Steven Stein
Executive Vice President and Chief Medical Officer at Incyte
Thank you, Barry. Starting on Slide 11. As Herve mentioned, we have two exciting program updates we want to highlight from this quarter. First for ruxolitinib cream, the primary endpoint was met in the Phase 3 TRuE-AD3 trial in pediatric atopic dermatitis patients aged two to 12. The top line results showed that significantly more patients achieved Investigator's Global Assessment Treatment Score or IGA-TS with ruxolitinib cream 0.75% and 1.5% and with the vehicle control. No new safety signals were observed and the overall safety profile is consistent with previously reported data.
The long-term safety portion of the trial is ongoing and data will be submitted for presentation at an upcoming scientific meeting. We also plan to discuss these data with regulatory agencies and we anticipate a submission in the first quarter of 2024. We are excited about the potential relief ruxolitinib cream can bring to the roughly 2 million pediatric atopic dermatitis patients in the United States.
Moving to Slide 12. In partnership with Syndax, the AGAVE-201 study, the global pivotal trial evaluating axatilimab in patients with chronic graft-versus-host disease after two or more prior therapies, met its primary endpoint of overall response rate across all three treatment cohorts with the 0.3 milligram per kilogram every two week dose, achieving a 74% overall response rate.
In the 0.3 milligram per kilogram cohort, 60% of responders maintained a response at one year, and 55% of patients achieved at least a 7 point decrease in a modified Lee Symptom Scale indicating that responses were both durable and with symptom improvements. Axatilimab was well tolerated and the most common adverse events were consistent with on-target effects. The full dataset is planned for presentation at a scientific meeting later this year with the potential BLA submission by year end 2023. We are excited about the potential of axatilimab in chronic graft-versus-host disease and in this heavily pre-treated and severe patient population. The Phase 1/2 trial of axatilimab in combination with ruxolitinib is also being planned.
Moving to Slide 13, an updates on our broader dermatology pipeline. For Opzelura, in addition to the positive top line pediatric AD data, three Phase 2 studies were lichen planus, lichen sclerosis and hidradenitis suppurativa have completed enrollment. For povorcitinib, the Phase 2 study in prurigo nodularis has completed enrollment and we expect to have data in this indication later this year. Additionally, we previously announced the expansion of povorcitinib development into inflammatory and autoimmune diseases beyond dermatology and now have initiated two Phase 2 trials in asthma and chronic spontaneous urticaria, CSU.
On Slide 14, I want to provide a little more detail on our studies in asthma and chronic spontaneous urticaria. Asthma is a chronic inflammatory disease with two endotypes. Type 2 eosinophilic asthma, the most common type, is primarily driven by Th2 cytokines, whereas non-type 2 asthma is characterized by neutrophilic response. Many asthma patients have disease progression despite therapy with inhalers. Povorcitinib appears to have efficacy in both type 2 and non-type 2 endotypes.
In preclinical data, povorcitinib results in a reduction of eosinophil activation and may potentially reduce neutrophil activation as well. The Phase 2 study has been evaluated in moderate-to-severe uncontrolled type 2 and non-type 2 asthmatic patients. Unlike monoclonal antibodies that target a single cytokine, povorcitinib inhibits the actions of multiple cytokines, potentially providing superior efficacy in both endotypes.
CSU is a mast-cell driven disease, presenting with hives in severe chronic itch. Over-activation of dermal mast-cells and basophils results in increased serum levels of Th1, Th2 and Th17-related cytokines. We know JAK inhibition can modulate mast-cell activation, including the granulation in cytokine production, both of which are drivers of chronic spontaneous urticaria. The Phase 2 study has been evaluated in patients who are inadequately controlled or progress on second-generation antihistamines.
Moving to hematology and oncology. We achieved multiple clinical milestones across our high potential portfolio during the second quarter. We continue to make progress in myeloproliferative neoplasms or MPNs, where we presented updated clinical data at ASCO for our ALK2 and BET program. We also initiated the Phase 1 study of INCA33989, a mutant CALR anybody, and as previously discussed, axatilimab met the primary endpoint in chronic graft-versus-host disease.
For oncology, both of the Phase 3 studies evaluating tafasitamab in first-line diffuse large B-cell lymphoma and in relapsed or refractory follicular and marginal zone lymphoma are fully enrolled, and the small molecule oral PD-L1 program continues to advance with multiple new studies initiated.
Turning to Slide 16, and an update on our small molecule oral PD-L1 program. Immune checkpoint inhibitors have transformed cancer treatment for patients. Despite the remarkable clinical benefits, intravenous formulations have disadvantages and there is ample opportunity for innovation and improved outcomes in the space. As the first company to demonstrate clinical activity with an orally available PD-L1 targeted agent, we have an unique opportunity for differentiation.
As an oral small molecule INCB99280 has a short half-life, which can reduce the burden of managing immune-related toxicities and provides a switch-off option if needed, which may offer improved overall safety, especially when combined with other agents. Additionally, the convenience of an at-home oral administration is often preferred by patients and may offer the potential for an improved quality of life.
On the right, you can see the current studies of INCB99280. We've initiated monotherapy Phase 2 studies in both checkpoint inhibitor naive patients and in cutaneous squamous cell carcinoma. We also initiated two Phase 1/2 combination studies with axitinib and ipilimumab. A third Phase 1/2 study in combination with adagrasib is in preparation. We also announced last night that in partnership with Replimune, we are starting a neoadjuvant study to evaluate 280 in combination with RP1, a tumor-derived oncolytic immunotherapy in patients with cutaneous squamous cell carcinoma.
RP1 is Replimune's lead oncolytic immunotherapy product and is based on a proprietary new strain of herpes simplex virus engineered for robust tumor selective replication and is genetically armed with a fusogenic protein and GM-CSF. RP1 has already demonstrated substantial activity in cutaneous squamous cell carcinoma.
At ASCO, we presented data for the zilurgisertib, a ALK2 inhibitor in patients with myelofibrosis. Initial data from 36 patients demonstrated early signs of clinical activity through hepcidin reduction and anemia response in monotherapy and in combination with ruxolitinib. Zilurgisertib was well tolerated with a favorable safety profile allowing for continued dose escalation. We have added an additional treatment group in first-line JAK naive myelofibrosis patients with anemia and we plan to have updated data later this year.
Additional data presented at ASCO for our BET inhibitor, our INCB57643, demonstrated improvement in spleen volume and symptoms in both the monotherapy arm and in combination with ruxolitinib. It was generally well-tolerated with two dose limiting toxicities observed in the higher 12 milligram once daily monotherapy arm. We believe we have an active compound with encouraging early data. Dose-finding work is ongoing with 10 milligrams once daily as monotherapy, as well as continued dose escalation in the combination arm.
Turning to Slide 19. We continue to make progress in other development programs. During the quarter, INCA33890, a TGF-beta R2 by PD1 bispecific antibody entered the clinic and a Phase 1 study was initiated. Additionally auremolimab, anti-IL-15 receptor beta antibody received IND clearance and we plan for to enter the clinic later this year. Retifanlimab which is recently approved in Merkel cell carcinoma has completed enrollment in the Phase 3 non-small cell lung cancer study and in the squamous cell anal carcinoma study.
Finally, on Slide 20, we have a number of upcoming data readouts and other exciting milestones expected and we look forward to sharing additional details throughout the remainder of this year.
With that, I'd like to turn the call over to Christiana for the financial update.
