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Edited Transcript of ADVM earnings conference call or presentation 7-Nov-19 9:30pm GMT

Q3 2019 Adverum Biotechnologies Inc Earnings Call

MENLO PARK Nov 8, 2019 (Thomson StreetEvents) -- Edited Transcript of Adverum Biotechnologies Inc earnings conference call or presentation Thursday, November 7, 2019 at 9:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Myesha Lacy

Adverum - Vice President of Investor Relations and Corporate Communications

* Leone Patterson

Adverum - Chief Executive Officer

* Aaron Osborne

Adverum - Chief Medical Officer

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Conference Call Participants

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* Tyler Van Buren

Piper Jaffray - Analyst

* Phil Nadeau

Cowan and Company - Analyst

* Patrick Dolezal

LifeSci Capital - Analyst

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Presentation

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Operator [1]

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Good afternoon and welcome to the Adverum Biotechnologies Third Quarter 2019 Corporate Update Conference Call. (Operator Instructions) I would now like to hand the conference over to Myesha Lacy, Vice President of Investor Relations and Corporate Communications of Adverum. Please go ahead.

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Myesha Lacy, Adverum - Vice President of Investor Relations and Corporate Communications [2]

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Thank you. And welcome everyone. Today, we issued a press release reporting our financial results for the third quarter of 2019. A copy of this release is available on the press releases page of the Investor Relations section of our corporate website at www.adverum.com.

Please note that a replay of today's call also will be available on the events and presentations section of our website. Joining me for the prepared remarks portion of the call today is Leone Patterson, Chief Executive Officer and Dr. Aaron Osborne, Chief Medical Officer. Then Leon, Aaron and Chief Financial Officer Thomas Leung, will be available for the Q&A portion of the call.

As a reminder, we will be making forward looking statements regarding our product development plan, research activities and operations as well as our financial outlook. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those forecasted.

A description of these risks can be found in our most recent form 10-Q on file with the SEC. I would now like to turn the call over to CEO Leone Patterson.

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Leone Patterson, Adverum - Chief Executive Officer [3]

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Thank you, Myesha. Good afternoon, everyone and thank you for joining us today. I'll provide a recap of our recent progress advancing ADVM-022 as well as give a corporate update. Aaron will then further review the progress with ADVM-022, including the OPTIC Phase 1 trial and the data that were presented at [AAO]. We'll then open up the call for questions.

As very much focused on delivering what we believe can be transformative therapies for patients living with serious [otra and rare] diseases, the therapeutic potential of long lasting [gene] therapy approaches is rapidly gaining momentum across many areas of medicine.

Adverum is part of this exciting field with our clinical candidate ASVM-022, a differentiated gene therapy approach that we are developing in our first indication with [AND], which is a leading cause of visual loss in patients over 60 years of age.

We have made significant progress over the past year with ADVM-022. This time last year, we had just [dosed] our first patients in the OPTIC Phase 1 trial. Now, with positive data from our first cohort of six patients in OPTIC, we are continuing to evaluate this therapy's potential, having completed the (inaudible) cohort two, and announcing our plan to dose additional patients in a third and fourth cohort.

In addition, we are planning on developing ADVM-022 for a second indication, diabetic retinopathy with a planned [IND] submission in the first half of 2020. Over the past few months, we have presented at three congresses, data from our first cohort of six patients in the OPTIC Phase 1 trial.

First, on September 12th, we presented interim 24 week data at [Resna Society] and then o October 11th at AAO. We presented median 34 week follow up data. Last week, we presented an encore presentation of these data to a gene therapy focused audience at the European Society of Gene and Cell Therapy.

In summary, the data presented on ADVM-022 a single (inaudible) [ingestion] therapy demonstrated the following, durable efficacy with a median follow up of 34 weeks was generally safe and well tolerated with no SAEs and that no patient received a rescue injection.

The clinical data has generated positive interest from the medical and the scientific communities and we look forward to further engagement with these very important groups as we continue to develop ADVM-022.

We also hosted an investor event at AAO, with three leading [KOLs] who shared presentations on the key learnings from the OPTIC Phase 1 trial, real world outcomes with (inaudible) treatment for [win AND], and also future therapeutic approaches for long lasting (inaudible) suppression and with [AND].

These [KOLs] deeply understand the challenge of treating this patient population, who requires frequent [AD] (inaudible) injections to maintain their vision, and they truly appreciate the potential benefits to patients from a long lasting treatment with an intravitreal gene therapy approach such as ADVM-022.

While we continue to gain momentum with ADVM-022 program, we are also making great progress in other areas as well. We are looking forward to being able to occupy a new Redwood City headquarters by the end of this year.

The new facility will allow for the expansion of our in-house process development capacity to the 1,000 liter scale, which is important as we plan to move into later stage clinical trials and prepare for potential commercialization.

We also recently announced a new addition to our executive team with the appointment of Peter Soparkar, as Chief Legal Officer. Peter is an experienced leader who has a wealth of relevant industry experience. We're glad to have Peter onboard as we expand our executive team and bring deep industry expertise to this important function.

Adverum's formula for success is our commitment to developing novel technologies and therapies for patients and building a talented team who can execute and deliver on our mission to bring effective gene therapies to as many patients as quickly as possible. I'd now like to turn the call over to Aaron, who will provide further details on our progress with ADVM-022. Aaron?

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Aaron Osborne, Adverum - Chief Medical Officer [4]

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Thanks, Leone. We have achieved a major milestone this quarter, reporting the first clinical data for ADVM-022, our intravitreal gene therapy for wet AMD. These (inaudible) data are important as they demonstrate that ADVM-022 may provide a single injection option for patients who we otherwise require frequent eye injections to manage their wet AMD.

The clinical data has generated a lot of excitement for us here at Adverum, for our clinical investigators and the patients [they are enrolling into] OPTIC and also for the broader community of ophthalmologists and retina specialists who know firsthand how a truly long lasting anti-VEGF therapy could reduce treatment burden and improve real world vision outcomes for patients living with wet AMD.

ADVM-022 has a unique product profile as potentially the only treatment option that can deliver long term control of wet AMD disease activity in a single intravitreal injection. This could make it a truly convenient option that provides long term VEGF suppression and dramatically reduces treatment burden for managing wet AMD a lifelong disease.

Other long term approaches require a surgical procedure, which besides being less convenient can also entail additional risks beyond those associated with an intravitreal injection.

At AAO last month, we reported additional data from our first cohort of patients in OPTIC, our Phase 1 study. Importantly, the patients involved in OPTIC are not treatment naive patients. They are patients who previously have required frequent anti-VEGF injections to maintain vision.

In the eight months prior to enrolling in OPTIC, these six patients have received a total of 37 anti-VEGF injections. Following ADVM-022 administration in OPTIC with a median of eight months follow up, 0 anti-VEGF injections were required. Investigators and patients alike are excited about the transformative potential of our therapy based on these results.

During AAO, we also announced plans for additional cohorts in the OPTIC trial. Cohorts three and four will enroll more patients at the same doses used in cohorts one and two, [6E to the 11] and [2E to the 11] vector genomes per (inaudible) respectively, we hope to address two key objectives with cohorts three and four.

Firstly, a further 18 patients to be dosed to support [dose ranging] and to confirm the positive efficacy signal observing cohort one. Secondly, [that's a] prevention of inflammation with six weeks of coverage with prophylactic steroid eye drops instead of 13 days with prophylactic oral steroids, as was used in cohorts one and two.

We believe the data generated from these cohorts in addition to the data from cohorts one and two will provide more robust evidence on which doses and steroid regimens best support the further clinical development of ADVM-022.

The switch from oral steroids to steroid eye drops will decrease the systemic exposure to steroids and allow for a longer period of steroid coverage, potentially reducing the occurrence of the generally mild inflammatory events that have been reported after cessation of oral steroids.

The goal is to provide a more effective [prophylactic] for ocular inflammation with steroid eye drops. Dosing is currently underway in the third cohort [of nine] patients,. And this will be followed by enrollment of another nine patients in the fourth cohort.

Looking at future development opportunities for ADVM-022, we are moving forward with our plans to evaluate a second indication. Diabetic retinopathy represents another large and underserved market that may benefit from a long lasting anti-VEGF gene therapy.

Of the estimated 8 million people living with diabetic retinopathy in the US, only 2 billion are diagnosed and only 1 million are being treated. Diabetic retinopathy is the leading cause of vision impairment and blindness amongst working age adults.

As the prevalence of diabetes continues to grow, the prevalence of diabetic retinopathy is expected to increase. There is significant unmet needs for more effective and more curable anti-VEGF therapies that could reduce the incidence of sight threatening complications and improved outcomes in patients with diabetic retinopathy.

We believe maintain consistent levels of VEGF suppression with ADVM-022 could be particularly important for this rapidly progressing disease, potentially improving treatment outcomes over currently available therapies. We look forward to submitting and [IND] for this indication in the first half of 2020. I'll now turn the call back to our CEO, Leone Patterson. Leone?

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Leone Patterson, Adverum - Chief Executive Officer [5]

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Thanks, Aaron. And we'll now open the call to questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions). Our first question or comment comes from the line of Tyler Van Buren, from Piper Jaffray. Your line is open.

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Tyler Van Buren, Piper Jaffray - Analyst [2]

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Hey, guys, good afternoon and congrats on all the progress during the quarter. I guess my first - you know, the concept of topical steroids and having longer coverage versus the oral steroids is interesting. Of the 19 inflammatory events, which I believe was the last number reported, is it possible to tell us how many of those occurred between the 13 days and say - you know, the end of six weeks? Or just give us an understanding of that?

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Leone Patterson, Adverum - Chief Executive Officer [3]

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Yes, Tyler, thanks for the question. I think - I will turn it over to Aaron to answer specifics on the steroid regimen and also the inflammatory response, but what I think I would say is that obviously as we've said all along that inflammation is - can be expected [and not in gene] therapy, and [I say continent of what the story regimen] that we believe will be appropriate [is really being reflected] of what we've seen in the first cohort of patients.

And I think it'd be helpful for Aaron to give some context to the actual timing and why we [think] the prophylactic steroid eye drops will be appropriate.

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Aaron Osborne, Adverum - Chief Medical Officer [4]

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Thanks, Leone. The - generally these inflammatory events were mild, meaning that they were often asymptomatic, though the first time that they were spotted by investigators was typically after the oral steroids [has stopped].

As you remember, we we're giving a total of 13 days of oral steroids in cohorts one and two, that's six days at 60 and then there was a seven day taper. And what we saw was that there were no early inflammatory events that broke through those oral steroids. We saw no clinically significant inflammation during those early periods.

But what we saw was after the oral steroids had stopped, that we saw some of these events be reported. And generally, the peak incidents was in the period of around four to six weeks after administration of ADVM-022. And this is really similar to what has been seen in also some other gene therapy trials.

So, based on this experience from cohort one, we felt it would be better, after extensive discussions with our investigators and other [KOLs] to move to providing a longer coverage, but also something that provides, you know, less systemic steroids as well. Because we know this is a local response. It's generally mild, and therefore a topical approach with eye drops seems to be sufficient.

We haven't seen any case of inflammation breaking through those steroid eye drops, which have been used, and inflammation has generally been highly responsive or that. So, with the topical steroids, we'll provide longer coverage and we hope to reduced the number of those adverse events that we've seen.

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Tyler Van Buren, Piper Jaffray - Analyst [5]

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OK, that's helpful color, and is there any mechanistic rationale why it appears to kind of come back up at around four to six weeks?

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Aaron Osborne, Adverum - Chief Medical Officer [6]

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So, I would go back to the - to the first one, we did not really see any early inflammation. And sometimes early inflammation can be - you know, concerning for physicians because it can resemble an infection for example after an injection, and I think it's important to remember we did not see any significant inflammation immediately afterwards.

What we're seeing again is it's kind of peaking - you know, several weeks afterwards. And you know, [viral] (inaudible) do persist in the eye for quite some time, so we think it's related to that foreign material being within the eye.

And really, the first time that we're seeing anything - you know, that's clinically reportable, it's generally in that time period, a little bit later, so again, that's why we're still at the local steroid approach with drops - should help to address that.

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Tyler Van Buren, Piper Jaffray - Analyst [7]

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OK, that's helpful. And then just taking a step back, we've got - you know, soon here, four cohorts ongoing that we're all kind of - you know, the last three being launched in a relative short period of time, and we're going to be learning a lot as you drop down a dose and then move to topicals.

But I guess can you - you know, maybe just discuss whether you think more cohorts will be needed or at which point you will know whether you'll need more cohorts or whether you'll move to Phase 2? And exactly - you know, what you'll be looking to learn over the course of the next year?

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Leone Patterson, Adverum - Chief Executive Officer [8]

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Sure, and it's true, Tyler, we definitely - we've got our hands full in terms of trying to dose more patients, because we do think it's going to be important to have more patients dosed at the current doses we have and to see the impact of the prophylactic steroid eye drops.

And I think with that in totality, looking at those two cohorts, then obviously being open label study, we can see how the impact will be happening over time, along with a longer follow up period for cohorts one and two. I think when you look at the totality of [that pack], because that will provide us more insight into how we should proceed forward, either additional cohorts or [faster moving into a pivotal] study. We - we'll need more...

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Tyler Van Buren, Piper Jaffray - Analyst [9]

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great.

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Leone Patterson, Adverum - Chief Executive Officer [10]

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... information I think [is further point].

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Tyler Van Buren, Piper Jaffray - Analyst [11]

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Understood, makes sense. Thanks for taking the questions.

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Operator [12]

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Thank you. Our next question or comment comes from the line of Alethia Young from Cantor Fitzgerald. Your line is open.

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Unidentified Participant Cantor Fitzgerald - Analyst [13]

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Hi, this is [Emma], I'm in for Alethia, I guess just following up on that, can you help us frame what you expect to see at the lower dose in cohort two, you know, from a (inaudible) [and safety] perspective, just based on your pre-cohort and [what] do you think there would be - you know, any rationale to dose down even further than that?

And then second just also curious to hear your thoughts on the [Regenex] clinical hold that was announced earlier this week and just how that impacts your competitive position?

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Leone Patterson, Adverum - Chief Executive Officer [14]

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Sure, so we'll take the first one and talking about the cohort two data. You know, obviously as we had said, we had seen a robust [anatomical spots in] our first cohort dose [6E] level, and therefore, we thought it was appropriate to dose down, along with our [KOLs] [and a] second cohort, and so - which is at [2-11].

So, I think for us, it's early in the follow up period. We are - just completed dosing in August, and we'll be looking forward to provide an update in the first half of 2020.

But in terms of the efficacy and safety profile, given this is a dose ranging study, we are looking for dose response [and wanting] to make sure we had the appropriate doses, so we'll definitely be looking for that, but I think it's [early to] predict or provide any information, but we do look forward to providing that data in the first half of 2020.

And then as it relates to the second question on the [Regenex Bio] clinical hold, you know, based on the public information available, it appears that it's to do with the device, and clearly this is something that we're all trying to figure out the right [way to move the spor] for patients, in terms of a gene therapy approach.

And our program obviously does not involve a device or a surgical procedure and is an individual approach which we see as a huge advantage, specifically for patients and even for the retinal specialists who are delivering it. So, in our minds, we believe that our individual approach is still superior but in terms of any impact on us, compared to what they have gone through, clearly it's a device issue, which we don't have any of that to be concerned about.

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Unidentified Participant Cantor Fitzgerald - Analyst [15]

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Great. Thank you.

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Operator [16]

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Thank you. Our next question or comment comes from the line of Phil Nadeau, from Cowan and Company. Your line is open.

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Phil Nadeau, Cowan and Company - Analyst [17]

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(Inaudible) taking my questions. First a follow up to Tyler's question on the steroid regimen, if memory serves me, at AAO, there [was still] I think two or three patients who had some signs of inflammation in their eye, out through the end of the evaluation period, can you talk about those patients and how the steroid drops [can prophylact against that]?

Do you think that that was due to the (inaudible) still being in the patient's eye? Or was that a process that was stated much earlier - and by giving the drops earlier therefore you wouldn't - you wouldn't see [a - inflammation] lasting out through the week [24-30]?

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Leone Patterson, Adverum - Chief Executive Officer [18]

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Thanks, Phil. I'll start it, I'm sure Aaron will be able to add some more detail, so just to be clear that - what the follow up period we're referring to is the 24 weeks, where we did give some insight that there were three patients who were still on top of the steroids at that point in time, but two of them were [sort of in the tapering] period and one was still in active steroid regimen. And as it relates to the timing and the steroid use, I will turn it over to Aaron.

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Aaron Osborne, Adverum - Chief Medical Officer [19]

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[I mean - so] Phil, I think it's important to remember that none of these patients was treated with steroid eye drops to start with, so we had just the 13 day course of the oral steroid, and really it was a learning process in cohort one.

So, what we saw was that - you know, a topical steroid was started at different time points for these patients, so I think it's important to remember that none of these patients was on a course of steroid eye drops throughout that 24 weeks. Rather, they tool orals initially and then there was some varying use of the - of the steroid eye drops.

And I think that's really what we're looking to assess further in cohorts three and four. So, by using that consistent steroid eye drop approach for every patient for the first six weeks, you know, we hope to get on top of that inflammation and then we hope to see some benefits down the line, but obviously, you know, we can't predict the future, and we're looking forward to seeing what data comes through in cohorts three and four.

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Phil Nadeau, Cowan and Company - Analyst [20]

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And on the steroid regimen, how much flexibility do you have in terms of dose and schedule when assigning a regimen? Is it - is it possible to give low dose topical or high dose topical or does topical come really just in kind of single flavor?

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Aaron Osborne, Adverum - Chief Medical Officer [21]

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Yes - no, we're using - it's a great question, we're using a single - a single approach. We're using [ditupregnate] through this cohort three so that we have that consistency amongst sites.

Again, as alluded to, you know, there was some experimentation early on. The learning has been that the inflammation's been very responsive to those topical steroids, so now we're looking to have that consistent approach across the sites and see what data we get with that.

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Leone Patterson, Adverum - Chief Executive Officer [22]

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I think the only thing I would add is we've said that there was going to be a tapering - obviously [at six week during the] regimen, but [it'll] start tapering at the three week time point to really taper down on a slow fashion so that there is basically [a drop over] time in terms of the amount of steroids are given over that six week time period.

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Phil Nadeau, Cowan and Company - Analyst [23]

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Apologies, this may be a naive question, but if you had to go to a more potent topical steroid regimen, is that - is that possible or is this regimen kind of as powerful as it gets?

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Aaron Osborne, Adverum - Chief Medical Officer [24]

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You can potentially go up - I mean what we - what we are providing is drops four times a day. And we expect, based on the experience that we've had thus far, that the inflammation will be very responsive to that.

Again, you know, we can't necessarily predict the future and whether ever patient will respond to that, so certainly we are in discussions around what a second line treatment could look like or if we need to sort of step up treatment in the future.

And so potentially, that could be more steroid eye drops or potentially that could be - you know, you can administer an injection of steroid around the eye, and that's something that's commonly done for - when there's - when there - for example [vitrectomy] surgery performed. And we know patients tolerate that well.

You can also - beyond that, there can also even be steroids [that implant that] can be placed inside the eye. So, there's a variety of different steroid approaches that we could consider, but based on the response we've seen to the steroid eye drops, we think that the steroid eye drops are the logical point to start at, and we expect, based on what we've seen so far, that the inflammation will respond to that.

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Phil Nadeau, Cowan and Company - Analyst [25]

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Good. And that's helpful. And then last question from me is - and - what are your recent thoughts or most recent thoughts on assessing (inaudible) levels directly in cohort three or cohort four?

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Leone Patterson, Adverum - Chief Executive Officer [26]

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I'll start, but I'm sure Aaron will add. So, we believe that as we said all along, the clinical outcomes are the most meaningful signal of - for [sitting] these patients. however, I think Aaron would - probably would add some more on this in terms of what we may be looking to do with cohorts three and four.

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Aaron Osborne, Adverum - Chief Medical Officer [27]

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Yes, so just to pick up on that point, I mean it was such an extensive preclinical package that we've generated with - you know, a lot of dose ranging, a lot of protein levels were taken there. These were obviously - you know, animals that do not have wet AMD. Here we're treating humans that have wet AMD. We have OCT. We have clinical examination, and those premises are much more important than anything else.

Having said that, you know, additional information can be helpful and therefore, we have implemented optional [aquis human sampling] to look at protein levels and also you know, other things as well, but that is really exploratory and potentially supportive.

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Phil Nadeau, Cowan and Company - Analyst [28]

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Perfect. Thanks for taking my questions.

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Unidentified Speaker [29]

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[OK, thanks].

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Operator [30]

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Thank you. Our next question or comment comes from the line of [June Leef] from SunTrust. Your line is open.

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Unidentified Participant Cantor Fitzgerald - Analyst [31]

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Hi, thanks for taking my questions and congrats on all the progress. Just sticking with the theme of [core flexes - theracore flexes], just help me understand, you said that you don't really see as much inflammation in the beginning, [but those inflammation] pop up later during the course, isn't that just because you're on - the patients are on oral prophylactics earlier on that they don't see inflammation?

And if you take them away, I mean are you not concerned that [those inflammation] would pop up earlier? And why couldn't you just combine oral and topical together? Or is it just too much steroid? Thank you. And I have a follow up.

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Aaron Osborne, Adverum - Chief Medical Officer [32]

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It's a - it's a really good question. What we - so the oral steroids could be working in terms of preventing any early inflammation, and what we haven't seen is any inflammation that presents on top of those oral steroids of any clinical significance. So, either the oral steroids are working or they're not needed.

But we are not going to be taking away steroid coverage altogether, we're just reducing that, so rather than providing steroids to the whole system, we're just providing the steroids to the - to the eye now. And I think, you're right though, that's the time point at which we need to watch those patients carefully in sort of the first - you know, week to 10 days because there we will have a - you know, potentially a weaker steroid regimen [that's] only focused on the eye.

So, we - so we need to look and see if there's any - you know, breakthrough information in those first few days, and that will be something that we're looking out for in cohort three and four.

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Unidentified Participant Cantor Fitzgerald - Analyst [33]

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OK, and you know, I noticed that looking at your plans for the drug [in cohorts] - for the cohort three, [do] you stay with the lower dose? And with the new topical steroid regimen, but for the cohort four, you go back up to the original higher dose with the - with the new topical steroid regimen. Are you seeing something from the lower dose in cohort two that is driving the decision to retest the higher dose?

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Leone Patterson, Adverum - Chief Executive Officer [34]

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No, I think what I would says is that this a dose ranging study and we believe that we need to find not only the dose, but also the right steroid regimen, so for us, it's important to really have - see more patients, as you heard from Aaron's prepared remarks that this will give us an additional 18 patients of data - at those two doses, which would be potentially what we could be taking forward.

And we just need to make sure we have the right prophylactic steroid regimen that would be useful with those patients carrying forward [in] development. So, it was really driven by pursuing what we believe is the way to manage information, which is with the topical steroids. So, that's really what's driving that, and wanting to see that at both of those doses.

And clearly, we've seen, as we've signaled around [60-11] as the cohort four does, that we've seen [a - anatomical] response. But really, this is being driven by wanting to make sure we have the right [steroid regimen] as you move the program forward.

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Unidentified Participant Cantor Fitzgerald - Analyst [35]

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OK, thank you. And the last question is [on] - you know, certain [zero rescue] is a great achievement, but what would you say is the threshold that would lead ophthalmologists and patients to choose [at variable to 2 over in frequent] injections? Is it one or two or - is there some magical threshold number that would drive commercial adoption?

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Unidentified Participant Cantor Fitzgerald - Analyst [36]

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(Inaudible).

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Leone Patterson, Adverum - Chief Executive Officer [37]

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(Inaudible) yes, clearly you're seeing six patients with zero (inaudible) the three to four week period is a - is a meaningful response. I think from a - renal specialists or a (inaudible) perspective or a physician [and patients] is [they're seeing] a significant reduction in number of injections, given what they're living with today, would be meaningful for these patients.

So, that means - so if you were coming in every four to eight weeks to get an injection and you can significantly reduce that, then that's going to be meaningful for patients and physicians as they think about patients going - sorry, in terms of enrolling patients on the study and as a product going forward.

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Unidentified Participant Cantor Fitzgerald - Analyst [38]

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All right, thank you so much.

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Operator [39]

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Thank you. (Operator Instructions). Our next question or comment comes from the line of Patrick Dolezal from LifeSci Capital. Your line is open.

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Patrick Dolezal, LifeSci Capital - Analyst [40]

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Hi, thanks for taking the questions. And apologies in advance, my first one is actually on inflammation as well. So, I thought the duration of topical steroid use is particularly interesting being six weeks, I was just curious if that [time course] was typically what was required in cohort one for patients to respond? Or what gives you confidence in that duration?

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Aaron Osborne, Adverum - Chief Medical Officer [41]

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Thank you, Patrick. So, the - it is - it is based on what we've seen. And it's not just based on what we've seen in OPTIC. It's also based on what we've seen in other ocular gene therapy trials, which have used, you know, a variety of steroid approaches. And that is that the first sign of inflammation is often being observed in that type of time period, so that is kind of a peak incidence.

And what the hope here is - is that if we dose frequently with the topical steroids and we can avoid the onset of that inflammation, that we're putting that patient on a - on a better trajectory and can not only reduce the number of inflammatory adverse events that happen within that period, but hopefully can make an impact on the subsequent period as well.

And that is - it's kind of a time period of drops that is - you know, very typically used again after something like a retinal surgery approach, often patients will get four to six weeks of drops, so we know that that's very manageable from a patient perspective.

And as Leone mentioned as well, there will be a gentle taper on those drops. So, it's four times a day for three weeks, and then it is tapering down to one drop a day, by the sixth week. But if we do see - you know, any persistent signs of inflammation on any patient, then that period of drops can be extended with a - with a longer and more gentle taper.

So, we - we're now doing that experiment obviously in cohorts three and four and really looking forward to getting the data from that and presenting it as quickly as possible.

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Patrick Dolezal, LifeSci Capital - Analyst [42]

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Great. That's helpful. And on transduction efficiency, should we expect any differences based on the use of the oral versus topical regimen? There is actually a poster at [ESGCT] last year that indicated that there might be some differences there. I was just curious what your thoughts are and what your experience is with that?

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Aaron Osborne, Adverum - Chief Medical Officer [43]

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I'll take that one - yes, we - certainly those - there was some interesting data, as in I think a very small number of animals. And based on a - you know, our collective discussions and what we have learned, we don't expect to see any significant differences there.

Obviously, you know, we're going into the experiment now. We'll look forward to seeing what data we do get with these cohorts three and four. And again, we are looking at implementing that optional [A quiz] sampling as well, so potentially can get some additional data points that could address that question, but you know, right now, we do not expect to see any significant differences.

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Patrick Dolezal, LifeSci Capital - Analyst [44]

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OK, great, thanks. And then the last one is just if you have any additional granularity on the timing of the 52 week data for cohort one and the 26 week data for cohort two?

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Leone Patterson, Adverum - Chief Executive Officer [45]

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So, as we've said, we will be presenting the 52 week data of cohort one in the first half of next year. There's a number of conferences where that could happen. And we're - we will be able to announce it as we get closer to the time.

And I think the second question was to do with the 24 week, cohort two data, and similarly, we - we'll be announcing that in the first half of next year, and we'll be again, doing it at a - hopefully in a way that we can get that out there as soon as possible at a scientific conference.

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Patrick Dolezal, LifeSci Capital - Analyst [46]

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Great, thank you.

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Operator [47]

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Thank you. I'm showing no additional questions in the queue at this time. I'd like to turn the conference back over to [@room CEO] Leone Patterson.

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Leone Patterson, Adverum - Chief Executive Officer [48]

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Thanks again, everybody for joining the call today. I just want to reiterate how encouraged we are by the [policy] and clinical results we presented for ADVM-022. We're excited to advance this important therapy for patients with wet AMD and diabetic retinopathy.

And looking ahead, we're approaching [a - multiple milestones] for our programs which we just went through. We plan to announce 52 week data for the first half - for the - sorry, the first cohort and 24 week data from the second cohort of the OPTIC trial in the first half of 2020.

We're also looking forward to completing enrollment in cohort three and beginning the patient enrollment in cohort four in the first quarter of 2020. And finally, we plan to submit an [IND] in diabetic retinopathy in the first half of 2020 to expand [the potential on a] second indication.

We look forward to providing timely updates on that clinical execution and maintaining a productive and transparent dialog with investors and the medical community as we advance our programs and build (inaudible) for Adverum.

This has certainly been a year of progress and accomplishments for Adverum and I look forward to continued momentum in the months ahead. In closing, I'd like to thank the patients, the care givers, and the retinal specialists who have participated in the OPTIC trial.

And importantly, I would like to thank our employees for their commitment and hard work to advance our programs to what our broader mission to deliver (inaudible) gene therapies for patients. Thank you for your time, and this concludes our call.

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Operator [49]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating, you may now disconnect.