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Nearly 60% of patients with IgAN in the SPARTAN Study achieved complete remission when using FILSPARI as first-line treatment SPARTACUS Study, PROTECT open-label extension, and real-world evidence presentations highlight initial safety and efficacy data of FILSPARI in combination treatment in IgAN Late-breaking presentation demonstrates sparsentan delivered rapid and sustained proteinuria reduction, and long-term kidney health benefits in a subset of patients with genetic, often treatment resistant, FSGS SAN DIEGO, Oct. 26, 2024 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc., (Nasdaq: TVTX), presented new data further demonstrating the clinical benefit of FILSPARI (sparsentan) in IgA nephropathy (IgAN) and reinforcing its potential in focal segmental glomerulosclerosis (FSGS) at the American Society of Nephrology (ASN) Kidney Week 2024. “The data presented at ASN provided additional evidence that FILSPARI is effective across all subgroups of IgAN patients studied to-date, and that it achieved significant levels of complete remission when used in newly diagnosed patients. We also shared initial data showing that FILSPARI safely induced further proteinuria reduction when used with SGLT2 inhibitors or steroids, supportive of the flexibility to be used in combination with other medicines as needed,” said Jula Inrig, M.D., chief medical officer of Travere Therapeutics. “Furthermore, we shared data exploring a subgroup of genetic FSGS patients in our DUPLEX Study. Genetic FSGS patients are often treatment resistant so the significant reductions in proteinuria and benefit on outcomes reported in this group are very encouraging.” Key Findings from the PROTECT Study Subgroup Analysis of Patients with Proteinuria Above and Below 1 g/g FILSPARI delivered superior proteinuria reduction, and complete proteinuria remission earlier and more frequently compared to irbesartan regardless of baseline UPCR, including those at less than 1.0 g/g. Key Findings from the SPARTAN Study Evaluating FILSPARI as a First-Line Therapy FILSPARI delivered a rapid and sustained reduction in proteinuria of approximately 70% from baseline over 24 weeks in newly diagnosed, RASi-naïve patients, and nearly 60% of patients in the SPARTAN study achieved complete remission of proteinuria at any point in time during the treatment period. Throughout the 24 weeks, estimated glomerular filtration rate was stable. Key Findings from the SPARTACUS Study, PROTECT OLE and Real-World Use Evaluating FILSPARI in Combination Therapy for IgAN Interim data from the SPARTACUS Study demonstrated that FILSPARI, when added to stable SGLT2i, was generally well tolerated. Approximately one-third of patients had their proteinuria reduced by at least 50%, and two-thirds of patients by at least 30% when measured after 24 weeks of treatment.Data from the ongoing PROTECT Study open-label extension and real-world use showed favorable safety and additive efficacy results when SGLT2i or immunosuppressants were combined with foundational FILSPARI treatment. Key Findings from the DUPLEX Study Evaluating Sparsentan in Focal Segmental Glomerulosclerosis In a late-breaking presentation from the DUPLEX Study in a subset of patients with genetic mutations in podocyte proteins, a high-risk, treatment resistant FSGS, sparsentan delivered a rapid and sustained proteinuria reduction, including some patients who achieved complete remission and long-term kidney health benefits.An analysis of patient-reported outcomes from 306 adult patients in the DUPLEX Study showed that health-related quality of life for these patients with FSGS on sparsentan was stable over the two-year treatment period, and that patients’ burden of kidney disease was improved compared to those receiving irbesartan. Key Findings from the EPPIK Study Evaluating Sparsentan in Rare Proteinuric Disease in Pediatric Patients Preliminary data from the EPPIK Study showed that children with a range of rare proteinuric glomerular disease treated with sparsentan experienced rapid and robust proteinuria reduction of approximately 50% over 12 weeks. About IgA Nephropathy IgA nephropathy (IgAN), also called Berger's disease, is a rare progressive kidney disease characterized by the buildup of immunoglobulin A (IgA), a protein that helps the body fight infections, in the kidneys. The deposits of IgA cause a breakdown of the normal filtering mechanisms in the kidney, leading to blood in the urine (hematuria), protein in the urine (proteinuria) and a progressive loss of kidney function. Other symptoms of IgAN may include swelling (edema) and high blood pressure. IgAN is the most common type of primary glomerulonephritis worldwide and a leading cause of kidney failure due to glomerular disease. IgAN is estimated to affect up to 150,000 people in the U.S. and is one of the most common glomerular diseases in Europe and Japan. About Focal Segmental Glomerulosclerosis Focal segmental glomerulosclerosis (FSGS) is a rare proteinuric kidney disorder in both children and adults that is estimated to affect more than 40,000 patients in the US with similar prevalence in Europe. The disorder is defined by progressive scarring of the kidney and often leads to kidney failure. FSGS is characterized by proteinuria, where protein leaks into the urine due to a breakdown of the normal filtration mechanism in the kidney. Once in the urine, protein is considered to be toxic to other parts of the kidney, especially the tubules, and is believed to contribute to further disease progression. Other common symptoms include swelling in parts of the body, known as edema, as well as low blood albumin levels, abnormal lipid profiles and hypertension. Sparsentan is not approved for use in FSGS. There is currently no approved pharmacologic indicated for the treatment of FSGS. About Travere Therapeutics At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com FILSPARI® (sparsentan) U.S. Indication FILSPARI (sparsentan) is indicated to slow kidney function decline in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression. IMPORTANT SAFETY INFORMATION BOXED WARNING: HEPATOTOXICITY AND EMBRYO-FETAL TOXICITY Because of the risks of hepatotoxicity and birth defects, FILSPARI is available only through a restricted program called the FILSPARI REMS. Under the FILSPARI REMS, prescribers, patients and pharmacies must enroll in the program. Hepatotoxicity Some Endothelin Receptor Antagonists (ERAs) have caused elevations of aminotransferases, hepatotoxicity, and liver failure. In clinical studies, elevations in aminotransferases (ALT or AST) of at least 3-times the Upper Limit of Normal (ULN) have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. Measure transaminases and bilirubin before initiating treatment and monthly for the first 12 months, and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN. FILSPARI should generally be avoided in patients with elevated aminotransferases (>3x ULN) at baseline because monitoring for hepatotoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity. Embryo-Fetal Toxicity FILSPARI can cause major birth defects if used by pregnant patients based on animal data. Therefore, pregnancy testing is required before the initiation of treatment, during treatment and one month after discontinuation of treatment with FILSPARI. Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for one month after discontinuation of treatment with FILSPARI. Contraindications FILSPARI is contraindicated in patients who are pregnant. Do not coadminister FILSPARI with angiotensin receptor blockers (ARBs), ERAs, or aliskiren. Warnings and Precautions Hepatotoxicity: Elevations in ALT or AST of at least 3-fold ULN have been observed in up to 3.5% of FILSPARI-treated patients, including cases confirmed with rechallenge. While no concurrent elevations in bilirubin >2-times ULN or cases of liver failure were observed in FILSPARI-treated patients, some ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin prior to initiation of treatment and monthly for the first 12 months, then every 3 months during treatment. Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching) to immediately stop treatment with FILSPARI and seek medical attention. If aminotransferase levels are abnormal at any time during treatment, interrupt FILSPARI and monitor as recommended. Consider re-initiation of FILSPARI only when hepatic enzyme levels and bilirubin return to pretreatment values and only in patients who have not experienced clinical symptoms of hepatotoxicity. Avoid initiation of FILSPARI in patients with elevated aminotransferases (>3x ULN) prior to drug initiation because monitoring hepatotoxicity in these patients may be more difficult and these patients may be at increased risk for serious hepatotoxicity. Embryo-Fetal Toxicity: FILSPARI can cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. Advise patients who can become pregnant of the potential risk to a fetus. Obtain a pregnancy test prior to initiation of treatment with FILSPARI, monthly during treatment, and one month after discontinuation of treatment. Advise patients who can become pregnant to use effective contraception prior to initiation of treatment, during treatment, and for one month after discontinuation of treatment with FILSPARI.FILSPARI REMS: Due to the risk of hepatotoxicity and embryo-fetal toxicity, FILSPARI is available only through a restricted program called the FILSPARI REMS. Prescribers, patients, and pharmacies must be enrolled in the REMS program and comply with all requirements (www.filsparirems.com).Hypotension: Hypotension has been observed in patients treated with ARBs and ERAs. There was a greater incidence of hypotension-associated adverse events, some serious, including dizziness, in patients treated with FILSPARI compared to irbesartan. In patients at risk for hypotension, consider eliminating or adjusting other antihypertensive medications and maintaining appropriate volume status. If hypotension develops, despite elimination or reduction of other antihypertensive medications, consider a dose reduction or dose interruption of FILSPARI. A transient hypotensive response is not a contraindication to further dosing of FILSPARI, which can be given once blood pressure has stabilized.Acute Kidney Injury: Monitor kidney function periodically. Drugs that inhibit the renin-angiotensin system (RAS) can cause kidney injury. Patients whose kidney function may depend in part on the activity of the RAS (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute kidney injury on FILSPARI. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in kidney function while on FILSPARI.Hyperkalemia: Monitor serum potassium periodically and treat appropriately. Patients with advanced kidney disease, taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia. Dosage reduction or discontinuation of FILSPARI may be required.Fluid Retention: Fluid retention may occur with ERAs, and has been observed in clinical studies with FILSPARI. FILSPARI has not been evaluated in patients with heart failure. If clinically significant fluid retention develops, evaluate the patient to determine the cause and the potential need to initiate or modify the dose of diuretic treatment then consider modifying the dose of FILSPARI. Most common adverse reactions The most common adverse reactions (≥5%) are hyperkalemia, hypotension (including orthostatic hypotension), peripheral edema, dizziness, anemia, and acute kidney injury. Drug interactions Renin-Angiotensin System (RAS) Inhibitors and ERAs: Do not coadminister FILSPARI with ARBs, ERAs, or aliskiren due to increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure).Strong and Moderate CYP3A Inhibitors: Avoid concomitant use of FILSPARI with strong CYP3A inhibitors. If a strong CYP3A inhibitor cannot be avoided, interrupt FILSPARI treatment. When resuming treatment with FILSPARI, consider dose titration. Monitor blood pressure, serum potassium, edema, and kidney function regularly when used concomitantly with moderate CYP3A inhibitors. Concomitant use with a strong CYP3A inhibitor increases sparsentan exposure which may increase the risk of FILSPARI adverse reactions.Strong CYP3A Inducers: Avoid concomitant use with a strong CYP3A inducer. Concomitant use with a strong CYP3A inducer decreases sparsentan exposure which may reduce FILSPARI efficacy.Antacids and Acid Reducing Agents: Administer FILSPARI 2 hours before or after administration of antacids. Avoid concomitant use of acid reducing agents (histamine H2 receptor antagonist and PPI proton pump inhibitor) with FILSPARI. Sparsentan exhibits pH-dependent solubility. Antacids or acid reducing agents may decrease sparsentan exposure which may reduce FILSPARI efficacy.Non-Steroidal Anti-Inflammatory Agents (NSAIDs), Including Selective Cyclooxygenase-2 (COX-2) Inhibitors: Monitor for signs of worsening renal function with concomitant use with NSAIDs (including selective COX-2 inhibitors). In patients with volume depletion (including those on diuretic therapy) or with impaired kidney function, concomitant use of NSAIDs (including selective COX-2 inhibitors) with drugs that antagonize the angiotensin II receptor may result in deterioration of kidney function, including possible kidney failure.CYP2B6, 2C9, and 2C19 Substrates: Monitor for efficacy of concurrently administered CYP2B6, 2C9, and 2C19 substrates and consider dosage adjustment in accordance with the Prescribing Information. Sparsentan decreases exposure of these substrates, which may reduce efficacy related to these substrates.P-gp and BCRP Substrates: Avoid concomitant use of sensitive substrates of P-gp and BCRP with FILSPARI. Sparsentan may increase exposure of these transporter substrates, which may increase the risk of adverse reactions related to these substrates.Agents Increasing Serum Potassium: Monitor serum potassium frequently in patients treated with FILSPARI and other agents that increase serum potassium. Concomitant use of FILSPARI with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that raise serum potassium levels may result in hyperkalemia. Please see the full Prescribing Information, including BOXED WARNING, for additional Important Safety Information. Forward Looking StatementsThis press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “on-track,” “positioned,” “look forward to,” “will,” “would,” “may,” “might,” “believes,” “anticipates,” “plans,” “expects,” “intends,” “potential,” or similar expressions. In addition, expressions of strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, references to: statement related to the potential for FILSPARI to be used as a first-line treatment for IgAN and the flexibility of FILSPARI to be used in combination with other medicines; statements relating to clinical studies, including but not limited to trial design, results and timing related thereto; and prevalence estimates. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks related to the timing and outcome of the studies described herein and uncertainties associated with the regulatory review and approval process, as well as risks and uncertainties associated with enrollment of clinical trials for rare diseases, and risks that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. The Company also faces risks related to its business and finances in general, the success of its commercial products and risks and uncertainties associated with its preclinical and clinical stage pipeline. Specifically, the Company faces risks associated with the ongoing commercial launch of FILSPARI, market acceptance of its commercial products including efficacy, safety, price, reimbursement, and benefit over competing therapies, as well as risks associated with the successful development and execution of commercial strategies for such products, including FILSPARI. The risks and uncertainties the Company faces with respect to its preclinical and clinical stage pipeline include risk that the Company’s clinical candidates will not be found to be safe or effective and that current or anticipated future clinical trials will not proceed as planned. There is no guarantee that regulators will grant approval of sparsentan for FSGS. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company’s dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company’s products, and technological changes that may limit demand for the Company’s products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. Contact Info Media:888-969-7879mediarelations@travere.comInvestors:888-969-7879IR@travere.com

SOUTH SAN FRANCISCO, Calif., Oct. 24, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. ("Rigel") (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, today announced it is issuing a Dear Health Care Provider (DHCP) letter related to a new safety signal for GAVRETO® (pralsetinib) after consultation with the U.S. Food and Drug Administration (FDA). GAVRETO is for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by a 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). The DHCP letter has been posted to the GAVRETO Healthcare Provider website at . Patient safety is Rigel's highest priority. We are committed to ensuring healthcare providers are aware of this update. Healthcare providers and patients are encouraged to report adverse events in patients taking GAVRETO to the Rigel Medical Communications Center at 1-800-983-1329 or [email protected]. You may also report adverse events associated with taking GAVRETO directly to the FDA. Visit or call 1-800-FDA-1088 (1-800-332-1088). Rigel announced the completion of the transfer to Rigel of the New Drug Application (NDA) for GAVRETO from Blueprint Medicines Corporation in June 2024. About GAVRETO® (pralsetinib) INDICATIONS GAVRETO (pralsetinib) 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 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)* *This 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). IMPORTANT SAFETY INFORMATION Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal ILD/pneumonitis can occur in patients treated with GAVRETO. Pneumonitis occurred in 12% of patients who received GAVRETO, including 3.3% with Grade 3-4, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD. Hypertension: Occurred in 35% of patients, including Grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity. Hepatotoxicity: Serious hepatic adverse reactions occurred in 1.5% of patients treated with GAVRETO. Increased aspartate aminotransferase (AST) occurred in 49% of patients, including Grade 3 or 4 in 7% and increased alanine aminotransferase (ALT) occurred in 37% of patients, including Grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range: 5 days to 2.5 years) and increased ALT was 24 days (range: 7 days to 3.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity. Hemorrhagic Events: Serious, including fatal, hemorrhagic events can occur with GAVRETO. Grade ≥3 events occurred in 4.1% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage. Tumor Lysis Syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving GAVRETO. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. Risk of Impaired Wound Healing: Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established. Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the last dose. Common adverse reactions (≥25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia, and cough. Common Grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased leukocytes, decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium, and increased bilirubin. Avoid coadministration of GAVRETO with strong or moderate CYP3A inhibitors, P-gp inhibitors, or combined P-gp and strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong or moderate CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose. Lactation: Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose. Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur. You may report side effects to the FDA at 1-800-FDA-1088 or . Please click here to see the full Prescribing Information and Patient Information for GAVRETO. GAVRETO is a registered trademark 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 . Forward Looking Statements This press release contains forward-looking statements relating to, among other things, safety signal and warnings and precautions regarding the use of GAVRETO (pralsetinib) and has direct reference to a dear doctor letter which further discusses ad hoc analysis from the AcceleRET-Lung trial and corresponding updates to the product label. 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 "forthcoming," "potential", "may", "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 GAVRETO; risks that the FDA or other regulatory authorities may make adverse decisions regarding GAVRETO; risks that GAVRETO may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop market and distribute GAVRETO; risks related to the transition of GAVRETO to Rigel, including risks related to the effectiveness of transition services and drug continuity; market competition for GAVRETO; 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

Enrollment on track in registrational Phase 2 portion of PYNNACLE clinical trial evaluating rezatapopt as monotherapy in patients with TP53 Y220C and KRAS wild-type advanced solid tumors; more than 75% of sites activated across the U.S., Europe, and Asia-Pacific; interim analysis expected by mid-2025 Dose-limiting toxicities observed in rezatapopt and Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) combination arm of Phase 1b PYNNACLE trial; rezatapopt 500 mg once-daily in combination with pembrolizumab 200 mg every three weeks established as maximum tolerated dose; due to limited clinical benefit at this dose, PMV is discontinuing enrollment in the Phase 1b combination arm PMV Pharmaceuticals is collaborating with MD Anderson Cancer Center (MDACC) and Memorial Sloan Kettering Cancer Center (MSK) to support an investigator-initiated Phase 1b study evaluating rezatapopt monotherapy and in combination with azacitidine in patients with recurrent or refractory AML/MDS harboring a TP53 Y220C mutation PRINCETON, N.J., Oct. 23, 2024 (GLOBE NEWSWIRE) -- PMV Pharmaceuticals, Inc. (Nasdaq: PMVP), a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53, today provided an update on the Phase 2 monotherapy and Phase 1b combination portions of the ongoing PYNNACLE clinical trial. PYNNACLE Phase 2 Monotherapy Update Enrollment is on track in the Phase 2 monotherapy portion of the PYNNACLE clinical trial. The multicenter, single-arm, registrational, tumor-agnostic Phase 2 trial is assessing rezatapopt as monotherapy at a dose of 2000 mg once-daily in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. The primary endpoint of the trial is overall response rate per blinded independent central review. The trial is designed to enroll 114 patients across five cohorts at approximately 60 sites. More than 75% of sites have been activated across the U.S., Europe, and Asia-Pacific. PMV plans to provide data from the interim analysis of the Phase 2 monotherapy portion of the PYNNACLE trial by mid-2025 and anticipates submitting a New Drug Application by the end of 2026. PYNNACLE Phase 1b Rezatapopt in Combination with Pembrolizumab Update PMV has decided to discontinue enrollment in the Phase 1b combination arm of the PYNNACLE trial evaluating rezatapopt in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced solid tumors harboring a TP53 Y220C mutation. Nineteen patients were enrolled in the combination arm of the trial. This decision was driven by dose-limiting toxicities (DLTs) observed at the 1000 mg dose of rezatapopt once-daily plus pembrolizumab 200 mg every three weeks. The DLTs were Grade 2 and 3 and included AST increase, platelet count decrease, pancreatitis, dehydration, and rash. No Grade 4 or 5 adverse events were observed. The safety profile of the rezatapopt and pembrolizumab combination has been consistent with each agent as monotherapy with no new safety signals observed. Per protocol, these observations established rezatapopt 500 mg once-daily in combination with pembrolizumab 200 mg every three weeks as the maximum tolerated dose. Patients dosed with rezatapopt 500 mg once-daily in combination with pembrolizumab did not experience a clinically meaningful benefit, informing the decision to discontinue enrollment in the combination arm of the PYNNACLE trial. MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center to Initiate a Phase 1b Study in Recurrent/Refractory AML/MDS PMV Pharma is collaborating with MD Anderson Cancer Center (MDACC) and Memorial Sloan Kettering Cancer Center (MSK) to support an investigator-initiated Phase 1b study. The study is designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of rezatapopt monotherapy and in combination with azacitidine in approximately 25 patients with recurrent or refractory acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) harboring a TP53 Y220C mutation. Enrollment is planned to begin in the first quarter of 2025 across two sites. “There is an important need for new treatment options for patients with recurrent or refractory AML or MDS harboring a TP53 Y220C mutation, as this mutation is often associated with poorer prognosis and resistance to conventional therapies” said Courtney DiNardo M.D., MSCE, Department of Leukemia, Division of Cancer Medicine at MDACC. “Based on proof-of-concept data demonstrating the ability of rezatapopt to selectively reactivate p53 in locally advanced/metastatic solid tumor patients with a TP53 Y220C mutation, we believe that rezatapopt in combination with azacitidine has the potential to significantly benefit this patient population.” Eytan M. Stein, M.D., Chief, Leukemia Service at MSK commented, “Patients with p53 mutant AML currently have no effective standard of care treatment options that lead to long term survival, so this important trial using rezatapopt is the first step in developing a focused, mutation specific strategy, for this patient population.” David Mack, Ph.D., President and Chief Executive Officer of PMV Pharma commented, “While we are disappointed to discontinue enrollment of the trial evaluating rezatapopt in combination with pembrolizumab, we look forward to the initiation of the AML/MDS study and evaluating rezatapopt in other settings. I would like to thank the patients and investigators for their time and commitment to the Phase 1b combination portion of the PYNNACLE study. We remain excited by the potential for rezatapopt as a monotherapy in patients with advanced solid tumors harboring a TP53 Y220C mutation and KRAS wild-type and look forward to providing interim data in the middle of next year.” KEYTRUDA® (pembrolizumab) is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About Rezatapopt Rezatapopt (PC14586) is a first-in-class, small molecule p53 reactivator designed to selectively bind to the pocket in the p53 Y220C mutant protein, restoring the wild-type tumor-suppressor function. The U.S. Food and Drug Administration (FDA) granted Fast Track designation to rezatapopt for the treatment of patients with locally advanced or metastatic solid tumors with a TP53 Y220C mutation. About the PYNNACLE Clinical Trial The ongoing Phase 1/2 PYNNACLE clinical trial is evaluating rezatapopt in patients with advanced solid tumors harboring a TP53 Y220C mutation. The primary objective of the Phase 1 portion of the trial was to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D) of rezatapopt when administered orally to patients. Safety, tolerability, pharmacokinetics, and effects on biomarkers were also assessed. In Phase 1, an overall response rate of 38% (6/16 evaluable patients) was achieved at the RP2D of 2000 mg daily reflective of the Phase 2 patient population (TP53 Y220C and KRAS wild-type). The median duration of response was seven months. The Phase 2 monotherapy portion is a registrational, single-arm, expansion basket clinical trial comprising five cohorts (ovarian, lung, breast, endometrial cancers, and other solid tumors) with the primary objective of evaluating the efficacy of rezatapopt at the RP2D in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. For more information about the Phase 1/2 PYNNACLE clinical trial, refer to www.clinicaltrials.gov (NCT trial identifier NCT04585750). About PMV Pharma PMV Pharma is a precision oncology company pioneering the discovery and development of small molecule, tumor-agnostic therapies targeting p53. TP53 mutations are found in approximately half of all cancers. Our co-founder, Dr. Arnold Levine, established the field of p53 biology when he discovered the p53 protein in 1979. Bringing together leaders in the field to utilize over four decades of p53 biology, PMV Pharma combines unique biological understanding with a pharmaceutical development focus. PMV Pharma is headquartered in Princeton, New Jersey. For more information, please visit www.pmvpharma.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding our future plans or expectations for rezatapopt, including our ability to obtain approval as a treatment option on a tumor-agnostic basis and as a monotherapy or in combination with other agents, expectations regarding timing for interim data readouts and success of the Phase 2 portion of the PYNNACLE trial, our expectation and timing of NDA filing(s) with the FDA for the current clinical trial for rezatapopt, the current and future enrollment of patients in our clinical trials, the timing, progress and activation of sites for our clinical trials, and plans for MDACC and MSKCC’s investigator-initiated study assessing rezatapopt as monotherapy and in combination with azacitidine for treatment of recurrent or refractory AML/MDS patients. Any forward-looking statements in this statement are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of our product candidate development activities and planned clinical trials, our ability to execute on our strategy and operate as a clinical stage company, the potential for clinical trials of rezatapopt or any future clinical trials of other product candidates to differ from preclinical, preliminary or expected results, our ability to fund operations, and the impact that a global pandemic, other public health emergencies or geopolitical tensions or conflicts may have on our clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in the section entitled “Risk Factors” in our Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the “SEC”) on February 29, 2024, our Quarterly Report on Form 10-Q for the three months ended March 31, 2024, filed with the SEC on May 9, 2024, and our other filings filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Investors Contact:Tim SmithSenior Vice President, Head of Corporate Development and Investor Relationsinvestors@pmvpharma.com Media Contact:Kathy VincentGreig Communicationskathy@greigcommunications.com