About Rigel Pharmaceuticals

Rigel Pharmaceuticals, Inc. operates as a biotechnology company. The company engages in discovering, developing, and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Its pioneering research focuses on signaling pathways that are critical to disease mechanisms. The company’s first product approved by the U.S. Food and Drug Administration (FDA) is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only approved oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The product is also commercially available in Europe and the United Kingdom (U.K.) (as TAVLESSE), and in Canada and Israel (as TAVALISSE) for the treatment of chronic ITP in adult patients. The company’s second FDA approved product is REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. The company began its commercialization of REZLIDHIA (olutasidenib) in December 2022. The company in-licensed olutasidenib from Forma Therapeutics, Inc. (Forma), with exclusive, worldwide rights for its development, manufacturing and commercialization. The company conducted a Phase 3 clinical trial evaluating fostamatinib for the treatment of warm autoimmune hemolytic anemia (wAIHA) and announced that the company did not file a supplemental New Drug Application (sNDA) for this indication considering the top-line data results and guidance received from the FDA. The company announced the completion of the FOCUS Phase 3 clinical trial of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19. Fostamatinib is being studied in a National Institute of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) sponsored Accelerating COVID-19 Therapeutic Inventions and Vaccines Phase 2/3 trial (ACTIV-4 Host Tissue Trial) for the treatment of COVID-19 in hospitalized patients. The company’s other clinical programs include its interleukin receptor-associated kinase (IRAK) inhibitor program, and a receptor-interacting serine/threonine-protein kinase (RIPK1) inhibitor program in clinical development with partner, Eli Lilly and Company (Lilly). In addition, the company has product candidates in clinical development with partners, BerGenBio ASA (BerGenBio) and Daiichi Sankyo (Daiichi). Strategy The key elements of the company’s strategy include growing sales of TAVALISSE in the global ITP market; expanding its hematology-oncology portfolio with REZLIDHIA for the treatment of R/R AML patients with a susceptible IDH1 mutation, a well-identified patient population of approximately 1,000 patients, part of an AML market estimated to have an incidence of 20,000 cases in the U.S. and estimated 120,000 cases globally; and expanding its development pipeline on the company’s own and/or with collaboration partner(s). Commercial Products TAVALISSE/Fostamatinib in ITP The company’s Fostamatinib for Immune Thrombocytopenia (FIT) Phase 3 clinical program had a total of 150 ITP patients, which were randomized into two identical multi-center, double-blind, placebo-controlled clinical trials. In August 2015, the U.S. Food and Drug Administration granted the company’s request for Orphan Drug designation for fostamatinib for the treatment of ITP. In August 2016, the company announced the results of the first FIT study, reporting that fostamatinib met the study’s primary efficacy endpoint. In October 2016, the company announced the results of the second FIT study, reporting that the response rate (16% in the treatment group, versus 4% in the placebo group) was consistent with the first study, although the difference was not statistically significant. In the ITP double-blind studies, the most commonly-reported adverse reactions occurring in at least 5% of patients treated with TAVALISSE were diarrhea, hypertension, nausea, dizziness, increased alanine aminotransferase, increased aspartate aminotransferase, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Serious adverse drug reactions occurring in at least 1% of patients treated with TAVALISSE in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis. TAVALISSE was approved by the U.S. Food and Drug Administration in April 2018 for the treatment of ITP in adult patients who have had an insufficient response to a previous treatment, and successfully launched in the U.S. in May 2018. In January 2020, the European Commission (EC) granted the company’s Marketing Authorization Application (MAA) in Europe for fostamatinib (TAVLESSE) for the treatment of chronic ITP in adult patients who are refractory to other treatments. In February 2020, Kissei Pharmaceutical Co., Ltd. (Kissei) was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic idiopathic thrombocytopenic purpura for fostamatinib in chronic ITP. In December 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved the NDA for fostamatinib in chronic ITP. The company’s marketing and sales efforts are focused on hematologists and hematologist-oncologists in the U.S. who manage chronic adult ITP patients. The company has a fully integrated commercial team consisting of sales, marketing, market access, and commercial operations functions. The company’s sales team promotes its products in the U.S. using customary pharmaceutical company practices, and the company concentrate the company’s efforts on hematologists and hematologists-oncologists. The company’s products are sold initially through third-party wholesale distribution and specialty pharmacy channels and group purchasing organizations before being ultimately prescribed to patients. To facilitate the company’s commercial activities in the U.S., the company also enters into arrangements with various third parties, including advertising agencies, market research firms and other sales-support-related services as needed. In addition, the company’s collaborative partner Grifols has launched TAVLESSE in the U.K. and certain countries in Europe, including Germany, France, Italy and Spain; and continues a phased rollout across the rest of Europe. Also, the company’s collaborative partner Medison has launched TAVALISSE in Canada and Israel. Fostamatinib in Global Markets The company has entered into various license agreements to commercialize fostamatinib globally. The following describes the arrangements the company has in place with Grifols, Kissei, Medison Pharma Trading AG (Medison Canada) and Medison Pharma Ltd. (Medison Israel, and together with Medison Canada, Medison), and Knight Therapeutics International SA (Knight). The company retains the global rights to fostamatinib outside of the Grifols, Kissei, Medison and Knight territories. Fostamatinib in Europe/Turkey In January 2019, the company entered into a commercialization license agreement with Grifols with exclusive rights to commercialize fostamatinib for human diseases, including chronic ITP and AIHA, and non-exclusive rights to develop, fostamatinib in their territory. Grifols territory includes Europe, the U.K., Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent States). The company is responsible for performing and funding certain development activities for fostamatinib for ITP and AIHA and Grifols is responsible for all other development activities for fostamatinib in such territories. The company remain responsible for the manufacturing and supply of fostamatinib for all development and commercialization activities under the agreement. In January 2020, the EC granted a MA for fostamatinib for the treatment of chronic ITP in adult patients who are refractory to other treatments. Fostamatinib in Japan/Asia In October 2018, the company 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. Kissei is a Japan-based pharmaceutical company addressing patients’ unmet medical needs through its research, development and commercialization efforts, as well as through collaborations with partners. In September 2019, Kissei initiated a Phase 3 trial in Japan of fostamatinib in adult patients with chronic ITP. The efficacy and safety of orally administered fostamatinib was assessed by comparing it with placebo in a randomized, double-blind study. In February 2020, Kissei was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP. In December 2021, Kissei reported positive top-line results for a Phase 3 clinical trial of fostamatinib in adult Japanese patients with chronic ITP, meeting its primary endpoint. The Phase 3 clinical trial showed that patients receiving fostamatinib achieved a stable platelet response significantly higher than patients receiving a placebo control. Based on the positive Phase 3 results, in April 2022, Kissei submitted an NDA to Japan’s PMDA for fostamatinib in chronic ITP. In December 2022, Japan’s PMDA approved TAVALISSE for the treatment of chronic ITP. Fostamatinib in Canada/Israel In October 2019, the company entered into exclusive commercial and license agreements with Medison to commercialize fostamatinib in all potential indications in Canada and Israel. Pursuant to this exclusive commercialization license agreement, in August 2020, the company entered into a commercial supply agreement with Medison. In November 2020, Health Canada approved the New Drug Submission for TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to other treatments. In August 2021, Medison Israel received the licenses for registrational approval from the Ministry of Health, which triggered the first milestone that is the regulatory approval of the product in Israel for the first indication. In November 2022, Medison Israel made its first commercial sale of TAVALISSE. Fostamatinib in Latin America In May 2022, the company entered into commercial license agreement with Knight for the commercialization of fostamatinib for approved indications in Latin America, consisting of Mexico, Central and South America, and the Caribbean (Knight territory). The company is also responsible for the exclusive manufacture and supply of fostamatinib for all future development and commercialization activities under a Commercial and Supply Agreement. REZLIDHIA in R/R AML with mIDH1 In July 2022, the company entered into a license and transition agreement with Forma for an exclusive license to develop, manufacture and commercialize olutasidenib, Forma’s proprietary inhibitor of mIDH1, for any uses worldwide, including for the treatment of R/R AML and other malignancies. Olutasidenib is an oral, small molecule drug designed to selectively bind to and inhibit mIDH1. REZLIDHIA (olutasidenib) is an oral, small molecule, inhibitor of mIDH1 designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells. On December 1, 2022, the U.S. Food and Drug Administration has approved REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML with IDH1 mutation as detected by an FDA approved test. On December 22, 2022, the company began the commercialization of REZLIDHIA and made it available to patients. The recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or unacceptable toxicity. The U.S. Food and Drug Administration approval was based on the NDA for olutasidenib for the treatment of m1DH1 R/R AML submitted by Forma, that had a PDUFA action date for the application of February 15, 2023. The NDA application was supported with Forma’s Phase 2 registrational trial for olutasidenib in mIDH1 R/R AML. Interim results from Forma’s Phase 2 registrational trial were reported at the American Society of Clinical Oncology (ASCO) annual meeting in June 2021. Olutasidenib was designated by the U.S. Food and Drug Administration as an orphan drug for the treatment of acute myeloid leukemia in April 2017. On November 3, 2022, the company announced the presentation of five posters highlighting data from the company’s commercial and clinical hematology-oncology portfolio at the 64th ASH Annual Meeting and Exposition, which was held in December 2022. An updated interim analysis from the Phase 2 registrational trial of olutasidenib in patients with R/R AML demonstrated robust efficacy and safety results. On November 10, 2022, the company announced the publication of data in The Lancet Haematology, which summarizes the Phase 1 results of the Phase 1/2 trial of olutasidenib. In January 2023, the company announced that REZLIDHIA (olutasidenib) has been added by the National Comprehensive Cancer Network (NCCN) to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML. REZLIDHIA is included as a recommended targeted therapy for adult patients with R/R AML with IDH1 mutation. In February 2023, the company announced peer-reviewed publication data in Blood Advances, which summarize clinical results from the Phase 2 registrational trial of REZLIDHIA (olutasidenib) in patients with mIDH1 R/R AML. The company plans to pursue strategic actions to further develop olutasidenib for the treatment of other malignancies and expansion of commercialization. REZLIDHIA is highly synergistic with the company’s existing hematology-oncology focused commercial and medical affairs infrastructure. The company’s commercial efforts will focus on targeting hematologists and hematologist-oncologists who manage patients with R/R AML with mIDH1. The company plans to enter collaborations with third parties to commercialize REZLIDHIA outside of the U.S. Clinical Stage Programs R289, an Oral IRAK1/4 Inhibitor for Autoimmune, Inflammatory and Hematology-Oncology Diseases During the second quarter of 2018, the company selected R835, the active metabolite of R289, a proprietary molecule from the company’s IRAK 1/4 preclinical development program, for human clinical trials. This investigational candidate is an orally administered, potent and selective inhibitor of IRAK1 and IRAK4 that blocks inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 receptor (IL-1R) family signaling. R835 prevents cytokine release in response to TLR and IL-1R activation in vitro. R835 is active in multiple rodent models of inflammatory disease, including psoriasis, arthritis, lupus, multiple sclerosis and gout. Preclinical studies show that R835 inhibits both the IRAK1 and IRAK4 signaling pathways, which play a key role in inflammation and immune responses to tissue damage. Dual inhibition of IRAK1 and IRAK4 allows for more complete suppression of pro-inflammatory cytokine release than inhibition of either one individually. In October 2019, the company announced results from a Phase 1 clinical trial of R835 in healthy subjects to assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics. The Phase 1 trial was a randomized, placebo-controlled, double-blind trial in 91 healthy subjects, ages 18 to 55. The company continues to advance the development of its IRAK1/4 program, completing the evaluation of a new pro-drug formulation of R835, R289, in single-ascending and multiple ascending dose studies with positive safety results in 2021. In January 2022, the company received clearance from the FDA on the company’s clinical trial design to explore R289 in low-risk MDS. The open-label, Phase 1b trial will determine the tolerability and preliminary efficacy of R289 in patients with low-risk MDS who are refractory or resistant to prior therapies. In December 2022, the company announced that the company dosed the first patient in its Phase 1b trial of R289. The Phase 1b trial of R289 is expected to enroll approximately 22 patients. Fostamatinib in Hospitalized COVID-19 Patients In November 2020, the company launched its FOCUS Phase 3 clinical trial to evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. In December 2021, the company 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 FDA and Department of Defense, the company also updated the primary endpoint for the trial 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 clinical trial with fostamatinib and various other NIH-sponsored trials, such as the ACTIV-4 Host Tissue Trial, which uses a similar outcome measure as a primary endpoint. In July 2022, the company completed enrollment with 280 patients. The trial had originally targeted a total of 308 patients; however, the company determined the trial would be sufficiently powered with 280 patients to potentially provide a clinically meaningful result and determine the efficacy and safety of fostamatinib in hospitalized COVID-19 patients. On November 1, 2022, the company announced the top-line results of the FOCUS trial. The company is evaluating the opportunity and discussing next steps with the FDA and in collaboration with the company’s partner, the U.S. Department of Defense. In September 2020, the company announced a Phase 2 clinical trial sponsored by the NIH/NHLBI to evaluate the safety of fostamatinib for the treatment of hospitalized COVID-19 patients. This multi-center, double-blind, placebo-controlled trial randomly assigned fostamatinib or matched placebo (1:1) to 59 evaluable patients. The trial completed the enrollment in March 2021. In April 2021, the company announced that the Phase 2 clinical trial met its primary endpoint of safety. In May 2021, the NIH/NHLBI Phase 2 clinical data were submitted as part of a request for an EUA from the FDA for fostamatinib as a treatment for hospitalized patients with COVID-19. In August 2021, the FDA informed the company that the clinical data submitted from the NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat hospitalized patients suffering from COVID-19 was insufficient for an EUA. In June 2021, the company announced that fostamatinib had been selected for the NIH ACTIV-4 Host Tissue Trial in hospitalized patients with COVID-19. The ACTIV-4 Host Tissue Trial, initiated and funded by NHLBI, is a randomized, placebo-controlled trial of therapies, including fostamatinib, targeting the host response to COVID-19 in hospitalized patients. In July 2020, the company announced a Phase 2 clinical trial sponsored by Imperial College of London to evaluate the efficacy of fostamatinib for the treatment of COVID-19 pneumonia. This is a two-stage, open label, controlled clinical trial with patients randomized (1:1:1) to fostamatinib plus SoC, ruxolitinib plus SoC, or SoC alone. Fostamatinib in wAIHA The company completed its Phase 2 clinical trial, also known as the SOAR study, in patients with wAIHA. This trial was an open-label, multi-center, two-stage study that evaluated the efficacy and safety of fostamatinib in patients with wAIHA who had previously received treatment for the disorder but have relapsed. In January 2021, the company announced that the FDA had granted Fast Track designation to fostamatinib for the treatment of wAIHA. The FDA previously granted fostamatinib Orphan Drug designation for the treatment of wAIHA in January 2018. In March 2019, the company initiated its wAIHA pivotal Phase 3 clinical trial of fostamatinib, known as the FORWARD study. The clinical trial protocol calls for a placebo-controlled study of 90 patients with primary or secondary wAIHA who have failed at least one prior treatment. In November 2020, the company reached an agreement with the FDA on the durable response measure for the primary efficacy endpoint of the trial, as well as the inclusion of additional secondary endpoints. In November 2021, the company completed the enrollment of this study. In April 2022, the company completed the treatment period for the last patient under the trial. In June 2022, the company announced top-line efficacy and safety data from the FORWARD study with 90 patients. In October 2022, the company announced that the company received guidance from the FDA’s review of these findings. Based on the result of the trial and the guidance from the FDA, the company did not file an sNDA for this indication. Of the 90 patients that completed the FORWARD study, 71 (79%) enrolled in the open-label extension study. The company plans on closing this study in 2023. Partnered Clinical Programs BGB324 – BerGenBio The company has an exclusive, worldwide research, development and commercialization agreement with BerGenBio for the company’s investigational AXL receptor tyrosine kinase inhibitor, BGB324/R428 (now referred to as bemcentinib). In October 2022, BerGenBio announced the initiation of a Phase 1b/2a trial evaluating bemcentinib in combination with the current SoC, checkpoint inhibitor pembrolizumab and doublet chemotheraphy, for the treatment of first line non-small cell lung cancer patients harboring serine/threonine kinase 11 mutations. In February 2023, BerGenBio also announced positive data from Phase 2 trial of bemcentinib in combination with pembrolizumab in patients with 2L+ non-small cell lung cancer (NSCLC). DS-3032 - Daiichi DS-3032 is an investigational oral selective inhibitor of the murine double minute 2 (MDM2) protein investigated by Daiichi in three Phase 1 clinical trials for solid and hematological malignancies, including AML, acute lymphocytic leukemia, chronic myeloid leukemia in blast phase, lymphoma and MDS. Preliminary safety and efficacy data from a Phase 1 trial of DS-3032 suggests that DS-3032 may be a promising treatment for hematological malignancies, including R/R AML and high-risk MDS. In September 2020, worldwide rights to DS-3032 (milademetan) were out-licensed from Daiichi to Rain Oncology Inc. (Rain). In July 2021, Rain announced that it initiated a Phase 3 trial to evaluate the efficacy and safety of milademetan (RAIN-32) for the treatment of well-differentiated/dedifferentiated liposarcoma, a rare cancer originating from fat cells located in the soft tissues of the body and in August 2022, Rain announced the completion of enrollment of its Phase 3 trial for milademetan in liposarcoma. In late 2021, Rain commenced its second clinical trial for RAIN-32 in patients with MDM2-amplified advance solid tumors, and in November 2022, Rain provided an interim analysis of the trial which showed that the drug safety profile of milademetan is preliminary consistent with its prior Phase 1 trial. Intellectual Property As of December 31, 2022, the company owned or had exclusive license to 48 pending patent applications and 376 issued and active patents in the U.S., as well as corresponding pending foreign patent applications and issued foreign patents. The company’s material patents relate to fostamatinib, an oral SYK inhibitor, that is the active pharmaceutical ingredient in TAVALISSE, and olutasidenib, an oral mIDH1 inhibitor that is the active pharmaceutical ingredient in REZLIDHIA. These patents will expire at various dates from 2026 to 2032 for fostamatinib and from 2035 to 2039 for olutasidenib. Fostamatinib: Fostamatinib is covered as a composition of matter in a U.S. issued patent that has an expected expiration date of September 2031, after taking into account a patent term adjustment and extension rules. Additional patents covering fostamatinib composition of matter, methods for use, formulations, methods for making and intermediates expire at various dates from 2023 to 2041. Corresponding applications have been filed in foreign jurisdictions under the PCT, and are at various stages of prosecution. Of note, a patent covering fostamatinib as a composition of matter and in compositions for use treating various diseases has been granted by the European Patent Office. Olutasidenib: Olutasidenib is covered as a composition of matter in a U.S. issued patent that has an expected expiration date of December 2036, after taking into account patent term extension rules. Additional patents covering olutasidenib compositions of matter, methods for use, solid forms, methods for making and intermediates expire at various dates from 2035 to 2042. Several corresponding applications have been filed in foreign jurisdictions under the PCT and are at various stages of prosecution. History Rigel Pharmaceuticals, Inc. was incorporated in Delaware in 1996.