Q3 2019 Earnings Call
Good afternoon, everyone and welcome to evokes Pharmaceuticals third quarter 2019 earnings webcast and conference call.
Today's call is being recorded.
At this time I would like to turn the call over to Barbara Ryan Elecsys Investor Relations Officer. Please begin.
Thank you operator, welcome and thank you for joining up this afternoon for review.
Cynical third quarter.
Opened 19 financial results.
Joining me this afternoon, Robert Board, Chairman, Chief Executive Officer Me like Pharmaceuticals.
Well, he's our chief operating officer.
Dr., Tom Haverty, our Chief Medical Officer, and Greg Weaver, our Chief Financial Officer before we begin I'd like to remind you that any statements made during this call that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act up 1995.
Actual results may differ materially from those indicated by these statements as a result, a very important factors, including those discussed.
Dr Section in our most recent annual report on <unk>.
Okay filed with the Securities Exchange Commission and our other reports filed with the FCC.
Any forward looking statements represent our views as of today November Fab 2019.
A replay of this call will be available on the company's website www Dot E. last pharma dotcom following the call. It now my pleasure to turn call over to Robert War, Chairman and Chief Executive Officer Afimoxifene topical. Thank you Barbara.
Welcome to he likes its third quarter 2019 earnings webcast and conference call.
This was an excellent quarter could you walk in addition to advancing our clinical and scientific programs. We've also strengthened the leadership team with the appointment of Dr., Tom Haverty as our Chief Medical Officer, Tom as a board certified Nephrologist say brings an established track record of successful drug development and R&D leadership from senior executive role.
From companies like Schering Plough, and Mark Thompson consulting with us for most of the past here and we're pleased to having joined our team.
Today will provide an update on our progress in the clinic with our phase two clinical programs that cystic fibrosis am system houses.
As we guided our Cystinosis trial has progressed to a point where without our first important clinical observations doctors Williamson haverty will share the progress and observations with you in a moment.
We will have a steady cadence of additional data and updates as we move to the upcoming quarters. Just this past week the locks team make for scientific presentations on deal like so too at the North American cystic fibrosis conference, including the full results of our Mad study, which reinforce the emerging overall fate.
Verbal Tolerability profile subcutaneous you know like so too.
We have an opportunity to hold and that's the greatest maybe engage the scientific community and to meet with it see out than other potential strategic partners.
The expressed level of interest and support for cystic fibrosis program has really been quite remarkable.
Currently our phase two program consists of two trials one for clinical investigators enrolling patients at sites in Europe in Israel, where today, we have multiple sites open in Israel, and we expect the European sites to open this quarter.
Our second phase two trial focuses on sites, the United States, where today Boston Children's Hospital is open and we're expecting Additionally, U.S. clinical trial sites opened this quarter as well.
Our expansion of our cystic fibrosis program to the U.S. has been made possible in part by the support provided by the cystic fibrosis Foundation and the therapeutic development network.
We're aware that they're available patients who have expressed interest in participating in our trials.
And the extended period of opening this clinical sites will mean that are.
Cystic fibrosis trials will be fully enrolled during the first quarter of 2020.
As a result, we're changing our guidance for top line data in cystic fibrosis to the first half of 2020.
For Phase two program and Cystinosis I'm pleased to report that we're on track to report topline data this quarter.
We've already observed meaningful activity for elect so too in this patient population.
Cystinosis program dose escalate each patient through the three doses studies in the program.
After treatment at each dose level. The safety review committee meets to evaluate safety and Tolerability before patients are escalate until the next tired dose level.
Today, we have completed the first and second doses in the first cohort and after the successful review by the Safety Review Committee, we're now dosing patients with the third and final those were very encouraged I'm pleased to report that the preliminary data show that you feel like so too has been well tolerated and we're already seeing.
Significant reductions in white blood cell cystine levels. The primary measure of efficacy for approved drugs in this indication.
Upon completion of the third and final dose, we will discuss the data with our principal investigator as well as a panel of scientific and clinical experts before reporting our topline data later this quarter.
Later this week, our Helocs team will be participating in kidney week to present, new data on our completed renal impairment study and the share additional preclinical data on the activity of electro too and supporting studies for Cystinosis and other kidney disorders.
During the quarter, we continued to advance our work in ophthalmology as our team achieved an important proof of concept milestone demonstrating that our E.R.S.G. compounds can restore protein production and the API when injected intravitreal, even in an animal model.
Our screening programs continue evaluate opportunities to advance feel like so two for new indications or other novel molecules from our Ers to library.
Fans on luck, we're advancing our screening work to include diseases, such as primary ciliary dyskinesia in the I, we're evaluating osher syndrome, and other disorders of the photo receptors or retinal pigment appeal. So.
We believe that the encouraging result, salt from our ongoing Cystinosis study support expanding our research and the kidney into diseases, such as autosomal dominant polycystic kidney disease, where there's a high prevalence of nonsense mutation patients.
We are the most advanced company.
Tackling the great challenges of developing new therapies for nonsense mutations and there's a high level of interest and enthusiasm in the scientific clinical and business communities for our programs, we remain actively engaged and pursuing strategic business relationships to expand our therapeutic footprint.
And accelerate our progress.
We ended the second quarter of 2019 with 64.9 million in cash and cash equivalents, we are well funded to advance our clinical programs and deliver topline data in cystic fibrosis and Cystinosis advance the screening programs for elect so too and our library of molecules into additional.
Occasions into 2021.
Our talented and highly experienced team is committed to our mission upbringing safe and effective medicines to patients who need them as rapidly as possible.
I'd now like to turn the call over to Dr., Greg Williams, our Chief operating Officer Who'll provide you with an update on our phase two clinical programs.
Thank you Bob.
I'd like to provide you with an update on our phase two programs for helix Hutu in cystic fibrosis and Cystinosis.
As Bob mentioned, we presented the results of our multiple ascending dose for Mad study Realec seemed to have to 20 routine North American cystic fibrosis Conference last week and also had a meeting with our U.S. clinical investigators.
The man study provided us with the opportunity to explore the safety and pharmacokinetics of to alternative dealix into drug concentrations.
Along with ascending doses.
The study results indicated that they were consistent dose proportional increases and C. Max and that you see across the dose range with no accumulation.
And then elimination is primarily renal as parent compound and is essentially complete within 24 hours post dose.
To date.
It looks so too has been generally well tolerated in clinical studies with 105 volunteers exposed and no reported on fees were renal findings.
Rule. These results support our ongoing phase two programs.
As you know RCM phase two program. Currently consists of two trials, one in Europe , and Israel and the second in the U.S.
There's a high level of interest and support for these trials in both the U.S. and globally.
Both of these trials, we're aware that there are available patients who have expressed interest in participating in the extended period for opening clinical trial sites means that our cystic fibrosis trials will be fully enrolled the first quarter 2020 .
[noise] in Europe , and Israel, Professor and Karen MD head of the Division in Pediatrics Children's Hospital adopts a medical center in Israel is the global lead investigator.
Our phase two protocol has been given the high priority ranking by the European Cystic fibrosis Society clinical trial network.
We are actively enrolling patients in Israel and expect European sites to open this quarter.
In the U.S.
Dr. Amit EULAR director be adult cystic fibrosis program, the Boston Children's Hospital, Brigham and Women's Hospital CE Center is the lead investigator.
We're very pleased with the high quality the clinical sites were working with.
Boston Children's hospitals opened for enrollment, we're expecting additional U.S. clinical trial sites to open this quarter as well.
We appreciate the support of CFO .
In advancing our U.S. trial.
We will provide an update at our phase two CF program when we announce our system notices topline results later this quarter.
Regarding our Cystinosis program, we previously reported that our phase one renal impairment study has been completed and this Thursday, we will be presenting the results of that study in the American Society of Nephrology kidney week in Washington DC.
Since most patients with neuropathic cystinosis have real efficiency.
The results of our phase one renal impairment studies have been important in helping us correctly to fund the doses for these patients.
As I reflect on the past year than I've been with the logs. We completed the said mad and renal impairment trials and have now started three phase two trials in multiple countries.
During October 2019, we also completed an interim CMC review meeting with the U.S. food and drug administration.
And we have gained alignment with the agency on our manufacturing formulation and process.
Which we believe will be suitable for expected drug supply needs through completion of our pivotal trials.
I'd like to introduce Dr., Tom heavy or Chief Medical officer to discuss the advances in our work genetic kidney diseases.
Thank you Greg.
Now for passing Cystinosis isn't genetic kidney disease, where patients are lacking transporter persisting and accumulates in the kidney I am pancreas. Among other organs that leads to end stage renal disease, and kidney transplantation and has been treated with sustaining preparations which breakup assisting boats.
Just a gun infosys be were approved on the ability to lower white blood cell 16, So there's a validated biomarker cystinosis, which we can employ and our trial using DLX owed to prepare for access nodes.
And never Patrick Cystinosis, we're pleased to be advancing our phase two clinical trial with Dr., Paul Goodyear Professor in Pediatrics, and Mcgill University, who is serving as our principal investigator the trials evaluating multiple doses of the elect so too, but the primary endpoint of safety and exploratory endpoints that will include white.
Blood cell system levels, our phase two cystinosis problems I fell to two separate cohorts with three escalating doses and three patients per cohort.
Cohort is complete when each patient has escalated through each of the three dosing levels or safety Review Committee recommends halting escalation.
Following the completion of each dose safety review Committee meets to review the patient safety data prior to the installation to the next dose level.
First two doses in the first cohort are complete and the safety Review committee as authorized us to start the final dose in this first cohort which is currently ongoing.
The second 1.0 milligram per kilogram dose level, you elect spoke to is already demonstrating in the preliminary analysis, a statistically significant reduction in white blood cell cystine levels.
Upon completion of the first cohort, we will review data with the principal investigator and conduct a separate review with the panel assistant doses scientific and clinical EQT birds before reporting top line data later this quarter.
We believe the emerging profile if you elect owed to persist analysis is suitable for continued development and we intend to seek regulatory advice when topline results.
Initiating an extension study for patients in the first cohort and to expand the trial to include sites and patients in the United States.
We believe that achievement of proof of concept for you elect to insist analysis will provide a basis for expansion to studies of additional kidney diseases caused by non sense mutations.
One such genetic kidney disease is autosomal dominant polycystic kidney disease for AG PK PD.
The relative common inherited genetic kidney disease occurring in between one and 401 of the thousand patients as the fourth leading cause of end stage renal disease in the United States.
Were 25% of the primary genetic changes that caused 80, PKD or nonsense mutations where premature stop code under the gene leads to a truncated often unstable protein.
I'd like to return the call back to Greg for an update on the portfolio.
Tom.
We continue to expand our research capabilities and are pleased to report the advances of the hit to see a program ongoing in Europe .
Earlier this year, we joined CF consortium to support the collection of cystic fibrosis patients right, we're going to light in the initiative to conduct a prospective clinical trial to evaluate the predictive potential of people working with model.
To date.
It has collected samples from 100 individuals very rare nonsense mutations in the CF TRG.
It's CF will develop organizations from these samples and test the or doing three ILEC so to responsiveness in the laboratory.
We intend to the program is to enroll the individuals and clinical trial to evaluate their cystic fibrosis responses.
We believe this program will continue to expand the applications of working with technology from good drug discovery through the drug approval and treatment process.
We've also continued to develop our pipeline of new indications and our library of novel compounds.
We have completed screening on three of the most active for read through agents in our PR industry novel compound Library.
Dialogue hold global rights and has an extensive patent portfolio with long life on composition of matter. The news for all of these compounds.
We believe there were multiple opportunities to extend our pipeline by advancing these novel molecules in new routes of administration and or by addressing new therapeutic indications.
For example, this quarter, we evaluated the three most prevalent.
D PKD nonsense mutations.
In vitro read through asset and have demonstrated.
Significant substantial levels of read through for Galaxy, two and several library compound.
In developing a new indication demonstrating substantial activity.
In the in vitro mutations specific asset.
First step in our preclinical development toward have ended.
We intend to evaluate additional cellular and work animal models.
PKD.
Positive result advance toward R&D submission.
In our inherited retinal disorder program, where there remains a high unmet medical need and prevalence of nonsense mutations we are conducting feasibility and I'd, enabling studies for Ers you'd library content.
We believe that our intravitreal.
He RSV approach.
Could provide restoration of critical proteins to preserve more restore visual function across the nonsense related inherited retinal disorders landscape.
As we previously reported library compounds have demonstrated dose dependent read through using ever in vitro and say platform and acceptable Intravitreal tolerability.
During the quarter, we achieved an important clinical milestone demonstrating that several of our library compounds successfully restored protein production in an animal model.
We conducted studies in a mouse model with a naturally occurring nonsense mutation in the oversee a two gene which results in the form of albinism presence in human type too.
Okay low transcutaneous optimism.
And this model.
Our 262 X mutation results in a lack of associate to channel protein, which is needed to establish the ph of the organelle that produces pigment the millennial site.
Lots of the functional oversee a two protein results in a lack of pigment and the retinal pigment at the field and the underlying core right.
Multiple belongs he or she compounds have demonstrated an increase in pigment an indication of functional restoration of the oversee a two channel. After a single Intravitreal injection you logs, we are as cheese.
We have used the dose range of 50 to 200 nanograms per ml side, which we believe provides a window for efficacy based on our current tolerability profile.
This outcome demonstrates that ers she compounds can reach inherited retinal disorders relevant to shoot layers beyond the photo receptors.
These data support that he or she compounds, maybe applicable to a wider range of inherited retinal disorders and first anticipated as the compounds can impact so deep in the neurosensory retina, including the retinal pigment feel even toward.
This means the potential suction therapeutic could extend to additional nonsense mediated inherited retinal disorders, including best disease and Choroideremia.
Furthermore, we are encouraged that this is achievable through intravitreal delivery, which provides a global distribution of the compound toward tissues of the pie.
We are pleased you lock Eureste feud library screening is progressing and identifying new indications for the expansion will be like so to potential therapeutic uses and to enable further development of the lead library compounds.
We are actively exploring opportunities to accelerate 100 development through strategic partnerships.
I would now ask Greg Weaver, our Chief Financial Officer to provide a review of our financial results for the third quarter of 2020 .
Thanks, Greg.
The September Thirtyth 2019.
We reported total cash, including cash equivalents marketable securities of $64.9 million, which we believe will fund the company's operations through topline data in cystic fibrosis in Cystinosis.
And into the first quarter of 2021.
The third quarter 2019 change in total cash was $11.4 million.
For the quarter ended September Thirtyth, the company incurred a net loss of 12.9 million or 32 cents per share.
As compared to a net loss of 11.2 million were 32 cents a share for the same period in 2018.
One of our key accomplishments in the third quarter was entering into our agreement with the cystic fibrosis Foundation will provide $1.6 million in funding contributing towards our us ceased to cystic fibrosis thing.
In the third quarter noncash stock compensation expense totaled $3 million was 2.3 million allocated to Gionee and point 7 million to R&D.
Third quarter 2019, R&D expense totaled 6.8 million as compared to 5.4 million for the same period in 2018.
Quarter to quarter R&D expense increase was driven by growth in our phase two clinical activities costs related to renal study the Mad phase one study along with preclinical and CMC operating costs and non cash stock comp.
Gene expense for the third quarter 2019 was 6 million a slight increase from 5.9 million for the same period in 2018.
Moving to the nine month year to date numbers the company incurred a net loss of 39.2 million or a dollar and five cents per share as compared to a net loss of 33.2 million.
Also a dollar five cents per share for the same period in 2018.
The $6 million increase in net loss was driven primarily by the higher R&D expenses.
Non cash stock comp for the nine months of 29 team was 8.6 note.
Was 6.6 million recorded the Gionee and 2.0 million into R&D.
Year to date R&D expenses totaled 20.2 million compared to 14.0 for the same period 2018, an increase of 6.2 million.
The year over year, R&D increase was driven by growth in our multiple phase one phase two clinical trials, along with expanded preclinical operations and non cash stock comp.
Year to date, GE and expense totaled 18.9 million, which was flat with year over year year to date DNA in 2018.
And for modeling purposes total shares outstanding at September Thirtyth, 2019 was 40.0 million shares.
Concludes the financial comments and I'll turn the call back to Bob. Thank you Craig we've accelerated expanded our clinical development efforts to conduct our phase two clinical trials with cystic fibrosis and cystinosis in top sites with leading investigators in the U.S. Europe , Israel in Canada.
We expect to be reporting a steady cadence of clinical results over the coming quarters, including our topline Cystinosis data later this quarter.
We're very pleased that our phase two clinical trial Cystinosis is enrolling patients with the support of non dilutive funding genome, Quebec, Canada preliminary data from this trial are already showing significant biologic activity with substantial reductions of white blood cell sustained levels. We believe these results formed.
The basis of proof concept with implications in a broad number of additional indications and meaningfully de risk other studies and this dose and tranche.
We're pleased that our CF phase two clinical trial protocols receive financial support from the cystic fibrosis Foundation and our protocol has been sanctioned by the therapeutic development network.
We appreciate Dr. Ahmet learn from Boston Children's Hospital, serving as the lead for our trial, the U.S. and Dr. ATM characters from the adoption Medical center, serving as our global lead investigator.
With the opening of sites in cystic fibrosis, we expect that enrollment worker rapidly as patients have already been identified.
We will provide an update on cystic fibrosis enrollment when we report topline Cystinosis data, we expect the CF trials to be fully enrolled in the first quarter of 2020.
We continue to advance our portfolio of novel Ers GE molecules, we believe that several of these compounds demonstrate encouraging levels of read through activity and preliminary tolerability data, which supports their potential therapeutic development.
Anticipate driving progress across the portfolio in both Standalone and partnered programs. We continued to be very active in business development across our portfolio library in a variety of indications and geographies.
This Thursday will be presented the results of our renal impairment study at the American Society of Nephrologist kidney week in Washington DC.
We will also be making presentations and hosting one on ones that the Piper Jaffrey Conference in New York City on December Threerd.
Evercore ISI second Daniel help contacts on December 4th in Boston.
We thank you for joining us on our third quarter 2019 earnings call and look forward to continuing to update you on our progress. Thanks again for attending today's call. Operator, you can now open up the call for questions.
And thank you, ladies and gentlemen, I say reminder, to ask the question you need to press Star one on your telephone to withdraw your question. Please press the pound or hash key please standby, while we compile the acuity roster.
And our first question is from Michelle Gilson with Canaccord. Please go ahead.
Hi, Thank you. Thanks for taking my question in congratulations on the early days are I guess I was hoping you could clarify for us.
You talked about.
Statistically significant reductions in.
T Mobile's white blood cells.
For the first two doses yes.
How should we be thinking about.
Topline data when there was.
Well, David with respect to caused.
Significantly.
Reductions for shows clinically meaningful should we be.
Impairing.
Thank you my boats to pushes near 60 gone target levels under one Mike Mauler should be looking for normalization I guess, Oh, what would you like you as the bar or models that you think would establish access to and yeah.
Let's move to Monotherapies.
Yes. Thank you Michel I'm all turned to my clinical colleagues in a moment to provide some additional comments, but I just wanted to remind everyone jet engine phase two study again cystinosis.
The primary endpoint relates to safety and Tolerability. So an important part of the trial is the completion of the currently ongoing highest dose endpoint after which there's a follow up period of additional safety data. That's collected and then there is a review of the totality of the data.
So when we think of the preclinical data that's supported our move into this indication Michelle we've seen consistent dose response across whether its cellular models animal models in vitro models and once again with three doses will be looking for a dose response I just wanted to.
Clarified that the one point Omega per kilogram dose was the second dose of the two doses that had been administered weather.
Substantial reduction of white blood cell assisting occurred so with the third dose will first be looking for dose response curve.
Now I'll ask Dr. haverty.
To comment in a moment on how we interpret the clinical benefit associated with this and how we evaluate the totality the data, but I would remind everyone that if you have the opportunity to read the proceeds be current package insert it would say that the goal of therapy is too.
Dose escalate patients to a point, where this 16 levels are below that one.
Milligram, perhaps this team make a protein levels. So there is a target level that guided the process be experience.
Dr. Haverty as you think about the totality of the data from phase two.
Can you help set expectations of what will we be talking with expert panel about and how will we interpret selection of dose to take into additional clinical studies.
Sure Bob Thanks, and thanks for the question Michelle Yes, I think the one animal haps 15 per milligram of Whitesell protein is a good bar to try and aim below since that's what.
Mr guided process be have achieved I would also point out that the third cohort will be dose that two milligrams per kilogram and for two weeks. So we will have the opportunity to get.
As improved dose response on dose as well as a duration response and as Bob mentioned, we will.
Joe This data to 16.
Clinical experts in the.
Fourth quarter.
To clarify what.
What you'd be achieved and how to selected those going forward.
Yes.
Okay.
So what do you.
Yes, yes definitely thank you.
So I'm wondering.
If you consider increasing the Joe's given the safety profile demonstrated that are you.
You see a dose response.
And then.
Yes, you are targeting a youre targeting.
Jordan exposures at each dose level and now.
Are you able to reach those targets with what's a good though so that you have been giving patients.
Okay.
Yes, so Michelle remember this Thursday, our team will be presenting a doctor Williams will be presenting the renal impairment study and we know that renal clearance plays an important role in dose selection and remember with Cystinosis patients.
They often experience.
Impairment, so different levels of renal function until the dose has to be adjusted for them.
Dr. Williams do you want to just remind us of how we use animal models to pick those range, we want to explore and how that then shapes. The dosage range that selected for the Cystinosis and the cystic fibrosis drama.
Sure. Thank you Bob.
So.
As we thought about the exposure range that would be appropriate for patients both insist to knows it's as well as in cystic fibrosis, we looked across our translational animal models, where the.
Nonsense mediated genes were spliced into those animals, we looked at the exposure levels that demonstrated efficacy and then we matched those exposure levels.
Our dosage range in patients so with the Cystinosis trial, we're looking at.
Three.
Ascending doses.
With the first dose zero point talk milligram per kilogram, the secondary one milligram per kilogram and the top dose at two milligrams per kilogram.
Recognizing that because these patients have different levels of renal impairment. We are adjusting the dose based on our renal impairment study data and based on their individual BGF ours to achieve the exposures of 47 and a half.
90, and 195 microgram hours per mill.
Meets 47, and a half 95 and.
Microgram hours per mill. So we are maximizing exposure, while maintaining a safety margin. That's acceptable is it possible. We could go higher in future studies or future cohorts, yeah. That's possible, we need to make sure that the drug is well tolerated in patients and we.
We will confirm with some additional safety data as we go forward.
Oh, it's we're now we see from the freight reach.
The rate range to achieve efficacy and that's safe and tolerable dose.
Yes, So I was just going to remind everyone remember when we talk with regulators, they're really looking for us to identify the lowest dose that which one achieves.
The efficacy goals of the treatment thats being developed because it's viewed that.
The lowest effective dose is one where are you still achieved the desire therapeutic outcome.
By minimizing drug exposure of the best safety or Tolerability profile. So.
As Greg pointed out yes, the sad study up to 7.5 milligrams per kilogram single dose exposure five milligrams per kilogram.
Single dose daily exposure highs daily exposure in that study, we're not at those levels, but we are based on our exposure in the animal models in the range, where we're looking for.
Okay efficacy in both indications is that accurate doctor with.
Absolutely Bob Thank you.
Thank you thanks for taking my question.
You bet.
Thank you and ladies and gentlemen, as a reminder to ask a question just press Star then one on your telephone keypad. Our next question is from young zone with Janney. Your line is open.
Hi, Thanks for taking my question. So are the first question is about I'll, just toxicity and a normal audio from that you saw from the M. D study and I wonder how long of a treatment period. After how long of treatment period did you see those adverse event and in the phase two study if you.
I have any patient discontinuation due to similar used would I have a big impact on data analysis.
Thank you are you into the question remember has been 105 individuals that have been exposed to feel like so too.
Across our sad and Mad study and renal impairment and now three patients in the Cystinosis trial, and you're referring to the hearing variation, which I'd ask dr. William to remind us out of the 105 individuals expose today what is the rate at which they were.
Some reports of hearing variation and how does that compare to what might have been associated with the meaningful exercise as I recall, new glycoside. This year reversible bilateral spreads to additional frequencies I'm could you help us understand what was observed in the hearing test to date across our program.
Right. So there were three total healthy volunteers out of 100 spot exposed that experienced shifts in high frequency Audiometry studies.
Most of that occurred out of the normal hearing range they were no.
Clinical symptoms.
The patients had been on drugs for some time.
Great News is that because we were testing extensively.
We sound these shifts in high frequency audiometry. This is frequently associated with or or an analogy is use that this is the dictionary and coal mine.
When we determine these changes then.
We discontinued study drug in the patients were all resolved or trending toward resolution. One study drug was removed. This is clearly these were clearly reversible changes. This is incomplete contrast to what's typically observed with.
Glycoside antibiotics, where those changes or irreversible musical like a solid antibiotics typically.
Results in your reversible and permanent hearing changes so the safety profile that we've observed we feel like so too and our library of yards cheese. Thus far is distinctly different from that of a meaningful at the start of Biopics.
And this safety review committee that meets in the Phase two trials do they evaluate hearing as well as the parameters.
So we are continuing in our phase two program with.
A dedicated audio that stipulate Aerie safety review group.
That assesses patients.
We're dosing.
After each week of dosing and as part of their safety review assessments. That's conducted after each treatment group of patients have been cleared continue with no meaningful changes. That's the same procedure that we follow during our Mad study, where we had regular.
AB safety review.
Formed as well as a R&D SMB. So we've got cheerful expert monitoring.
I Love hearing.
Throughout the study.
And thus far.
Safety profile in our phase two trial has been the drugs been very well tolerated.
With no study drug treatment emergent events reported today.
Okay. So I'm thinking and also full question about them study design of the phase two study.
To the information posted on clinical trials talked about the eight patients in the U.S. will include four patients homozygous, where the G. By 40 shoot that's a mutation, but the other piece would be homozygous patients with.
You do cost one or cost to mutation. So my question is is that the same for the study you and Israel and so the reason for the design is.
Because you want to see different or different.
Treatment outcome in different patient populations.
So you remember when we talk now about our cystic fibrosis trial.
The way that we defined responsive genotypes is by screening in the organized a wide variety of genotypes, where previous research has established that organized responses have shown a high correlation to clinical trial outcomes of both sweat chloride or EFI, one and so the GE five.
For two X. genotype. This is whether its homozygous or heterozygous has shown a nice responsiveness to elect so two in the organized model. So in all of our phase two trials every individual will have GE five four to acts on one or both bills.
So dr. Williams as we think about achieving our full enrollment in the first quarter with enrollment actively ongoing now in Israel with our opening of sites in Europe with Boston Children's Hospital opened for enrollment at additional U.S. sites coming along the trial is not.
Not yet fully enrolled.
Our the Guidances for homozygous heterozygous mix based on the investigators identifying patients who meet the inclusion exclusion criteria are they have fixed ratio.
Right. So we're looking to include up to four Han Homozygote, Chief I for two X and the U.S. and.
Up to four in Europe in Israel as well in terms of heterozygous, we're looking as Bob said at patients with GE front for two Exxon, one LDL and minimally responses.
Deals on the second.
They could be.
They could include a one to wait ex they could include Fivefive.
Three they could involve.
A number of others that are mentally responses.
Our goal is to.
Is to demonstrate to evaluate both safety and efficacy in patients with these nonsense minimally responsive on mutations that are consistent with what we've seen in our nonclinical data.
Did that answer your question you.
I believe so yes, thank you for the answers.
Yeah, and one thing I would just mentioned remember we've talked about being part of the hit CF consortium weather hit CF is of course funded by the European Union and it's done in collaboration with the European Medicines agent I believe the FDA is also consulting.
Where samples from says grosses patients with rare mutations are being collected there'll be tested in the laboratory and then a prospect of trial run to determine how the organized responses. This predicted outcomes in the clinical trial, we're very pleased to hear from hits CF consortium that they've already collected samples from 100 nonsense.
Patients patients for which the developing the organized and he'll Expo two will be.
Be screened.
So we do feel that hit CF is making terrific progress and we look forward to having these identified additional patients.
The European.
Work that they are conducting as well.
Great. Thank you.
Thank you and our next question comes from Ted Tenthoff with Piper Jaffray. Please go ahead.
Great. Thank you very much I wanted to know what next steps where with respect to the ocular program I'm pleased to see all the progress on the.
Other programs too.
Yeah. Thanks, Ted we think that the onto their program really has a tremendous potential since there are large number of individuals with different diseases, where nonsense mutations underlies the underlying disease state remember when we achieve our desired concentration of drug in the target tissue we believe.
We will be unable to read through nonsense mutation found in that target tissue. So establishing a dosage range for Intravitreal administration, we believe will give us the opportunity to address multiple indications. So dr. Snyder would you talk a little bit about our progress to.
Awards are.
Q2.
Staying release formulation for Intravitreal administration.
Sure. Thank you Bob.
Delighted with the emerging data profile of our E. G focused on how your D. and we are pleased to have determined our target does seem levels for IBT or Intravitreal administration.
A key next step is using distant from nation term form our sustained release program assuring that we achieved a long duration injection profile.
So we are aware that today for Intravitreal administration.
Once a month administration, such as I, Leah or Lucentis, originally launched with that as formulation technologies improved that therapies are tending towards.
Once or twice a year as the desired target.
We'd like to establish at least a two week formulation, which would use as the basis for high end the filing and moving into a human studies, but said one of the important milestones what's really the demonstration in the mouse pigment model that are molecules are biologically active.
Matt could you just remind us how does that model inform us on the ability to generate protein.
I appreciate that.
Okay.
Yes, Hi, Ted So this is Matt could area.
And we were really eager to look for a model that had a nonsense mutation in irrelevant tissue that we are targeting.
So at this model allowed us to do test, whether or not functional protein could be made after an intravitreal injection we.
Tested multiple ers cheese, and we are able to see positive responses in those molecules in the model.
So with that nanogram exposure to our next step is to.
Engage with the sustained release partner and develop a sustained release profile. That's at least by monthly and then that would be what we'd go forward with Ryan the filing.
[noise] makes a lot of sun. Thank you somewhat for that thorough update.
Thank you and we have a follow up from the line of Yumes along with Janney. Your line is open.
Hi, Thanks for taking the follow up question. So just wanted to come from when you report topline data from this notice. This study will not only from three patients in the first cohort.
You're correct.
We're going to take our topline data from the first cohort both report topline, but also use that data to engage with the regulatory agencies to look at creating an extension program for the patients in that cohort as well as looking to open up additional sites for the trial here in the U.S., but.
We're going to have our key investigator and clinical expert meeting this quarter and the that'll be the basis of those next steps.
Okay. So does the planned for the second cohort will still to be determined based on your discussion with them the panel.
I think that at this point in time, we're very pleased with the progress we're making and were evaluating is this an opportunity to accelerate the program.
Okay. So then just might be a full question previous question. So do you think you would have to show superior outcome as compared to Cisco and push this to be due to be commercially viable product at this point.
Early to talk about that.
Well when you think about target product profile when a drug is being developed we write a target product profile that describes the clinical outcomes as well as patient reported outcomes that go along with therapeutics. So this is both acceptability of route of administration. So for example.
The subcutaneous self administered dose a frequency and volume that's acceptable to patients we listen to patients as they talk to us about the suitability and acceptance of therapy.
Remember one of the challenges right now in the Cystinosis population.
Is inherent to existing therapy now.
Now also when we talk to both patients who shared some anecdotal observations with US right now as wells with physicians.
Our understanding if theres a belief in the clinical community that restoration of the Cystinosis transporter May result in other clinical benefits than would be found with Cisco to mean, helping to push 15 out of other pathways.
Our desired goal here is to.
Restore the pathway that would typically be present with functioning cystinosis.
I think that one of the key discussions that will come from talking with the Cystinosis experts.
We will be what is the full range of clinical data that will be looking for we definitely believe that the bio marker is an important standpoint and I believe.
Did that answer your question I'm sure Dr. Haverty would have some thoughts to share with you as well.
Yeah, I think that's that's pretty helpful and thank you very much.
Thank you and we have a question from your line of Joel Beatty with Citi. Your line is open.
Hi, guys. This is Sean Egan, calling in for Joel I apologize for my questions already been asked I'm, a little bit late to the call, but have you disclose how many patients were included in 15 with significant 15 reduction and maybe could you also talk about how quickly that reduction was observed and maybe by what magnitude.
Yes, Sean So we'll give full topline results when the first cohort as completed all three doses. So the three patients enrolled in the first cohort.
Dr ones, you want to describe the enrollment of the patients and.
Flow of how the data response will go on this quarter.
Sure so.
The each cohort consists of three patients and there are three doses within each cohort.
First cohort is patients that are 18 years and older. The second cohort includes patients 12 years and older. So.
As each cohort is conducted as the first couple just conducted will conduct a full additional safety follow up before we begin second cohort and in cohort one.
The doses airports funds.
1.0, and then 2.0 builder milligrams per kilogram.
We are dose adjusting based on their individual level of real impairment.
And there is a school safety review conducted between each co each dose group before dose escalation is approved by the safety Review Committee.
When we have the data from the third dose group.
Which is about halfway done now.
We will.
Have they review by a group of.
Clinical cystinosis experts.
We will review those data with the investigator and then we will release topline data on co one which is three patients.
And yes, Sean when we talked about the statistically significant reduction assisting level observed that the second dose the one make per keurig. It was with the three patients in the first cohort.
We will give additional data out as as we release our topline data later this quarter.
Sure I really appreciate that there'll answer and then just as a quick follow up nowadays successfully demonstrated kind of in vitro read through from a number of different compounds in your library and a few different indications maybe talk about how you're prioritizing development each and are there some agents you'd like to partner and others that you'd like to kind of keep an eye off.
Yeah, I think Sean that's a terrific question, what we've done is valuated.
Both kidney disease lung disease in the API and look at it as the ability to either introduce a novel compounds. So for example to work in the I will be with a novel compounds.
With cystic fibrosis and Cystinosis currently being DLX, so too it's an opportunity for us to continue to extend to elect so too. So for example for 80 PKD both via Alexa two and other library compounds have shown activity. So since deal Ekso to further advance, hoping it I envy and 80 PKD as.
Much faster with the Alexa to than it is to complete all the I, Andy enabling studies with a novel compounds. So time for development is an important consideration.
The relative profiles important consideration as well and as you mentioned.
Different strategic partners bring different opportunities to the table. So we're undergoing a process now to make sure that as we move forward to our next trials that we'll be making the right strategic choices as to whether they're novel molecules or continue to extend audio like so too.
Thank you so much appreciate it.
Thank you ladies and gentlemen, this concludes our Q and a session I would like to turn Nicole back to the proper ward for his final remarks.
Thank you carbon and thank you everyone, who joined our call. This evening, we're very pleased with the progress the team continues to make.
We'll look forward to seen you again on our next call remember will be a kidney week. This week and then at Investor conferences, as we move to the five quarters of the year. Thanks, So much for times like.
And with that we thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.