Q4 2023 Design Therapeutics Inc Earnings Call
Participants
Sean Jeffries; COO; Design Therapeutics, Inc.
Pratik Shah; Co-Founder, President, and Chairperson; Design Therapeutics, Inc.
Presentation
Operator
And welcome to design's conference call at this time. All participants are in a listen only. There will be a question and answer session after that prepared be advised that this call is being recorded at the company's request. I would now like to turn the call over to Dr. Sean Jeffries, Chief Operating Officer of design Therapeutics.
Sean Jeffries
Yes, welcome, and thank you for joining us today. Earlier we issued a press release outlining our fourth quarter and full year 2023 financial results and updates across our portfolio of gene tech, small molecule genomic medicines. The slides that we'll be using today during today's call will be available along with the recording of this call in the Investors section of our website at design team. I'm Sean Jefferies, Chief Operating Officer of design; and I'm joined today on the call by our Chairman and CEO, Dr. Pratik Shah.
Pratik Shah
During this call, we will use forward-looking statements related to our current expectations and plans, including our program development plans, which are subject to risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the Risk Factors section of our most recently filed Form 10 K. These statements represent our views as of this call and should not be relied upon as representing our views as of any date in the future. We take no obligation to publicly update any forward-looking statements. With that, I'd like to turn the call over to Dr. Shah.
Thank you, Dr. Jefferies, and good afternoon, everyone. I'm excited to present design Therapeutics' First significant update for 2020 for what makes this company unique and compelling is that we have discovered a new class of small molecules that are designed to dial up or dial down the expression of an individual gene in the gene. When you think about the role of individual genes in disease, there are many monogenic disorders where the single gene that causes the disease is well established. Our vision is to develop small molecules that can provide a restorative therapy and work with the patient's natural genome to help cells. You read the genes in a manner that restore cellular health.
Despite the presence of the mutations, we are working on at least four major such disorders, Friedreich's ataxia, Fuchs, endothelial, corneal dystrophy, Huntington's disease and myotonic dystrophy. Each of the programs we are pursuing in these areas have the potential to be first in class or best in class and protect Sean, I serve as the CEO. I was previously Chairman of synthetics, which is now part of Sanofi as a result of a $2.5 billion acquisition. And prior to that, I was CEO of Auspex Pharmaceuticals, which was acquired for $3.5 billion. There, we had discovered and developed osteo, which is now doing over $1 billion in annual revenue.
And I'm joined by an accomplished and capable leadership team and design, including Dr. Sean Jeffries, our Chief Operating Officer, and Dr. Jae Kim, our Chief Medical Officer designs, genomic medicine platform has the potential to surpass competing modalities like gene editing and gene therapy for the treatment of these diseases. In addition, we have a five year operating runway, which enables us to generate clinical proof of concept on up to four programs. Success in any one of these programs has the potential to generate enormous value for patients and shareholders. Each of our programs is pursuing the treatment of monogenic diseases where the single gene root cause is known and our therapeutic strategies to restore the normal gene expression state of this known single gene driver, each of our programs has a first or best in class profile, which has highly differentiating features.
Each of these are substantial market opportunities. Friedreich's ataxia or FA is a debilitating neuromuscular disorder with hypertrophic cardiomyopathy is the primary cause of death is caused by a GA. repeat mutation in the frataxin gene, which is broadly expressed in the body. The goal of our genomic medicine is to increase levels of endogenous frataxin and address the monogenic cause of FA. We will address the background in greater detail later in the presentation, we had taken our lead molecule DT. two one six for Friedreich's ataxia into clinical trials in 2022 and 23 and confirmed that DT. 2.6 can increase the level of frataxin RNA expression in patients with FX.
We also learned about limitations to the prior formulation in human studies. Today, we would like to announce a new drug product using the same DT. two and six drug substance. As before, we refer to this new drug product as DT. two N. six P. two, which we believe has properties that resolve these prior barriers to progressing BT. two and six further into development. The market opportunity for a systemic therapy that can restore endogenous frataxin levels remains large and unaffected by progress by others in the field. The prior DT. 206 drug product had a rapid elimination from plasma during a period called the alpha phase and its exposure profile. And therefore, drug levels in the plasma were low after only a few hours.
The orange curve shows the pharmacokinetics of the prior DT. two and six drug product in nonhuman primates in green is the PK of DT. two and 62, which has a shorter alpha phase and a more rapid transition to the beta phase and therefore, a substantial increase in drug levels over a much longer period of time. Due to this increase in exposure, lower levels of administered drug are needed to achieve these desired profile. In addition, a favorable injection-site reaction profile had has been seen with the new drug product in nonclinical studies. With this new advance, we are back on a path to continue further development of DT. two and six for patients with FX. In the time since our last update, we have also advanced the gene tech platform and have refined our strategy and priorities for the programs.
Our FACT program data have now been reviewed by the FDA, resulting in an IND cleared to proceed. As a result, we plan to initiate Phase one development for DT. one six eight this year. We have also decided to conduct an observational study in patients with SCCD. prior to conducting an investigational drug treatment trial patients. We are also announcing for the first time, our Huntington's disease program, where we have identified small molecule candidates that exhibit allele selective reduction of mutant Huntington expression considered an ideal, although elusive profile for molecules that could be reasonably advanced as systemically administered and widely distributing compounds.
Similarly, we have identified compounds exhibiting allele, selective inhibition of mutant DMPK, which is the root cause of myotonic dystrophy with what we believe are best in class foci reduction and splicing restoration data. We aim to advance both HD. and DM. one programs declared development candidate, gene editing and gene therapy have understandably captured the imagination of humankind ever. Since we learned that mutations in single genes cause disease, there has been a desire to edit the genome in some fashion to restore normal cellular health. Other approaches have also emerged that tried to get at the root cause of monogenic diseases.
However, if gene tech molecules work in patients, that would be little doubt that they represent the best option in genomic medicine since Genentech molecules from systemically administered can distribute widely to a broad set of tissues into target cells broadly to affect the desired outcome without altering a patient's natural genome. Furthermore, investments into new platform companies often suffer from frequent rounds of dilution due to the necessary high R&D burn rates that often require investors that time their investment decisions with great care designs, approaches more cost effective, making an investment decision for a longer horizon, potentially quite attractive.
The advantage of gene tech molecules become more apparent when you consider how much smaller these molecules are than those of competing modalities, which further explains the broad distribution properties also by restoring endogenous gene expression like in FA, the gene products are entirely normal And under normal physiologic control. The mechanism of action of these gene type molecules, which drive these remarkable observations are shown in this animation that I'll walk you through. First, we start with FX. Fa is caused by low levels of frataxin, which is a protein that's systemically expressed in the body. So if you look inside the cell and inside the nucleus.
The frataxin gene has a GA. repeat expansion shown in red, which causes the RNA polymerase to slow down through this region and produce low levels of frataxin protein mRNA and therefore, low levels of Express translated protein. And that's what drives that this function. Genentech candidates are hetero bifunctional. Small molecules were one into the molecule has been designed to specifically recognize the GA expanded repeat when this compound is administered systemically and distributes widely gets into the cell gets into the nucleus and then recognizes the GA. repeat expansions by binding to the minor groove of Intact double-stranded DNA, the frataxin gene and the other end of the molecule recruits, a transcriptional elongation comp.
The presence of these transcriptional elongation complexes enables the RNA polymerase to now rapidly read through the repeat region and therefore produce normal levels of the frataxin pre mRNA. Because the repeat expansion is in an interferon. That portion of the RNA is just spliced out normally to produce normal levels of intact. Full-length endogenous mRNA, which produces normal endogenous frataxin protein with all of its natural isoforms under the native regulatory control, this restores frataxin levels and therefore solid health.
Now for the other side of the platform, long repeat expansions in non-coding regions of genes are shown in red in the upper half. This is the case in diseases like Fuchs, endothelial, corneal dystrophy and myotonic dystrophy. Repeat expansions and coding regions of genes are shown in the lower half in red, as is the case in Huntington's disease, and it only takes one in Lille to cause the disease. So patient has one wild type Lille shown in this trend without the red and a mutant allele shown in this trend with the red expanded reach now in the upper half, this mutant allele is transcribed by RNA polymerase to create RNA, which then folds over on itself causes tangles and sequesters MBNO proteins. This causes nuclear foci and slight softness in other cellular dysfunction. Now in the lower half, the RNA is transcribed and then translated by ribosomes to make toxic mutant proteins. These proteins cause toxic aggregates, as is the case in mutant Huntington protein causing Huntington's disease gene tech molecules selectively target these abnormal yields at the repeat expansions shown in red, and they've dialed down transcription of toxic mutant gene products and thereby restore cellular how the wild type of deals continue to function normal.
This slide summarizes the mechanism of action that we've just reviewed in the animation and now for a deeper dive into our FA program. The root cause of FA lies in the single gene protection and the reduction and reduction in frataxin expression that causes the dysfunction, whether it's in the CNS, musculoskeletal tissues, cardiac hypertrophy or metabolic problems that patients face when we look at frataxin levels and healthy individuals, carriers and patients, we see that carriers have approximately half the level of their frataxin, as indicated by the black line representing the group average carriers do not have FA and have no disease burden.
Fa patients have a quarter to a fifth of normal frataxin levels on average, of course, around every means of distribution and there may be individuals who are above or below the mean and different individuals might require different levels of restoration to get back into the normal zone, which is somewhere near carrier levels. And that is the therapeutic goal, which is thought to be about a double. Now most of the general population has less than 34 J. repeats in their frataxin gene but someone with FA has 400 or over 1,000 of these repeats reduce the level of normal frataxin. And it turns out you can measure this reduction with a blood test what's shown on the top right as a result of a PCR test conducted on blood cells from patients.
You can see in the gray bar on the graph that RNA levels are low in patient cells when compared with frataxin from an unaffected sibling who has to normal copies in the frataxin gene, you can imagine our excitement when we were able to observe that when cells from patients are incubated with Gentech molecules, there's a restoration of frataxin to normal levels in a dose-dependent fashion. And when cells from unaffected siblings are incubated with the compounds of frataxin levels remain unaltered. This is exactly what one would wish for an FA, a medicine that restores natural levels of the single gene product that causes all of these problems. And that's what's so exciting about design is we have an opportunity to provide a restorative therapy of natural frataxin from the patient's own genes and to do it with a small molecule.
We've seen that this effect is observed in a wide variety of cell types tested. Shown here is the result of treating terminally differentiated neurons taken from patient-derived IPS cells on the left is an increase in frataxin RNA. And on the right is an increase in frataxin protein, which follows a few days later. It has a long half-life of several days. DT. two one six was taken into clinical trials in patients with FA in 2022 and 23 with a prior formulation and the trial design it's shown here. We learned from the human studies that the duration of adequate levels of exposure of DT. two one six was much shorter than expected.
While we knew that the drug was short lived in plasma human studies showed by muscle biopsy that it was also short-lived in tissue. And that what you observe in plasma is predictive of what is observed in tissue. The tissue levels from human muscle biopsies were approximately only eight to 10 nanomolar at day two, and the drug was almost gone with levels at one nanomolar by day seven. Well, despite that, there was a clear increase in frataxin expression observed in treated patients in a dose-dependent fashion with one patient's frataxin level going to clinically normal carrier levels as shown in the right. However, the effect was transient because the drug exposure was transient.
So we needed to develop a new drug product that could sustain this drug exposure while the drug was generally well tolerated. There were injection site thrombus for various events observed, which limited the frequency and levels of dosing with the prior product candidate. Nonclinical study showed that these reactions were attributable to the formulation excipients in the drug product. We have now conducted new non-GLP animal studies with DT. 262, which lead us to believe that these issues have now been solved and we can progress two confirmatory GLP studies to get back into the clinic. Furthermore, this new drug product appears suitable for IV administration compatible with injections or infusions, peripheral or Central and also appear suitable for a subcutaneous route of administration.
As we showed in the beginning, the new drug product, DT. two and six b. two has a much more sustained exposure profile as seen in the single dose IV PK curve from nonhuman primates. You can see between day one and day seven levels are 10 to perhaps 100 fold higher than the prior drug product, even with a quarter to approximately a 10th of the reference dose. This is because of a shorter alpha phase and the elimination half-life between the prior and new drug products are very similar. This profile has been achieved by using a proprietary and novel excipient in the formulation 52 and 62 also has a sustained exposure profile when administered by subcutaneous route of administration.
As shown on the right slide, this profile has a blunted C-max and a sustained exposure with low peak to trough level fluctuations. We have flexibility in both route of administration as well as frequency of dosing as seen here with both a daily or weekly subcutaneous injection in nonhuman primates. In the clinical trial, we observed that the tissue level as measured by muscle biopsy was in line with the plasma exposure. And this is typical of a small molecule drug. The new drug product also shows that the tissue levels as measured by muscle biopsy in nonhuman primates is in line with plasma exposures, providing comfort that the extended profile seen in plasma will provide the desired extended profile in tissue.
Repeat-dose studies done in non-GLP assessments have also been encouraging, and the program will be proceeding to GLP studies, which are planned to be completed by the end of this year to support patient dosing in 2025. Given the very different PK profile seen in the preclinical studies, our plan is now to conduct a Phase one clinical trial in healthy volunteers. So as to confirm the pharmacokinetics and also to confirm injection site tolerability. This will also help us in choosing a dosing route and dosing frequency for longer-term studies. Subsequent trial will be in FA patients, which we plan to conduct to determine safety, tolerability and the effect of treatment on endogenous frataxin levels Solaris is now approved for the treatment of FA and its uptake confirms that this is a large market opportunity.
Since SkyTerra's does not affect frataxin levels. We believe this approval has no appreciable impact on the potential opportunity for DT. 200. As we've discussed before, Gene tech small molecules have several potential advantages over any other genomic medicine modalities. Now in case, you see any literature reports of possible effects of other molecules on frataxin expression. We show here that gene tech molecules restore frataxin in a more substantial way than anything else. Reported in the literature, which is not surprising, given it's direct an elegant mechanism of action. Fuchs, endothelial corneal dystrophy or FECD. is a degenerative disease of the cornea that's been known for over 100 years.
The literature widely cites that This disease affects 4% of all adult Americans over the age of 40 only in the last decade, though, has it been shown that approximately 70% to 80% of these adults get the condition due to inheriting a monogenic repeat CTG. expansion in the PCF. four G. based on the current census, this works out to approximately 4.6 to 5.3 million. USFCCD. patients are no approved disease-modifying prescription drugs for FTCD. and treatment is restricted to things like hypersonics ceiling drops of trying to dehydrate the cornea. Eventually a small fraction of patients get a corneal transplant surgery, which they're about 18,000 to 30,000 corneal transplant surgeries done in the United States annually. And that's a very small fraction and represented by the red figure, most patients unfortunately, classically suffer from declining visual quality on the right is a Photoshop image composed by a patient to communicate her loss of visual quality.
In late-stage view, the analogy is sometimes that of a foggy and rainy windshield, resulting in loss of low contrast visual acuity, glare and contrast sensitivity. And we have heard from a number of clinicians who see these patients that it was if there was anything that slowed progression and was well tolerated, they would treat everyone, even patients who are presymptomatic efficiencies caused by dysfunction in the cells and the endothelium mono layer of the cornea. And these cells have a role in maintaining a dehydrated stroma to keep the cornea free of extracellular matrix deposits D-cell. They're slowly lost over time due to the disease and their stake because of the TCI.
Four mutation, which is the CTG. repeat expansion in the non-coding region of the gene. This inherited mutation can be detected by means of a blood. So how can we then develop a therapy for this by helping restore cellular health to the end of telomere length? And this cell dysfunction arises from this single inherited mutant Lille. Preliminary reads that meet the Lille and makes an RNA containing these repeats. The RNA folds over on itself creates tangles, and you can see that you can stain for them. These tangles sequester, MB&O splice proteins and cause mispricing of a number of downstream genes, which then drive cellular dysfunction. We have designed gene tax to bind and recognize these long CTG. repeat regions in the meat, Newdeal and shut off production of the toxic TCR for mutant RNA.
This slide shows the effectiveness of the Genentech molecule. Recall I said that you could sustain for these new InfoSight. They're shown in the above panel in the middle section as data that light with a fluorescent label probe inside the nucleus of endothelial cells taken directly from discarded cornea of patients who've undergone surgery on the lower panel, we observed that these foci largely go away when these patient corneal cells are treated with DT. one six eight. The compound has low nanomolar potency as shown in the dose-response curve on the right. This slide shows the results of asking for wild-type TCI. four transcripts from patient cells. As shown here, drug treatment has no effect on the wild type TCFR. expression. This is an allele selective inhibition, which is highly desirable.
This slide looks at Mist splicing that occurs in a variety of downstream genes at baseline in light green and with drug treatment as mutant TCF for expression has dialed down and sequestered splicing proteins are released. Downstream normal splicing is restored, leading to a treatment of the cellular dysfunction. Not only do we see an allele selective effect, which is the desired product profile. We have also been able to formulate those to be suitably delivered as an eyedrop. All the required nonclinical safety studies have been conducted and reviewed by the FDA, resulting in a 90 that's been cleared. We plan to initiate Phase one development for DT. one six eight in 2024. We now need to determine the impact of this type of treatment on the progression of this degenerative corneal disease.
And for that purpose, we need to gain experience with various possible endpoints and patient characteristics therefore, prior to jumping into an interventional trial in patients, we believe the correct strategy for clinical development is to first run an observational study with patients diagnosed Fuchs who have a genetically confirmed PCF. four expansion mutation. We have begun enrollment in such a trial and plan to recruit 200 patients during the year and plan to follow them for two years. This will enable us to understand the patient characteristics and endpoints that allow us to measure that as function and progression in these patients. Once we have gathered sufficient data to measure disease progression and the performance of various endpoints, we will then focus on an interventional treatment trial.
These endpoints include measures of visual quality, interior I. tomography and also microscopic visualization of the corneal endothelium. We are revealing for the first time our program for Huntington's disease. As you know, HD. is a devastating neurodegenerative disease caused by an exotic repeat expansion in the Huntington gene. A long-standing objective in the field has been for there to be a selective inhibition of the mutant Huntington, the deal with a molecule that can distribute widely to the affected cells. And this has been a very elusive profile to achieve here is data looking at the effect of one of our two candidate molecules on wild type and mutant Huntington RNA from treated patient fibroblast cells.
The left panel shows data from a normal onset H genotype and the right panel. The effect on an early onset HD. genotype, which contains a longer repeat expansion we observed and a Lille selective inhibition of mutant Huntington RNA. The effect is even more pronounced in the early onset genes. This is particularly encouraging because regardless of the genotype, it is known that the repeats undergo somatic expansion of various lengths in different neurons over time. And this data suggests that the compound would have an even more profound impact on those cells, which have undergone a longer schematic expansion of there.
Cag repeat this slide shows that the RNA effect shown earlier translated to the expected effect on mutant Huntington protein. The above panel shows that a mutant Huntington selective antibody is able to detect mutant protein disappearing with increasing concentrations of drug. The middle panel uses an antibody to detect both wild-type and mutant Huntington. And you can see an expected reduction due to the mutant protein being reduced. The size of these proteins are hard to resolve in the normal onset genotype in the left panel gels. But in the early onset genotypes, the mutant and wild type proteins are different enough in size to actually show up as two bands on the middle panel on the right, yes, this is the RNA inhibition data from Canada to showing a similar LDL selective inhibition.
And this is the protein inhibition data from Canada to also showing an effect as expected from the RNA inhibition. We expect to choose one of these compounds to move forward with as a development candidate once further testing is conducted. Having seen these exciting profiles, we are encouraged at the preliminary non-GLP tolerability of these molecules in both rodents and nonhuman primates. We've conducted pharmacology assessments of these molecules and have selected a widely used Q1 75 D and pharmacodynamic mouse model to SaaS PD.
We observed in this study that with systemic administration, there is an over 50% reduction of mutant Huntington RNA and protein in the striatum of mice, which supports the idea that this compound is able to get into the brain and get into the cells and have the intended effect with systemic administration. We are very encouraged to see this in vivo confirmation of the activity seen and cells derived from patients. If this pans out HD. gene tech molecules hold the potential of selectively reducing mutant Huntington with a widespread distribution profile and systemic administration regardless of the patient's HDG. and over time, this would be a best in class profile.
Our next milestone for the program is to choose a development candidate. We are also working on a program in myotonic dystrophy. Dm one is caused by ICTG. repeating the DMPK gene in the three prime on translated region, much like the SECD. story, Newton DMPK, RNA form toxic foci and downstream splicing dysfunction. It would be highly desirable and a best-in-class profile to have a selective inhibitor of mutant DMPK for the treatment of myotonic dystrophy that would distribute broadly in all affected tissues and cell types. This data shows that we have a gene tacked molecule that reduce these toxic DMPK foresight with low nanomolar potency. This is a splicing index from panel of misplaced genes with seven days of treatment from patient-derived Microtune's showing that the DM1 foci reduction does have beneficial downstream effect on cellular health.
The next milestone for this program is DC declaration. In summary, we have a promising new platform for genomic medicine that is meaningfully differentiated from other genomic medicine modalities. We have four drug programs each in significant markets and with highly differentiated profiles The first two of which are expected to be clinical-stage next year, we ended 2023 with approximately $281 million, and this gives us a cash runway for the next five years pending future R&D results and ongoing strategic review, this cash runway would support generating clinical proof-of-concept data in up to four projects.
We believe each of these programs has the potential to transform the treatment of these debilitating conditions and success in any one of these would create significant value for investors. We are dedicated to moving these molecules forward, and welcome you to participate in this journey and help us get to success. This concludes our prepared remarks, and we'll now move to Q&A. Operator, please open the line for questions.
Question and Answer Session
Operator
(Operator Instructions) (technical difficulty).
Pratik Shah
Thank you, Joe, for the question on the exposure profile. As a reminder, one of the major learnings from our prior clinical trial was that the levels of drug required in tissue are similar today in vitro EC90. So that eight to 10 nanomolar exposure that we saw in muscle in patients from the trial is something that sets a target. The prior drug product had the disconnect between the duration of plasma and tissue levels in animals. We did not observe any such disconnect in humans and the new drug product, 82 and 62 is well behaved in that even in animals. There's no longer a disconnect between plasma and tissue levels. And this is what you would expect with a small molecule drug.
If you reference some Slide 22 muscle biopsies showed that tissue levels were predicted by plasma levels. And that turns out to then also be true with RDT. two and 62 were on the right. You see that in nonhuman primate studies, the plasma levels are much higher. And so the tissue levels as shown by muscle biopsy from these NHP's. In addition, we have some additional confirmatory data in a rack distribution study, which we can show you in a subsequent slide here that there's adequate levels of drug seen and a broad set of tissues against that target level of eight to 10 nanomolar that we require to see a biological effect.
And so once you exceed the threshold required for biological effect, there's no excessive pharmacology. So we feel that the ex the exciting results we've seen with the plasma PK do also set us up well for good tissue distribution. On your other question about injection site reactions, nonclinical studies show that the injection site reactions were attributable to the excipients in the prior clinical formulation and now the new non-GLP studies that we've conducted with DT. two and six p. to support the conclusion that this formulation has resolved the injection site issues and is suitable to progress into confirmatory GLP studies. And in fact, in one arm of the study, we've included daily injections over four weeks, which gives us further confidence the injection site tolerability issues appear resolved.
Yes, everyone, this is Navin on for Leo. Thank you for taking your questions. So just a couple from us. How are you thinking about designing your Phase one for DT. two and P. two? And then if you show frataxin expression increases in patient two things and that that might potentially open a path forward for accelerated approval given some of the latest understanding of biology, the FDA's views on that? And then should we also expect similar patient numbers to the original SAD in that study.
Sean Jeffries
Okay. Okay. And thank you for the question. With regard to the on Phase one studies, because we see on this remarkably different PK profile that hits all of the criteria that we were looking for. Our approach here is to first conduct our Phase one PK study in healthy volunteers, and this is to confirm the encouraging PK profile of DT. 2.6 p. two. Once we get data from that study, we then plan to conduct patient studies beginning in 2020.
With regard to your next question, on some of your FDA endpoints? I would say that some of the unmet need here is high. We don't have anything to add in terms of what the FDA it may or may not require in the future. We've had productive engagement with the FDA previously, and we'll continue to engage with the agency upon resumption of clinicals 30.
Pratik Shah
Okay. And Laura, what Yes, sorry about that. Thank you very much for taking the question. I believe you are also working in parallel on some new method development with respect to frataxin, just detection on a protein level. Wondering if you can share any details kind of on where that methodology stand at present and maybe kind of timing to advance those efforts? And then I have one quick follow up. Thank you, Laura. We are dedicated to continuing to work on whatever improvements we can make in measurement of frataxin levels. We have robust assays that we've already used in prior clinical studies for measurement of frataxin RNA. And we continue to make improvements on our ability to reliably measure frataxin protein and possible changes in frataxin protein. And we'll provide updates on that progress as we as we progress to the clinic.
Okay. Thank you very much. And then just quickly with respect to Fuchs, and I know this may come out in your observational study. But I'm kind of curious, with AMD and visual acuity measurements are pretty straightforward, but contrast that with something else like geographic atrophy and it's a little bit more challenging and to characterize progression or loss of vision. So I'm curious, where does Fuchs kind of shakeout in that spectrum and any ideas in terms of kind of measurements that you think might be most promising? You?
Pratik Shah
Thank you for the question. We are conducting an observational study in patients with Fuchs with a confirmed TCFR. mutation to better understand both patient characteristics as well as the characteristics of and the endpoints and disease progression. And those come in three different broad buckets. One is a variety of measures of visual quality. And there are numerous reports in the literature of ways to measure the loss of visual quality in patients with Fuchs. And we'll be getting direct experience with those types of measures. Second is measures of edema or fluid buildup in the cornea because the endothelial cell layers of function is to dehydrate the stroma and keep the cornea clear.
And there are ways in the clinic to measure this subclinical edema using using interior eye tomography, for example. So we including those measures in the observational study. And third, some interest you've seen in the back of the eye in geographic atrophy, there are analogous or corresponding ways to directly visualize the corneal endothelium in patients. I'm using specialized microscopy. And so we'll be including those measures as well. And that will give us a variety of tools to examine the characteristics of the patients and disease progression.
Thanks very much, Al.
Pratik Shah
Well, thank you, everyone, for joining us on today's call, and we look forward to updating you as we continue to make exciting progress.
Operator
This concludes today's program.