• GAVRETO^® (pralsetinib) is an FDA approved targeted therapy for the treatment of RET fusion-positive metastatic non-small cell lung cancer and advanced or metastatic thyroid cancer
• Acquisition of established U.S. marketed product further expands Rigel's portfolio and leverages Rigel's existing infrastructure in both the institutional and community settings
• GAVRETO generated ~$28M in U.S. net product sales in 2023

SOUTH SAN FRANCISCO, Calif., Feb. 22, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. ("Rigel") (Nasdaq: RIGL) today announced that it has entered into a definitive agreement to acquire the U.S. rights to GAVRETO^® (pralsetinib) from Blueprint Medicines Corporation ("Blueprint"). GAVRETO is a once daily, small molecule, oral, kinase inhibitor of wild-type RET (rearranged during transfection) and oncogenic RET fusions. GAVRETO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

"NSCLC is the most common type of lung cancer in the U.S. with RET fusions representing 1-2% of the patient population. GAVRETO is a targeted treatment option with an established safety profile that has shown durable responses in RET fusion-positive NSCLC patients and represents a compelling addition to our commercial portfolio," said Raul Rodriguez, Rigel's president and CEO. "We are excited about this transaction, as we continue to realize our corporate strategy to grow our hematology and oncology business while leveraging our existing commercial and medical affairs infrastructure and expertise. GAVRETO is the third commercial product in our portfolio, supporting top line growth and our commitment to providing differentiated therapies to patients in need."

"GAVRETO is one of only two approved RET inhibitors on the market for patients. We are confident in our ability to effectively transition GAVRETO to our distribution network and utilize our robust capabilities to enable both existing and new patients to continue to have access to this important treatment option," said Dave Santos, Rigel's chief commercial officer. "The addition of GAVRETO will be highly synergistic with our current product portfolio, leveraging our existing commercial infrastructure and enabling us to expand into solid tumors."

GAVRETO is also approved 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). This indication was 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). Discussions with the FDA regarding confirmatory requirements are ongoing.

Under the terms of the agreement, Blueprint will receive a purchase price of $15.0 million, $10.0 million of which is payable upon first commercial sale by Rigel and an additional $5.0 million of which is payable on the first anniversary of the closing date, subject to certain conditions. Blueprint is also eligible to receive up to $97.5 million in future commercial milestone payments and up to $5.0 million in future regulatory milestone payments, in addition to tiered royalties ranging from 10% to 30%. Patents that have issued or are expected to issue covering GAVRETO will have statutory expiration dates between 2036 and 2041. Rigel expects to complete the transition of the asset and start recognizing product sales in the third quarter of 2024. Rigel will provide additional details on this transaction at its upcoming quarterly earnings call in early March. 

Rigel's acquisition of the U.S. rights to GAVRETO is concurrent to a previously announced Roche decision to terminate the GAVRETO collaboration agreement with Blueprint effective February 22, 2024. According to a statement from the company, Genentech, a member of the Roche Group, is committed to patients and working with Rigel and Blueprint to ensure current and newly prescribed patients can access GAVRETO without interruption through the transition period, with specific next steps and timing to be communicated to key stakeholders, including healthcare providers, in the next few weeks.

About NSCLC

It is estimated that over 230,000 adults in the U.S. will be diagnosed with lung cancer in 2024.  Lung cancer is the leading cause of cancer death in the U.S, with NSCLC being the most common type accounting for 80-85% of all lung cancer diagnoses.¹ RET fusions are implicated in approximately 1-2% of patients with NSCLC.²

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 www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please click here to see the full Prescribing Information and Patient Information for GAVRETO.

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 www.rigel.com.

1. The American Cancer Society. Key Statistics for Lung Cancer. Revised November 20, 2023. Accessed February 7, 2024: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
2. Kato, S. et al. RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin Cancer Res. 2017 April 15;23(8):1988-1997. doi: 10.1158/1078-0432.CCR-16-1679

Forward Looking Statements

This press release contains forward-looking statements relating to, among other things, the potential benefits of Rigel's acquisition of U.S. rights to GAVRETO, including opportunities in NSCLC and DTC, Rigel's ability to leverage its existing commercial infrastructure to market and distribute GAVRETO, Rigel's ability to transition GAVRETO to its distribution network and provide patients with access to GAVRETO, the payment and timing of milestone and royalty payments and Rigel's ability to start recognizing product sales in the third quarter of 2024 and the market opportunity for GAVRETO. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "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 September 30, 2023 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.

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