Calithera Biosciences, Inc. is a fully-integrated, clinical-stage precision oncology biopharmaceutical company. The company is advancing a pipeline of investigational, small molecule oncology compounds with a biomarker-driven approach, focused on improving the lives of people impacted by cancer.
Business Overview
Calithera's core expertise lies in oncology, with a deep understanding of cellular metabolic pathways and the role of enzymes like glutaminase and arginase in tumor metabolism and the anti-tumor immune response. The company's lead product candidates, sapanisertib and mivavotinib, are both in Phase 2 clinical trials, targeting specific genetic vulnerabilities in cancer.
Sapanisertib
Sapanisertib, a potent and selective dual mTORC1/2 inhibitor, is being evaluated in a Phase 2 trial for the treatment of NRF2-mutated squamous non-small cell lung cancer (sqNSCLC). This patient population has a poorer prognosis and limited treatment options, making sapanisertib's potential a significant opportunity. Preclinical data has shown that sapanisertib has potent anti-tumor activity in NRF2-mutant cell lines, while being inactive in NRF2 wild-type cells.
Mivavotinib
Mivavotinib, a spleen tyrosine kinase (SYK) inhibitor, is being evaluated in a Phase 2 trial for the treatment of relapsed or refractory non-GCB (activated B-cell, or ABC) diffuse large B-cell lymphoma (DLBCL), with enrichment for tumors harboring MYD88 and/or CD79b mutations. This patient population also faces a poor prognosis, and mivavotinib has demonstrated compelling single-agent activity in this setting, with a 53% overall response rate in non-GCB DLBCL patients in a prior study.
In addition to its lead programs, Calithera has a preclinical pipeline focused on synthetic lethality targets, including a novel series of VPS4A inhibitors that have shown promise in preclinical studies.
Financials
Calithera's financial performance has been challenging, with the company reporting an annual net loss of $18.9 million in 2022, no revenue, an annual operating cash flow of -$43.6 million, and an annual free cash flow of -$43.7 million. The company's cash and cash equivalents stood at $34.1 million as of September 30, 2022.
In the third quarter of 2022, Calithera reported a net loss of $9.8 million, with no revenue generated. Research and development expenses were $6.4 million, while general and administrative expenses were $3.1 million. The company's cash burn rate remains high, with $35.0 million in cash used in operating activities during the first nine months of 2022.
Risks and Challenges
The company's ability to continue as a going concern is in question, as it has stated that there is substantial doubt about its ability to do so for at least the next 12 months. Calithera is currently evaluating all options for its programs, including strategic collaborations, licensing agreements, and the potential sale of certain assets, in an effort to extend its cash runway.
The challenges facing Calithera are not unique in the highly competitive and capital-intensive world of precision oncology drug development. The company's focus on targeting specific genetic vulnerabilities in cancer, however, remains a promising approach, and its lead product candidates, sapanisertib and mivavotinib, have shown encouraging early-stage clinical data.
Outlook
Sapanisertib's potential in NRF2-mutated sqNSCLC and mivavotinib's activity in non-GCB DLBCL, particularly in the MYD88 and/or CD79b mutated subsets, represent significant opportunities for Calithera. The company's ability to navigate the regulatory landscape and secure the necessary funding to advance these programs will be critical to its long-term success.
Calithera's preclinical pipeline, including its VPS4A inhibitor program, also holds promise, but the company will need to carefully prioritize its resources to ensure the most efficient path forward.
Conclusion
The road ahead for Calithera is not without its challenges, but the company's focus on precision oncology and its promising lead product candidates suggest that it may be able to overcome its current financial hurdles and deliver meaningful advancements in the treatment of difficult-to-treat cancers. Investors will need to closely monitor the company's progress and its ability to secure the necessary funding to advance its pipeline.