Pablo Cagnoni
President, Head of Research and Development at Incyte
Thank you, Herve, and good morning, everyone. In the first quarter, we continued to make solid progress across our pipeline, which is focused on three areas: MPNs and graft versus host disease, oncology and inflammatory diseases. In MPNs and graft versus host disease, we initiated a Phase I study earlier this quarter were a JAK2 V617F inhibitor. As a reminder, the JAK2 V617 mutation is the most common somatic mutation in myeloproliferative neoplasms and is present in 55%, 60% and 95% of patients with MF, ET and PV, respectively.
Unlike ruxolitinib, which inhibits both wild-type and V617F mutation positive cells, 058 selectively binds to the JAK2 JH2 site, disrupting the V617F induced confirmation and thus allowing selective inhibition of mutant activity in the JAK2 receptor while sparing wild type. Together with our anti-mutCALR program, these two potentially disease-modifying programs represent a fundamentally new approach to addressing MF, ET and PV, and could help to solidify our leadership in MPNs.
As previously disclosed, we submitted a BLA for axatilimab for the treatment in third-line chronic graft versus host disease late last year. In February, the filing was accepted for prior review and we anticipate a decision by the FDA in the second half of 2024. We are excited by the possibility of bringing new treatment options to patients with this devastating complication of hematopoietic stem cell transplant.
In oncology, we continue to build out a robust pipeline with the potential to deliver meaningful innovation for patients. This quarter, we initiated a Phase I study with our KRAS G12D inhibitor, iNCb-161734. 734 is a potent, selective and orally bioavailable KRAS G12D inhibitor. And as highlighted at AACR earlier this month, it has shown excellent efficacy in several preclinical models. With no currently approved G12D targeting agents, 734 could address an important patient need as the KRAS G12D mutation is found in 40% of pancreatic ductal adenocarcinoma, 15% of colorectal cancers and 5% of non-small cell lung cancers.
In dermatology, we continue to maximize the potential of ruxolitinib cream and povorcitinib and believe the acquisition of Escient Pharmaceuticals will substantially expand our IAI pipeline by adding two first-in-class medicines with the potential to address a number of medical needs. The key driver of our interest in Escient is our MRGPRX2 program. MRGPRX2 is a specific novel mechanism for blocking mast cell activation independent from IgE and has been a high-priority target to add to our IAI pipeline.
EP262 is a first-in-class medicine, which entered the clinic in January of 2023 and has been evaluated in Phase II studies. In the Phase I healthy volunteer study, EP262 was well tolerated, had low interpatient PK variability, and achieved exposures well above predicted efficacious levels. EP262 is currently in a Phase Ib open-label study in SYNdu and in two randomized Phase II studies in CSU and atopic dermatitis, with data for all three studies expected by early 2025.
EP547 is a potent and highly selective antagonist of MRGPRX4. MRGPRX4 is expressed on neurons in the dorsal root ganglia and specifically activated by bile acids that are increased in cholestatic patients. Initial evaluation is being conducted in cholestatic pruritus with clinical proof of concept for cholestatic pruritus associated with PBC and PSC anticipated by early 2025. A number of exciting readouts are expected by early 2025 with a potential first launch in CSU by 2029.
At AAD earlier this quarter, we presented additional data from the randomized Phase II study of ruxolitinib cream in patients with mild to moderate hydranitissuprativa reinforcing the potential ruxolitinib cream in this indication. The study met its primary endpoint, demonstrated a significantly greater reduction in abscess and inflammatory natural count compared to control at week 16, and further reinforces the efficacy and safety profile of ruxolitinib cream. We are currently engaging with the FDA to obtain agreement on a potential Phase III design.
We also presented positive data at AAD from the randomized Phase II study evaluating povorcitinib in patients with prurigo nodularis and are on track to initiate a Phase III study in the coming months. As highlighted on Slide 21, the study met its primary endpoint of a four or greater point improvement in the Itch Numerical Rating Scale score, which was achieved by significantly more patients who received povorcitinib across all dosing groups at week 16 versus placebo.
We believe that with ruxolitinib cream and povorcitinib, we will be the only company with the ability to potentially provide both atopical and oral option for a number of indications, including prurigo nodularis, hedrinatesuprativa and vitiligo.
We continue to make important progress in the first quarter by achieving several clinical and regulatory milestones. Within our oncology pipeline, we believe that our potentially best-in-class CDK2 inhibitor is an active agent, and we look forward to sharing data as well as our development plan later this year. In addition, the pivotal trial of tafacitamab in patients with follicular and marginal zone lymphoma, also known as NMIND, will read out later this year, and we look forward to sharing those results.
With the BLA for axatilimab submitted late last year, we look forward to working with the FDA to make axatilimab available to patients with chronic graph versus host disease later this year, and to initiate additional combination studies in patients with less pretreated chronic graft versus host disease. Within our dermatology portfolio, we expect to submit the sNDA for Opzelura for pediatric atopic dermatitis and expect multiple data readouts throughout the year.
With that, I would like to turn the call over to Christiana for the financial update.
