Q4 2019 Earnings Call

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Ladies and gentlemen, please stand by Youre, Adverum Biotechnologies fourth quarter and you're in 2019 corporate update conference call begin momentarily. Thank you for your patience inflexion Bye bye.

Operator: Ladies and gentlemen, please stand by. Your Adverum Biotechnologies fourth quarter and year-end 2019 corporate update conference call will begin momentarily. Thank you for your patience, and please stand by.

Hi.

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Unnamed Speaker: [inaudible] BF-WATCH TV 2021, [inaudible]

Good afternoon, and welcome to the Adverum Biotechnologies fourth quarter and year end 2019, corporate update conference call. At this time all participants are in listen only mode. Later, we will conduct a question answer session and after the prepared remarks as a reminder.

Operator: Good afternoon, and welcome to Adverum Biotechnology's fourth quarter and year-end 2019 Corporate Update conference call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session after the prepared remarks. As a reminder, this conference call is being recorded. I would now like to hand the call over to Maisha Lacey, Vice President of Investor Relations and Corporate Communications at Adverum.

This conference call is being recorded I would now like to hand, the call over to my usually see vice President of Investor Relations and corporate communications of Adverum. Please go ahead.

Maisha Lacey: Thank you, Operator, and welcome, everyone. Today, we issued a press release reporting our financial results for the fourth 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 calls will also be available on the Events and Presentations section of our website. Joining me for the prepared remarks portion of the call today is Leonie Patterson, President and Chief Executive Officer, and Dr. Aaron Osborne, Chief Medical Officer. Then, Leonie, Aaron, and our Chief Financial Officer, Thomas Leong, 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 plans, 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 10-K, which was filed this afternoon. I would now like to turn the call over to our president and CEO, Leonie.

Thank you operator and welcome everyone. Today, we issued a press release reporting our financial results for the fourth quarter of 2019.

A copy of this release is available on the press release. This page at the Investor Relations section of our corporate website at Www dot at their own Dot Com. Please note that a replay of todays call also will be available on the events and presentations section of our website Joe.

Joining me for the prepared remarks portion of the call today isn't Leoni Patterson, President and Chief President Chief Executive Officer, and Dr., Aaron Osborne, Chief Medical Officer, then Leoni, Erin and our Chief Financial Officer, Thomas Leon will be available for the Q1.

On a portion of the call.

As a reminder, we will be making forward looking statements regarding our product development plan research activity.

An operation as well as our financial outlook.

These statements are subject to risks and uncertainties that may cause actual results to differ materially from Ddos forecasted.

Description of de risk can be found in our 10-K, which was filed this afternoon I.

I would now like to turn the call over to our President and CEO Leone Patterson.

Leonie Patterson: Thank you, Maisha. Good afternoon, everyone. And thank you for joining us today. Before we dive into our business progress, I'd just like to acknowledge the fluid situation as it relates to the coronavirus and the broader community. Like many companies, we are taking necessary precautions to support our employees and our business. And we will continue to monitor the situation closely.

Sure Good afternoon, everyone and thank you for joining us today.

Before we dive into a business corporate or just like to acknowledge the fluid situation as it relates is corona bars and their go to community like many companies, we're taking necessary precautions to support our employees and their business and we will continue to monitor the situation closely.

During this call will review the significant momentum in advancing balancing our lead gene therapy candidate I give you might you too and also provide a corporate update.

Leonie Patterson: During this call, we will review the significant momentum in advancing our lead gene therapy candidate, AWMO22, and also provide a corporate update. Aaron will then review the significant clinical progress with ADVM-022 targeting wet AMD, including recent data presentations and our plans for advancing a second indication, diabetic retinopathy (DR). We will then open the call for questions. This is an exciting time to be working in gene therapy and to be part of what many consider to be a gene therapy revolution in treating serious diseases. At Adverum, we are focused on delivering what we believe can be transformative therapies for patients living with serious arthral and rare diseases. We believe our lead gene therapy program, ADVM02, has the potential to be a one-time introvitral injection gene therapy approach for our lead indication, WET-AMD. This past year, we have gained significant momentum with our clinical progress in the development of OQ-2 in the OPT-X Phase I dose ranging study. As a reminder, we have been exploring two doses in the OPTEC trial at 6E11 and a three-fold lower dose of 2E11.

Or who will then review the significant clinical progress with 80 via mostly to targeting with a and b, including recent data presentations and our plans for advancing a second indication diabetes ignore policy or the are.

We would then open the call for questions.

This is an exciting time to be wouldn't gene therapy and can be proud of what many considered to be a gene therapy revolution in treating serious diseases.

And it varies <unk>, we have focused on delivering what we believe could be transformative therapies for patients living with serious October in rare diseases.

We believe a lead gene therapy program 80 via Lucky to has the potential to be a onetime intravitreal injection gene therapy approach for our lead indication we aim to be.

This past year, we have gained significant momentum with our clinical Congress and the development about Q2 in the opposite phase one dose ranging study.

As a reminder, we has been exploring two doses in the Arctic trial, It's 60, 11, and a threefold mode. Those.

To 11.

We have presented data from if there's two cohorts and I'm excited to announce that we recently completed dosing or nine patients enough food cohort.

Leonie Patterson: We have presented data from our first two cohorts, and I'm excited to announce that we recently completed dosing all nine patients in our third cohort. We are now focused on completing enrollment in cohort four, and screening of patients has begun. The clinical data presentations on OPTIC Cohorts 1 and 2 have been very promising, where 8082 demonstrated robust efficacy and evidence of a dose response. We look forward to presenting new clinical data from OPTIC in May this year. Additionally, we plan to present data from all four cohorts in OPTIC in the second half of this year.

We can now focused on completing enrollment <unk> four and screening of patients has begun.

The clinical data presentations on opposite cohorts, one or two had been very promising where 80 rectitude demonstrated robust efficacy evidence of a dose this bodes well.

We look forward to proceed they knew clinical data football in May this year. Additionally, we plan to present data from all four cohorts an uptick in the second half of this year.

We also plan to develop a Q2 and a second indication diabetes and obviously it would be our with an eye in d. submission in the first half of twin between eight and a phase one two beginning in the second half of the year.

Leonie Patterson: We also plan to develop O2-2 and a second indication, Diabetes Rheumatoid Arthritis, or DR, with an IND submission in the first half of 2020 and a Phase 1-2 beginning in the second half of the year. We are positioning our company to be a leader in gene therapy. Beyond ADVM-022, we are focused on developing a pipeline of novel gene therapy.

We are positioning our company to be a leader in gene therapy beyond 80 via mostly too we have focused on developing a pipeline of novel gene therapy.

Leonie Patterson: Our industry-leading AAV platform provides us with a number of compelling options for expansion, and we look forward to talking about this progress during the course of this year. Meanwhile, we are making great strides in other areas of our business. First, at the beginning of the year, we moved to our new headquarters in Redwood City. This move supports our growth plans and enables us to expand our core capabilities, including process development and manufacturing. Next, we appointed Angela Sidinger as Chief Technology Officer. Angela brings deep and relevant experience in gene therapy as she led Avexis efforts in developing the Early Manufacturing Strategy, which enabled them to transition the early-stage AEV manufacturing process to a scalable commercial manufacturing process. Azure will focus on leading our manufacturing strategy as we advance toward later stage clinical trials and prepare for potential commercialization.

Industry, leading Avi platform provides us with a number of compelling options for expansion and we look forward to talking about this progress during the course of this year well, so we're making great strides in other areas of business food at the beginning of year, we moved to a new headquarters in Redwood City. This move support.

Our growth plans and enables us to expand our coal capabilities, including crosses development and manufacturing.

Next we appointed and putting it as Chief Technology Officer extra brings deep and relevant experience and gene therapy. As you made a VIX, if but and developing but really manufacturing strategy, which enabled them to transition to early stage Avi manufacturing process to a scalable commercial manufacturing process.

And your will focus on leading our manufacturing strategy as we advance toward later stage clinical trials and prepare for potential commercialization.

And finally, we are in a strong financial position with over 300 million and cash after completing a public follow on offering last month, raising net proceeds of approximately 141 million, which together with a yearend cash of 166 million is expected to fund operations into.

Leonie Patterson: And finally, we are in a strong financial position, with over $300 million in cash. After completing a public follow-on offering last month, raising net proceeds of approximately $141 million, which together with a year in cash of $166 million, is expected to fund operations into 2022. Before turning the call over to Aaron, I want to just share how excited I am to be leading this company, where we are at the cutting edge of developing a potential one-time treatment for patients with wet A&D in DR. We are committed to our mission to advance these programs in a pipeline of novel gene therapies for patients with serious ocarin rare diseases. I'd now like to turn the call over to Aaron, who will provide further details on our Aaron?

2022.

Before turning the call at the error I Wonder just how excited I used to be leading this company, where we are the cutting use of developing a potential onetime treatment for patients with with the India.

We are committed to a mission to advance these programs and our pipeline of novel gene therapy for patients with serious grim rare diseases.

I'd now like to tend to collect the Aaron who will provide further details on their clinical progress for 80 alert you to Aaron.

Dr. Aaron Osborne: Thanks Leone. Our primary focus as a company is always on the needs of our patient population. In this regard, to date, we are not aware of any specific coronavirus impact on the OPTIC trial. We are continuously monitoring the evolving situation with the coronavirus and are in regular communication with our clinical trial sites and our vendors involved in our clinical trials. Our thoughts and wishes are with everyone who has been impacted by COVID-19. Now, turning to optics, this has been a truly exciting time for ADVM-022 as we advance optics for wet AMD and develop plans for a second clinical indication in diabetic retinopathy. Optics continues to progress very well.

Thanks, the only.

Our primary focus as a company is always on the needs of our patient population.

The trick.

Okay, we're not aware of any specific corona virus impact on the optic trial, we're continuously monitoring the unfolding situation with Corona virus underwritten regular communication with our clinical trial sites and vendors involved in our clinical trials.

Some wishes with everyone who has been impacted by call. It nine thing.

Now turning to optic this has been a truly exciting times, absolutely as we advance optic for west Sandy.

Plans for a second clinical indication in diabetic retinopathy.

Okay continues to progress very well I've already mentioned, we recently completed patient dosing cohort three.

Dr. Aaron Osborne: As Leonie mentioned, we recently completed patient dosing in Cohort 3 and opened screening for Cohort 4. There is strong support from the investigators and clinical sites to quickly enroll this cohort to allow us to share data from all four cohorts in a total of 30 patients later this year. In January of this year, Dr. Charles Wyckoff presented detailed efficacy and safety data from Cohort 1 patients. Then, in February, Dr. David Boyer presented a further update from Optic, including data from patients in Cohort 2 who received a three-fold lower dose of ADVM-022. To briefly summarise the data from Cohorts 1 and 2, ABVM 022 demonstrated a robust efficacy signal and evidence for the dose response, which we measured as follows. In Cohort 1, we used a dose of 6e to the 11 vector genomes per eye.

Screening for Copel for their its strong support from the investigators and clinical sites to quickly enrolled this cohorts to allow us to shut data from all four cohorts in a total of 30 patients like to this year.

In January of this the Dr. Charles why cough presents a detailed efficacy and safety data from cohort one patients.

Then in February Dr., David point presents a further update from optic including data from patients with two he received a threefold lower dose of 88 you too.

Briefly summarize the data from cohorts, one and two.

Dr. Aaron Osborne: Six of six patients remained rescue injection-free at a median follow-up of 50 weeks, with three of those patients out to 52 weeks or beyond. In Cohort 2, using a three-fold lower dose of 2 e to the 11, 4 of 6 patients were injection-free at 24 weeks. This provides us further evidence of robust efficacy in addition to a dose response. In both cohorts combined, 10 of 12, or 83% of patients remained rescue injection free.

She to demonstrate to the robust efficacy signal and evidence to the dose response, which we measure is as follows.

Cohort, one using a dose of fixed fee to the 11 that to chinos per.

Fix it six patients remains rescue injection free at a median follow up 50 weeks with three of those patients out to 50 weeks 52 weeks or beyond.

In Q2, using a threefold lowest dose that to eat the 11 for six patients for injection free at 24 weeks. This provides us further evidence of robust efficacy. In addition to dose response.

In both cohorts combined 10, or 12 or 83% to patients remained rescue free rescue injection free.

Dr. Aaron Osborne: For these patients, vision was generally maintained as demonstrated by stable mean best corrected visual acuity compared to baseline. Retinal anatomy improvements were achieved and maintained as demonstrated by mean central subfield thickness compared to baseline. It's important to remember that patients in OPTIC previously required frequent anti-VEGF injections to maintain their vision. In Cohorts 1 and 2, patients had received an average of more than 9 anti-VEGF injections in the 12 months prior to receiving ADVM-022 in October. The assessment of safety is of paramount importance in early phase clinical trials, and we are pleased to report AVVM 022 continues to demonstrate a favorable safety profile, with no drug-related or procedure-related serious adverse events, no drug-related systemic adverse events, and no adverse events meeting the criteria for dose-limiting toxicity.

So these patients vision was generally maintained as demonstrated by stable mean, that's correct due to the acuity compared to baseline.

Rational and lastly improvements were achieved some maintained as demonstrated by me central subsea fitness compared to baseline.

It's important to remember the patients that uptick previously required frequent entity that Jeff injection to maintain that vision.

Cohorts, one and two patients had received an average of over nine on T. Digest injections in the 12 months prior to receiving ATM Oh, two to an uptick.

The assessment the safety is paramount importance in early phase clinical trials and we're pleased to report 82 to continue to demonstrate favorable safety profile with no drug related or procedure related serious adverse events no drug related systemic adverse events are no adverse events meeting the criteria for it.

Dose limiting toxicities.

No great information that is responsive to steroids I talk treatment has been commonly reports it.

Dr. Aaron Osborne: Low-grade inflammation that is responsive to steroid eyedrop treatment has been commonly reported. However, importantly, we have seen no evidence of vasculitis, retinitis, or choroiditis following intramuscular ADVM-022 administration. In Cohorts 3 and 4 of OPTIC, we're administering prophylactic steroid eye drops instead of prophylactic oral steroids, as were used in Cohorts 1 and 2. We believe that the use of 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 in We look forward to sharing the data from Cohorts 3 and 4 later this year.

Importantly, we have seen no evidence of vasculitis recognize this all corridor following intravitreal ATM energy to administration.

In Cohu stream for of uptick we're administering prophylactic steroids eyedrops instead of price elastic oral steroids as well used in cohorts one or two.

We believe that the use of Starwood eye drops will decrease the systemic exposure to steroids and allow for a longer period of steroids coverage potentially reducing the occurrence of the generally mild in cemetery events that have been reports is off to cessation of oral steroids in cohorts, one and two.

We look forward to sharing that data from cohort three and four later this year.

Given the promising thanks to their own ATP ammo to two presented today, we're excited to move forward without plans to school second indication diabetic retinopathy.

Dr. Aaron Osborne: Given the promising data on ADVM-022 presented today, we're excited to move forward with our plans to explore a second indication, diabetic retinopathy. This represents another large and underserved market that may benefit from a one-time, long-lasting, intravitreal, anti-VEGF gene therapy. Of the estimated 8 million people with diabetic retinopathy in the US, only 2 million are diagnosed, and only 1 million are treated. Retina specialists are very excited by the potential that a one-time, intravitreal anti-VEGF therapy could offer. Currently, most patients with diabetic retinopathy do not receive anti-VEGF therapies due to concerns around their short duration of effect and subsequent risk of diabetic retinopathy progression and sight loss. Diabetic retinopathy is the leading cause of vision impairment and blindness amongst working-age adults.

Diabetic retinopathy represents another launch an underserved market that may benefit from a onetime long lasting intravitreal anti VEGF gene therapy.

But the estimated 8 million people with diabetic retinopathy in the U.S., only 2 million diagnosed and only 1 million a treated.

Retina specialists, a very excited by the potential done a onetime intravitreal anti VEGF therapy could offer.

Currently most patients with diabetic retinopathy do not receive anti VEGF therapy is due to concerns around that short duration of effect and subsequent risk diabetic retinopathy progression and fight loss.

Diabetic retinopathy, if the leading cause of vision impairment and blindness amongst working age adults.

At the prevalence of diabetes continues to grow the prevalence of diabetic retinopathy is expected to increase there was significant unmet needs for more effective and more durable anti VEGF therapy that can reduce the incident sight threatening complications and improve outcomes.

Dr. Aaron Osborne: As the prevalence of diabetes continues to grow, the prevalence of diabetic retinopathy is expected to increase. Consequently, there are significant unmet needs for more effective and more durable anti-VEGF therapies that can reduce the incidence of site-threatening complications and improve outcomes. We believe maintaining 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 and allowing for an earlier time point of intervention. I will now turn the call back over to Leonie.

We believe maintaining consistent levels of betcha suppression with ATM or two to could be particularly important but this rapidly progressing disease potentially improving treatment outcomes currently available therapies and allowing for an earlier time point of intervention.

Ill now turn the call back over to the only.

Thanks, Aaron we would now I'm going to co two questions operator.

Leonie Patterson: Thanks Aaron. We will now open the call to questions. Operator?

Operator: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A room. Our first question comes from Alicia Young with Cantor. You may proceed with your question.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw your question on press the pound Keith Please stand by we compile the Q and a roster.

Our first question comes from a via young with Cantor you May proceed with your question.

Leonie Patterson: Hey guys, thanks for taking my questions one or two and congrats on the progress with angiogenesis. So maybe two things for me: I just wanted to maybe talk a little bit about kind of the potential speed of enrollment in Cohort 4. I don't know, I figured there was probably good demand in Cohort 3. So just wanted to see if there was any kind of perspective you could get on how fast that could enroll or do you kind of already have the people staked out? And my second question is about diabetic retinopathy. Can you talk about any kind of potential read-throughs that we might be able to start making from the AMD data that we've seen? And when we start thinking about potential efficacy there, and then maybe just can you touch upon how you think this therapy might be potentially more impactful and competitive than, perhaps, let's say, like, a monthly dosing drug like an ILEA or something like that versus kind of the standard of care which still remains pretty prevalent in that population? Thanks.

Hey, guys. Thanks for taking my.

Question from our two.

And congrats on the progress from angiogenesis, So maybe two for me.

Just wanted to maybe talk a little bit about.

Kind of potential state of enrollment and cohort for I don't know I figured there was probably good demand and couple or three so just wanted to see if there was any kind of perspective, you could give up given how fast that could enroll or do you kind of already have the people staked out.

Second question is on diabetic retinopathy can you talk about any kind of potential read throughs that we might be able to start making from the AMC data that we've seen.

Let me start thinking about potential efficacy there and then maybe just can you touch upon how you think this therapy might be potentially more impactful and comparative than like perhaps lets say like a like a monthly dosing drug like an ilea or something like that versus kind of the standard of care, which still remains pretty prevalent population. Thanks.

Sure. This is on the only so in terms of state of enrollment sell side analysts. Your parents has anything to add but so we screen. We currently screening patients.

Leonie Patterson: Sure, this is Leonie. So in terms of the state of enrollment, I'll start and see if Aaron has anything to add. But we're currently screening patients, and obviously, we're focused fairly heavily on getting those patients enrolled as soon as possible. And it's very much part of what we're focused on primarily getting that enrollment done. And at 6011, as you may recall, the efficacy we had with the first cohort, which is the same dose as cohort four, is that we are still really showing robust efficacy and durability out to the longest time point now, 50 weeks. So we believe that there is a lot of interest, and we continue to hear from investigators to enroll patients in that cohort at 6011. So Aaron, I'll see if you have anything to add to that, and we can go to the other two points as well.

Obviously, where we are focusing heavily on getting those patients enrolled as soon as possible and it's very much part of.

What we focus on primarily used to get better moment done and 60 11 as you may recall the efficacy we had with the first cohort which is the same dose cohort for is that we still would have really showing right about the efficacy durability out to the longest time point now 50 week medium. So we believe that there is a lot of interest and we continue.

To hear that from a basic items to enroll patients and that cohort. It's six you live in San I'll see if you have anything to add on that or we can go the other two points as well.

Dr. Aaron Osborne: Now just to add that we're in sort of daily contact with the investigators, we've got sites in the US, we know these investigators really well and that they're truly excited about Cohort 4, and we're actively screening patients; we have many lined up and hope to rapidly enroll Cohort 4.

Not just at the you know we're in sort of in daily contact with the investigate says we've got sites in the U.S.. We know these investigations really well and that that truly excited about couple for actively screening patients. We have many lined up and Ah I too rapidly enroll hopeful.

Right and then in terms of beyond the potential read through I think first of all obviously on the safety perspective, the phase one for uptick as the phase one safety study and so therefore, the first and foremost thing is does the safe Harbor safety profile and that's why I think <unk> screen for a important because they are using put select exterior.

Leonie Patterson: Great And then in terms of DR and the potential read-through, I think, first of all, obviously from a safety perspective, phase one for Optum is the phase one safety study, and so therefore, the first and foremost thing is in terms of a safe safety profile, and that's why I think cohorts three and four are important, because we're using prophylactic steroid eye drops, which will hopefully manage the steroids, sorry, the inflammation So we do believe that there is some read-through that will be apparent from even the data we've presented when it comes to safety, along with what we'll see in cohorts three and four when using steroid eye drops as a prophylactic measure.

Hi, drops, which will hopefully a managed to steroids sorry, the information that might have been seen earlier on income was one and two so we do believe that there was some read through that will be apparent from even the data we presented on with that comes to safety along with what we'll see in Q3, and four and using steroid eye drops as opposed to like major.

Leonie Patterson: And as it relates to efficacy, yes, I think there can be some read-through, and I'll have Aaron speak to the disease, the difference in the disease between wet AMD and DR, because there are obviously some differences, and whether the doses that we would use in DR would be the same as what we would use in wet AMD, I think it would be useful to talk about the levels of VGF compared to the two in the

And as it relates to if it could say, yes, I think they can be some read through and don't have Aaron speak to the disease difference in the disease can wait aimed in d. I, because there's obviously some differences and with as the doses that we would use in D.R. would be the saying this what we would use and we then do you think would be useful to talk about the levels of AJ.

Compared to the to the patient profile.

Yes.

Dr. Aaron Osborne: Thank you very much. Thank you. Thank you.

Dr. Aaron Osborne: Yeah, so the anti-VEGF agents that are approved at the moment, most of them are approved for use in diabetic macular edema as well as in wet AMD, and those doses have generally been the same. So drugs, the dose of anti-VEGF that is effective in wet AMD will generally be effective in treating diabetic macular edema and also in improving diabetic retinopathy, and there's a lot of So the efficacy that we're seeing in OPTIC is really exciting in terms of its possible applicability to diabetic retinopathy and diabetic macular edema, and I think just the second part of the question, which was on the difference between O2-2 and currently available anti-VEGF drugs which are approved for diabetic retinopathy but are not currently used to any great extent, I think this really comes back to durability.

Yes so.

So the answer is that your agents that are approved at the moment. Most of them are approved for use in diabetic macular edema as well as in what they empty and those doses have generally been the same.

So drugs the dose events, even Jeff is effective in west Sandy will generally be effective in treating diabetic macular edema, and also improve and also improving diabetic retinopathy and there's a lot evidence around that that exist already so the the efficacy that we're seeing an uptick is really exciting in terms of its Paul.

A couple applicability to diabetic retinopathy same diabetic macular edema, and I think just the second part the question, which was on the difference between our two two and currently available and see that Josh which are approved for diabetic retinopathy, but not currently used.

Two at 20, Great extent I think this really comes back to that your ability and diabetic retinopathy is a disease that lost the separately for several years and what can happen with the anti VEGF therapy is they're available is that they can superficially gives the appearance trip improved the disease, but because of that short duration of action than the pace.

Dr. Aaron Osborne: And diabetic retinopathy is a disease that lasts for several years, and what can happen with the anti-VEGF therapies that are available is that they can superficially give the appearance to have improved the disease, but because of their short duration of action, then the patient can actually experience a complication if they do not come back to the clinic. And I think this is the promise of a sustained delivery approach in diabetic retinopathy that you can provide long-lasting, sustained anti-VEGF, which can, you know, hopefully tie that patient through the most active period of their diabetic retinopathy and could reduce the risk of those life-threatening complications, and, you know, importantly, it's something that lasts for several months or years rather than something that, you know, lasts for just a few weeks.

And can actually experience.

Complication, if they do not.

Come back to the clinic and I think this is the promise of a sustained delivery approach in diabetic retinopathy that you can provide long lasting sustained and see that Jeff.

Which can you know hopefully tied that patient through the most active period that diabetic neuropathy and could reduce the risk if they start threatening complications.

Importantly, it's something that loss for several months or years, rather than something that you know last but just a few weeks, but that's for the when it starts to wear off if it does start to wear off this would happen much further down the line and the patient would be much less likely to experience. It aside threatening complications and I think thats why the retina community is really.

Dr. Aaron Osborne: So, therefore, when it starts to wear off, if it does start to wear off, it would happen much further down the line, and the patient would be much less likely to experience a life-threatening complication. And I think that's why the retina community is really excited about the potential of intravitreal gene therapy to make a big difference in diabetic retinopathy.

Thoughts about the potential Intravitreal gene therapy to make a big difference in diabetic retinopathy.

Operator: Awesome guys, thanks for all the details. Great.

Awesome guys. Thanks for a lot of all the detail.

Great.

Operator: Thank you. Our next question comes from Tara Bancroft with Piper Sandler. You may proceed with your question.

Thank you. Our next question comes from tear Bancroft with Piper Salmon you May proceed with your question.

Hi, guys, it's great to hear your progress so far and also really promising to hear that you've had something to be experiencing any delays or the opportunity to combat that's great. So I was just wondering.

Leonie Patterson: Hi guys, it's great to hear your progress so far, and it's also really promising to hear that you guys don't seem to be experiencing any delays with OPTIV due to COVID. That's great. So, I was just wondering if maybe I could get your thoughts on the recent safety signals that we're seeing with Bayovu and what it was about the product that you think may have led to that. And do you think there's any read through to intravitreal therapy in general and how this may affect sentiment towards a longer-lasting therapy like O2-2? Thanks.

Maybe I can get your thoughts on the recent safety signals that we're seeing with bank of you and what it was about the product that you think may have less that do you think there's any read through.

Intravitreal therapy in general and how this may affect sentiment towards longer lasting therapy like onto two could be thanks.

Leonie Patterson: having worked on a number of other anti-VEG-S, I think he could answer more specifically. But what I can say is it's very different. The type of inflammation that we're experiencing, which as you know is low-grade, manageable with topical steroids, is very different than the type of inflammation that has been experienced in those patients who are on BOVU. So with that, I'll turn it over to Aaron to talk about some of the hypotheses on what's happening, but I think it will be really important to emphasize the difference between where we are incurring the type of inflammation we have versus BOVU and also where the inflammation is occurring. So I'll hand it over to you, Aaron. Thanks.

Great question Terry. Thank you, so I think on something and obviously with his experiences and ophthalmologist and having worked on the number the other NPV, Jason I think he could I ask the most specifically, but what I can say, it's it's very different types of information that we are experiencing.

What gives you know as low grade manageable the topical steroids, it's very different than the type of inflammation that has been experienced at those patients who on buses. So well then it shouldn't have to and talk about some of the hypothesis on whats happening, but I think it will be really important things. Besides the different some way we we're incurring the type of information we have.

This is by the but also we are the inflammation as the carrying so on that on the Aaron.

Thanks, the only yeah I don't see we're concerned to hit those reports and the information would be I view, which has been associated with site loss has been reported to be a posterior inflammation. So in inflammation in the back part of the vitreous body, but most worrying me that's been a basket likes it does that mean.

Dr. Aaron Osborne: inflammation with BOV which has been associated with sight loss has been reported to be a posterior inflammation so an inflammation in the back part of the vitreous body but most worryingly there's been a vasculitis so that means an inflammation affecting certain retinal vessels which has resulted in the blood not being able to get to the retina and patients losing vision and that could potentially be permanent and that's called a vasculitis so this is what really concerns I think the retina community and there was a lot of discussion about that at recent ophthalmology meeting so in terms of what that potential root cause could be you know we're focused on O22 but some of the things that come up are potentially something around this is let's remember that BOV is a novel therapy which is a different called a single-chain antibody fragment and those are not used that widely so it's conceivable that there could be an issue with the production and there could be some contaminant there or it could be related to that another thought is that it could be related specifically to it being a single-chain fragment which may penetrate deeper into the retina and may be causing some problems in certain patients. I think the third theory that people discuss is the fact that it's a very high dose of anti-VEGF it's around you know 24 times the dose of ranibizumab or 12 times the dose of an ILEA intravitrol injection so those are sort of three areas that people are looking at to potentially explain what is happening here.

As an information affecting certain retinal vessels, which has resulted in the plug not being able to get the retina and patients losing vision and that could potentially be permanent that's cool vasculitis. So this is what really concerns I think the retina community and there was a lot of discussion about that recent.

Ophthalmology meeting so in terms of what that potential root cause could be we're focused on two two but some of the things that come up a potentially something around this is let's remember that view is a novel therapy, which is a different cost sort of single China antibody Franklin and does it not used that way.

Let me so it's conceivable that there could be an issue with the production and that could be some contaminants that or it could be related to that another thought is that it could be related specifically to it being single chain, frankman, which made penetrate deeper into the retina and maybe causing some problems in certain patient.

The third theory that people discussed is the fact that it's a very high dose event that Jack it's around 24 times. The dose of ran a busy model or 12 times the dose of an idea I'm intravitreal injection. So those are sort of three three areas that people are looking out to potentially explain what's happening here I think importantly.

Dr. Aaron Osborne: I think importantly with O22 we have not seen any evidence of retinal vasculitis we've not seen any evidence of any sort of inflammation. We do commonly see a low-grade inflammation which affects the front part of the eyes following intravitrol injection of O22 and this is expected we're injecting viral material and we expect some degree of immune response but that inflammation is very low grade it predominantly affects the front part of the eye and it's it's something that lasts over a longer period of time and it's manageable with topical steroids so it's a very different type of inflammation and we have not seen any evidence of that type of inflammation with ADDM O22.

He will oversee too.

We have not seen any evidence of retinal vasculitis, we've not seen any evidence at any sorts of rational inflammation, we do commonly see a low grade information, which affects the front parts of the ice following.

Dr. Aaron Osborne: Great, thank you.

Intravitreal injection 022, and this is expected were injecting viral material and we expect some degree of immune response, but that inflammation is very low grade and predominantly affects the from parts of the eye and it's it's something that loss over a longer period of time and its manageable with topical steroids. So.

That's very different types of inflammation and we've not seen any evidence that type of information with 80 demo to.

Great. Thank you.

Thank you. Our next question comes from Phil Naidu with Cowen and co. You May proceed with your question.

Operator: Thank you. Our next question comes from Phil Nadeau with Cowan & Co. You may proceed with your question.

Thanks for taking my questions.

Leonie Patterson: Good afternoon. Thanks for taking my questions. Maybe a couple on the information that you've seen. Have you decided on the steroid regimen that you're going to use in the DR trial now, or does that await data from Cohorts 3 and 4?

Maybe a couple on that information that you've seen have you decided on the steward regimen that you're going to use in the immature trial down 4% Kuwait data for of course praying for.

So basically I think thank you for bringing that up so a couple of things one as I just I mentioned earlier we.

Leonie Patterson: So basically, I think, thank you for bringing that up. There are a couple of things.

Leonie Patterson: One, as I just mentioned earlier, we've completed dosing in Cohort 3, and obviously, this is an open-label study. And we have rolled right into our Cohort 4 using the same protocols, steroid eye drops over six weeks, prophylactic steroid eye drops over six weeks tapering.

<unk> three we've completed dosing obviously was an open label study and we have rolled dryden to outcome for using the same protocols Stuart I drops over six week, a person like Exterran eye drops over six week type right. So that gives you seem to that level of confidence in comfort to move forward with that approach and that cohort four which is that 60.

Leonie Patterson: So that gives you a sense of our level of confidence and comfort to move forward with that approach in our Cohort 4, which is at 6011. The second part, in terms of what we'd be using going forward for DRDME, obviously, we haven't submitted. We're still in the process of submitting our ID, which we said we would get that done in the first half of this year. Then we would have been able to share a little bit more about the protocol design. But it's fair to say that given this is a patient population that would benefit from using topical steroids as opposed to oral, that we'll be clearly looking at that as our potential way of managing any inflammation that we would see in that study. But in terms of hearing that definitively, we'll need to wait till we actually get to the protocol design and are willing to share that.

We live events, the chicken pot and teams of the what we'd be using going forward for the idea me. Obviously, we have been submitted listed on the process of.

So many ideas, which we said we'd get that down in the face. After this year and then we would have dealt to share a little bit more about the protocol design, but it's safe to say that given this is a a patient population that would benefit from using just oh, I'm, sorry, topical steroids as opposed to Aro that will be clearly looking at that has the potential way of men.

Is there any information that we would stay in that study, but we wouldnt you have good to hear that definitively will need to wait till we actually get to the protocol design.

Willing to say that.

Leonie Patterson: Got it. And just to follow up on your comments about the open-label nature of cohort 3, could you talk about that maybe in a bit more detail? What are you seeing there?

Got it and just follow up on your comments book or open label nature Coordthree could you talk to that maybe in a bit more detail. What are you seeing there and I guess in particular, how many patients are past six week and of.

Leonie Patterson: And I guess, in particular, how many patients are past the six-week end of the prophylactic steroid regimen today so you can see what the long-term efficacy is of the six-week cohort, I mean the six-week dosing paradigm?

Prophylactic steroid Richmond today, So you can see with the long term.

Efficacies after six weeks Kumar prime into six week dosing paradigm.

I think I want to concise it obviously at some point, we'll release the real data so, but I think what we can say is just to remind you with a nine patients that were enrolled we enrolled our first patient in November we not ciber momentum in November. So you could escape inside that we have a number of those places out beyond me six weeks.

Leonie Patterson: I think what I can say is that obviously, at some point, we'll release the real data, Phil, but I think what we can say is just to remind people that there were 9 patients that were enrolled. We enrolled our first patient in November, we announced enrolment in November, so you can, it's fair to say that we have a number of those patients out beyond that 6 weeks, and I think the only thing I can say to that, since we haven't presented data, is that we felt confident enough with what we were seeing to proceed with our dosing up to 6-11.

And I think the only thing I can say that since we haven't seen a dangerous to say that we felt confident with what we're seeing the brick to proceed with dosing back to 60 11, using that same store regulation I know topical steroids over six weeks and cure furnished the dose of the topical steroids would it be possible to increase the dose for cohort four if there was no sir.

Leonie Patterson: And Q-minus the dose of the topical steroids, would it be possible to increase the dose for cohort 4 if that was necessary?

Dr. Aaron Osborne: I'll have Aaron answer that question. Go ahead, Aaron.

Oh have Aaron I answer that question going in there.

Dr. Aaron Osborne: Yes, so we're giving four drops three times a day for three weeks, then three times a day for a week, twice a day for a week, once a day for a week, and then we stop. But the maximum frequency is four times a day, and eye drops can potentially be given more frequently than that, so, you know, that certainly would be one option if we needed to increase the amount of steroids being given. But, based on the experience in Cohorts 1 and 2, the inflammation that we've seen has been manageable with those topical steroids, so, you know, obviously, we're now doing that experiment in Cohorts 3 and 4, and look forward to getting the data as quickly as possible.

Yes, thanks, giving four times a day drops for three weeks and then three times a day for a week twice a day for wheat once a day for a week and then stop.

For the maximum frequency is four times today, and I, Charles can potentially be getting more frequently than that so.

That's that's certainly would be would be one option that we needed to increase the amount of steroids being given.

But based on experience can cover was one and two the information that we've seen has been has been manageable with those topical steroids. So obviously, we're not doing the experiment and in cohorts three and four and look forward to getting the data as quickly as possible.

Dr. Aaron Osborne: Got it. That's very helpful. Thanks for taking my questions.

That's very helpful. Thanks for taking my questions.

Leonie Patterson: Thanks, Bill.

Thanks, though.

Operator: Thank you, and as a reminder, to ask a question, you will need to press star 1 on your telephone. Our next question comes from Patrick DeLozo with Lifestyle Capital. You may proceed with your question.

Thank you and as a reminder to ask a question you'll need to press star one on your telephone. Our next question comes from Patrick the low so with lifecycle capital you May proceed with your question.

Hi, Thanks for taking the question I was just hoping you could guide expectations at Argo did update.

Leonie Patterson: Hi, thanks for taking the questions. I was just hoping you could guide expectations for the Arvo data update.

Sure. So as you might you probably have paid today that are very especially as the into some meeting has was can't so today. However, you also see that we write in our press release and what we sit today in our remarks that we do still playing to present data on the uptick trial in May and 10, so the.

Leonie Patterson: Sure, so as you may probably have heard today that Arvo officially, as the in-person meeting has was cancelled today. However, you will also see that we wrote in our press release and what we said today in our remarks that we do still plan to present data on the OPTIC trial in May. In terms of the ways that we'll do that, obviously we're waiting to hear back from Arvo. They are offering different ways to present data as still part of under Arvo, but without saying that we would still present data, we still plan to present data on OPTIC in May, as we've said, and either it'll be as part of the Arvo umbrella in whatever way they plan to allow presentations to still occur virtually, or whatever way that happens, or it'll be, and or it'll be some form of a webcast that we would do to support that as we have done previously and when we've done presentations of data.

The way that we'll do that obviously, we're waiting to hear back from either they are offering different ways to proceeds data, it's still part of under various but without saying that we would still proceeds.

Data, we still kinds of between data on uptick and in my as we said and it'll be as part of the I've umbrella in whatever way they plan to allow presentations to still a kid virtually or whatever way that happens or it'll be and or it'll be some form of the way past that we would do to support that as we have done.

Obviously, we done presentations of data.

Great. Thank you and then I guess kind of playing off of Phil's question. If possible can you provide any additional color on the status of the tape really steroid use and cohorts one and two.

Leonie Patterson: Great, thank you. And then, kind of playing off of Phil's question, if possible, could you provide any additional color on the status of the tapering of steroid use in cohorts one and two?

So we you know I think one or do some what we can talk about just want to be presented and Joe I think in terms of any updates we'd be providing that in light of time point, but I think fair to say that ER as we continue forward with the protocol in Q3 and four that does give some level of insight that we are comfortable with using.

Leonie Patterson: So we, you know, I think what I'll do is, what we can talk about is what to be presented at Angio. I think in terms of any updates, we'll be providing that at a later time point, but I think it's fair to say that as we continue forward with the protocol in cohorts three and four, that does give some level of insight that we are comfortable with using steroid eye drops as a measure of prophylactically managing any inflammation that we see. But I will see if Aaron has anything more to add on the tapering, and I think a reminder of what the investigators can do beyond the tapering period might be useful as well.

Stuart eye drops as a major Pennsylvania directly managing any information that we see but I see apparently if anything more to add there on the tapering and I think reminder, what they see guidance can do beyond the typing period might be useful as well.

Sure. So if you remember in cohort one we had all patients were treated with pretty flat to oral steroids and there was really a learning process on.

Dr. Aaron Osborne: Sure. So, if you remember in cohort one, all patients were treated with prophylactic oral steroids, and there was really a learning process. And after that, different types of topical steroids were given, and some patients even got some more oral steroids, and the timing of that was kind of variable amongst the group.

After that that in a different types of topical steroids, we Kevin and some patients even go some oral steroids and the timing if that was kind of variable amongst the group but.

Through December 1st which was the last time point that we analyze the data. So we had one patient you had has an unrelated series.

Dr. Aaron Osborne: Through December 1st, which was the last time point that we analyzed the data, we had one patient who had an unrelated serious adverse event of a retinal detachment and was post-surgery. And actually, that one patient, who remains under follow-up in optic, that was the only patient that had any cellular inflammation, which potentially was post-surgical. You would expect some cellular inflammation post-retinal detachment surgery

This event of a retinal detachment and was post surgery and actually that one patient who remains on the follow up an uptick that was the only patients had any cellular inflammation, which switch which potentially was post surgical you would expect some sending their information post retinal detachment century, the five others none of those had.

Dr. Aaron Osborne: The five others, none of those had any cellular inflammation at that time point. And we had two other patients; two of those five patients were on a tapering amounts of steroid, which was two drops a day each, and the other three were no longer on any topical steroids. So certainly, the cellular inflammation was resolving or resolved, and we had two patients remaining outside the one who was post-surgical; we have two patients who were taking topical steroids. So that's cohort one, and the other data point that we have is cohort two, which was at the lower dose, a three-fold lower dose, as you remember.

Any cellular information at that time point, and we had two two other patients two of those five patients where on the tight cream amounts of steroids, which was to drops today each.

And the other three would no longer on any topical steroids. So certainly the cellular information was resolving all resolved and we had two patients remaining of those outside of the one he was post surgical yet to patients who were taking topical steroids does cohort one and the other the other data point that we have just two which.

Below the lower dose a threefold lower doses you remember as we had.

Dr. Aaron Osborne: And there we had out of the six patients through 24 weeks of follow-up, two of the patients had not required any steroid eye drops after their initial oral course and had zero or next to zero inflammation. We had two other patients who had absolutely minimal inflammation of a maximum of half plus, and those who had short courses of topical steroids, and the inflammation had resolved. And then we had another two patients who had more significant inflammation, but that was improving or resolved, and they were on tapering eye drops. So we had two patients in cohort two who were on drops at week 24. So Cohort 3 obviously comes next, and there we have all of the patients that are getting the six weeks of topical eye drops, and we're hoping that those six weeks of topical eye drops can reduce the occurrence of having any adverse events or spikes in inflammation early on and can hopefully put the patients on a better course. But I think it's important to remember this inflammation has been low grade, the vast majority of it has been asymptomatic, with nothing affecting the back of the eye, so it's a predictable inflammation that seems to be very manageable with the topical steroid approach.

We had out the six patients through 24 weeks follow up to the patients have not required any any any any steroid eyedrops. After their initial oral course in that had zero on next Tuesday right.

It's a nation and we have two other patients who had absolutely minimal inflammation of a maximum of half Clos and those that have short course, who the topical steroids and the information and resolved and then we had another two patients you'd had.

A significant information, but that had a was improving all resolved and they won't pay pretty Nitrox Korea to patients in cohort two who are you on drops at week 20 pool.

The cohort three when she comes next and that we have all the patients to getting the six weeks of topical eye drops and we're hoping that those six weeks, we've talked a lot of drops can reduce the occurrence of of having any adverse events will spikes in inflammation early on I cannot keep up the patients on a better on a better cost.

It's important remember this information has been low grade the vast majority of as Dean asymptomatic nothing affecting the backup the eyes. So it's a it's a it's a predictable inflammation that seems to be very manageable with the topical steroids approach.

Great.

Thank you I'll now turn the call back to Adverum, President and CEO, we only Patterson.

Operator: [inaudible]

Leonie Patterson: Thank you. I will now turn the call back to Adverum's President and CEO, Leonie Patterson.

Alright. Thank you again for joining our call today, we have made significant progress. This past year looking ahead key catalyst freight volume this year I presented data from uptick in my submitting an idea in diabetic neuropathy and the first half of this year initiating a phase one two clinical trial and beyond the second half of the year.

Leonie Patterson: All right, thank you again for joining our call today. We have made significant progress this past year. Looking ahead, key catalysts for Adverum this year are presenting new data from OPTIC in May, submitting an ID and diabetes recognopathy in the first half of this year, initiating our Phase 1-2 clinical trial in DR in the second half of this year, and finally presenting data for all four cohorts of OPTIC in the second half. We look forward to further sharing our clinical progress and continued execution as we advance the development of our novel In closing, I'd like to thank the patients, caregivers, and retina specialists who are participating in the OPTIC trial. And, last but certainly not least, I want to thank the Adverum employees for their tireless efforts. Our achievements at Avera wouldn't be possible if it weren't for the dedication of this team. Thank you for your time, and this concludes our call. Thank you, ladies and gentlemen. This concludes today's conference call.

And finally, presenting data for all four cohorts about that and the second huh.

We look forward to fit a sharing a clinical progress and continued execution as you advanced the development of and not one gene therapy, and if you're lucky to for the treatment of serious diseases.

In closing I'd like to thank the patient kick of is it retina specialists, who are participating in the optical and last but certainly not least I want to thank you had their employees for their tireless if it.

Our achievements that advair wouldn't be possible. If it went for the dedication of this pain.

Keep lead time and this concludes alcohol.

Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.

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

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