Q3 2019 Earnings Call
Please standby.
Good day, ladies and gentlemen, welcome to the Kodiak Sciences third quarter 2019 business highlights conference call.
He's program is being recorded.
At this time I would like to hand, the conference over to Mr., John Ferguson CFO . Please go ahead Sir.
Thank you for joining Kodiak Sciences third quarter, 29, P. business highlights conference call.
On Borgeson Kodiak, Chief Financial Officer.
Joining me today, our victory cool, Chairman and CEO , and Jason Ehrlich, Chief Medical Officer in Chief Development Officer.
After our prepared remarks, well open the call for acuity [noise].
What portion of this call can be contains a slide presentation that we will refer to during the call. Those following along in the problems we wish to access the slide fortunate because presentation. They do so on the Investor Relations section of our website.
An archive of this webcast will be available.
I'd also like to remind you that remarks made on this call. Today includes forward looking statements about Kodiak more complete description of these and other material risks can be found in Kodiak filings with the Securities and Exchange Commission, including its Form 10-Q , two the quarterly period ended September Thirtyth 2019, which has been filed with the.
Yes, he see today.
Well not undertake any obligation to update probably any forward looking statements were the result, as a result of new information future events or otherwise.
No I'm pleased to turn the call over to Victor pulled off our CEO .
Thanks, John .
Good afternoon, everyone and thank you for joining us this.
This is the first end of quarter business highlights conference call, we got hosted.
Dive right in.
[noise], where a public retina focused ophthalmology medicines development company, we've applied and continue to apply a creative and thoughtful approach to science and medicines design and development, most notably with our anti body vital polymer conjugate platform and our lead acid parasites real one.
Which was built on this platform.
Our objective is to design develop and ultimately commercialize new standard of care.
Best in class medicines for the leading causes of blindness in the developed world, which diseases are driven by the growing demographics of aging hands of diabetes.
We are focused exclusively in ophthalmology and retina and we believe this gives us a distinct advantage retina is highly technical area for medicines that element and there are increasing returns to focus overtime.
On slide four for those of you who did not get watched a live webcast from our October 14th R&D day event. We encourage you to do so and it can still be found on the IR page of our company website over three hours, we took the time.
To introduce the platform with a bit of a deep dive into the underlying philosophy and concepts and to review the data of our K S. Three a one AIDC medicine.
And to provide first line of sight to a registrational path forecasts eye Q3 or one.
And Jason and I together discuss these items with clinical end market experts.
R&D day events being not quite one month ago as you listening to todays update you can see in here the progress we.
We are making at Kodiak and field the acceleration of our efforts and acceleration that has been 10 years into making.
You are on slide four you can see the components of our APC platform.
Where we bring novel anti bodies together with a state of the art phosphorus Colin based biopolymer to form steeply linked biologics that are designed for increased durability and efficacy after intravitreal ophthalmic injection.
We call them, the same where it matters administered in the same way as a biologic in an optically clear solution and formulation and with fast and potent clinical responses in different where it counts importantly, our bio polymer is not dumb math or size, it's a form of macro molecular weight.
Water.
It is a biocon should get with an integrated set of properties and allows us to enhance okcular durability enhance potency enhancing bio availability to the retina enhanced stability and at the same time designing in a rapid systemic clearance. This is truly a niche.
Generation platform to service the pipeline of future retinal medicines.
On slide five you can see the application of our APC platform across this next generation of retinal medicines, including Mano specific agencies like K OSI Threeo, one by specific apc's like our Ks high fiber, one and our new triplet cvcs.
Deeper in our pipeline.
On slide six.
We took a no compromise approach to the design of care side, three or one our lead asset our anti VEGF agents.
We have an industry, leading molecular weight, which drives the durability at 950000 molecular weight versus idea at 115000 molecular weight.
And most of which in our conjugated is really that phosphorus, calling based macro molecular water.
And we achieve this molecular weight with a high formulation strength such that we are dosing five milligrams of product. This allows us to achieve a three and a half ex moeller excess of anti VEGF finding units versus I Leah it's label dose and we have an industry, leading half life, which over time.
Translate into a powerful concentration advantage in the high versus the market at anti VEGF biologics.
Our objective at Kodiak is to develop Capesize real one to demonstrate a meaningfully differentiated profile in each of the four major retinal vascular diseases. The way to think about it is our phase one study is treating treatment naive patients.
Each of the for anti VEGF retinal vascular diseases wedding MD.
Hi, Bentek macular edema, or DMV retinal vein occlusion ARVO and also diabetic retinopathy as a component of DMV.
In the design of the phase one be allows us to generate data that we believe can be predictive of how kansai can perform an indication specific pivotal studies in the same and are very similar patient populations.
And we want to design each pivotal to have primary and secondary endpoints such that if we hit them, we would be clearly differentiated from the pack of existing anti VEGF biologics interviews, namely I Leah Lucentis, the new video view and Avastin.
This group, which dr. whole camp Synthesised at our most recent R&D day as essentially similar medicines traveling in a common pack our medicine Kansai three a one has the potential to be the unique medicine. The unique biologic separate from the pack. Our objective is to run pivotal studies in each made.
Sure of disease, and in which we have a differentiated design and.
In which we have a high probability of technical and regulatory success based on our APC design and our data being generated in our phase one of these studies for example.
In wet AMD.
Our objective and being explored in our dazzle pivotal is to bring nearly all patients to in every three month durability interval versus 40% to 50% with beer view and to bring more than half of patients to every four months or longer between injections.
And for example in DMD, our objective and to be explored and a pivotal study is to have only three loading doses versus five loading doses with a leah and to bring nearly all patients to and every 345 or even six month durability interval.
And in diabetic retinopathy, our objective tends to be explored and pivotal study is to have no loading doses versus five loading doses for I Leah and to explore two three and four times per year dosing.
This could have a very phenomenal public health in back 10 in retinal vein occlusion, our objective and to be explored in Q pivotal studies is to have two loading doses followed by every eight week or longer dosing versus a leah with its once a month regimen.
So what I have discussed thus far is really a repeat in the speedier manner of what we described in the R&D day now I would like to move into today's update.
In the third quarter of 2019 and into the early fourth quarter highlights of our activities at Kodiak have included.
We initiated enrollment in recruitment into our pivotal dazzle clinical trial of KC 301 in patients with treatment naive wedding MD and we're very pleased with the investigator engagement in the Doozy hasn't.
We also presented together with Dr., Charles White cost promising clinical safety.
Efficacy and durability data from the ongoing phase one study of Ks Eye Q3 a one at the American Academy of Ophthalmology written a sub special today on October 11th.
We presented at R&D day event on October 14 for the first time and accelerated development plan and including line of sight to registration for K Aside three a one by way of our video.
More recently and since the R&D day event, we have completed a type of be end of phase and meeting with FDA and to phase II, where we discussed in agreed on.
The recommended clinical Nonclinical can manufacturing activities to support the licensure of KSD, three or one and importantly, the older in number of clinical studies required to support an initial biologics license application delay in RV.
And supplemental delays in what AMC, DMV and D.R. without damaging.
Specifically.
We will require.
Two pivotal studies in ARVO, one in branch train one in central vein to support our initial BLE.
Then.
We will require one pivotal study in wet MD, our dazzle study and one pivotal study in DMD.
Each of which will confirm the other and together form an integrated supplemental BLA filing of both indications.
Diabetic retinopathy without DMD requires an additional pivotal study and.
Likely will drive a further spls.
Consequently, we now intend to initiate at least for US you based pivotal trials in 2020.
One is central ARVO, one in branch ARVO, one in DMD and one NDR. These studies.
Other with our ongoing dazzle study in wet MD will be the basis of our intended de la and Spls submissions.
We now have clarity on a 2022 vision that if successful would result in an initial ft approval of Ks Eye Q3 or one in 2022 for RV show and supplemental BLA submissions in 2022 for wet AMD, DMV and possibly dealer.
That is we now have clarity in line of sight to approval.
Of Ks Eyeq, three or one in all four major anti VEGF indications and the ability to do so in a time and capital efficient manner.
It is really a combination of our continuing clinical data and our regulatory feedback that support our confidence to accelerate our development efforts.
What we really like about our phase one study design is that we're generating data in treatment naive patients in all four of the major anti VEGF indications of retinal vascular disease.
Our data in each indication is supportive of the others in all of them are showing the expected rapid and high magnitude responses.
And we like the consistency, we're seeing across the by now for data cut offs.
If you remember the Srs meeting in July the European meetings that view retina Immaculate Society in September .
In October and now in our adjacent 10-Q here in September we see consistent results all of this with an impressive.
Really differentiated durability profile, even with a limited number of loading doses in the retinal diseases with the highest VEGF drive at his GMI and ARVO.
None of these data.
No one disease and no cohort is in a silo here, we now have supportive data and four of the four major indications and remember each diseases phenotypically different in variable, which makes the fact that the data is directionally supportive with magnitude responses in the expected range and Uh huh.
Highly differentiated durability profile impressive and therefore supportive from our view of a full on pivotal stage development program.
With study is an indication that run in parallel rather than how it has been done historically, which was in series and doing it in parallel has a number of operational regulatory and financial efficiencies, which we plan to take advantage of.
On slide eight.
2022 vision that becomes clear it's a pull forward of all four major anti VEGF retinal diseases into the 2022 calendar, specifically topline data in ARVO to support our initial BLE filing in 2022.
Topline data in wedding, MD dazzle and in DMD in 2022 to support the supplemental BLA.
And topline data NDR without DMD is also possible in 2022, but perhaps in 2023.
As a company then.
By the end of 2022, we hope to have Kansai three on marketed in the us in our view.
We hope to have our spls submitted for when DMD and DMV.
And we hope to have topline data for dealer without damaging.
We also intend to have phase one a one be clinical data for our K OSI fiber one by specific APC and to have a third a b C. In the clinic and we're building our pipeline capabilities.
With the goal to have a steady stream of retina focused on Sundays on an annual basis and supporting our profile as a global high science retina focused company.
On slide nine you can find further detail of our planned efforts and catalysts for 2020.
2021 and 2022.
Do you follow closely to division just articulated.
Our operational objectives, then our clear and we are rolling up our sleeves in order to do that work with the excellence. It deserves at this point I will turn it over to Jason who will now provide more details on the underlying clinical planning.
As well as the next few into our emerging phase one data.
Jason.
Thank you Victor and good afternoon, everyone. That's been an exciting quarter for the Kodiak clinical team and before getting into the updated phase when be data I wanted to take just a moment to thank everybody has contributed our clinical investigators the whole Kodiak team here, our partners and most importantly, the patients who are participating in our clinic.
We'll studies of KSS, we are one.
So as Victor mentioned current Intravitreal anti VEGF medicines for Claire frequent injections in order to achieve the best clinical results. So personally as an ophthalmologist and drug developer I'm really excited about the potential of our APC platform and of cash three a one to address this challenge.
We believe the emerging calcitriol, one phase one be clinical data support meaningfully differentiated clinical profiles of cafeteria, one relative to standard of care in each of the major retinal diseases treated today with the existing anti VEGF therapies.
So looking at Slide 10, then as Victor said were with deepening and accelerating the development program for cancer three a one on the basis of the data and our recent end to phase meeting with FDA.
This was really a very collaborative discussions on the net result of that meetings that we can achieve a potential approval for three or one in the key anti VEGF indications on the basis of the plan described on the slide here. So two pivotal and ARVO for an initial BLA and then one pivotal study each in wet AMD the in DMD for form the basis of a supplement and then.
One additional pivotal study for D.R. without DMV that would be a third supplement beleodaq second supplement.
The information shown on this slide 10 reflects our current thinking as to the duration and the size of these studies now getting these plays going is of course, a big operational lift and we're really pleased so far with the infrastructure that we put in place for our dazzle study and the progress we're making there and so we plan to leverage and expand that to efficiently run. These additional studies in.
Parallel.
So changing gears than to the phase when these data and believe the data update let's move to slide 11.
A few words first about the objectives of the phase when these study.
It's designed to provide a scientific and clinical proof of concept for the safety efficacy and durability of Kansai three a one and the APC platform in patients with the most common retinal diseases treated with anti VEGF, So wed MD DMD AMDR and retinal vein occlusion and we're studying treatment naive patients in the phase one be because we believe this is.
The most representative population that will provide the most confidence in the design of our current and our proposed pivotal studies.
So in the next three slides I'll briefly review to study designs, the retreatment criteria and the baseline characteristics just as a reminder.
So on the next slide slide 12.
In the phase when these studies. So these treatment naive patients with MDD Amir ARVO received three monthly loading doses of Kansai three alone at either the two and a half or five milligram dose levels and then there followed thereafter. The studies open label the patients were randomized to the two different dose levels at a one to three ratio.
After the three initial monthly doses patients are followed an additional retreatments occur according to disease specific protocol specified retreatment criteria.
Now the overall study duration was originally 36 weeks and actually now that we've seen promising safety efficacy and durability, we're extending that treatment and follow up period to 72 weeks were 18 months.
In terms of the study include division, which is measured this change in best corrected visual acuity or PCBA using the standard each drs testing protocol and retinal anatomy, which is measured as change in retinal central sub feel sickness, where CST using optical coherence tomography imaging or HCT. We also seen other images in the study such sourcing and job.
Fee color funds photos and OTN geography.
Turning to slide 13.
These are the retreatment criteria, which are specific to each disease state and we designed these criteria in conjunction with the phase when the investigators and based on the evolving knowledge from previous clinical trials as well as our objective which was to understand the clinical durability of kept by through one in these different patient populations.
The criteria are meant to individualize, the dosing regimen to the patient based on their disease activity vision and retinal anatomy and of course also we want to understand chronic safety. So in the case of wet MD, which is the most chronic of the diseases. Under study. We also kept the maximum retreatment interval at every six months.
In addition to the protocol specified objective criteria. Because this was an early phase study investigators also have the option to retreat at their discretion. If there is significant disease activity present in our opinion that needs treatment, but doesn't meet the other criteria.
On the next slide slide 14.
We see the baseline characteristics of the three different groups.
Again, all these patients are treatment naive and the basin the baseline characteristics or what you would expect for us based.
Treatment naive study population now since we allow patients with vision as good as snellen 2025 to enroll in this study the baseline vision in the wet AMD MGMT groups is in particular very good better than even in some of the recent phase three studies patients are presenting to the retina specialists sooner and with better vision. So it's important to allow these patients in the study.
But better based on vision does affect how much provision improvement as possible due to the so called ceiling effect division can only be so good echoing proof so much the specialty have underlying diseases like AMDR diabetic retinopathy. So these baseline characteristics are important keep in mind, when evaluating data within and across trials, particularly looking back over over.
Trials it was on a long time ago, when baseline vision might have been worse.
So then turning to slide 15.
Just before we get to the latest data maybe just a couple of words about what was presented a month ago at the age of that in the sub specialty day, we observed encouraging safety and efficacy data in the phase Oneb study and I would say really very promising durability data in wet AMD.
Our next generation Intravitreal biologic did bring nearly all patients to a three month the longer dosing interval and that area. We showed that 80% of wedding be treated eyes, and 78% of Dimitri device has been extended to four months or longer without receiving retreatment.
And in DMD as you know this is a pan retinal disease that typically has a high initial treatment burden and we observe that durability benefit following only three initial loading doses.
We also saw promising signs of early signs of improvement in diabetic retinopathy severity and then in retinal vein occlusion that disease, which typically requires monthly therapy to achieve the best results, we observe that over half the patients were extended beyond three months without Ics receding retreatment after only three loading doses and the efficacy through 16 weeks with strong.
And appropriate for anti VEGF across all the diseases and finally safety was quite encouraging with no cases of inter ocular inflammation. After over 300 doses and over 100 patients. So let's start them to look now at the latest data and I'll walk you through this.
It's been about a month since IPO and through November Eightth. These patients each of about one month longer follow up and just this had a high level across all three diseases understudy improvements in vision and retinal anatomy were observed through 20 weeks of patient follow up with stability in RCT envision overtime in the monthly follow of intervals.
First on turn next to slide 16.
The latest data on durability of case, our three a one in wet AMD patients.
No again as Victor mentioned remember that with the current agents in wet AMD only approximately 40% of patients can be maintained on every 12 week, where three month dosing interval over a two year period. That's the best data from the Hakan Harrier Burleson of studies. So the remaining 60% of patients require every other month therapy monthly therapy.
Or even on occasion treatment as often as every two weeks.
So our objective with cash through one in letting the is to do a lot better than that develop a therapy, where the vast majority of patients on every 12 week dosing or better with at least 50% of patients maintained on an every four or five month dosing regimen.
So we present the durability data as swimmer plots. So you can see how long each individual patient was followed for and when they were retreated since the studies ongoing and the patients have variable follow up time based on when they were recruited we think this is a useful and transparent way to review and understand the data.
During the phase one be study we've observed thus far that 83% of the wet AMD patients have reached four months for longer until the first through treatment and actually many patients have not receive their first retreatment until five or even six months. After last loading dose. This intriguing that we're observing the high proportion of phase when new patients about half of them so far apart.
Our reaching or will reach the six month cap without retreatment. After the initial loading doses. So these emerging data underscore the potential of cancer Threea, one and a b C platform to achieve truly long interval dosing with an intra that truly administered therapy.
So now let's look at changes and best correct Division and LCT, Let's turn to the next slide slide 17.
So a visual acuity and retinal anatomy improvements continued to be durable and the follow up data as well. These are data from the 25 wet AMD patients pooled between the two and a half in five milligram dose levels, who reached the week 20 visit prior to the data cutoff date of November eight 2019 remember that area. We presented data through 16 weeks on these patients.
And Thats through week 20.
In the period between week 12, 12, and we 20 that is months one to three after the loading phase the treatment effect is maintained with only a 15.3 micron change in average center some feel sickness on FCC and between week 16, and 28. This change was only 5.7 microns. This is consistent with an extended durability effective case, our three alone.
And compares favorably to the OTC fluctuations observed with the existing anti VEGF agents that are given on shorter dosing intervals.
Similarly, best corrected vision was also generally stable over these intervals consistent with a prolonged duration of effect of case, our three a one as you know Thats correct division tends to fluctuate by small amount on a month to month basis in clinical trials and we see that here you can see the changes all within the standard or the mean error bars as you might expect.
So now turning to slide 18.
In the phase one be study the average retinal thickness or HCT data as reported by our investigators includes the height of pigment fields attachments, where pdbs PD eastern anatomic feature in some patients with let Andy and treatment success. In these patients does not necessarily imply complete flattening of the PPD, but rather eliminating the intermittently.
Retinal fluid, particularly when the PD is very high prior to anti VEGF treatment starting.
Additionally comparison across studies of obesity mean, CST values and mean change values can be difficult because it is often not clear, we're not disclosed and presentations and publications whether the data include or exclude the height of the PD among other reasons.
On this slide the graph showed the best corrected vision and Otcs CST change and the wet AMD be subjects, excluding the two patients that presented with a very high PD at baseline.
More than 500 microns of total CSD.
The best corrected vision and curves are similar in shape to those of the full cohort, but the OGC centers. Some feel thickness values are lower at baseline and over time and the FCM error bars are narrower demonstrating the relative weight those two patients having a small cohort so they pull the overall mean CST value up in the prior slide.
In summary, then these two patients are sort of outliers and baseline fitness, but not in treatment response.
So overall, we're really very pleased with the data out Sali Q2 0 in the wet AMD patients.
So we've been reporting on the patients who are essentially the group recruited into the study first and thus have the longest follow up time the needs of the patients that weve been successively looking at it Srs matching the society in.
And now so we also wanted to show how the rest of the cohort is doing so far because there's other patients in the study so let's move to slide 19.
So when considering the larger group of patients who have data through the first 12 weeks of the ongoing study. We also see nice improvements in vision and retinal anatomy.
So here's 30 to 31 wet AMD patients who have reached 12 weeks of follow up you can see we have 6.6 letters visual acuity improvement from baseline and the 93 micron improvement in HCT.
And then on the next slide.
If you exclude those two patients with a very high PD. So I described previously we can see through 12 weeks an improvement of seven high chart letters and LCT improvement 89, microns down to an average center suffield thickness of 287 microns. So we feel really good about division in the city outcomes were seeing here in response to Catseye through.
So in treatment. So overall what have we learned.
These data collectively demonstrate that in that case I throw one cents a potent anti VEGF effect.
Both on Thats, correct Division improvement and retinal drawing in wet AMD patients the clinical benefit appears in line with existing agents.
Especially when considering differences and baseline characteristics and we're observing substantially longer durability of clinical effect with case I throw one than you might expect with existing agents. So although the phase when these studies open label. We believe these results are representative booked because the patients in the study a randomized two to two dose levels and because the key assessments vision.
The team are measured objectively and in a standardized reproducible manner.
The very high proportion of phase one be wet AMD patients, who have been extended to four or five or even six months without receiving retreatment. Also further supports the design of our ongoing pivotal study Basil in which Kansai Threea. One is administered to treatment naive wet AMD patients on every three four or five month regimen as compared to aflibercept on it.
Every two months regimen, each after three monthly loading doses.
So let's move to slide 21, now and the latest in diabetic macular edema.
So as you might remember in BMD.
Currently approved anti VEGF medicines are labeled for either monthly or every other month dosing. After five months, we loading doses in the National Institute funded DRC, our net collaborative group study of DMD patients almost all patients required six initial monthly loading doses under the DRC our treatment algorithms and a median of nine to 10 doses were administered in the first.
To your therapy for all of the tested agents Aflibercept services and have Atlanta, Bismarck they'll needed about the same number of injections per year.
Our objective with Capex, we are one in DMD is thus twofold first to reduce the number of initiating we're loading doses and then second to extend the treatment interval in the maintenance space to three months and beyond so, let's turn to slide 22, and a swim lane plot for DMD.
So these are the data as of November Eightth.
We have observed at 72% of any treated eyes has been extended to four months or longer after the three loading doses of case by 301 without receiving retreatment with most patients not yet receiving any retreatment, including patients followed for as long as five to seven months after the initiating doses. So.
So personally having worked in the DRD in the field for some time now going back to the original Lucentis phase three studies before there was any intravitreal medicine approved in the us for diabetic eye disease patients I'm really very excited about the potential for case, our three alone based on what we're seeing here to date.
So then turning to slide 23.
The visual acuity in LCT improvements continue to be durable in the follow up data as well. So these are data for the 15 DMD patients through reached the week 20 visit prior to the data cut off in the period between week 12 in week 20 that is one to three months after the loading face the treatment effect is maintained with only a small 19.2 micron.
Change in average CST observed between week 12 of them with 20 in between 16 and 20. This change was only 13.6 microns.
So again this is consistent with the extended durability effective case I throw one and I think it compares very favourably to existing anti VEGF agents, particularly.
With a reduced number of loading doses that were given.
Similarly, that's correct Division also was stable over these intervals consistent with a prolonged duration of effect of case, our three alone.
So now turning to slide 24.
So the somewhat bigger group of patients who have data through the first 12 weeks of the ongoing study results are consistent and encouraging with an improvement in best corrected vision of 7.1 letters and improvement of obesity of 136 microns. So these data again collectively demonstrate the kids that through one has a potent anti VEGF effect in DMD patients.
The clinical benefit appears in line with existing agents and we're observing substantially longer durability of kit with case I throw one than expected from the existing medicines and these results were achieved with fewer loading doses. So these data support a pivotal study design, where kevsat threea one would be given on an every three to six month interval after three loading doses compared to stand.
Third of care Aflibercept on its approved every other month regimen after five loading doses.
So lets turn then to retinal vein occlusion on slide 25.
So our video is a disease, which has higher.
Which has higher levels of intraocular VEGF on average than wedding, MD and GMI and so we would expect the highest treatment frequency here in our phase Oneb study as well, we remember that the since our labeled for monthly dosing and then Moreover, the recent UK study in patients with central ARVO called the Leabo trial demonstrated that less than monthly dosing of aflibercept deficit.
And at or around the business could be associated with loss of maximal treatment effect, both on vision and RCT.
So our objective with case I realized in our view is US also twofold first to reduce the number of loading doses and second to extend the treatment under both the two months where beyond compared to the current standard which is monthly.
So looking to slide 26, the swim lane plot for ARVO.
In our phase one study we've observed thus far that all RV or eyes treated with five milligram kiss everyone has been extended to two months for longer after last loading dose with 50% of patients extended to three months or longer. So I continue to be really encouraged by these data as well.
Let's move to slide 27.
Visual acuity and those UTI improvements continued to be durable in the most recent follow up data on this slide we see the 15 ARVO patients who reached the week 20 visit prior to the data cut off in the period between week 12, and week 20 that is months one to three after the loading phase the treatment effect is maintained with only a nine and a half micron change.
In average center, some feel fitness on FCC and between 12 and 16 midstream is only 21.6 microns consistent with the observation that some patients required and receive retreatment at week 16, eight weeks after the last loading dose.
So Dan we theater consistent with extended durability effective kiss, a three alone and I think it again compares favourably to the existing medicines.
Really best contribution was also stable over these intervals consistent with prolong duration of effect in an average improvement from baseline of 21.3 I chart letters, which is over four I chart lines was observed at week 20.
Looking then to slide 28 here, we have the bigger group of patients with data through week 12, we have 32 patients. So we can see an average vision improvement of 19.8, I tried letters and a 401 micron improvement in OTC thickness really pleased with these data too.
So overall and ARVO, what do we learned these data collectively demonstrate again that across our three alone has a potent anti VEGF effect, both on vision improvement and retinal drying and orbio patients.
The clinical benefit appears in line with existing medicines with substantially longer durability than expected with existing medicines and the effects were achieved with fewer loading doses. So these data would support a pivotal study designs were kept that three to one would be given on every two months or potentially longer interval compared to standard care flip receptive and monthly.
Okay. So that's the latest updates on efficacy and durability across the indications turning to slide 29.
Look at safety.
So on Slide 30, then is the latest update.
The safety profile of case is real and continues to be very encouraging with no intra ocular inflammation or study I okcular serious adverse events reported across now 338 injections given to 116 patients in the phase one a in phase when the program as of November 9th either in single or multiple dose exposure.
The systemic safety profile continues to be consistent with that expected for intravitreal anti VEGF agents and for patients with these diseases and in these age ranges.
Maybe a brief we're here about anti drug antibodies were immunogenicity since that's a topic thats become of maybe more interest in the community lately, we have some more details in the 10-Q and so far it's early data. We've tested 362 samples from the phase one a and B program, representing 103 subjects no patients have shown pre existing anti drug antibodies.
Only four samples from three patients have tested positive those four samples all have very low titers at or below the minimum required assay dilution. So it's a very small number of patients with 80 is to date and a review of the corresponding clinical and safety data for these three subjects did not show the 88 positivity BB correlated with other loss of clinical efficacy.
Vision, LCT or earlier need for retreatment or correlated with any ocular or non ocular safety funding. So although those that are preliminary they provide an additional window into the safety of case I for one.
So thats really a lot of updates on the phase. When these studies are the material I presented today is of course part of the slide presentation that is available on IR website.
Also part of our 10-Q. So just in summary, then im really very pleased with the continued evolution of the durability and the longer term efficacy data and the safety profile, we're seeing with case, a three to one that we're sharing with you today I'm also really pleased with FDA and the phase meeting outcomes and the pivotal study designs that result from those discussions and from the emerging clinical data it.
Gives us confidence to move forward and accelerate the development program towards our very exciting 2022 vision and with that I'll turn it back over to Victor.
Thank you Jason.
In summary, we were very pleased with the business highlights for the third quarter in the first part of the fourth quarter and we now open the floor to questions.
Operator thanks.
Thank you, Sir ladies and gentlemen, if you have a question. Please press star one on your telephone keypad, if you're using any speakerphone. Please make sure your mute button is turned off.
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Once again star one if you have a question, we'll go first and Matthew Harrison Morgan Stanley .
Hi, This is Mac score on for Matthew I was wondering if you can comment on the Capesize CMC activities and how the FDA feedback compares with your current plan. Thank you very much.
Sure. Thanks Max.
At this Victor.
Thanks.
Obviously with the no inflammation in any patient record that we maintain.
Having in the phase one and the one be.
We feel.
Very good about the manufactured quality of the material.
That we've made.
To date.
And we have spent a lot of time and effort.
Some treasure.
To build a manufacturing.
Path that we feel a from a technical standpoint will scale up well.
And.
We.
I think received.
Very positive feedback from FDA kind of on the manufacturing framework for the anti body intermediate for the bio polymer intermediate for the drug substance Biocom target and also for the drug product. Another outcome from our meeting was an agreement that CMC specific meeting with at key next year when we.
So that we're ready for that.
Certainly.
We believe.
That our timelines and the 2022 vision that we articulate also includes our views on requisite timing and activities to service. The initial BLA and then those supplemental delays. So we have spent a lot of time and effort thinking about and executing on our CMC.
Plans.
And they are kind of included under the Hood here into 2020 2 million.
Okay. Thank you very much.
Our next question will come from Gena Wang Barclays.
Hi, This is Peter Virginia, Congratulations on all companies and progress and thanks for taking my questions.
Few from US first on the confirmatory phase three study, which no longer seems to be required could you give us some color enough day feedback and.
It sounded like it was part of an SPL they could each of the I feel like the approval on its own or do both studies have to meet positive to to be required I have a couple of more almost thank you.
The the path that we discussed in.
Agreement with.
From Sta is really an integrated package. So the ARVO dual pivotals with their six month endpoint, which we expect to start let's say mid next year.
We will form the basis of an initial.
Okay submission that stands on its own.
Hum.
We're running the dazzle pivotal in wet AMD currently and we have plans and discuss to structure for again the pivotal that we expect also to start up mid next year.
Neither of those Pivotals will stand on their own.
As part of an ESP la filing rather for wet AMD pivotal dazzle and a new DMD pivotal together will be confirmatory in a way of each other will be submitted as part of an integrated SPD package.
Yes, so Peter I think the you know the.
The key to advancement here is that rather than having to do to redeem these studies.
And to Dan. These studies, we could be one of each one and submit those together as a supplement and get approved in both right and as a result of that we're going to slightly increase the power of those individual studies, that's part of our plan.
And.
At the same time.
That represents.
A powerful cost efficiency.
And time efficiency.
Operational kind of efficiency for the company.
Got it.
Just couple of more I guess, just following up on that.
The increase in size assuming just.
For example are already in the assuming no standard over 12 12 to 13 on the baseline like how much power increase are you gaining with the extra under 50 and do you still have the optionality of expanding patient.
With mass analysis.
Yes, so so.
Thats right here, so as we discussed before the Dazzle study protocol has built into it a masks sample size we assessment.
So that is still the plan I think we would we would anticipate based on some of the.
Other more recent phase three studies that if we wanted to have let's say at least 90% power or even more that sample size would be what we should expect.
For that study.
But the the exact final number will be determined on the basis of that math sample size reassessment when were further on into recruitment.
But the idea I'd say would be that like the study should probably each be at least 90% power from a non inferiority perspective right.
Great. That's that's extremely helpful and last last one from me I think.
Appreciating in a small number of patients and difference in 60 measurement in definition.
Like.
Right when you compare of magnitude of CST reduction to produce season at any any thoughts here.
And thank you very much forgetting congratulations.
Yes, I mean I think.
For instance, if you look at that.
Slightly larger dataset, there that we presented through week 12, where.
And.
For instance, if you take out those two patients with a very high PDF and you look at the average thickness of the rest of like whatever so 287 microns that we 12 so I.
I think that.
Our LCC values are are really appropriate we're getting in that normal range.
Obviously, you know you know how they directly compare to each other outside of a head to head study, where they're done at the same reading center. So that the images are ECLI assessment graded in the same way on.
So I guess the bottom line is we're very happy with where things seem to be netting out on the LCT values on the extent to the retinal drawn.
And I think that overall the data, including the durability.
Efficacy and safety kind of speak on their own as a as an integrated package.
Thank you.
Once again, ladies and gentlemen, please press star one if you have a question next step will go to <unk>.
Yeah.
Hi, Thanks to the increased visibility and the articulation of your path forward.
So two questions first is could you talk a little bit more about the impact of announced clinical trials on cash Brian maybe at a minimum just the timing of 21 any upticks could happen.
And whether for example, it makes sense now or later to find a partner for ex us markets. So I'll pause there before question too.
Thanks Mola.
Well.
Yep.
Our.
Our plans are.
To look for additional capital in the fourth quarter of this year or in the first quarter of next year.
We've had quite a lot of progress in the company over the past couple of months and it's been great to see the increased interest in the company.
Both from the standpoint of.
Investors.
But also.
From the standpoint of I would say potential.
No strategic partners for for the assets in particular with a view towards like ex us partnering.
We've been very thoughtful if you look back over the past 10 years in terms of to build up the company right in terms of.
The decisions in choices, we made from an R&D design standpoint, right because at any point you can make decisions that decrease your future optionality in the R&D side of a company, but we've also been thoughtful from the corporate side in terms of decisions that we've made him that could decrease our future Optionality I think.
As we look at cash burn obviously, we're excited by the potential right in our 2022 vision right as we talked about in terms of.
The efficiencies that come out of the end of phase two meeting and the ability and desire to run our studies more unparalleled right to capture those efficiencies.
But also of course recognized the cash burn required to really do that I think we're very pleased with the growing interest in the company and definitely feel that the capital needed to run the plan in 2020 2021 in 2022 right through approval can be there for the company based on the interest.
That we're seeing I think we don't necessarily believe that we have to raise all the capital at one time and that certainly is not our current plan I think we are looking forward to raising capital like inappropriate traunches right over the next several years starting in Q4 Q1, and we also as you know there's an increasing set of.
Kind of alternative financing kind of.
Approaches that Kodiak as a company with the kind of.
Let's say increasingly de risked assets that we have can turn to right not just necessarily ex us partnering of course, we do on global territorial rights for the product currently so I think the long answer to your question is.
That we think capital as many different types is going to be available to kodiak to make sure that we can properly execute on this kind of accelerating vision for the product in the company and we have our eyes on that and I think will hopefully have more to say over the next three to six months.
Great and then the second question, we've seen 'em up couple of your gene therapy competitors being quite volatile of late.
Anthony had competitor data around your R&D day than a partial clinical hold all done a lawsuit with the Ftn. Another thing started dosing and new cohorts. So my question is given that you have new data updated data, what's your updated perspective on where Ks fax or email one sits relative to the gene therapies.
One of the things I think Thats interesting. This Victor just to give a quick view and I think Jason can can speak speak longer I think and better that we do with Ks high three a one in terms of our durability I think in some way less white space.
There is for more exotic approaches right, whether they're surgical approaches or whether they're sort of earlier gene therapy in place I think as Jason mentioned were quite intrigued to see quite a high percentage of patients capping out at the six month treatment.
And our wedding MD.
And also seeing a number of patients in DMD, where we don't cap right, reaching 456 anything seven months post loading dose.
So the better we do I guess as an intravenous really injected.
Optically clear solution right injected in the same way with an intriguing safety profile.
I guess the question is well why should somebody turned to a very different approach right why wouldn't we want to stay with the tried and true approach the same where it matters for a different where accounts kind of approach and not just for case I have three a one right, but in the context of a broader pipeline.
As our company focused right broadly across retina. So that's one one way to look at it.
From a simple persons point of view I think to dig in more deeply nascent Andy can weigh in terms of what we think some of our thoughts on on gene therapy.
Yes, Victor I think you you articulated it very nicely.
Yes, I think theres.
People are exploring a variety of different types of.
Platforms and approaches because this question of.
How do you get a longer therapeutic effect in the <unk>. This question is really important right.
And so we've seen.
A lot of different types of approaches over time, and and you know the reality is it's a very hard problem. It's a very hard problem to solve a and so you know there's the surgical implants, there's intravitreal approach like our APC platform and there's no gene therapies, either with no concomitant surgery or or intra.
The drill those are all things that are in the clinic now.
And were platform developers here at Kodiak, right and I think we've been thoughtful in patient.
And platforms are tough right.
Yes got the science right. If you have the manufacturing right.
And so I think on the basis of the data that we're seeing we're we're accelerating into a phase three sort of comprehensive program.
Well I think we can do very well in each of those studies that we described.
Which is you know I'd say independent of.
How the competitors May do you know last month versus next month versus overtime I think we're moving ahead as expeditiously and thoughtfully as we can.
And a lot of these other platforms are still quite early and I think again is as Victor said.
You know the better our durability continues to be or is and continues to be I think the less white space for is for the exotic approaches and surgical approaches where the short and long term safety may not be as good as Intravitreal administration right I mean intravitreal.
Injections of turned out to be waste safer than anybody thought they were gonna be 15 years ago. When we started doing them for.
You know these kinds of retinal vascular diseases.
So maybe I'll stop there.
Great. Thanks, a lot and congrats on the progress.
Thanks Paula.
And everyone at this time there no further questions I'd like to hand things back.
Sure.
For any additional or closing remarks.
Thank you well. Thank you very much for joining us today, and we look forward to further progress so with Kodiak. Thanks, so much.
Ladies and gentlemen that does conclude today's conference. Thank you off your participation today you may now disconnect.
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