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Enanta Pharmaceuticals at H.C. Wainwright: Strategic Shift to Immunology - March 27
On Thursday, 27 March 2025, Enanta Pharmaceuticals (NASDAQ: ENTA) presented at the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference. The company unveiled its strategic pivot from virology to immunology, emphasizing unmet needs in type two immune diseases. While Enanta boasts a strong financial position, challenges remain in developing novel treatments in a competitive landscape.
Key Takeaways
Enanta is transitioning its focus from virology to immunology, leveraging its expertise in small molecule drug discovery.
The company ended 2024 with a cash position of $217 million, excluding a $30 million tax refund, ensuring financial stability until fiscal year 2028.
Enanta’s pipeline includes promising programs targeting KIT and STAT6, with plans to introduce a third immunology program this year.
The company is aiming for Phase II data in its virology programs and seeks partnerships post-readout.
A strategic focus is on oral therapies for type two immune diseases with high unmet needs.
Financial Results
Cash Position: Enanta finished 2024 with approximately $217 million.
Tax Refund: The company expects a $30 million refund from the IRS.
Financial Runway: Current funds are projected to last until fiscal year 2028.
Operational Updates
Pipeline Expansion: Transitioning from virology to immunology, focusing on type two immune diseases.
KIT Inhibitor Program: EPS 1421 shows nanomolar potency and selectivity; IND enabling studies and drug supply scale-up are ongoing.
STAT6 Program: Prototypes discovered with nanomolar potency; a development candidate will be selected later this year.
New Immunology Program: A third program is planned for introduction this year.
Virology Programs: Phase II data anticipated, with partnership pursuits post-readout.
KIT Inhibitor Program: Focus on IND enabling studies and clinical trial preparation for EPS 1421.
STAT6 Program: Selection of a development candidate is expected in the second half of the year.
Pipeline Growth: Continued expansion of the immunology portfolio with a new program.
Partnerships: Plans to pursue collaborations for clinical stage virology programs.
Q&A Highlights
Tara Kiefer emphasized the strategic shift to immunology due to its overlap with infectious diseases and Enanta’s internal capabilities.
The company aims to replicate the success of Dupixent in atopic dermatitis through its STAT6 program.
Initial proof of concept data is expected from the chronic spontaneous urticaria indication.
Enanta’s comprehensive strategy and robust financial health position it well for future growth in the immunology sector. Readers are encouraged to refer to the full transcript for more detailed insights.
Full transcript - H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference:
Vivian, Analyst, H. C. Wainwright: Good morning, everyone, and thank you for joining the H. C. Wainwright Third Annual Autoimmune and Inflammatory Disease Conference. My name is Vivian, and I’m an analyst on the corporate access team. H
Now I would like to hand it off to Tara Kiefer, the chief product strategy officer at Ananta Pharmaceuticals.
Tara Kiefer, Chief Product Strategy Officer, Ananta 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 Ananta Pharmaceuticals. And 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.
And for a summary of risks associated with those statements, please see our filings on sec.gov or on our website. So For those of you less familiar with AMANTA, 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 thirty 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 Mavrid, 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 $217,000,000 which doesn’t include a $30,000,000 tax refund due to us from the IRS and this cash position gives us runway into fiscal twenty twenty eight. So 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. And 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 or mast cell associated diseases such as urticaria. Late last year, we announced our second program to develop inhibitors for STAT6 for type two immune diseases such as atopic dermatitis. We plan to continue to build out that immunology portfolio going forward.
So with that, let’s dive into immunology. So how did we get into immunology and why did we choose this area to expand into? So first, 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 and when these fundamentals are in place. So 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.
And 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 biologics and so we aim to capitalize on Enanta’s small molecule drug discovery expertise to deliver oral options and with potentially better profiles for some of these immunologic indications. So, before I get into our specific programs, I just wanted to take a moment to briefly describe sort of the framework that we’ve been using to select targets for our immunology pipeline. So, we look to identify targets that have potential in multiple disease areas and then to leverage that expertise in drug discovery to develop best in class small molecules.
So I’m just gonna highlight four of the key criteria that we used in the selection process. So first is strong target rationale or, you know, how well the target is validated. And 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 derisk the target early on in development or the program early on in development.
And then lastly, we’re looking for diseases that have significant unmet need and large market opportunities. With that in mind, we initially focused on type two immune or type two 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 two cytokines. For example, IL-four, IL-five, IL-thirteen, as well as antibodies, like IgE that will recruit and activate cell types like mast cells, eosinophils, and basophils that then further drive inflammation. So this type II 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. So the development of treatment for Type two 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 five billion and atopic dermatitis, which is about thirty billion.
And there’s plenty of room for growth in these areas. As type two 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’ve rolled out are KIT and STAT6, both of which target underlying disease biology in multiple Type II indications, encompassing serious disease areas with a significant unmet need for patients, including asthma and COPD. So, let’s now dig into more detail on both of these programs and the mechanisms and some of the data we’ve generated. So let’s first look at our initial program targeting KIT inhibition.
So why are we excited about targeting KIT? So KIT is a tyrosine kinase that’s critical for regulating mast cell activity and 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. So KIT signaling is actually required for cell survival, for mast cell survival. And so when you block this, it results in apoptosis or cell death.
So, KIT inhibitors will directly reduce the quantity of mast cells available to drive pathology. And 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. And 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. And so, our goal is to replicate this efficacy with an oral therapy and potentially improve on the overall profile. So as I mentioned before, we believe CSU or chronic spontaneous urticaria is a good indication to generate initial proof of concept data.
So what is CSU? It’s a chronic, severely debilitating inflammatory skin disease where patients can develop these itchy highs and or angioedema or deep tissue swelling. And it’s quite, quite impactful for these patients even beyond the skin. So patients can experience numerous quality of life challenges like sleep disturbances, fatigue, irritability, anxiety and depression. And the disease is quite prevalent.
It’s affecting up to a whole percent of the global population. And there’s substantial need for an efficacious oral agent. So currently, the standard of care is antihistamine, 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.
So turning to our program, we recently selected and announced a development candidate, which is EPS fourteen twenty one. And so I’m gonna briefly summarize its characteristics here and then we can have a look at the data. So EPS fourteen twenty one 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. So, this slide shows you the potency data that I mentioned with activity in both binding and cellular assays. So 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. So the mice are treated orally with EPS fourteen twenty one and then they’re challenged with SCS.
That’s the ligand for KIT, which triggers mast cell degranulation and histamine release. And you can see here a very nice dose response. And we we observe an EC50 of 0.25 nanomolars. That’s quite potent. So, this slide shows the selectivity and you can see EPS fourteen twenty one is very selective with greater than five five hundred fold selectivity for kit over other kit family members.
So we’re looking at CSF. Sorry. CSF one r, PDGFR alpha, PDGFR beta, and then FLT three. Now let’s turn to our STAT6 program. STAT6 inhibitors offer a tremendous opportunity and the potential to create an oral Dupixent.
As I mentioned previously, type two dysregulation is responsible for multiple allergic and autoimmune diseases including asthma and atopic dermatitis. So STAT6 is a transcription factor that’s required for IL4, IL13 signaling, which drives a TH2 dominant phenotype. There’s genetic validation for this target from patients that have gain of function variance, which result in severe atopic dermatitis. And then more recently in the literature, there’s been patients described with loss of function variance that can protect against type two high asthma. But otherwise, these patients have no additional phenotype, which provide confidence for a good safety profile in STAT6 inhibition.
Lastly, clinical validation of the IL4, IL13 pathway exists with the antibody DUPIXENT. And so 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. So 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 seven percent 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-four, IL-thirteen 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 boxed warning for a number of safety concerns.
So the goal of our program is to develop novel, potent and selective oral STAT6 inhibitors and 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 STAT. 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 IL4. And we can also prevent the production of TARK, which is a STAT6 driven biomarker of type two inflammation after IL4 induction in human PBMCs. You can see the prototype EC50 is in the range of six to 20 nanomolar here, as this is compared to a JAK inhibitor where EC50s are generally in the same range.
So we’re seeing really good potency with our prototypes. So looking at the selectivity, we see no inhibition of other stat in human PBMCs that’s detailed in this table where all of the stats one through five, 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 STAT. And then lastly, I’ll just talk about our in vivo mouse model data for the prototype.
So in this case, we deliver our prototypes orally to the mouth and then we take the blood and stimulate ex vivo with IL-four. That should drive phospho phosphorylation of STAT6 and we’re detecting that here. And you can see in this figure, this results in near complete inhibition of phospho STAT6. 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 phospho STAT6.
So with that, I will conclude by reviewing our upcoming key catalysts for this year. For our clinical stage virology programs, we anticipate a Phase II 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 EPS1421 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.
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I hope that you continue to follow Enanta for further updates. Thank you very much for joining today’s presentation.
Vivian, Analyst, H. C. Wainwright: Tara, thank you so much for leading a very productive and informative presentation on behalf of the Enanta Pharmaceuticals team. H. C. Wainwright is grateful for your participation in today’s conference.
https://www.investing.com/news/transcripts/enanta-pharmaceuticals-at-hc-wainwright-strategic-shift-to-immunology-93CH-3952596
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