Q2 2023 Apellis Pharmaceuticals Inc Earnings Call
Okay.
Good day and thank you for standing by welcome to the Palace Pharmaceuticals second quarter 2023 earnings Conference call.
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I would now like to hand, the conference over to speak today Meredith Kaya. Please go ahead.
Good morning, and thank you for joining us today earlier. This morning, we reported our second quarter 2023 financial results will be happy to take questions from you on these results and the Q&A session. However, we'll be focusing our prepared remarks today on say February including feedback from the recent answer at the annual meeting and an update on our comprehensive review.
The rest of the theater.
With me on the call our co founder and Chief Executive Officer, Dr. Cedric Francois Chief Commercial Officer, Adam Townsend, Chief Medical Officer, Dr. Caroline Bomber, and Chief Financial Officer, Tim Sullivan.
Before we begin let me point out that we will be making forward looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties and actual results may differ materially.
Or would you to consult the risk factors discussed in our SEC filings for additional detail now I'll turn the call over to subject.
Thank you Meredith and thank you all for joining us today.
As Meredith said, we are going to take a different approach on today's call.
Focus the discussion on the rare events of escalators, we have seen with Tysabri.
We know you have questions and we will do our best to answer as many of them as we can.
But before we do let me provide some overarching comments.
I have never been prouder to be part of their various team.
The past few weeks have been challenging and once again the team has shown incredible dedication and resilience.
Second we had a strong second quarter.
We reported approximately $90 million in total product sales, including $67 million for safe overeat, demonstrating the early strength of this launch.
With more than 68000 vials of safe over eating now distribute its two physicians safe ovary is having a positive impact on the lives of tens of thousands of patients across the United States.
And third Saiful re continues to demonstrate increasing effects overtime.
Data from our Gale long term extension study showed a reduction in non support GE aviation growth of up to 45% between months 24, and 30 as compares to project that Jim.
These are incredible findings further strengthening our understanding of <unk> as an important treatment for patients with <unk>.
With that let's get into the discussion.
Patient safety is our top priority and we care deeply for the physicians who rely on us.
We are conducting a comprehensive investigation into the potential causes of the events of vasculitis working closely with the retinal community.
We do not know the cause yet.
And realistically, we may never identify a singular cost.
What we do know however is that these events have been very rare and sporadic and.
<unk> zero events were reported in our clinical studies.
Say for he is our newly launched drug.
A new disease.
With a new mechanism of action it.
It is not unexpected that events may emerge when bringing a drug into the real world.
But it is expected that we take them very seriously.
Now, let's get into some of your questions.
First what do we know so far about these events and what are the visual outcomes for these patients.
I will hand, it over to Carolyn to speak about this Caroline.
Thank you Cedric.
If we get into the detail I want to recognize that patients and physicians, who have been impacted by these rare but serious event.
I will reiterate what Cedric said patient safety is and has always been our top priority along with providing physicians with the information they need to make the best decisions for their patients.
Let me share what we know today.
Overall these events have been rare we have confirmed seven events since our launch in March and one additional reported event is being evaluated by a pellet.
More than 68000 vials of Tysabri have been distributed to physician practices and based on our research we estimate over 60000 of those have been administered to patients.
These events occurred sporadically.
Events following injections in April two in May and three in June .
This is important because that's the number of injections increased each month, there was not a corresponding increase in the number of vasculitis event.
Each event happened between seven and 13 days following drug administration, and all cases reported to a palace occurred after the first injection.
We recognize that the numbers, we reported on Saturday are slightly different than the numbers presented by Srs.
This is because we make determinations based on the information that we received directly from the treating physician and following review by external retina and uveitis specialists.
Given the physician confidentiality, we must be careful what we share regarding detailed patient information.
Additionally, these are highly complex cases and are sometimes difficult to interpret.
However, we are working closely with <unk> to make sure we are better aligned and how we evaluate each of these events going forward.
It is still too early to know the outcome is for each of these patients right.
Retinal vasculitis by definition is a severe inflammatory event that can potentially lead to significant vision loss.
With standard of care treatments, we hope patients will recover but this can take up to a few months.
Of the seven confirmed patients reported to us to date.
So you have recovered vision nearly back to baseline to have severe vision impairment and are unlikely to be resolved and three are still evolving.
For the one suspected case the patient's vision has already returned to baseline.
Working with the physicians, we are monitoring each of these patients very closely.
Thank you Carolyn.
The next question is why these events are happening what are we doing to find the cost and what do we know so far.
These are really important questions and we have been collaborating with the retina community to better understand the potential factors contributing to these events.
One of the first questions. We ask herself was why we did not see this in the clinical trials.
There is a robust process for evaluating safety in a clinical study.
Patients are assessed by the trial investigator and all imaging from this study is reviewed by a masked independent reading center.
Following more than 23000 psi over injections administered in our studies to date.
Zero events of vasculitis had been reported.
To confirm these findings one of the first things we did upon receiving these case reports is go back to our phase III data to make sure that nothing was missed.
We reviewed all cases of intraocular inflammation, and retinal vascular occlusion and confirmed no vasculitis event.
Additionally, we ask the panel of retina and uveitis specialists to re review all severe intraocular inflammation events.
As well as two leading neuro ophthalmologists to rearview or ischemic optic neuropathy events.
Both of whom further confirmed that there were no vasculitis events.
We also know from our clinical trials that there was no indication of drug related immunogenicity.
Data showed no correlation between Io I events, and any antidrug antibodies, providing evidence that these events were unlikely to be caused by an immune response to either the peptide or to polyethylene glycol.
These findings are important to our investigation as there were no changes in the formulation of the product between clinical and commercial supply.
Thank you Carolyn.
If we did not see anything in the clinical trials then what else are we looking into as a potential cost.
The next important area, we look into was manufacturing processes and drug quality and there's no indication that these contributed to the vasculitis event.
No single manufacturing lot was implicated no manufacturing issues were identified related to ensure care inflammation.
And no quality issues or contamination, such as endotoxin as were found.
There has been some confusion around safe over at being a biologic and that these events may have been due to endotoxin took.
To clarify <unk> is not a biologic is a synthetic peptide that binds specifically to see three and see three b.
Levels of drug product endotoxin, and all clinical and commercial batches of typo rates are significantly lower than the reporting threshold and the fda's expectation for app download dosage forms for injection.
As for what else we.
We are continuing to investigate potential contributing factors.
This includes looking into patient characteristics as well as evaluating any variations from the clinical trials to real world. We don't have any answers on these today.
Thanks, again Caroline Okay.
Now that we've talked about the investigation, let's turn to how the conversations have been with physicians over the past few weeks and of course, specifically here at Srs.
Kevin Why don't you start and then turn it over to Adam to share what your both hearing from the retina community and what this might mean for treatments going forward.
Sure Thanks, Jack over.
Over the past two weeks, we have been deeply engaged with the physician community and as Adam will share also conducted some early market research to better understand perception and impact.
Upon hearing of these events. The first thing I did was reach out to multiple physician practices to better understand their experiences with <unk> so far.
These are physicians, who in total have administered thousands of sites over injections to date and they have not seen any cases of vasculitis.
Since then we have continued to talk with dozens of leading experts in our field and just spent the past four days with hundreds of retina specialists at the Srs meeting in Seattle.
Overall physicians are eager for more information and this will take time and more data.
These are serious safety events and physicians need to understand how to think about treatment.
As a retina physician I can attest that my colleagues are experts when it comes to treating their.
Their patients, especially with interim vitriol injection.
They are thoughtful and visit in the decisions that they make I understand the risks associated with these therapies and can effectively communicate the benefit risk profile to their patients.
I'll turn it over to Adam to share a bit of what he and his team are also hearing thanks.
Thanks, Caroline and good morning, everyone. The commercial team has also spent an enormous amount of time engaging with the retina doctors over the past few weeks and then in passing this weekend at ASR us.
Our number one priority is to make sure that physicians know that we are sharing information with them as quickly as we can and that we are available to answer any questions. They have.
Following the member communication from ASR S. We have sent to communications to physicians sharing additional color and context about these events and held numerous calls with our physicians and our speakers the.
The feedback we're getting from the field is very consistent with what Caroline spoke to earlier.
Additionally, prior to the Srs meeting we conducted some early market research with U S. Retina specialists, most of whom had previous experience treating patients with <unk>.
The key takeaways of this survey.
One third of the survey doctors said they plan to continue using <unk> as they had been prior to the vasculitis events in both new and existing patients.
The next fed said they plan to continue using <unk> in their existing patients, but may pause use in new patients.
And the remaining third of doctors said they plan to pause treatment until they have more information or until their patient request treatment.
Based on this we do anticipate some sales bumping us in the near term as many seek to gain more information.
Our job is to be as thoughtful transparent partner over these next few months. We believe it is important to continue to bring this treatment to the millions of people suffering from Gi in the U S and to be ready to bring this to patients worldwide very soon.
A quick update on the latter our marketing applications are under review in multiple territories worldwide, including the EU and we expect approval decisions starting in early 2024 with that Cedric I'll hand, it back to you. Thank you Adam.
Okay. Another question on everyone's mind is how we think these rare events will impact <unk> sales and ultimately of course, our cash runway and how are we thinking about financing at this point Tim can you comment on this course, thanks Patrick.
As of the second quarter, we had $616 million in cash based on our current assumptions. This provides us with a runway into the first quarter of 2025. However, the safety events may impact our sales trajectory in the near term, but because it is all very new we don't know the magnitude.
We are monitoring demand very closely and in parallel looking at our overall spend to ensure we are being disciplined and thoughtful going forward.
We will be transparent with you, but we don't have it all of the details for you today.
As for financing, we are not under any immediate pressure to raise money as.
As we always do we will evaluate multiple ways in which to finance the company at the right time and with our shareholders in mind.
Thank you Tim.
Onto the last question because the SaaS was not just about safety for US. This weekend. We also presented some exciting new data from our Gale long term extension study.
Can you please give us an overview about some of the new data that was shared.
Yes, absolutely thanks Cedric.
We had a strong presence at <unk> this weekend with seven podium presentations.
Notably we shared for the first time data from our Gale extension study reinforcing the long term efficacy and safety of <unk>.
These data demonstrated that <unk> reduced GAA lesion growth by up to 39% in the monthly arm between months 24, and 30 as compared to the projected Sham arm.
What we were most excited about what the effects seen in non <unk> patients as Cedric mentioned earlier.
Between months 24, and 30, <unk> reduced <unk> G. A lesion growth by 45% in the monthly arm.
This means that within three years patients with non symposium lesions are seeing the rate of GAA progression slow by nearly half.
This is the first time, we have seen flowing of GAA lesion growth at this level and a large well controlled study the safety profiling Gayle was consistent with previously reported phase III data.
In addition to the Gal data, we also shared data using AI technology, demonstrating effective <unk> and protecting photoreceptor cells degeneration.
Our scepter cells are responsible for visual acuity.
The degradation of the photoreceptor cells are significantly reduced upon initiation of <unk> treatment.
Both the Gail and the photoreceptor data along with additional analysis presented over these past few days contribute to the most robust data set against gea and reinforce the importance of treatment with <unk> to help to protect against this irreversible disease.
I'll turn it back over to Cedric for closing remarks.
Thank you Carolyn.
Very excited about the data presented at <unk>.
Although it has been a turbulent few weeks, we believe that we have a strong future ahead of us.
We are closely monitoring the safety of <unk> in the real World and we will formally update on the rate of events on our quarterly calls.
We will not be commenting on future individual cases, we intend to handle this situation with your utmost integrity and transparency and do what is right for our patients physicians and investors.
Blazing, a new trail and geographic atrophy is not easy.
But I am confident India business team and we look forward to bring <unk> to patients in need worldwide.
We are also proud of the impact that <unk> is having on patients with <unk> <unk>.
Additionally, we continued to advance a robust clinical and preclinical pipeline to achieve our goal of improving the lives of people living with debilitating diseases by bringing new and innovative complement therapies to market.
That is now open the call for questions operator.
Thank you.
Minor to ask a question. Please press star one one on your telephone and wait for your name to be announced towards draw. Your question. Please press star one again, please stand by while we compile the Q&A roster.
Yes.
Our first question comes from the line of Omar <unk> with Evercore. Your line is now open.
Hi, guys its actually John on for Amit I would love a little bit more clarity on the inventory in that 60 8-K.
<unk> shipped as of the last as of this past weekend.
Can you confirm how much inventory and average docs keeps on Stefan stock and how much inventory would be in the channel at any given time.
And then Furthermore.
One bit of feedback that we're hearing out of answer is that there may have been a change from trial to commercial.
So was there a supplier for the trials that had automatic draw.
The <unk> solution.
Commercial docs have been complaining that drops from the vial, obviously is challenging and that's a little bit different for this product. So is that something that could be driving this or something you've looked into.
Thank you John .
I will have the first question over to Adam and then take the second one hi, John It's Adam So yes.
The 8000 vials those have been distributed to physician practices and we we contacted our top prescribers and on average we after those discussions our top prescribers tell us they held approximately a week's worth of inventory within the fridges.
So the vast majority of those 68000 vials are likely not sitting in fridges, there probably being used with patients. So on average about a week held in a refrigerator hopefully that answers. The first part and then I'll hand back to Cedric. Thank you Ed.
So I think John .
We had an important objective this weekend coming to Srs and that was.
First of all to work closely with Srs and get a very good sense of what is happening nationwide I E. How large is this problem is there something that we have missed and secondly is this rates changing over time right and so it's very important here and the key objective of this weekend and the research that we did in the past couple of weeks.
Is that we can conclude that these events are very rare and the scale that I mentioned earlier that they don't increase overtime right theres sporadic in nature I think that is really really important that of course comes the question. What is the potential etiology behind this and as you can imagine of course and as you mentioned.
The best starting point is what was different in the clinical trials versus the real world. We are going to be very methodical and we are not going to engage in hypothesizing until we have data and I think that it's really important that is something that we owe to physicians and to patients.
And that investigation. The first step was to find out is the direct products that we are delivering to physicians today. The same as the drug product that we used in the clinical trials and the answer is yes. We are now going to take next steps to evaluate other factors that could affect it rule, but we will only communicate on those.
When we have more clarity.
So when you see that the product is.
Youre, specifically not talking necessarily about any of the additional materials that may have come along with the bile a drug like syringes drop.
Ting devices things like that.
All of this will be part of our investigation.
Alright, Thank you very much.
Thank you John .
Thank you.
Our next question comes from the line of <unk> with Bank of America. Your line is now open.
Hi, Good morning, guys. Thanks for taking my questions.
Also I wanted to clarify apart some of your prepared remarks so.
Cedric how are you thinking about on a go forward basis, a risk mitigation plan. Maybe this is appropriate for Adam because Adam you've talked about what you've done so far but I think <unk>, probably will benefit from from guidance from the company going forward and so where are you in trying to plan that out.
Secondly, I wanted to clarify where all of the cases that have escalators that were reported to Srs, where they buy what they injected by retina specialists or were any of them.
Done by General Ophthalmologists, and then I have a follow up.
Thank you so much.
First of all briefly on the risk mitigation and docks cadence I think it is really important here is that we have a label that we have a way of.
We have thoroughly evaluated in clinical trials.
Of distributing this product and using this product and that is something that we of course want to stick to as closely as possible.
Communicated with physicians through letters.
To update them and we'll continue to do so to make sure that the relative communication. Our thorough we will continue to work with the Srs as far as it relates to.
Breakfast mitigation steps et cetera, we are going to be working with the rest of the community, but the retina community is better positioned than anyone right to talk about how this should be handled I think again, the most important effect that we wanted to get <unk>.
Our hands on this weekend was to understand the rates and the sporadic nature and to communicate that.
With Srs to the community. So I think that is really important.
The vasculitis cases that were already purchased.
Take care of them with I believe we're all done by retina doctors.
That is correct yes.
Okay. Thanks, and then lastly.
I think a srs that that there has been a.
That's a case that maybe hasn't been confirmed that occurred after the second <unk> injection.
I think this was not reported to you but over the past week and have you had the opportunity to learn a little bit more about that particular patient characteristics.
Yes, I think it's important to point out here that suspected cases are suspected for a reason right in the sense that there.
There are many confounding factors that come into this this is not an exact science right.
But the key thing is that after kind of a really thorough search nationwide right. We ended up realizing that we are very close to where we were a few weeks ago right. There was no hidden tsunami.
That all of a sudden came our way so.
There will in all likelihood be new cases.
We will take those and evaluate those we will continue to work with Srs.
With the knowledge that the rates and the sporadic nature of these events.
Creates a risk benefit profile that physicians can then openly communicate about with their patients.
Okay. Thanks, Patrick.
Thank you Kelly.
Thank you and our next question comes from the line of <unk> Rama with Jpmorgan. Your line is now open.
Hey, guys. Thanks, so much for taking my question.
Maybe a question on how you segmented the physician so the one maybe the one third of physicians, who you've talked to that are remaining going to continue to prescribe can you give us a sense of where these physicians fall into sort of what <unk> seen is amongst your top prescribers to date.
Adam Yes.
So yes, the the one third of our market research so they.
They tend to be actually a mix. So there are a mix of our top prescribers large accounts, but they're also slightly smaller accounts. So.
Saif over users within our market research had between one and 250 patients. So you can tell that there is a broad.
Bolus of Sapphire for use within that snapshot market research, we did prior to Srs. So we tend to get usage across the large p/e backed accounts and smaller accounts as well so in our market research that was consistent within that third.
Thanks, so much for taking our question.
Thanks, Jonathan.
Thank you. Our next question comes from the line of Choline coffee with Baird. Your line is now open.
Okay.
Good morning, and thanks for taking our questions. So we've heard similar feedback on the needle and the commercial kit or are there any.
Progress is there any progress made on potentially developing a pre filled syringe first iPhone <unk> and how long would that take to bring to market.
Yes.
Thank you Colin so again as mentioned earlier, our investigation around the ancillary as part of the overall investigation and of course, a pre filled syringe is an important objective for us it was before these events.
Occurred as well that is unfortunately, something that takes several years of developments as was the case for Lucentis and Eylea as well.
We are working very hard towards that but that is not something that you should expect in the near future.
That's helpful. Thank you and a follow up so at least one of the patient's vision did recover encouragingly anything notable about that case that you think can be applied in future cases come up any.
Any guidance on how you think the best treatment for these cases would be in the future.
Carolyn.
Thank you.
Sure.
As I presented.
Earlier in this talk that two of the patients have recovered vision nearly back to baseline and three cases are still an evolution, but I would say is that these cases are so rare and complex it's difficult to make any interpretation about treatment guidelines at the present, but we will.
Continue to communicate with the retina community and update them when we have some guidance.
Thank you and last one from US just in Europe have you submitted these that's why out of cases to European regulators and do you expect that to be a part of their review.
Of course, we communicate.
All safety events to all the regulatory authorities.
Great. Thanks for taking my questions.
Thank you Kevin.
Thank you. Our next question comes from the line of Hugo <unk> with Citigroup. Your line is now open.
So as you can see them. Thanks for taking my questions on the survey you conducted just you mentioned that the market research is conducted before SK Srs. So just when you presented the survey to the physicians was that just based on the contents of the Srs letter from mid July or were there any further details that they were given with respect to either the retina.
Images or detailed.
Aspects of the case studies presented on Saturday.
Thank you you got a good hearing you Adam Yeah, Hi, Yigal. So what we did was with the survey we only use the latter from a srs as the as the basis for that.
Okay. Thanks.
And then just being very specific with respect to the statement around drug product manufacturing.
I mean are you are you, saying that that percent that excludes the potential would be underlying mechanism of action of <unk> inhibition or do the drug product manufacturing to supply to the way the excipient were produced or any other aspects of the.
The manufacturing process, but not necessarily the <unk>.
Motive action itself.
Yeah. So the motive action is going to be part of the broader investigation, but again the motive action was the same in the clinical trials of course as it wasn't the real world. So again no answers there yet or we can say is that the product that was manufactured and used in the clinical trials.
The same product as the product that we are distributing to physicians to date all within the same specs and the same manufacturing process.
Okay, and then I know Caroline mentioned two times. These are highly complex cases cases.
And I don't think I saw on the answer our slides any demographics on the other than that.
Is there anything you can say any potential commonality in terms of.
Comorbidities or other.
Conditions are disease conditions that may be at least a hypothesis that youre going to pursue.
Are these all just highly divergent highly complex.
No clear nuclear wait up to pursue.
Hypothesis other than obviously, the commonality of all having GAA.
Thank you Hugo These cases are so rare that as you can imagine.
Kind of trying to find commonalities between patients require something.
<unk>.
With require a much larger denominator numerator so.
We're going to continue to track it and continues to investigate but right now all we have done is be able to exclude manufacturing the rest will be subject to further research.
Okay. Thanks Cedric.
Thank you.
Thank you. Our next question comes from the line of Stephen feed House with Raymond James Your line is now open.
Yes, hi, good morning, Thanks for taking the questions I have a commercial one and then a follow up for Caroline if I could the some of the numbers.
We now have enhance a 42000 barrels distributed to offices in the second quarter.
60000 per day Srs letter as of July 15th.
That implies if we back out <unk> as well in places like eight or 9000, let's say in the first two weeks of July that were distributed and then we had the 65000 number on July 20, <unk> 68000 on July 29 that you are updating.
<unk> as well, which would imply like 8000 bottles distributed in the second half of July .
So can you just corroborate that math I mean, I appreciate you said that.
Do you expect some sales impact in certainly the survey work suggests that but it really does look like the first half in the second half of July had about the same number of vials distributed.
Thank you, Steve Adam Hi.
Hi, Steve Yes I.
I think your math is right, but one thing to think about it.
Is this week and Thats.
Sorry, the week just gone and this current week is obviously the ASR us.
And so a lot of physicians are actually here. We're here in Seattle. So we always calendar is some some bumping us for this week is physicians tend to attendees at these conferences.
The orders for vials are continuing and have have continued throughout the last couple of weeks as <unk> explained.
Yes.
Okay. Thanks in for Caroline.
There seemed to be some discussion during the Srs panel presentation on Saturday.
Catherine inject for instance, especially vancomycin is not necessarily an optimal approach for management of retinal vasculitis if that is expected.
Which it wasn't because it hadn't been observed in the clinical study and based on the deal have you experienced I think something like inter ocular steroids, especially early on might be a better approach and can maybe mitigate some of the worse.
Outcomes.
This is a known possibility so is that characterization accurate and do you think visual outcomes could be improved on that basis alone going forward. If this happens in the future. Thanks.
Yeah.
Well as I said before and thank you for that question. These cases are complex and there.
They're not all bound by commonality.
Think we have more to learn with our retina colleagues on management of these cases.
Great. Thanks.
Thank you.
Sure.
Our next question comes from the line of Phil Nadeau with TD Cowen. Your line is now open.
Good morning, Thanks for taking my questions a couple from US first on the conclusion that manufacturing wasn't involved can you discuss a bit more of the basis for that conclusion, what assays were.
Performed.
And generally what analysis did you do to conclude manufacturing is not an issue.
Thank you Phil So as you know.
The way these investigations starts by looking into manufacturing actually.
Quite well standardized right. So our CMC group is a process to go through where.
Lots of specifically.
Specifically gets investigated to find out that all of these cases were not related to one specific look we then look whether all the direct product that was shipped was within the specs that are pre defined in our registrational batches and through the NDA.
And then much more work around testing and evaluating whether the possibility of the introduction of a manufacturing problem was involved in these cases and the uncertainty of that wasn't up.
You may recall, the <unk> situation about 20 years ago, where <unk> was associated with retro equation I think it turned out to be the change like this.
Prior the rubber stoppers.
Thats totally innocuous.
If that same situation had been the case here with the analysis you did to look at manufacturing supply picked up that as a potential cause.
Are they are they that detail.
If there was a change between what we did in the clinical trials in terms of how we manufacture the product and what we do now in the real World. We would have told you.
So this is all within the same specs in the same using the same manufacturing process that we used in our clinical trials as well.
And then second question there are some questions from physicians on the per patient incidents since.
It seems to happen after the first dose physicians were wondering what would be the risk of a naive patients going on therapy do you have any estimates as to how many patients are on therapy, So where does it go.
Per patient incidence of a naive patient getting the vascular eyes.
Thank you so much for that question, Phil It's very early of course to look into something like that.
Of course, the majority of these estimated 60000 injections in the real world are probably going to we'll probably have been first time injections and first time patients.
So that of course provides a huge denominator from which to work.
And now we're going to find out right I mean, whether this is the first injection phenomenon subsequent injections.
Just don't know a lot yet.
Other than the fact that it's an extremely rare event.
And that it is an event that is sporadic in nature right and I think that's really important.
Bear in mind is that the retina community.
Ran through kind of a very traumatizing event, a couple of years ago.
Where product was introduced.
And the increased incidence over time, what's taking place where this product was sensitizing patients in more and more patients came out of the woodwork and physicians that is absolutely not what is happening here. So I think that's important too.
Did that categorically.
Last question from Us in terms of the path going forward.
Do you have any information on when <unk> could provide an update on its analysis of cases or does propel us have any timelines to providing our next disclosure on either a root cause analysis or <unk>.
Incidence of progression correction.
Yeah. So as we mentioned we will provide quarterly updates as it relates to the rates.
And we are going to provide updates on the investigation.
When we have things to tell right. So we're not going to.
Making update unless we have real clarity around understanding this and we are going to continue to work with our service and we're very grateful for the partnership that we have with them.
Great. Thanks for taking my questions.
Thank you Phil.
Thank you. Our next question comes from the line of Justin Kim with Oppenheimer <unk> Company. Your line is now open.
Hi, good morning, Thanks for taking the questions.
Maybe shifting gears a little bit towards scale.
You know just in the context of the safety events and given that scale, it's really delivering on showing those increasing effects over time.
I'm just wondering how you've heard the feedback in terms of patient participation in the U S for.
For the clinical study.
And whether sort of those subgroups are continuing on especially given that these events arent being observed in clinical study.
Yes. Thank you so much for that question Justin So first of all as you may recall the number of patients that went from Derby and Oaks into Gil was very high rent approximately 80% of the patients in the trial decided to go into this three year extension study where actually.
Think months away from having the first patient who has been on treatment for five years with <unk> already in the <unk> study, so an incredibly rich and enforcement data base for us to understand not just the safety, but also as you mentioned the efficacy as Caroline mentioned earlier, if you have patients with extra fulfilled lesions and us.
A reminder, for those that are not familiar with this these are patients who have <unk> in the periphery of their vision, so still with typically a good ability to read and recognize objects with their central vision in other words patients that can really benefit being able to slow down the progression of the disease, but something that looks like it's close to.
<unk>, 50%.
Of course incredibly important.
And with all of these things of course, we have the safety events, which we take very seriously, which we will investigate on the flip side. The efficacy profile is also evolving.
Very exciting I think for patients to look forward to.
Thank you.
Our next question comes from the line of.
Derrick <unk> with Wells Fargo. Your line is open.
Hey, good morning, and thanks for taking the questions just two from US I guess.
First of all can you just remind us how many patients present with bilateral disease.
Do you think the ASR as notification may deter docs from doing injections in both eyes and then also I know you haven't said Youre still working on the investigation, but no similarities or commonality between these patients experiencing retinal vasculitis has been determined but if there is would you expect future label language.
Which that could direct patients or sorry, direct docs to the patients who are best suited for therapy is that something that would ultimately end up happening.
Thank you Derek let me start with the second question.
It is way too early to talk about test we are obviously in very close communication with the FDA on all of these things.
It is something that we will evaluate and potentially to win more information is available.
As it relates to bilateral patients Kevin maybe you could speak to that thank you Cedric.
As the Srs did prevent.
They did present that one bilateral case and I think that.
You know that is we have retina physicians, who are very thoughtful in what they do and we typically do include bilateral injections and our treatment paradigm and however that case does highlight that.
When we have a new product it.
It may be prudent to consider unilateral injection first timing with you.
Got it thank you so much.
Thank you Derek.
Thank you.
Our next question comes from the line of Ellie Merle with UBS. Your line is now open.
Okay.
Thanks, so much.
Excellent.
What's your what's your standing in the cases.
If all of the bergevin using that provided administration materials or just any of the physicians choose to use that.
<unk> for the injection or maybe deviate in any way from the proper administration procedures and then just also you alluded to.
Submitted the safety findings to the EMA.
Just any color.
So far from those interactions.
Thank you so much.
So again I think it's important to note here that we are very fortunate that the retina community is so professional and experienced with <unk> injections right. I mean, this is the heart and the bread and butter of these practices for the last 15 years or so.
So that is something that needs to be remembered here.
Syringes and so there is as mentioned before it will be part of a broader investigation and we will comment on that when we have more information.
As it relates to the EMEA, we communicate as I mentioned everything of course to these agencies and becomes part of the evaluation and that evaluation with EMEA. So far has been going well. So for now we don't see any changes.
Great. Thanks, and just a quick follow up and the patients that had <unk>.
It didn't have retinal vasculitis I guess did they have any vision impact and any color on if those cases fully recovered.
Yes, I think that is.
Very important question early because.
There is a bit of a misconception with the way the slate was presented that Iowa cases of escalators.
Im confused with each other.
Ocular inflammation is very normal with intra vitriol injections and the rates of intra ocular inflammation that we have seen in our trials and in the real world are in line with what we saw in the clinical trials and with what we saw.
Or what you would see with anti VEGF injections in general so.
And we have no concerns it's of course, these cases of escalators, which.
Do look like they are kind of a severe complication of severe inflammation.
Our special attention.
So I think that's an important difference there.
Hi cases without vasculitis typically have a much better recovery I don't know, Kevin if you would like to add something.
We looked into we're looking into every single case that is reported to us and the rates of Iowa that we've seen in the railroads are consistent with the clinical study.
Great. Thanks, so much guys.
Thank you.
Thank you.
Our next question comes from the line of Annabel <unk> with Stifel. Your line is now open.
Hi, Thanks for taking my question.
Just wanted to go back to the.
The methods that we use in clinical trials for exit methods that are being used.
Real World is there anything that you can sense from.
The way physicians are assessing a patient.
Now in the real world for treatment versus what was done in clinical trials.
You, obviously didn't see entities.
These cases retinal vasculitis and anything that you can gather from that too.
I guess to develop some kind of risk mitigation plan or some kind of protocol. So they can better.
Assessor patients going forward.
Yeah. Thank you Annabel so.
Look as mentioned before.
We have a strong and desirous anyone more probably than anyone.
Try to understand this but it is very important to be methodical in that process, which is something that we are very much dedicated to so we don't want to comment about what could be we are going to look into everything and when we have more information we will share it.
Of course, as a general comment.
And that is how it works right clinical trials are different from the real world, where there is much more variability on every front and being able to understand the signals, which again.
It's unfortunate but it is not at all unique many direction when they go into the real world will run into unexpected findings at that point in time.
It is on the company on us as a sponsor to be diligence to take these cases seriously and to evaluate them and communicate them appropriately.
Okay, Great and then as far as the differences between what was recorded to apollo's versus what Srs reported on.
Are you going to be getting cases are reviewing them or and.
And.
To what extent is your independent panel overlapping at all with the <unk> panel is there any other perhaps left there or are they completely different subsets physicians.
Yes. Thank you so much further question so the wonderful news here.
From my Vantage point is that this partnership that we had with the risk committee and with Srs.
It was a very thorough process and a collaborative process where.
Many of these cases.
Shared overlap as you could see firm that slides and importantly, we set in stone, but the rate is extremely rare in that it is sporadic in nature, right and being up or down one case, we ended up remarkably close to each other right. So now about the exact nature of these cases <unk>.
Non occlusive, depending on which expert to show. This to you are going to get different answers red but the most important thing here is you cannot count these cases as to one of our one down or even to their nature, but we are very much in the same ballpark right. So this is a very rare event, Fortunately and one again that is sporadic.
Its distribution over time.
Okay, Great and then if I could just one more.
I know that a lot of people have been making our balance sheet.
Comparison.
And maybe just to repeat in context for us one more time why.
This is not going away.
Maybe in terms of the onset and the rarity.
Could you speak to that again.
Sorry, I put that in context.
Yeah. Thank you Annabel so we're very fortunate because Caroline was actually.
The lead author on the paper on the Doj investigation and the work that was done there. So she is uniquely positioned to comment on this.
Thank you Cedric.
I think that what we have seen with Tysabri is very rare in contrast, right of vasculitis with <unk> plus three 3% in patients who are in the Hopkins Harrier studies.
We did not see this at all in our clinical studies.
So as you alluded to the onset and the clinical features differ from what was seen with promises of map.
Okay.
Okay fair enough.
The onset.
Well, so with promises of Mab. The onset was typically after three to four week and of note having the events were more common with multiple injections with a shorter time intervals between injections and this played a role in there.
Discontinuation of some of the published clinical studies.
As well for listening to map caused an auto writers and different sorts of features on clinical exams.
Okay, great. Thanks, so much for the color.
Thank you Kevin.
Thank you. Our next question comes from the line of Joseph Stringer with Needham <unk> Company. Your line is now open.
Hi, Thanks for taking my questions.
Just curious can you comment on.
Yeah.
Turns of files on what visibility you have into this more specifically.
How many miles have been returned and or how many practices have returns at <unk>.
Thank you Julien Adam, Yes, Hey, Joey.
So yes, we have seen some viral returns, but the number is actually very small.
Okay. Thank you for taking my questions.
Thank you Zoe.
Thank you.
Question comes from the line of Douglas Tsao with H C. Wainwright. Your line is now open.
Hi, good morning, Thanks for taking the questions.
Just.
First I am just curious Adam in terms of the market research for the physicians, who said that they are either pausing altogether or.
Third we're starting with new patient starts and just curious if you've got a sense from and maybe this is more anecdotal, but just what would they sort of does it do they need to see to restart.
Yes, thanks for the question.
So within the recession with our compensations of Srs. This weekend I think a lot of physicians.
Are the ones that have said they would cause they want to just see what happens over the next couple of weeks right. This has all happened relatively quickly over the last few weeks and they want to see that stability. They want to see if any more information comes out.
They have found having conversations with their patients about our rate would be important.
And they want to hear updates from our pallets in a very transparent way that tends to be the theme for those physicians that either pausing new starts or.
It has have decided to pause for enough time to get more information that was a consistent theme of Srs is also within our research Caroline I don't know if you want to add anything to that based on your positions.
Caroline says the same thing so that's.
That's where we are.
So to clarify just to be clear so Adam so it's not as if they are waiting for some definitive.
Sort of conclusion on this issue there just seems like they are waiting more to see.
Some stability for lack of a better word to sort of get a sense of now that come to life more cases aren't coming out of the woodwork et cetera.
Correct.
Alright, Great and then just as a follow up I think somebody asked and I'm not sure maybe I missed the answer but just you know of the 68000, how many were first injections right now.
We don't know, but our assumption is that the vast majority of our first test injections.
Okay, Great and then just one final quick one are you continuing with DTC work or I know you had just started the Henry Winkler campaign or is that on pause right now.
Yeah. It's a great question. So DTC has had a really good impact and has driven patients to have conversations about losing vision.
I think we'll be very thoughtful moving forward, how we how we use that now is the time for us to have really transparent open conversations with physicians.
But the DTC impact in getting patients to go and check that vision I think it's a good thing for all patients who have a certain age. So I'm very proud of that work, but we will be thoughtful in how we use that moving forward.
Okay, great. Thank you so much.
Thank you. Our next question comes from the line of Laura Chico with Wedbush. Your line is now open.
Hey, good morning, guys. Thanks, very much for taking the question I had.
Just one clarification question I apologize if I missed this but I think breast noted there was one incident that occurred after a second injection. So I just wanted to clarify if I have that correct, but also.
How a palace came to kind of a different conclusion there.
And then I have a follow up.
Yes. Thank you Laura so that was a suspected case, we need to look into that.
Based on our findings all so far where first injections.
Okay. Thank you and then just kind of going back Adam. Thank you for the market research color I guess I realize it's premature but what is your expectation around how the dosing interval frequency might.
Evolve over time here now that we've kind of encounter these safety events.
How do you think physicians are going to lean one way or another in terms of the dosing interval with type O great. Thank you.
Youre welcome Sir yes, absolutely so.
Our assumption to my assumption was prior.
Prior to these vasculitis RAF vasculitis events. The vast majority of physicians were using every other month type dosing.
And I think this just confirms that again every other month dosing will be used by the <unk>.
Vast vast majority moving forward.
And.
I expect that to be consistent for for for.
For the future and I think as we progressed through this and people look at the.
The <unk> data and the increasing effects over time and once the physician segment that needs to get comfortable with these safety events gets comfortable I think youll start to see it.
A little bit of fluctuation is monthly dosing moves, but every other month will be the vast majority.
Caroline from your perspective anything you want to add.
I think that physicians are very very thoughtful and.
But very experienced with this type of medication and that the vast majority of physicians.
Appreciate having a label that so flexible.
I've heard all different sorts of things, but I think between every six to eight weeks with every other month dosing is the preferred paradigm.
Thanks, very much guys.
Thank you. Thank you.
I'd now like to hand, the conference back over to Cedric Francois for closing remarks.
Thank you very much well in closing thank you all for joining us today.
It's been of course.
<unk>.
Intense couple of weeks for us, but we are very happy with how we come out of Srs because we believe that we have gained significant clarity we are ready to take on the next couple of weeks.
We'll continue the investigation and promised to continue to be as transparent as we have been.
We have around later today and tomorrow. If you have any additional questions feel free to reach out to Meredith. Thank you.
This concludes today's conference call. Thank you for your participation you may now disconnect.
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