Good morning, everyone, and thank you for joining the HC Wainwright Third Annual Autoimmune and Inflammatory Disease Conference. My name is Vivian, and I'm an analyst on the Corporate Access team. HC Wainwright is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 650 companies covered across all sectors. If you would like more information, please visit hcwco.com. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. With that said, we wish you a productive and enjoyable day. Now, I would like to hand it off to Tara Kieffer, the Chief Product Strategy Officer at Enanta Pharmaceuticals.
Great. Thank you, Vivian. Good morning, everyone, and thank you to the conference organizers for inviting me here today to present on behalf of Enanta Pharmaceuticals. Before I begin, I'd just like to—oops, sorry. Before I begin, I'd just like to remind you that I'll be making forward-looking statements. For a summary of risks associated with those statements, please see our filings on sec.gov or on our website. For those of you less familiar with Enanta, we have a long history in infectious disease, and specifically in virology, with expertise in small molecule drug discovery and early development over the past 30 years. We're probably best known for our work in hepatitis C, where we worked on protease inhibitors, ultimately leading to the discovery of glecaprevir, which is one of the two components in Mavyret, a leading cure for HCV, where we cured over a million patients.
More recently, we've been focused on developing a pipeline in immunology, and I'll be discussing these specific programs in my presentation today. We have a strong balance sheet and ongoing royalties to fund our efforts. We finished 2024 with about $217 million, which does not include a $30 million tax refund due to us from the IRS, and this cash position gives us runway into fiscal 2028. This is our pipeline with HCV at the top, and from there, we expanded into other liver viruses with a program in hepatitis B. We then broadened into respiratory viruses, where we currently have multiple clinical stage programs for RSV as well as COVID. In the past several years, we've focused on how to build out the company and what the next pillar might be for Enanta. We landed on immunology for a number of reasons.
I'll talk about that a little bit later, but certainly, it's an area where there is overlap with infectious disease, and we actually have a lot of capabilities and experience internally. Early last year, we announced our first program in immunology, which is targeting inhibitors against KIT for mast cell-associated diseases such as urticaria. Late last year, we announced our second program to develop inhibitors for STAT6 for type 2 immune diseases such as atopic dermatitis. We plan to continue to build out that immunology portfolio going forward. With that, let's dive into immunology. How did we get into immunology, and why did we choose this area to expand into?
If we go to the bottom of the slide and think about Enanta's foundational capabilities, we are well known for our strong medicinal chemistry, along with core capabilities in preclinical development, including biology, drug metabolism, pharmacokinetics, and toxicology, demonstrating strong molecule expertise and a proven drug discovery platform. Most of these disciplines are generally applicable across disease areas when these fundamentals are in place. I think the key is really understanding the underlying biology and disease pathology and the assays and animal models, as well as biomarkers and early clinical development. Given that immunology and virology are scientifically adjacent areas, many of our leaders and scientists and other team members bring significant immunology expertise. Immunology is also a broad therapeutic area with significant unmet need in several diseases.
Many treatments for this space are biologic, and we aim to capitalize on Enanta's small molecule drug discovery expertise to deliver oral options with potentially better profiles for some of these immunologic indications. Before I get into our specific programs, I just wanted to take a moment to briefly describe the framework that we've been using to select targets for our immunology pipeline. We look to identify targets that have potential in multiple disease areas and then leverage that expertise in drug discovery to develop best-in-class small molecules. I'm just going to highlight four of the key criteria that we used in the selection process. First is strong target rationale, or how well the target is validated.
What I mean by that is that we have confidence based on either clinical or human biology data that the target has a link to the disease and that modulating it is likely to result in clinical benefit. Second, we'd like there to be a clear means to differentiation due to either being drugged by injectables or being marginally treated by suboptimal orals, or it's just yet to be drugged at all. The third is something where there's a quick path to clinical proof of concept, either with a predictive biomarker or early clinical signals that can de-risk the target early on in development or the program early on in development. Lastly, we're looking for diseases that have significant unmet need and large market opportunities.
With that in mind, we initially focused on type 2 immune or type 2 inflammatory diseases, which are characterized by an overactive immune response, usually in response to some sort of allergen or pathogen that results in the overproduction of these type 2 cytokines, for example, IL-4, IL-5, IL-13, as well as antibodies like IgE that will recruit and activate cell types like mast cells, eosinophils, and basophils that then further drive inflammation. This type 2 immune phenotype plays a significant role in many severe and chronic diseases where patients have limited or inadequate treatment options, leaving a significant unmet need.
The development of treatment for type 2-driven diseases, which is comprised of multiple indications, presents, as you can imagine, a tremendous opportunity with fast proof of concept achievable in indications like urticaria, which alone is estimated at about $5 billion, and atopic dermatitis, which is about $30 billion. There is plenty of room for growth in these areas. As type 2 diseases are addressable with multiple targets, we have the potential to treat broad patient populations in numerous disease areas. Specifically, the first two targets that we have rolled out are KIT and STAT6, both of which target underlying disease biology in multiple type 2 indications, encompassing serious disease areas with a significant unmet need for patients, including asthma and COPD. Let's now dig into more detail on both of these programs and the mechanisms and some of the data we have generated.
Let's first look at our initial program targeting KIT inhibition. Why are we excited about targeting KIT? KIT is a tyrosine kinase. It's critical for regulating mast cell activity. Mast cells are known to be the primary driver of inflammation in the skin. They're implicated in a number of allergic diseases, including urticaria, asthma, eosinophilic esophagitis, or EoE, and prurigo nodularis, or PN. KIT signaling is actually required for mast cell survival. When you block this, it results in apoptosis or cell death. KIT inhibitors will directly reduce the quantity of mast cells available to drive pathology. That's very different than other mechanisms that are currently in development, which either inhibit mast cell activation or downstream mediators but don't address the mast cells themselves.
Finally, perhaps the most compelling reason to like this target is that there is clinical proof of concept with phase two data from a monoclonal antibody that has shown what we think is some of the best in disease efficacy. Our goal is to replicate this efficacy with an oral therapy and potentially improve on the overall profile. As I mentioned before, we believe CSU, or chronic spontaneous urticaria, is a good indication to generate initial proof of concept data. What is CSU? It is a chronic, severely debilitating inflammatory skin disease where patients can develop these itchy hives and/or angioedema or deep tissue swelling. It is quite impactful for these patients, even beyond the skin. Patients can experience numerous quality of life challenges like sleep disturbances, fatigue, irritability, anxiety, and depression. The disease is quite prevalent.
It's affecting up to a whole percent of the global population. There's substantial need for an efficacious oral agent. Currently, the standard of care is antihistamines, but unfortunately, only about half of the patients get adequate relief. There is one indicated biologic, but a small portion of patients go on to receive this treatment. As you can imagine, this leaves tremendous room for an efficient, efficacious oral treatment, which is the goal of our program. Turning to our program, we recently selected and announced a development candidate, which is EPS- 1421. I'm going to briefly summarize its characteristics here, and then we can have a look at the data. EPS- 1421 inhibits KIT with nanomolar potency. We've seen this in both binding and cellular assays.
It demonstrates subnanomolar activity in vivo and in vivo ADME properties with good PK across multiple preclinical species, no GSH adducts or reactive metabolites detected either in vitro or in vivo, which is important to screen out for safety. We also see a low potential for DDIs via CYP inhibition. This slide shows you the potency data that I mentioned with activity in both binding and cellular assays. This table shows you the binding data for KD of 0.8, and then the remainder here are cellular assays where you can see the EC50s are generally ranging in the low single-digit nanomolar. The right-hand side here shows inhibition in a mouse model where SCF-mediated histamine release is inhibited in mice. The mice are treated orally with EPS- 1421, and then they're challenged with SCF. That's the ligand for KIT, which triggers mast cell degranulation and histamine release.
You can see here a very nice dose response. We observe an EC50 of 0.25 nanomolars, so it is quite potent. This slide shows the selectivity, and you can see EPS- 1421 is very selective with greater than 500-fold selectivity for KIT over other KIT family members. We are looking at CSF1R, PDGFR alpha, PDGFR beta, and then FLT3. Now let's turn to our STAT6 program. STAT6 inhibitors offer a tremendous opportunity in the potential to create an oral Dupixent. As I mentioned previously, type 2 dysregulation is responsible for multiple allergic and autoimmune diseases, including asthma and atopic dermatitis. STAT6 is a transcription factor that is required for IL-4, IL-13 signaling, which drives a TH2-dominant phenotype. There is genetic validation for this target from patients that have gain-of-function variants, which result in severe atopic dermatitis.
More recently in the literature, there have been patients described with loss of function variants that can protect against type 2 high asthma. Otherwise, these patients have no additional phenotypes, which provide confidence for a good safety profile in STAT6 inhibition. Lastly, clinical validation of the IL-4, IL-13 pathway exists with the antibody Dupixent. By inhibiting STAT6, we are just targeting a bit downstream from that and blocking the same signaling pathway with the goal of recapitulating the Dupixent biology. Currently, there are no oral therapies selectively targeting this pathway. Our initial clinical focus for proof of concept is atopic dermatitis, which is a chronic skin disease that results in dry, red, inflamed, irritated, and itchy skin with quality of life impacts beyond the skin, including limited lifestyle, avoidance of social interaction, and impacted activities.
This disease is quite prevalent, so it's affecting over 7% of US adults, of which nearly half of them have moderate to severe symptoms. There is significant need for an efficacious and safe oral agent. Current therapy is predominantly the IL-4, IL-13 monoclonal antibody, where the market is dominated by Dupixent here. There are JAK inhibitors, which are oral, and they actually have better efficacy. However, their safety profile regulates treatment to limited use, as you can see here. There's a box warning for a number of safety concerns. The goal of our program is to develop novel, potent, and selective oral STAT6 inhibitors. We have discovered prototypes that hit these goals. I'm going to be showing some new data today on these prototypes that will show inhibition of STAT6 with nanomolar potency in both binding and cellular assays.
These prototypes demonstrate STAT6 target engagement in vivo, and they are highly selective for STAT6 versus other STATs. We have also seen good in vitro and in vivo ADME properties. We're currently optimizing these prototypes and have a goal of selecting a development candidate in the second half of this year. This slide shows the potency of these prototypes. They exhibit nanomolar inhibition in both biochemical and cellular assays. You can see here, we see inhibition of phosphorylation of STAT6 in human PBMCs after stimulation with IL-4. We can also prevent the production of TARC, which is a STAT6-driven biomarker of type 2 inflammation after IL-4 induction in human PBMCs. You can see the prototype EC50 is in the range of 6-20 nanomolar here, as this is compared to a JAK inhibitor where EC50s are generally in the same range.
We're seeing really good potency with our prototypes. Looking at the selectivity, we see no inhibition of other STATs in human PBMCs. That's detailed in this table where all of the STATs 1 through 5, we have EC50s of greater than 5,000 nanomolar. If you compare that to JAK inhibitors, they're much, much more selective. We also see greater than 1,000-fold biochemical selectivity for STAT6 over other STATs. Lastly, I'll just talk about our in vivo mouse model data for the prototypes. In this case, we deliver our prototypes orally to the mouse, and then we take the blood and stimulate ex vivo with IL-4. That should drive phosphorylation of STAT6, and we're detecting that here. You can see in this figure, this results in near complete inhibition of phosphoSTAT6. These prototypes have good intrinsic permeability, and they are orally bioavailable.
In vivo, STAT6 target engagement is observed here after a single dose, and we see rapid and complete inhibition of phosphoSTAT6. With that, I will conclude by reviewing our upcoming key catalysts for this year. For our clinical stage virology programs, we anticipate a phase two readout, and we'll be pursuing partnerships for those programs going forward. Getting back to immunology, for our KIT inhibitor, this year, we will be focusing on IND-enabling studies for EPS- 1421, as well as scale-up of drug supply for clinical trials. For the STAT6 program, our goal is to select a development candidate in the second half of this year. Finally, we will continue to expand our immunology portfolio by introducing a third program this year. I hope that you continue to follow Enanta for further updates. Thank you very much for joining today's presentation.
Alright, thank you so much for leading a very productive and informative presentation on behalf of the Enanta Pharmaceuticals team. HC Wainwright is grateful for your participation in today's conference.