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 with Fuchs, who have a genetically confirmed TCF4 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 the dysfunction 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, anterior eye tomography, and also microscopic visualization of the corneal endothelium. We are revealing for the first time our program for Huntington’s disease. As HD is a devastating neurodegenerative disease caused by an exonic repeat expansion in the Huntington gene. A longstanding objective in the field has been for there to be a selective inhibition of the mutant Huntington allele with a molecule that can distribute widely to the effect 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 HD genotype and the right panel, the effect on an early onset HD genotype, which contains a longer repeat expansion.
We observe an allele selective inhibition of Mutant Huntington RNA. The effect is even more pronounced in the early onset genotype. 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 somatic expansion of their CAG repeats. This slide shows that the RNA effect shown earlier, translated to the expected effect on mutant Huntington protein. The above panel shows that Mutant Huntington selective antibodies able to detect mutant protein disappearing with increasing concentrations of drug. The middle panel uses an antibody that detects both wild type and Mutant Huntington, and you can see an expected reduction due to the mutant protein being reduced.
Now, 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 side. This is the RNA inhibition data from candidate two, showing a similar allele selective inhibition, and this is the protein inhibition data from candidate two. 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 non-human primates.
We’ve conducted pharmacology assessments of these molecules and have selected a widely used Q-175DN pharmacodynamic mouse model to SaaS PD. We observe 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 in cells derived from patients. If this pans out, HD GeneTAC molecules hold the potential of selectively reducing mutant Huntington with a widespread distribution profile and systemic administration regardless of the patient’s HD genotype.
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. DM1 is caused by a CTG repeat in the DMPK gene in the three prime untranslated region. Much like the FECD story mutant 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 GeneTAC molecule that reduce these toxic DMPK foci with low nanomolar potency. This is a splicing index from panel of splice genes with seven days of treatment from patient derived myotubes, 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 programs. 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.
Operator: [Operator Instructions] That will come from the line of Joseph Schwartz with Leerink Partners.
Joseph Schwartz : I was wondering if you could tell us more about the tissue distribution relative to the plasma distribution for DT-216P2 in all of the relevant tissue types for patients affected by FA? And then have you gone back and back tested the ISR profile for the original formulation of DT-216, as well as the new one.
