Executive Summary / Key Takeaways

• Dual Commercial Success: Syndax has successfully launched two first-in-class therapies, Revuforj and Niktimvo, demonstrating strong early uptake and exceeding initial expectations, with Revuforj's recent NPM1m AML approval significantly expanding its market.
• Technological & First-Mover Advantage: Revuforj, as the first and only FDA-approved menin inhibitor for multiple acute leukemia subtypes, and Niktimvo, as a novel CSF-1R blocking antibody, possess distinct technological differentiators and a crucial first-mover advantage that underpins their competitive positioning.
• Robust Pipeline Expansion: The company is aggressively advancing both assets into earlier lines of therapy, including pivotal frontline trials for acute leukemia and chronic GVHD, and exploring new indications like idiopathic pulmonary fibrosis (IPF), aiming to unlock a combined market opportunity exceeding $10 billion.
• Clear Path to Profitability: Supported by a strong balance sheet ($456.1 million in cash as of Q3 2025) and a commitment to stable operating expenses, Syndax is on track to achieve profitability based on its relapsed/refractory indications alone, with increasing cash flow contributions from both products.
• Efficacy-Driven Competitive Edge: In efficacy-driven markets like acute leukemia, Revuforj's compelling and consistent data across multiple patient subtypes, coupled with its manageable safety profile, positions Syndax for dominant market share against existing and emerging competitors.

Introduction: A New Era of Oncology Leadership

Syndax Pharmaceuticals, Inc. (NASDAQ:SNDX) is rapidly emerging as a formidable specialty oncology company, transitioning from a clinical-stage developer to a commercial leader with two first-in-class therapies addressing significant unmet needs in cancer treatment. Founded in 2005, Syndax's strategic journey has been marked by pioneering innovation and strategic partnerships, culminating in the recent FDA approvals of Revuforj (revumenib) and Niktimvo (axatilimab-csfr). The company's overarching strategy is to leverage its differentiated technology and first-mover advantage to dominate niche oncology markets, expand into earlier lines of therapy, and ultimately achieve sustained profitability. This ambition is set against a backdrop of an oncology market increasingly driven by precision medicine and the urgent need for highly efficacious targeted therapies.

Technological Differentiation and Innovation

At the core of Syndax's investment thesis lies its highly differentiated technological platforms: menin inhibition and CSF-1R blocking. These platforms represent foundational strengths, providing distinct competitive advantages in their respective therapeutic areas.

Revuforj (revumenib): A Pioneer in Menin Inhibition

Revuforj is an oral, first-in-class menin inhibitor, a novel mechanism targeting the menin-KMT2A interaction crucial for certain acute leukemias. This technology offers tangible benefits by disrupting a key oncogenic pathway in genetically defined acute leukemias. The drug has demonstrated compelling and consistent efficacy across multiple genetic subtypes. In relapsed/refractory (R/R) NPM1 mutated AML, Revuforj achieved an approximately 50% overall response rate (ORR), a 5-month median duration of CR/CRh, and a 17% transplant rate, with a 2-year median overall survival observed among responders. For R/R KMT2A-rearranged acute leukemia, the drug has also shown strong clinical activity. These performance metrics are critical in an efficacy-driven market like acute leukemia, where physicians prioritize therapies that can induce deep and durable remissions, often leading to potentially curative stem cell transplants.

Syndax's R&D initiatives for Revuforj are focused on expanding its utility across the entire treatment continuum. The company is actively pursuing its REVEAL trials, which will evaluate revumenib in combination with intensive chemotherapy in newly diagnosed acute leukemia patients with NPM1m or KMT2A-rearranged AML who are fit for intensive chemotherapy, with trial initiation expected by the end of 2025. Additionally, the pivotal Phase 3 EVOLVE-2 trial is underway, evaluating revumenib in combination with venetoclax and azacitidine in newly diagnosed NPM1m AML patients unfit for intensive chemotherapy. This trial, the first pivotal frontline trial for a menin inhibitor, aims to support potential accelerated and full FDA approval through dual primary endpoints of complete remission and overall survival. The potential use of revumenib as an MRD (measurable residual disease) eraser in HOX/MEIS-driven tumors is also an area of high clinical interest, with multiple ongoing studies exploring this. These R&D efforts aim to solidify Revuforj's position as a cornerstone therapy, significantly expanding its market opportunity and competitive moat by addressing broader patient populations and treatment settings.

Niktimvo (axatilimab-csfr): A Novel CSF-1R Blocking Antibody

Niktimvo is a first-in-class colony stimulating factor-1 receptor (CSF-1R) blocking antibody, approved for chronic graft-versus-host disease (cGVHD). This technology targets CSF-1R to reduce the drivers of inflammation and fibrosis, which are hallmarks of cGVHD. In clinical trials, Niktimvo has shown rapid and durable improvements across difficult-to-treat organs like the lungs and skin, with some patients remaining on therapy for over three years. This long-term benefit and tolerability are significant in a chronic disease setting.

Syndax, in partnership with Incyte , is advancing Niktimvo into earlier lines of cGVHD therapy, with two ongoing trials evaluating combinations with ruxolitinib (Phase 2) and corticosteroids (Phase 3). Beyond cGVHD, Niktimvo is being investigated in the MAXPIRe Phase 2 trial for idiopathic pulmonary fibrosis (IPF), with enrollment expected to complete by the end of 2025 and topline data anticipated in the second half of 2026. The preclinical evidence showing significant reduction in lung fibrosis markers with CSF-1R inhibition, bolstered by positive lung responses in the AGAVE-201 trial, provides a strong rationale for its potential in IPF, a market with high unmet need despite existing therapies. The "so what" for investors is clear: these technological differentiators and strategic R&D initiatives aim to create durable competitive advantages, drive market penetration, and unlock multi-billion dollar market opportunities for both assets.

Competitive Landscape and Positioning

Syndax operates in highly competitive oncology and rare disease markets, facing both large, established pharmaceutical companies and other specialized biotechs. Key direct competitors in oncology include Bristol-Myers Squibb (BMY), Pfizer (PFE), Merck (MRK), and Jazz Pharmaceuticals (JAZZ), all of whom possess substantially greater financial, technical, and human resources. However, Syndax's strategic positioning is built on its first-mover advantage and the differentiated profiles of Revuforj and Niktimvo.

Revuforj stands out as the first and only FDA-approved menin inhibitor for multiple acute leukemia subtypes, including R/R KMT2A translocation and R/R NPM1m AML. This breadth of indication and first-mover status provides a significant competitive moat. While other agents are in development for similar populations, Syndax's multiyear head start and compelling efficacy data across various patient subtypes position it for dominant market share. Physicians prioritize efficacy in acute leukemia, and Revuforj's robust response rates and manageable safety profile are key differentiators. The company's commercial organization has established a broad and growing prescriber base, with 70% of Tier 1 and Tier 2 accounts using Revuforj, and a highly efficient limited distribution model ensuring rapid patient access (less than 4 days from prescription to first fill). This customer experience and early market penetration create a high bar for potential "me-too" competitors.

In the cGVHD market, Niktimvo competes with approved drugs like ibrutinib (Imbruvica), belomosidil (Rezurock), and ruxolitinib (Jakafi). Despite this competition, Niktimvo has demonstrated robust early growth, with sales tracking in line with REZUROCK's first-year performance, which annualized at over $500 million within three years. Niktimvo's unique mechanism of action targeting CSF-1R and its ability to address both fibrosis and inflammation provide a distinct advantage. The co-commercialization partnership with Incyte , a leader in GVHD, further strengthens Niktimvo's market penetration and commercial synergies. Syndax's strategy emphasizes leveraging these technological and commercial advantages to capture significant market share and expand into earlier lines of therapy, aiming to transform treatment paradigms in these efficacy-driven disease areas.

Commercial Performance and Operational Details

Syndax's transition to a commercial-stage company has been marked by impressive early performance for both Revuforj and Niktimvo.

Revuforj Performance

For the third quarter ended September 30, 2025, Revuforj generated $32.01 million in net revenue, representing a 12% increase over the prior quarter. Total Revuforj prescriptions and new patient starts saw a robust 25% increase quarter-over-quarter. In the first 10 months since its November 2024 launch, Revuforj has generated nearly $90 million in net revenue, significantly exceeding launch benchmarks for other AML therapies. The drug is rapidly becoming the standard of care for R/R KMT2A, with approximately 50% of usage now in the second line of therapy. This earlier use is translating into better patient outcomes, with an estimated 35% to 40% of KMT2A patients proceeding to a potentially curative stem cell transplant, a higher rate than observed in pivotal trials. Post-transplant, approximately 35% to 40% of patients have restarted Revuforj for maintenance therapy, a percentage expected to grow. The average duration of therapy for KMT2A patients is anticipated to be 4 to 6 months in 2025, extending to 6 to 12 months in 2026 as treatment patterns mature. The recent FDA approval for R/R NPM1m AML on October 24, 2025, is a major growth driver, tripling the addressable patient population from approximately 2,000 to 6,500 incident patients in the R/R setting, representing a market opportunity exceeding $2 billion. Cost of product sales for Revuforj was $2.1 million for Q3 2025 and $4.26 million for the nine months ended September 30, 2025.

Niktimvo Performance

Niktimvo, co-commercialized with Incyte (INCY), achieved $45.8 million in net revenue in Q3 2025, a robust 27% increase over the prior quarter. Syndax's share of this product contribution, recognized as collaboration revenue, amounted to $13.9 million for Q3 2025. In its first eight months of launch, Niktimvo is annualizing at nearly $200 million, tracking in line with first-year sales of Sanofi (SNY)'s REZUROCK. The drug has seen strong uptake, with 8,500 infusions administered to 1,100 patients since launch through Q3 2025. Approximately 80% of patients who started Niktimvo in Q1 2025 remain on therapy, highlighting its durability. Usage is predominantly in the fourth line, but growing in the third line, correlating with a decrease in REZUROCK sales. Over 90% of bone marrow transplant centers in the U.S. are prescribing Niktimvo.

Operational Details

Research and development (R&D) expenses for Q3 2025 decreased by $14.70 million from the comparable prior year period, primarily due to the completion of a registrational trial for NPM1m AML in 2024 and reduced CMC expenses. However, R&D expenses for the nine months ended September 30, 2025, increased by $4 million, driven by planning and initiation of frontline trials for revumenib and higher costs for the Phase 2 IPF trial and frontline cGVHD combination trial. Selling, general and administrative (SG&A) expenses increased by $13.80 million and $46.60 million for the three and nine months ended September 30, 2025, respectively, reflecting commercialization costs for both product launches and increased personnel.

Financial Health and Liquidity

Syndax maintains a strong financial position, with $456.10 million in cash, cash equivalents, and short- and long-term investments as of September 30, 2025. This capital base is deemed sufficient to fund existing and planned cash requirements and achieve profitability. Historically, Syndax has incurred significant losses, with an accumulated deficit of $1.40 billion as of September 30, 2025.

However, the company's net loss for the nine months ended September 30, 2025, improved to $217.40 million from $224.60 million in the prior year.

Cash flow from operations remains negative, with net cash used in operating activities increasing to $253.50 million for the nine months ended September 30, 2025, from $217.50 million in the prior year, primarily due to increases in accounts receivable and inventory.

Investing activities provided $208.50 million in cash, largely from maturities of investments, while financing activities provided $7.76 million, mainly from stock option exercises. The company's $350 million royalty financing deal with Royalty Pharma (RPRX) in November 2024, exchanging rights to certain U.S. net sales of Niktimvo for upfront capital, significantly bolstered its balance sheet. Royalty interest expense from this agreement was $8.30 million for Q3 2025 and $24.20 million for the nine months ended September 30, 2025.

Syndax also has $157.90 million available under its 2023 At-the-Market (ATM) Program. Management is confident that the increasing gross contribution from Revuforj and collaboration revenue from Niktimvo, coupled with stable operating expenses, will drive the company to profitability.

Strategic Outlook and Guidance

Syndax's outlook is characterized by aggressive market expansion and a clear path to profitability. Management expects sales growth for Revuforj to "meaningfully accelerate" over the coming quarters, driven by the NPM1m AML approval and increasing duration of therapy in KMT2A as more patients receive post-transplant maintenance. The average duration of therapy for KMT2A patients is projected to increase from 4-6 months in 2025 to 6-12 months in 2026. Revuforj's gross-to-net adjustments are expected to remain within the 20% to 25% range, and channel inventory levels are anticipated to stay at 2 to 3 weeks.

For Niktimvo, the margin contribution (collaboration revenue as a percentage of net sales) is expected to be in the 25% to 30% range in the near term, increasing longer term as sales grow. This growth is underpinned by the chronic nature of cGVHD and the potential for patients to remain on therapy for years.

A major strategic priority is the expansion of both Revuforj and Niktimvo into the frontline setting, which represents a combined market opportunity exceeding $10 billion. The company is on track to initiate its REVEAL trials for Revuforj in newly diagnosed fit patients by the end of 2025. For Niktimvo, enrollment in the MAXPIRe Phase 2 trial for IPF is expected to complete by the end of 2025, with topline data in H2 2026. Operating expenses (less non-cash stock compensation) are guided to remain stable at $95 million to $100 million for Q3 2025, with a full-year 2025 guidance of $370 million to $390 million. This stable expense base, combined with growing revenues, is central to the company's path to profitability.

Risks and Challenges

Despite significant progress, Syndax faces several inherent risks. Revuforj's label includes a boxed warning for differentiation syndrome (which can be fatal) and QTc prolongation/Torsades de Pointes. While management asserts these are manageable in clinical practice, undesirable side effects could still impact regulatory approval, commercial scope, or lead to product liability claims. Competition is intense, with larger pharmaceutical companies possessing greater resources. Although Revuforj holds a first-mover advantage, other agents are in development, and existing cGVHD therapies compete with Niktimvo.

Operational risks include potential disruptions at regulatory agencies due to funding shortages, which could delay product reviews. Macroeconomic factors like unfavorable interest rates, geopolitical conflicts (e.g., Russia-Ukraine, Israel-Hamas), inflation, and supply chain constraints could increase operating costs and impact capital markets, affecting financing efforts. The company's reliance on future equity offerings, debt financings, and collaboration arrangements for additional capital means there is no committed external source of liquidity beyond existing agreements. While management is confident in its path to profitability, the process of testing product candidates is costly and uncertain, and actual results could differ from estimates.

Conclusion

Syndax Pharmaceuticals is at a pivotal juncture, successfully transforming into a commercial oncology leader on the strength of its two first-in-class therapies, Revuforj and Niktimvo. The company's strategic focus on pioneering novel mechanisms, securing first-mover advantages, and aggressively expanding into broader patient populations and earlier lines of therapy is yielding tangible results, as evidenced by robust early commercial performance and a rapidly advancing pipeline. With Revuforj now approved for both KMT2A-rearranged and NPM1-mutated acute leukemias, and Niktimvo demonstrating strong uptake in cGVHD, Syndax is capitalizing on its technological differentiation in efficacy-driven markets.

The clear roadmap for frontline expansion, supported by ongoing pivotal trials and a commitment to stable operating expenses, underpins management's confidence in achieving profitability with existing funds. While competitive pressures and inherent drug development risks persist, Syndax's strong balance sheet, coupled with the compounding revenue growth from increasing duration of therapy and new indications, positions it for sustained long-term growth. Investors should closely monitor the continued commercial ramp of both products, the progress of frontline clinical trials, and the successful integration of post-transplant maintenance therapy, as these factors will be critical in solidifying Syndax's leadership and realizing its multi-billion dollar market potential.