Steven Stein
Executive Vice President & Chief Medical Officer at Incyte
Thank you, Barry. On Slide 15 is a snapshot of a few of our programs, including our high-potential programs as depicted in the red and blue boxes segmented by estimated launch timing.
Over the next six to 18 months, many of these programs will be expanded into new indications, new combination studies and into pivotal trials. By focusing resources on these assets, it could allow for an acceleration of certain timelines and increased efficiency as we bring these innovative therapies to patients. We are well positioned for growth and diversification with multiple launches expected in the near to mid-term.
Moving to Slide 16. We made significant progress across our high-potential dermatology programs. Opzelura was approved for vitiligo in Europe and we presented new data for both Opzelura and Povorcitinib at two major dermatology conferences. We also progressed into new indications, including prurigo nodularis with Opzelura and asthma and chronic spontaneous urticaria with Povorcitinib.
Now to highlight our dermatology portfolio in more detail, starting with Opzelura and the recent European approval on Slide 17. The label was very favorable with regards to both efficacy and safety. The full indication is for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age upwards. This encompasses the majority of vitiligo patients in Europe, where roughly 85% of all vitiligo patients have non-segmental disease and where around 60% to 80% have facial involvement.
Regarding safety, the most common adverse reaction was application site acne. No black triangle was placed on the label, and the regulatory agency determined that the class effect identified for the oral class were not considered relevant for Opzelura. And as such, the label does not include any special warnings or precautions as seen with the oral JAK inhibitors.
Turning to Slide 18. We recently initiated two Phase III studies evaluating Opzelura in prurigo nodularis, a disease driven by inflammation and characterized by hard nodules and an intense itch. TRuE-PN1 and TRuE-PN2 of 52-week studies where patients will receive ruxolitinib cream or vehicle for 12 weeks followed by a 40-week open-label extension.
The primary endpoint is WI-NRS which is defined as a four point or greater improvement in worst itch numerical rating scale score from baseline to week 12. There is a strong rationale for Opzelura in prurigo nodularis where we have seen promising early data and where there is already a regulatory precedent for approval with clearly defined endpoints. With no topical or oral therapies approved, we have a significant opportunity to help a large population of patients who are suffering from this disease.
Turning to Slide 19. We continue to expand the development of Opzelura into new indications, it has the potential to provide significant value as either the first approved therapy or first topical therapy for patients living with these dermatologic conditions.
Moving to Povorcitinib on Slide 20. We recently presented positive Phase II results at the American Academy of Dermatology Annual Meeting, highlighting the effect of Povorcitinib on repigmentation in patients with extensive vitiligo. Substantial repigmentation was seen with Povorcitinib treatment and continue to improve with longer duration of therapy with up to 36% of Povorcitinib-treated patients achieving a facial VASI75 by week 36. Based on these positive Phase II results, we plan to move into Phase III development.
Being able to provide patients with an effective oral therapy to treat their vitiligo is part of our strategy to strengthen our leadership in vitiligo and to be able to provide multiple treatment options for patients across the entire disease spectrum.
On Slide 21, at the European Hidradenitis Suppurativa Foundation Conference, we presented Phase II data showing that 52% to 56% of patients treated with Povorcitinib achieved a HiSCR50 at week 16. Perhaps even more impressive was that up to 29% of patients on Povorcitinib reached HiSCR100 at week 52, which is a 100% reduction in abscess and nodule count with no increase in abscess or draining tunnels relative to the baseline. This is a very high clinical bar of efficacy. We are the first to ever present the achievement of HiSCR100 in HS.
Based on the Phase II results, we initiated two Phase III trials, STOP-HS1 and STOP-HS2. Similar to ruxolitinib cream, we are building a portfolio for Povorcitinib around the science all while leveraging our extensive dermatology capabilities. As mentioned earlier, we are initiating two phase trials in moderate to severe asthma and chronic spontaneous urticaria.
Given what is known about the involvement of the JAK pathway in the regulation of cytokines and Th2 cells, initiating a study in asthma is a logical next step for the development of Povorcitinib. Likewise, we know JAK inhibition can modulate mast cell activation, including degranulation and cytokine production, both of which are drivers of chronic spontaneous urticaria.
Moving to our hematology and oncology portfolio on Slide 23. Looking at our high-potential oncology programs, we continue to make progress in myeloproliferative neoplasms, or MPNs with our ALK2 and BET program and axatilimab in chronic graft versus host disease.
Our small molecule RO PD-L1 program is advancing into multiple Phase II studies in combination with adagrasib, ipilimumab and axitinib. For our early stage assets, we recently presented data at the American Association for Cancer Research Annual Meeting for CDK2 and our newly disclosed bispecific TGFBR2 PD-1 antibody. And lastly, we recently announced the approval of Zynyz for Merkel cell carcinoma, which is currently in Phase III trials in squamous cell anal carcinoma and non-small cell lung cancer.
Turning to Slide 24. We have several programs progressing in MPNs in graft versus host disease. Zilurgisertib is in dose escalation. We are currently at doses of 400 milligrams once daily in combination with ruxolitinib, and we were adding a treatment arm for newly diagnosed patients. We continue to see signs of clinical activity, including decreased levels of hepcidin as well as hemoglobin responses with no dose limiting toxicities to date.
For our BET inhibitor, dose escalation is ongoing, where we are currently at doses of 6 milligrams once daily in combination with ruxolitinib. In monotherapy and in combination therapy, we have seen reductions in spleen length and volume as well as improvements in both symptoms and hemoglobin, suggesting 57643 is an active compound.
INCA33989, our mutant CALR antibody is on track to enter the clinic later this year and the study evaluating Cellenkos' CK0804 in combination with ruxolitinib continues to progress. Lastly, we expect results from the AGAVE-201 study later this year.
Before moving on to the next slide, I did want to speak briefly on the CRL for ruxolitinib XR. The FDA determined that while bioequivalence was achieved in the area under the curve or AUC, they had questions around semen [Phonetic] and its correlation with efficacy. We will work with the FDA to determine the appropriate next steps and we will provide an update at that time.
Turning to Slide 25. Preclinical data from our CDK2 and TGFBR2 PD-1 bispecific. INCB123667, a selective oral small molecule CDK2 inhibitor is in a Phase I dose ranging study in advanced solid tumors. CDK2 in complex with Cyclin E is a cell cycle regulator, which when inhibited has been shown to suppress tumor growth, mainly in Cyclin E high tumor models in vivo.
On the right is INCB33890, a TGFBR2 PD-1 bispecific, which has been engineered to invoid the known toxicity of broad TGF-beta pathway blockade. 33890 has a tenfold higher affinity for PD-1 and TGFBR2 and blocks TGF-beta signaling in cells co-expressing PD-1, thus potentially protecting normal tissue. Preclinical in vivo data presented at AACR showed that 33890 has a greater antitumor effect and individual benchmark antibodies or a simple combination of these.
Turning to Slide 26. For the remainder of the year, we expect numerous data readouts and important strategic decisions for many of our high potential programs and we look forward to updating you throughout the year.
With that, I would like to turn the call over to Christiana for the financial update.
