Rigel(RIGL) - 2022 Q4 - Annual Report

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Business Rigel Pharmaceuticals is a biotechnology company focused on developing novel therapies for hematologic disorders and cancer, with commercial products TAVALISSE and REZLIDHIA, and a pipeline of clinical programs - Rigel Pharmaceuticals is a biotechnology company focused on hematologic disorders and cancer, with a strategy to expand its commercial business in the US and globally through partnerships[16][42] - The company's commercial products include TAVALISSE (fostamatinib) for chronic ITP and REZLIDHIA (olutasidenib) for relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible IDH1 mutation[17][18][43] - Key development programs include an IRAK1/4 inhibitor (R289) for low-risk MDS, fostamatinib in COVID-19 (Phase 3 did not meet statistical significance), and partnered RIPK1 inhibitors with Eli Lilly and Company[19][27][30][33] Overview Rigel Pharmaceuticals is a biotechnology company dedicated to discovering, developing, and providing novel therapies for hematologic disorders and cancer, focusing on critical signaling pathways - Rigel Pharmaceuticals is a biotechnology company dedicated to discovering, developing, and providing novel therapies for hematologic disorders and cancer, focusing on critical signaling pathways[16] - TAVALISSE (fostamatinib) is the only approved oral spleen tyrosine kinase (SYK) inhibitor for chronic immune thrombocytopenia (ITP) in adults, commercially available in the US, Europe, UK, Canada, and Israel[17] - REZLIDHIA (olutasidenib) was FDA-approved in December 2022 for adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible IDH1 mutation, with commercialization beginning in December 2022[18] - fostamatinib's Phase 3 trial for warm autoimmune hemolytic anemia (wAIHA) did not lead to an sNDA filing due to top-line data and FDA guidance, and its FOCUS Phase 3 trial for hospitalized COVID-19 patients was completed but did not meet statistical significance in the primary endpoint[18] - Other clinical programs include an IRAK inhibitor (R289) and a RIPK1 inhibitor program partnered with Eli Lilly and Company, along with product candidates with BerGenBio ASA and Daiichi Sankyo[19] Business Updates Rigel's business updates include TAVALISSE sales growth, REZLIDHIA FDA approval and launch, R289 Phase 1b initiation, and fostamatinib trial results for COVID-19 and wAIHA TAVALISSE Net Product Sales (2021-2022) | Year | Net Product Sales (Millions USD) | Change YoY | Primary Drivers | | :--- | :------------------------------- | :--------- | :-------------- | | 2022 | $75.8 million | +20% | Increased quantities sold, price per bottle. Offset by higher revenue reserves (rebates). | | 2021 | $63.0 million | - | - | - REZLIDHIA (olutasidenib) received FDA approval on December 1, 2022, for R/R AML with a susceptible IDH1 mutation, with commercialization starting on December 22, 2022, generating $0.9 million in net product sales in 2022[22][24] - Rigel in-licensed olutasidenib from Forma Therapeutics, Inc. for an upfront fee of $2.0 million, with potential milestone payments up to $67.5 million (development/regulatory) and $165.5 million (commercial), plus tiered royalties[25][26] - Rigel dosed the first patient in a Phase 1b trial of R289, an IRAK1/4 inhibitor, for low-risk Myelodysplastic Syndromes (MDS) in December 2022, aiming to assess tolerability and preliminary efficacy[27] - The FOCUS Phase 3 clinical trial of fostamatinib for hospitalized COVID-19 patients completed enrollment in July 2022, but top-line results in November 2022 did not meet statistical significance (p=0.0603) for the primary efficacy endpoint[30] - The FORWARD study, a Phase 3 trial of fostamatinib in warm autoimmune hemolytic anemia (wAIHA), did not demonstrate statistical significance in its primary efficacy endpoint, leading Rigel not to file a supplemental New Drug Application (sNDA) for this indication[32] - Rigel has a global exclusive license and collaboration agreement with Eli Lilly and Company for RIPK1 inhibitors (R552 for non-CNS diseases and other RIPK1 inhibitors for CNS diseases), with Lilly advancing R552 into a Phase 2a trial for rheumatoid arthritis in H1 2023[33][35][37] - Rigel filed a patent infringement lawsuit against Annora Pharma Private Limited in July 2022 regarding a generic version of TAVALISSE, following Annora's Abbreviated New Drug Application (ANDA) submission[38] - The COVID-19 pandemic has adversely impacted Rigel's business, including reduced patient-doctor interactions and sales force visits, but the company did not experience significant supply chain disruptions[39][40] Strategy Rigel's strategy focuses on expanding its commercial presence in hematology-oncology and growing its development pipeline through internal efforts and partnerships - Rigel's goal is to be a successful commercial-stage biopharmaceutical company by expanding its commercial business in the US and globally through partnerships, focusing on hematology-oncology[42] - Key value drivers include growing TAVALISSE sales in the global ITP market (estimated over $2.0 billion), expanding the hematology-oncology portfolio with REZLIDHIA for R/R AML (targeting ~1,000 patients in a US market of ~20,000 cases), and expanding the development pipeline[43] Commercial Products Rigel's commercial products include TAVALISSE (fostamatinib) for chronic ITP and REZLIDHIA (olutasidenib) for R/R AML with mIDH1 TAVALISSE/Fostamatinib in ITP TAVALISSE (fostamatinib) is an oral SYK inhibitor approved for chronic ITP, demonstrating stable platelet responses and facing competition from existing and generic therapies - Chronic ITP affects an estimated 81,300 adult patients in the US, characterized by immune system attack on blood platelets, leading to bruising, bleeding, and fatigue[44] - fostamatinib, an oral SYK inhibitor, blocks the activation of SYK inside immune cells, interrupting platelet destruction in ITP[45] - TAVALISSE was FDA-approved in April 2018 for chronic ITP, and subsequently received marketing authorization in Europe (January 2020) and approval in Japan (December 2022)[48][67] - A post-hoc analysis of Phase 3 data showed a 78% response rate when TAVALISSE was used as a second-line therapy in chronic ITP[49][50] - Rigel's commercial efforts for TAVALISSE in the US target hematologists and hematologist-oncologists, supported by a fully integrated commercial team and patient support programs like Rigel OneCare (ROC)[52] - TAVALISSE faces competition from existing ITP therapies like corticosteroids, TPO-RAs (PROMACTA, Nplate, DOPTELET), and immunosuppressants, with potential future competition from generic versions, including an ANDA filed by Annora Pharma[54][55][56][58][59] Fostamatinib in Global Markets Rigel has established global partnerships for fostamatinib commercialization, involving upfront payments, milestones, and royalties, with key achievements in Japan and Israel - Rigel partnered with Grifols for exclusive commercialization rights of fostamatinib in Europe, UK, Turkey, Middle East, North Africa, and Russia, receiving a $30.0 million upfront payment and potential milestones up to $297.5 million, plus tiered royalties[62][63](index=63