Business Overview and History
Chimerix, a biopharmaceutical company, is dedicated to developing medicines that meaningfully improve and extend the lives of patients facing deadly diseases. With a focus on oncology, the company's pipeline includes its lead asset, dordaviprone (ONC201), and a second-generation compound, ONC206, both targeting critical unmet needs.
Chimerix was founded in 2000 and has steadily expanded its research and development efforts over the past two decades. The company's initial focus was on the development of small-molecule antiviral compounds, including brincidofovir (TEMBEXA), which was approved by the FDA in 2021 for the treatment of smallpox. However, the commercial success of brincidofovir was limited, and in 2022, Chimerix sold the exclusive worldwide rights to the drug to Emergent BioSolutions for an upfront payment of $238 million.
This sale allowed Chimerix to shift its focus to its oncology pipeline, particularly its lead product candidate, dordaviprone (ONC201). In 2021, Chimerix acquired Oncoceutics, a privately-held biotechnology company that had been developing dordaviprone, which brought the imipridone class of compounds into the company's pipeline.
Throughout its history, Chimerix has relied on a combination of government grants, collaborations, and equity financings to fund its research and development activities. The company has faced financial challenges, particularly during periods of clinical development setbacks, but has managed to maintain a relatively strong cash position through these challenges.
Despite the promising data on dordaviprone, Chimerix has faced challenges in advancing the drug through clinical development. In 2021, the company initiated a Phase 3 clinical trial, known as the ACTION study, to evaluate dordaviprone in patients with H3 K27M-mutant diffuse glioma. Enrollment in this trial has been a significant challenge, as H3 K27M-mutant glioma is a rare disease, and the company has had to work with investigators around the world to recruit patients.
Financials
The company's financial performance has been marked by consistent losses, reflecting the inherent challenges of drug development. For the year ended December 31, 2023, Chimerix reported a net loss of $82.1 million, with an accumulated deficit of $795.5 million as of that date. However, the company maintains a strong balance sheet, with $189.1 million in current assets, including $182.8 million in cash, cash equivalents, and short-term investments, as of December 31, 2023.
For the fiscal year 2023, Chimerix reported revenue of $324,000, a net loss of $82,095,000, operating cash flow of -$69,088,000, and free cash flow of -$69,177,000. In the most recent quarter (Q3 2024), the company reported revenue of $26,000, a net loss of $22,879,000, operating cash flow of -$20,294,000, and free cash flow of -$20,320,000. Notably, revenue increased by 136.4% year-over-year, while net income, operating cash flow, and free cash flow remained relatively flat.
For the nine months ended September 30, 2024, Chimerix reported total revenues of $155,000, compared to $320,000 in the same period in 2023. The decrease was primarily related to support provided to Emergent in 2023 following the sale of Chimerix's TEMBEXA program. Research and development expenses were $56.92 million for the nine months ended September 30, 2024, compared to $53.14 million in the same period in 2023. The increase was primarily related to the continued development of dordaviprone and ONC206. General and administrative expenses were $15.25 million for the nine months ended September 30, 2024, compared to $19.43 million in the same period in 2023. The decrease was primarily related to a decrease in compensation expense.
Dordaviprone (ONC201): Addressing a Significant Unmet Need
Dordaviprone is a first-in-class imipridone that selectively binds to the mitochondrial protease ClpP and the dopamine receptor D2 (DRD2). This unique mechanism of action allows the compound to alter key epigenetic modifications, including the reversal of H3 K27me3 loss, which is a hallmark of H3 K27M-mutant gliomas.
Chimerix is currently evaluating dordaviprone in the Phase 3 ACTION study, which is enrolling H3 K27M-mutant diffuse glioma patients at over 145 sites across 15 countries. The company expects to report interim overall survival (OS) data from this pivotal trial in the third quarter of 2025. The ACTION study is nearing complete enrollment, with the first interim data readout potentially less than a year away.
Notably, the company has also initiated the evaluation process for dordaviprone to be considered for Provisional Registration in Australia. This three-step process involves a pre-submission meeting, a provisional determination application, and a final application for provisional registration. If successful, this could potentially lead to the accelerated approval of dordaviprone in Australia, with possible commercial availability as early as 2026. Chimerix is preparing to file a new drug application (NDA) for provisional approval of dordaviprone in Australia around the end of 2024.
ONC206: Advancing a Second-Generation Imipridone
ONC206 is a second-generation imipridone that is 10 times more potent than dordaviprone in vitro and has also demonstrated monotherapy anti-cancer activity in various in vivo models, including central nervous system (CNS) tumors.
Chimerix is currently conducting two Phase 1 dose escalation trials of ONC206, in partnership with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and the National Institutes of Health (NIH). These studies have enrolled over 80 pediatric and adult patients with unselected CNS tumors, and the company expects to complete enrollment in the remaining two dose escalation cohorts by the end of 2024.
The safety profile of ONC206 has been consistent across both pediatric and adult populations, with the majority of treatment-related adverse events being mild to moderate, including fatigue, lymphocyte count decrease, and vomiting. Importantly, no dose-limiting toxicities have been observed to date, even as the dosing has escalated and intensified from once per week to twice per day on three consecutive days per week.
Chimerix plans to assess any objective responses in the first half of 2025, allowing sufficient time for response onset and confirmation in current and future dose cohorts. Additionally, the company is conducting ongoing nonclinical studies to identify candidate oncology indications and biomarkers to inform future development plans for ONC206. The company plans to announce next steps for the ONC206 program in the coming months.
Financial Performance and Outlook
Chimerix's financial performance has been characterized by consistent losses, which is typical for a clinical-stage biopharmaceutical company. For the year ended December 31, 2023, the company reported a net loss of $82.1 million, with an accumulated deficit of $795.5 million as of that date.
However, the company maintains a strong balance sheet, with $189.1 million in current assets, including $182.8 million in cash, cash equivalents, and short-term investments, as of December 31, 2023. This provides Chimerix with a cash runway extending into the fourth quarter of 2026, based on the company's current operational plans.
In the third quarter of 2024, Chimerix reported a net loss of $22.9 million, compared to a net loss of $24.0 million in the same period of the previous year. Research and development expenses increased to $19.6 million, driven primarily by the ongoing Phase 3 ACTION study of dordaviprone, while general and administrative expenses decreased to $5.2 million.
Liquidity
Chimerix maintains a strong balance sheet, with $189.1 million in current assets, including $182.8 million in cash, cash equivalents, and short-term investments, as of December 31, 2023. This provides the company with a cash runway extending into the fourth quarter of 2026, based on current operational plans.
As of the third quarter of 2024, Chimerix reported $23.64 million in cash and cash equivalents. The company has a 4-year secured revolving loan facility with Silicon Valley Bank for up to $50 million, of which no amount has been drawn as of Q3 2024. Chimerix's debt-to-equity ratio is 0, and both its current ratio and quick ratio stand at 6.33, indicating a strong liquidity position.
Risks and Uncertainties
As with any clinical-stage biopharmaceutical company, Chimerix faces several risks and uncertainties that could impact its future performance. These include the potential failure or delay of its clinical trials, the inability to obtain regulatory approvals for its product candidates, competition from other therapies, and the company's ability to successfully commercialize any approved products.
Specifically, the company's lead asset, dordaviprone, is still in the late-stage of clinical development, and there is no guarantee that the Phase 3 ACTION study will be successful or that the compound will receive regulatory approval. Additionally, the company's ability to advance ONC206 into later-stage trials and eventual commercialization is dependent on the successful completion of the ongoing Phase 1 studies and the identification of suitable indications for further development.
Chimerix also faces the risk of potential delays or disruptions to its clinical programs due to factors such as the COVID-19 pandemic, supply chain issues, or other global events that could impact the company's operations and the availability of necessary resources.
Conclusion
Chimerix is a promising biopharmaceutical company focused on developing novel therapies for deadly diseases, with a particular emphasis on oncology. The company's lead asset, dordaviprone, is in late-stage development for the treatment of H3 K27M-mutant diffuse glioma, a rare and aggressive form of brain cancer with a significant unmet need.
Additionally, the company's second-generation imipridone, ONC206, is progressing through Phase 1 studies, with encouraging safety and pharmacokinetic data, and the potential to address a broader range of oncology indications.
While Chimerix has faced consistent financial losses, the company's strong balance sheet and cash runway provide it with the resources necessary to advance its pipeline and potentially bring much-needed therapies to patients. The company is preparing for the potential commercialization of dordaviprone, forecasting a global market opportunity over $750 million. However, the inherent risks and uncertainties associated with drug development must be carefully monitored, as the company's future success is largely dependent on the successful outcomes of its clinical trials and regulatory approvals.