Q4 2021 Iveric Bio Inc Earnings Call

February 24, 2022

Okay.

Good morning, and welcome to <unk> Bio's conference call, representing <unk> bio today are Mr. Glenn <unk>, Chief Executive Officer.

Dr. Praveen Dougal President, Mr. Keith Westby, Chief operating officer.

Mr. Dave Carroll, Chief Financial Officer, Dr. Double decide Chief Development Officer, Mr. Chris <unk>, Chief Commercial officer, and we are pleased to welcome Mr. Tony give me as Chief business and strategy Officer, Tony joined the company in mid December .

Pleasure to have you with us Tony.

I would like to remind you that today, we will be making statements relating to <unk> bio's future expectations regarding operational financial and research and development matters. These statements constitute forward looking statements for the purposes of the Safe Harbor provision under the private Securities Litigation Reform Act of 1095. These statements cover.

Many events and matters.

That are subject to various risks that could cause actual results to differ materially from those expressed in any forward looking statement.

We refer you to our SEC filings and in particular to the risk factors included in our quarterly report on Form 10-Q filed on November nine 2021 for a detailed description of the risk factors affecting our business that could cause actual results or events to differ materially from the forward looking statements that we make.

In addition, any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date, while we may elect to update these forward looking statements at some point in the future. We disclaim any obligation to do so except as required by law.

I'd now like to turn the call back to Glenn.

Thanks, Kathy and good morning, everybody and thank you for joining our fourth quarter and year end conference call.

As we think about 2022, we continue to focus on execution as evidenced by gathered two our second phase III clinical trial, because the more with the treatment of geographic atrophy.

<unk>, which continues to exceed our expectation with an injection fidelity rate well above our stated goal of greater than 90% at month 12.

We look forward to share top of sharing top line data in the second half of the year. This will be approximately one year. After the enrollment of the last patient in plus as you know the needed time to do with the database lock and analysis, which Keith will speak to in a few moments.

If the 12 month results are positive we plan to file applications with the U S FDA as well as the European Medicines agency for marketing approval Oxymora NGA.

As we get closer to reporting the gathered two data we continued our efforts internally to prepare for potential filing of a new drug application for some more for the treatment of <unk>. We continue to gain momentum in building out our medical affairs team led by double beside our chief.

Our Chief Development Officer, and the commercial infrastructure led by Chris <unk>, Our Chief commercial officer.

Our two experienced and well seasoned leaders with.

And with experience in working in launching retina drugs with blockbuster potential.

We continue to execute on our IP strategy for Tomorrow earlier this month.

Patent and trademark office or lab claims for patent coverage covering methods of abuse.

Zimbra to treat Gi.

Once issue is expected to expire in 2034.

We're also excited to announce the results of a post hoc analysis that evaluated various gea growth parameters to explore the rate of disease progression within the regions in the phobia and a subset analysis of patients from gather one which is our phase III clinical trial for the treatment of some more NGA. These.

These data were recently presented at this year's Andrew.

Exploration and degeneration conference and <unk> will provide more details on the analysis in a few moments and you'll see why we are quite excited by this new data.

As we think back over the past year, we successfully achieved a number of major milestones that we believe have laid the groundwork for 2022 to be a banner year for us.

Let me briefly recap some of the significant highlights.

First we received a written.

Agreement from the U S FDA under a special protocol assessment or STI for the overall design of gathered to the.

The agreement further solidifies our plans to file an NDA with the FDA for marketing approval of Zamora for GE.

Ongoing gather two clinical trial meets its primary endpoint at 12 months.

As you know the more met its primary efficacy efficacy endpoint at 12 months with statistical significance in a previous completed gather one pivotal trial.

In July we announced the completion of patient enrollment and gather two this was four months ahead of our original schedule.

We also started the planning to initiate a phase III clinical trial studying zamora in patients with intermediate AMD in the second half of this year.

We continue to enroll patients in our star clinical trial. This is our phase II b screening trial of some more for treatment of autosomal recessive <unk> disease.

We also initiated a number of preclinical tolerability and pharmacokinetic studies for IC 500, or <unk> one inhibitor.

However, we anticipate that the started the IND, enabling tox studies will be later than originally planned. This is primarily due to the availability or lack of availability of study slots and contract research organizations in the wake of COVID-19 pandemic.

We expect to submit an investigational new drug application or IND to the FDA for IC.

500 during the mid 2023.

Sure.

We also strengthened our balance sheet by raising approximately 108 and 163 million in net proceeds from public offering in July and October 2021, respectively.

Dave will cover our cash and cash run rate later in the call. We believe that these funds.

The capital raise enabled us to accelerate preparations for a potential commercial launch of Zamora.

And allow us to continue to invest in manufacturing capacity.

In addition, we continue to invest additional money additional lifecycle initiatives towards the more in order to expand the patient population population with additional indications.

Which is the initiation of an intermediate AMD trial and investing in multiple sustained release delivery technologies.

On the corporate front, we're excited to welcome Christine Miller, who is the president and Chief Executive Officer, Melinda Therapeutics to our board of directors, we're thrilled to have somebody of christine's caliber join our board.

Christine has extensive background in commercialization and supply chain management will be a valuable addition to our board of directors.

We're also as Kathy just mentioned excited to welcome Tony Gibbons to our company he joined as Chief business and strategy Officer. This past December .

Tony is an experienced biotech executive and former investment banker and as you know is well known throughout our industry. We look forward to tonys leadership and extensive experience and contributing to our future success.

Ask Tony to say a few words about our business development strategy later on in this call.

Like to now turn the call over to Keith.

Thanks, Glenn and good morning, everyone.

As Glenn mentioned, we completed patient enrollment and gather two in July 2021, with 448 patients enrolled four months ahead of our original schedule.

Based on this timeline, we expect topline gathered to data to be available in the second half of 2022.

<unk> one year after the enrollment of the last patient plus the time needed for database lock and analysis.

We are actively working internally and with our third party vendors to prepare for the gather to database lock.

A major priority for us is to continue to aggressively drive patient retention, and therefore and thereby further derisk. The gather two clinical trial as Glenn mentioned, we are targeting patient retention, where they gather two trial as measured by injection fidelity rate through month 12 of greater than 90% <unk>.

Injection fidelity is calculated by dividing the total number of actual injections by the total number of expected injections, we consider injection fidelity to be the most important and stringent measure of patient retention because it reflects the timely administration of the drug or sham into the patient.

As of today, we continue to maintain an injection fidelity rate of well above our 12 month target of greater than 90%.

As a comparison the 12 month injection fidelity rate for our gather one trial, which showed a statistically significant reduction in VA progression at 12 months was 87%.

We continue to focus on injection fidelity not only to protect the integrity of the data, but also to observe.

Potentially observed the early and increasing treatment effect, we previously observed in gather one.

Patient retention is clearly an integral part of the gathered to outcome to date. We are excited to have reached a trial completion rate of 84% for year one.

<unk> for the primary efficacy endpoint of the trial, therefore with only approximately 16% of your one visits remaining and gather too we are encouraged to see that our efforts to maximize patient retention and gather to have resulted in even greater patient retention than was observed in gather one through the same time period.

Summarize gather two has exceeded our expectations correct patient recruitment patient retention and injection fidelity.

We continue to work with our investigators to provide a safe environment for patients, which we believe increases the patient comfort and confidence to continue to participate in the gather two clinical trial.

As we discussed in the past, we implemented a number of initiatives to reduce the risk and exposure to COVID-19 for our patients and the stack treating them well.

We have found that many principal investigators are enthusiastic and committed to participating and gather two clinical trial. We believe the positive gather 112 months data further supported by the positive 18 months efficacy results and the safety profile that was maintained throughout the trial along with the early and increasing treatment effect observed and gather one.

Our key motivators for retention and gather too.

In addition, there are currently no therapies approved for <unk> in either the U S or the European Union.

Turning to starve our disease patient enrollment in the Star trial is ongoing with the goal of enrolling approximately 25 additional patients for a total of approximately 120 patients.

The results of this trial are expected after the topline results together too.

Thanks for your time and I will now turn the call over to Praveen.

Thank you Keith Thank you all for joining the call. This morning, I hope that you all well.

On our previous earnings call, we discussed that part of the gathered program. In addition to evaluating the overall rate of <unk> growth.

We're going to be investigating can be supportive analyses, whether it's maura has.

Potential to slow the progression of <unk> into the phobia.

Thereby preserving central vision, which would otherwise be lost in this relentless relentlessly progressive blinding disease.

Two weeks ago data from a post hoc analysis that evaluated various growth parameters to explore the rate of disease progression within various regions in this Bolivia and a subset of patients from the gathering one clinical trial were presented at the angiogenesis Exudation and DJ.

<unk> conference by Dr. Glenn Jaffe director of the Duke Reading Center, and Chief of the Retina Division of the Duke ice venture and Robert marketing Professor of Ophthalmology.

Consistent with the overall results gathered volume.

In the new analysis and reduction in lesion growth in five standardized regions surrounding including with central bogey or area was observed for patients receiving some more at two milligrams as compared to patients receiving sham over a period of 18 months.

We believe the observed pattern of reduction in G&A growth in the different regions.

With the natural history of the disease and recent clinical trial results in which complement inhibition has been observed to be associated with a greater reduction in <unk> growth in.

In patients with non <unk>.

Which is known from the natural history to be faster progressing then.

Albeit involving gea.

This analysis supports our expectation that we would see a greater reduction in growth away from the global center with collecting the circumferential glu pattern typical for gea patients.

<unk> has a major impact on functional vision.

Could all toward the quality of life and independence of affected individuals.

We believe that the results from this exploratory analysis.

Another step.

Studying the potential of Zamora to preserve central vision by slowing the progression of GA.

The significance of this data is that it has the potential to bridge anatomical results to functional outcome in other words Mike.

By preserving the central phobia, the patient may have the opportunity to continue to drive lead.

Independently et cetera for a longer period of time as compared to the natural history of the disease.

Additionally, while preserving the central fovea, we believe we have the potential.

To show a visual acuity benefit.

Overtime.

It must be stressed however that this is an exploratory post hoc analysis that requires confirmatory post spectra trials.

Over time, we anticipate performing similar analysis will gather two to further build upon these insights.

Turning to earlier stages of AMB based on our hypothesis regarding complement inhibition as a mechanism of action to treat AMD.

And the previously announced results from a post hoc analyses from gather one evaluating the progression of incomplete.

No.

<unk> and outer retinal atrophy or IRA to complete retinal pigment epithelium, and outer retinal atrophy or see lora and the progression of <unk> into <unk> and there has been more of a two milligram and sham control groups.

To initiate a phase <unk> clinical trial that moves more in patients with intermediate AMD.

Our stage prior to the occurrence of GAA.

Second half of 2022.

We expected intermediate AMD trial to be an international randomized double masked sham controlled multicenter trial with approximately 200 patients per treatment group, we expect to treat and follow all patients or 24 months.

We plan to obtain feedback.

Feedback from regulatory authority that will influence the ultimate design of this clinical trial and our development strategy.

Indication before initiating this trial.

<unk> is a hallmark of the onset and progression of AMD.

We estimate that by 2039, there will be approximately 6 million individuals with <unk> in the United States and 8 million individuals with Doosan in the EU countries.

The population, we look to enroll.

The intermediate AMD trial.

Of.

The prevalent population.

We have been exploring several lifecycle management initiatives for tomorrow with efforts focused on potential sustained release delivery technologies.

Our goal is to derive a formulation of Zamora with a sustained release delivery technology that reduces the frequency of anchor the drill injection, while maintaining comparable efficacy and safety to monthly injections.

And exploring and evaluating a number of potential sustained release delivery technologies, including conducting feasibility studies with various technology providers and analyzing the results on formulations containing zamora and the sustained release delivery technology.

If any of these technologies meet the performance thresholds that we have established we may pursue longer term development collaborations.

We are fully committed to delivering treatments for AMD.

<unk> earlier stages.

Of the disease, such as intermediate AMD.

We believe we are well positioned to expand <unk> indications build in AMD franchise.

And subject to regulatory approval commercialize memorial with GE as the market leader.

Thank you for your time I will now turn the call over to Tony.

Thank you Hey, good morning, everyone.

It is truly a pleasure to be here with you. This morning, I'm excited to join <unk> and to work with Glenn and others on the leadership team, who I've known for many years as well as prevent Dave and all my new colleagues I appreciate the.

<unk> to say a few words about our business development priorities and broader strategy.

We're continuing to explore all options for the future development and potential commercialization, because tomorrow, including potential collaborations outside of the U S. I.

I wanted to reiterate our plan to develop and commercialize them or in the U S, where we can leverage our retinal expertise, particularly well.

As we continue the development of our product candidates and programs and prepare for the potential commercialization of tomorrow. We will continue to pursue selective business development opportunities that advance us towards our long term strategic goal of becoming a dominant and sustainable leader in retinal diseases.

We plan to continue to evaluate on a selective and targeted basis opportunities to obtain rights to additional product candidates and technologies for retinal diseases. That's preventing just mentioned with a near term focus on sustained release delivery technologies presume Mauro.

Thank you for your time this morning, I look forward to connecting with all of you soon I will now turn the call over to Dave.

Thank you Tony and good morning, everyone I'd like to highlight a few items from our press release of this morning, and provide some guidance our expected year end cash balance and our expected cash runway for the quarter, our net loss totaled $33 million or 29 cents per share compared to a net loss of $25 $4 million were <unk> 27 per share for <unk>.

Q4 2020.

This increase in net loss was driven primarily by an increase in R&D expenses associated with ours or more clinical programs increased manufacturing activities for tomorrow and increases in personnel costs, including stock compensation associated with additional R&D staffing.

For the full year, our net loss totaled $114 5 million or $1 12 per share compared to a net loss of $84 5 million or $1 14 per share for 2020 again, primarily due to an increase in R&D expenses.

Turning to our expected year end cash balance and cash runway. We now expect our yearend cash balance to range between $215 million and $225 million, we estimate that our cash cash equivalents and marketable securities will be sufficient to fund our planned capital expenditures and operating expenses through at least mid 2024.

These estimates are based on our current business plan, which includes the continuation of our ongoing clinical development programs for Zamora, NGA and Starbucks and the initiation of intermediate AMD clinical trial preparation of potential filing of an NDA and MAA frigid Lora continuing preparations for potential commercial launches tomorrow investing in sustained release Dill.

Every technologies for Tomorrow.

Advancement of our IC 500 development program.

Excluded from these estimates or any potential approval or sales milestones payable to the architects corporation for any potential expenses to the actual commercial launch tomorrow, including Salesforce expenses and any additional expenditures related to potentially studying zamora and indications outside of GAA star.

Star Wars and intermediate AMD.

Resulting from the potential in licensing or acquisition of additional product candidates or technologies or any other associated on that we may pursue.

And I will turn the call back over to Glenn. Thank you for your time.

Thanks, Dave as we look ahead to 2022, we'll continue to focus on the execution of gather too with the retention of patients and preparing for potential commercialization of tomorrow in the U S. As our top priority we.

We will continue our internal efforts to prepare for a potential filing of an NDA because of more for the tree.

<unk>.

Just to gather two results are positive.

We also look forward to initiating a phase III is a more intermediate AMD trial and investing in additional lifecycle initiatives such as sustained release technologies towards the more I.

I want to thank you all today for listening in and your continued support and we look forward to providing you with updates on our progress as we move along.

Now turn the call over to the operator, so we can open up the lines for questions Keith I'll turn it to you yes. Thank you at this time, we will begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone.

If you are using a speaker phone please pickup your handset before pressing the keys to withdraw your question. Please press Star then two.

Time, we will pause momentarily to assemble the roster.

And the first question comes from Ken Cacciatore with Cowen and company.

Hey, good morning team.

Congratulations on all the progress.

Your competitors' results really help nicely confirm the impact on complement inhibition studying extra <unk> lesions and obviously, you're a post hoc analysis also focusing on your enrichment strategy really validated. So just wondering could you talk about the percentage of <unk> patients that have extra phobia lesions talk about how easy it is to <unk>.

Diagnose I know once a product is approved I would imagine you can implement a strategy to really help educate clinicians on earlier diagnosis, but I'd like to hear about that and then maybe talk about how the FDA.

Would handle a label here in terms of extra full deal versus full field. So that's question number one with a couple of parts and then just question number two you talk about the progress on looking for extended release formulations, just like to hear a little bit more about the ease or maybe lack thereof of zamora in.

Formulating into extended release kind of what are you seeing in your early.

Work here and then maybe.

Talk about.

The implant be something that you'd looked at there seems to be some success right now moving forward with the PK is on an implant strategy is just a little bit more around the the sustained release formulation work. Thanks, so much.

Well thanks, Kevin.

Work on question, one, which I think has three parts.

And we'll break it up amongst obtained in the first part is the.

The amount of extra wholesale.

Patients in the total population of Gi, which we estimate to be about $1 $5 million in the U S and of that.

About two thirds have extra flow deal.

So I hope that helps with that the second question on really diagnosis.

Funding these patients Praveen, let me turn it over to you and maybe we'll tag team on the NDA and for the extended release will maybe ask Tony to.

Comment so Permian under diagnosis question.

Thank you Glenda and Ken. Thank you for your question the diagnosis part Ken.

It's really.

Funded examination essentially one can see these patients and see the geographic atrophy with a with a with a.

Routine fund does the valuation now you can also see it very clearly with an auto fluorescence.

And this is the diagnosis, that's really will be made not just by retinal specialists, but by general ophthalmologists as well as optometrists.

And that's where most of the extra full youll patients currently reside.

There is a referral bias as you can imagine for retinal specialists because they are usually referred the most severe patients that means school will be involving.

However.

The ones that youre, referring to the extra mobile is really the vast majority of the patients.

And these currently reside with general ophthalmologists and optometrists and our expectation is that once there's a therapy for these patients and these patients will be referred to retinal specialists as was the case for wet macular degeneration now it's important to state that these patients are really do suffer from a loss of visual function, although their visual acuity.

Judy maybe 2020 now they may not be able to see a straight line they.

They may not be able to finish reading a sentence or finish reading of excel table now because of a blind spots. So that these patients that we would imagine would be younger in the workforce and therefore, much more desperate and much more compliant as well.

In regards to the other questions Glenn I'll turn it back to you I'm happy to answer as you.

<unk> direct.

Okay. Thank you Pervenche, let's we'll come back to your NDA question, Kevin I, just wanted to get clarification on exactly what youre looking for but Tony a couple of words about extended release and <unk>.

The early work that we're doing there and the type of technologies that may be.

The applicable here.

Sure happy to so.

Looking at a number of technologies.

It really is across the spectrum of available technologies.

Back of the eye diseases, some of which are quite.

Late stage and validated and some that are really more emerging technologies I have to say I think <unk> given that it's in afterwards.

Rather stable seems to be rather conducive to a number of the technologies, but not every technology. So as we look at the feasibility we are looking at.

Implant technologies or looking at micro particles, we're looking at others.

And as we continue to gauge the feasibility or really our targeted goals.

Truly move forward those that are most amenable to zamora and meet our targeted goals for for sustained delivery.

In a way that really doesn't compromise patient care, but it really continues.

The benefits that we're seeing with <unk> it.

It is current formulation so stay tuned.

Great and my question was on the label, obviously, there seems to be impact on.

All areas of the slope of the Atlanta and extra Fulvio, but just wondering how do you think the agency will handle the label given the patient enrichment for for gather wanted too.

Yes, so Kevin Firstly, I think we need to obviously see the data from from gathered to before we talk about label strategy.

But I'll, let <unk> answer that Chris I think we have some thoughts on how we would position our data.

With the agency for me.

Thank you Glenn and Ken. Thanks, again, so I must say from the very start that we haven't had any formal labeling discussions with the FDA, obviously, it would be premature to do so.

What I will tell you that our expectation.

Is that the label will be broad now it doesn't mean that complement inhibition doesn't work in patients with phone via affecting lesions is just that the delta given the natural history would be.

It would be less.

And Thats exactly what we see in our studies and in our competitors' studies as well. So the one thing that I would take home from this is that we certainly de risked gatherer too, but peaking picking the proper patient population now again, our expectation is that if we're able to slow down a faster growing geographic atrophy safely.

There is no reason that we wouldn't be allowed to treat patients with a slower growing geographic atrophy, having met a much higher borrowers scrutiny I think the FDA completely understand how important it is for patients with full be affecting geographic atrophy to have some area in the peripheral deal.

Areas survive their patients that I remember I used to treat that had lesions in the tariff OBL area with eccentric fixation and they would use that that area to stop from bumping into furniture or.

Stop their hands from getting burned in a hospital that's terribly important.

<unk> to measure, but it's terribly important and we feel that the FDA will recognize that and allow a broad label.

Great. Thanks team real exciting time for the company congratulations on the progress ill go back in the queue.

Thanks, Ken.

Thank you and the next question comes from Michael <unk> with Morgan Stanley .

Yep.

Guys. Thanks for taking the questions.

Quickly on gatherer too in terms of the injection fidelity rate, you're obviously tracking above your goal of 90% and thats exceeding your expectations, but I'm just curious more recently <unk> seen a break in the trend there at all due to <unk>.

Yes, Mike Thanks for the question and I think one of the reasons we wanted to.

Reinforce our progress today is that <unk>.

Of those present complications, but I think we were able to knock on wood manage through that so that's why we wanted to give the numbers both on injection fidelity running well ahead of our <unk>.

Projected guidance and also a key point that Keith where it is today is where we are in the injunction progress which was 84% so I think.

Yes.

The protections we put in early on for both patients and health care workers.

As it related to the pandemic I think continue to pay off and in fact keeps team.

Put a little bit extra diligence as <unk> started to hit its peak to be sure that patients were managed patient Scott type of visits a lot of prep work and then a lot of follow up work. So that was the reason we talk about injection fidelity today, because we feel we're in real good shape.

Got it that's helpful. And then maybe just just a follow up on the intermediate AMD study that youre going to start in the second half.

You gave us some sense at a high level of how youre thinking about the design, but youre also planning to meet with the FDA prior to starting the study so just curious.

What are the areas you are looking for feedback from the FDA as it.

Is it endpoints is it enrollment criteria or any color you can provide there. Thanks.

Great Great question, Mike do you want to take that one in terms of the design.

Sure and good morning, Mike and thank you for the questions first of all I want to say if you just look at the biology of this disease.

Complement inhibition works in extra Foveole geographic atrophy, you can be quite confident that it will work in earlier stages, because thats, where complement is even more active which is intermediate AMD. What the FDA has stated publicly is to say look this is a major problem.

And there is a major advantage to not only slowing down the desk of photoreceptor cells, but preventing it altogether. So we're extraordinarily fortunate to have a very very collaborative.

And consistent FDA and the purpose of our meetings is that really nobody has done. This study before so the answer to your question Mike Yes, all of the above we intend to sit with them and say look here are the parameters that we know from working with the community as as we are in we have with with the groups like Camber Cam group in the magnet stores.

Group and say look here are the parameters that we know are predictive of geographic atrophy and this is what we would like to study and these are the patients that we'd like to enroll and that's the discussion we intend to have.

Again, the FDA is extraordinarily collaborative and that we believe that whatever feedback they give us but will greatly influence the design and the development of this trial.

Got it thank you.

Thank you and the next question comes from Thiago <unk> with credit Suisse.

Hey, Thanks for taking the questions and congrats on the progress so far so just to go back to a point you've mentioned on gather to being relatively de risked based on patient selection. So again, we haven't seen building oaks fully replicate enterprising and Philly.

And maybe baseline characteristics could have played a role there. So can you just kind of recap kind of the factors that make you confident that gathered two will actually replicate gathered one finding.

And why you can expect a potentially different outcome than what you suffer a competitor and a quick follow up and you guys alluded to some new IP that you have.

Okay.

Recurring portfolio doctoral property.

And also any outstanding financial obligations to our cabinet based on potential approval and launch.

Sorry.

<unk> part question there.

Okay.

Yes, no problem Thiago I think we have three questions.

First on the gathered to and how we're feeling.

<unk>.

The Derisking I think Theres, a few things to cover and I'll, let <unk> to my commentary one we have an unusual situation that we have one of two phase III trials done. So we have the benefit of the gather one data and we also have the benefit of the.

And the 12 month data was the primary endpoint, but also in gathered one we had the benefit of the 18 month data to see what happened in the six months after and as you know we continue to see the separation of the curves.

As to another factor did you pick the right patients we always believe that we did.

And then with our competitor's data with their subset analysis of extra Fulvio lesion showing quite.

Similar numbers in terms of efficacy we felt that that's a further derisking.

The.

Recruitment and the reason, we put the concept of injection fidelity and obviously to keep the integrity of the study you want.

High retention rates and we felt the best way to measure that was through rejection fidelity. That's why we created that concept and we continue to update that.

And the fact that we're running well ahead of our guidance and we're well into the 80% range.

Demonstrates that these patients are coming back and also going back to gather one we had a terrific.

Trial and data to show those patients we finished a phase III trial. So I hope that created some momentum and I think our investigators to talk to their patients about that so far all of the above in the Permian.

Some additional commentary on that we feel that we have seen a number of signs that are encouraging as we get to the end of gather too.

Pardon me.

Okay. Thank you Glenn and Tiago good morning, and thank you for the question, let me divide my answer into two parts. The first part would be the consistency and validity of gather one and the second part would be how we view risk gather two and both are really important questions.

So if you go back and look at the other one and now that there is more data coming from our competitors and others.

You will see it this remarkable consistency in terms of the efficacy profile and in terms of the safety profile. So in terms of the efficacy profile you will see as you know is an immediate separation with the delta getting bigger and bigger with every visit and Thats true in the two milligram dose that's true and the four milligram dose that's true whether it's states where.

<unk> transformation analysis or non square root transformation analysis unless.

Actually even true in all of the retrospective studies, we've done so that kind of consistency should give us a great deal of confidence in the robustness of the data and it's the same thing that you see on the safety side as well I mean, you see a superior safety profile and you see a dose dependent response, so with everything.

And gather one what I would tell you is that the confidence that we get is from the absolutely remarkable consistency of the data which is in line with the science now the second part is how have we derisk gathered to that.

The most important answer is really by having gather one as Glenn said.

It's really unusual in fact, I don't recall a time in my 30 year career doing clinical trials, where I've ever recruited for the second part of the Phase III study.

The first phase III study already being so overwhelmingly positive, but the other ways that we recruit with de risk gathered two is by taking the proper patient population and we did this for several reasons, but the important one hears the biologic one which is that as when complement is most active in geographic atrophy in the earlier stages.

Clearly that was confirmed by our competitors results. The second is that we have a mixed random effects model that is particularly stringent and validated by the FDA as you recall, we've got a spa agreement, where all of the trial has been looked at including our mix rental effects model and thirdly.

And what we are doing right now and Keith and Evelyn Harrison and doubled assign their group are doing so well is to have that injections fidelity at a number that's just unheard of which is above 90%.

And that's despite having no vaccine, having delta having almost front our guidance hasn't changed. So we believe we are doing everything they can possibly be done.

To Derisk gatherer too in the face of an overwhelmingly positive and consistent results for gathered one.

Thanks for being until go to your second question around the patent I think it's one of our multi pronged strategy that we laid out.

For lifecycle of this service product this is a patent that.

Have those methods of using Zamora.

Once issued.

It is expected to expire in 2034.

It's under the umbrella of lifecycle, Tony spoke a little bit about the <unk>.

Initiatives for extended delivery obviously.

Strengthening the IP portfolios part of that and we'll look to continue to find ways to extend the franchise. So we were happy to.

Report today on that patent, which is just one step in a number of things that we're working on.

The third question Thiago was related to financial obligations and I'm going to ask Dave to cover that sure. Thanks Thiago. Thanks for the question and.

Let me just open up with it's a really great deal for US there is no royalties on some more whatsoever first off.

And then the total payments related just the first indication is in the $20 million to $25 million range 23, five something like that this will all be in our 10-K and actually in last year's 10-K also.

And then.

No royalties and those milestones just related to that.

Clinical and regulatory milestones that's it.

Thanks Bruce.

And you're saying now.

Good night.

Yeah.

Thank you.

The next question comes from Annabel <unk> from Stifel.

Hi, Thanks for taking my questions I had a couple here so.

I guess theres been some question about.

Patient motivation to.

Physician motivation to trade as high patient motivation.

To continue to treat chronically I would say at the late stages of disease.

They are starting to see functional issues.

Likely higher but I'm, just a little bit curious and.

The intermediate stages of disease.

<unk> are these patients compromised functionally and.

I know it's.

You are motivated.

To try to treat these patients as early as possible.

I guess I'm trying to understand that patient motivation to treat earlier in disease.

And maybe you can just talk about that in terms of.

Where do you think the most likely treatment and will be even if you have.

Meaningful data on the intermediate population.

And I guess the.

Second question I have.

Is on the 84% completion that you just talked about.

Are all of these patients expected.

In Q.

<unk> portion of the trial and if so or if it's in.

Cheng.

And to what extent have these patients.

84% also moved into the ATM a question on the trial.

Thanks, Dan.

Okay. Thanks, Annabel so two questions there.

Praveen answer the first question because as I.

In a prior life as a treating physician I guess, there is nobody better to talk about patients and patients motivation on this disease and on the completion rate.

<unk> answered that including what.

What happens to these patients at the end of their 12 months what happens in year. Two so Keith we'll lay that out for you. So praveen, let me turn it over to you first.

Great and about good morning, and thank you for your question. Let me just divide the answer institute different parts, the GAA part as well as the intermediate AMD part.

And there is a.

Theres really a policy out there that with geographic atrophy. This is a disease that occurs in.

Our older patients and the disease progresses extremely slowly.

We simply know that that is not true we know the disease that occurs as early as the patients in their <unk> and <unk> and all.

<unk> starts extra full deal always progressive circumferential Lee fairly rapidly and I use that word rapidly deliberately if you look at great natural history studies that have been done by Genentech Roche Youll see that that movement of geographic atrophy occurs in a matter of months not years, we're talking about four to six months.

So another way of looking at this is that there was a recent.

Article that looked at the entire UK database that was offered.

The senior author was <unk> that showed that patients with geographic atrophy end up losing.

Driving vision, 60% or so lose driving vision and one six years, which is just really stunning.

And about <unk>.

About three years, 40% or so have their central fovea completely obliterated. So this is truly a relentless relentlessly progressing blinding disease and these patients again that we're targeting are the whole gamut of patients with early disease as well as late disease. You can imagine that these are these.

Or are patients who may be in their <unk> and <unk> that may not be able to see a straight line and functioning as an architect and engineer or may not be able to read finished reading a sentence centers are functioning as the attorney or an accountant and these are people that have 2020 vision, but are visually completely dysfunctional and we.

Believe that there'll be a very motivated when there is a treatment available to slow down the progression of this disease.

And again those patients are not necessarily all with retinal specialists at this point.

They are with optometrists and general ophthalmologists, but once there is a treatment available. We believe those patients will be referred rapidly to the retina specialists and we've seen this in wet macular degeneration as well now switching to intermediate macular degeneration. Typically these patients can be identified as early as <unk>.

In their Thirty's, forty's and you're exactly right a lot of them in the very early stages are not symptomatic in the later stages of intermediate AMD. They are symptomatic when the same kind of reasoning that I mentioned, where they.

They may be able to have visual dysfunction, because of not seeing straight line with the <unk> or scatoma or blind spots.

And.

Currently with the version one of Zamora, we feel that there is there are enough patients with intermediate AMD, where that impact will be made to prevent progression to a blinding disease, which is geographic atrophy and that'll be very important for the earlier stages.

Our lifecycle management of some more of that Tony referred to are terribly important we.

We believe that if we can have a sustained delivery type strategy, where patients have to come in to the retinal specialist maybe once every six months or once every year that will be quite acceptable to prevent them from <unk>.

Having to suffer through geographic atrophy I hope I've answered your question. Okay. Thanks, Thanks for the question.

Thank you.

Thanks Annabel this is Keith for your question on the 84% completion.

Just a couple of things. So you are correct, 84% complete.

Completion of year, one gathered she was designed as a two year study. So as these patients complete year. One they are rolled into year two of the study just important to note. The design. So as patients receive monthly injections that are on the two milligrams or more arm in year. One at the 12 month time point. They are re randomized to either continue to re.

<unk> monthly injections of Zamora, two milligram or every other month the sham patients continue on sham.

Hope that helps to answer your question.

Yes, and all of them had been re randomize all the 84% that have completed have been randomized.

That's correct yes.

Correct, so that patients can they they go into year two.

Okay, great. Thank you.

Thanks Annabel.

Thank you.

And this concludes our question and answer session and I would like to turn the photo management for any closing comments.

Well, thank you Keith for moderating today, and I want to thank everybody for joining and we look forward to continued dialogue about our progress through the rest of the year.

By everybody and have a good day. Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.

[music].

Good morning, and welcome to <unk> Bio's conference call, representing <unk> bio today are Mr. Glenn <unk>, Chief Executive Officer, Dr. Praveen Dougal President, Mr. Keith Westby, Chief operating Officer Mr.

Mr. Dave Carroll, Chief Financial Officer, Dr. Adult decide Chief Development Officer, Mr. Chris Simms, Chief Commercial officer, and we are pleased to welcome Mr. Tony give me as Chief business and strategy Officer, Tony joined the company in mid December it's a pleasure to have you with us Tony.

Many events and matters.

That are subject to various risks that could cause actual results to differ materially from those expressed in any forward looking statements I refer you to our SEC filings and in particular to the risk factors included in our quarterly report on Form 10-Q filed on November nine 2021 for a detailed description of the risk fact.

It is affecting our business that could cause actual results or events to differ materially from the forward looking statements that we make in.

Yes.

Thanks, Kathy and good morning, everybody and thank you for joining our fourth quarter and year end conference call.

As we think about 2022, we continue to focus on execution.

As evidenced by gathered two our second phase III clinical trial, because tomorrow for the treatment of geographic atrophy.

Our gx, which continues to exceed our expectation with an injection fidelity rate well above our stated goal of greater than 90% at month 12, we look forward to share top sharing top line data in the second half of the year. This will be approximately one year after the enrollment and the last patient in.

No the needed time to do the database lock and analysis, which Keith will speak to in a few moments.

If the 12 month results are positive we plan to file applications with the U S FDA as well as the European Medicines agency for marketing approval of some more <unk>.

As we get closer to reporting the Gaba two data we continued our efforts internally to prepare for potential filing of a new drug application for some more for the treatment of <unk>.

We continue to gain momentum in building out our medical affairs team led by double the size of our chips.

Our Chief Development Officer, and the commercial infrastructure led by Chris <unk>, Our Chief commercial officer.

These are two experienced and well seasoned leaders.

Experience in working in launching retina drugs with blockbuster potential.

We continue to execute on our IP strategy for Tomorrow earlier this month the U S.

Patent and trademark office to lab claims for patent covered covering methods of abuse.

Maura to treat.

The patent once issue is expected to expire in 2034.

We're also excited to announce the results of a post hoc analysis that evaluated various G&A growth parameters to explore the rate of disease progression within the regions in the fovea and a subset analysis of patients from gather one which is our phase III clinical trial for the treatment of some more NGA.

These data were recently presented at this year's Andrew.

Exploration and degeneration conference and <unk> will provide more details on the analysis in a few moments and you'll see why we are quite excited by this new data.

As we think back over the past year, we successfully achieved a number of major milestones that we believe have laid the groundwork for 2022 to be a banner year for us.

Let me briefly recap some of the significant highlights first.

First we received a written.

Agreement from the U S FDA under a special protocol assessment or Spi, the overall design of gathered too.

The agreement further solidifies our plans to file an NDA with the FDA for marketing approval of some more <unk> if the <unk>.

Ongoing gather two clinical trial meets its primary endpoint at 12 months.

As you know the more met its primary efficacy efficacy endpoint at 12 months with statistical significance in a previous completed gather one pivotal trial.

Yeah.

In July we announced the completion of patient enrollment.

Two this was four months ahead of our original schedule.

We also started the planning to initiate a phase III clinical trial studying zamora in patients with intermediate AMD in the second half of this year.

We continue to enroll patients in our star clinical trial. This is our phase II b screening trial of some more for treatment of autosomal recessive <unk> disease.

We also initiated a number of preclinical tolerability and pharmacokinetic studies for IC 500, or <unk> one inhibitor.

However, we anticipate that the started the IND, enabling tox studies will be later than originally planned. This is primarily due to the availability or lack of availability of study slots at contract research organizations in the wake of COVID-19 pandemic.

We expect to submit an investigational new drug application or IND to the FDA.

500 during the mid 2023.

We also strengthened our balance sheet by raising approximately 108 and $163 million in net proceeds from public offering in July and October 2021, respectively.

Dave will cover our cash and cash run rate later in the call. We believe that these fund these.

This capital raise enabled us to accelerate preparations for a potential commercial launch of Zamora.

And allow us to continue to invest in manufacturing capacity.

In addition, we continue to invest additional money and additional lifecycle initiatives towards the more in order to expand the patient population population with additional indications.

Such as the initiation of an intermediate AMD trial and investing in multiple sustained release delivery technologies.

On the corporate front, we're excited to welcome Christine Miller, who is the president and Chief Executive Officer, Melinda Therapeutics to our board of directors. We're thrilled to have somebody of christine's caliber join our board Youre seeing his extensive background in commercialization and supply chain management will be valuable.

<unk> to our board of directors.

We're also as Kathy just mentioned excited to welcome Tony Gibbons to our company he joined as Chief business and strategy Officer. This past December .

I will ask Tony to say a few words about our business development strategy later on in this call I'd like to now turn the call over to Keith.

Thanks, Glenn and good morning, everyone as Glenn mentioned, we completed patient enrollment and gather two in July 2021, with 448 patients enrolled four months ahead of our original schedule.

Based on this timeline, we expect topline gathered to data to be available in the second half of 2022, approximately one year. After the enrollment of the last patient plus the time needed for database lock and analysis.

We are actively working internally and with our third party vendors to prepare for the gather to database lock.

A major priority for us is to continue to aggressively drive patient retention, and therefore and thereby further derisk. The gather two clinical trial as Glenn mentioned, we are targeting patient retention for the gather two trial as measured by injection fidelity rate through month 12 of greater than 90% <unk>.

As of today, we continue to maintain an injection fidelity rate well above our 12 month target of greater than 90%.

As a comparison the 12 month injection fidelity rate for our gather one trial, which showed a statistically significant reduction in VA progression at 12 months was 87%.

We continue to focus on injection fidelity not only to protect the integrity of the data, but also to observe.

Potentially observed the early and increasing treatment effect, we previously observed in gather one.

Patient retention is clearly an integral part of the gather to outcome to date. We are excited to have reached a trial completion rate of 84% for year. One the time point for the primary efficacy endpoint of the trial, therefore with only approximately 16% of your one visits remaining and gather to where.

We're encouraged to see that our efforts to maximize patient retention and gather to have resulted in even greater patient retention than was observed in gather one through the same time period.

To summarize gather two has exceeded our expectations support patient recruitment patient retention and injection fidelity.

As we discussed in the past, we implemented a number of initiatives to reduce the risk and exposure to COVID-19 for our patients and the stock trading them.

Our key motivators for retention and gather two.

In addition, there are currently no therapies approved for <unk> in either the U S or the European Union.

Turning to starboard disease patient enrollment in the star trial is ongoing with the goal of enrolling approximately 25 additional patients for a total of approximately 120 patients. The results of this trial are expected after the topline results together too.

For your time and I will now turn the call over to Praveen.

Thank you Keith Thank you all for joining the call. This morning, I hope that you all well.

On our previous earnings call, we discussed that part of the gathered program. In addition to evaluating the overall rate of growth, we're going to be investigating through supportive analyses, whether it's the more it has the potential to slow the progression of <unk> into the phobia.

Thereby preserving central vision, which would otherwise be lost in this relentless relentlessly progressive blinding disease.

Two weeks ago data from a post hoc analysis that evaluated various growth parameters to explore the rate of disease progression within various regions in the <unk>.

In a subset of patients from the gather one clinical trial were presented at the angiogenesis Exudation and degeneration conference by Dr. Glenn Jaffe director of the Duke Reading Center and Chief of the Retina Division of the Duke ice sensor and Robert marketing Professor of Ophthalmology.

Consistent with the overall results will gather one.

In the new analysis and reduction in lesion growth in five standardized regions surrounding and including with central bogey or area was observed for patients receiving some more at two milligrams as compared to patients receiving sham over a period of 18 months.

We believe the observed pattern of reduction in G&A growth in the different regions.

System with the natural history of the disease and recent clinical trial results in which complement inhibition has been observed to be associated with a greater reduction in G&A growth in patients with non <unk>.

Which is known from the natural history to be faster progressing then.

Albeit evolving.

This analysis supports our expectation that we would see a greater reduction in growth away from the Foveole center with collecting the circumferential group pattern typical for Gi patients.

<unk> has a major impact on functional vision.

Could all toward the quality of life and independence of affected individuals.

We believe that the results from this exploratory analysis are another step.

Studying the potential of Zamora to preserve central vision by slowing the progression of GA.

The significance of this data is that it has the potential to bridge and ophthalmic older adults to functional outcome in other words Mike.

While preserving the central phobia the patient may have the opportunity to continue to drive lead.

<unk> independently et cetera for a longer period of time as compared to the natural history of the disease.

Additionally, Bob.

Preserving the central Fovea, we believe we have the potential.

To show a visual acuity benefit.

Overtime.

It must be stressed however that this was an exploratory post hoc analysis that requires confirmatory post spectra trials.

Over time, we anticipate performing similar analysis will gather two to further build upon these insights.

Turning to earlier stages of AMD based on our hypothesis regarding complement inhibition as a mechanism of action to treat AMD and.

And the previously announced results from a post hoc analysis from gather one evaluating the progression of incomplete retinal pigment epithelium and outer retinal atrophy or IRA.

Complete retinal pigment epithelium, and outer retinal atrophy or see lora and the progression of <unk> into <unk>.

We're more of a two milligram and sham control groups.

We plan to initiate a phase <unk> clinical trial that means the more in patients with intermediate AMD.

<unk> prior to the occurrence of GE in the second half of 2022.

We expect this intermediate AMD trial to be an international randomized double mass.

<unk> controlled multi center trial with approximately 200 patients per treatment group.

We expect to treat and follow all patients for 24 months.

We plan to obtain feedback.

Feedback from regulatory authority that will influence the ultimate design of this clinical trial and our development strategy.

Indications before initiating this trial.

<unk> is a hallmark of the onset and progression of AMD.

We estimate that by 2039, there will be approximately six new individuals with crews in the United States and 8 million individuals with Doosan in the EU countries.

The population, we look to enroll.

The intermediate AMD trial.

Of the prevalent population.

We have been exploring several lifecycle management initiatives towards the Morrow efforts focused on potential sustained release delivery technologies.

Our goal is to derive a formulation of Zamora with a sustained release delivery technology that reduces the frequency of intuitive drill injection, while maintaining comparable efficacy and safety to monthly injections.

We have been exploring and evaluating a number of potential sustained release delivery technologies, including conducting feasibility studies with various technology providers and analyzing the results on formulations containing zamora and the sustained release delivery technology.

If any of these technologies meet the performance thresholds that we have established we may pursue longer term development collaborations.

We are fully committed to delivering treatments for AMD, including earlier stages.

Of the disease.

Immediate AMD.

We believe we are well positioned to expand <unk> indications build in AMD franchise.

Subject to regulatory approval commercialize the Mora with GE as the market leader.

Thank you for your time I will now turn the call over to Tony.

Thank you prevent and good morning, everyone.

It is truly a pleasure to be here with you. This morning, I'm excited to join <unk> and I'm here with Glenn and others on the leadership team, who I've known for many years as well as prevent Dave and all my new colleagues I appreciate.

The opportunity to say a few words about our business development priorities and broader strategy.

We are continuing to explore all options for the future development and potential commercialization, because tomorrow, including potential collaborations outside of the U S.

To reiterate our plan to develop and commercialize them or in the U S.

Where we can leverage our retinal expertise, particularly well.

As we continue the development of our product candidates and programs and prepare for the potential commercialization of tomorrow, we will continue to pursue selective business development opportunities.

And it's us toward our long term strategic goal of becoming a dominant and sustainable.

Leader in retinal diseases.

Thank you for your time this morning, I look forward to connecting with all of you soon I will now turn the call over to Dave.

For 2020 this increase in net loss was driven primarily by an increase in R&D expenses associated with or is it more a clinical programs increased manufacturing activities for tomorrow and increases in personnel costs, including stock compensation associated with additional R&D staffing.

For the full year, our net loss totaled $114 5 million or $1 12 per share compared to a net loss of $84 5 million or $1 14 per share for 2020 again, primarily due to an increase in R&D expenses.

Turning to our expected year end cash balance and cash runway. We now expect our yearend cash balance will range between $215 million and $225 million, we estimate that our cash cash equivalents and marketable securities will be sufficient to fund our planned capital expenditures and operating expenses through at least mid 2020 for.

These estimates are based on our current business plan, which includes the continuation of our ongoing clinical development programs for some more NGA in Stark arts and initiation of intermediate AMD clinical trial preparation of potential filing of an NDA and MAA frigid Bora continuing preparations for potential commercial launches tomorrow investing in sustained release <unk>.

<unk> technologies for Tomorrow.

Advancement of our IC 500 development program.

Excluded from these estimates or any potential approval or sales milestones payable to the architects corporation for any potential expenses to the <unk>.

<unk> commercial launches of more including Salesforce expenses, and any additional expenditures related to potentially studying zamora and indications outside of GAA Stark.

AMD.

<unk> from the potential in licensing or acquisition of additional product candidates or technologies or any other associated on that we may pursue.

And I will turn the call back over to Glenn. Thank you for your time.

Thanks, Dave as we look ahead to 2022, we'll continue to focus on the execution of gather too with the retention of patients and preparing for potential commercialization of some more in the U S as our top priority.

We will continue our internal efforts to prepare for a potential filing of an NDA because of more for the treatment of GAA. If together two results are positive.

We also look forward to initiating a phase III is a more intermediate AMD trial and investing in additional lifecycle initiatives such as sustained release technologies towards the more.

I want to thank you all today for listening in and your continued support and we look forward to providing you with updates on our progress as we move along.

I'll now turn the call over to the operator, so we can open up the lines for questions. Keith I'll turn it to you yes. Thank you at this time, we will begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone. If you are using a speakerphone. Please pick up perhaps that before pressing the keys.

Your question. Please press Star then two.

This time, we will pause momentarily to assemble the roster.

And the first question comes from Ken Cacciatore with Cowen and company.

Hey, good morning team.

Congratulations on all the progress.

Your competitors' results really help nicely confirm the impact on complement inhibition studying extra popeil lesions and obviously, you're a post hoc analysis also focusing on your enrichment strategy really validated. So just wondering could you talk about the percentage of patients that have extra phobia lesions talk about how easy it is to.

We handle a label here in terms of extra full deal versus bulk deal. So that's question number one with a couple of parts and then just question number two you talk about the progress on looking for extended release formulations, just like to hear a little bit more about the ease or maybe lack thereof of zamora in.

Formulating into extended release kind of what are you seeing in your early.

Work here and then maybe.

Talk about.

The implant be something that you've looked at there seems to be some success right now moving forward with the TK is on an implant strategy, just a little bit more around the.

The sustained release formulation work thanks, so much.

Okay.

Well, thanks, Ken and work on question, one, which I think has three parts.

And we'll break it up amongst obtained in the first part is the <unk>.

The amount of extra phones.

Patients in the total population of G&A, which we estimate to be about $1 $5 million in the U S and of that.

About two thirds have extra ferrovial.

So I hope that helps with that second question.

Question on really diagnosis.

Finding these patients Permian, let me turn it over to you and maybe we'll tag team on the NDA and for the extended release will maybe ask Tony to.

Comment so for being on the diagnosis question.

Thank you Glenn and Ken. Thank you for your question the diagnosis part Ken.

Really.

The fund is examination essentially one can see these patients and see the geographic atrophy with a with a with a.

Routine fund as evaluation now you can also see it very clearly with an auto fluorescence.

And this is the diagnosis, that's really will be made not just by retinal specialists, but by general ophthalmologists as well as optometrists.

And that's where most of the extra bulb youll patients currently reside.

As a referral bias as you can imagine for retinal specialists because they are usually referred the most severe patients that mean school will be involving.

However.

The ones that youre, referring to the extra mobile as really the vast majority of the patients.

And these currently reside with general ophthalmologists and optometrists and our expectation is that once there's a therapy for these patients. These patients will be referred to retinal specialists as was the case for wet macular degeneration now it's important to state that these patients are really do suffer from a loss of visual function, although their visual acuity.

Judy maybe 2020, and they may not be able to see a straight line but.

But they may not be able to finish reading a sentence or finish reading of excel table now because of a blind spot. So these patients we would imagine would be younger in the workforce and therefore, much more desperate and much more compliant as well.

In regards to the other questions Glenn I'll turn them back to you I'm happy to answer as you.

<unk> direct.

Okay. Thank you prevent let's we'll come back to your NDA question, Ken I, just wanted to get clarification on exactly what youre looking for but Tony a couple of words about extended release.

The early work that we're doing there and the type of technologies that may be.

The applicable here.

Sure happy to so.

Looking at a number of technologies and it really it really across the spectrum of available technologies.

Back of the eye diseases, some of which are quite late stage and validated and some that are really more emerging technologies.

Have to say I think <unk> given that it's an aptamer.

Rather stable seems to be rather conducive to a number of the technologies, but not every technology and so as we look at the feasibility we are looking at.

Implant technologies or looking at micro particles, we're looking at others.

And as we continue to gauge the feasibility or really our targeted goal is to truly move forward. Those that are most amenable to zamora and meet our targeted goals for for sustained delivery in a way that really it doesn't compromise patient care, but it really continues.

The benefits that we're seeing with Zimbra and his current formulation so stay tuned.

Great and my question was on the label, obviously, there seems to be impact on all areas of the slope of the Atlanta and extra folio, but just wondering how do you think the agency will handle the label given the patient enrichment for for gather wanted too.

Yes, so Kevin Firstly, I think we need to obviously see the data from from gather to before we're talking about label strategy.

But I'll, let <unk> answer that because I think we have some thoughts on how we position our data with the agency for me.

Thank you Glenn and Ken. Thanks, again, so I must say from the very start that we haven't had any formal labeling discussions with the FDA, obviously, it would be premature to do so.

What I will tell you that our expectation.

Is that the label will be broad now it doesn't mean that complement inhibition doesn't work in patients with fully affecting lesions is just that the delta given the natural history would be.

It would be less.

And that's exactly what we see in our studies and in our competitors' studies as well. So the one thing that I would take home from this is that we certainly derisk gatherer too, but peaking picking the proper patient population now again, our expectation is that if we're able to slow down a faster growing geographic atrophy safely.

Areas survive their patients that I remember I used to treat that had lesions in the <unk> area with eccentric fixation and they would use that that area to stop from bumping into furniture or.

Stopped their hands from getting burned in a hot stove that's terribly important.

<unk> to measure, but it's terribly important and we feel that the FDA will recognize that and allow a broad label.

Great. Thanks team real exciting time for the company congratulations on the progress I'll go back in the queue.

Thanks, Ken.

Thank you and the next question comes from my calls with Morgan Stanley .

Yes.

Guys. Thanks for taking the questions.

Quickly on gather too in terms of the injection fidelity rate, you're obviously tracking above your goal of 90% and thats exceeding your expectations, but I'm just curious more recently <unk> seen a break in the trend there at all due to <unk>.

Yes, Mike Thanks for the question and I think one of the reasons, we wanted to re.

And for US our progress today as the <unk>.

Those present complications, but I think we were able to knock on wood manage through that so that's why we wanted to.

The numbers both on the injection fidelity running well ahead of our.

Projected guidance and also a key point that Keith where it is today is where we are in the injunction progress which was 84% so I think.

The protections we put in early on for both patients and health care workers.

Is it related to the pandemic I think continue to pay off and in fact keep team.

Put a little bit extra diligence.

<unk> started to hit its peak to be sure that patients were managed patients got to visit a lot of prep work and then a lot of follow up work. So that was the reason we talked about injection fidelity today, because we feel we're in real good shape.

Got it that's helpful. And then maybe just just a follow up on the intermediate AMD study that you're going to start in the second half.

You gave us some sense at a high level of how you're thinking about the design, but you are also planning to meet with the FDA prior to starting the study so just curious.

What are the areas youre looking for feedback from the FDA as it.

Is it endpoints is it enrollment criteria or any color you can provide there. Thanks.

Great Great question, Mike prevent you want to take that one in terms of the design.

Sure and good morning, Mike and thank you for the questions first of all I want to say if you just look at the biology of this disease.

Complement inhibition of works in extra Foveole geographic atrophy, you can be quite confident that it will work in earlier stages, because thats, where complement is even more active which is intermediate AMD. What the FDA has stated publicly is to say look this is a major problem.

And there is a major advantage to not only slowing down the desk photoreceptor cells, but preventing it altogether. So we're extraordinarily fortunate to have a very very collaborative.

Again, the FDA is extraordinarily collaborative and we believe that whatever feedback they give us but will greatly influence the design and the development of this trial.

Got it thank you.

Thank you and the next question comes from Thiago <unk> with credit Suisse.

Hey, Thanks for taking the questions and congrats on the progress so far so just to go back to a point you've mentioned on gather to being relatively de risked based on patient selection. So again, we haven't seen them go the notes will be replicating their findings in Philly.

And why you can expect a potentially different outcome than what you suffer a competitor and a quick follow up and you guys alluded to some new IP that you have.

Okay.

The current portfolio doctoral property.

And also any outstanding financial obligations to our cabinet based on potential approval and launch.

Multi part question there.

Yes.

Yes, no problem Thiago and I think we have three questions.

First on the <unk>.

Gathered to and how we're feeling.

Bell Creek.

The Derisking I think Theres, a few things to cover and I'll, let <unk> to my commentary one we have an unusual situation.

We have one of two phase III trials done. So we have the benefit of the gather one data and we also have the benefit of the.

And the 12 month data was the primary endpoint, but also and gather when we had the benefit of the 18 month data to see what happened in the six months after and as you know we continue to see a separation of the curves.

As to another factor did you pick the right patients we always believe that we did.

And then with our competitor's data with their subset analysis of extra Fulvio lesion showing quite.

Similar numbers in terms of efficacy we felt that that's a further derisking.

The.

Recruitment and the reason, we put the concept of injection fidelity and obviously to keep the integrity of the study you want.

High retention rates when we felt the best way to measure that was through rejection fidelity. That's why we created that concept and we continue to update that.

And the fact that we're running well ahead of our guidance and well into the 80% range.

Demonstrates that these patients are coming back and also going back to gather one we had a terrific.

Trial and data to show those patients. We finished the phase III trial. So I hope that created some momentum and I think our investigators to talk to their patients about that so far all the above in the Permian.

Some additional commentary on that we feel that we've seen a number of signs that are encouraging as we get to the end of gathered too.

Pardon me.

Yes, Thank you Glen and Tiago good morning, and thank you for the question, let me divide my answer into two parts. The first part would be the.

Consistency and validity of gather one and the second part would be how we view risk gathered two and both are really important questions.

So if you go back and look at the other one and now that there's more data coming from our competitors and others.

You will see this remarkable consistency in terms of the efficacy profile and in terms of the safety profile. So in terms of the efficacy profile you will see as you know is an immediate separation with the delta getting bigger and bigger with every visit and Thats true in the two milligram dose that's true and the four milligram dose that's true whether it's safe.

Our Retrans formation analysis or non square root transformation analysis.

Actually even true in all of the retrospective studies, we've done so that kind of consistency should give us a great deal of confidence in the robustness of the data and it's the same thing that you see on the safety side as well you see a superior safety profile and you see a dose dependent response, so with everything in <unk>.

Gather one what I would tell you is that the confidence that we get is from the absolutely remarkable consistency of the data which is in line with the science now the second part is how do we derisk gathered too.

The most important answer is really by having gather one as Glenn said.

It's really unusual in fact, I don't recall a time in my 30 year career doing clinical trials, where I've ever recruited.

For the second part of the Phase III study.

With the first phase III study already being so overwhelmingly positive, but the other ways that we recruit derisk gathered to us by picking the proper patient population and we did this for several reasons, but the important one here as the biologic one of which is that as when complement is most active in geographic atrophy in the earlier stages.

And what we are doing right now and Keith and everyone Harrison and doubled assign their group are doing so well is to have that injections fidelity at a number that's just unheard of which is above 90%.

And that's despite having no vaccine, having delta having almost front our guidance Hasnt changed. So we believe we are doing everything they can possibly be done.

To Derisk gatherer too in the face of an overwhelmingly positive and consistent results for gathered one.

Thanks for being so I'll go to your second question around the pattern I think.

One of our multi pronged strategy that we've laid out.

For lifecycle of this product. So this is a patent that.

Covers methods of using Zamora.

Once issued.

It is expected to expire in 2034.

It's under the umbrella of lifecycle, Tony spoke a little bit about the.

Initiatives for extended delivery obviously.

Strengthening the IP portfolios.

To that end, we'll look to continue to find ways to.

The franchise, so we were happy to.

For today on that path, which is just one step in a number of things that we're working on.

The third question Thiago was related to financial obligations.

Dave to cover that sure. Thanks, Thiago Thanks for the question and.

Let me just open up with it's a really great deal for US there's no royalties on some more whatsoever first off.

And then the total payments really just the first indication is in the $20 million to $25 million range I think it's $23 five something like that this will all be in our 10-K and actually in last year's 10-K also.

And then.

No royalties and those milestones just related to that.

Clinical and regulatory milestones that's it.

Thanks.

Yes.

Yes go ahead.

Got it.

Okay.

Thank you.

The next question comes from Annabel <unk> from Stifel.

Hi, Thanks for taking my questions I had a couple here so.

I guess theres been some question about.

Patient motivation.

<unk>.

Oh physician motivation to trade as high patient motivation.

To continue to treat chronically I would say it's at late stages of disease.

They are starting to see a functional issues.

Likely highest but I'm, just a little bit curious.

The intermediate stages of disease.

<unk> are these patients compromised functionally and.

I know you are.

You're motivated.

To try to treat these patients as early as possible in disease, but I guess I'm trying to understand that patient motivation to treat earlier in disease.

And maybe you can just talk about that in terms of.

Where do you think the most likely treatment will be even if you have.

Meaningful data on the intermediate population.

And I guess the.

Second question I have.

Is on the 84% completion that you just talked about.

Are all of these patients expected in Q.

In my portion of the trial.

So Tim.

Ken.

And to what extent have these patients.

Have those 84% also moved into the 8-K my question of the trial.

Thanks, Dan.

Okay. Thanks, Annabel so two questions there and I'll hop.

<unk> answer the first question because as a.

Prior life as a treating physician I guess, there's nobody better to talk about patients and patients motivation on this disease and on the completion rate I'll have Keith answered that including.

What happens to these patients at the end of their 12 months what happens in year. Two so Keith we'll lay that out for you. So praveen, let me turn it over to you first.

Great and about good morning, and thank you for your question. Let me just divide the answer institute different parts, the GAA part as well as the intermediate AMD part.

And there is there's really a policy out there that with geographic atrophy. This is a disease that occurs in.

Far older patients and the disease progresses extremely slowly.

We simply know that that is not true we know the disease that occurs as early as the patients and their <unk> and <unk>.

These starts extra full deal always progressive circumferential fairly rapidly and I use that word rapidly deliberately if you look at great natural history studies that have been done by Genentech Roche Youll see that that movement of geographic atrophy occurs in a matter of months not years, we're talking about four to six months.

So another way of looking at this is that there was a recent <unk>.

Article that looked at the entire UK database that was offered.

Senior author was <unk> that showed that patients with geographic atrophy ended up losing.

Driving vision, 60% are still lose driving vision and one six years, which is just really stunning.

<unk>.

And about three years, 40% or so have their central fovea completely obliterated. So this is truly a relentless relentlessly progressing blinding disease and these patients again that we're targeting are the whole gamut of patients with early disease as well as late disease, you can imagine that these.

These are patients who may be in their <unk> and <unk> that may not be able to see a straight line and functioning as an architect and engineer or may not be able to read finished reading a sentence are functioning as the attorney or an accountant and these are people that have 2020 vision, but are visually completely dysfunctional and.

And we believe that there'll be very motivated when there is a treatment available to slow down the progression of this disease.

And again those patients are not necessarily all with retinal specialists at this point.

They are with optometrists and general ophthalmologists, but once there is a treatment available. We believe those patients will be referred rapidly to the retina specialists and we've seen this in wet macular degeneration as well now switching to intermediate macular degeneration casino typically these patients can be identified as early as <unk>.

<unk> and <unk> and you're exactly right a lot of them in the very early stages are not symptomatic in the later stages of intermediate AMD. They are symptomatic when the same kind of reasoning that I mentioned, where they.

They may be able to have visual dysfunction because of not seeing straight line was the <unk> or scatoma a blind spots.

And.

Our lifecycle management of some more of that Tony referred to it's terribly important.

We believe that if we can have a sustained delivery type strategy, where patients have to come in to the retinal specialists, maybe once every six months or once every year that will be quite acceptable to prevent them from.

Having to suffer through geographic atrophy I hope I've answered your question. Okay. Thanks, Thanks for the question.

Thank you.

Thanks Annabel this is Keith for your question on the 84% completion.

Just a couple of things. So you are correct, 84% complete.

Completion of year, one gather two is designed as a two year study. So as these patients complete year. One they are rolled into year two of the study just important to note that design. So as patients receive monthly injections that are on the two milligrams or more arm in year. One at the 12 month time point. They are re randomized to either continue to risk.

<unk> monthly injections of Zamora, two milligram or every other month the sham patients continue on sham.

Hope that helps to answer your question.

Yes, and all of them have been re randomize all the 84% that are completed have been randomized.

That's correct.

Correct, so that patients can they go into year two.

Okay, great. Thank you.

Thanks Oliver.

Thank you.

And this concludes the question and answer session I would like to turn the floor to management for any closing comments.

Well, thank you Keith for moderating today, and I want to thank everybody for joining and we look forward to a continued dialogue about our progress through the rest of the year.

Goodbye, everybody and have a good day. Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.

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