Q3 2022 Clearside Biomedical Inc Earnings Call
Ladies and gentlemen.
The conference will begin shortly thank you for your patients.
Vince will begin shortly.
[music].
Yeah.
Good morning, ladies and gentlemen.
Welcome to tier site biomedical incorporated third quarter 2022 earnings call.
At this time, all participants have been placed on a listen only mode and the floor will be opened for questions and comments after the presentation.
It is now my pleasure to turn the floor over to your host Jenny coping with Investor Relations Ma'am the floor is yours.
Good morning, and thank you for joining us on the call. This morning on todays call. We will have a brief discussion around clear side third quarter financials, followed by the results from the Oasis phase once you're on it.
<unk> trial.
Before we begin I would like to remind you that during today's call, we will be making certain forward looking statements. Various remarks that we may make during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the private Securities Litigation Reform Act.
<unk> 1095.
<unk> results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31, 2021, and our other SEC filings available on our website.
In addition, any forward looking statements represent our views 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 in the future. We specifically disclaim any obligation to do so even if our views change.
On today's call, we have George <unk>, our Chief Executive Officer, Dr. Thomas Ciulla, Our Chief Medical Officer, and Chief Development Officer, Charlie Deignan, Our Chief Financial Officer, and Dr. <unk>, Our shot Konami, who was a managing partner at Sierra Eye Associates, and a clinical associate professor.
The University of Nevada Reno.
The remarks on todays call will be accompanied by a slide presentation, which is available in the events section of clear sight Investor Relations website at clear side by Dot com.
I would now like to turn the call over to George.
Thank you Jenny and thank you all for joining us this morning.
For today's call I will make some opening remarks, and then I will turn the call over to Dr. Tom Ciulla, Our Chief Medical Officer, and Chief Development Officer, who will walk through our CLS Ax.
Phase one two clinical trial entitled real wages.
We are also joined this morning by Dr. Arshad Khan Donnie.
Retinal specialist with extensive experience treating multiple back of the eye diseases.
After our formal remarks, we will take your questions.
Okay.
This morning, we issued our press release on the Oasis data as well as our quarterly earnings announcements, where we reported that our current cash and cash equivalents as of September 32022 totaled $53 $4 million.
As of now this gives us a financial runway into 2024.
And we will be able to further refine our financial runway once we finalize our plans for a randomized controlled CLSA ex phase III trial.
Today, we are going to focus on at CLSA.
X data.
So Charlie Dignan is on the call with us to take any questions if needed.
Our Oasis update includes the final data from all four dosing cohorts for the three months endpoints of the trial as well as interim data from the extension study with a data cut as of October 27 2022.
The extension study follows patients in cohorts, two three and four who.
Who agreed to be monitored for an additional three months, making it a total of six months after a single dose of CLR CTX.
Moving now to slide three in the presentation.
We are very pleased to report the data today from the Oasis trial of single dose escalating trial anti VEGF treatment experienced sub responders.
Primary endpoint for Oasis with safety and Tolerability and we saw a very favorable safety profile for CLSA X at all doses and time points throughout the study.
In addition, we are very encouraged by the durability data that has emerged from the trial to date at higher doses in cohorts three and four.
As Tom will elaborate CLSA ex provided at least 73% reduction in treatment burden to the three month time point in Oasis.
From the ongoing extension study our interim data shows at least a 90% reduction in treatment burden from the average monthly injections in the six months before CLS Ax administration.
Further the Oasis study demonstrated both the stable mean best corrected visual acuity and stable mean central subfield thickness at both the three month time point and to date in the extension study.
In the extension study anatomical signs of CLSA ex biological effect were also observed on OTT and the sub responder population.
While we will continue to follow the remaining eight patients in our extension study. This data gives us very high confidence to move ahead with future CLSA ex clinical trials.
We expect to report the final extension study data in the first quarter of 2023.
I will now turn the call over to Tom to review our Oasis results.
Thank you George and good morning, everyone I'll start with a very quick overview of our program and then review the data.
Slide four summarizes the benefits of CLSA ex our proprietary suspension of except nib delivered via our SCS microinjection enter a supercritical states.
The CLSA X program, we're bearing a very highly potent tyrosine kinase inhibitor that inhibits all digit receptors with a potential court retinal tissue targeting benefits of <unk> delivery and with respect to durability preclinical studies show that exiting up levels in the retina choroid and sclera were maintained at.
Levels, well above the IC 50, but the bedroom receptor to up to six months after <unk> injection.
With a novel delivery system, we're able to specifically target the affected Korea retinal tissue for potential efficacy benefit.
And we can compartmentalize, our therapy away from uninfected tissue for potential safety benefits.
Delivery of small molecules via our SCS Microinjection <unk> has been commercially accepted by retina physicians following the launch of its IPO.
For the sake of time, we've included additional background rationale in the appendix of the slide deck, which is available online.
Slide five outlines our Oasis phase one two clinical trial in treatment experienced patients with active wet AMB lasers is an open label single dose escalating study to evaluate safety and Tolerability of <unk> administered via <unk> injection.
There were four cohorts of patients treated with escalating doses of CLS Ax.
<unk> screening patients receive a dose of a flavor for your individual injection. They returned one month later, we receive a dozen CLS Ax and then return for follow up visits at one two and three months. There is an ongoing extension study that facilitates an additional three months of follow up for a total of six months.
I wanted to take a moment to discuss in more detail. The patient population. We chose for Oasis, we intentionally chose wet AMD patients who are heavily anti VEGF treatment experience all patients were sub responders with active disease screening, which was confirmed by an independent reading center.
Consequently, we chose the most difficult to treat patients for this study.
So why chose this group of patients and so it takes them to get control disease, while our primary objective for the study was safety and Tolerability. We wanted to see if we could observe signs of biologic effect and if we can lower the anti VEGF treatment burden.
By assessing sub responders, we minimize the risk of false signals of biological effect since inactive treatment treated patients may not require further therapy for many months.
This anti VEGF treatment experienced population with active disease represents a significant number of patients in clinical practice, and what's more than 30% or sub responders and have high need for effective therapy with lower treatment burden.
Accordingly, we believe that the conducting daily wafer study in such a patient population. The data is particularly promising essentially observe signs a clinically relevant benefit in this first in man trial.
On slide seven we breakdown select based on baseline demographics and characteristics of the enrolled patients.
As you can see the <unk>.
<unk> had a history of wet AMD for over four years on average and we're very highly treatment experienced somewhat after 90 prior anti digest injections and all had active disease as confirmed by independent reading center on screening.
It should be noted that unlike treatment naive patients. The main central subfield thickness was essentially normal thus, creating a floor effect, which is unlikely to significantly significantly improved with treatment.
Similarly, some of the patients showed best corrected visual acuity in the 'twenty over 32 wings, which creates a ceiling effect and it's unlikely to significantly significantly improved with treatment.
Our ongoing hypothesis is that the higher dose of the CLSA acts in cohort three and four may keep both the D. CVA in CFT staple throughout the study and thereby show potential for the reduction in treatment burden in these patients.
We are extremely pleased with the robust safety results that we've seen in the trial across all four cohorts.
As you can see on slide nine there've been no serious adverse events and no treatment averse.
That's related to a flipper set CLS ax or the Super <unk> injection procedure, there were no dose limiting toxicities no.
Adverse events related to inflammation vasculitis or vascular occlusion and there were no vitreous floaters or dispersion of CLSA X into the vitreous.
Next I'll review, the promising durability results from the trial.
Slide 11 shows the prior anti VEGF therapy, and the treatment administered donor during the study for all patients treated to the three months of wasted endpoint in.
In the middle of a swim lane the calm of red dots represent the slivers of administrative screening.
Everything to the left of that column represents the patients prior six months anti VEGF treatment regimen as you can see most of the patients were being treated monthly.
The Green column <unk> got showed the CLSA ex injection at baseline and then the patients were followed at one two and three months the blue dots represent additional therapies administered per protocol criteria.
The olive colored dots represent therapy administered not in accordance with the defined protocol criteria for additional treatment.
Importantly, the vast majority of these cases, the independent reading center did not verify the rationale for additional treatment. We detailed the reasons. The investigator did not treat per protocol defined criteria in the appendix, which is also available online.
Now onto the data going forward I'll focus on the discussion I will focus the discussion on cohort three and four at these higher doses are the most meaningful and one or both of them are utilizing our future clinical trials as you can see the results show that in cohorts, three and 411% or 16 or 69% of patients did not receive additional.
<unk> therapy to three months.
On Slide 12, this swim lane plot shows only the patients treated per protocol criteria here.
Here in cohorts, three and 411 of 12 or 92% of patients treated per protocol did not receive additional therapy to three months, we're extremely encouraged with these results.
We're also pleased to report that CLSA ex reduce the treatment burden across all cohorts two month free as seen on slide 13, again, we showed treatment across all therapies on the left and per protocol treatment on the right importantly in cohorts three and four there was at least a 73% reduction in treatment burden from the average.
Monthly injections in the three months before CLSA ex injection this reduction reached 100%.
The cohort four one milligram dose.
Moving now to the interim results of the extension study on Slide 14, we show the prior anti VEGF therapy and the treatments administered for all 14 patients who agreed to participate in the extension study from our data cut as of October 27 2022.
For today's discussion I'll focus on the 12 patients enrolled at the higher doses in cohorts three and four eight.
<unk> patients are still being monitored in the study.
As you can see two month for eight of 10 patients had not received additional there too.
Among five seven of eight patients have not received additional therapy and two months six three or four patients have not received additional therapy.
Once again on slide 15.
<unk> flagship only the patients treated per protocol criteria. This line is important as you can see that to date only one patient in cohort three has received additional therapy prior to the six month time point and one patient was dosed at month six and.
In cohort four no patients in the extension study have received additional therapy per protocol criteria to date.
This breaks down as follows two month for eight of nine patients have not received additional therapy to month five seven of eight patients have not received it still therapy and to month six three or four patients have not received additional therapy.
To illustrate this data further as the graph on slide 16 shows the supplemental anti VEGF injection free rate up to each visit.
Pleased to note that so far 88% of the patients have not required any additional therapy two month, five and 75% of the patients have not required any additional therapy to month six.
As you can see on slide 17 cohorts three and four also showed a meaningful reduction in treatment burden to date.
This data compares treatment received during the six months before CLSA ex administration to treatment in the six months after CLS Ax.
Again, we show anti VEGF treatment burden across all therapies on the left and per our protocol criteria on the right.
And cohort three and four there was at least a 90% reduction in treatment burden.
Next I'll briefly review the biologic effect, we observed in cohorts three and four.
Slide 19 shows the main change in best corrected visual acuity results from screening for cohorts three and four in the graph cohort three are shown in green cohort four is shown in blue and the main change by ETE Drs letter. It has shown that the thick black line.
Accordingly, but we'd note is that over the three months of course are the way to study <unk> CLS Ax dosing the visual acuity remained stable.
Same data as part of it on the right, but we excluded the data post re treatment to be sure that the patients who received additional therapy werent driving these results interestingly, we see that the end result was essentially the same.
The key takeaway is that the BC VA data demonstrates that patients were stable during the three months post CLS ax.
Slide 20 shows the results related to the main change in central subfield thickness from screening for cohorts three and four on the left we include all data and you can see that the CST remained stable on the right. We exclude post REIT treatment data and again it looks similar.
Notably the CFT data demonstrates that patients were stable over the course of the three months post CLS Ax.
Similarly slides 21, and 'twenty two show that the main beef CVA CFT also remained stable through a total of six months in the extension study in cohorts three and four.
On slide 21 on the left we observe that over the six months post CLSA dosing. The visual acuity remained stable on average here you can see that there are some durability in the visual acuity at the six month time point with Arrow bars that crosses zero no change line at the sample size decreases over time in this interim analysis.
On the right with the same data.
Post REIT treatment excluded we can see that the end result was very similar this interim <unk> data indicates that so far the visual acuity of patients in the extension study has remained stable over six months post CLS ax.
On slide 22 again, all the data is graph on the left over six months post CLSA epitopes here you can see that there are some variability, but the CFT all within approximately 50 micron at the sample size decreases over time in this interim analysis. However, as shown by the overall mean in black the CF.
<unk> remained stable on the right with the post re treatment data excluded the results actually look similar.
<unk> interim data indicates that so far CFT measurements of patients in the extension study have remained stable over the course of the six months post CLSA.
Now I am going to walk through for case studies. Additionally, support the durability and biologic effect, we've observed from the Oasis extension study as a reminder for all of these examples the patient enters the trial at screening and received a flipper set individually.
This is followed one month later at baseline with a single dose of CLSA ex administered soup accordingly.
Slide 24, as a case study that supports the biologic effect and an anti digest sub response rate.
We can see that the patients entered the study with a relatively good D. CPA of 75 letters or 'twenty over <unk>, 32, which tends to create a ceiling effect in these treatment experienced patients.
<unk> measured at 265 microns.
<unk> sub foveole fluid and the fiber basket pigment epithelium detachment or Ped all marked the patient received a flipper step at the screening visit and returns one month later and Youll note that the sub retinal fluid has improved but does persist to some extent.
<unk> received CLSA exit this baseline visit and then we know overtime at month, one two and three with folio fluid improve and finally at month four sub folio fluid is essentially resolved. The BCA has remained stable throughout the.
CFT has improved from 218 microns, one month after flipper set to.
182, microns four months after CLSA.
Importantly, the CFT is actually better for months after CLS ax versus one month after a flipper set.
Sequence a month for the agitation recurs and at month six the patient receives additional therapy.
Slide 25 represents another case study that showed that after CLSA X durable stability in both BCA CFT once again the anatomy as noted in the upper left.
We can see of screening the patients entered the study with a <unk> of 37 letters and the CFT of 228 microns.
Mild inter retinal fluid this mild sub foveole fluid as well as the shallow fiber vascular ped.
Patient received CLSA exit at baseline and over five months of follow up the BCA CFT and macular anatomy range stable. This patient has yet to return for the month visit.
Slide 26 is another example of the potential durability to the six month time point in the upper left the anatomy, so theres, some fiber vascular ped and mild sub foveole fluid.
<unk> entered the study with the <unk> 42 letters and CST of 194 microns.
After receiving treatment with CLS Ax the month free visit in the lower left in the month six does it in the lower right show that the patient has stable <unk> CVA and stable CFT as well as stable macular anatomy.
Slide 27 shows our final case study demonstrating durable stability to the six month time point the patient interest in study with BCD at 72 letters and CFT of 262 microns and the top left corner. We note that this cross section is superior to the folio in the central South.
And in that we can see the fiber vascular PBT as well as sub retinal fluid.
At baseline they return with stable CBA and a sub retinal fluid is essentially resolved.
The month three month six visits showed that the patient has stable CVA and stable CFT as well as stable Macedonia entity.
In conclusion, I would like to briefly summarize our discussion of next steps for our CLSA X program.
129 is a very detailed summary of our results alongside the competitive advantages for our program.
Importantly, CLS ax delivered into the Super core it'll stay severe our proprietary SCS microinjection <unk> demonstrated an excellent safety profile at all doses and all time points, including no adverse events related to inflammation the.
The data suggests that our SCS micro injector potentially allows for in office setting with no risk of implant migration and very very low risk of the vitreous floaters are hayes as well as very low risk with ocular hypertension or glaucoma plug.
The SCS micro injector has been commercially accepted by retina physicians following the launch of the dice here for the treatment of macular edema associated with UV items.
We feel that our CLS Ax program, they have strong competitive advantages in treating retinal diseases.
<unk> is a well characterized small molecule with the potential of a lower risk of inflammation than a novel biologic agents.
Except nib, it's the most potent tyrosine kinase inhibitor currently in development for retinal diseases, and it's Pan VEGF inhibition that differentiated from those agents, which focus on verge FAA blockade.
These potential benefits of exiting a further leverage with super portal delivery that targets high levels of the drug to be affected core regret.
Our Oasis trial data and the interim extension study data showed very encouraging signs of durability and biologic effect and a difficult to treat patient population of anti VEGF treatment experienced sub responders. This durability may compare favorably to other current PKI formulations and investigational <unk>.
<unk> biologic agents.
Moving now to slide 13, we lay out our current status and future plans for CLS Ax, we will continue to follow the eight patients remaining in the extension study until they all reached the six month time point and we expect to report this data in the first quarter of 2023.
<unk> planning for the initiation of a randomized controlled phase II clinical trial in the first quarter of 2023, and wet AMD <unk> diabetic retinopathy.
We're very pleased to have Dr. <unk> with US today, Dr. <unk> is a managing partner director of clinical research and director of Fellowship at Cri Associates, and one of the leading research centers in the country and he's a clinical associate associate professor at the University of Nevada Reno.
School of Medicine, he has been a top and roller for multiple phase 1% to three.
Free trials.
Member of numerous clinical trial steering committees and scientific Advisory Board is full bio was available in the event Dr.
<unk> will make some summary remarks, and then we'll open the call for questions.
Dr. <unk>. Thank you again for joining us on this call can you provide our listeners with a brief background of your practice.
Thank you Tom and congratulations on this data and Marsha <unk> surgical and medical retina specialists I'm in private practice.
Nevada.
This is as you mentioned heavily.
Focus on clinical trials from early stage and late stage.
On a cold trials, new mechanism of action and new delivery methods and I'm excited to be here, especially talking about TGI is a.
Very interested in Kpis for multiple reasons and we'll discuss that and we also recently published an article about <unk> really reviewing the landscape so excited to be here.
Well. Thanks again I enjoyed your article I thought it was really terrific.
So speaking of PKI, what's your rationale on pks, and particularly of CLS Ax administered super quarterly to treat wet AMD.
I think as I feel we are always looking to do better than what we currently do with the anti VEGF agents and recent leave it by specific antibodies and I think <unk> are interesting because of the fact that they can lead to then but yet inhibition with the routine drop or anti <unk>.
Bodies, we are we are dropping the X.
<unk>.
Jeff Here, you are actually targeting and just generally and youre able to do a pan VEGF blockade, we actually have seen.
Better efficacy when we target <unk> other programs. So I think this idea of having one injection.
Doing a <unk> inhibition is very exciting.
Cited above CLS ax, because as you mentioned.
Validated delivery system. So when you look at new molecules you need to look at what are the variables in those molecules hydrogeology of polymers.
And on top of the drug delivery system that are saying, Hey, you have super global delivery, which is FDA approved.
And many of the retina physicians, who are involved in the trial are now not involved in the trial are using commercially approved idea for <unk> macular edema. So so the delivery is very exciting it's easy.
It's predictable and then the next thing about exiting that business. It is the most potent PKI because it has.
Highest affinity so so I think leveraging the delivery that's validated using a molecule that is most important in the class of <unk>.
It's exciting because of the fact that when you look at new MLA delivery system, you need to get the.
The best in terms of delivery in terms of needle size in terms of the molecule and I think that's what we're doing here.
Well thanks for your insights.
Of your impressions of the data, particularly with respect to safety durability and biologic effect.
I think for any new MLA, new new molecule <unk> fair amount. So it is super exciting to see that at this stage, we have not seen any safety signals with the other <unk> programs. We have had particles that vertical migration in the front, we have been involved at all.
<unk> trials, so I think.
Having a good and favorable safety profile is is crucial to take the program.
Forward and then the other thing here is the fact that we have seen biological effect, which is very hard to see in many other programs. So this.
<unk> population is very different than what we enrolled in other pgi program. So we are enrolling into other TGI programs. Currently so I think when you look at the data, it's very easy people want that cross trial compared the durability if people want to cross trial compared the topline results I think that's something.
To keep in mind that here your bar is much much higher because you are taking this patient population thats difficult to treat so having that date with patient population and the OCD as you have shown it clearly shows a biological effect because I think it's important for companies to see the signal early.
You feel like you see a signal, but there is no signal and programs sales so I think derisking.
Graham was was a really good idea and then in terms of efficacy you are maintaining <unk> CSP of course in previously treated patients. We don't expect improvement. So I think having a stable <unk> CVA, having stable CSD is is is very meaningful and that has been up.
Primary endpoints, where some durability trials.
For new new agents or new delivery system that FDA has approved and then the last thing is durability.
Just to treat population is very hard to get durability. These are heavily pretreated patients meeting needing frequent injections and you can take a patient on <unk> that is not well controlled with every four to six weeks of injections and you give them.
CLSA accident, you're able to extend them to three months or longer I think that is very meaningful.
The clinician because youre targeting two things youre targeting this high need patient population that is a third of your practice and then even extending patients further out so what it shows to me that if you took stable patients and you gave him the streetman. They will go much further than they would be current agents. So so really overall.
The efficacy durability and biological effect is positive in my opinion to take the program forward.
Thanks for your insights I wanted to briefly touch upon.
Not per protocol re treatment that we observed and I just wanted to share my thoughts and.
And hear your perspective.
As I mentioned earlier, we intentionally toes wet AMD patients who are heavily anti VEGF treatment experienced and as you just alluded to in all of these patients are sub responders. They all had active disease screening and that was confirmed by independent Reading Center and these patients have received frequent anti VEGF injections prior to the study enrollment in one of my colleagues.
First with this group of patients has anti Digest Alex.
Consequently, we chose these most difficult to treat patients for this first in man study, which as you alluded to involve a new therapy delivered to the supercritical space for the first time. So naturally during the course of the study investigators who had previously treated these patients frequently did not note prompt improvement with this novel treatment somewhat Erin.
Side of caution and treat given their prior experience with these particular patients.
This behavior somewhat understandable in these early stage trials.
Some of our peer companies have noted this behavior of near trials as well. So a doctor can only do agree on what do you think what's your perspective on that.
No I agree with what you said, Tom I think these are super high need patients and we know their treatment history, and we know that David quite a frequent injections and even with frequent injections. They are not well controlled so I think as it.
Clinician and a physician.
And as a company I mean, all of US are doing this to help our patients.
And if you have.
Early stage trial, and Youre seeing some fluid I think it's a knee jerk reaction.
To treat these patients we have seen that the gene therapy trials you have seen the other trials, but I think phase ones are obviously, a learning opportunity and I think what we have seen here is that biological activity will happen with this with this molecule delivered to the supercritical space. So I think.
Treating patients if there is fluid.
Is our standard of care, but I think with the new MLA and the sustained delivery I think that behavior is changing we actually saw that the port delivery system and other modalities will be doing sustained delivery, including gene therapy as I mentioned.
It's a learning opportunity so going forward I think having having discussions about the re treatment criteria that the investigators and convincing them that this is a very durable.
Molecule based on the data we have seen I think that that will help physicians understand and not.
Treat a protocol acutely.
Great. Thank you for your perspective, so it got to kind of you have a lot of experience treating wet AMD patients in your busy practice in numerous clinical trials in <unk>.
Nice to have a variety of companies.
Many of our listeners are not retina specialists don't.
Normally looking at OTT in the course of your work and I thought it might be valuable for our listeners if you might expand a little bit on the OTT case studies that we've reviewed and maybe further discuss.
Some of your impressions and insights.
I think Tom showing cases, I think it's super important to understand the value of a molecule. Many presentations, we see there we don't see the detail. So so thank you to you and the team for actually being very transparent and showing us cases to actually see the biological effect.
Said this patient population is not the patient population that was enrolled in other TK I trials.
And sometimes when patients are enrolling the trial they have to have a history of neovascular AMD, but most trials with Teekay is don't require any fluid and this idea that maybe the disease was borne out in these patients never needed injections.
Kind of give us just a question mark about durability, we actually saw that in the Harbor study, where there were a subset of patients. After three injections never required injections. They were treated PRN. So I think this patient population that you have really enroll in this trial shows that they have active disease.
So number one that is.
Convincing to me just seeing that these are high need patients have active disease.
Now comes the fact that how can we help them with.
With this.
New MLA and supercritical delivery and seeing that effect after a flipper set by screening and then seeing that effect after CLS ax.
Literally convincing to me as a physician that we are seeing biological activity and.
There is no question that this molecule is helping patients now of course, the learning is how fast is helping and how long, it's helping and that is going to really help us design. The next stage, but at this stage. It is it is very convincing to me as a clinician that.
<unk> is actually.
Especially this one is helping our patients control disease, so disease control and durability, both or whether it being shown by these case studies.
Thanks for your insights and thanks for your comments on transparency in the appendix of the deck, which are available for download we actually include.
In particular for cohort three and four all of their prior treatment history going back three years as well as all the subject level data. So we have every every visit every CFT and everyday CBA.
Plotted out.
In the appendix of the deck.
And so finally.
One last question.
What is your opinion of the future of CLS Ax.
I think based on the data you have shown safety efficacy and durability.
Obviously, we need to take this program forward.
Being involved in all the Tbi trials and written extensively about <unk> I personally always thought that you guys were just four well controlled patients, but I think here I am seeing a signal.
That he can actually benefit our our high need patients.
CLS Ax deliver supra broadly so it's exciting to see that this is not just for a subset of patients it can actually benefit from it.
<unk> were up over our patients and and going forward. Obviously now you have seen biological activity. If you do a controlled trial with a comparator in stable patients I think youre going to see durability, that's going to be even better than what you have already already shown so I think looking at.
At stable patient population not just the high need population and then.
Designing a trial with an active control with non inferiority in <unk> primary endpoint I think that's the way to go forward, but it's exciting that I actually looking at this data alone and I'm thinking that <unk> not just for stable patients, but actually all patients can.
Benefits from it.
Once again, thanks for insight I'm now going to turn the call over to George.
Thanks, Tom Thanks to you and Dr <unk> before.
For that.
Discussion.
And I want to thank everyone on this call for your attention during our presentation I'd now like to ask the operator to open the call up for questions.
Thank you ladies and gentlemen, the floor is that we're open for questions and if you have any questions or comments. Please press star one on your phone at this time, we ask that while posing your question you. Please pickup your handset assisting on speaker phone to provide optimum sound quality. Please hold while we pull for questions.
Thank you. Our first question is coming from Andreas aggregate eyes with Wedbush. Please go ahead.
Good morning, and thanks for taking my question and congrats on the updated results.
Tom you did a great job of asking a lot of our questions. So forgive us if we if we repeat them some form.
So can you just give us a sense of how these results inform planning and expectations for the phase III, specifically around dosing patient selection.
You also give us more color on how stabilizing <unk> would translate to achieving our primary endpoint of Jensen active comparator.
So Dr. <unk> based on the results with durability around five months or so where do you where do you see.
CLSA exiting in the treatment paradigm.
Stabilizing <unk> goal for CLI.
Alright, Tom I think you and Dr. Konami over a couple of questions that you need to answer it so.
Please proceed.
Thanks, Andreas and thanks for the list of questions.
I think the first question was.
Next steps and I think the important point here is that this was interim data with regards to the extension study. So we want to follow the patients to the end of the extension study.
<unk> confirmed these initial results, but I do want to point out that as I mentioned.
Eight of the patients in the extension study have made it too.
It's eight or 12 patients in the extension study have made it to month five.
And only one was treated prior to month five so so I think I think we have a fairly good sampling.
Of the of all the patients in the extension study, but we still want to follow these patients out to the completion of the trial and so obviously, we will be analyzing the data the next cut.
When these patients finished and that will inform our future plans and I think.
Your next question is.
I think around.
Just generally a clinical trial design I think doctor <unk> alluded to this and I'll, let him expand on as well, but so the point I think you are making is that if you have treatment experienced patients.
And you provide a.
Our sustained release therapy.
That's meant to really stabilize them and reduce treatment burden. The question is what is the endpoint.
And thankfully, we have a model for that with.
The port delivery system, so that was a.
That was studied in phase III trials is now commercially.
<unk> approved and available.
And in that trial.
Patients with <unk>.
What I would call much more lightly treatment experience they had a diagnosis of neovascular AMD within nine months.
Had two prior treatments they enroll in the trial and then the gold trial with stabilized and so really if you look at the visual acuity curve even in the label.
Prescribing information.
You can see that what they've achieved with stability and they compare it to an active comparator thats dosed.
For its label.
Ultimately.
They show non inferiority as Dr. Akin oni alluded to and that led to approval. So we have a model.
For a therapy that is approved for essentially maintenance of stability.
And.
Again, we're still analyzing this interim data and we're still we still need to decide on the best patient population going forward as Dr. <unk> mentioned.
Less treatment experienced patients we might expect even better signs of biologic effect and durability. So I'll now turn this over to Dr. Economics, I think you had some questions specifically for him as well.
<unk>.
Thanks, Tom I think I agree with you that we have and we have a model to go after and I think in that trial as you remember patients were allowed to get supplemental injection at month, four or five after the surgery or after the last detail if they met the pre specified disease activity.
Criteria and those were.
Very strict criteria. So I think the bottom line for me is the fact that the.
And the differences that you have you're right we have super <unk> delivery that you Didnt <unk> validated FDA approved.
And then do you have a molecule that has good safety.
Whenever there is a new treatment not only do you have to look at your ability I think we have great anti VEGF agents currently as I said, so the safety bar is very high so in terms of the question from Andreas about patient population, where this will be utilized I think as Tom you said, we're still learning.
The durability and gathering data, but I think looking at it.
Clearly the stable patients on current treatment can go longer.
Vic.
This molecule. So that's one patient population and Thats actually the majority of our patients who are stuck at between four to eight weeks and maybe that's going to be eight or 12 weeks with <unk>.
So that's a mab or mobile MAU, so I think taking these patients.
The longer treatment interval, John you have done a lot of work about real world data and published extensively that did even if patients are getting injections every two months or so.
So they don't come to a clinic in their vision is worse over time, so I think as a clinician.
Just not looking at a percent durability I wanted to make sure. These patients actually maintain their visual acuity long term I want to make sure that any new treatment I give does not have adverse events or irreversible vision loss like PSC and when policy isn't that so I think the fact is that if you can take those plantations in <unk>.
Last week when treatment I think we will be able to stabilize their visual acuity longer I think it's all about.
Having patients keep the independence enable to drive able to function I think those are important parameters NBC vision loss over time, So Andre stable population, obviously, it's a no brainer and then I said earlier about higher neat population that comes in frequently every four to six weeks.
I'll have persistent fluid. So I think we are still learning if we can add on this therapy or use this therapy, primarily for that patient population and then the last question, obviously always naive patient population I think after controlling the disease acutely. This will also fit in nicely. So so I think.
Broad patient population may benefit from from this molecule. If if obviously, we continue to see the efficacy safety and durability.
Okay, great. Thanks for your insights and congrats on the results.
Thank you. Our next question is coming from Annabel <unk> with Stifel. Please go ahead.
Hi, Thanks for taking my question and congratulations on strong data.
Just to reiterate the point you guys are doing a great job of explaining everything so I'm just going to ask for a couple.
Clarification question so.
When you think about.
Defining our sub responder.
Is it just about fluid or is about non optimal.
Digital acuity or.
It has.
The CST you said reached sort of a floor. So therefore, you're not really seeing improvement, but would you have seen improvement and.
Visual acuity as well so it is it only fluid that make some non responder. So I guess, that's one of the points that I want to understand better.
So that's where I think great question Annabel.
So the question I think is what is the non responder and I don't think.
It's a it's a binary.
Determination, there either non responder or.
Responder and that's why we.
I call them sub responders and.
Got it.
Yes.
Couple of a couple of items here so.
As clinicians as investigators as sponsors of trials.
CFT, because it's convenient it's a convenient measurement youre measuring the central one millimeter.
That includes the fovea.
And.
It includes the thickness of the retina and that would encompass often sub retinal fluid and inter retinal fluid. So so it's an easy convenient measurement.
The machine in <unk>.
Clinic automatically essentially it's it helps them within within minutes within a minute.
And so.
Its numerical it's easy to grouse wounds itself, while the statistical analysis, but.
She is cheap doesn't correlate.
Perfectly with vision.
I think it's an important point.
But theres other aspects here.
Affect division you can have atrophy.
Which often occurs in wet AMD dry AMD as well so they had atrophy you can have scarring from uncontrolled.
[noise] Neovascular AMD you can have fluid under the RPE layer, what should we call. It pigment epithelium attachment and all of this isn't captured by the CFT, but again, we like CFT, because it's convenient and loans itself Baltimore analysis and graphing.
And so when we think of Sop responders.
S T doesn't capture all of it. So so yes, I mentioned there is a floor effect, but you can see.
For example in the second case that I showed and again this will be available online.
The CFT was essentially normal, but yet when you look at the actual anatomy.
The images you can see that there is mild sub 12, youll fluid there is mild into retinal fluid and.
So I think it is important to look at these these cases and I think when I think of sub responders.
I think of patients that have persistent fluid on the OTT and again the images that we see in <unk> almost.
Our printed out almost immediately.
It's convenient and I think most clinicians would consider persistent fluid on an OTT image after an anti VEGF injection.
Sub responder, so so theres nothing I don't think Theres, a clear cut definition, but I do think.
That.
Counting patients with persistent fluid after anti VEGF therapy is quite common for at least 30% of our patients.
And.
Persistent fluid it's been shown.
Overtime to be bad there is a paper from from.
The cat study that showed that patients who have persistent inter retinal fluid over two years have a worse prognosis digitally so so I guess to summarize.
Sure.
There arent there might be as clear cut correlations that we all like CFT is really something that we conveniently plot.
The images as retina specialists is really what we'd like to see and we have papers, suggesting that at least 30% of patients some people suggest more.
At least 30% of patients have persistent fluid.
<unk> imagine most retina specialists would agree that those are sub responders Dr.
Dr <unk>.
Any any more thoughts so do you agree.
No I agree I think those are great.
<unk> one thing I would add is that in a busy clinical batches I'm seeing 80 to 90 patients and the visual acuity in clinical practice is actually could be variable because of dry eye because of who our effort.
CSD and OCD images.
Our not subjective or objective tests and they give us the data right away we call it a digest meter.
Having flu.
Fluid or having.
Disease activity in <unk> is what we treat patients for as explanations and of course, that's not a regulatory endpoint vision is but I think we know from multiple trials. As you mentioned all can hear your cat island that fluctuations in CSD actually are bad for the retina and can end up.
With long term vision.
<unk> decline. So all these patients that I know were getting monthly injections, we may do them in a week or two after the injection and they may not have fluid and then they come back in a month and absolutely those are suboptimal responders because they are having fluctuations in their fluid status theyre very high need patients and thats.
Patient population.
Rolled in the trial. So the hope is that with this molecule if he can stabilize CSD or improve fluid than what it was with standard.
Frequent injection I think that's going to be meaningful for patients in the future.
Okay, but there is no there is no expectation that you would be improving.
Visual acuity on that just you don't want worsening, but when you want to maintain stability I mean.
I guess I'm trying to understand the visual luxury side, yes, yes, better visual acuity.
Yes, I think Thats a really good good question, Tom can I take that.
I am sure, yes sure yes.
Yes perfect.
These are super high need patients is all about maintaining where they are otherwise or the CSD fluctuations. There then they're going to get worse over time. So I think yes, we don't expect visual acuity improvement even in patients who don't have long term disease like in the port delivery system.
We saw that patients.
As Tom said, it very recent disease and they got stabilized with with minimum of two anti VEGF injections, we didn't see visual acuity improvement, but rather maintenance. So I think the acute improvements happen quickly, but theres long term visual acuity lost because of noncompliance because of CSD fluctuations.
So those are my comments to your question Tom.
Yes, So let me sometimes.
Especially as were too close to it to really let me let me broaden the focus.
So with treatment naive patients.
We have approved agents.
That are treated with.
What I call an injunction dosing there given monthly therapies initially and if you look actually on your prescribing information that you can you can see the visual acuity curves and what Youll notice is not.
The visual acuity improves rapidly.
In treatment naive patients who undergo this initial induction phase.
And the visual acuity improvement somewhere in the order of depending on the trial and the therapy, but somewhere in the order of eight to 10 letters on average so they improve within the first three or four months by 8% to 10 letters there.
Ben.
The curve plateaus.
And so these patients come in every four to six weeks and their visual acuity is what it is.
And these are the one.
One of my Colleague's comments. These are the veg F. Alex that they have to keep coming in because.
If they if they don't come in for their treatment.
They are persistent fluid which tends to progressive.
It leads to a visual decline from that plateau and a doctor can only published extensively on real world outcomes, and we know that in the real world patients can't keep up.
And so ultimately.
They lose vision from that plateau.
So in this treatment experienced patients they have already undergone that induction phase it's inherent in your prior treatment and they were on the plateau. So you can see from the from the swim Lane plots, we show both six months prior and up to three years. Prior at these patients receiving frequent injections. So theres already plateaued and we don't expect them.
To improve now in other patient populations with Doctor can already mentioned the treatment naive patients.
Potential to see improved vision.
I think I think I think we answered your question.
Any follow up does that clear, yes, no that actually.
Lastly, and just I guess following on to that treatment experience treatment naive population. So.
As you move into phase you have a pretty good model as you said, where you want stability.
<unk>.
PCB as well as ICT.
Is there any other.
And client that you're I mean, obviously you are looking at that.
The reduction.
Any further treatment.
The reduction of treatment burden is.
Is it strictly about stability in the CVA and OTT are you also need that that reduction in treatment, Brian is that going to be like a key endpoint that people look at.
Outside the durability.
Then.
Treatment do you have any intention of moving into treatment naive patients.
Under the impression that anti VEGF is the most rapid acting.
I guess agent that you can use for stabilized when these patients does.
At Teekay.
Have that rapid.
As well or can you just not know at this.
At this stage because it hasnt been studying that treatment naive population.
Annabel. This is a great question. So let me let me start with the first one so the question is.
Endpoint and as Dr.
<unk> mentioned the primary endpoint for four trials generally visual function in this case visual acuity so that has to be.
Endpoint and so generally.
These trials.
Keep using the port delivery system as a model, but it's a good model is can we can we maintained after patients undergo injunction naphtha they've risen the visual acuity has risen on that plant to the plateau can we maintain their visual acuity often a non inferiority trial with the standard of care fixed frequent injections and so visual acuity almost always.
The primary endpoint. These other endpoints are interesting because they support the primary endpoint they suggested biologic mechanism.
And then.
A little bit more about your first question on visual improvement.
Patients who.
Or have chronic neovascular, AMD or chronic neovascular AMD with elements of geographic atrophy.
Those patients often can't improve because great, scoring so I just wanted to follow that up and then your second question no would we enroll treatment naive patients in the next trial.
I think you've answered your own question, we just don't know yet we want to follow the patients in the extension trial up to the completion, but the beauty of this patient population is that we've shown a biological effect and a very difficult to treat patients and this opens up potential for.
A variety of patient populations with Dr. <unk> alluded to Dr. Counting any any other follow up comments.
No I think I think you answered the question very well Tom So I think we'll learn as we generate more data and then that's really helpful. If you have biological activity in high need patients. Then you know that youre going to have activity in every other patient population.
Still learning about how fast.
<unk>.
Help control disease of course.
Your technology is different because it's not a hydrogel or a polymer.
Micro particle.
<unk>.
Injected in the vitreous I think.
With your program I think you may see biological effect to affect quicker than others, but we are still learning how quick that effective so that we can help design. The next study.
Okay. Thanks, Thanks, a lot.
Thank you. Our next question is coming from John <unk> with JMP Securities. Please go ahead.
Thanks for taking the questions and congrats on the data and thanks for the thorough relief.
One for Dr. Konami, if I may and then a follow up for management.
Wondering how frequently do you want to see your patients per day.
When we have this longer durability agents, becoming available what do you need to see from a clinical program through.
Lengthen that frequency or you said that you wanted to see your patients are honest that schedule how are you.
Thinking about I guess durability of effect in your practice and patients.
Thanks, that's a really really good question. So I think there is a difference in following these patients in clinical trials versus following these patients in clinical practice. So obviously in clinical trial, we want to follow these patients monthly in most trials to look for any safety issues any adverse.
Event, and then of course look at the disease control patients are very heterogeneous they are different in all aspects. Once you dive into real world. So I think once we have control of data about how how long we can take majority of patients then youll have to individualize treatment too.
Patients. So for example, somebody who is very high need.
Let's say like Dennis patient population meeting monthly injection and you give them.
This molecule <unk> cm monthly initially to see how fast you get two disease control and then once you figure out what's golar sweet spots, we do treat and extend in our clinic currently with anti VEGF trying to find that sweet spot where a patient is stable then you only see that patient.
That often given that you are not looking for intraocular inflammation, given youre not looking for like we did report delivery conjunctiva erosion and retraction and end up the Midas. So I think you have to balance the efficacy safety and durability, but if I add location that can go four or five months.
On this molecule or six months that was on ones.
Month or every other month treatment then after that first cycle I'll be comfortable seeing that patient at that time interval and then lastly, we have home monitoring and OTT almost <unk> and other things that are coming in pipeline, where we will be able to monitor these patients remotely. So so overall I think using technology.
New mechanism of action, we will be able to significantly decrease treatment burden for patients and that's my hope.
That's very helpful and then maybe one for Tom.
Are you thinking about growing the subsequent studies and dose selection, we see pretty good durability of both cohorts three and four for a little bit better smaller number of patients shorter follow up but then when you factor in CSD. It looks like it's worsening a bit in cohort four wall core three things stable improved.
But then visual acuity dropping off a quarter with a longer follow up how do you factor in all of these things and safety, we don't have it by goes but.
And it looks good so far so what's the most important metric for you guys when you're thinking about preferred dose moving forward.
Well I think the most important things that we follow the patients in an extension study.
See what happens in a broader patient population.
Your point about the BCD and CFT as I mentioned in my prepared comments.
Since it is an interim analysis the sample size really drops.
Quite significantly.
Hit months six in fact.
The <unk> curve, when we exclude data app additional therapy that month six.
Time point really only consists of three patients and I think.
You can look at the subject global curves yourself, but I think it's driven by one patient.
So I don't I don't really agree that division drops off.
Yeah.
We want to be transparent and we wanted to provide the results, but what is that.
Small sample size. This one could conclude that on the CFT curves.
Cohort three it looks like it improves in cohort four it looks like it worsened slightly but but sample size, it's really small and I think with anything you need to look at the the mean of the two groups in order to increase the sample size a little bit in the main looks quite stable and if anything.
One could conclude that the CFT gets better at six months.
But again small sample sizes, we don't want to make much of it I think overall, we would say that the CFT of BCA stable over six months.
And then the second part of your question.
Let's see more data and wait for that.
Final analysis.
But I think the good thing is that we saw really pristine safety, we saw really no safety signals at all at both doses.
And I think.
The biologic effect in fact, all the cases I showed.
We're from cohort three because we are just slightly longer follow up.
So I think the biologic effect is there in cohort three.
And we're going to analyze cohort four and more extensively and once we have more follow up so I think I think it's premature to comment on the dose that we would take forward if we take one or both doses, but we still we're still design.
Got it thanks for taking my questions and congrats on the data.
Okay.
Thank you. Our next question is coming from <unk> Chen with H C. Wainwright. Please go ahead.
Thank you for taking my questions you mentioned that.
The screening the patients have active disease does that mean <unk> patients had excess fluid.
At the time of screening.
Well, that's a great question, so as I mentioned at screening.
The patients were all assessed by an independent reading center.
The independent Reading center defined.
Active sub focal accordingly vascular membrane.
Having some mobile quarterly vascular membrane on and geography, which leaks.
Yeah.
Having either.
Sub retinal fluid.
Inter retinal fluid and the central subfield that the OTT.
So yes, they had they had to have.
<unk> on the OTT.
<unk>.
So.
Is there a reason that.
<unk>.
The clinical study would exclude patients who.
Do not have access fee.
So we excluded patients who who don't have after disease, who don't have fluid.
But we included patients who have had fluid who had sub retinal inter retinal fluid in the central subfield and the degree of that fluid.
We did not specify it just had to have an active quarter neovascular membrane because these patients were heavily treated.
Most of them did not have.
Very thick C. As Ts, but these were patients who had high high need patients who came back frequently so they had they had fluid on their OTT.
As well as in actively leaking so probably acromion vascular membrane on the angiogram as defined by the reading Center.
Does that suggest asics.
Is not.
As good a drug for those patients who do not have excess glue.
I'm not sure what you mean by excess fluid, we didn't exclude patients who had.
Sure.
Lots of fluid.
But because these patients are all treatment experience.
Not going to have lots of fluid Mr treatment naive and it goes back to my comments earlier with Annabel.
Patients.
When they're first diagnosed oftentimes you'll have very kick OTT visual acuity growth dropped they undergo induction dose induction dosing, which is often monthly.
And then the Occ's improved position improves and then they were there.
On the plateau that visual acuity curve and they often have some patients respond they can become inactive and some patients have smoldering.
Gauge, where leakage that comes back if they go too long between treatments.
Okay and would you expect the upcoming phase II trial to have the same criteria.
Well, we're still evaluating all the we have a lot of potential with this agent.
We're still evaluating we're still waiting for the.
For the final analysis from the extension study.
Okay got it.
And <unk>.
So regarding the rescue free right.
Versus the rate.
Per protocol criteria would you say the former one.
What would.
Would it be more.
Similar to <unk>.
Real World practice scenario.
I'm not sure if I understand the question can you.
For example for the three months time point, you reported a 69% of patients did not receive additional.
<unk> versus 92%, who did not receive additional therapy per protocol criteria.
Asking whether the former situation.
Be more similar to real world.
Correct.
Scenario in terms of rescue free right.
Again, I am not sure if I understand the question but.
Okay.
In the real World some patients I think I think the most common.
<unk> regimen as a treat and extend regimen. So patients with for example, a naive patient willing to go monthly induction dosing the visual acuity improved the OTT improves.
They go to the to the plateau that visual acuity.
Improvement curve.
Then oftentimes.
The integral is extended I think most retina specialists will extend by two weeks at a time.
And then at subsequent visits if a fluid starts to recur the vision starts to drop.
Bill then contract by two weeks and there are patients who have.
Kind of almost a personalized.
Integral where they can go in it's very hard to get patients beyond.
Beyond two months with the current agents. So I think that's probably what we see in the real World and Dr. <unk> do you want to expand since since you are a busy practice and are most familiar with.
Real World.
<unk> regimens.
Yes of course.
Thank you.
So the question is how does real world practice differ from from clinical trials and.
This off protocol treatment versus protocol treatment. So I think what I'm participating in a trial, obviously I want to make sure that.
Design, well and it has.
No safety net for my patients and.
Some trials.
Have criteria that are unrealistic and they do OCD and vision and this and that and then you ended up having patients to actually get worse in that trial and Thats not the case I think these are high need patients as we discussed.
And what happens is if you are in an early stage study and you gave the treatment and the patient.
Still has fluid your expectation was well maybe the treatment is not working and then you try to give them an off protocol treatment just nervous that is going to get worse, but here, we actually saw that the fluid gets better over time. So this learning about following the protocol will be helpful. When we go.
<unk> to the next stage. So we can convince of our colleagues at Hey. This treatment is working it is going to improve you just have to be.
Just have to be patient and I think I just want to comment to the earlier question about this patient population. So this nation population as I said is very different than other <unk> studies, whether you look at.
Other <unk>.
The reason is the criticism DDI studies get it while youre enrolling these patients who have not shown fluid for last five years, what are the diseases burned out and you're just treating them. Because you are scared about Disney is coming back locations getting active. This is the only dk I study that we are participating and actually is requiring.
Active fluid so this actually.
Shows a biological activity and it's convincing for the community and me as a clinician that do you guys clearly can benefit of our patients.
Thank you.
Our next question is coming from Serge Belanger with Needham <unk> Company. Please go ahead.
Hi, good morning, Thanks for taking my questions.
I'll just stick to two.
First one for Tom can you just talk about.
And your plans for the Phase III trials you mentioned.
Also evaluating <unk> in diabetic retinopathy patients just curious if that would be a separate study or it would be part of the phase two trial.
And then secondly for Dr. Kulkarni.
Given your expertise with tyrosine kinase inhibitors.
The drug class that's been around for a long time, but I think it has had mixed results in retinal diseases, so far and some of it has been due to the.
Delivery mechanism, but just curious why do you think it's been difficult for this drug class is it a question of.
Finding the right molecule in the right delivery mechanism or.
The treatment burden.
Provides a high hurdle for success.
So I'll take that first question and turn the second question over to Dr. <unk> as you've correctly so.
So I think you asked about diabetic retinopathy potential study design and again, we're considering all options. We think we have a lot of potential with this therapy.
And so we mentioned it in our in our.
Remarks, as a potential with an obvious.
Potential.
And how we design the trial again, we're still featuring all options and I'll turn the second question.
To Dr <unk>.
Yeah.
Thanks, Tom by the way I agree with diabetic retinopathy, the VEGF levels or low end.
We have standard treatments event at that Jeff.
The majority of the patients are not getting those treatment because of the frequency of visits I think there is some indication obviously if you look into the second question about as a field what do we think about <unk> because we have had some some not so promising results in some trials and I think as you alluded to.
Those were because of the safety concerns those world because of not taking the right patient population and adverse event P&L pressure issues corneal toxicity articles going into the front of the eye, but I think we have.
Evolve from the version one <unk>.
P. J is like GBP 102 to now in a situation that you have a delivery super gorilla delivery, which is validated.
And FDA approved and then you have a space where you are awaiting exposure.
To the front of the eye or to the vitreous cavity. So as I said I always and conservative in terms of looking at things and I always thought that <unk> are probably best fit for very stable patients receiving injections every two or three months and maybe if we can go to six months that would be meaning.
Full but here for the first time I am seeing.
Activity in these patients that actually were very very high high need. So I think we still need to generate evidence.
And the reason for that is that we have really good treatments. Currently we have multiple FDA approved treatment MBA <unk> that can take patients longer but it's incremental benefit it's not a six month benefit is not.
Benefit it's close to anywhere from two to four months and we are moving that needle forward. We are getting these stations.
A little bit longer.
What did in the past so I think we're still open to new options, but the bar again is very high in terms of safety efficacy and durability and the trials continue to generate data on multiple DTI programs. So, we'll see where it takes us but at least for this program I am pleased to see that we are seeing biological activity.
Very safety favorable safety profile.
Really points to taking this program forward.
Okay.
Thank you.
Next question is coming from <unk>, Tommy with B Riley. Please go ahead.
Good morning.
Thanks for taking our questions and congrats on the data so maybe just sticking with the prior.
Dramatic conversation with Dr. Konami.
So induction therapy has also been very different across these <unk> studies.
So could you just comment on.
As you think of.
Going forward with this agent.
What have been the learnings here then.
Actually if you think about active disease.
Ensure that youre getting that induction.
As important so could you maybe comment on that and also at <unk> as you know.
The high dose Eylea.
The discussion was very relevant so maybe if you could also put that in context would be very helpful. And then I have a <unk>.
Follow up for Tom about the data to date.
Sure I think those are those are all excellent questions and you're right.
Ending on the Tbi trial, whether you get in a flipper set up or anti VEGF at screening or you'll get at.
Four to six weeks prior and then you'd get at a month after you dose with Pgi. So it is variable between between trials. So I think this phase one as a learning opportunity for us once we get full data set will be able to see.
Where we want.
Load these patients whether it's screening whether.
After.
Things like that will be relevant as you take the program forward because I agree with you I think we need to control these patients and give them some time to kick in.
And so that they don't get worse over time, but here.
Unlike other studies there was no <unk> given a month after TGI. So we're actually seeing an effect post dosing at two or three or four months, which is actually directly a result of the T Guide not a result of that just given a month after <unk>. So thats why its important to <unk>.
Look at the data in detail and not just cross trial compare.
Topline durability percentages as I said, because the patient population is very different among the trials as well as the treatment regimen and then the question about.
High dose Eylea, obviously, that's a very detailed conversation for a later time, but I think again as I've said with anti VEGF injections, putting a little bit more may give you a little bit longer half life, but you are seeing incremental benefits a week or two week at a time youre not seeing a benefit thats lot.
Thing lasting six months. So I think it's always good to add new agents, but I think a new mechanism of action designed for sustained delivery is clearly exciting.
Thank you that's very helpful and maybe for you Tom.
Terms of follow up as part of the trial protocol, maybe I missed that.
Are there any patients lost in follow up you've got olive garden.
Then.
Any of those.
The protocol.
Observations what could have been the reasons for that.
Just clarify that.
Sure in terms of follow up we've had we have data on all the patients who enrolled in the in the parent study and the cream of parents study and then those patients as George mentioned initially or offer the opportunity to participate in the extension study and we haven't had any of those patients.
Who actually.
Who actually.
So we can participate in the expansion study and showed up for their month fourth is it.
So far not show for here.
Subsequent visits.
Oh.
Or tell us that they're not going to show up for their subsequent business I believe if you look at this one lane plots youll see that there are still patients who have showed up for a month forward and we're still following that but but so far we haven't had any patients show up for their first extension study visit.
Then indicate that they are dropping out.
Got it.
Yes, thanks for taking my questions and congrats again.
Thank you.
As there appear to be no further questions in queue I will hand, it back to Mr. <unk> for any final comments.
Thank you for your time and attention this morning, I'd, especially like to thank Dr. <unk>.
<unk> for joining us on the call today, I think we had a great discussion.
I want to note that we have a clear sight has an active investment conference schedule coming up starting with the Stifel Healthcare Conference next week.
Also look forward to participating in the <unk> Ophthalmology day with Piper Sandler Health care conference and Cantors medical and aesthetic dermatology ophthalmology in Med Tech conference.
We appreciate your continued interest in clear sight now.
We look forward to updating you on our progress in the future operator, you may now disconnect.
Thank you ladies and gentlemen, this does conclude today's conference call. You may disconnect. Your lines at this time and have a wonderful day, we thank you for your participation.
Yeah.