Eloxx Pharmaceuticals, Inc.
Q3 2018 Earnings Call Transcript

Published: 10 Nov 2018

[Operator:]

Good morning, everyone, and welcome to Eloxx Pharmaceuticals Third Quarter 2018 Earnings Webcast and Conference Call. Today’s call is being recorded. At this time, I would like turn the call over to Barbara Ryan, Eloxx’s Investor Relations Officer. Please begin.

[Barbara Ryan:]

Thank you, Liz. Welcome, and thank you to all of you joining us this morning for a review of Eloxx Pharmaceuticals Third Quarter 2018 Financial Results and Business Update. Joining me this morning are Robert Ward, Chairman and Chief Executive Officer of Eloxx Pharmaceuticals; Dr. Greg Williams, our Chief Operating Officer; David Snow, our Chief Business Officer; Greg Weaver, our Chief Financial Officer; and Dr. Matthew Goddeeris, Senior Principal Scientist. Before we begin, I would 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 of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the Risk Factors section in our most recent annual report on Form 10-K and other reports filed with the Securities and Exchange Commission. Any forward-looking statements represent our views as of today, November 8, 2018, only. A replay of this call will be available on our company website, www.eloxxpharma.com, immediately following the call. I would now like turn the call over to Robert Ward, Chairman and Chief Executive Officer of Eloxx Pharmaceuticals.

[Robert Ward:]

Thank you, Barbara, and welcome to Eloxx Third Quarter 2018 Earnings Webcast and Conference Call. We’re pleased to report that we continued to make substantial progress in growing our company and advancing our lead investigational compound, ELX-02, in cystic fibrosis, cystinosis and advancing our new inherited retinal disease program. We’re pleased to report today that we have received orphan drug designation for ELX-02 in cystic fibrosis from the European Medicines Agency. On October 18, we presented exciting new data at the North American Cystic Fibrosis Conference in Denver, Colorado, which showed that ELX-02 is the first read-through agent to demonstrate dose-responsive increases in CFTR function, and that this correlates with Messenger RNA elevations to levels at or above wild type using highly specific NanoString Technology. In a few moments, Dr. Matt Goddeeris, Eloxx Senior Scientist and a distinguished cell biologist, a rare disease expert, will review these new data with you. This data was very well received by the scientist’s community and key opinion leaders and a stimulated increased interest in our cystic fibrosis program. In the quarter, we also initiated a new program focused on inherited retinal disorders. We’ve advanced several new investigational product candidates from our library into IND-enabling studies and currently available data demonstrates positive activity on nonsense mutations that cause different inherited retinal disorders and a favorable tolerability profile. We believe that these data will support the use of these compounds for intravitreal injection with the potential for development focusing on Usher syndrome, Leber’s congenital amaurosis and other forms of retinitis pigmentosa caused by nonsense mutations. We’re on track to nominate the lead candidate for this ocular program later this year to advance to clinical development. We’re proud to announce today that we have entered into a wide-ranging partnership with the Foundation Fighting Blindness. Their urgent mission is to drive the research that will provide preventions, treatments and cures for the entire spectrum of retinal degenerative diseases. Our partnership with the Foundation Fighting Blindness will include broad scientific engagement supporting the Eloxx ocular portfolio development through scientific consultation, advisory support, clinical protocol reviews and other activities. We are proud to support My Retina Tracker, a registry of patients affected by inherited retinal degenerative diseases, which is designed to accelerate the discovery of treatments and cures. As a national partner, we’re also excited to support the foundation’s programs for educating individuals affected by retinal degenerative disease. We share a common goal with the Foundation Fighting Blindness, and we believe that our partnership may lead to the acceleration of efforts to develop therapies with the potential to improve the lives of patients with high unmet medical needs in ocular disease. As a reminder, our clinical trial application for ELX-02 for cystic fibrosis has been approved by the Federal Agency for Medicines and Health Products in Belgium and our Phase II programs have been given a high priority ranking by the European Cystic Fibrosis Society Clinical Trial Network. We plan to initiate a Phase II clinical trial on cystic fibrosis patients with G542X-CFTR mutation, which is the second most common mutation globally and accounts for about 5% of the cystic fibrosis population. We’re in the process of finalizing our Phase II protocol with investigators to ensure rapid enrollment and completion of this trial, we are on track to report top line data in 2019. During the quarter, Eloxx also participated in Emily’s Entourage scientific symposium with a scientific presentation and more recently the cystic fibrosis research externally-led Patient-Focused Drug Development Conference, or PFDD meeting. At this meeting, the FDA’s Dr. Robert Lynn participated and voiced a commitment to support innovative approaches and new ways to connect more cystic fibrosis patients with new therapies. We believe that the HIT-CF program in Europe advancing the applications of organoids in development of new cystic fibrosis therapeutics represents such an innovative approach and the organoids will play an increasingly important role in the near future. In addition, our IND for ELX-02 in the U.S. for cystinosis is now open. We’re in the process of finalizing our Phase II protocol with investigators to ensure rapid enrollment and completion and on track to report top line data in 2019. As we’ve previously reported, we’ve successfully manufactured a lyophilized dosage form of ELX-02, which is convenient for physicians and patients and can be stored at room temperature. This is a significant milestone towards development of a final commercial drug product. We ended the quarter with $55.3 million in cash and cash equivalents and are well funded to advance our clinical programs, deliver top line data in cystic fibrosis and cystinosis and expand into inherited retinal disorders. I’m highly confident in the talented and experienced team at Eloxx and their ability to accomplish our mission of bringing safe and effective medicines to patients who need them as rapidly as possible and to do that on time and on budget. You should expect we’ll continue to attract and add key talent as part of our commitment to delivering on our clinical and corporate milestones. I’d now like to ask Dr. Goddeeris to discuss highlights from the exciting new ELX-02 data we presented at the North American Cystic Fibrosis Conference in October.

[Matthew Goddeeris:]

Thank you, Bob. As we shared earlier this year, Eloxx is collaborating with the HUB, a nonprofit organization associated with the [indiscernible] University on a series of studies using CF patient derived organoids and a swelling assay, which is broadly used in CF as a complement to the human bronchial epithelial cell model in understanding how different cystic fibrosis mutations respond to ELX-02. At the North American Cystic Fibrosis Conference in Denver on October 18, we shared new data in the organoid assay that demonstrates the reproducibility of the assay and its dependence on CFTR activity. And that the significant cystic fibrosis organoid response to ELX-02 occurs across a range of CFTR activating forskolin concentrations. ELX-02 is the first investigational compound to show these beneficial effects in organoids derived from patients with nonsense mutations. We shared, for the first time, new data that enable a better understanding of the mechanism of action underlying ELX-02’s activity in CF and other forms of nonsense-mediated disease. When essential genes hold a nonsense mutation, the introduced aberrant stop codon not only reduces the production of an essential protein, it also can lead to the target Messenger RNA being degraded. This reduction in Messenger RNA is attributed to nonsense mediated decay, a rapidly emerging science in the field of RNA biology. This double hit, reduced Messenger RNA and inefficient translation leads to dramatic reductions in essential proteins like CFTR. Therefore, patients who have these nonsense mutations often have the highest burden of disease and few, if any, treatment options. Our study was designed to determine if ELX-02, in addition to increasing function of CFTR activity as measured in the swelling assay, would also increase CFTR Messenger RNA levels consistent with the reduction in nonsense mediated decay. In this experiment, we applied NanoString Technology, which tags florescent bar codes to the mRNA of interest to precisely measure changes in CFTR. Our data showed reduced CFTR Messenger RNA in untreated patient organoids when compared to healthy wild-type controls, consistent with previous studies. When treated, ELX-02 demonstrated dose responsive increases in CFTR mRNA in these cystic fibrosis patient-derived organoids restoring them to levels equivalent to or greater than wild type. We observed increased Messenger RNA following ELX-02 across multiple CF nonsense mutations. These data are consistent with an interruption in the nonsense mediated decay process by ELX-02. We are encouraged by the data that showed it is possible to restore the reduced CFTR nonsense mutation mRNA steady-state with ELX-02 to normal levels. After all, ELX-02’s retroactivity depends on an adequate pool of target Messenger RNA, which is used by the cell to make CFTR protein. These Messenger RNA data provides strong support for the substantial increase in CFTR function found in the organoid swelling assay when ELX-02 is administered. We believe that the substantial response observed in the organoid derisks our Phase II clinical trial design focusing on patients with G542X mutations. I would now like to turn the call back over to Bob.

[Robert Ward:]

Thank you Dr. Goddeeris. I’d now like to ask Dr. Greg Williams to give you an update on our two clinical programs for ELX-02 in cystic fibrosis and cystinosis.

[Greg Williams:]

Thank you, Bob. I’m very pleased to have the opportunity to provide you with an update on our development programs for ELX-02 and our pipeline. We have submitted the results for our completed Phase I SAD study in a manuscript, which we expect to be published soon. I’m also pleased to report that we have begun the fifth cohort of the MAD study. As we have previously announced, we are adding additional cohorts through the MAD study to evaluate different drug concentrations. We expect to complete the MAD study and submit the results for scientific presentation or publication. We expect to initiate our Phase II studies and report top line data in 2019. As Bob mentioned earlier, in cystic fibrosis, our clinical trial application has received final approval and ELX-02 has been granted [indiscernible] designation by European Medicines Agency. We plan to initiate Phase II clinical trials in both cystic fibrosis and cystinosis. For cystic fibrosis, we’ll be evaluating changes in sweat chloride at multiple ascending doses of ELX-02, which is consistent with other successful Phase II programs for approved drugs as the traditional biomarker measuring CFTR activity. Our planned Phase II clinical trial in cystic fibrosis will enroll no more than 24 patients with the most prevalent nonsense CFTR mutation, G542X on at least one allele. The protocol calls for multiple increasing doses in order to identify an optimal dose to carry into further development, and the study will be posted on [clintrial.gov]. We expect to report Phase II top line clinical results in cystic fibrosis in 2019. Similarly, in cystinosis, our IND in the U.S. is now open, and the FDA has granted orphan drug designation for ELX-02. We are very pleased to have alignment with the FDA on a focused Phase II clinical trial enrolling six cystinosis patients. In this study, we will be measuring the dose-dependent effect of ELX-02 on cystine levels and white blood cells, the biomarker used in the development of most recently approved drugs for cystinosis. Cystine levels in white blood cells inform on the total cystine burden in the body, and a decrease in these levels may be considered a surrogate marker likely to predict clinical benefit. As you know, cystinosis is a genetic metabolic disease typically diagnosed by the age of 2. The disease is progressive with low life expectancy, and most patients will have a kidney transplant by the age of 20. In cystinosis, data have previously been reported at the world symposium by Dr. Paul Goodyer, which showed that ELX-02 decreases the cystine content in cellular and animal models. He has continued this work and extended his findings to include combination use with cysteamine. We anticipate presentation of this work at a future scientific meeting. In the past month, the scientific team at Eloxx has submitted two additional scientific articles for future publication. In summary, we plan to report the Phase II top line results of ELX-02 on both sweat chloride in cystic fibrosis patients and on white blood cell levels of cystine in cystinosis patients in 2019. As Bob previously mentioned, we will be using the lyophilized dosage form we are now manufacturing in these clinical trials, which is convenient for both patients and physicians and an important accomplishment on the path to final commercial product. Regarding our pipeline, we have 170 compounds in our library and have completed screening on 30 of the most active read-through agents in the series. In the ocular program, we currently have multiple compounds progressing in IND-enabling studies, and our data demonstrated positive activity on nonsense mutations in inherited retinal disorders. These data show a favorable profile for these drug candidates, and we are on track to select one of these candidates as our lead compound for clinical development in inherited retinal disease this year. We are particularly pleased with the emerging tolerability profile, which has preserved the electroretinogram wave forms at concentrations, where aminoglycosides commonly show wave attenuation or ablation. With all of these compounds, Eloxx holds global rights and has an extensive patent portfolio with long life on composition of matter and use. I look forward to keeping you appraised of our continued progress this year and next as we complete the MAD study and report top line results from our 2 Phase II studies for ELX-02 in cystic fibrosis and cystinosis in 2019. I’d now like to turn the call back over to Bob.

[Robert Ward:]

Thank you, Greg. I’d now like to ask Greg Weaver, our Chief Financial Officer, to provide you with a review of our financial results for the third quarter and for the first nine months of 2018.

[Greg Weaver:]

Thank you, Bob. For the three months ended September 30, 2018, the company reported a loss of $11.2 million or $0.32 per share compared to $4 million for the three-month period ended September 30, 2017, or $1.15 per share. The operating loss included $2.7 million of noncash stock-based compensation. Our operating use of cash in the third quarter of 2018 was $8.1 million. For the nine months ended September 30, 2018, the company reported a loss of $33.2 million, or $1.05 per share, compared to a net loss of $10.6 million for the nine months ended September 30, 2017, or $2.92 per share. The operating loss for the nine months of 2018 included $9.6 million of noncash stock-based compensation. Our operating use of cash for the first nine months of 2018 was $22.3 million. R&D expenses were $5.4 million for the three months ended September 30, 2018, compared to $3.3 million in the prior year, an increase of $2.1 million. R&D expenses were $14 million for the nine months ended September 30, 2018, as compared to $8.2 million for the nine months ended October 30, 2017, an increase of $5.8 million. Our R&D costs have increased in 2018 to support clinical activities for ELX-02 in cystic fibrosis and cystinosis along with increased preclinical and CMC costs and investing in our IND-enabling studies for the inherited retinal disease program. Our G&A expenses were $5.9 million for the three months ended September 30, compared to $0.7 million for the three months ended September 30, 2017, an increase of $5.2 million. For the nine months ended September 30, 2018, expenses were $18.9 million compared to $1.6 million for the same period a year ago, an increase of $17.3 million. The increase in G&A were primarily related to an increase in headcount and salaries, other personnel-related costs and professional service fees. G&A expenses have increased as we build our organization and capabilities and add additional headcount. As of September 30, we had cash and equivalents of $55.3 million. We expect that our current cash is sufficient to fund operations to 2020 and to top line data for the Phase II trials for our lead investigational product, ELX-02, in cystic fibrosis and cystinosis. And for your modeling, total shares outstanding as of September 30, 2018 was 35.1 million shares. I’ll now turn the call back over to Bob.

[Robert Ward:]

Thank you, Greg. It’s both a busy and exciting time at Eloxx. We have the team in place to accomplish our goals on time, on budget and deliver important new medicines for the patients that need them. We’re pleased that our CTA in Belgium for cystic fibrosis is approved and that ELX has been granted orphan drug designation by EMA. Our IND for the U.S. on cystinosis is open, and the FDA has also granted ELX-02 orphan drug designation. We expect to initiate Phase II trials of these indications, and we’re are on track to report top line data in the new year. We remain very encouraged as ELX-02 is the only read-through agent to have demonstrated substantial activity in cystic fibrosis patient-derived organoids bearing nonsense mutations. We believe the consistent positive data meaningfully derisk our planned Phase II studies. We’re on track for top line data from our planned studies in both cystic fibrosis and cystinosis. We’re pleased to have initiated a new program focusing on inherited retinal diseases and with the emerging favorable tolerability profile demonstrated by several compounds from our library. We’re gratified to be partnering with the Foundation Fighting Blindness, and we expect to advance a novel molecule towards ocular clinical development this year. Later this month, we’ll be participating in ISI’s [Healthconnex] Conference as well as the Piper Jaffray Health Care Conference. On December 5, we’ll be at the Citi Global Healthcare Conference. We want to thank you for joining us on our third quarter earnings call, and we look forward to continuing to update on our progress. Operator, you may now open up the call for questions.

[Operator:]

[Operator Instructions] Our first question comes from Joel Beatty with Citi. Your line is now open.

[Shawn Egan:]

Good morning. This is Shawn, calling in for Joel. Thank you for taking my question. Can you talk a bit about how big the nonsense mutation populations are in the inherited retinal disorder populations you’re pursuing? And maybe also [indiscernible] to understand why your compound will have a differential safety profile compared to other aminoglycosides in ocular indications?

[Robert Ward:]

Sure, Shawn. Thanks for joining us today. There are 300 inherited retinal diseases which have a genetic component. So across those different diseases, in some cases, as many as 40% of the patients may have nonsense mutations as the primary mutation, and in other inherited disorders, it’s the more typical 10% to 15% of the patient population. Now remember, of those 300 diseases, that means that’s the diagnosis. Each of those diseases may have multiple proteins or different mutations. So for example, in LCA, where often people talk about RPE65 and its essential role in the ability of the retina to absorb light, the reason why a gene therapy is a attractive proposition, that Spark has brought forth, is because that restores the gene regardless of the underlying mutation. However, there are a subset of patients where the underlying defect is actually nonsense mutation. So by enabling read-through of the protein, those patients may have an option of whether they would choose to go for gene therapy or whether they would look at for infrequent intravitreal injection, much like Lucentis or Eylea in intraocular injections. Now remember, the molecules we’re talking about are novel molecules. So when Dr. [indiscernible] developed the molecules, the screening approach is that the binding site on the ribosome had been identified based on crystallization worked some time ago. And so it’s the disassembled reassembled groups and put active constituents in the structure that had not been naturally occurring. They were screened for their ability to – on the human cytoplasmic ribosome enable read-through while having reduced inhibition on the mitochondrial ribosome as well as the molecules we’re talking about have little or no activity in the bacterial ribosome. So for aminoglycosides themselves, in the eye, it’s none that they can be associated with retinal bleaching or with changes in the electroretinogram. Now these are waveforms that just measure activity of cells in the retina and it’s known that at certain doses the waveforms are either halted or reduced in amplitude suggesting that there’s interference with the neurons of the eye. So when we screen for safety, we perform the assay. We look for retinal whitening. We look for changes with the electroretinogram. And we see a profile that’s really quite different with no observations of retinal bleaching and the dosage range that we’ve looked at. Where aminoglycosides show alterations in waveform, we do not see the changes in waveform. Now that could be attributed to the fact that our molecules are selective for the cytoplasmic ribosome with reduced inhibition on mitochondrial ribosome. Does that help, Shawn?

[Shawn Egan:]

Yes, that’s very interesting. And maybe as a brief follow-up. Can you talk a bit on the things you’ve learned in both your cystic fibrosis and cystinosis studies so far? Do they give you confidence in these additional ocular indications?

[Robert Ward:]

Yes, remember when you think about read-through, how do you establish that the drug is at sufficient – it’s the question of tissue for a sufficient period of time to restore protein production. So for example, in cystic fibrosis, where we look at the organized – now remember these are stem cells from individual patients grown in culture. And when stimulated with forskolin, a drug that restores transporter function allows them to transport fluid and they swell. Well, part of the understanding underneath that is their sufficient Messenger RNA to enable protein production. Now a second question is in the individual patients, what gives you confidence? In drug development, we do a separate set of experiments on whole animals that ask what drug concentration that’s achieved in specific tissues based on subcu injections. So we look to see do our animal studies support doing subcu inject, where in the dosage range where our cellular study say there’s a concentration of which the dose has activity. So today, I think we’re comfortable that the dosage range that we believe will be efficacious in cystinosis that we’ve completed the range of studies to enable that dosage range. And in cystic fibrosis, we believe that we’ll cover the dosage range of activity on completion of our MAD study. So we’ll be able to work through dose ranging studies that cover the expected range of activity. Does that make sense, Shawn?

[Shawn Egan:]

Absolutely.

[Operator:]

Our next question comes from Edward Nash with SunTrust Robinson Humphrey. Your line is now open.

[Frank Atkins:]

Hey, good morning. This is Frank, on for Edward. Congratulations on the progress. I have three questions. My first one is, can you tell us about the reason for adding additional cohorts in the MAD study?

[Robert Ward:]

Sure, Frank. When you think of pivotal trial design, when you go to Phase III, to be a pivotal trial, the drug has to be produced from the site of manufacturing that you’re expect of commercial supply. And it has to have been made in a batch that’s at least 20% of your expected commercial scale. So that was why we were talking about having lyophilized drug product and why that’s such an important component of doing a pivotal trial. The second piece on a pivotal trial is you want to make sure that you pick the right dose and that the way the drug is being administered optimizes the overall safety and tolerability profile. So the time to work out the dosing schedule, the form of the drug is during this Phase I, Part B multiple ascending dose study. So we’ve added some cohorts to look at different drug concentrations, because we believe that we understand that there’s an optimal concentration for injection that provides the most favorable tolerability profile and we’re looking to confirm that. So when we started our pivotal trial that we’re able to say this is the dose we want to study and this is the volume of injection and the concentration range. So we want to answer all those questions in our MAD study before we start the pivotal trials. Now keep in mind, we have streamlined these trials. When you think of the speed with which Galapagos finished their Spiro 1, Spiro 2 trials, they were started and completed in a year. And their trial design allowed within patient escalation. So we think that those are very efficient trial designs. And so we’ve been working in parallel to ensure that we have Phase II study designs that answer the important questions that the investigators are comfortable that the amount of assessments is appropriate and we’re looking at the right endpoints. But that also we can recruit and complete them. So that’s where we’re comfortable with our guidance of top line data in 2019 because we believe our efficient trial design allows us to work through these questions in our MAD study to make sure we go to the pivotal with the right dose and concentration. Does that make sense?

[Frank Atkins:]

Yes, that’s very helpful. And my second question is on the Phase II study you planned in 2019. And – so just based on your preclinical study, and also the data from organoids, can you help us to frame in terms of what percent of reduction in the – sweat chloride are you expecting? And also I remember you talked – you proved submission that you measured FEV not as a primary endpoint but probably as a secondary endpoint. And also what’s your expectation? I know that given the trial size, it’s probably not powered to show statistical significance, but can you also give us some expectations? And so what are you expecting in regard to the numerical reduction?

[Robert Ward:]

Sure. And I think that’s a really terrific question. Because we internally in designing the trial look at what has been demonstrated in previous trials and how is that a guide for our development. So we look at the KALYDECO trials. Remember sweat chloride is really the endpoint that many of the key opinion leaders have told us they have a strongest confidence of picking that as the go, no-go to pivotal trial, because Phase II trials are smaller than Phase III. And you’re right, in Phase III, it’s a population assessment of a treatment group versus a control group where we look at the average change in lung function and look at it for difference between the two groups. Because in Phase II these are smaller trials, we expect to enroll no more than 24 patients in our Phase II program. Sweat chloride is still the type of measure where you can get a healthy statistical lead on it. When we look at the KALYDECO trial, we know that at lower doses, when there’s a 10 milliequivalent change in sweat chloride, then that’s seen as a drug that has biologic activity. But if you think back to the way the KALYDECO data was presented, it showed that patients moved back into the range of "normal sweat chloride" and that was the 55 – approximately $55 milliequivalent change. We’re looking for the same sort of benchmark range. In dose escalation in the patient population, we expect that the first dose that we are looking for signs of biologic activity, and then we’re going to look to identify the dose at which we move sweat chloride back into the range where we think it’s the clinically significant values that you see and "the normal population." Now, from an FEV1 perspective, of course, we’ll be measuring FEV1, but because it’s a small trial, it’s more likely that it’s discussed in terms of individual patients than it is based on population. Because that population assessment is what the Phase III trial is about. Now the reason why we feel that our Phase II programs are derisked is that in cystic fibrosis today the organoid response is being used in Europe to enable reimbursement for currently approved drugs for patients that show an organoid response. So we see in the G542X population or the focus of our Phase II program that we’ve had a substantial organoid response in previous studies with other manufacturer’s drugs. The amount of FEV1 response in clinical trials is thought to be proportionate to the size of the FIS response in organoids. We’ve seen a pronounced FIS response and that gives us confidence that it’s a drug that we would expect to show significant activity in our Phase II trial. So it’s both what is the genotype we’d focus in on, but also are we seeing a response that based on historical data would suggest clinical activity. Now again on the cystinosis side, really Dr. Goodyer’s work in both the knockout mouse model and on the fiberglass with cystinosis have shown that we’ve been able to achieve a 30% reduction in cystine levels in the livers of the intact animals and also reduced cystine in the fiberglass model. And we expect that the dosage range that it took to cause those changes falls within the dose escalation range. And so those are the preclinical endpoints that give us confidence on our upcoming clinical trials.

[Frank Atkins:]

If I may, for last question. So in your presentation, you mentioned there are four ocular indications on the slides. And – can you just tell us like how you’re going to prioritize among those 4 indications? And the lead compound you’re going to choose, is it going to be one of those four indications?

[Robert Ward:]

Yes, so again – and here we’re talking about inherited retinal disorders accessible through intravitreal injection. As I mentioned earlier, it’s achieving the right concentration of drug in the tissue over the right period of time. When that occurs, we would anticipate that for nonsense mutations at that tissue location, we can enable read-through. So we look across the range of disorders to ask, is there a patient population that’s large enough to design a clinical trial? Are there endpoints that are suitable for Phase II dose ranging? As well as an example where the agency has accepted an endpoint as the point of registration. So if you think of LCNA, because of Sparks pioneering work, we know that for visual field over one- or two-year period of time, that, that’s an acceptable endpoint. Because if you think of dose ranging, we want a dose ranging endpoint that allows us to take different doses and have a physiologic measure of response. Some monitoring visual field over a long period of time would not be ideal for dose ranging. So as we look across the indications, it’s activity of the drug, confidence we can achieve the right tissue concentration and then what do we know about development path. How can we make sure that what be design for Phase II, we have an endpoint that’s measurable that could tell us why one dose would be different than another. So that dose would be the criteria we use for prioritizing.

[Frank Atkins:]

I appreciate taking the question. Thanks again.

[Operator:]

Our next question comes from Arlinda Lee with Canaccord. Your line is now open.

[Ben Shim:]

Good morning. It’s Ben Shim, in for Arlinda. And thanks for taking our questions. Bob, maybe you can help us understand a little bit about the additional legwork that is going to lead up to the initiation of the Phase II trial in cystic fibrosis? And can you tell us maybe what the expected duration of treatment will be? And maybe what age groups these 24 patients will be? As well as maybe a little bit more light on the timing of the start. And that probably ducktails, sort of, the first question.

[Robert Ward:]

Sure, Ben. When we develop drugs in rare disease, whether it’s cystinosis or cystic fibrosis, intervening early in the patient’s life would be our desired goal. But in drug development, if you think of the vertex portfolio, just this year, the youngest age group was approved for drugs that were approved for clinical use many years ago. Because in drug development, we’re always asked to study an older patient population to establish efficacy and safety before moving to younger groups. And this is just a way for us to work with regulators and ensure that when we’re working with the youngest patients that we have the clearest idea of the overall profile of drugs. So in both of these indications, we’ll be working with older patient populations first. When you think of the cystic fibrosis, we anticipate will be the only drug program that’s actively recruiting patients at the genotypes that we look for right now, the ELX-02 is the first read-through agent to demonstrate activity in the organoids. We’re very encouraged by this because from our understanding view, drugs that have failed to show response in organoids have later failed to show activity in the clinic. So we’re very pleased to see an activity profile that’s encouraging us to move forward. And because we’ll be the only company recruiting, we anticipate that we’ll be able to enroll patients at a rapid clip. Now fortunately, cystic fibrosis is a very sophisticated field, and really the Cystic Fibrosis Foundation here in the U.S. and also in Europe deserves a great deal of credit for patients knowing their sequence and being enrolled in patient registries and both the clinical trial network in Europe and here in the U.S. are coordinated with those patient advocacy groups. And so investigators who’ve worked in the disease state are available and investigators who are aware of patients that could be eligible are accessible as well. So those are all reasons to point to rapid recruitment. Cystinosis, the field has not had a molecular product brought forth previously. So McGill University is leading the charge with a program that’s enabling patients to be sequenced, so that as we move forward with the trial looking for patients where the disease has a nonsense mutation, those sequences are available. But it’s a field that’s still emerging as compared to cystic fibrosis. And again if you think across the retinal disorders, certainly, Usher syndrome is an area where strong patient advocacy and a high amount of sequencing means that the molecular basis of the disease is well understood. Other areas of retinitis pigmentosa with some of the genetic basis is still being explored. So we want to pick areas to work where being able to identify qualified investigators and make patients aware of the trial and get enrollment moving forward is viable. And so we believe that whether it’s Foundation Fighting Blindness in the ocular disorder who has worked to be such great partner and has a patient registry or the work of the Cystic Fibrosis Foundation here in the U.S., we believe patient advocacy groups are critical for success in both these cases.

[Ben Shim:]

That’s very helpful. Thank you very much.

[Operator:]

I’m showing no further questions in queue at this time. I’d like to turn the call back to Mr. Ward for closing remarks.

[Robert Ward:]

Thank you, Liz, for hosting, and I appreciate the questions on the portfolio. This is a fantastic year for Eloxx as we build a team and now expand into a new therapeutic area. We think the promise of read-through has never been higher, and we’re delighted with new dose response data showing the Messenger RNA biology as well. So thank you, everyone, for joining us, and we look forward to talking with you on our next quarter’s call. That would conclude our call for today.

[Operator:]

Ladies and gentlemen, thank you for your participation in today’s conference. This concludes the program, and you may now disconnect. Everyone, have a great day.