Categories Earnings Call Transcripts, Health Care

Applied Genetic Technologies Corp. (AGTC) Q4 2020 Earnings Call Transcript

AGTC Earnings Call - Final Transcript

Applied Genetic Technologies Corp.  (NASDAQ: AGTC) Q4 2020 earnings call dated Sep. 09, 2020

Corporate Participants:

Sue Washer — President and Chief Executive Officer

Mark S. Shearman — Chief Scientific Officer

William A. Sullivan — Chief Financial Office


Joe Pantginis — H.C. Wainwright — Analyst

Matthew Luchini — BMO Capital Markets — Analyst

David Nierengarten — Wedbush Securities — Analyst

Zegbeh Jallah — ROTH Capital Partners — Analyst

Kristen Kluska — Cantor Fitzgerald — Analyst

Yanan Zhu — Analyst

Prepared Remarks:


Good morning, and welcome to the AGTC Fourth Quarter and Fiscal Year 2020 Financial Results Conference Call. Today’s call is being recorded.

Before we get started, I’d like to remind everyone that during this conference call, AGTC may make forward-looking statements, including statements about the company’s financial results, financial guidance, its future business strategies and operations and its product development and regulatory progress, including statements about its planned Phase 2/3 clinical trial.

Actual results could differ materially from those discussed in these forward-looking statements due to a number of important factors, including uncertainty inherent in the clinical development and regulatory process, the extent and duration of the impact of the COVID-19 pandemic, and other risks described in Risk Factors section of AGTC’s most recently filed annual report on Form 10-K and other periodic reports filed with the SEC. AGTC undertakes no obligations to update any forward-looking statements after the date of this call.

For introductions and opening remarks, I’d like to turn the call over to Sue Washer, Chief Executive Officer of AGTC. Ms. Washer, please go ahead.

Sue Washer — President and Chief Executive Officer

Good morning, and thank you all for joining us. With me on today’s call are Bill Sullivan, our Chief Financial Officer; and Mark Shearman, Chief Scientific Officer.

Today, we will begin by providing a management update on our plans for our X-linked retinitis pigmentosa or XLRP clinical program and a brief overview of our other activities.

Next, Mark will review our clinical programs with additional details on our XLRP Phase 2/3 plans based on FDA feedback, as well as new preliminary data for the higher dose Group 5 from the ongoing Phase 1/2 trial review our preclinical pipeline, and then Bill will review our fourth quarter and fiscal year-end 2020 financial results. We will then take your questions.

I would like to begin today’s call by noting that we have achieved several critical milestones. As we announced in July, the FDA provided a comprehensive written feedback on our End of Phase 2 submission regarding the protocol design and conduct of our next trial to support future regulatory submissions related to our clinical program and patients with XLRP due to mutations in the RPGR gene.

We continue to move forward as planned with manufacturing, clinical site preparation and other activities to enable initiation of a Phase 2/3 study in the first quarter of 2021. Mark will provide additional information about the expected design of the Phase 2/3 trial a bit later in the call.

In parallel, we plan to expand the ongoing Phase 1/2 trial in order to dose approximately 12 patients in two randomized and masked dosing arms to collect additional data, including a functional mobility course added as a supplemental endpoint. This type of mobility course was used to support FDA approval of Luxturna, the first gene therapy for an inherited retinal disease.

We have already begun prescreening additional patients and expect to begin enrolling in the fourth quarter of 2020. Mark will also provide details on new preliminary data for the higher dose Group 5 in the ongoing Phase 1/2 dose escalation trial, which shows a favorable safety profile, in line with the safety profile previously reported in this trial, as well as the consistent responder rate when analyzing visual sensitivity.

Given this encouraging data, we currently plan to include the higher dose used in the Group 5 as one of two dose levels we move forward in our clinical development. In addition to these exciting developments, we initiated activities designed to support the successful clinical development of both our XLRP and achromatopsia gene therapy candidates, with the launch of a nationwide mobile vision testing program for patients in the ongoing Phase 1/2 trials.

We are also excited to have formally launched a Patient Advisory Council that will initially focus on ensuring that patient and caregiver voices are incorporated into the XLRP clinical program. The Patient Advisory Council includes advocates from the inherited retinal disease global community and will also help to inform development of our ongoing achromatopsia clinical programs and programs in our preclinical pipeline.

We remain on track to report data from the two highest dose groups of the ongoing XLRP clinical trial and our two ongoing Phase 1/2 trials in patients with achromatopsia due to mutations in the CNGB3 or CNGA3 gene before the end of 2020. We continue to advance our pipeline across ophthalmology, otology and CNS and have multiple preclinical programs that are positioned for IND-enabling studies. Mark will provide an update on these programs later in the call.

Our XLRP program is advancing towards a Phase 2/3 trial, which we expect will commence in the first quarter of 2021. We believe the sustained improvement in visual function that we have observed in the Phase 1/2 trial to date gives us an industry-leading position in this indication.

We have also seen early evidence of biological activity in both achromatopsia trials. We believe that our robust technology platform unmatched manufacturing productivity and extensive capabilities to support our preclinical and clinical programs demonstrate that we have the expertise to develop best-in-class therapies that provide meaningful benefit to patients.

As discussed, during our third quarter 2020 call, AGTC has been taking steps to manage through the COVID-19 pandemic and has been able to limit the disruption to our operations and manufacturing.

I have previously detailed several innovative and creative approaches that we are taking to proactively address potential pandemic-related challenges, including a mobile vision testing program that allows us to gather data from patients in our ongoing clinical trials who are unable to travel to the site, whether they would ordinarily undergo evaluation.

There is a high enthusiasm for this program among patients, physicians and clinical investigators. We believe that it validates both our commitment to the patients who participate in our trials and our ability to create innovative solutions that address the real-world challenges of gene therapy development. We have conducted more than 25 visits to date.

I will now turn the call over to Mark for an update on our clinical and preclinical programs. Mark?

Mark S. Shearman — Chief Scientific Officer

Thank you, Sue. Today, based on our analysis of the comprehensive written feedback from the FDA, I will present several changes we have made to our XLRP clinical development plan, adjusting the clinical endpoint for visual sensitivity, including two masked active arms in the Phase 2/3 study and extending analysis time prior to dosing the contralateral eye. I will also briefly review the status of the achromatopsia clinical trials, the preclinical pipeline and provide an update on our vector manufacturing platform.

Let me begin with an update on our ongoing Phase 1/2 clinical program in XLRP, which as Sue noted, is moving toward a Phase 2/3 trial, which we expect will commence in the first quarter of 2021.

The data we have presented previously demonstrate that our XLRP candidate provides early and sustained improvements in visual sensitivity in centrally dosed patients that are supported by encouraging trends in visual acuity and quality of life survey results, suggesting that these improvements are positively impacting patients’ day-to-day life. We have completed the initial targeted enrollment with 28 patients dosed across six dose groups and the patients dosed to date continue to demonstrate a favorable safety profile.

To provide context for our discussion today, let me briefly review those results. The chart on Slide 10 shows sustained increase in visual sensitivity in the four responders of eight centrally dosed and evaluable patients in Groups 2 and 4 with the treated eye shown in red and the untreated eye shown in gray. This increase in visual sensitivity, as measured by mean change in sensitivity within the treated area, was sustained through the six-month time point.

On Slide 11, the graph show a positive trend in visual acuity in seven of nine centrally dosed patients, with treated eye shown on the left and untreated eyes on the right. Again, this is sustained through the six-month time point. Some patients who improved in either visual sensitivity or visual acuity also anecdotally reported noticeable improvement in visual function, including clearer vision and reduced night blindness.

The second way to analyze microperimetry data is to use pointwise analysis. That is to say identify points within a given increase or decrease in sensitivity at each loci to be consistent with feedback from the FDA and mirror how other research groups in the XLRP gene therapy space are analyzing visual sensitivity data.

In future trials, we will define the responder as a change in visual sensitivity of at least seven decibels in at least five 5 loci at month 12, which could represent a clinically meaningful benefit.

To this end, we present in Slide 12, a reanalysis of the MAIA microperimetry data from centrally dosed Group two and four patients at month six. In addition, we are also reporting for the first time the same analysis from the Group 5 dosed group at month six.

When the patients analyze using our new definition of visual sensitivity response, seven of the 15 centrally treated patients from all three dose groups combined had at least 5 loci that increased by at least seven decibel, six patient at month six and one patient at month three.

Focusing on the Group 5 dose group, a dose level that we are planning to move forward. In this analysis, four of seven patients met the response criterion. Of note, if using the inclusion/exclusion criteria for visual sensitivity planned in the upcoming Phase 2/3 trial, one Group 5 patient would be removed, such that the responder rate in this case would be four of six or 67%.

We do not currently have a complete set of month 12 data available, which will be necessary to fully evaluate this promising Phase 1/2 finding. In addition, our Phase 1/2 did not include a control arm for comparison, which will be included in our Phase 2/3 and necessary to fully evaluate efficacy.

Other companies have reported visual sensitivity using another analytical method, the static full-field analysis via the Octopus perimeter. This device measures visual sensitivity across a wider area of the retina as compared to the MAIA to include areas outside the macular and into the periphery.

Slide 13 reports perimetry data as retinal sensitivity improvements using pointwise analysis, plotting the points on the perimetry grid and indicating an increase or decrease in at least seven decibels for a given loci. We have provided example data from three patients comparing the treated and untreated eyes and which represents in green, all loci increasing by at least seven decibels at the time points indicated.

While challenging to compare across research groups, due to variations in grid patents used and bleb placements achieved, we believe this analysis shows our XLRP product produces comparable results to those reported by others via the Octopus perimeter. We also believe that since the injection of the product is in the central macular region that MAIA provides a higher resolution measurement of retinal sensitivity in the target area.

Based on the publicly available information from our competitive XLRP program, we are confident that we have a very strong competitive position in this indication. As shown in the previous Slide 11, referring to BCVA, we are the only company to record positive trends in visual acuity in our Phase 1/2 clinical study and we have reported early and sustained improvements in visual sensitivity.

We have also demonstrated superior gene expression in side-by-side non-human primate studies and conducted a more extensive analysis of the stability profile for the gene construct.

Finally, we believe that we may have a safety advantage in that unlike data reported in competitive studies, we have not seen evidence of late-stage inflammation in any patients, allowing for a wider dose range to be advanced into late-stage trials.

Slide 15. This slide outlines the proposed design of the Phase 2/3 trial. For ophthalmology studies, in general, there is often a concern of possible patient bias that could influence endpoints due to the psychometric nature of the test protocols, and that to the extent possible this should be minimized.

We plan to enroll approximately 60 patients across two masked active arms and an untreated control group. The dose concentrations used will be 1.2E+11 vg/mL Group 2 in the Phase 1/2 trial and 1.1E+12 vg/ml Group 5 in the Phase 1/2 trial, providing a tenfold dose range.

We also plan to add an important secondary endpoint, a standardized functional mobility test that captures real-world impacts on XLRP patients by objectively assessing changes in patient mobility that are secondary to improvements in vision, resulting from therapeutic intervention.

In addition, other planned secondary endpoints will include BCVA, full-field sensitivity threshold or FST, and changes in contrast sensitivity. We plan to submit a six-month interim analysis of the data to the FDA to discuss final planning. Based on those discussions, we may modify the final trial designs, enrollment numbers and statistical analysis plan.

We also want to discuss with the FDA the possibility of finalizing the dose selection for the treatment of the contralateral eye based on this six-month interim data. AGTC expects to begin this trial in the first quarter of 2021 and provide results from a six-month interim analysis in the third quarter of 2022.

After any adjustments made based on this feedback, if the totality of the data collected shows a compelling benefit risk balance, we believe it will support a BLA filing. Timing of the reporting of these data may be impacted by future effects of the COVID-19 pandemic on clinical trial enrollment, which, as previously indicated, has impacted pediatric enrollment in our achromatopsia trial.

As Sue noted on Slide 16, we also plan to expand the Phase 1/2 trial to include approximately 12 additional patients and expect to begin enrolling in the fourth quarter of 2020. We expect these data to provide a near-term assessment of the correlation between changes in visual sensitivity and patients’ ability to navigate the functional mobility course.

Slide 17 outlines our next steps in moving forward with XLRP clinical development. We are on track to finalize the protocol and initiate the Phase 2/3 in the first quarter of 2021. We have begun manufacturing the clinical material for this trial at overlapping CDMOs and GLP testing labs, which will support our timeline for initiation.

We expect to report data from the ongoing Phase 1/2 trial in the fourth quarter of 2020, which will include 12-month data for Groups 1 through 4, evaluating durability of effect and continued safety. And interim data from Groups 5 and 6, which will inform our understanding of safety and efficacy of our XLRP candidates at higher doses.

Now, I will move on to discuss our ongoing Phase 1/2 trials in achromatopsia. As previously announced in both achromatopsia studies, we have seen early signs of biologic activity supported by patient reported outcomes with no dose limiting toxicity, as well as DSMC-approved dosing of pediatric patients to the highest dose.

Enrollment of the adult cohorts is complete and enrollment of pediatric cohorts is ongoing, with four pediatric patients dosed in each trial. We look forward to sharing additional data with you before the end of 2020.

I will now move on to discuss our preclinical pipeline and progress in our manufacturing platform. Our preclinical pipeline includes two ophthalmology programs, one of which targets the dry form of age-related macular degeneration or AMD and three programs targeting central nervous system, CNS disorders.

The CNS programs address adrenoleukodystrophy, as well as two additional rare genetic CNS indications, frontotemporal dementia and amyotrophic lateral sclerosis. These represent diseases with substantial patient populations that have well-defined genetic and clinical phenotypes. The targets for these indications are progranulin and C9orf72.

We have also collaborations with Otonomy and Bionic Sight for genetic forms of hearing loss and optogenetics, respectively. Our pipeline program is built on our industry-leading AAV manufacturing technology and expertise, while enabling us to expand into a broader array of indications that have substantial unmet clinical need.

For example, a 50-liter manufacturing run using the process which we are using to provide material for our Phase 2/3 trial can produce an estimated 2,000 ophthalmology doses.

Based on data generated at our facility and by our CDMOs, we believe that our manufacturing process is not only more productive than other methods, but also produces material with greater purity, in that the percent of vectors containing the desired gene of interest is nearly 90% and process residuals are generally below the detectability of current test methods.

I will now turn the call over to Bill, who will briefly review our fiscal results for the fourth quarter and 2020 fiscal year.

William A. Sullivan — Chief Financial Office

Thank you, Mark. For the fourth quarter of 2020, we recorded a net loss of $14.5 million compared to a net loss of $10.5 million for the fourth quarter of 2019. The increase in net loss was primarily due to a $2.1 million increase in R&D expenses, a 600,000 increase in G&A expenses, and an $800,000 decrease from investment and other income.

The $2.1 million increase in R&D expenses was primarily the result of increased XLRP spending, associated with Phase 2/3 clinical trial activities, which will enable us to initiate our studies as quickly as possible, increased achromatopsia spending associated with patient enrollment, and increased employee-related costs.

G&A expenses increased $600,000, primarily due to higher employee-related costs and other G&A associated with normal business operations, partially offset by decreased share-based compensation expense and legal and professional fees.

Now move on to our financial guidance. We ended the fourth quarter of 2020 with a strong balance sheet. Total cash, cash equivalents and investments as of June 30, 2020 were $80.5 million. We believe these funds be sufficient to allow AGTC to generate data from our ongoing clinical programs, initiate the XLRP Phase 2/3 clinical trial and advance our preclinical programs into the fourth quarter of calendar year 2021.

That concludes the team’s remarks today. Operator, you may now open the line for a question-and-answer period.

Questions and Answers:


Thank you. Now, we’ll be conducting a question-and-answer session. [Operator Instructions] Our first question today is coming from Joe Pantginis from H.C. Wainwright. Your line is now live.

Joe Pantginis — H.C. Wainwright — Analyst

Hi, good morning, everyone. Thanks for taking the question and hope you’re all doing well. Two questions. First, as we’re looking at increasing visibility for all the three programs, it’s nice to see the competitive slide that you put in your presentation today.

And one of the things I wanted to focus on is, when you look at the improvements or lack of improvements in BCVA, depending on the program, just curious if you can comment on baseline characteristics of some of these programs that you might be aware of, because as we’ve been talking to physicians in the space, there’s a lot of dependency on the baseline characteristics?

Sue Washer — President and Chief Executive Officer

Well, good morning, Joe. Thank you for joining us today. First of all, we don’t have detailed information about the baseline characteristics or the patients or even detailed data from our competitors in the field. We can only speak to our data.

And what we can say for BCVA is that, it is not the best endpoint to look at in XLRP, because I think, as you may remember from our discussions, XLRP patients do retain central vision into good central vision, very good central vision late into the disease progression, because this is a disease that starts in the periphery.

So depending on where those baseline patients start with really good vision, it’s hard to see an improvement in that really good vision. And so that’s why we’ve always characterized our BCVA data is very supportive and encouraging, but not statistically significant. And why we feel visual sensitivity or visual fields or microperimetry, however, you want to characterize that endpoint is the better endpoint for XLRP.

Joe Pantginis — H.C. Wainwright — Analyst

No, that is a very good reminder and helpful feedback. Thanks, Sue. And then my last question is really just looking forward right now, obviously, these are orphan indications, but the unmet need is there. So as you look towards commercialization, you’re obviously doing a lot of good background activities with regard to manufacturing that you reminded us today as well. Any thoughts around business development around any of your programs?

Sue Washer — President and Chief Executive Officer

So as we have stated before, we are continuing to have discussions with potential partners, both for our XLRP program internationally, as we’ve discussed in previous calls, as well as our extensive preclinical programs. We have some that are interested in potentially partnering with us on those, so that we can move a greater percentage of them forward quickly into the clinic.

Joe Pantginis — H.C. Wainwright — Analyst

Fantastic. Looking forward to the data in the fourth quarter. Thanks a lot.

Sue Washer — President and Chief Executive Officer

Thank you, Joe.


Thank you. Our next question today is coming from Matthew Luchini from BMO Capital Markets. Your line is now live.

Matthew Luchini — BMO Capital Markets — Analyst

Great. Thanks for taking the questions. Good morning, everyone, and congrats on the progress. So wanted to first ask, with regards to the Phase 2/3, this interim analysis that will be submitted to FDA and the potential for modification to design, numbers, stat plan, et cetera. Can you just talk a little bit about, I guess, what it could be that would be driving those changes?

And maybe more importantly, how confident or how we should be thinking about the probability that the design, trial size, et cetera, that you’re putting forward today will be what you’re actually able to take across the finish line? And then I have a couple of others after that.

Sue Washer — President and Chief Executive Officer

Good morning, Matthew. Thanks for joining the call. So that’s a very pertinent and important question, obviously. We based our trial design, based on both the data from the Phase 1/2 and the feedback from the FDA on our submission. And obviously, we’ve adjusted the definition of a responder and adjusted that visual sensitivity analysis.

And for that reason, we thought a six-month IA to look at the data at an interim time point to just double check that with this new analysis and use of a control arm as a competitor that we got consistent data with the appropriate.

And then Mark, do you want to go into some of the more details about what we’ll be looking for there? And how we made the decisions on dose selection and patient numbers going forward?

Mark S. Shearman — Chief Scientific Officer

Sure. Yes. Good morning, Matthew. So as you’re aware, we conducted an extensive series of preclinical work to establish an effective dose range. And so we’ve been monitoring the activity in the Phase 1/2 trial during the dose escalation phase to see the correspondence of that. And I think the important thing is that we are able to select two doses that have about a tenfold difference.

We — as of now, we don’t see clear evidence for dose response, but we want to give ourselves the best chance of being able to differentiate the low dose from the high dose. And so that was part of the rationale for selecting the Group 2 dose and the Group 5 dose.

And then as Sue mentioned, we have evidence from the dose escalation Phase 1/2 of the relative activity responder rate using MAIA perimetry. We will replicate that in — attempt to replicate that in the Phase 2/3. And in addition in the Phase 1/2 expansion, where the two doses will be masked, to try to really firm up the data set, so we’ll have a robust basis on which to make the final decisions around the Phase 2/3 trial.

Matthew Luchini — BMO Capital Markets — Analyst

Okay, great. Thank you. That’s helpful. And then two other questions for me. First on the mobility course, it sounds like what you’re using is quite similar to what Spark used with Luxturna. Can you just remind us what, I guess, similarities or differences we should be aware of that are — that matter versus what they did?

And I guess, what validation work is needed on that course before it could be sort of fully blasted into the Phase 2/3? And then lastly, just, I guess, this a yes, no. I just wanted to confirm that in the Group 5, there was also no inflammation that requires secondary dosage of steroids, because that seems to be a good nice point of differentiation for your program relative to some of the others? And with that, I will get back in the queue. Thank you.

Sue Washer — President and Chief Executive Officer

Yes. So, Matthew, I’ll start from the bottom and go up. So on the inflammation, we have not seen in Group 5 any of that secondary inflammation that others have reported. And so the safety profile continues to be the same as what we’ve reported for Groups 1 through 4.

And then I’ll let Mark address more of the details about the mobility test. You’re right, Matthew, that is very similar to that used by Luxturna. We are working with a third-party CRO, who has already been using a mobility test in other retinitis pigmentosa trials. So we’re quite confident in their ability to move forward with us.

But, Mark, do you want to describe the test in a little bit more detail?

Mark S. Shearman — Chief Scientific Officer

Yes. So I think it’s really a simple concept. It’s essentially an obstacle course that patients have to navigate at different light levels. And so since we have evidence of improvements in retinal light sensitivity in the Phase 1/2 dose escalation, it made a lot of sense to see if that MAIA perimetry data translates to an improvement in performance in the maze test.

And so we’ll be looking at that at different light levels to see if the two things correspond. And we want to get it as quick a read on that as possible. And that’s why we’ve also included that in the Phase 1/2 expansion, as well as in some of the–

Sue Washer — President and Chief Executive Officer

No just the — sorry. The last thing that I’ll mention is that, we thought that the maze test was a good kind of intermediary step to connect the quantitative visual sensitivity change in decibels to the patient reported outcome survey.

So that maze test in the middle kind of allows us to correlate in a slightly quantitative way, what patients are reporting to us about improvements in visual function and tie it more concretely to changes in visual sensitivity.

Matthew Luchini — BMO Capital Markets — Analyst

Great. Thank you so much for all the color. Congrats on the progress.


Thank you. Our next question today is coming from David Nierengarten from Wedbush Securities. Your line is now live.

David Nierengarten — Wedbush Securities — Analyst

Thanks for taking the questions. I have two. First off, on the patients, the 12 patients that you’re adding to Phase 1/2, is there any chance to use them as part of the final data set from the Phase 2/3?

And then the second question is relating to that, is there — can you put a finer point, I mean, should we expect a — I don’t know if you can define significant change in numbers for a Phase 2/3 upon further discussions with the FDA? Or are we talking plus or minus 5% or 10% patient number as you refine the plan with the FDA, if that’s possible to give a finer detail on your expectations there? Thanks.

Sue Washer — President and Chief Executive Officer

So good morning, David. I hope you’re doing well. And the question about the six-month IA, I think that one of the reasons we’re doing that six-month IA is, because our Phase 1/2 did not have randomization and masking and did not have a specific control arm. We have done extensive analysis of the data from the Phase 1/2 and are quite confident in the trial design and the statistical analysis plan that we’ve put together.

But because we didn’t have the control arm and because we specifically didn’t have the maze test in the Phase 1/2. We want to take that opportunity at the six-month IA. So we can’t say what changes there may be there, but we feel that the plan we put together has a very good chance of being the final plan. But we just want to base that at that IA on some real data with the maze test, with the control arm before we get all the way to the 12-month study.

And then I’ll let Mark address the first question about the Phase 1/2 expansion. Mark, you might be on mute.

Mark S. Shearman — Chief Scientific Officer

I’m sorry, yep. Hi, David.

David Nierengarten — Wedbush Securities — Analyst


Mark S. Shearman — Chief Scientific Officer

Yes. So I think the plan really is to collect as much data as possible. If you recall the Phase 1/2 study is using a different clinical trial material lot. So we have a new improved process, what we call process three that will be used in the Phase 2/3 study. So we’re also doing comparability between those two lots of material, lot two processes. I think overall, the intention is to collect as much data as possible and to use the totality of the data in any subsequent submission knowing that it’s generated in slightly different circumstances.

David Nierengarten — Wedbush Securities — Analyst

All right. Thank you. Those helpful reminder of the difference in processes. Thanks.


Thank you. Our next question today is coming from Zegbeh Jallah from ROTH Capital Partners. Your line is now live.

Zegbeh Jallah — ROTH Capital Partners — Analyst

Good morning. Congrats on the data and thanks for taking my question. Just have two quick ones. Can you speak a little about the enrollment criteria that will be used for Phase 2/3, since you did mention that there was a patient in Group 5 that would have been excluded based on that criteria.

And then after the six months interim analysis for the Phase 2/3 study, where you’re probably going to discuss the potential to dose the contralateral eye. I’m just wondering how that data may perhaps factor into the approval since it’s going to be based on 12-month data and that’s just going to be six-month data? And if you also explore the contralateral eye dosing in the Phase 1/2 extension phase?

Sue Washer — President and Chief Executive Officer

So I’ll make a comment and then — and put it over to Mark to provide some additional information. We — the trial — the Phase 2/3 trial is set up to dose the first one eye and it is statistically powered based on the one eye data. So we’re — the trial itself does not require the dosing of the contralateral eye to be able to see a difference between the active arms and the control arm.

And by the time of any submission, given that we have a positive discussion with the FDA, the six-month part IA, we will have had additional testing in that contralateral eye that will be able to include in any future submission. So the powering of the trial, the significance of the trials not dependent on that contralateral eye.

And then over to Mark for the previous question.

Mark S. Shearman — Chief Scientific Officer

Yes. So the design of the two additional studies that we’ve mentioned are obviously based on our experience with the Phase 1/2. So most, many of the inclusion criteria remained the same, which are related to the ability of the patients to perform the various tests as well as the requirements of them in terms of the genetic mutation and so on.

So we don’t have any major changes to that really other than those based on the data that we currently have and how that has influenced the perimetry results. And so that’s pretty much the path forward. We have vetted this with a what we call a protocol advisory board. And so for both the Phase 1/2 expansion, as well as the Phase 2/3, I think, we’re pretty much ready in that regard.

Zegbeh Jallah — ROTH Capital Partners — Analyst

Thanks, guys, really helpful. And then for the Phase 1/2 extensions, you’re not going to be dosing contralateral eye, just one eye?

Mark S. Shearman — Chief Scientific Officer

So for the Phase 1/2 just one eye. Yes.

Zegbeh Jallah — ROTH Capital Partners — Analyst

Thanks, guys. Congrats again on the data.

Sue Washer — President and Chief Executive Officer

Thank you, Zegbeh.


Thank you. [Operator Instructions] Our next question today is coming from Kristen Kluska from Cantor Fitzgerald. Your line is now live.

Kristen Kluska — Cantor Fitzgerald — Analyst

Hi, good morning, everyone. Thanks for taking my question. The first one I have is with regards to the six-month interim analysis with the agency that you are guiding could occur during the third quarter of 2022. Do you expect that this will include six months data from the entire patient set, meaning that you’re roughly guiding to fully enroll the trial in about a year? Or are there a certain number of patients the agency requested to see at this time point?

Sue Washer — President and Chief Executive Officer

So to be clear, the six months IA, Kristen, was at our discretion, because we wanted to be able to get an early read with the modified endpoint, as well as the two masked arms compared to a contralateral arm and we didn’t want to wait all the way to the end of 12 months to get that — to get a look at the data.

So the six-month interim analysis was at our discretion, and then we’ll be able to take the data to the FDA and ask for their feedback. And double check that we took their recommendations and their feedback into account as we design the trial. We do not plan to wait to do that six months IA until all patients are doses — dosed. It will be — the six-month IA will be based on a subset.

Kristen Kluska — Cantor Fitzgerald — Analyst

Okay, great. Thank you. And then I know, you recently reported some data in a — in the human gene therapy publication. So, curious, as you look at XLRP in general, now that you’ve reported data from five different dose cohorts. How you think that matches up with the canine model and the different models that you’ve looked at in-depth in the preclinical development, both on safety and efficacy? And how these findings might help you with some of your earlier stage pipeline where you’ll be in CNS, otology, and additional ophthalmology programs, potentially looking at dose escalation effects there as well?

Sue Washer — President and Chief Executive Officer

Well, thank you for that question, Kristen, because we really do believe that the breadth and depth of preclinical work that we do to support our clinical programs is one of the things that sets us apart. We’re one of the few organizations that works with large animal models on a regular basis, not just the naturally occurring dog models that you mentioned, but also extensive non-human primate work to make sure we’re targeting cells appropriately. And we think this is a critical part of our ongoing product development.

And I’ll turn it over to Mark to provide some more details about how we feel that, that preclinical work correlates to our work in the clinic. Mark?

Mark S. Shearman — Chief Scientific Officer

Yes. Hi. Hi, Kristen. So — yes, so you’ll see that we’ve released the dose levels for the planned clinical study. And those were really predicated on the biologic activity that we had witnessed in the canine model now accepting that it’s only a model of the disease with different characteristics.

I think it was very gratifying to know that the dose range that we found activity with in the dog model has essentially held up in the human studies to date, meaning that the Groups 2 and 5, for example, are both active doses preclinically. So all in all, I think, we’ve been very pleased that we feel that there is some predictive validity of the dog model for what we’re seeing in humans.

Kristen Kluska — Cantor Fitzgerald — Analyst

Great. Thank you.


Thank you. Our next question today is coming from Jim Birchenough from Wells Fargo. Your line is now live.

Yanan Zhu — Analyst

Hi, thanks for taking the questions. This is Yanan on for Jim. Congratulations on the data. So first, just wondering for the new responder analysis on visual sensitivity. Could you share the data on the untreated eye?

Sue Washer — President and Chief Executive Officer

So in the untreated eye, we did not see the same kind of responder rate that we saw with the treated eye. And I don’t think we have that specific information at hand, but would be happy to pull it and get back to you, Yanan.

Yanan Zhu — Analyst

Got it. Thanks, Sue. And in a — you might have touched on this earlier. So apologize if I missed that. In the Phase 2/3 study for the efficacy analysis, what would be used as the control? Would it be the untreated eye or the eye from the untreated control subjects?

Sue Washer — President and Chief Executive Officer

Yes. The trial, Yanan, the Phase 2/3 trial, as well as the Phase 1 — as the Phase 2/3 trial is set up to compare each active arm individually to the control arm. We will also be able to do analysis, obviously, between the treated and untreated in the active arms. But the statistical analysis plan is set up to determine a difference between each active arm and the control arm.

Yanan Zhu — Analyst

I see. And because the treated arm has the bleb, how would you match that to the untreated patients? How do you determine, I guess, what would the bleb be placed in a control patient — in an untreated patient?

Sue Washer — President and Chief Executive Officer

So going forward in Phase 2/3 development, as well as in the Phase 1/2 expansion, we are really trying to standardize as much as is surgically possible the placement of the blood in the central macular region. And so the analysis will be done by the same — in the same set of loci within the treated eye in the active arm as the untreated eyes in the control group.

Yanan Zhu — Analyst

Got it. And last question, how many centers would be included in a Phase 2/3? And how do you think about the surgeon training for consistency in the subretinal injection? Thanks.

Sue Washer — President and Chief Executive Officer

So we’re not guiding right now to the exact number of sites. We are still actively contracting and negotiating contracts with sites, both in the United States as well as ex-U.S. We plan to conduct this Phase 2/3 globally. And when it comes to surgeon training, we have a very detailed surgical plan that I know we’ve discussed with many of you on the phone previously. But we are tailoring the surgical training to the background of each surgeon.

So if a surgeon has worked with us previously, obviously, then we fully trained them through our program and they’re ready to go. If the surgeon has done extensive amounts of other gene therapy subretinal injections, then they might have a very short training program that they go through with us and so and so on. So we have a very tiered approach to training the surgeons.

Yanan Zhu — Analyst

Got it. Thanks, Sue.


Thank you. We have reached the end of our question-and-answer session. I’d like to turn the floor back over to Sue Washer for any further closing comments.

Sue Washer — President and Chief Executive Officer

Thank you, operator. We are really excited to close out our 2020 fiscal year with a path toward reporting data readouts for all three of our clinical programs by the end of this year and initiating a Phase 2/3 trial for our XLRP program in the first quarter of 2021.

I’m incredibly proud of our team and their ability to continue advancing our clinical programs and working towards our corporate objectives, despite the challenges of the COVID-19 pandemic. The progress we are making in our clinical programs, our manufacturing campaign shows us well for the future.

We have much work to do. But we retain the high level of commitment to patients that has always driven us to achieve our objectives. This commitment has only been enhanced by the productive and insightful interactions we are having with our newly launched patient advisory council. And we expect that the patient and caregiver voices the council provides, together with the clinical and scientific feedback from our scientific advisory board, will help us to develop innovative gene therapies that have clinical and commercial prudential, and so meaningfully improve patients’ lives.

As I always do, I’ll close today’s call by thanking the patients, physicians and the AGTC team for their dedication to our cause and their support of our efforts to transform the treatment of rare ophthalmic, otologic and CNS diseases.

I would also like to thank all of the healthcare workers and first responders who are carrying tremendous burns in order to protect our health and care for our friends, families and colleagues. I look forward to sharing additional achievements with you in the months ahead, and I hope you and your families are safe and healthy. Thank you.


[Operator Closing Remarks]


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