Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company at the forefront of developing novel cancer therapies. The company's journey began in 2005, and through its unwavering commitment to innovation and patient-centric research, it has emerged as a trailblazer in the oncology arena.
Company Background
Syndax Pharmaceuticals, Inc. was incorporated in Delaware in 2005 with operations in New York, NY and Waltham, MA. The company was founded with the mission to develop and commercialize innovative cancer therapies. In 2016, Syndax made a significant move by entering into a license agreement with UCB Biopharma Sprl, securing a worldwide, sublicensable, exclusive license to develop and commercialize axatilimab, an anti-CSF-1R monoclonal antibody. This was followed by another important agreement in 2017 with Vitae Pharmaceuticals, Inc. (now a subsidiary of AbbVie Inc.), which granted Syndax an exclusive, sublicensable, worldwide license to a portfolio of preclinical, orally available, small molecule inhibitors of the Menin-KMT2A binding interaction, including the compound now known as revumenib.
The early years of Syndax were not without challenges. As a clinical-stage biopharmaceutical company, Syndax incurred net losses in each period since its inception, with the exception of 2021. The company had no products approved for commercial sale and had not generated any product revenues, instead continuing to incur significant research and development and other expenses related to its ongoing operations and clinical development of its product candidates.
Recent Milestones
In August 2024, Syndax's first commercially approved product, Niktimvo (axatilimab-csfr), received FDA approval for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kilograms. This milestone marked Syndax's transition from a development-stage organization to an integrated commercial-stage company, positioning the firm to make a significant impact on patients' lives.
Syndax's financial position has been strengthened by the recent $350 million royalty funding agreement with Royalty Pharma, which provides the company with the capital to fund its operations through profitability. This transaction underscores the vast potential of Niktimvo and the market's underappreciation of its value.
Pipeline and Clinical Progress
Alongside the approval of Niktimvo, Syndax has made remarkable progress in advancing its robust pipeline of cancer therapies. The company's lead product candidate, revumenib, a selective menin inhibitor, is poised to receive FDA approval in the fourth quarter of 2024 for the treatment of relapsed or refractory (R/R) KMT2A-rearranged acute leukemia. The anticipated approval of revumenib is a testament to the compound's compelling clinical profile, which has consistently demonstrated robust and durable responses in heavily pretreated patients.
Syndax's commitment to expanding the potential of revumenib is further evidenced by the ongoing development of the drug in additional indications. In the third quarter of 2024, the company announced positive pivotal topline results from the R/R mutant NPM1 acute myeloid leukemia (AML) cohort in the AUGMENT-101 trial. These results, which met the primary endpoint with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23%, highlight the consistency of revumenib's clinical profile and pave the way for a supplemental NDA filing in the first half of 2025.
Beyond the anticipated approvals of Niktimvo and revumenib, Syndax continues to advance its pipeline, including the exploration of axatilimab, the company's monoclonal antibody targeting the colony-stimulating factor-1 receptor (CSF-1R), in idiopathic pulmonary fibrosis (IPF). The ongoing Phase 2 trial evaluating axatilimab on top of standard of care in patients with IPF is expected to report topline data in 2026, further diversifying Syndax's portfolio and offering the potential for additional value creation.
Financials
Syndax's financial performance has been marked by significant investment in research and development, as evidenced by the company's operating expenses. In the third quarter of 2024, Syndax reported research and development expenses of $70.97 million and selling, general, and administrative expenses of $31.11 million. For the full year 2024, the company has narrowed its guidance, expecting research and development expenses to be $245 million to $250 million and total expenses to be $365 million to $370 million. This guidance includes an estimated $41 million of non-cash stock compensation expense, which is down from the previously estimated $43 million.
The company's financial results for the most recent fiscal year (2023) showed no revenue, a net loss of $209.36 million, and operating cash flow (OCF) and free cash flow (FCF) of -$160.60 million. In the most recent quarter (Q3 2024), Syndax reported revenue of $12.50 million, a net loss of $84.13 million, and OCF and FCF of -$62.32 million. The revenue in Q3 2024 was primarily derived from milestone payments related to the approval of Niktimvo and the Eddingpharm license agreement, totaling $16 million for the first nine months of 2024. The company did not generate any product sales revenue during this period.
The decrease in net income, OCF, and FCF in the quarter was primarily due to increased research and development expenses related to the continued development of the company's lead product candidates revumenib and axatilimab. It's worth noting that the company did not have any revenue in the prior year quarter, so there is no year-over-year growth to report.
Liquidity
The company's cash, cash equivalents, and short- and long-term investments as of September 30, 2024, stood at $399.6 million. This financial position, combined with the $350 million received from the Royalty Pharma transaction, provides Syndax with the necessary resources to fund its operations through profitability, ensuring the successful launches of Niktimvo and revumenib while supporting the continued development of its pipeline.
Syndax's liquidity position remains strong, with no outstanding debt as of September 30, 2024, resulting in a debt-to-equity ratio of 0. The company's cash and cash equivalents totaled $133.02 million, with an additional $256.59 million in short-term investments and $10.03 million in long-term investments. Notably, Syndax also held $217 million in restricted cash. The company's current ratio and quick ratio both stood at 6.99 as of September 30, 2024, indicating robust liquidity and the ability to meet short-term obligations.
Transformation and Achievements
Syndax's transformation from a development-stage to a commercial-stage company has been marked by several key milestones. In addition to the FDA approval of Niktimvo, the positive data from the AUGMENT-101 trial for revumenib in R/R mutant NPM1 AML, and the company's robust financial position, Syndax has also been recognized for its innovative approaches.
The company's menin inhibitor, revumenib, has received Breakthrough Therapy and Fast Track designations from the FDA, underscoring the unmet need in the acute leukemia landscape and the potential of this novel therapy. Additionally, Niktimvo's inclusion in the latest NCCN Clinical Practice Guidelines in Oncology further solidifies its position as a valuable treatment option for patients with cGVHD.
Challenges and Resilience
Syndax's success has not been without its challenges, however. The company has navigated the complexities of drug development, clinical trials, and regulatory approvals, overcoming hurdles and setbacks to deliver on its mission. The COVID-19 pandemic and the ongoing geopolitical tensions, including the wars between Russia and Ukraine and Hamas and Israel, have introduced additional challenges, but Syndax has demonstrated its resilience and adaptability in the face of these disruptions.
Future Outlook
As Syndax looks to the future, the company is poised to capitalize on the momentum created by the recent approvals and positive data readouts. The anticipated launch of Niktimvo in early 2025, followed by the potential approval and launch of revumenib in R/R KMT2A-rearranged acute leukemia and R/R mutant NPM1 AML, positions Syndax as a leading force in the oncology landscape.
Furthermore, the company's commitment to advancing its broader pipeline, including the exploration of axatilimab in IPF, underscores Syndax's vision to address unmet medical needs and improve patient outcomes across various disease areas. The company's strategic partnerships, such as the collaboration with Incyte for the development and commercialization of axatilimab, further strengthen its capabilities and market reach.
Conclusion
In conclusion, Syndax Pharmaceuticals has emerged as a transformative force in the oncology industry, leveraging its innovative pipeline, recent regulatory approvals, and robust financial position to drive meaningful progress in the fight against cancer. With its first commercially approved product, Niktimvo, and a promising pipeline led by revumenib, Syndax is well-positioned to make significant strides in the treatment of various cancers and other diseases.
The company's financial strategy, characterized by substantial investments in research and development, coupled with strategic partnerships and a strong liquidity position, provides a solid foundation for future growth. As Syndax continues to navigate the challenges and capitalize on the opportunities before it, the company remains poised to deliver long-term value for patients, healthcare providers, and shareholders alike.
The upcoming launches of Niktimvo and potentially revumenib, along with the ongoing development of axatilimab in IPF, showcase Syndax's commitment to addressing unmet medical needs across multiple indications. With a clear focus on innovation, strategic execution, and patient-centric approaches, Syndax Pharmaceuticals is well-equipped to continue its trajectory as a leading player in the biopharmaceutical industry, driving advancements in cancer treatment and beyond.