RegulationAccelerated Approval (United States), Orphan Drug (United States), Priority Review (China), Breakthrough Therapy (China), Conditional marketing approval (China), Breakthrough Therapy (United States)

Structure/Sequence

Molecular FormulaC27H32FN9O2

InChIKeyGBLBJPZSROAGMF-RWYJCYHVSA-N

CAS Registry2097132-94-8

Clinical Trials associated with Pralsetinib

NCT06563999

/ RecruitingPhase 2IIT

Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

Start Date01 Nov 2024

Sponsor / Collaborator

Sun Yat-Sen University

NCT04760288

/ WithdrawnPhase 3

A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for Treatment of RET-Mutated Medullary Thyroid Cancer.

A study to evaluate the efficacy and safety of pralsetinib compared with SOC treatment (cabozantinib or vandetanib) for participants with RET (rearranged during transfection)-mutant MTC who have not previously received a SOC MultiKinase Inhibitor (MKI) therapy. Participants will be randomized in a 1:1 ratio into one of two treatment arms: Arm A (pralsetinib) or Arm B (investigator's choice of either cabozantinib or vandetanib for adults and vandetanib for adolescents). Participants whose disease progresses during SOC treatment will be offered the option to cross over to receive pralsetinib after confirmation of progressive disease by blinded independent central review (BICR).

Start Date30 Nov 2023

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

CTR20232998

/ CompletedNot Applicable

评估受试制剂普拉替尼胶囊（规格：100 mg）与参比制剂普吉华®（规格：100 mg）在健康成年受试者空腹状态下的单中心、开放、随机、单剂量、两制剂、两序列、四周期、完全重复生物等效性研究

[Translation] A single-center, open-label, randomized, single-dose, two-drug, two-sequence, four-cycle, fully repeated bioequivalence study was conducted to evaluate the bioequivalence of the test formulation Pratinib Capsules (100 mg) and the reference formulation Pujihua® (100 mg) in healthy adult subjects under fasting conditions.

主要试验目的：研究空腹状态下单次口服受试制剂普拉替尼胶囊（规格：100 mg，凯莱英生命科学技术（天津）有限公司生产）与参比制剂普拉替尼胶囊（普吉华®，规格：100 mg；Catalent CTS, LLC生产）在健康受试者体内的药代动力学特征，评价空腹状态口服两种制剂的生物等效性。次要试验目的：研究受试制剂普拉替尼胶囊（规格：100 mg）和参比制剂普拉替尼胶囊（普吉华®）（规格：100 mg）在健康受试者中的安全性。

[Translation]

The main purpose of the study is to study the pharmacokinetic characteristics of the test preparation pralatinib capsule (specification: 100 mg, produced by Alexin Life Science Technology (Tianjin) Co., Ltd.) and the reference preparation pralatinib capsule (Pujihua®, specification: 100 mg; produced by Catalent CTS, LLC) in healthy subjects after a single oral administration under fasting conditions, and to evaluate the bioequivalence of the two preparations when taken orally under fasting conditions. Secondary purpose of the study is to study the safety of the test preparation pralatinib capsule (specification: 100 mg) and the reference preparation pralatinib capsule (Pujihua®) (specification: 100 mg) in healthy subjects.

Start Date30 Oct 2023

Sponsor / Collaborator

Cornerstone Pharmaceutical Co., Ltd

100 Clinical Results associated with Pralsetinib

100 Translational Medicine associated with Pralsetinib

100 Patents (Medical) associated with Pralsetinib

318

Literatures (Medical) associated with Pralsetinib

01 Apr 2025·MOLECULAR DIVERSITY

Targeting AFP-RARβ complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma

Article

Author: Dev, Radul R ; Soman, Sowmya ; Banjan, Bhavya ; Raju, Rajesh ; Vishwakarma, Riya ; Rehman, Niyas ; Kalath, Haritha ; Kumar, Pankaj ; Revikumar, Amjesh ; Abhinand, Chandran S ; Ramakrishnan, Krishnapriya

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARβ interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARβ complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARβ complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

17 Mar 2025·CLINICAL CANCER RESEARCH

YAP Regulates HER3 Signaling–Driven Adaptive Resistance to RET Inhibitors in RET-Aberrant Cancers

Article

Author: Matsui, Yohei ; Nakamura, Ryota ; Morimoto, Kenji ; Arai, Sachiko ; Tokuda, Shinsaku ; Kawachi, Hayato ; Tanimura, Keiko ; Date, Koji ; Horinaka, Mano ; Sakai, Toshiyuki ; Yano, Seiji ; Fujimoto, Daichi ; Yamada, Tadaaki ; Fujisaka, Yasuhito ; Sakata, Yoshihiko ; Katayama, Yuki ; Nishino, Kazumi ; Uehara, Hisanori ; Goto, Yasuhiro ; Takeda, Takayuki ; Watanabe, Satoshi ; Saito, Go ; Muto, Satoshi ; Tsuchiya, Michiko ; Hirai, Soichi ; Takayama, Koichi ; Tamiya, Akihiro ; Ishida, Masaki ; Furuya, Naoki

Abstract:

Purpose::

Rearranged during transfection (RET) aberrations represent a targetable oncogene in several tumor types, with RET inhibitors displaying marked efficacy. However, some patients with RET-aberrant cancer are insensitive to RET tyrosine kinase inhibitors (TKI). Recently, drug-tolerant mechanisms have attracted attention as targets for initial therapies to overcome drug resistance. The underlying mechanisms of drug-tolerant cell emergence treated with RET-TKIs derived from RET-aberrant cancer cells remain unknown. This study investigated the role of YAP-mediated HER3 signaling in the underlying mechanisms of adaptive resistance to RET-TKIs in RET-aberrant cancer cells.

Experimental Design::

Four RET-aberrant cancer cell lines were used to assess sensitivity to the RET-TKIs selpercatinib and pralsetinib and to elucidate the molecular mechanisms underlying adaptive resistance using RNA sequencing, phospho–receptor tyrosine kinase antibody arrays, chromatin immunoprecipitation assay, and luciferase reporter assays. Clinical specimens from patients with RET fusion–positive lung cancer were analyzed for pretreatment YAP expression and correlated with treatment outcomes.

Results::

In high YAP-expressing RET-aberrant cancer cells, YAP-mediated HER3 signaling activation maintained cell survival and induced the emergence of cells tolerant to the RET-TKIs selpercatinib and pralsetinib. The pan-ErBB inhibitor afatinib and YAP/tea domain inhibitors verteporfin and K-975 sensitized YAP-expressing RET-aberrant cancer cells to the RET-TKIs selpercatinib and pralsetinib. Pretreatment YAP expression in clinical specimens obtained from patients with RET fusion–positive lung cancer was associated with poor RET-TKI treatment outcomes.

Conclusions::

The YAP–HER3 axis is crucial for the survival and adaptive resistance of high YAP-expressing RET-aberrant cancer cells treated with RET-TKIs. Combining YAP/HER3 inhibition with RET-TKIs represents a highly potent strategy for initial treatment.See related commentary by Ortiz-Cuaran and Leonce, p. 958

01 Mar 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis and evaluation of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives as next generation selective RET inhibitors overcoming RET solvent front mutations (G810C/R)

Article

Author: He, Jiahuan ; Zhang, Shuyao ; Yang, Gangpeng ; Ma, Haowen ; Xu, Mingjin ; Tan, Li ; He, Rui ; Wu, Kaifu ; Peng, Lijie ; Zhang, Zhang ; Cai, Qian

RET is a well-recognized drug target for cancer treatment. Despite the promising efficacy of selective second-generation RET inhibitors Selpercatinib and Pralsetinib, the clinical benefits have been compromised due to the quickly developed resistance to these drugs. RET G810 mutations at the solvent front site have been identified as the major on-target mutations contributing to resistance against Selpercatinib and Pralsetinib. Therefore, there is an urgent need for the development of next-generation RET inhibitors to overcome acquired solvent-front resistance mutations. In this study, a series of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives have been identified as selective next-generation RET inhibitors. The representative compound, CQ1373 exhibits potent cellular potency with IC₅₀ values of 13.0, 25.7 and 28.4 nM against BaF3 cells expressing CCDC6-RET, CCDC6-RET-G810C and CCDC6-RET-G810R, respectively. A comprehensive selectivity profile across 89 kinases reveals that CQ1373 demonstrates good selectivity toward wild-type RET and solvent front mutants G810C/R with IC₅₀ values of 4.2, 7.1 and 32.4 nM, respectively. Furthermore, western blot analysis reveals that CQ1373 effectively inhibits RET phosphorylation and downstream signaling through SHC. It also induces apoptosis and cell cycle arrest in a dose-dependent manner in BaF3 cells harboring CCDC6-RET, CCDC6-RET-G810C and CCDC6-RET-G810R fusions. More significantly, CQ1373 exhibits promising in vivo anti-tumor efficacy in a CCDC6-RET-G810R mice xenograft model, highlighting its potentials for RET-driven cancers treatment.

News (Medical) associated with Pralsetinib

04 Mar 2025

·www.prnewswire.com

Rigel Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update

Fourth quarter 2024 total revenue of approximately $57.6 million, which includes TAVALISSE® net product sales of $31.0 million, REZLIDHIA® net product sales of $7.4 million and GAVRETO® net product sales of $8.1 million 2024 total revenue of approximately $179.3 million, which includes TAVALISSE® net product sales of $104.8 million, REZLIDHIA® net product sales of $23.0 million and GAVRETO® net product sales of $17.1 million R289 granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS and Orphan Drug designation for the treatment of MDS by the FDA 2025 Outlook: Total revenue of approximately $200 to $210 million Conference call and webcast scheduled today at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., March 4, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today reported financial results for the fourth quarter and full year ended December 31, 2024, including sales of TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP); REZLIDHIA® (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and GAVRETO® (pralsetinib) for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) and advanced or metastatic thyroid cancer, and recent business progress. "2024 was a year of significant accomplishments for Rigel. We continued to focus on commercial expansion and execution, achieving record net product sales of $144.9 million, an increase of 39% compared to 2023. Coupled with Rigel's commitment to financial discipline, for the first time we generated full-year net income of more than $17 million and increased our cash balances by more than $20 million," said Raul Rodriguez, Rigel's president and CEO. "These outstanding commercial and financial results provide us the resources to advance our promising internal development programs in 2025, including our ongoing Phase 1b clinical study of R289 for the treatment of lower-risk MDS and the initiation of a Phase 2 clinical study of olutasidenib for the treatment of recurrent glioma." Business Update Commercial Commercial strength continued in the fourth quarter for all products with record bottles shipped to patients and clinics and total bottles sold. The following table summarizes total bottles shipped for the fourth quarter: Rigel's partner Kissei Pharmaceutical Co., Ltd. (Kissei) announced in January that The Korean Ministry of Food and Drug Safety approved TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic idiopathic thrombocytopenic purpura who have had an insufficient response to a previous treatment. In the first quarter of 2025, Rigel will recognize a $3.0 million regulatory milestone earned from Kissei in connection with the approval. In December, Rigel's partner Knight Therapeutics announced Mexico's Comisión Federal para la Protección contra Riesgos Sanitarios approved TAVALISSE for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. Rigel entered into an exclusive license agreement with Dr. Reddy's Laboratories Ltd. (Dr. Reddy's) in November to develop and commercialize REZLIDHIA in all potential indications throughout Dr. Reddy's territory, which includes Latin America, South Africa, certain countries in the Commonwealth of Independent States (CIS), India, certain countries in Southeast Asia and North Africa, Australia and New Zealand. Rigel received an upfront cash payment of $4.0 million with the potential for up to $36.0 million in future regulatory and commercial milestone payments. Clinical Development R2891, a novel and selective dual IRAK1/4 inhibitor, has been granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS and Orphan Drug designation for the treatment of MDS by the U.S. Food and Drug Administration (FDA). Rigel continues to advance its Phase 1b clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of R289 in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). Enrollment in the fifth dose level (500mg / 250mg split dose) is complete and the new sixth dose level (500 mg twice daily) is now open for enrollment. Rigel presented initial data from the ongoing Phase 1b clinical study of R289 at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in December, demonstrating that R289 was generally well tolerated with preliminary signs of efficacy in this heavily pretreated R/R lower-risk MDS patient population, the majority of whom were high transfusion burden (HTB) at baseline. Also at the ASH Annual Meeting, four posters were presented on olutasidenib, which included data that adds to the growing body of evidence supporting the benefits of its use in patients with mIDH1 AML. CONNECT, an international collaborative network of pediatric cancer centers, in collaboration with Rigel, opened for enrollment the "TarGet-D" study, a Phase 2 study (NCT06161974) evaluating olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy, as maintenance therapy for newly diagnosed adolescent and young adult patients (ages 12 to 39 years) with a high-grade glioma (HGG) harboring an IDH1 mutation. Rigel and The University of Texas MD Anderson Cancer Center (MD Anderson) have now opened for enrollment the four studies outlined in the multi-year strategic development alliance. Olutasidenib will be studied in disease areas where mIDH1 can play a role, including AML; higher-risk MDS, chronic myelomonocytic leukemia (CMML) and advanced myeloproliferative neoplasms (MPN); clonal cytopenia of undetermined significance (CCUS) and lower-risk MDS/CMML; and as post-transplant maintenance therapy. In November, the National Comprehensive Cancer Network® (NCCN®) added olutasidenib to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myelodysplastic Syndromes. Olutasidenib was added as a recommended option to the following treatment algorithms: Management of Lower-Risk Disease, Management of Lower-Risk Disease - Evaluation of Related Anemia and Management of Higher-Risk Disease, and was recommended as NCCN Category 2B in all circumstances. If mIDH1 positive, olutasidenib was either recommended as a single agent, in combination with azacitidine, or both.* *NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Publication Highlights A paper titled "Long‑term safety and efficacy of fostamatinib in Japanese patients with primary immune thrombocytopenia," was published in January by Masataka Kuwana, M.D., Ph.D., professor and chairman of the Department of Allergy and Rheumatology at Nippon Medical School Graduate School of Medicine in the International Journal of Hematology. The paper reported the 3-year safety and efficacy data from the Phase 3 trial of fostamatinib in Japanese patients with ITP, which included no new safety signals and a sustained platelet response during treatment. A paper titled "Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial," was published in January by Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator, in the Journal of Hematology and Oncology. A paper titled "Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm," was published in December by Stéphane de Botton, M.D., Ph.D., head of translational research in hematology, Institut Gustave Roussy, France, in the British Journal of Haematology. Fourth Quarter and Full Year 2024 Financial Update For the fourth quarter ended December 31, 2024, total revenues were $57.6 million, consisting of $31.0 million in TAVALISSE net product sales, $7.4 million in REZLIDHIA net product sales, $8.1 million in GAVRETO net product sales, and $11.1 million in contract revenue from collaborations. TAVALISSE net product sales grew 21% compared to $25.7 million in the same period of 2023. REZLIDHIA net product sales grew 92% compared to $3.9 million in the same period of 2023. GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations primarily consisted of a $4.0 million upfront cash payment from Dr. Reddy's; $3.6 million of revenue from Grifols S.A. (Grifols) related to delivery of drug supplies and earned royalties; $2.9 million of revenue from Kissei Pharmaceutical Co., Ltd. (Kissei) related to delivery of drug supplies; and $0.3 million of revenue from Medison Pharma Trading AG (Medison) related to delivery of drug supplies and earned royalties. Total costs and expenses were $40.9 million compared to $33.8 million for the same period of 2023. The increase in costs and expenses was mainly due to higher research and development costs driven by timing of clinical activities, increased personnel-related costs and increased commercial-related activities. In addition, cost of product sales increased, driven primarily by increased products sales, higher royalties and a sublicensing revenue fee, and higher amortization of intangible assets. Rigel reported net income of $14.3 million, or $0.81 basic and $0.80 diluted per share, compared to a net income of $0.7 million, or $0.04 basic and diluted per share, for the same period of 2023. The basic and diluted share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split effected on June 27, 2024 on a retroactive basis. For the full year 2024, total revenues were $179.3 million, consisting of $104.8 million in TAVALISSE net product sales, $23.0 million in REZLIDHIA net product sales, $17.1 million in GAVRETO net product sales, and $34.4 million in contract revenue from collaborations. TAVALISSE net product sales grew 12% compared to $93.7 million in the same period of 2023. REZLIDHIA net product sales grew 118% compared to $10.6 million in the same period of 2023. As mentioned above, GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations primarily consisted of $20.4 million from Kissei related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies; $9.1 million from Grifols and $0.5 million from Medison related to delivery of drug supplies and earned royalties; and $4.0 million from Dr. Reddy's related to an upfront fee from sublicensing olutasidenib. Total costs and expenses were $155.1 million compared to $137.4 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales driven primarily by increased products sales, sublicensing revenue fees and increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs, stock-based compensation expense and commercial-related expenses. These increases were partially offset by decreased research and development costs due to the timing of clinical trial activities related to R289, Rigel's dual IRAK 1/4 inhibitor program, as well as reduced trial activities related to the completed Phase 3 clinical trial of fostamatinib in patients with warm antibody hemolytic anemia (wAIHA). Rigel reported net income of $17.5 million, or $0.99 basic and diluted per share, compared to a net loss of $25.1 million, or $1.44 basic and diluted per share, for the same period of 2023. As discussed above, the share and per share amounts have been restated to reflect the 1-for-10 reverse stock split on a retroactive basis for the respective periods presented. Cash, cash equivalents and short-term investments as of December 31, 2024 was $77.3 million, compared to $61.1 million as of September 30, 2024 and $56.9 million as of December 31, 2023. 2025 Outlook Rigel anticipates 2025 total revenue of approximately $200 to $210 million, including: Net product sales of approximately $185 to $192 million. Contract revenues from collaborations of approximately $15 to $18 million. The company anticipates it will report positive net income for the full year 2025, while funding existing and new clinical development programs. Conference Call and Webcast with Slides Today at 4:30pm Eastern Time Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time). Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company's website at . The webcast will be archived and available for replay after the call via the Rigel website. About ITP In patients with immune thrombocytopenia (ITP), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. Patients suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 22,010 new cases in the United States, most in adults, in 2025.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About NSCLC It is estimated that over 226,000 adults in the U.S. will be diagnosed with lung cancer in 2025. Lung cancer is the leading cause of cancer death in the U.S, with non-small cell lung cancer (NSCLC) being the most common type accounting for 85-90% of all lung cancer diagnoses.5 RET fusions are implicated in approximately 1-2% of patients with NSCLC.6 About TAVALISSE® TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Please click here for Important Safety Information and Full Prescribing Information for TAVALISSE. About REZLIDHIA® REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. Please click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING, for REZLIDHIA. About GAVRETO® GAVRETO is indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).* *Thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Please click here for Important Safety Information and Full Prescribing Information for GAVRETO. To report side effects of prescription drugs to the FDA, or call 1-800-FDA-1088 (800-332-1088). TAVALISSE, REZLIDHIA and GAVRETO are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 16, 2025. Accessed January 31, 2025: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed January 31, 2025: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed January 31, 2025. doi: The American Cancer Society. Key Statistics for Lung Cancer. Revised January 16, 2025. Accessed January 31, 2025: Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin Cancer Res. 2017;23(8):1988-1997 doi: 10.1158/1078-0432.CCR-16-1679 Forward Looking Statements This press release contains forward-looking statements relating to, among other things, expected commercial and financial results for the fourth quarter and year ended December 31, 2024, projected financial performance and outlook for 2025, expectations to grow and advance our commercial portfolio and hematology and oncology pipeline, results of our study of R289 in lower-risk MDS including safety and efficacy data, continued ability for developing and commercializing TAVALISSE, REZLIDHIA, and GAVRETO domestically and in certain international markets, and expectations for Rigel's partnering and collaboration efforts. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "anticipates", "plan", "outlook", "potential", "may", "look to", "expects", "will", "initial", "promising", and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultLicense out/inPhase 1ASHPhase 2

07 Nov 2024

·www.prnewswire.com

Rigel Reports Third Quarter 2024 Financial Results and Provides Business Update

Third quarter total revenue of $55.3 million, which includes TAVALISSE® net product sales of $26.3 million, REZLIDHIA® net product sales of $5.5 million and GAVRETO® net product sales of $7.1 million Entered into an agreement with Kissei to develop and commercialize REZLIDHIA in all potential indications in Japan, the Republic of Korea and Taiwan, recording an upfront cash payment of $10.0 million during the third quarter Initial data from the ongoing Phase 1b study evaluating R289, a dual IRAK1/4 inhibitor, in LR-MDS to be presented at the 66th ASH Annual Meeting Conference call and webcast scheduled today at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., Nov. 7, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today reported financial results for the third quarter ended September 30, 2024, including sales of TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP); REZLIDHIA® (olutasidenib) for the treatment of relapsed or refractory (R/R) mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and GAVRETO® (pralsetinib) for the treatment of metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) and advanced or metastatic thyroid cancer, and recent business progress. "2024 has been a significant year for Rigel, marked by the acquisition of GAVRETO, our third commercial product, strong revenue growth across our commercial portfolio, and the advancement of our development pipeline," said Raul Rodriguez, Rigel's president and CEO. "This great progress is underpinned by our focus on financial discipline, resulting in positive third-quarter and year-to-date net income. As we close out the year, we will continue driving momentum in our commercial portfolio and hematology and oncology development pipeline." Third Quarter 2024 Business Update Commercial Update Commercial strength continues for all products with record bottles shipped to patients and clinics and total bottles sold. GAVRETO became commercially available from Rigel in June 2024. Third-quarter results reflect the successful transition of existing patients on therapy to Rigel's product. For the fourth quarter, the focus will be on continuing to transition patients. The following table summarizes total bottles shipped for the third quarter: In September, Rigel entered into an exclusive license and supply agreement with Kissei Pharmaceutical Co., Ltd. ("Kissei") to develop and commercialize REZLIDHIA in all potential indications in Japan, the Republic of Korea and Taiwan. Under the terms of the agreement, Rigel received an upfront cash payment of $10.0 million from Kissei, with the potential for up to an additional $152.5 million in development, regulatory and commercial milestone payments. In late October, Rigel issued a Dear Health Care Provider (DHCP) letter related to a new safety signal for GAVRETO after consultation with the U.S. Food and Drug Administration (FDA). The DHCP letter has been posted to the GAVRETO Healthcare Provider website at . Clinical and Development Update Rigel continues to advance its Phase 1b clinical study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of R2891, a novel and selective dual IRAK1/4 inhibitor, in patients with R/R lower-risk myelodysplastic syndrome (LR-MDS). Enrollment in the fifth dose level (500mg / 250mg split dose) is underway. In early November, Rigel announced six poster presentations highlighting data from the company's commercial and clinical-stage hematology and oncology portfolio at the upcoming 66th American Society of Hematology (ASH) Annual Meeting and Exposition. Initial data from the ongoing Phase 1b study evaluating R289 in patients with R/R LR-MDS indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population, the majority of whom were high transfusion burden at study entry. As of the data cutoff, 14 of 19 patients were evaluable for efficacy and per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks. RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent. The company will also present additional data for olutasidenib in patients with R/R mIDH1 AML and MDS. In September, Rigel announced the first patient was enrolled in a Phase 1b/2 triplet therapy trial of decitabine and venetoclax in combination with REZLIDHIA in patients with mIDH1 AML, which is being sponsored and conducted by The University of Texas MD Anderson Cancer Center (MD Anderson). This is the first trial in Rigel's multi-year strategic development alliance with MD Anderson. A paper detailing the differences in molecular structure, binding characteristics and clinical outcomes between olutasidenib and ivosidenib, including response rates in patients previously treated with ivosidenib or venetoclax, was published by Dr. Justin M. Watts, Associate Professor of Medicine, Division of Hematology, Chief, Leukemia Section at the University of Miami Health System, in Current Treatment Options in Oncology in October 2024. Third Quarter 2024 and Year-To-Date Financial Update For the third quarter ended September 30, 2024, total revenues were $55.3 million, consisting of $26.3 million in TAVALISSE net product sales, $5.5 million in REZLIDHIA net product sales, $7.1 million in GAVRETO net product sales, and $16.4 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $24.5 million in the same period of 2023. REZLIDHIA net product sales grew 107% compared to $2.7 million in the same period of 2023. GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $13.0 million from Kissei Pharmaceutical Co., Ltd. (Kissei) related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $3.3 million from Grifols S.A. (Grifols) and $0.1 million from Medison Pharma Trading AG (Medison) related to delivery of drug supplies and earned royalties. Total costs and expenses were $41.3 million compared to $32.6 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales, driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs and commercial-related expenses. Rigel reported net income of $12.4 million, or $0.71 basic and $0.70 diluted per share, compared to a net loss of $5.7 million, or $0.33 basic and diluted per share, for the same period of 2023. The basic and diluted share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split effected on June 27, 2024 on a retroactive basis. For the nine months ended September 30, 2024, total revenues were $121.7 million, consisting of $73.8 million in TAVALISSE net product sales, $15.6 million in REZLIDHIA net product sales, $9.0 million in GAVRETO net product sales, and $23.3 million in contract revenue from collaborations. TAVALISSE net product sales grew 8% compared to $68.1 million in the same period of 2023. REZLIDHIA net product sales grew 133% compared to $6.7 million in the same period of 2023. As mentioned above, GAVRETO became commercially available from Rigel in June 2024. Contract revenue from collaborations consisted of $17.5 million from Kissei related to an upfront fee from sublicensing olutasidenib and delivery of drug supplies, as well as $5.5 million from Grifols and $0.2 million from Medison related to delivery of drug supplies and earned royalties. Total costs and expenses were $114.1 million compared to $103.5 million for the same period of 2023. The increase in costs and expenses was mainly due to higher cost of product sales driven primarily by increased products sales, a sublicensing revenue fee to Forma, increased royalties and amortization of intangible assets. In addition, there were increases in personnel-related costs, stock-based compensation expense and commercial-related expenses. These increases were partially offset by decreased research and development costs due to the timing of clinical trial activities related to R289, the company's dual IRAK 1/4 inhibitor program, as well as reduced trial activities related to the completed Phase 3 clinical trials of fostamatinib in patients with COVID-19 and in patients with warm antibody hemolytic anemia (wAIHA). Rigel reported net income of $3.1 million, or $0.18 basic and diluted per share, compared to a net loss of $25.8 million, or $1.49 basic and diluted per share, for the same period of 2023. As discussed above, the share and per share amounts for the prior period have been restated to reflect the 1-for-10 reverse stock split on a retroactive basis for the periods presented. Cash, cash equivalents and short-term investments as of September 30, 2024 was $61.1 million, compared to $49.1 million as of June 30, 2024, and $56.9 million as of December 31, 2023. Conference Call and Webcast with Slides Today at 4:30pm Eastern Time Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time). Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company's website at . The webcast will be archived and available for replay after the call via the Rigel website. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About NSCLC It is estimated that over 230,000 adults in the U.S. will be diagnosed with lung cancer in 2024. Lung cancer is the leading cause of cancer death in the U.S, with NSCLC being the most common type accounting for 80-85% of all lung cancer diagnoses.5 RET fusions are implicated in approximately 1-2% of patients with NSCLC.6 About TAVALISSE® TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Please click here for Important Safety Information and Full Prescribing Information for TAVALISSE. About REZLIDHIA® REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. Please click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING, for REZLIDHIA. About GAVRETO® GAVRETO is indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test and adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).* *Thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Please click here for Important Safety Information and Full Prescribing Information for GAVRETO. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). TAVALISSE, REZLIDHIA and GAVRETO are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised June 5, 2024. Accessed June 30, 2024: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed June 30, 2024: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed June 30, 2024. doi: The American Cancer Society. Key Statistics for Lung Cancer. Revised January 29, 2024. Accessed June 30, 2024: Kato, S. et al. RET Aberrations in Diverse Cancers: Next-Generation Sequencing of 4,871 Patients. Clin Cancer Res. 2017;23(8):1988-1997 doi: 10.1158/1078-0432.CCR-16-1679 Forward Looking Statements This press release contains forward-looking statements relating to, among other things, expected commercial and financial results, expectations for developing and commercializing REZLIDHIA in certain international markets, study results relating to safety and tolerability of R289 for the treatment of lower-risk myeloid dysplastic syndrome, expectations for development of Rigel's commercial portfolio and hematology and oncology pipeline, and expectations for Rigel's partnering and collaboration efforts. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "will", "initial", and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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05 Nov 2024

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Rigel Announces Six Poster Presentations at the 66th American Society of Hematology Annual Meeting and Exposition

- Initial data from the ongoing Phase 1b study evaluating R289, a dual IRAK1/4 inhibitor, in LR-MDS - Additional data for REZLIDHIA® (olutasidenib) in patients with mIDH1 AML and MDS SOUTH SAN FRANCISCO, Calif., Nov. 5, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced upcoming presentations of six posters highlighting data from their commercial and clinical-stage hematology-oncology portfolio at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, California and virtually. Rigel's presentations will include data from the ongoing Phase 1b dose escalation/expansion study evaluating R2891, a potent and selective dual inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS) who are relapsed or refractory (R/R) to prior therapies; REZLIDHIA® (olutasidenib) for the treatment of R/R mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and TAVALISSE® (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP). "We look forward to the presentation of posters at ASH from across our product portfolio. We are very encouraged by the preliminary safety and efficacy data from our ongoing Phase 1b study of R289 in lower risk MDS. R289 was generally well tolerated and demonstrated responses in heavily pretreated LR-MDS patients, a population with a critical unmet need," said Raul Rodriguez, Rigel's president and CEO. "In addition, data from olutasidenib will be presented that adds to the growing body of evidence showing the benefits of its use in patients with mIDH1 AML." ASH Annual Meeting abstracts may be accessed online at . Details of the poster presentations and publications, which will be available in the poster hall and via the virtual event platform, are as follows: Abstract #: 4595 Title: R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower-Risk Myelodysplastic Syndrome (LR-MDS): Initial Results from a Phase 1b Study Presenter: Guillermo Garcia-Manero, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT Initial data from the dose escalation phase using a July 15, 2024 data cutoff date indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population (median number of prior therapies was 4; 79% had received an hypomethylating agent), the majority of whom were high transfusion burden (received ≥8 units red blood cells in 16 weeks prior to enrollment) at study entry. Fourteen of 19 patients were evaluable for efficacy (received ≥1 dose of study drug with ≥1 efficacy assessment). Per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks (range 12.4-35.9 weeks). RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent. Updated data as of October 25, 2024 data cutoff will be presented during the poster session. Abstract #: 1514 Title: Time to Response and Overall Survival in Patients with mIDH1 Relapsed/Refractory Acute Myeloid Leukemia Treated with Olutasidenib Presenter: Stéphane de Botton, M.D., Ph.D. Time: Saturday, December 7, 2024, 5:30pm to 7:30pm PT Results show that while some patients with mIDH1 R/R AML achieve response to olutasidenib very quickly, within 1-2 months of treatment, other patients responded after 6 months of treatment for complete remission (CR) plus CR with partial hematologic recovery (CRh) and up to 10 months for overall response. These results support the prescribing information that suggests treating for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity. A Cox regression model showed no significant association between time to response and overall survival in the overall responders and those with a CR/CRh response. Abstract #: 2886 Title: Combination of Olutasidenib and Azacitidine Induces Durable Complete Remissions in mIDH1 Acute Myeloid Leukemia: A Multicohort Open-Label Phase 1/2 Trial Presenter: Jorge E. Cortes, M.D. Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT Olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R mIDH1 AML, in the first reported analysis of a combination therapy with an mIDH1 inhibitor and a hypomethylating agent focused on the R/R AML setting. CR/CRh was achieved in 31% (21/67) of patients and median duration of CR/CRh was 15 months. Abstract #: 4600 Title: Olutasidenib Alone or in Combination with Azacitidine in Patients with mIDH1 Myelodysplastic Syndromes/Neoplasms: Final 5-Year Data Presenter: Jorge E. Cortes, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT Olutasidenib demonstrated encouraging response rates with durable remissions and an acceptable and manageable safety profile in patients with intermediate to very high-risk mIDH1 MDS treated with olutasidenib monotherapy or in combination with azacitidine. In a sub analysis of the 19 efficacy evaluable patients, 79% (11/14) of patients responded to combination therapy and 40% (2/5) responded to monotherapy, which included both patients (2/2) using the approved dose of 150 mg BID olutasidenib. Abstract #: 1525 Title: Effectiveness of Olutasidenib Versus Ivosidenib in Patients with Mutated Isocitrate Dehydrogenase 1 Acute Myeloid Leukemia Who Are Relapsed or Refractory to Venetoclax: The 2102-HEM-101 Trial Versus a US Electronic Health Record-Based External Control Arm Presenter: Catherine E. Lai, M.D. Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT This study provides the first evidence suggesting favorable effectiveness of olutasidenib versus ivosidenib in patients with mIDH1 AML who were R/R to a venetoclax-based regimen. As with any real-world experience study, limitations include risk of unmeasured confounding and differential outcome reporting. Abstract #: 5080 Title: Real-World Experience with Combination Therapy of Fostamatinib and Thrombopoetin Receptor Agonists (TPO-RAs) for Treatment of Immune Thrombocytopenia (ITP): Patient-Reported Outcomes Presenter: Elizabeth Bowhay-Carnes, M.D. Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT This real-world study treating patients with fostamatinib and a thrombopoetin receptor agonist (TPO-RA) demonstrated that the combination led to a clinically meaningful response in a majority of patients with ITP. ASH Publication Abstract #: 7908 Title: Treatment Patterns and Outcomes of Olutasidenib in Patients with Relapsed/Refractory (R/R) mutated IDH1 Acute Myeloid Leukemia (AML) in the Real World Authors: Aaron Sheppard, Ph.D.; Lixia Wang, Ph.D.; Ravi Potluri, MBA; Eros Papademetriou, MA About R289 R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family 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.2 About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.3 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.4 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.5 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About REZLIDHIA® INDICATION REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence. Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity. ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. DRUG INTERACTIONS Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. LACTATION Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose. GERIATRIC USE No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age. HEPATIC IMPAIRMENT In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome. Click here for Full Prescribing Information, including Boxed WARNING. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). REZLIDHIA and TAVALISSE are registered trademarks of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA. Sallman DA et al. Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype. Front Oncol. June 16, 2016. Accessed September 30, 2024. DOI: The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised June 5, 2024. Accessed September 30, 2024: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed September 30, 2024: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. Accessed September 30, 2024. doi: Forward-Looking Statements This press release contains forward-looking statements relating to, among other things, clinical information regarding studies of Rigel's products, including; the progress of the Phase 1b clinical trial of R289 for the treatment of lower-risk myeloid dysplastic syndrome; olutasidenib as a treatment for mIDH1 Relapsed/Refractory Acute Myeloid Leukemia, use of olutasidenib with azacitidine, and use of olutasidenib versus ivosidenib; and, fostamatinib in combination with thrombopoetin receptor agonists for treatment of immune thrombocytopenia, and fostamatinib as early treatment of immune thrombocytopenia. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "look to", "expects", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of fostamatinib, olutasidenib and pralsetinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib, pralsetinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib, pralsetinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 646.461.6387 [email protected] SOURCE Rigel Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultPhase 1ASH

100 Deals associated with Pralsetinib

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KEGG	Wiki	ATC	Drug Bank
D11712	Pralsetinib	L01XE	DB15822

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Switzerland	Blueprint Medicines Corp.	06 Aug 2021
RET fusion-positive Thyroid Cancer	United States	Blueprint Medicines Corp.	01 Dec 2020
RET Mutation-Positive Medullary Thyroid Cancer	United States	Blueprint Medicines Corp.	01 Dec 2020
RET fusion-positive Non-Small Cell Lung Cancer	United States	Rigel Pharmaceuticals, Inc.	04 Sep 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Thyroid Cancer	NDA/BLA	European Union	Roche Registration GmbH	-
metastatic non-small cell lung cancer	Phase 3	China	Blueprint Medicines Corp.	27 Apr 2023
metastatic non-small cell lung cancer	Phase 3	China	Cornerstone Pharmaceutical Co., Ltd	27 Apr 2023
Adenocarcinoma	Phase 3	United States	-	24 Jul 2020
Adenocarcinoma	Phase 3	Japan	-	24 Jul 2020
Adenocarcinoma	Phase 3	Argentina	-	24 Jul 2020
Adenocarcinoma	Phase 3	Australia	-	24 Jul 2020
Adenocarcinoma	Phase 3	Belgium	-	24 Jul 2020
Adenocarcinoma	Phase 3	Brazil	-	24 Jul 2020
Adenocarcinoma	Phase 3	Costa Rica	-	24 Jul 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03037385 (ARROW, Pubmed \| Future Oncol)	Phase 1/2	RET fusion-positive Non-Small Cell Lung Cancer RET fusion+	281	Pralsetinib	pklosxasmm(wsuhdnblkd) = severe side effect in untreated patients nfyuwfzcfm (ssvjdkyabp ) View more	Positive	01 Feb 2024
NCT03037385 (ARROW, Pubmed) Manual	Phase 1/2	RET fusion-positive Thyroid Cancer Rearranged During Transfection -Altered	145	Pralsetinib 400 mg once daily	zxdyrkpnuv(dvzotsmhqc) = blfjbnolsi wfakjefuqt (lrtxmjwtcl, 42.4 - 68.5) View more	Positive	01 Jan 2024
				PralsetinibPralsetinib 400 mg (treatment-naïve patients with RET-mutant MTC)	zxdyrkpnuv(dvzotsmhqc) = qjektqlaxv wfakjefuqt (lrtxmjwtcl, 65.0 - 87.1) View more
NCT03037385 (ARROW, Pubmed)	Phase 1/2	RET fusion-positive Non-Small Cell Lung Cancer	68	Pralsetinib 400-mg once-daily oral	tehwkiiwal(crutfuteyt) = rtrvtsuuyi mfzjhnhyur (gtqggnfpjz, 48.2 - 82.0) View more	Positive	06 Jun 2023
NCT03037385 (ARROW, ESMO_ASIA2022) Manual	Phase 1/2	RET fusion-positive Non-Small Cell Lung Cancer RET fusion+	68	pralsetinib,400 mg (previously treated with platinum-based chemotherapy)	qvssktlqub(jrsssnefuz) = bfzatbdfoo czhbiiokkd (fszxdtpwvi, 48 - 82) View more	Positive	03 Dec 2022
				pralsetinib,400 mg (treatment-naïve)	qvssktlqub(jrsssnefuz) = miqsoqupnu czhbiiokkd (fszxdtpwvi, 65 - 94) View more
Pubmed Manual	Not Applicable	RET fusion-positive Non-Small Cell Lung Cancer RET fusion-positive	59	Pralsetinib (overall)	ssmpppsxsa(lisrcjgpro) = iokjepzqgc gtmshjuykb (jetxzyrbue, 4.7 - NA) View more	Positive	09 Nov 2022
				Pralsetinib (patients with measurable brain metastases)	whribhaqbg(kbwgeorkxe) = brdlliawzd hiazgjttnu (nxoflzxmix ) View more
NCT03037385 (ARROW, ESMO2022) Manual	Phase 1/2	Thyroid Cancer RET-altered	175	pralsetinib,400 mg QD ( Pts with RETm MTC previously treated with C/V)	dfwtuawpdv(odeismkdcq) = gcukmdzwlk uvhirirtam (ybgyrijbhs, 39.7 - 64.6) View more	Positive	10 Sep 2022
				pralsetinib,400 mg QD (Treatment-naïve pts with RETm MTC)	dfwtuawpdv(odeismkdcq) = icnqbsniew uvhirirtam (ybgyrijbhs, 59.3 - 82.0) View more
NCT03037385 (ARROW, ESMO2022) Manual	Phase 1/2	Non-Small Cell Lung Cancer CCDC6-RET Fusion \| KIF5B-RET Fusion \| RET Fusion	233	Pralsetinib 400mg/day (KIF5B)	lkrvytcfyg(ylgpkuymco) = bbsblociso mfynjrhckc (dcgfsmjoxq, 60.0 - 74.8) View more	Positive	10 Sep 2022
				Pralsetinib 400mg/day (CCDC6)	lkrvytcfyg(ylgpkuymco) = zfkutbomvw mfynjrhckc (dcgfsmjoxq, 51.9 - 81.9) View more
ESMO2022	Not Applicable	RET fusion-positive Non-Small Cell Lung Cancer	60	Pralsetinib	kvijcktbeb(fxdcpytlwz) = cxzwdpufqh kckwjsefoz (avyxqlbmyw ) View more	-	10 Sep 2022
NCT03037385 (ARROW, ESMO2022)	Phase 1/2	RET fusion-positive Non-Small Cell Lung Cancer	281	Pralsetinib 400mg	glgxahkfci(mapyaxjksl) = ejwfiemkbv cuxtbinojc (ivqcxnzmdn ) View more	-	10 Sep 2022
NCT03037385 (ARROW, Pubmed \| Nat Med) Manual	Phase 1/2	RET fusion-positive Solid Tumors RET fusion-positive	29	Pralsetinib	izlvaffxae(owzcnbbyns) = ezoyhlvgsa xfrowbimmw (wcdrwfjuch, 35 - 77) View more	Positive	12 Aug 2022

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