Q3 2023 Belite Bio Inc Earnings Call
And how one Zhang Chief financial officer of be liked by out before we begin let me point out that we will be making forward looking statements that are based on current expectations and beliefs. These statements are subject to certain risks and uncertainties and actual results may differ materially we encourage you to consult the risk factors.
Got you in our SEC filings for additional detail now I'll turn the call over to Dr. Lynn.
Thank you.
Thank you for joining our reporting for the third quarter.
So youll see lifestyle, joining me is our CFO Nathan as CFO.
I'd like to start off by giving you an overview.
Yeah.
So <unk> is a novel once a day oral tablets designed to barneys.
So retinal binding protein or noise, albeit before.
As it means to specifically.
There is great deal of delivery to the eye.
This approach is intended to slow or stop the formation of toxic retinal derived by products.
In the visual cycle.
The progression of <unk> disease and geographic atrophy.
Indeed to dry AMD.
We believe that early intervention directive emerging retro pathology.
There's no media mediated inflammation will be the best approach.
The slow disease progression and startups disease and geographic atrophy.
There is still a significant unmet need for both indications.
Early days no approved treatments for startups disease.
Currently no approved oral treatments for Ta.
We are already a global phase III trials for both indications.
So far we have been granted fast track designation rare pediatric disease designation and orphan drug designation.
We have several families and less composition of matter patents lasting until 2040.
Patent term extension and new patent suit.
We will have patent protection way past the 2014.
So we still have a very long patent life on this drug and we are already in late stage development.
Costanza indications.
Phase III is already fully enrolled.
Estimated interim readouts by second half of 2024.
We've also just recently presented a positive three four months treatment results from a phase II, which may say, we will be presenting the results thereon.
So <unk> <unk> dry AMD indication the phase III is already enrolling subjects.
I'd like to pass this onto our CFO to give you an update on our clinical trials Nathan.
Thank you Tom so I'd like to start by giving you an overview of our clinical trial designs and startups disease I'd like to first start however, just to Orient everyone that it is important to note that the reduction of atrophic lesion growth rate as measured by retinal imaging is the FDA accepted primary endpoint for both startups disease and geographic atrophy in startups disease.
Terrific lesion is called they definitely decreased auto fluorescence lesion, just keep that in mind, whereas in geographic atrophy simply refer to as atrophic lesion growth, but it is essentially the same thing back to the start of our trial design. There are two trials that one we've recently completed and one that's ongoing as Tom mentioned the ones shown on the left hand side is our open label phase two.
<unk> trial enrolling 13 adolescent subjects age 12, 12 to 18 years of age from Australia, and Taiwan. This was a two year study looking primarily at safety and Tolerability. We have identified the optimal dose in a previous phase one b that optimal dose being five milligrams daily and I'll show you some of the pharma pharmacodynamic data from that dose.
We're looking primarily in terms of efficacy at the atrophic lesion growth, but in startups disease. We're also looking at a predecessor of the atrophic lesion growth, which is auto fluorescent lesions that are referred to as Questionably decreased auto fluorescent or <unk> in this phase II study. The 13 subjects enrolling only started with us early lesion types.
They did not have a terrific lesions. So we want to measure two things in this study one the conversion time from the acuity of lesion to the atrophic lesion that DDS leisure and then also once the GDS lesion is formed we want to measure the growth rate of that incident, eds lesion and I'll share some of that data with you in a moment and you can see at the bottom there the key inclusion criteria.
12 to 18 years of age. These all of these subjects have been both clinically and <unk> confirmed as having startups disease the.
The other study that we're doing in <unk> is our pivotal phase III study called Dragon. This study as Tom mentioned has just recently completed enrollment at 104 subjects. It's important to note that all of these subjects in the phase II trial will have a terrific lesions at baseline because that's the only way that you can really measure the endpoint that is growth of atrophic lesions.
When you have a baseline so that we will be doing in phase III. This is a global study thats. The only way we could get a 104 subjects. In fact this is the largest.
Study <unk> in adolescent patients ever conducted you can see the randomization. There is two to one flavorings and layer about it as a two year study with the same efficacy endpoints that we're looking at in the Phase II. We're also looking obviously at vision, we're looking at anatomic markers by spectral domain optical tomography, and we're looking at retinal sensitivity by micro Perimetry.
At the very bottom there you see the key inclusion criteria very similar to the open label Phase III, except we've expanded the age range. Another two years to go from 12 to 20 years of age and we have also defined daily upper size of the lesion at 762. So all of these subjects will have lesions that size or smaller and youll see there the BCA vision requirement.
R 2200 or better.
With that I'd like to next go to the next slide and talk to you about some of the Pharmacodynamic data I just mentioned earlier, what Youre seeing here is a pharmacokinetic and pharmacodynamic profile of five milligrams can layer events in those adolescence target subjects that were participating in the open label Phase II. The Blue line shows the level of <unk> in blood and the Red line.
Shows our Pharmacodynamic biomarker retinal binding protein for this is what the drug is hitting and you can see here that there is a very nice correlation between the increase of <unk> <unk> in blood and the decrease of retinal binding protein for in blood until we withdraw the drug at March 24, and you'll see a very rapid reverse stability over about 28 days of drugs.
Cessation. So we got about 87% of return that is of the baseline value at the end of the study but during study we have approximately 80% reduction of retinal binding approaching 14. The blood. This is important to note because in a prior clinical study not conducted with <unk>, but a different <unk> and targets, we found that a dose of <unk>.
70, sorry, a reduction of 7% or more of retinal binding protein for was effective to produce a slowing of lesion growth in patients with geographic atrophy. So this has become our target threshold for arguably four reduction we want to achieve at least a 70% reduction or more in here with a five milligram daily dose, we're achieving a mean, 80% <unk>.
Reductions in all subjects that have been dosed.
Next slide please.
I mentioned to you that in this open label Phase II of what Youre looking at the 24 month data at right now.
Adolescence targets subjects did not have atrophic lesions at baseline only auto fluorescent lesions.
And we wanted to understand if we're actually having a treatment effect over 24 months of treatment. So what we did is we did a comparator study we compared our data to data from the largest natural history study of startups conducted to date that study is known as Prague started was conducted over several years involving four to 500 patients in these studies.
Most of those subjects, where adult startups subjects. However, there was a sub population within that larger group of about 50 subjects that had the exact same baseline characteristics as our services in the open label Phase II that is they were 18 years or younger and they had no atrophic lesions at baseline. So this subgroup serves as a nice apples to apples compare.
<unk> for our analyses and Youre looking at them here on the left hand side. What you are looking at is the growth of incident atrophic retinal lesions over the course of 24 months in each group. The promised our group has shown in Blue and our group of Tulare about treatment as shown in Red. So neither group had atrophic lesions. So we're measuring the time to the <unk>.
<unk> lesion growth and then we're measuring the growth of the incident.
Profit lesion over time and you can see that at every time point from six months to 24 months, we consistently have a lower reduction or sorry, a lower a DDS lesion growth compared to probably start such that by the end of this trial at 24 months, we have a highly statistically difference between pronged store growth and our growth that is our leisure growth being about <unk>.
50% lower than what was published in the <unk> studies. This is phenomenal in fact has never been reported before the other important aspect of this study is among the subjects that we hadn't study five of them did not convert to any atrophic lesion and that again is another important finding because it suggests that our drug is slowing the conversion of the.
Early Liza type order fluorescent lesion types to the atrophic lesion types. That's the first observation the second observation being once those incident lesions are formed we have a slowing of the growth rate of those lesions compared to natural history. So it's important to note that this phenomenon, we're seeing the slowing of lesion growth is statistically significant at every time point that we've measured.
And in fact as I said before has really never been demonstrated in another interventional treatment trial of our analysts and startup patients.
Next slide please so now I'd like to show you. Our 24 month visual acuity data, which you are looking at is the visual acuity data from both the study eye, which is designated at baseline and the fellow eye.
This disease is a bilateral disease. So the disease will affect both eyes equally in our drug of course is systemic so it will affect both eyes equally but what we're showing you here is both is just to show you over time, we're getting stabilization in each of the of each buy of each patients over 24 months. This is significant because although this study was not powered for.
Treatment efficacy against vision is important to see stabilization over 24 months because these subjects will in fact lose vision annually over time. So the fact that we're slowing lesion growth and also stabilizing vision is a very important finding the other point I want to make is that visual acuity losses or gain within 10 letters is not considered clinically significant.
So what we have here really is potential test retest variability affecting these data so until you get outside of 10 letters. There really is nothing clinically significant to say about the data, but it is important to note that theres stabilization. While we are in fact slowing lesion growth as I've showed you in the previous slide.
Next slide please.
Now I'd like to show you the drug related adverse events. It's important to note that although this is a still a systemic drug there had been no clinically significant findings the relation of vital signs physical exams cardiac health or organ function. What we see are two anticipated ocular drug related aes that we would like to see because there.
Telling us we are having the intended biological effect on the retina. The first is a form of Chromatopsia called Xanthopsia. This is mediated by cone photoreceptors. This is Phil.
Receptor subtype, and your retina, which confers bright light and color vision, so when subjects under our treatment.
Transition suddenly from a very dark and environment to a bright environment. This activates cone photoreceptors cone photoreceptors will demand chromophore under our treatment regimen that promo for OLED slowly supplied to the cone photoreceptor, so there'll be a delay in their timing to obtain the maximum bright light sensitivity during that time, there will be an artificial.
In electrical.
Produced few of color in the visual field in this case yellow it can last seconds to sometimes a few minutes. It is important to note that these subjects are reported as mild and of course, it's transient the majority of subjects have been evident.
Encountered this AE 10 of 13, but no. One has left study because of them. The other manifestation is called delayed dark reputation and this is mediated by another photoreceptor cell type called the Rod photoreceptor, which confers dim light vision, so when subjects under our treatment transitions suddenly from a very bright light to a very dark environment directive.
It's rod photoreceptors. They will also demand chromo forward to maintain dim light sensitivity under our treatment regimen that <unk> will be slowly supplied so there will be a period during which subjects will have will not have maximum dim light sensitivity. They will eventually gain it it's somewhere between eight to perhaps 15 minutes delay, but it will be attained.
And this is not night blindness, and once again, you can see a high number of subjects, having this this AE, but nobody leaving study because of it because again it is mile. It is transit and of course, it's fully reversible so.
So we believe this drove five milligrams daily is effective to achieve what we want in the retina with these very mild and well tolerated aes. It's also important to note that in our treatment. Overall. This has been very well tolerated again, no systemic aes and only ocular drug related aes, which we need to see as they are intended.
To have this effect on the retina.
Next slide.
I will now show you our trial design for geographic atrophy or this is a phase III trial design is going to look very similar to our phase III trial and startups disease with two important exceptions, the indication geographic atrophy instead of startups disease and the number of patients 430 to reflect the higher prevalence of <unk> in the population.
Of course, it will be a global study same randomization scheme as in the Phase III Star trial 201, favoring <unk> two years in duration were going to be looking at the same efficacy measures of course here. We're looking at a terrific lesion growth. It is the same as <unk>, but just named differently, but it is the same phenomenon and of course, we're looking at visual acuity outcomes anatomical outcomes.
SD OTT and retinal sensitivity by micro Perimetry and there will be an interim analysis at one year as there was in the phase III as there will be in the phase III Star trial.
Excellent.
With that I'd now like to throw it back to <unk>. So he can discuss the Q3 2023 financial results. Thank you.
Thank you Nathan.
So in Q3, we had $8 7 million R&D expenses increased from $1 2 million for the same period last year.
The increase resulted primarily from increase in expenses were conducting a dragon in Athena study in Arizona, the wages and salaries due to share based compensation <unk> R&D team in QC.
We had higher expenses this quarter, because we met several development milestones on both Dragon in Phoenix study such as the completion of the enrollment of Dragon and the first patient in containers.
On the G&A expenses, we had $2 2 million G&A expenses compared to $1 4 million for the same period last year may increase again.
<unk> is now primarily from an increase in the share based compensation 2000 in Q3.
Net loss, we had a net loss of $10 9 million compared to $2 4 million for the same period last year.
In terms of cash we received $6 5 million cash inflow from warrant exercises from ATM offering and R&D refund.
With approximately $9 4 million cash outflow, our net cash outflow in Q3 is around $2 9 million, leaving us with 54 5 million cash by end of Q3. Thank.
Thank you and to you Tom.
Thanks.
So I would like to conclude work the key milestones that we have achieved this year.
In Q1, we initiated our phase III study in geographic atrophy secondary to dry AMD.
In Q3, we completed the enrollment for the phase III study in <unk> disease.
We also just recently completed our phase II study in <unk> disease, and presenting presented very promising and positive results.
Last week.
And finally, we are expecting interim results from our phase III <unk> trial in the second half of 2024.
Thank you.
Okay.
So we will start to take questions. If anyone who has questions. Please raise your hand.
I got.
Jennifer Kim and Cantor.
The operator, please on mute janitor.
Hi can you hear me.
Yes, we can hear thank you.
Okay, great. Thanks for taking my questions and congrats on the progress this quarter.
A few questions. The first is there anything you can say in terms of the number of patients you've enrolled so far in Phoenix and how many clinical sites up and running and then my second question is more of an Opex question.
The higher R&D expenses, how much of that was due to the development milestone and aren't expected to repeat in future quarters.
A similar on the G&A side incentive point 10 million.
Fair way to think about.
Base going forward. Thanks.
I'll take the first question, yes, I can handle that clinical trial questions. So Jennifer in the phase III start study we've enrolled 104 subjects. We have some baseline demographic data from those subjects that show is actually very favorable balance in terms of the prognostic factors that would be predictive of disease for instance.
Our full wheel involvement on 98% of our subjects are fully involved the CVA all the subjects have similar be CVA. They all have similar lesion size, which is a smaller leisure side, that's exactly what we're going for because it gives us an opportunity to interrogate. This hole early intervention, a differentiator, which is what we believe our drug will be able to do so with a smaller.
Lesions fully involvement these two things alone allow us to test. This idea about early intervention as well as potential of visual acuity benefit because these lesions are and coaching to the fovea. These kids will be losing vision over two years. So I think everything is up.
Turning out very well in terms of the baseline value in terms of the baseline demographics for this our phase III <unk> study. The other two questions were largely financials I'll throw those to how yet.
Actually I think I was asking the Phoenix trial on the <unk> side, our enrollment and coupon there.
Oh, sorry, yeah. So we've just begun enrollment I think we've got up to 687 subjects that we've only been added a couple of months. So we're really just starting to ramp up that recruitment effort again, we're going after 430 subjects. So we predict probably another year to maybe 14 months to complete that enrollment and again, we're really just beginning in the early phases of that enrollment effort.
Okay.
Okay.
Yes, so about the R&D questions. So for this quarter it has had a.
The milestone was hit I think we paid about <unk>.
<unk> million dollars.
Or.
Dragon study.
And also for the <unk>, adding about $1 9 million on participation screen and dose.
So we don't really at this high expenses moving forward.
Sure.
As you guys may recall, we had much lower Q2 expenses.
We have over a sign up on Dragon study, we wanted to enroll only 90.
But before we closed enrollment aways already 104 subtests sign up.
We had to wait for the <unk>.
Last one.
The schedule for dosing S. Why we had to delay the milestone on being fully enrolled from Q2 to Q3. That's why the Q2 expenses was much lower than what we expected because you didn't have the milestone and often accused team he does and the Tuesday.
You have the drag and truly our enrollment milestone here you got a glass of Dragon study milestone hit as well and so you have that Phoenix.
First patient dose Myles.
Milestone hit as well so that's why you see a much higher Q3 expenses off of moving forward.
Our goals now too.
Ah.
And Timna.
Half 2 million lower given we don't have those milestones.
Or that the.
The Dragon to continue in the following quarters.
And then on the SG&A side.
<unk>, we don't really know at the.
A moment to give a very accurate.
Accurate expenses forecast because you all highly depends on.
The progress of the sites and the screening on and catching up and the cost while also highly depends on the progress on that as we kind of can have a like a full year yet.
Four corner by corner, we probably will have to wait and see the site to start up and running for a bit to be able to know.
Like how fast the IOP approve the contract the study in wholesale.
How fast the Pis and call back their patients are now while we have is like how many patients they add.
But until they in a non till they actually call the patient to schedule a visit and we wouldn't really know how fast those patient will be able to come in sometimes you have many patients. They all want to come in the same week.
But there's just not enough manpower to handle so many patients and they will have to reschedule dose patients, adding I will have a better idea probably in Q1 next year once we have more sites up and running.
Yes.
Thank you.
Our next question is from Mark off on Leerink.
Alright and him yes.
Yes.
Hi, This is Matt on for Mark.
We have a question about whether you guys have any more announcements already can't analysis of the phase two data.
Related to this genotype and phenotype of the patients.
But I mean anything in polka multifocal and the different mutations.
The patient that way enrolled in batteries can and.
How are you cannot.
Regarding <unk> and lean which is back end are you tied to match some of the baseline characteristics when it comes to phenotype and genotype.
Safe to or is it a little bit different.
Yes, so Bob let me take that question so regarding the.
Phase II data will we be providing additional data analysis. The answer is yes, so I'm actually presently preparing an abstract for ARVO 2024 that makes in Seattle in May to talk exactly about that to provide those those are genotypic data because we were very surprised to see <unk>.
No DDS lesion growth in five of 12 subjects throughout two years of treatment and we thought maybe it's possible that these kids have more mild mutations in fact, that's not the case. They all have very severe mutations so the finding that they're not converting from the early auto fluorescent lesion type to the atrophic lesion type is actually very profound so we provided providing <unk>.
The genotypic and phenotypic data and a better breakdown of the lesion growth on a subject level basis. So that will be provided at ARVO in terms of paralleling the phase II phase III trial designs. The study designs themselves are essentially identical that is it's a two year study looking at the same endpoint with the same dose five milligrams daily.
And of course, it's the same patient population we've increased the age range from 18 to 24 in the phase II. It was 12 to 18 in the phase III will be 12 to 20 and that was at the behest of principal investigators who are wanting to get their patients and but other than that theres nothing.
No real difference other than the main difference which is in the phase III. These kids will have to have atrophic lesions at baseline that's necessary in order to meet the requirement for the endpoint, which is slowing the growth of atrophic lesions that is what the FDA wants. So you have to start with some measure of atrophic lesions at baseline, whereas in the phase II.
The open label study all of these children. These kids had earlier lesions. They only had the auto fluorescent lesion types and so that's really the big difference between the phase II and the phase III and of course, we're not trying to match the genotypic profiling that we saw in phase II with what we're seeing in phase III, where basically it's eight <unk>.
Commerce as long as they fit our inclusion exclusion criteria without respect to genotype.
Thank you so much.
Thank you for the question.
And next questions, we got E Chen <unk> alright.
Thank you for taking my questions.
My first question is is there so that in the Dragon trial, the lesion size at baseline and smaller them.
At baseline and the phase two and how is that going to impact the data readout.
Yes, so it's important to note as I mentioned earlier in phase two we don't have any atrophic lesions at baseline. So these patients only had auto fluorescent lesions and they were they were varied sizes. One patient has a lesion as low as a small as a one millimeter. Another patient has a auto for us at least as big as 11 millimeters. So theres, a very big size range.
In the auto fluorescent lesion types and of course, we will be presenting that as part of the ARVO abstract and presentation that I spoke earlier about top to bottom up.
In terms of the.
Balancing in the phase III.
The Liza type as I mentioned earlier is actually quite small which is what we want so we look at the mean lesion type at baseline in the phase III trial, and we see in atrophic lesion means.
Mean size of two millimeters square, which is great. So when you're asking are the lesion.
Sizes differ between two studies, yes, because the lesion types are different between the two studies, but in this phase III trial, we are exactly what we are shooting for we want to start with smaller lesions at baseline and quite honestly the smallest detectable leaves us about <unk> <unk> five millimeter. We're at two millimeter and we believe based upon some other trial results from other companies that these smaller.
Lisa types will respond to this type of pharmacotherapy. So that was sort of a long winded way of answering your question, but I hope I got the answer for you.
Thank you.
The decent size at baseline and the Dragon trial is that representative of.
Overall patient population the railroad.
Very tough to say so remember we are a 104 adolescence startup subjects from all over the Globe, China, Europe, North America and other countries. So this is a good representative sampling of all of the genotypes and phenotypes of our manifest in adolescence targets disease.
This is the largest study of its type it's never been done before so if there's any true sort of.
Homer homogeneity of the demographics. This study would tell you what it is there is no. Other study that we can look to and say well we want to match that demographic because that fits best our patient population no one's ever done a long term epidemiological study or natural history study in just star versus these with the exception of Prague Star, where they have a subset of patients that.
We are of the same baseline.
Same aged and lesion characteristics as our patients in the phase II, but in terms of in atrophic lesion type that it would be representative of the startup population I would say we have it because again this is the largest.
A collection of adolescence startups subjects in any investigational trial that I'm aware of.
So.
My bad.
That Pall mall in fact, all studies right now.
Most of those patients came from North America and.
Europe.
Gulf of observational studies, such as <unk>.
Truck stop they are.
Mainly patients from North America and.
And Europe sell so what's and reported out there at publish update.
It's all somewhat genotype I believe.
Thank you and how.
How much slowing of the lesion growth rate and the Dragon trial will allow the company to ask for accelerated approval from the FDA.
Okay.
Oh, sorry.
No Tom please.
So we had discussions with FDA regarding this I think at this moment in the FDA.
Doug.
As I've mentioned this is the first ever study, especially in pediatric Bob <unk> the lesson.
Solid disease.
So the FDA right now.
Asked us to show them the data so right now David.
Not giving too much away.
So I guess that sustained that response from the FDA. So they wanted to see the data subs.
Got it and my last question is if the Phoenix trial.
Has data similar to what has been observed from the phase III Star trial. The later Dragon trial, how competitive do you think <unk> as compared to.
Trucks already approved for triad NGA.
Okay. Thank you I'll take this.
Yeah, absolutely I think it's going to be a game changer I mean, so if we look at the approved drugs for <unk> right now youre, not getting anything better than about 20% treatment effect on slowing lesion growth and youre not getting much of a visual acuity benefit and you have a significant safety risks with an oral therapeutic that achieves the same level of efficacy.
That is a 20% slowing of lesion growth with a very clean systemic safety profile and no potential for adverse.
Thank you very easily be permanent such as the <unk> occlusive retinal vasculitis, it's been documented in rare cases with with the appellate drug when you have that and you're reducing the treatment burden so significantly with an oral once a day I think patients will flock to this oral once a day treatment because it's going to be superior in terms of benefit to the patient in terms of reducing treatment burden and reduced.
Any potential risk to their ocular health and safety. So thats. The one thing. The other thing is that these drugs. The complement inhibitors that have been approved by the appellate drug divert drug. These are anti inflammatory agents. So they atalay address late stage disease, which is driven by inflammation. They will knock those drugs with <unk>.
Not be effective in early stage disease, which is one of our differentiators because theres no inflammation in early stage or early stage Star Guard. So we see there are another potential market opportunity for us because they cannot use their drug effectively and are subjects out of our our drug Kennedy is effectively both of the younger patient population as well as the late onset.
Sort of a maintenance therapy, so I see more of a synergy that I do our competitiveness, but in terms of what would be preferred I think if we achieve the same level of treatment effect with this very clean safety profile of our drug would certainly be a preferred by most ta subjects patients.
Thank you Robert.
I think there's a survey done 3000.
Ophthalmologists and I think over any offset.
Hum.
They say that that would have prescribed.
And at that complement injections for patients.
So it's very although overwhelming a surprising that even had drugs.
G H.
Most ophthalmologists told a prescriber.
Thank you.
Okay.
We also had growth on benchmark.
Hi, good afternoon, and thank you for the informative presentation.
Just one quick financial question, if I may.
The noncash expenses for the quarter do you have an estimate of the DNA and the stock comp.
I'm, sorry say again.
The noncash.
Cash expenses for the quarter.
That's mainly for the Aesop that we grant in Q3.
Okay.
Alright, that's it for me thank you.
Thank you well first thank you for asking that question, yes, we actually.
Even if you look at the income statement.
Looks like we have much higher extension expenses this quarter, but cash wise.
Without adding 2 million <unk>.
Noncash component.
And from that he thought that we grant <unk> quarter.
And also we do have.
We haven't seen more and more and people exercising the warrant from the follow on honestly, we did raise $5 million from the warrants in this quarter. So in fact, our net cash outflow in Q3 with only.
Close to $3 million, so it's not that significant financially cash wise, we're doing pretty well.
Okay.
Okay.
If anyone has any questions. Please raise your hand.
I don't have any written question on the platform here.
So if no other questions. We'll conclude today's presentation. Thank you for your time.