Patrick Burnett
Analyst · Guggenheim
Thanks, Rob, and good afternoon, everyone. I'm on Slide 13. I'd like to provide an update on what the R&D team has been doing to support grow, expand and build, starting with our clinical activities supporting the grow pillar. As Frank mentioned at the top of the call, we're excited to have initiated a new trial evaluating the use of ZORYVE cream 0.3% for the treatment of patients with moderate to severe atopic dermatitis. It's our belief that patients with this more severe burden of disease may benefit from the higher potency formulation of ZORYVE cream. This addition would provide HCPs even more flexibility in choosing ZORYVE for their AD patients across the spectrum of disease severity. Importantly, for patients receiving systemic therapy, other branded nonsteroidal topicals such as ruxolitinib are contraindicated. And so ZORYVE is an important treatment option for controlling residual disease and flares. As patients in this moderate to severe segment are the most likely to require biologic or oral therapy, this approach will provide a badly needed treatment option even if they transition to systemic therapy. This trial is just now getting underway, and we look forward to sharing further updates as it progresses. We also continue to prepare for our upcoming PDUFA action date on February 23, 2027, for the supplemental NDA for ZORYVE cream 0.05% for the treatment of mild to moderate atopic dermatitis in infants down to 3 months. This follows on our approval just last year for ZORYVE cream 0.05% for children with atopic dermatitis down to the age of 2. As I've mentioned previously, I'm a dermatologist still actively taking care of patients. So I know all too well the unique challenges of treating young patient population, particularly the very young infants and toddlers. The skin of infants in this 3- to 24-month age group is not yet fully developed, which can result in increased systemic absorption of topical agents. In addition, atopic dermatitis often affects more surface area in younger children compared to adolescents and adults. It's very hard for parents and caregivers to see their little ones suffer with atopic dermatitis. It's compounded by a concern for the potential harmful side effects of topical steroid use. Because of these factors, this young patient population represents one of the most urgent needs for a safe, effective and well-tolerated nonsteroidal topical. We're very excited to be on the threshold of bringing the innovation of ZORYVE to these patients and their parents and caregivers. If approved as anticipated, it will be a particularly gratifying milestone for our team. We continue to enroll patients in the 2 trials we initiated in the second quarter. The first is INTEGUMENT-ITCH, which we're conducting in adults to better elucidate ZORYVE's impact on pruritus or itch. As a reminder, we initiated this trial based on compelling data from the INTEGUMENT infant trial that showed reductions in itch within 10 minutes of the first application. The second trial is evaluating the impact of ZORYVE on nail psoriasis, a notoriously difficult-to-treat presentation of plaque psoriasis that often fails systemic therapy. We've seen some exciting signals of ZORYVE's efficacy in nail psoriasis through case reports as described previously and are eager to further evaluate the opportunity to help this subset of psoriasis patients. Now turning to our clinical progress under the expand pillar, which includes activities to extend the ZORYVE franchise to help individuals with additional chronic inflammatory diseases beyond our current approved indications. As Frank mentioned, we remain on track to report a readout for our vitiligo proof-of-concept trial this quarter and concurrently, a decision on whether to advance the program. I'll say more about the basis for our interest in vitiligo shortly. We also continue to enroll our Phase II proof-of-concept trials of ZORYVE foam for patients with hidradenitis suppurativa and expect to report trial results and a decision on advancement for that program in the first quarter of 2027. Hidradenitis suppurativa is a disease where ZORYVE could potentially provide an important and highly differentiated therapeutic option. There are currently no FDA-approved topical options for patients with HS, and none for milder patients, while more severe patients typically rely on systemic therapies. A topical therapy that could be used as monotherapy or in combination with systemic therapy without limitation would provide an important treatment option for patients and their health care providers. And our foam formulation could be a major additional benefit for patients as HS typically presents in hair-bearing areas like the groin or axillae. Separately, we're preparing to enroll a trial evaluating the impact of ZORYVE cream, 0.3% on cutaneous adverse events in cancer patients receiving PD-1 or PD-ligand 1 checkpoint inhibitor treatment. Such side effects occur in as many as half of patients receiving these life-saving treatments, and they often lead to interference with cancer therapy. If ZORYVE is able to effectively manage such treatment-related dermatosis, as suggested by the case reports we've seen, it may help cancer patients to persist with their treatment regimen. This trial is another meaningful example of the broad potential applications of ZORYVE across inflammatory skin conditions. Now finally, our build pillar and ARQ-234. This is our novel CD200R biologic for the treatment of atopic dermatitis. We've progressed it to the final single SAD cohort and have begun enrolling atopic patients into the multiple ascending dose component of the trial. We're pleased that we were able to enroll through all of the single ascending dose segments and encouraged by the safety profile that this begins to establish. As we've indicated previously, we plan to initiate a small proof-of-concept cohort after we've completed the MAD component of the study, and we will not be reporting out results from this trial until that proof of concept is completed. But we do look forward to sharing more data on the promise of ARQ-234 in the future. And moving now to Slide 14. As we approach the readouts from our initial proof-of-concept trials evaluating the indication expansion for ZORYVE, I would like to highlight some important aspects of ZORYVE's pleiotropic mechanism of action to help explain the breadth of potential applications that we're evaluating. ZORYVE inhibits phosphodiesterase 4 or PDE4, an enzyme that's widely expressed in cells throughout the human body, where it regulates cyclic adenosine monophosphate or cyclic AMP, an intracellular messenger that has various roles in cells depending on the cell type. PDE4 inhibitors have historically been viewed as immune modulating agents. And in fact, in immune cells, PDE4 inhibition impacts multiple biologic processes implicated in immune-mediated inflammatory skin conditions. Specifically, PDE4 inhibition reduces the expression of multiple key pro-inflammatory cytokines, including interferon gamma, type 1 interferon alpha, TNF alpha and then IL-4, IL-6, IL-17 and IL-23, which spans signaling through TH1, TH 2 and TH 17 immune-mediated responses. The PDE4 inhibition plays a far broader role than just immune modulation. For example, PDE4 also plays a role in sensory neuron activation. So inhibiting PDE4 likely directly mediates the itch sensation, consistent with the rapid and profound impact on itch demonstrated with ZORYVE across multiple studies. As mentioned, we're seeking to better define the speed of effect of ZORYVE on pruritus in atopic dermatitis through the INTEGUMENT-ITCH trial that we're currently enrolling. PDE4 inhibition also normalizes keratinocyte activation and differentiation, which can lead to mitigation of the epidermal barrier dysfunction that occurs in many inflammatory dermatoses. PDE4 inhibition in general and roflumilast specifically has also demonstrated antifibrotic properties across multiple diseases, including lung fibrosis and on keloids. There are fibrotic components to several inflammatory skin diseases, including hidradenitis suppurativa as we continue to evaluate ZORYVE's application in that indication. This component of roflumilast pleiotropic mechanism of action could potentially be very meaningful. The different elements of this mechanism highlighted on this slide and including the neuronal itch mechanism that I described earlier were reviewed in a recent publication by Dr. Raj Chovatiya? in the International Journal of Dermatology. As we think about each individual indication, these different elements of the PDE4 mechanism of action may be more or less relevant. For instance, in HS, in addition to controlling fibrosis, modulating neuronal signaling and suppressing the core inflammatory pathways that drive disease activity are all important. Approximately 50% of HS patients experience itch and 60% of patients rate their pain as moderate to severe. So potentially being able to address this directly and not just through modulating inflammation could be a benefit. In HS, the inflammatory profile includes TNF alpha and IL-17, where several biologic therapies have been approved. These are pathways clearly linked to PDE4 inhibition and implicated in the efficacy of ZORYVE in approved indications like psoriasis and seborrheic dermatitis. This appears to make ZORYVE and the PDE4 mechanism of PDE4 inhibition, a uniquely interesting fit for hidradenitis suppurativa, a disease which dramatically impacts quality of life and has historically been difficult to manage. And finally, as I now focus on vitiligo, PDE4 inhibition increases melanocyte proliferation, melanocytic gene and protein expression and protects melanocytes from apoptosis. These effects, taken together with the anti-inflammatory properties of ZORYVE, create a wholly differentiated approach to treating vitiligo, one that could potentially address both sides of the disease, putting out the fire by reducing the inflammatory signals driving melanocyte destruction while also rebuilding the house by supporting melanocyte recovery and repigmentation. This mechanistic rationale for ZORYVE's potential impact in vitiligo is one of the components of the basis of our interest in clinical evaluation for ZORYVE in that disease. Another component is the clinical signals that we've seen from the field. I'm now on Slide 15. As we presented at our R&D event last fall, our new indication exploration is guided by a large body of case reports from clinicians who have used ZORYVE in various inflammatory dermatosis beyond our current approved indications. We've been encouraged by multiple case reports from clinicians who pursued vitiligo as a novel application for ZORYVE, particularly in difficult-to-treat vitiligo presentations and the signal of efficacy repigmentation after prior inadequate response to other treatments with no adverse events reported. Today, I wanted to highlight the case of a 37-year-old male patient in Canada that was recently published in the Journal of Drugs in Dermatology. As you can see, this patient with recalcitrant and long-standing vitiligo experienced striking repigmentation across his face at 4 months that further deepened and was maintained at 7 months with the use of ZORYVE cream and narrowband ultraviolet B therapy. This type of case study makes it clear why we've been encouraged to further study the application of ZORYVE in vitiligo. Before moving on, I'll remind you of some aspects of our ongoing Phase II proof-of-concept study with ZORYVE foam 0.3% for the treatment of vitiligo. The purpose of this open-label, single-center proof-of-concept study is to determine whether the clinical signal with ZORYVE supports advancement into Phase III development. The study has met its enrollment target of 20 patients, and the primary endpoint of the study is a number of patients achieving a 50% improvement in their facial vitiligo Area and Severity Index score at week 24. As mentioned, we expect to report results in the fourth quarter, similar efficacy to approved therapies may be enough to support advancement of the program given ZORYVE's strong therapeutic profile with any potential separation in efficacy establishing a potential best-in-class profile. Of course, the Phase III data will influence whether and how we move forward and any registrational program would require alignment with regulatory authorities on the appropriate Phase III design. Even as we advance the vitiligo and HS studies, we continue to evaluate other diseases for similar proof-of-concept studies, and we will keep the investment community apprised if and when we decide to initiate additional proof-of-concept trials. With that, I'll turn it over to Latha to review the financial results.