes.
Speaker Change: These trials continue to progress well.
Speaker Change: Our long-term follow-up data from the Phase I-II subretinal trial out to four years have set the gold standard in clinical development for wet AMD gene therapy.
Speaker Change: We have also fully enrolled the open label fellow eye study evaluating 314 in patients previously treated with 314 in the other eye.
Speaker Change: This study is expected to support a label inclusive of bilateral use, representing a meaningful option for the significant number of patients with wet AMD in both eyes.
Steve Pakola: Also in WET-AMD, today we announced 314 was well tolerated at dose level 3 in the AVA trial for WET-AMD using in-office suprachoroidal delivery. We are encouraged by the positive safety profile seen to date. And we plan to enroll a new cohort at dose level four as we evaluate dose levels on a path toward pivotal. We continue to be encouraged by the progress on our 314 programs, and I'd like to particularly highlight the safety profile observed, including in our supracaroidal program. In more than 130 patients treated in-office, we're seeing a differentiated safety profile for ocular gene therapy, representing a meaningful potential treatment option for patients and physicians globally.
Speaker Change: Also in WET-AMD, today we announced 314 was well tolerated at dose level 3 in the AVA trial for WET-AMD using in-office suprachoroidal delivery.
Speaker Change: In patients who received short-course prophylactic steroid eye drops, there were no drug-related SAEs and no cases of intraocular inflammation, endophthalmitis, vasculitis, retinal artery occlusion, choroidal effusion, or hypotony.
Speaker Change: We are encouraged by the positive safety profile seen to date, and we plan to enroll a new cohort at dose level 4 as we evaluate dose levels on a path toward pivotal stage.
Speaker Change: We continue to be encouraged by the progress on our 314 programs, and I'd like to particularly highlight the safety profile observed, including in our supracaroidal programs.
Speaker Change: We are confident in our plan to advance into new disease states and dose levels because of this safety profile, particularly in the setting of short course seven-week prophylactic steroid eye drops.
Speaker Change: In more than 130 patients treated in office, we're seeing a differentiated safety profile for ocular gene therapies, representing a meaningful potential treatment option for patients and physicians globally.
Speaker Change: Finally, on RGX 121 being developed for the treatment of MPS2 or Hunter Syndrome.
Steve Pakola: In February at the World Symposium, we announced that the Campsite Pivotal trial met its primary endpoint with high statistical significance. We plan to share new data from the Campsite trial in the second half of this year. We believe RGX 121 is well-positioned to be the first gene therapy and one-time treatment for Hunter syndrome.
Speaker Change: In February at the World Symposium, we announced that the Campsite Pivotal Trial met its primary endpoint with high statistical significance.
Speaker Change: Patients treated with RGX-121 achieved decreased cerebrospinal fluid, CSF, levels of heparin sulfate D2S6, a key biomarker of brain disease activity, to below maximum attenuated disease levels.
Speaker Change: We plan to share new data from the campsite trial in the second half of this year.
Speaker Change: We believe RGX 121 is well-positioned to be the first gene therapy and one-time treatment for Hunter syndrome.
Steve Pakola: We've completed a successful pre-BLA meeting with the FDA that finalized details of our planned rolling BLA submission. The key takeaways from the meeting included alignment on the use of CSF D2S6 as the key biomarker and surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval. We also reached agreement on CMC manufacturing requirements and on the confirmatory trial design.
Speaker Change: We've completed a successful pre-BLA meeting with the FDA that finalized details of our planned rolling BLA submission.
Speaker Change: The key takeaways from the meeting included alignment on the use of CSF D2S6 as the key biomarker and surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval.
Speaker Change: We also reached alignment on CMC manufacturing requirements and on the confirmatory trial design.
Vittal Vasista: To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline. And with that, I'll turn the call over to Vitt to review our financial guidance. Thank you, Steve. Regenxbio ended the quarter on June 30, 2024 with cash, cash equivalents, and marketable securities of $327 million compared to $314 million as of December 31, 2023. R&D expenses were $49 million for the second quarter of 2024, compared to $60 million for the second quarter of 2023.
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.
Vittal Vasista: The decrease was largely driven by reduced manufacturing and clinical supply costs for AbbVie RGX 314 and RGX 202, and personal related costs as a result of reduced headcount. Regenxbio expects its balance and cash equivalents and marketable securities of $327 million as of June 30, 2024 to fund its operations into 2026. This cash flow and guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under AbbVie RGX 314 collaboration, including a potential $200 million, milestone for achievement of the first patient dose in the pivotal trial for supracortical delivery for treatment of DR. Additionally, our one-way guidance excludes the potential monetization of a priority review voucher that may be received for RGX 121.
Speaker Change: And with that, I'll turn the call over to Vitt to review our financial guidance. Vitt?
Vitt: Thank you, Steve.
Vitt: Regenxbio ended the quarter on June 30th, 2024 with cash.
Vitt: Cash equivalents in marketable securities of $327 million compared to $314 million as of December 31, 2023.
Vitt: The increase was primarily attributable to $131 million in net proceeds received from an upsized public offering of common stock and pre-funded warranted
Vitt: Completed in March 2024. Partially offset by cash used to fund operating activities in the first half of 2024.
Vitt: R&D expenses were $49 million for the second quarter of 2024, compared to $60 million for the second quarter of 2023.
Vitt: The decrease was largely driven by reduced manufacturing and clinical supply costs for AbbVie RGX 314 and RGX 202, and personal related costs as a result of reduced headcount.
Vitt: The decrease was partially offset by increases in clinical trial expenses for AbbVie RGX 314 and RGX 202.
Speaker Change: Regenxbio expects its balance and cash equivalents and marketable securities of $327 million as of June 30, 2024 to fund its operations into 2026.
Speaker Change: 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 AbbVie upon the achievement of development or commercial milestones under AbbVie RGX 314 collaboration.
Vitt: Including a potential $200 million dollars.
Speaker Change: milestone for achievement of the first patient dose in the pivotal trial for supracortical delivery for treatment of DR.
Curran Simpson: Additionally, our runway guidance excludes the potential monetization of a priority review voucher that may be received for RGX-121. With that, I will turn the call back to Curran to provide his first set of final thoughts.
Curran Simpson: Thanks, Vitt. Today was another exciting day for our 202 program with additional positive data.
Curran Simpson: As we look ahead to the rest of the year, we are encouraged by our discussions with the FDA and our finalizing pivotal plans that will enable us to utilize the Accelerated Approval Pathway to rapidly advance 202 as a potential best-in-class treatment for Duchenne.
Vittal Vasista: Additionally, we are pleased to be accelerating the end of Phase 2 meeting for DR in partnership with AbbVie to enable a pivotal start next year. Thank you. We will now begin the question and answer session. At this time, I would like to remind everyone that in order to ask a question, press the star and then the number 1 on your telephone keypad. If you are called upon to ask your question and are listening via the loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question.
Speaker Change: Additionally, we are pleased to be accelerating the end of Phase 2 meeting for DR in partnership with AbbVie to enable a pivotal start next year.
Speaker Change: As we close today and reflect on the first half of the year, I'll emphasize that our plans are on track and we continue to expand value as we make excellent progress in advancing therapies that address significant unmet needs.
Speaker Change: Thanks everyone for your time today. I'll turn the call over for questions. Operator?
Speaker Change: Thank you. We will now begin the question and answer session. At this time, I would like to remind everyone in order to ask a question, press the star and then the number 1 on your telephone keypad.
Speaker Change: If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. We do request per today's session that you please limit to one question and one follow-up.
Steve Pakola: We do request, per today's session, that you please limit to one question and one follow-up. The back and forth that will occur with the pivotal plan that will be submitted. We feel that, just in general, thinking about the field and what we've been able to glean from our investigators, that a level above 10% is likely to result in functional benefit. I think that will be a discussion that we have going forward, but if you think about our data, to date, every patient that we've published data on is above that threshold. We've also seen, as I have highlighted, excellent safety.
Speaker Change: We will pause for a moment to confile the question and answer roster.
Speaker Change: Your first question comes from the line of Gina Wong of Barclays. Please go ahead.
Speaker Change: Thank you.
Gina Wong: Congrats on the new data regarding the 202 in DMD. So I have two questions. One is the 202, I know you will meet with the FDA, finalize the pivotal study. Do you have a goal of a protein level you wanted to achieve and do you expect FDA will set some threshold in order for accelerated approval? And another question is regarding the 314 supercorrido indication in DR and the wet EMD. What's the reason for those level 4 and will you also include patient with existing neutralizing antibody?
Speaker Change: Thank you for the question Gina. In terms of, can I clarify the first question, a goal for
Speaker Change: We've proposed a threshold with FDA, and that's one of the things that we'll be waiting for, the minutes and sort of final agreement, in addition to the
Speaker Change: Back and forth that will occur with the pivotal plan that will be submitted.
Speaker Change: We feel that, just in general, thinking about the field and what we've been able to glean from our investigators, that a level above 10% is likely to result in functional benefit.
Speaker Change: I think that will be a discussion that we have going forward, but that's, if you think about our data, to date, every patient that we've published data on is above that threshold.
Steve: I'll field the second question to Steve if that's okay. Hi Gina, thanks for the questions. So 314 and going to dose level 4 in our phase 2 studies.
Curran Simpson: Why do that? We've certainly met our target product profile in diabetic retinopathy and that's why we're so excited with the advancement towards Pivotal that Curran and I have summarized
Speaker Change: We've also seen, as I have highlighted, excellent safety.
Curran Simpson: So I think the key consideration is we're going higher, in part, because we can. We really have the flexibility given the excellent safety that we believe is due to the compartmentalized route into the supracroidal space as opposed to less compartmentalized spaces like the intravitreal space and, particularly, with our product, RGX 314. So, in collaboration with AbbVie, we're doing this, and I think it also fits just general basic drug development where if you have good safety to really fully characterize a product, it makes sense to continue looking at higher doses if you can.
Speaker Change: So I think the key consideration is we're going higher in part because we can. We really have the flexibility given the excellent safety that we believe is due to the compartmentalized
Curran Simpson: Rao
Speaker Change: into the supracroidal space as opposed to
Speaker Change: and other less compartmentalized spaces like the intravitreal space and particularly with our product RGX 314.
Speaker Change: So, in collaboration with AbbVie, we're doing this. And I think it also fits just general basic drug development, where if you have good safety to really fully characterize a product, it makes sense to continue looking at higher doses if you can.
Speaker Change: Thank you.
Speaker Change: Your next question comes from the line of Vikram Purohit.
Curran Simpson: Thank you, Morgan Stanley, with the subretinal approach. Thanks. Sure, yeah, it was about the 314 Super Corridor in Wet AMD, just wondering what the path is to a pivotal program there, and... How do you see a potentially pivotal effort for 314 and Red Amps? This is Curran.
Speaker Change: Of Morrigan's Townie. Please go ahead.
Bikram Parahim: Great, thanks for taking our questions. We had two first on.
Bikram Parahim: 202, could you just speak a bit more about the functional assessment data we're going to be getting later this year, what your guidance is to best interpret that to
Speaker Change: Get a sense of differentiation, real-world differentiation, and...
Speaker Change: How that data set might play into discussions with regulators on next steps.
Speaker Change: And then secondly on 3.1.4 for suprachoroidal and wet AMD, could you talk a bit about how you see that program moving towards a pivotal program and how that pivotal program potentially for 3.1.4 and wet AMD could overlap with efforts with the subretinal approach? Thanks.
Bikram Parahim: Okay, I can take the first question.
Speaker Change: or Steve do you want to start with the second one or could you that I missed the the second one could you repeat the second one
Speaker Change: Sure, yeah, it was about 314 supercoital and wet AMD, just wondering what the path is to a pivotal program there and how you see a potentially pivotal effort for 314 and wet AMD overlapping with your efforts with the subretinal program you currently have underway.
Speaker Change: Sure, so with all the experience we have with wet AMD, we have a pretty good sense of assessing both safety and efficacy, both from our subretinal experience and also the prior cohorts we've done with supercroidal.
Speaker Change: So, I think it's the usual endpoints that we think of. We get to take advantage of the totality of evidence on top of, of course, having good safety. So,
Speaker Change: biomarkers like retinal thickness, where we get a very good objective measure.
Speaker Change: BCBA and of course reduction in treatment burden.
Speaker Change: So we'll really look at all of those to see what type of response we get at six months and longer.
Speaker Change: And really compare that to what's been seen, for example, even in our subretinol program, where we want to see good durability and really maintain
Speaker Change: anatomic control as measured by retinal thickness
Speaker Change: BC VA control while dramatically reducing injection burden and we've often talked about at least 50% of patients not needing any injections and over 50% of patient reduction in injection burden
Steve Pakola: To the first question, in terms of functional data in the fall, just to baseline, we measure microdystrophin at a three-month time point, and then on the functional assays, we measure generally every three months, Vikram, you also had the question of how do we see this in the context of our ongoing pivotal Subretinal program for wet AMD when thinking about suprachoroidal, I think it's fair to say that both we and AbbVie really see opportunities in both, and that's why we both are together advancing further evaluation of, Your next question comes from the line of Paul Choi of Goldman Sachs. Please go ahead, and I'll turn it over to Steve to address the 314 question.
Speaker Change: And this is Curran. To the first question, in terms of functional data in the fall, just to baseline, we measure microdystrophin at a three-month time point, and then on the functional assays, we measure generally every three months.
Speaker Change: A number of functional assessments that...
Speaker Change: you've seen historically with other programs
Speaker Change: And in the fall, I would expect to see a significant amount of functional data out to 12 months for...
Speaker Change: the dose level one patients and for
Speaker Change: Some of the early dose level 2 patients, you'll see six and probably nine month data.
Speaker Change: for them, things like Time to Rise and NSAA as an example. We haven't finalized exactly what data will come out because it's still emerging, but that's the plan for the fall.
Speaker Change: Vikram, you also had the question of how do we see this in the context of our ongoing pivotal subretinal program for wet AMD when thinking about supracaroidal.
Speaker Change: I think it's fair to say that both we and AbbVie really see opportunities in both and that's why we both are together advancing further evaluation of
Speaker Change: SCS at DL4 for this while we continue with the pivotal program with subretinol. Certainly the opportunity that we see with subretinol given
Speaker Change: The gold standard in safety and efficacy that we've shown in excellent durability has us very excited about that. There's, of course, the...
Speaker Change: opportunity to expand the optionality by having an in-office procedure and we look forward to gathering more data in the additional cohort to to keep evaluating that option.
Speaker Change: That's helpful, thank you.
Speaker Change: Your next question comes from the line of Paul Choi of Goldman Sachs. Please go ahead.
Speaker Change: Hi, good afternoon and thanks for taking our questions. My first is, I was wondering if you could maybe just elaborate on
Paul Choi: Interest levels in the patient community and clinical community for 202, a potential pivotal trial later this year or early next year in the wake of the recent Elevitus label expansion and approval there. And then my second question on 314 is...
Speaker Change: With regard to dose cohort 4 here, I know you specified that there would be prophylactic steroid use here, but could you maybe comment on a view whether there would be potentially
Speaker Change: Reduced need for rescue VEGF use. A competitor recently provided some updated data for their program.
Speaker Change: And I think this came as a bit of a surprise, so just any thoughts there as to whether those Cohort 4 could potentially either increase the injection-free frequency or reduce the rescue usage as you prosecute that cohort? Thank you.
Speaker Change: I can take the first one and then I'll have Steve address the second question. I think on patient recruitment for 202,
Speaker Change: We've been able to check in with sites and investigators at meetings like PPMD and we've seen nothing but really strong interest in the program. Many of these centers have up to 100 patients and, you know, just to
Steve: Having discussions with the investigators around...
Steve: Are people still interested in our study given that there's a product on the market? The resounding answer is yes.
Speaker Change: There are many patients that are looking...
Speaker Change: At our program and seeing the differentiation that it offers, seeing the safety that's been demonstrated to date, and I would say that there's strong interest and therefore, on our end, strong confidence in our ability to recruit the study.
Steve: So, early days, I feel very confident in our ability to recruit the Pivotal program. And I'll turn it over to Steve to address the 314 question.
Steve Pakola: Regarding DL4, we certainly think there's the opportunity that we could decrease rescue use further than what we've seen, while maintaining visual acuity, benefit, instability, and also anatomic control. As I mentioned in one of the earlier questions, we have the flexibility to do that, and also if you start to run into the issue of how long a duration of prophylactic steroids can really be tolerated. So that's why we're very excited about our safety profile where we don't need extended prophylactic steroids.
Steve: Sure, so, regarding DL4...
Steve: assessment in these indications.
Steve: We certainly think there's the opportunity that we could decrease rescue use further than what we've seen while maintaining visual acuity benefit.
Steve: instability and also anatomic control. As I mentioned to one of the earlier questions, we have the flexibility to do that.
Speaker Change: [inaudible]
Steve: There's either a concern about additional safety issues, including immune response and inflammation.
Speaker Change: and also if you start to run into the issue of...
Speaker Change: How long a duration of prophylactic steroids can really be tolerated. So that's why we're very excited about our safety profile, where we don't need extended prophylactic steroids.
Steve Pakola: So I think the totality of that does give us the chance to go higher and see if we can reduce the injection burden further. And just one follow-on, Paul, to the question on recruitment, one of the purposes of the data release we did today was really to show people the differentiated level of microdistrophin in some of the older patients that have been treated, so that's just another piece of information that a patient can use when they're deciding what therapy to have their child treated with. So that was one of the purposes of that release, to help people understand our product Thanks for taking our questions, from Bank of America. Please go ahead. Hi, good afternoon. This is Mary Kate on for Alec today.
Speaker Change: So I think the totality of that does give us the chance to go up higher and see if we can reduce injection burden further.
Speaker Change: And just one follow-on, Paul, to the question on recruitment. One of the purposes of the data release we did today was really to show people
Paul Choi: The differentiated level of microdistrophin in some of the older patients that have been treated, so...
Speaker Change: That's just another piece of information that a patient can use when they're deciding what therapy to have their child treated with. So that was one of the purposes of that release is to help people understand our product a bit more.
Speaker Change: from Bank of America. Please go ahead.
Speaker Change: Hi, good afternoon. This is Mary Kate on for Alec today. Thanks for taking our question.
Curran Simpson: Thanks for taking our, Given questions around safety for others in the field, what kind of safety database do you expect you'll be required to collect for approval in terms of size and duration of follow-up? Thank you. We have a commercial-ready process that we won't make changes to in terms of product profile during the pivotal studies.
Speaker Change: Yeah, that's, I think, something that we're still working on and probably will...
Speaker Change: Tie out completely in the pivotal plan that we'll submit to FDA.
Speaker Change: So we're really not able to comment in terms of the very specifics there.
Speaker Change: I think in general, our proposal on sample size is in the...
Curran Simpson: And so that should reduce the sample size. And second, the initial safety record that we've already demonstrated in the trial to date should be positive in terms of how FDA might view the program and how they assess what the sample size should be. So we feel like we're in a good position there, and I think that gives us a good feeling that the recruitment will be accelerated into next year. Your next question comes from the line of Annabel Samimy of Stipo. Please go ahead. Hi, thanks for taking my question. We also have two.
Speaker Change: The in terms of product profile during the pivotal studies and so that should reduce the sample size and second the initial safety record that we've already demonstrated in the trial today.
Speaker Change: what the sample size should be. So we feel like we're in a good position there and I think that gives us a good feeling that the recruitment will be accelerated into next year.
Speaker Change: Your next question comes from the line of Annabel Samimy of Stipo. Please go ahead.
Steve Pakola: First on DMD: stratifying those patients based on age group and measuring them on different metrics depending on their age, and then matching against the natural history for that specific age group. So how much granularity might we see already? And maybe what are you possibly baking into phase three?
Annabelle Samani: Hi, thanks for taking my question. We also have two. First, on DMD, just bringing back the...
Annabelle Samani: The question of functional data and what you might be looking for, given the broad age group that you're looking at and maybe the different levels of ambulation, are you giving any consideration to stratifying those patients based on age group and measuring them on different metrics depending on their age and then matching it against the natural history for that specific age group? So how much granularity might we see already and maybe what are you possibly baking into phase three? And then on 314, I guess I'm trying to understand how you're thinking about this dose level four in light of other competitors in the space.
Steve Pakola: And then on 314, I guess I'm trying to understand how you're thinking about this Dose Level 4 in light of other competitors in the space. Do you feel that the benchmark for you is your subretinal? Or is it the benchmark for you, other competitors in the space?
Speaker Change: Do you feel that the benchmark for you is your subretinal? Is it the benchmark for you, other competitors in the space? And given, I guess, maybe a little bit of a race in the gene therapy space, is there less urgency to be the first one out there or the one to get it right?
Steve Pakola: And given, I guess, maybe a little bit of a race in the gene therapy space, is there less urgency to be the first one out there or the one to get it right? But along with that, of course, we're measuring functional data along the way, and initially, what I would expect in the fall is likely a reference of functional data to baseline levels for the specific patient. Now, if we think about a confirmatory study, you're absolutely correct that studying natural history and matching patients either by age or by disease progression would be part of that strategy that we're having discussions about.
Speaker Change: The population is large, and maybe they're a little bit less desperate than, say, in the rare disease area. Are people looking at this competitive landscape the wrong way? So, a little broader question. Thanks.
Speaker Change: but along with that of course we're measuring functional data along the way and initially what I would expect
Speaker Change: Now, if we think about a confirmatory study, you're absolutely correct that studying natural history
Steve Pakola: So it's actually, I would expect to see both sorts of views as it relates to functional data. So as far as benchmarking is concerned, as I mentioned, we got a lot of experience, many of us from prior programs as well, but certainly in-house, with our subretinal program.
Speaker Change: I'll turn it over to Steve for the 314 question.
Steve: Thanks, Annabel.
Steve: So as far as benchmarking, as I mentioned, we got a lot of experience, many of us from prior programs as well, but certainly in-house.
Steve Pakola: Really, the target is pretty similar in terms of what you have to show when we think of supracaroidal, although perhaps slightly a little broader given the non-surgical in-office opportunity of supracaroidal. I think an important context when thinking of different programs is, So we feel good about this approach, and we know how to look at safety and efficacy to really know when we're in a position to move forward. Your next question comes from Mani Purohit of Living Partners. Please go ahead. And we have made the decision to expand. Commentary: Hi, this is Eric Nassamjian calling you.
Steve: with our subretinal program. Really, the target is pretty similar in terms of what you have to show when we think of supracaroidal, perhaps slightly a little broader given the
Steve: Really assessing how much durability has really been shown.
Steve: So, really being able to look.
Steve: Out to six months and beyond relative to
Steve: When the last loading dose may have been given, for example, in indications like wet AMD,
Steve: And I think with certain agents that require repeat injection, even though they have greater durability.
Steve: There's the reality that at some point you're going to need the re-injection.
Steve: and if you're looking at a time point that's too early to...
Steve: to see that are you going to start seeing the need for rescue creep up and that's why we're excited about a gene therapy approach where you have stable, consistent.
Steve: Anti VEGF activity that can allow for really the ultimate goal of having in a sizable proportion of patients not needing any injections.
Steve: So, we feel good about this approach and we know how to look at the safety and efficacy to really know when we're in a position to move forward.
Steve: Okay, thank you.
Speaker Change: Your next question comes from the line of Mani Purohit of Leering Partners. Please go ahead.
Mani Puruvar: Could you please comment on your strategy in DMD?
Speaker Change: Are you targeting younger patients than SIRUPTA's current label since you've announced you've expanded the age range to 1-3 while SIRUPTA's youngest age is 4?
Steve: Hi, this is Curran. I think it's safe to say we want to build an adequate safety database at a minimum for the patients in ages 1 to 3, but we'll be enrolling across a wide variety of ages in the studies.
Speaker Change: and look at this broad age range including one to three before any elevitous label expansion. So we we've seen this opportunity and now with the
Steve: results safety that we've seen and the microdystrophin expression we've seen across a wide age range on the the upper end it's great opportunity to look at one to three year olds.
Speaker Change: Perfect. Thanks for your commentary.
Speaker Change: The question comes from the line of Eliana Merrill of UBS. Please go ahead.
Eric Masamuddin: Hi, this is Eric Masamuddin calling in for Eliana. Thanks so much for the question. My first one is on 202. Do you have any in-house data from patients already dosed with 202 beyond the three months to help us better understand their ability?
Mani Purohit: What the effects might be over time, and what do you expect to see over time? Do you expect labels to be stable for about three months or more, or do they deepen over time? And that's one follow-up.
Unknown Executive: Do you expect Label to be stable for three months or more? I'm sorry, are you referring to microdystrophin levels beyond three months or other functional data, for example? OK, or higher.
Speaker Change: I'm sorry, are you referring to microdystrophin levels beyond three months or other functional data for example?
Speaker Change: Yeah. OK.
Speaker Change: No, we're taking a biopsy prior to treatment and then at three months. We don't have biopsies beyond that time point, basically per direction with FDA.
Speaker Change: However, you know, we'll obviously be measuring durability in terms of functional outcomes, you know, in the out periods.
Speaker Change: has a longer half-life than microdystrophin that's devoid of that, so I would expect both higher levels of microdystrophin and perhaps sustained levels of microdystrophin
Speaker Change: relative to what you've seen in other literature.
Speaker Change: Got it. And just one quick follow-up. Is there anything that you've been able to identify in terms of patient characteristics that's correlated so far with a higher microdiscipline expression or higher functional assessment?
Unknown Executive: So, the usual caveat that... Your next question comes from the line of Luca Issi of RBC. Please go ahead. Oh great, thanks so much for taking my question. Congratulations on the progress, maybe Curran. Can you just expand a bit more on your recent end of phase two meeting with the FDA? I appreciate that you're still waiting for the minutes, but can you confirm that your read, that you can get accelerated approval and expression across all patients with DMD, and not only patients that are excluded from the Sarepta label today, either because of age or existing immunity? I think that's an important distinction, so any color would be much appreciated.
Speaker Change: So, the usual caveat that...
Speaker Change: there aren't enough patients that really have confidence in terms of predictors. I'd say that the biggest learning so far is actually that age.
Speaker Change: is not predicting a lower microdistrophin as you go up on age which has been a concern that the community has had whether that might be the case and some data from other programs suggest that
Speaker Change: That may be an issue, but we've not seen that at all. So I think the striking thing from our data is even in eight and older, we're seeing very robust microdystrophin levels.
Speaker Change: Beyond that, we're seeing microdystrophin levels across the patient, so no clear differentiator or predictor in this sample to date.
Speaker Change: Got it. Thank you.
Speaker Change: Your next question comes from the line of Luka Isi of RBC. Please go ahead.
Luka Isi: Oh, great. Thanks so much for taking my question. Congrats on the progress, maybe Curran. Can you just expand a bit more on your recent end of phase two meeting with the FDA? I appreciate that you're still waiting for the minutes, but can you confirm that your read
Speaker Change: is that you can get accelerated approval and expression across all patients with DMD, and not only patients that are excluded from the Sarepta label today, either because of age or existing immunity.
Curran Simpson: And maybe still on DMD, how are you thinking about a confirmatory trial? Will you still use NorSTAR as the primary endpoint, or do you think there are other endpoints that can be more sensitive here? Any color, much appreciated; thanks so much.
Speaker Change: We'll use North Star, but we're obviously measuring a number of additional functional indicators.
Speaker Change: not a narrow approval for only patients that are ineligible for current therapy and the basis for that is simply the differentiation of the product.
Speaker Change: that's I think one of the basic tenets of the accelerated approval is unmet need and we feel we have a really strong evolving case that addresses unmet need and our ambition will be to to obtain as broad a label as possible
Speaker Change: Got it. Thanks so much.
Steve Pakola: Your next question comes from the line of Brian Skorney of Baird. Please go ahead. Hey, thanks for taking the question. On the phase three plans for diabetic retinopathy, just trying to engage sort of your level of... What are some of the primary questions that all of these folks will get answered by the FDA or the FDA? I'll give a brief comment and then turn over to Steve. I certainly think that a road map for diabetic retinopathy that's been laid by repeat injection anti-digest that has really allowed us to know what you expect from a negative control arm if you're not receiving an active agent, and the end of Phase 2 meeting into Q4 instead of Q1 next year.
Speaker Change: Your next question comes from the line of Brian Scarney of Baird. Please go ahead.
Speaker Change: you think the FDA will need answers to at the end of phase two meeting.
Brian Scarney: to sort of ensure that this phase three gets kicked off. And maybe just some color on the DME cohort and is there a consideration to pursue these more progressed patients or is the thought here really just to supplement with some data in patients who have progressed on to DME?
Speaker Change: We and Abby have a really high level of confidence in DR progressing into Pivotal next year.
Speaker Change: And I think that's shown in the acceleration of the end of phase two meeting into this year. We're eager to get this study up and going. And I think
Steve: I'll let Steve comment on the details of the pivotal approach, but we feel like there's a very standard approach to developing in diabetic retinopathy established.
Steve Pakola: endpoints and precedent, but I'll let Steve comment on the details of what we're thinking and and how that study should go.
Steve Pakola: Yeah, fortunately, as Curran mentioned, there's a road map for diabetic retinopathy that's been laid by repeat injection anti-VEGF.
Steve Pakola: that has really allowed us to know what do you expect from a negative control arm if you're not receiving an active agent.
Speaker Change: We feel very confident that this is really de-risked quite a lot from a regulatory standpoint. So it's really assessing some things around the edges and some definitions.
Speaker Change: and the like, frankly, when it comes to the pivotal designs. So, I think that's one of the aspects that, given the positive results that we've seen, why we have been able to accelerate and bring this.
Steve Pakola: end of Phase 2 meeting into Q4 instead of Q1 next year.
Speaker Change: and then you're, you're, you know.
Steve Pakola: Yeah, so we are looking at center-involved EME, of course, that's the traditional indication. So, we don't see a need to go outside the box in terms of the type of patient population that we'd be looking at so that we can really have the context of what others have looked at and what others have seen. Hey guys, thank you for taking the question and congrats on your new role. I have a quick question about the WET-MD program, subretinol delivery.
Steve Pakola: Yeah, so we are looking at center-involved EME. Of course, that's the traditional indication.
Speaker Change: We don't see a need to go outside the box in terms of the type of patient population that we'd be looking at so that we can really have the context of what others have looked at and what others have have seen.
Steve Pakola: When do you anticipate sharing data from the fellow eye study? And as a follow-up to that, you know, how it translates to suprachoroidal injections, given those are more likely to interact with the immune system. What is your long-term strategy for treating fellow eyes using suprachoroidal delivery? Thank you.
Steve Pakola: I'll turn that one to Steve.
Speaker Change: up to six months or so from that would give you kind of a rough range of when we traditionally have been comfortable releasing data in this type of indication to really show
Speaker Change: safety and or efficacy when you dose the the second eye. Subretinal I think is the the most straightforward to feel confident that you won't have an issue dosing the fellow eye because of the immune privilege status of the subretinal space.
Speaker Change: supercoroidal, we've seen much less
Speaker Change: inflammation and no safety issues in terms of inflammation compared to, say, intravitreal administration. So that gives us confidence that
Speaker Change: So, we decided to take it one step at a time, first look at subretinal fellow eye, but over time certainly it would make sense to assess fellow eye with supracaroidal as well.
Speaker Change: Got it. Thank you very much for taking the question.
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