RIGEL PHARMACEUTICALS INC

Previous wording

This discussion and analysis should be read in conjunction with our financial statements and the accompanying notes included in this report and the audited financial statements and accompanying notes included in our Annual Report on Form 10-K for the year ended December 31, 2024 filed with the SEC on March 4, 2025. Our financial results for the three months ended March 31, 2025 are not necessarily indicative of results that may occur in future interim periods or for the full fiscal year.

Current wording

This discussion and analysis should be read in conjunction with our financial statements and the accompanying notes included in this report and the audited financial statements and accompanying notes included in our Annual Report on Form 10-K for the year ended December 31, 2024 filed with the SEC on March 4, 2025. Our financial results for the three and six months ended June 30, 2025 are not necessarily indicative of results that may occur in future interim periods or for the full fiscal year.

Previous wording

TAVALISSE (fostamatinib disodium hexahydrate) is our first product approved by the FDA. TAVALISSE is the only approved oral SYK inhibitor for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment. The product is also commercially available in Europe and the UK (as TAVLESSE), and in Canada, Israel and Japan (as TAVALISSE) for the treatment of chronic ITP in adult patients.

Current wording

TAVALISSE (fostamatinib disodium hexahydrate) is our first product approved by the FDA. TAVALISSE is the only approved oral SYK inhibitor for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment. The product is also commercially available in Europe and the UK (as TAVLESSE), and in Canada, Israel, Japan and Korea (as TAVALISSE) for the treatment of chronic ITP in adult patients.

Previous wording

For the three months ended March 31, 2025, net product sales of TAVALISSE were $28.5 million, increased by $7.4 million or 35% compared to $21.1 million net product sales in the same period in 2024. The increase was primarily due to increased quantities sold and higher price per bottle, and partially due to lower revenue reserves rate.

Current wording

For the six months ended June 30, 2025, net product sales of TAVALISSE were $68.5 million, increased by $21.1 million or 44% compared to $47.5 million net product sales in the same period in 2024. The increase was primarily due to increased quantities sold and higher price per bottle, and partly due to lower revenue reserves rate.

Previous wording

For the three months ended March 31, 2025, net product sales of REZLIDHIA were $6.1 million, increased by $1.2 million or 25% compared to $4.9 million net product sales in the same period in 2024. The increase was primarily due to increased quantities sold as well as higher price per bottle, partially offset byhigher revenue reserves rate.

Current wording

For the six months ended June 30, 2025, net product sales of REZLIDHIA were $13.1 million, increased by $3.1 million or 31% compared to $10.0 million net product sales in the same period in 2024. The increase was primarily due to increased quantities sold and higher price per bottle, which were partially offset byhigher revenue reserves rate.

Previous wording

We began our commercialization and started recognizing revenue from product sales of GAVRETO in June 2024. For the three months ended March 31, 2025, we recognized $9.0 million net product sales of GAVRETO. We expect to continue to leverage our existing commercial infrastructure to ensure current and newly prescribed GAVRETO patients have continued access to this important treatment option.

Current wording

We began our commercialization and started recognizing revenue from product sales of GAVRETO in June 2024. For the six months ended June 30, 2025, net product sales of GAVRETO were $20.8 million, compared to $1.9 million in the same period in 2024. We expect to continue to leverage our existing commercial infrastructure to ensure current and newly prescribed GAVRETO patients have continued access to this important treatment option.

Previous wording

We advanced the development of our dual IRAK 1/4 inhibitor program, following evaluation of single and multiple ascending doses of R289 in healthy subjects. The ongoing Phase 1b open-label, multicenter study evaluates the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS. This Phase 1b study is expected to enroll approximately 86 patients (up to 36 patients in the dose escalation phase, up to 40 patients in the dose expansion phase, and 10 less heavily pre-treated patients in an exploratory cohort). The primary objective of the study is safety, with secondary and exploratory objectives to assess preliminary efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safetyand efficacy data from this Phase 1b study is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS. In December 2024, initial data from the dose escalation part of the Phase 1b study was presented at the 66 th American Society of Hematology (ASH)Annual Meeting and Exposition. In summary, R289 was generally well tolerated with preliminary signs of efficacy in a heavily pretreated lower-risk MDS patient population, the majority of whom were high transfusion burden (HTB) at baseline. Red blood cell (RBC)-transfusion independence (RBC-TI) ≥8 weeks was achieved by three patients (1 at 500 mg QD and 2 at 750 mg QD); two HTB patients achieved RBC-TI >24 weeks. The median duration of RBC-TI was 29 weeks (range 12.7-51.9 weeks). One HTB patient receiving 500 mg QD achieved a minor hematologic improvement-erythroid (HI-E) response, with a 64% reduction in RBC transfusions compared to baseline. The three patients that achieved RBC-TI had peak hemoglobin increases exceeding 2.0 g/dL compared to baseline. To date, enrollment in the sixth dose level (500 mg twice daily) is ongoing.

Current wording

We advanced the development of our dual IRAK 1/4 inhibitor program, following evaluation of single and multiple ascending doses of R289 in healthy subjects. The ongoing Phase 1b open-label, multicenter study evaluates the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS. This Phase 1b study is expected to enroll approximately 86 patients (up to 36 patients in the dose escalation phase, up to 40 patients in the dose expansion phase, and 10 less heavily pre-treated patients in an exploratory cohort). The primary objective of the study is safety, with secondary and exploratory objectives to assess preliminary efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safetyand efficacy data from this Phase 1b study is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS. In December 2024, initial data from the dose escalation part of the Phase 1b study was presented at the 66 th American Society of Hematology (ASH)Annual Meeting and Exposition. In summary, R289 was generally well tolerated with preliminary signs of efficacy in a heavily pretreated lower-risk MDS patient population, the majority of whom were high transfusion burden (HTB) at baseline. Red blood cell (RBC)-transfusion independence (RBC-TI) ≥8 weeks was achieved by three patients (1 at 500 mg QD and 2 at 750 mg QD); two HTB patients achieved RBC-TI >24 weeks. The median duration of RBC-TI was 29 weeks (range 12.7-51.9 weeks). The three patients that achieved RBC-TI had peak hemoglobin increases exceeding 2.0 g/dL compared to baseline. We also reported that one HTB patient receiving 500 mg QD achieved a minor hematologic improvement-erythroid (HI-E) response, with a 64% reduction in RBC transfusions compared to baseline; however, in the July 15, 2025 data cut, we determined that this patient had received blood transfusions that were not captured in the database at the time of the initial data analysis. Accordingly, this patient was subsequently determined to be a non-responder. As the study is ongoing, interim results represent information at the time of the data cut, and final study results will be available after the database lock at the end of the study.

Previous wording

In January 2024, we announced our collaboration with CONNECT, an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate olutasidenib in combination with temozolomide in patients with HGG harboring an IDH1 mutation. Under the collaboration, CONNECT will include the olutasidenib treatment arm within CONNECT’s TarGet study, a molecularly guided Phase 2 umbrella clinical trial for HGG. In our sponsored arm, TarGet-D, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year. Under the collaboration, we will provide CONNECT with funding up to $3.0 million and study material over the four-year collaboration. The TarGet-D study is now open for enrollment.

Current wording

In January 2024, we announced our collaboration with CONNECT, an international collaborative network of pediatric cancer centers, to conduct a Phase 2 clinical trial to evaluate olutasidenib in combination with temozolomide in patients with HGG harboring an IDH1 mutation. Under the collaboration, CONNECT will include the olutasidenib treatment arm within CONNECT’s TarGet study, a molecularly guided Phase 2 umbrella clinical trial for HGG. In our sponsored arm, TarGet-D, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year. Under the collaboration, we will provide CONNECT with funding up to $3.0 million and study material over the four-year collaboration. The TarGet-D study is open for enrollment.

Previous wording

Lilly is continuing to advance ocadusertib (previously R552), an investigational, potent and selective RIPK1 inhibitor. Lilly has initiated the Phase 2 trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis. The Phase 2a enrollment is advancing well, with preliminary analysis of results in April 2025. RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis. The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.

Current wording

Lilly is continuing to advance ocadusertib (previously R552), an investigational, potent and selective RIPK1 inhibitor. Enrollment in Lilly’s Phase 2a clinical trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis is ongoing, with preliminary analysis of results in April 2025. RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis. The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.

Previous wording

Under the Lilly Agreement, we are responsible for 20% of the development costs for ocadusertib in the US, Europe, and Japan, up to a specified cap, and Lilly is responsible for funding the remainder of all development activities for ocadusertib and other non-CNS disease development candidates. Under the Lilly Agreement, we have the right to opt-out of co-funding the ocadusertib development activities in the US, Europe and Japan at two different specified times and as a result receive lesser royalties from sales. Following us providing the first opt-out notice to Lilly in September 2023, our cost share obligation for ocadusetib development ended on April 1, 2024. We paid Lilly a total of $21.4 million for our share of development costs incurred through April 1, 2024. Under the Lilly Agreement as amended, we have the right to opt-in to co-funding of ocadusertib development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement. On April 30, 2025, we provided notice to Lilly of our decision not to exercise our opt-in right following our evaluation of certain events specified in the Lilly Agreement. Following this notification, we are no longer obligated to share in any future global development costs, which resulted in the release of the $40.0 million remaining cost share liability currently on our condensed balance sheet.

Current wording

Under the Lilly Agreement, we were responsible for 20% of the development costs for ocadusertib in the US, Europe, and Japan, up to a specified cap, and Lilly is responsible for funding the remainder of all development activities for ocadusertib and other non-CNS disease development candidates. Under the Lilly Agreement, we have the right to opt-out of co-funding the ocadusertib development activities in the US, Europe and Japan at two different specified times and as a result receive lesser royalties from sales. Following us providing the first opt-out notice to Lilly in September 2023, our cost share obligation for ocadusertib development ended on April 1, 2024. We paid Lilly a total of $21.4 million for our share of development costs incurred through April 1, 2024. Under the Lilly Agreement as amended, we had the right to opt-in to co-funding of ocadusertib development, upon us providing notice to Lilly within 30 days of certain events, as specified in the Lilly Agreement. On April 30, 2025, we provided notice to Lilly of our decision not to exercise our opt-in right following our evaluation of certain events specified in the Lilly Agreement. Following this notification, we are no longer obligated to share in any future global development costs. As such, we released the $40.0 million remaining cost share liability and recognized the amount as contract revenues from collaboration in the second quarter of 2025.

Previous wording

We have a commercialization license agreement with Grifols for exclusive rights to commercialize fostamatinib for human diseases, and non-exclusive rights to develop, fostamatinib in their territory. Grifols territory includes EU, the UK, Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent States). In January 2020, the European Commission (EC) granted a centralized MA for fostamatinib (TAVLESSE) valid throughout the EU and which has been grandfathered in the UK, after the departure of the UK from the EU, for the treatment of chronic ITP in adult patients who are refractory to other treatments. Grifols has launched TAVLESSE in the UK and certain countries in EU including Germany, France, Italy and Spain, and continues a phased rollout across the rest of EU.

Current wording

We have a commercialization license agreement with Grifols for exclusive rights to commercialize fostamatinib for human diseases, and non-exclusive rights to develop, fostamatinib in their territory. Grifols territory includes EU, the UK, Turkey, the Middle East, North Africa and Russia (including CIS). In January 2020, the European Commission (EC) granted a centralized MA for fostamatinib (TAVLESSE) valid throughout the EU and which has been grandfathered in the UK, after the departure of the UK from the EU, for the treatment of chronic ITP in adult patients who are refractory to other treatments. Grifols has launched TAVLESSE in the UK and certain countries in EU including Germany, France, Italy and Spain, and continues a phased rollout across the rest of EU.

Previous wording

We have an exclusive license and supply agreement with Kissei to develop and commercialize fostamatinib in all current and potential indications in Japan, China, Taiwan and 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. Japanhas the third highest prevalence of chronic ITP in the world behind the US and Europe. Kissei was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP in February 2020. In December 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved TAVALISSE for the treatment of chronic ITP, and in April 2023, Kissei launched TAVALISSE for chronic ITP in Japan. In January 2025, Kissei announced 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.

Current wording

We have an exclusive license and supply agreement with Kissei to develop and commercialize fostamatinib in all current and potential indications in Japan, China, Taiwan and 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. Japanhas the third highest prevalence of chronic ITP in the world behind the US and Europe. Kissei was granted orphan drug designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP in February 2020. In December 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved TAVALISSE for the treatment of chronic ITP, and in April 2023, Kissei launched TAVALISSE for chronic ITP in Japan. In January 2025, Kissei announced 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 July 2025, Kissei announced that its licensing partner, JW Pharmaceutical Corporation, commercially launched TAVALISSE in Korea.

Previous wording

In May 2024, we announced the presentation of the five-year results from the registrational Phase 2 trial of REZLIDHIA in R/R mIDH1 AML patients at the 2024 ASCO Annual Meeting and EHA 2024 Hybrid Congress. The data published reinforces REZLIDHIA’s efficacy in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. The safety profile was consistent with what was previously reported. Further, REZLIDHIA was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with REZLIDHIA. REZLIDHIA was also effective in achieving remission in patients with mIDH1 R/R AML and served as a bridging strategy towards potentially curative allogeneic transplantation in a substantial subset of these previously ineligible patients. Additionally, REZLIDHIA was well tolerated in a subset of patients with myeloproliferative neoplasms mlDH1 AML, a patient population often associated with poor responses to available therapies.

Current wording

In May 2024, we announced the presentation of the five-year results from the registrational Phase 2 trial of REZLIDHIA in R/R mIDH1 AML patients at the 2024 ASCO Annual Meeting and EHA 2024 Hybrid Congress. The data published reinforces REZLIDHIA’s efficacy in heavily pretreated patients with mIDH1 AML, including those R/R to prior venetoclax. The safety profile was consistent with what was previously reported. Further, REZLIDHIA was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with REZLIDHIA. REZLIDHIA was also effective in achieving remission in patients with mIDH1 R/R AML and served as a bridging strategy towards potentially curative allogeneic transplantation in a substantial subset of these previously ineligible patients. Additionally, REZLIDHIA was well tolerated in a subset of patients with myeloproliferative neoplasms mIDH1 AML, a patient population often associated with poor responses to available therapies.

Previous wording

Taiwan. Kissei will initially seek approval for REZLIDHIA in Japan for R/R mIDH1 AML and will be responsible for conducting clinical studies as required by the Japanese PMDA. Weremain responsible for the manufacture and supply of olutasidenib for all development and commercialization activities and will supply Kissei with bulk drug product for use under the license and supply agreements.

Current wording

In September 2024, we entered into a collaboration and license agreement with Kissei, pursuant to which Kissei was granted exclusive rights to develop and commercialize olutasidenib in all human diseases in Japan, Korea and Taiwan. Kissei will initially seek approval for REZLIDHIA in Japan for R/R mIDH1 AML and will be responsible for conducting clinical studies as required by the Japanese PMDA. Weremain responsible for the manufacture and supply of olutasidenib for all development and commercialization activities and will supply Kissei with bulk drug product for use under the license and supply agreements.

Previous wording

The FDA granted GAVRETO new chemical entity exclusivity until September 2025 and orphan drug exclusivity until September 2027 with respect to the approval for treatment of adult patients with metastatic RET fusion-positive NSCLC as detected by an FDA-approved test. The FDA also granted GAVRETO two orphan drug exclusivities until December 2027 with respect to FDA approval for the treatment of 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), and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid carcinoma who require systemic therapy.

Current wording

positive NSCLC as detected by an FDA-approved test. The FDA also granted GAVRETO two orphan drug exclusivities until December 2027 with respect to FDA approval for the treatment of 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), and for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid carcinoma who require systemic therapy.

Previous wording

We advanced the development of our IRAK 1/4 inhibitor program, following evaluation of single and multiple ascending doses of R289, a new pro-drug formulation of R835, in healthy subjects. In January 2022, we initiated a Phase 1b open-label, multicenter study to evaluate the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS. In December 2022, we announced the dosing of the first patient. This Phase 1b study is expected to enroll approximately 86 patients (up to 36 patients in the dose escalation phase, up to 40 patients in the dose expansion phase, and 10 less heavily pre-treated lower-risk-MDS patients in an exploratory cohort). The primary objective of the study is safety, with secondary and exploratory objectives to assess preliminary efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safetyand efficacy data from this Phase 1b study is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS. In December 2024, initial data from the dose escalation part of the Phase 1b study was presented at the 66 th ASHAnnual Meeting and Exposition. In summary, R289 was generally well tolerated with preliminary signs of efficacy in this heavily pretreated lower-risk MDS patient population, the majority of whom were HTB at baseline. RBC-TI ≥8 weeks was achieved by three patients (1 at 500 mg QD and 2 at 750 mg QD); two HTB patients achieved RBC-TI >24 weeks. The median duration of RBC-TI was 29 weeks (range 12.7-51.9 weeks). One HTB patient receiving 500 mg QD achieved a minor HI-E response, with a 64% reduction in RBC transfusions compared to baseline. The three patients that achieved RBC-TI had peak hemoglobin increases exceeding 2.0 g/dL compared to baseline. To date, the enrollment in the sixth dose level (500 mg twice daily) is ongoing.

Current wording

We advanced the development of our IRAK 1/4 inhibitor program, following evaluation of single and multiple ascending doses of R289, a new pro-drug formulation of R835, in healthy subjects. In January 2022, we initiated a Phase 1b open-label, multicenter study to evaluate the safety, tolerability and preliminary efficacy of R289 in patients with R/R lower-risk MDS. In December 2022, we announced the dosing of the first patient. This Phase 1b study is expected to enroll approximately 86 patients (up to 36 patients in the dose escalation phase, up to 40 patients in the dose expansion phase, and 10 less heavily pre-treated lower-risk-MDS patients in an exploratory cohort). The primary objective of the study is safety, with secondary and exploratory objectives to assess preliminary efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safetyand efficacy data from this Phase 1b study is intended to inform the recommended dose of R289 for further clinical evaluation in lower-risk MDS. In December 2024, initial data from the dose escalation part of the Phase 1b study was presented at the 66 th ASHAnnual Meeting and Exposition. In summary, R289 was generally well tolerated with preliminary signs of efficacy in this heavily pretreated lower-risk MDS patient population, the majority of whom were HTB at baseline. RBC-TI ≥8 weeks was achieved by

Previous wording

We also have a collaboration with CONNECT to conduct a Phase 2 clinical trial to evaluate olutasidenib in combination with temozolomide in patients with HGG harboring an IDH1 mutation. Under the collaboration, CONNECT will include the olutasidenib treatment arm within CONNECT’s TarGet study, a molecularly guided Phase 2 umbrella clinical trial for HGG. In our sponsored arm, TarGet-D, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year. The TarGet-D study is now opened for enrollment.

Current wording

We also have a collaboration with CONNECT to conduct a Phase 2 clinical trial to evaluate olutasidenib in combination with temozolomide in patients with HGG harboring an IDH1 mutation. Under the collaboration, CONNECT will include the olutasidenib treatment arm within CONNECT’s TarGet study, a molecularly guided Phase 2 umbrella clinical trial for HGG. In our sponsored arm, TarGet-D, adolescents and young adult patients (<39 years old) with newly-diagnosed IDH1-mutation positive HGG will receive maintenance therapy with olutasidenib in combination with temozolomide for the first year after radiotherapy, followed by olutasidenib monotherapy for the second year. The TarGet-D study is open for enrollment.

Previous wording

Lilly is continuing to advance ocadusertib (previously R552) and has initiated the Phase 2 trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis. The Phase 2a enrollment is advancing well, with preliminary analysis of results in April 2025. RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis. The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.

Current wording

Lilly is continuing to advance ocadusertib (previously R552) and has initiated the Phase 2 trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis. Enrollment in Lilly’s Phase 2a clinical trial studying ocadusertib in adult patients with moderately to severely active rheumatoid arthritis is ongoing, with preliminary analysis of results in April 2025. RIPK1 is implicated in a broad range of key inflammatory cellular processes and plays a key role in tumor necrosis factor signaling, especially in the induction of pro-inflammatory necroptosis. The program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis.

Previous wording

We also have product candidates in clinical development with BerGenBio for the development and commercialization of AXL receptor tyrosine kinase inhibitor, R428 (now referred to as bemcentinib (BGB324)), and with Daiichi to pursue research related to MDM2 inhibitor, DS-3032 (now referred as melademetan). The worldwide rights to melademetan were out-licensed from Daiichi to Rain Oncology Inc. (Rain), which is now Pathos Al, Inc. (Pathos) after Pathos completed the acquisition of Rain in January 2024.

Current wording

We also have product candidates in clinical development with BerGenBio for the development and commercialization of AXL receptor tyrosine kinase inhibitor, R428 (now referred to as bemcentinib (BGB324)), and with Daiichi to pursue research related to MDM2 inhibitor, DS-3032 (now referred as milademetan). The worldwide rights to milademetan were out-licensed from Daiichi to Rain Oncology Inc. (Rain), which is now Pathos Al, Inc. (Pathos) after Pathos completed the acquisition of Rain in January 2024.

Previous wording

TAVALISSE net product sales for the three months ended March 31, 2025 were $28.5 million, increased by 35% compared to $21.1 million for the same period in 2024. The increase was primarily due to increased quantities sold and higher price per bottle, and partially due to lower revenue reserves rate. REZLIDHIA net product sales in the three months ended March 31, 2025 were $6.1 million, increased by 25% compared to $4.9 million for the same period in 2024. The increase was primarily due to increased quantities sold as well as higher price per bottle, partially offset byhigher revenue reserves rate. Following the commercialization of GAVRETO in June 2024, we started recognizing revenue from shipments to our distributors. For the three months ended March 31, 2025, we recognized $9.0 million of GAVRETO net product sales.

Current wording

TAVALISSE net product sales for the three and six months ended June 30, 2025 were $40.1 million and $68.5 million, respectively, increased by 52% and 44%, respectively, compared to $26.4 million and $47.5 million for the three and six months ended June 30, 2024, respectively. The increase was primarily due to increased quantities sold and higher price per bottle, and partly due to lower revenue reserves rate. REZLIDHIA net product sales for the three and six months ended June 30, 2025 were $7.0 million and $13.1 million, respectively, increased by 36% and 31%, respectively, compared to $5.2 million and $10.0 million for the three and six months ended June 30, 2024, respectively. The increase was primarily due to increased quantities sold and higher price per bottle, which were partially offset byhigher revenue reserves rate. Following the commercialization of GAVRETO in June 2024, we started recognizing revenue from shipments to our distributors. For the three and six months ended June 30, 2025, we recognized $11.8 million and $20.8 million of GAVRETO net product sales, compared to $1.9 million net product sales for the three and six months ended June 30, 2024.

Previous wording

Contract revenues from collaborations in the three months ended March 31, 2025 comprised primarily of revenue from Grifols of $4.7 million related to earned royalty and delivery of drug supplies, as well as revenue from Kissei of $4.6 million related to a milestone payment and delivery of drug supplies. Contract revenues from collaborations in the three months ended March 31, 2024 comprised primarily of revenue from Kissei of $2.3 million related to the delivery of drug supplies, and revenue from Grifols of $1.1 million related to earned royalty.

Current wording

Contract revenues from collaborations for the three and six months ended June 30, 2025 primarily consisted of $40.0 million of non-cash revenue related to the release of cost share liability from our collaboration with Lilly. In addition, for the three and six months ended June 30, 2025, contract revenues from collaborations includes revenue from Grifols of $2.0 million and $6.7 million, respectively, related to earned royalty and delivery of drug supplies, as well as revenue from Kissei of $0.4 million and $5.1 million, respectively, related to delivery of drug supplies and a milestone payment in the first quarter of 2025. Contract revenues from collaborations in the three and six months ended June 30, 2024 consisted primarily of revenue from Kissei of $2.2 million and $4.5 million, respectively, related to the delivery of drug supplies, and revenue from Grifols of $1.1 million and $2.2 million, respectively, related to earned royalty.

Previous wording

The cost of product sales includes the cost of inventories sold to our customers and to our collaborative partners. Certain inventories sold for the periods presented include inventory quantities acquired or produced prior to the FDA approval of the product, and do not reflect the full cost of the inventories sold, since such costs incurred prior to FDA approval were previously expensed and charged to research and development expense. In particular, we still utilize API with zero cost for our TAVALISSE inventories, which we expect to make use of for the next 12 months. As such, we recognize lower cost of product sales in the periods where we sell inventory quantities acquired or produced prior to the FDA approval of the product. As we acquire or produce more FDA approved inventory quantities in the future, our inventory cost in the balance sheet and cost of product sales will reflect the full cost of acquiring or producing such products. We rely and will continue to rely on certain third parties, including those located outside the US to manufacture our products. The imposition or threat of imposition of trade policies, tariffs (including retaliatory tariffs), taxes and other cross boarder operations could result in higher cost of product sales. Cost of product sales may also include reserves for potential excess, dated or obsolete inventories, estimated based upon assumptions about future demand and market conditions as well as product shelf lives. Cost of product sales also includes amortization of intangible assets acquired from in-licensing or acquisition of commercialized products, as well as sublicensing revenue fees and royalty expense.

Current wording

The cost of product sales includes the cost of inventories sold to our customers and to our collaborative partners. Certain inventories sold for the periods presented include inventory quantities acquired or produced prior to the FDA approval of the product, and do not reflect the full cost of the inventories sold, since such costs incurred prior to FDA approval were previously expensed and charged to research and development expense. In particular, we still utilize API with zero cost for our TAVALISSE inventories, which we expect to make use of for the next 12 months. As such, we recognize lower cost of product sales in the periods where we sell inventory quantities acquired or produced prior to the FDA approval of the product. As we acquire or produce more FDA approved inventory quantities in the future, our inventory cost in the balance sheet and cost of product sales will reflect the full cost of acquiring or producing such products. We rely and will continue to rely on certain third parties, including those located outside the US to manufacture our products. The imposition or threat of imposition of trade policies, tariffs (including retaliatory tariffs), taxes and other cross-border operations could result in higher cost of product sales. Cost of product sales may also include reserves for potential excess, dated or obsolete inventories, estimated based upon assumptions about future demand and market conditions as well as product shelf lives. Cost of product sales also includes amortization of intangible assets acquired from in-licensing or acquisition of commercialized products, as well as sublicensing revenue fees and royalty expense.

Previous wording

The increase in cost of product sales in the three months ended March 31, 2025 compared to the same period in 2024 was primarily due to increased royalties and amortization expense of $1.2 million. In addition, cost of product sales also increased by $1.2 million due to the increase in product sales and delivery of drug supplies to our collaboration partners.

Current wording

Cost of product sales increased in the three and six months ended June 30, 2025 compared to the same periods in 2024, primarily due to increased royalties of $1.3 million and $2.2 million, respectively, as well as increased cost of products and other increases of $0.4 million and $1.9 million, respectively, generally due to the increase in product sales and delivery of drug supplies to our collaboration partners.

Previous wording

The increase in research and development expense in the three months ended March 31, 2025 compared to the same period in 2024 was primarily driven by the increase in clinical trial related expenses of $1.9 million due to the timing of study progress activities on our ongoing IRAK 1/4 inhibitor program, and clinical development programs for olutasidenib. In addition, other various research and development expenses also increased by $0.6 million.

Current wording

The increase in research and development expense in the three months ended June 30, 2025 compared to the same period in 2024 was primarily driven by the increase in clinical trial related expenses of $0.9 million due to timing of clinical development programs for olutasidenib study, and the progress activities on our ongoing IRAK 1/4 inhibitor program. In addition, other various research and development expenses increased by $0.4 million.

Previous wording

We do not track fully burdened research and development costs separately for each of our drug candidates. Our research team is focused on identifying and evaluating product candidates in our focused range of therapeutic indications that can be developed into small molecule therapeutics in our own proprietary programs or with potential collaborative partners. “Research” expenses relate primarily to personnel expenses, lab supplies, fees to third-party research consultants and compounds. Our development group leads the implementation of our clinical and regulatory strategies and prioritizes disease indications in which our compounds may be studied in clinical trials. “Development” expenses relate primarily to clinical trials, personnel expenses, costs related to our regulatory filings, lab supplies and fees to third-

Current wording

We do not track fully burdened research and development costs separately for each of our drug candidates. Our research team is focused on identifying and evaluating product candidates in our focused range of therapeutic indications that can be developed into small molecule therapeutics in our own proprietary programs or with potential collaborative partners. “Research” expenses relate primarily to personnel expenses, lab supplies, fees to third-party research consultants and compounds. Our development group leads the implementation of our clinical and regulatory strategies and prioritizes disease indications in which our compounds may be studied in clinical trials. “Development” expenses relate primarily to clinical trials, personnel expenses, costs related to our regulatory filings, lab supplies and fees to third-party research consultants. “Other” expenses primarily consist of allocated facilities costs and allocated stock-based compensation expense relating to personnel in research and development groups.

Previous wording

“Other” expenses in the three months ended March 31, 2025 and 2024 consisted of allocated facilities costs of $0.1 million and $0.1 million, respectively, andallocated stock-based compensation expense of $0.9 million and $0.7 million, respectively.

Current wording

“Other” expenses in the three months ended June 30, 2025 and 2024 consisted of allocated facilities costs of $0.1 million and $0.2 million, respectively, andallocated stock-based compensation expense of $0.5 million and $0.3 million, respectively. For the six months ended June 30, 2025 and 2024, allocated facilities costs were $0.2 million and $0.3 million, respectively, and allocated stock-based compensation expense was $1.4 million and $1.0 million, respectively.

Previous wording

The decrease in selling, general and administrative expense in the three months ended March 31, 2025 compared to the same period in 2024 was primarily due to decreased stock-based compensation expense of $2.0 million primarily from our performance-based stock awards, and decreased other various sales, general and administrative expenses of $0.4 million. These decreases were partially offset by increased personnel-related costs of $1.5 million and increased commercial related expenses of $0.2 million.

Current wording

The increase in selling, general and administrative expense in the six months ended June 30, 2025 compared to the same period in 2024 was primarily due to increased personnel-related costs of $2.5 million and increased other various sales, general and administrative expenses of $1.0 million. These increases were partially offset bydecreased consulting and third-party services of $1.5 million, and decreased stock-based compensation expense of $1.5 million primarily related to our performance-based stock awards.

Previous wording

For the three months ended March 31, 2025, we recorded $0.1 million of provision for income tax primarily related to estimated state taxes. We do not expect to owe federal income tax due to sufficient net operating loss carryforwards that were generated prior to the enactment of the Tax Cuts and Jobs Act, as well as significant research and development credit carryforwards. We continue to record a full valuation allowance on our deferred tax assets considering our cumulative losses in prior years. For the three months ended March 31, 2024, we did not record a provision for income taxes due to our pre-tax book loss.

Current wording

The provision for income taxes for the three and six months ended June 30, 2025 was primarily related to estimated state taxes. For the three and six months ended June 30, 2024, we did not record a provision for income taxes due to our pre-tax book loss. We do not expect to owe federal income tax due to sufficient net operating loss carryforwards that were generated prior to the enactment of the TCJA, as well as significant research and development credit carryforwards.

Previous wording

As of March 31, 2025 and December 31, 2024, we had approximately $77.1 million and $77.3 million, respectively, in cash, cash equivalents and short-term investments. We continue to maintain investment portfolios primarily in money market funds, US treasury bills, government-sponsored enterprise securities, corporate bonds and commercial paper. Cash in excess of immediate requirements is invested with regard to liquidity and capital preservation. We view our investments portfolio as available-for-sale and are available for use in current operations. Wherever possible, we seek to minimize the potential effects of concentration and degrees of risk. We continue to monitor the impact of the changes in the conditions of the credit and financial markets to our investment portfolio and assess if future changes in our investment strategy are necessary.

Current wording

As of June 30, 2025 and December 31, 2024, we had approximately $108.4 million and $77.3 million, respectively, in cash, cash equivalents and short-term investments. We continue to maintain investment portfolios primarily in money market funds, US treasury bills, government-sponsored enterprise securities, corporate bonds and commercial paper. Cash in excess of immediate requirements is invested with regard to liquidity and capital preservation. We view our investments portfolio as available-for-sale and are available for use in current operations. Wherever possible, we seek to minimize the potential effects of concentration and degrees of risk. We continue to monitor the impact of the changes in the conditions of the credit and financial markets to our investment portfolio and assess if future changes in our investment strategy are necessary.

Previous wording

Following summarizes our cash flow activity for the periods presented:

Current wording

The following table summarizes our cash flow activity for the periods presented:

Previous wording

Net cash used in operating activities for the three months ended March 31, 2025 comprised net cash outflows from changes in assets and liabilities of $16.1 million, partially offset by net cash inflows from net income adjusted for non-cash items of $15.2 million. Cash outflows from changes in assets and liabilities during the three months ended March 31, 2025 were primarily due to timing of advance payments to our contract manufacturers and strategic development collaboration partner, as well as timing of payments of salaries and annual cash bonuses. Net cash used in operating activities for the three months ended March 31, 2024 comprised net cash outflows from changes in assets and liabilities of $2.1 million, and cash outflows from net loss adjusted for non-cash items of $2.9 million. Cash outflows from changes in assets and liabilities during the three months ended March 31, 2024 were primarily due to timing of inventory build-up and advance payments to our contract manufacturers, as well as timing of payments of salaries andannual cash bonuses.

Current wording

Net cash provided by operating activities for the six months ended June 30, 2025 comprised net cash inflows from net income adjusted for non-cash items, partially offset by net cash outflows from changes in assets and liabilities. Net cash used in operating activities for the six months ended June 30, 2024 comprised net cash outflows from net loss adjusted for non-cash items, and net cash outflows from changes in assets and liabilities. Net cash flows from changes in assets and liabilities for the six months ended June 30, 2025 and 2024 were primarily due to timing of inventory build-up, timing of advance payments to our contract manufacturers and strategic development collaboration partners, timing of payment of liabilities, and timing of collection of accounts receivable.

Previous wording

Net cash used in investing activities for the three months ended March 31, 2025 comprised net purchases of short-term investments of $10.6 million. Net cash provided by investing activities for the three months ended March 31, 2024 comprised primarily of net maturities of short-term investments of $0.5 million, partially offset by payment for acquisition of intangible assets of $0.1 million.

Current wording

Net cash used in investing activities for the six months ended June 30, 2025 primarily comprised net purchases of short-term investments of $33.8 million. Net cash provided by investing activities for the six months ended June 30, 2024 comprised primarily of net maturities of short-term investments of $11.6 million, partially offset by payments for acquisition of intangible assets of $0.4 million.

Previous wording

Net cash provided by financing activities for the three months ended March 31, 2025 comprised proceeds from issuance of common stock upon exercise of stock options of $0.5 million. Net cash used in operating activities for the three months ended March 31, 2024 comprised cost share payments to a collaboration partner of $2.6 million, partially offset by the net proceeds from issuance of common stock upon exercise of stock options of $0.1 million.

Current wording

Net cash provided by financing activities for the six months ended June 30, 2025 comprised net proceeds from issuance of common stock from equity plans of $0.9 million. Net cash used in operating activities for the six months ended June 30, 2024 comprised cost share payments to a collaboration partner of $3.6 million, partially offset by thenet proceeds from issuance of common stock from equity plansof $0.3 million.

Previous wording

the work order. In October 2024, we entered into an agreement with a third-party contract manufacturer to manufacture TAVALISSE that is expected to be delivered starting in 2026 through 2029. As of March 31, 2025, the contractual obligation not included in our financial statements related an agreement that may potentially be subjected to cancellation fees amounted to approximately $20.8 million, with approximately $2.8 million due in the remainder of 2025 and $9.7 million due in 2026 and 2027. As of March 31, 2025, we have not incurred any cancellation fees under our agreements with contract manufacturers.

Current wording

In the ordinary course of business, we enter into agreements with contract manufacturers to manufacture our inventory products. Although the agreements generally provide a termination clause with or without cause, we may still be subjected to payment of cancellation fees. The level of cancellation fees is generally dependent on the timing of the written notice in relation to the commencement of work, with the maximum cancellation fees equal to the full price of the work order. In October 2024, we entered into an agreement with a third-party contract manufacturer to manufacture TAVALISSE that is expected to be delivered starting in 2026 through 2029. As of June 30, 2025, the contractual obligation not included in our financial statements related to an agreement that may potentially be subjected to cancellation fees amounting to approximately $22.5 million, with approximately $3.0 million due in the remainder of 2025 and $10.5 million due in 2026 and 2027. As of June 30, 2025, we have not incurred any cancellation fees under our agreements with contract manufacturers.

Previous wording

As discussed in detail in “Note 4 – Sponsored Research, License Agreements and Government Contracts” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, under the Lilly Agreement, although our co-funding obligation for development of ocadusertib (previously R552) in the US, Europe, and Japan ended on April 1, 2024, we have the right to opt-in to co-funding, upon us providing notice to Lilly within 30 days of certain events, as specified in the agreement. On April 30, 2025, we provided notice to Lilly of our decision not to exercise our opt-in right following our evaluation of certain events specified in the Lilly Agreement. Following this notification, we are no longer obligated to share in any future global development costs, which resulted in the release of the $40.0 million remaining cost share liability currently on our condensed balance sheet.

Current wording

As discussed in detail in “Note 4 – Sponsored Research, License Agreements and Government Contracts” of our “Notes to Condensed Financial Statements” contained in Part I, Item 1 of this Quarterly Report on Form 10-Q, under the Lilly Agreement, although our co-funding obligation for development of ocadusertib (previously R552) in the US, Europe, and Japan ended on April 1, 2024, we have the right to opt-in to co-funding, upon us providing notice to Lilly within 30 days of certain events, as specified in the agreement. On April 30, 2025, we provided notice to Lilly of our decision not to exercise our opt-in right following our evaluation of certain events specified in the Lilly Agreement. Following this notification, we are no longer obligated to share in any future global development costs, which resulted in the release of the $40.0 million remaining cost share liability.

Previous wording

We have a contractual commitment with respect to our credit facility with MidCap. Under the amended Credit Agreement, the term loans mature on September 1, 2027, and the interest-only period is through October 1, 2025. As of March 31, 2025, the outstanding principal amount of the loan was $60.0 million, of which $15.0 million principal payments are due within 12 months. As of March 31, 2025, future interest calculated using the base interest rate as per the amended Credit Agreement, and the final fee payments associated with the credit facility amounted to $12.7 million, with approximately $6.2 million payable within 12 months.

Current wording

We have a contractual commitment with respect to our credit facility with MidCap. Under the amended Credit Agreement, the term loans mature on September 1, 2027, and the interest-only period is through October 1, 2025. As of June 30, 2025, the outstanding principal amount of the loan was $60.0 million, of which $22.5 million principal payments are due within 12 months. As of June 30, 2025, future interest calculated using the base interest rate as per the amended Credit Agreement, and the final fee payments associated with the credit facility amounted to $11.0 million, with approximately $5.8 million payable within 12 months.

Previous wording

As of March 31, 2025, we have a contractual commitment related to our sublease agreement with Atara which sublease will expire in May 2025. In February 2025, we entered into a lease agreement with 611 Gateway to lease the same office space currently subleased from Atara. As of March 31, 2025, our contractual commitment related to the lease agreements was $1.5 million, of which $0.6 million is payable in the next 12 months.

Current wording

As of June 30, 2025, we have a contractual commitment related to our lease agreement with 611 Gateway which lease will expire in July 2027. As of June 30, 2025, our contractual commitment related to the lease agreements was $1.4 million, of which $0.6 million is payable in the next 12 months.