Rigel Pharmaceuticals, Inc. provided the status of the Phase 3 study in COVID-19, and upcoming catalysts in 2022. Enrollment of Rigel's FORWARD study, a Phase 3 pivotal trial of TAVALISSE in patients with wAIHA, is complete. Rigel expects to report topline data from the 24-week study in mid-2022 and proceed with regulatory filings if the data is positive.

If approved, TAVALISSE has the potential to be the first-to-market therapy for patients with wAIHA in 2023. Rigel's Phase 3 clinical trial evaluating fostamatinib in high-risk patients hospitalized with COVID-19 has enrolled 231 of the targeted 308 patients to date. In December, Rigel expanded the inclusion criteria to include patients with more severe disease (NIAID Ordinal Scale 6) to more accurately reflect the clinically predominant patient population hospitalized with COVID-19 and help speed enrollment.

In collaboration with the United States Food and Drug Administration (FDA) and DOD, Rigel has also updated the primary endpoint for the study from progression to severe disease within 29 days, to the number of days on oxygen through day 29. This endpoint allows for closer comparison of the results with earlier results from the NIH/NHLBI Phase 2 trial with fostamatinib and various other NIH-sponsored trials, such as ACTIV-4, which uses a similar outcome measure as a primary endpoint. Rigel expects to complete enrollment and report topline data in mid-2022.

In addition to Rigel's Phase 3 study, fostamatinib is also being evaluated as a treatment for COVID-19 in two ongoing studies, the NIH/NHLBI-funded Phase 3 ACTIV-4 Host Tissue trial and a Phase 2 open-label clinical trial conducted by Imperial College London. Rigel expects to advance R2899, a potent and selective IRAK1/4 inhibitor, into an open-label Phase 1b/2 clinical study in patients with low-risk myeloid dysplastic syndrome (MDS) in First Quarter 2022. R289 blocks inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor family (IL-1R) signaling.

TLRs and IL-1Rs play a critical role in the innate immune response, and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients. R5529, a potent and selective RIPK1 inhibitor, will advance into Phase 2 development in psoriasis in the 1H 2022 with partner Lilly.

RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in TNF signaling, especially in the induction of pro-inflammatory necroptosis. The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer's disease and ALS. Rigel is completing early discovery work on a potential candidate that Lilly may advance into clinical development.

In December 2021, partner Kissei reported positive topline results for a Phase 3 study in ITP in Japan and is preparing a new drug application (NDA) for submission to Japan's Pharmaceuticals and Medical Devices Agency (PMDA). In October 2018, Rigel entered into an exclusive license and supply agreement with Kissei to develop and commercialize fostamatinib in all current and potential indications in Japan, China, Taiwan and the Republic of Korea. Fostamatinib has Orphan Drug Designation in Japan and Korea.