Executive Summary / Key Takeaways

• Rigel Pharmaceuticals has transformed into a profitable, self-sustaining biotechnology company, driven by robust commercial execution across its three FDA-approved products: TAVALISSE, REZLIDHIA, and GAVRETO.
• The company is experiencing accelerated top-line growth, with 2025 total revenue guidance raised to $285 million to $290 million, reflecting 55% to 59% year-over-year net product sales growth, significantly outpacing historical trends.
• Rigel's pipeline is advancing with promising assets like R289, a dual IRAK1/4 inhibitor for lower-risk MDS with Fast Track and Orphan Drug designations, and strategic collaborations for olutasidenib in various IDH1-mutated cancers.
• Strong financial discipline has led to consistent profitability and a healthy cash balance, enabling internal funding of key development programs and opportunistic business development.
• Key risks include intense competition, potential generic entry for TAVALISSE by Q2 2032, and the inherent uncertainties of clinical development and regulatory approvals.

A New Chapter: Rigel's Ascent in Hematology and Oncology

Rigel Pharmaceuticals, Inc. has undergone a significant transformation, evolving from a research-focused entity with a history of operating losses into a profitable, commercially vibrant biotechnology company. Founded in 1996, Rigel's journey was initially marked by substantial research and development (R&D) expenditures. The pivotal moment arrived in April 2018 with the FDA approval of TAVALISSE (fostamatinib disodium hexahydrate) for chronic immune thrombocytopenia (ITP), marking its entry into the commercial stage. This foundational product, coupled with strategic in-licensing and acquisitions, has propelled Rigel into a new era of growth and financial stability within the competitive hematology and oncology landscape.

The company's overarching strategy is clear: to expand its hematology and oncology business through aggressive commercial performance, strategic pipeline development, and unwavering financial discipline. This approach has yielded impressive results, positioning Rigel as a compelling investment opportunity.

Differentiated Technology Driving Market Presence

Rigel's core strength lies in its expertise in small molecule inhibitors targeting critical signaling pathways in hematologic disorders and cancer. This technological differentiation underpins its commercial portfolio and pipeline.

TAVALISSE (fostamatinib), an oral spleen tyrosine kinase (SYK) inhibitor, is approved for adult patients with chronic ITP who have had an insufficient response to previous treatments. Its mechanism of action, blocking SYK inside immune cells to interrupt platelet destruction, offers a distinct approach compared to other ITP therapies like thrombopoietin receptor agonists (TPO-RAs) or immunosuppressants. Clinical data from a Phase 2 trial demonstrated that fostamatinib significantly increased platelet counts in certain ITP patients. Post-hoc analysis from the Phase 3 program highlighted its potential benefit in earlier lines of therapy, and long-term studies have shown durable efficacy and safety for up to five years of treatment. This differentiated mechanism provides a competitive edge, fostering customer loyalty through specialized treatment.

REZLIDHIA (olutasidenib), Rigel's second FDA-approved product, is an oral, selective isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for relapsed or refractory (RR) acute myeloid leukemia (AML) with a susceptible IDH1 mutation. This targeted agent works by reducing 2-hydroxyglutarate levels and restoring normal cellular differentiation. In its Phase 2 registrational trial, REZLIDHIA demonstrated a complete remission (CR) plus CR with partial hematologic recovery (CRh) rate of 35%, with over 90% of responders achieving complete remission. Crucially, it showed an extended median duration of complete response of 28.1 months, significantly longer than reported with standard of care. Its efficacy in the post-venetoclax patient population is considered a clear differentiator by management, offering a vital option for difficult-to-treat patients.

GAVRETO (pralsetinib), the company's third commercial product, is a once-daily, oral kinase inhibitor targeting wild-type RET and oncogenic RET fusions. Approved for metastatic RET fusion-positive non-small cell lung cancer (NSCLC) and advanced thyroid cancers, GAVRETO is one of only two approved RET inhibitors on the market. Its targeted action addresses specific genetic alterations driving tumor growth, providing a precision medicine approach. The National Comprehensive Cancer Network (NCCN) Guidelines for NSCLC recommend pralsetinib as a preferred first-line treatment, underscoring its clinical significance.

Rigel's R&D efforts are focused on expanding these technological advantages. R289, a novel dual interleukin receptor-associated kinases 1 and 4 (IRAK1/4) inhibitor, is in a Phase 1b study for relapsed or refractory lower-risk myelodysplastic syndrome (MDS). Preclinical studies showed R835 (the active moiety of R289) blocks inflammatory cytokine production and is active in various inflammatory models. In a healthy volunteer study, R835 markedly suppressed LPS-induced cytokine release. Preliminary Phase 1b data in heavily pretreated MDS patients showed durable red blood cell transfusion independence (RBC-TI) for 8 weeks in 31% of evaluable transfusion-dependent patients receiving doses of at least 500 mg once daily and higher, with a median RBC-TI duration of 24.3 weeks. Plasma concentrations of R835 at 500 mg once daily correlated with 50% LPS-induced cytokine inhibition, suggesting a potential dose-response threshold. R289 has received FDA Fast Track and Orphan Drug designations, signaling an expedited regulatory path and potential market exclusivity.

The company is also strategically expanding olutasidenib's reach through collaborations. A multi-year alliance with the MD Anderson Cancer Center (MDACC) is evaluating olutasidenib in five studies across AML, MDS, and myeloproliferative neoplasms. A collaboration with the CONNECT Cancer Consortium is conducting a Phase 2 trial (TarGeT-D) for olutasidenib in combination with temozolomide for high-grade glioma (HGG) in adolescents and young adults. These initiatives, along with a planned Rigel-led Phase 2 study in recurrent glioma and a collaboration with MyeloMATCH for first-line AML and MDS, aim to leverage olutasidenib's mechanism in a cost-efficient manner across a broader spectrum of IDH1-mutated cancers.

Financial Performance and Operational Momentum

Rigel's strategic focus has translated into robust financial performance, particularly in 2025. For the nine months ended September 30, 2025, the company reported total revenues of $224.48 million and net income of $98.959 million. This marks a significant turnaround from historical operating losses, with 2024 being the first profitable year since 2010, achieving $17.5 million in net income.

The third quarter of 2025 showcased record performance, with total revenue reaching $69.5 million, a 65% year-over-year increase. Net product sales hit an all-time high of $64.1 million, also up 65% year-over-year. This strong growth was driven by increased demand across all three commercial products and favorable gross-to-net dynamics, partly influenced by the Inflation Reduction Act (IRA) which improved patient affordability for oral therapies. Net income for Q3 2025 was $27.9 million.

Product-specific performance highlights include:

• TAVALISSE: Net product sales of $44.7 million in Q3 2025, a 70% year-over-year increase. For the nine months ended September 30, 2025, sales reached $113.3 million, up 54% from the same period in 2024. This growth is attributed to consistent new patient demand and increased carryover.
• REZLIDHIA: Net product sales of $8.3 million in Q3 2025, a 50% year-over-year increase. Year-to-date sales were $21.4 million, up 38% from the prior year. The company observed increased breadth and depth of prescribers, driven by the product's efficacy in post-venetoclax patients.
• GAVRETO: Net product sales of $11.1 million in Q3 2025, a 56% increase compared to Q3 2024, its first full quarter under Rigel's commercialization. The seamless transition of GAVRETO patients and accounts from Blueprint Medicines (BPMC) demonstrated Rigel's agile operational capabilities, with Q4 2024 sales ($8.1 million) already exceeding the prior owner's annual run rate.

Operating expenses reflect strategic investments. Research and development expenses increased in Q3 2025 ($7.353 million) and 9M 2025 ($22.610 million) due to personnel costs and advancing clinical trials for R289 and olutasidenib. Selling, general, and administrative expenses also rose in Q3 2025 ($28.936 million) and 9M 2025 ($85.908 million) to support commercial expansion. Despite these investments, Rigel maintains impressive TTM margins: Gross Profit Margin of 93.10%, Operating Profit Margin of 42.17%, and Net Profit Margin of 40.17%.

Liquidity remains strong, with $137.1 million in cash, cash equivalents, and short-term investments as of September 30, 2025. Management believes these resources are sufficient to fund operations for at least the next 12 months. The company also has approximately $1.1 billion in potential future contingent payments from existing collaboration agreements, excluding royalties, which further bolsters its financial outlook.

Competitive Landscape and Strategic Positioning

Rigel operates in an intensely competitive biotechnology and pharmaceutical industry, facing both large, diversified pharmaceutical companies and niche biotechs.

In ITP, TAVALISSE competes with established therapies such as corticosteroids, TPO-RAs (e.g., Novartis 's PROMACTA, Amgen (AMGN)'s Nplate), and immunosuppressants. While these competitors benefit from strong brand recognition and broader distribution networks, TAVALISSE's unique SYK inhibition mechanism offers a differentiated treatment option, particularly for patients who have not responded to previous therapies. The future entry of a generic TAVALISSE in Q2 2032, following a patent litigation settlement with Annora Pharma, presents a long-term competitive challenge.

For mIDH1 AML, REZLIDHIA competes directly with Agios Pharmaceuticals (AGIO)' TIBSOVO (ivosidenib), another oral IDH1 inhibitor. Beyond targeted therapies, non-targeted treatments like venetoclax combinations and hypomethylating agents are also used. REZLIDHIA's demonstrated durable remissions and efficacy in post-venetoclax patients provide a crucial competitive advantage in this difficult-to-treat population.

In RET fusion-positive cancers, GAVRETO competes with Eli Lilly 's selpercatinib (Retevmo) and other multi-kinase inhibitors. GAVRETO's position as one of only two approved RET inhibitors, coupled with NCCN guideline recommendations for first-line use in NSCLC, solidifies its market standing.

The emerging lower-risk MDS market for R289 is also competitive, with therapies like erythropoiesis-stimulating agents (ESAs), luspatercept, and imetelstat. Current treatments achieve 8-week transfusion independence rates of only 38-40%, leaving a significant unmet need. R289's dual IRAK1/4 inhibition offers a novel mechanism to suppress marrow inflammation and restore hematopoiesis, potentially providing a new option for heavily pretreated, transfusion-dependent patients.

Compared to large pharmaceutical companies like Eli Lilly (LLY), AstraZeneca (AZN), Novartis (NVS), and Pfizer (PFE), Rigel is a specialized player. While these larger entities possess significantly greater financial resources, broader pipelines, and extensive global reach, Rigel leverages its agility and focused expertise in small molecule inhibitors to target underserved patient populations. This allows Rigel to achieve greater efficiency in niche applications and potentially faster innovation cycles. Rigel's strategic partnerships, such as those for olutasidenib with MDACC and CONNECT, enable it to expand its pipeline and market reach without incurring the full R&D costs, mitigating some of the disadvantages of its smaller scale. However, Rigel's financial performance, while strong, is more concentrated and susceptible to clinical trial outcomes compared to the diversified revenue streams of its larger rivals.

Outlook and Key Considerations

Rigel's management has expressed strong confidence in the company's trajectory, raising its 2025 total revenue guidance to $285 million to $290 million, including net product sales of $225 million to $230 million. This updated outlook implies a remarkable 55% to 59% year-over-year growth in net product sales, significantly exceeding its historical 32% compound annual growth rate. The company anticipates reporting positive net income for the full year 2025, a testament to its financial discipline even with ongoing investments in its pipeline.

Key assumptions underpinning this guidance include sustained commercial momentum for TAVALISSE, REZLIDHIA, and GAVRETO, continued benefits from improved patient affordability due to the IRA, and successful execution of pipeline milestones. The completion of R289's dose escalation phase and the initiation of its dose expansion, along with upcoming data presentations at ASH, are critical catalysts. Similarly, the advancement of olutasidenib through various collaborations and a planned Rigel-led glioma study will be important to watch.

Despite the positive outlook, investors should consider several risks. The intense competitive environment, particularly the potential for generic entry for TAVALISSE, could impact future revenues. Unforeseen safety issues, as highlighted by the GAVRETO Dear Healthcare Provider letter regarding infection risk, could lead to labeling changes or restrictions. Delays in clinical trials or regulatory approvals for pipeline assets, reliance on third-party manufacturers and distributors, and the inherent difficulties in forecasting sales for niche products remain pertinent challenges. Furthermore, the termination of the CNS disease program with Lilly underscores the risks associated with collaborative agreements. Rigel's ability to maintain its strong commercial execution, advance its differentiated pipeline, and manage these risks will be crucial for sustaining its growth and profitability.

Conclusion

Rigel Pharmaceuticals has successfully transitioned into a profitable and growing biotechnology company, firmly establishing its presence in the hematology and oncology sectors. The company's strategic focus on commercial execution, evidenced by the accelerating sales of TAVALISSE, REZLIDHIA, and GAVRETO, is generating significant revenue and enabling self-funded pipeline expansion. Rigel's technological differentiators, particularly its targeted small molecule inhibitors, provide a competitive edge in underserved patient populations, while strategic collaborations efficiently advance its promising clinical programs like R289 in MDS and olutasidenib in various IDH1-mutated cancers.

With a strong financial position and a clear roadmap for pipeline development, Rigel is poised for continued growth. The company's ability to leverage its specialized expertise and maintain financial discipline amidst a competitive landscape will be key to realizing its long-term potential. Investors should closely monitor the ongoing commercial performance, the progression of its clinical pipeline, and the company's strategic responses to competitive pressures and regulatory dynamics.