Calithera Biosciences, Inc. (CALA) is a clinical-stage biopharmaceutical company at the forefront of precision oncology, leveraging its expertise in tumor metabolism and tumor immunology to advance a pipeline of investigational small molecule compounds. With a relentless focus on improving the lives of cancer patients, Calithera is poised to make a significant impact in the treatment landscape.
Calithera’s Business Overview and History
Calithera was founded in 2010 with the mission of discovering and developing novel small molecule enzyme inhibitors to target cancer. Over the past decade, the company has established itself as a leader in the field of precision oncology, building a diverse pipeline of clinical-stage assets and a robust portfolio of intellectual property.
In its early years, Calithera advanced several proprietary product candidates into preclinical studies and clinical trials. One notable example was the glutaminase inhibitor telaglenastat, which entered phase 2 clinical trials for the treatment of non-small cell lung cancer in 2019. However, the phase 2 KEAPSAKE trial evaluating telaglenastat was discontinued in 2021 due to a lack of clinical benefit.
In 2020, Calithera received a $2.4 million award from the Cystic Fibrosis Foundation to support the development of its arginase inhibitor CB-280 for the treatment of cystic fibrosis. Despite this support, the company decided to discontinue the development of CB-280 in cystic fibrosis in 2022.
Another setback occurred in 2022 when Incyte notified Calithera of its intent to terminate their collaboration agreement for the arginase inhibitor INCB001158, leaving Calithera without plans to further develop that program.
In 2021, Calithera made a transformative move by acquiring the clinical-stage compounds sapanisertib and mivavotinib from Millennium Pharmaceuticals, a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited. This strategic acquisition significantly strengthened Calithera’s precision oncology pipeline, adding two product candidates with demonstrated single-agent clinical activity in biomarker-defined cancer patient populations.
Sapanisertib, a potent and selective dual mTORC1/2 inhibitor, is currently being evaluated in a Phase 2 study for the treatment of NRF2-mutated squamous non-small cell lung cancer (sqNSCLC), a patient population with a poor prognosis and high unmet medical need. Mivavotinib, a spleen tyrosine kinase (SYK) inhibitor, is being investigated in a Phase 2 trial for the treatment of relapsed or refractory non-GCB diffuse large B-cell lymphoma (DLBCL) with enrichment of MYD88 and CD79b mutations.
Calithera’s Financials and Liquidity
As of December 31, 2022, Calithera reported cash and cash equivalents of $25.45 million, providing the company with runway into the second quarter of 2023. The company’s net loss for the year ended December 31, 2022, was $39.65 million, with annual operating cash flow and free cash flow of N/A and N/A, respectively.
For the most recent quarter, Calithera reported revenue of $0, a net loss of $6,936,000, operating cash flow of -$8,598,000, and free cash flow of -$8,621,000. The company’s liquidity position shows a cash balance of $34.07 million, with a current ratio and quick ratio both at 3.60. Calithera does not have any reported debt, and information on available credit lines is not provided.
Calithera has faced challenges in recent years, including the termination of the Incyte Collaboration Agreement in 2022 and the discontinuation of the telaglenastat KEAPSAKE clinical trial in 2021. These events have impacted the company’s financial position, leading Calithera to actively explore strategic alternatives, including potential collaborations or the sale of certain programs, in order to extend its cash runway.
For the nine months ended September 30, 2022, Calithera reported a net loss of $32.71 million, compared to a net loss of $45.88 million in the same period of the prior year. The decrease in net loss was primarily due to a $15.94 million reduction in research and development expenses, primarily related to the discontinuation of the telaglenastat and CB-280 programs, partially offset by increases in the sapanisertib and mivavotinib programs. General and administrative expenses also decreased by $5.30 million during the period.
Product Segments and Clinical Developments
Calithera’s lead programs, sapanisertib and mivavotinib, have made significant strides in their clinical development. In October 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for sapanisertib for the treatment of adult patients with unresectable or metastatic sqNSCLC whose tumors have a mutation in NRF2 and who have received prior platinum-based chemotherapy and immune checkpoint inhibitor therapy.
Sapanisertib (CB-228.00) is a potent and selective dual mTORC1/2 inhibitor targeting a key survival mechanism in KEAP1/NRF2-mutated tumor cells. In a two-part phase 2 study, sapanisertib has demonstrated durable single-agent activity in a subset of heavily pretreated NRF2-mutated sqNSCLC patients, with a confirmed overall response rate of 27%. This compares favorably to a 17% response rate in KEAP1-mutated sqNSCLC and 0% in KEAP1-mutated/KRAS-mutated adenocarcinoma NSCLC. The NRF2-mutant cohort also had a median progression-free survival of 8.9 months, compared to 3-4.5 months with standard of care salvage chemotherapy. Sapanisertib has shown a well-established and manageable safety profile, with predominantly Grade 1-2 treatment-emergent adverse events.
Mivavotinib (CB-659.00) is a spleen tyrosine kinase (SYK) inhibitor targeting the constitutively activated B-cell receptor pathway in DLBCL and other non-Hodgkin lymphomas. Calithera has initiated a two-part phase 2 trial of mivavotinib in relapsed or refractory non-GCB (activated B-cell like) DLBCL, with enrichment for tumors harboring MYD88 and/or CD79b mutations. Mivavotinib has demonstrated compelling single-agent activity in this DLBCL subtype, with an overall response rate of 53% compared to 22% in the GCB (germinal center B-cell like) subtype. The median duration of response in non-GCB responders was 15.7 months.
The company’s Phase 2 trials for sapanisertib and mivavotinib have experienced enrollment challenges, leading to delays in initial data readouts, which are now expected in mid-2023. Despite these setbacks, Calithera remains committed to advancing its precision oncology pipeline and exploring potential strategic partnerships or asset sales to bolster its financial position.
Risks and Challenges
Calithera faces several risks and challenges that investors should be aware of. The company’s heavy reliance on the success of its lead programs, sapanisertib and mivavotinib, exposes it to significant clinical and regulatory risks. Delays in the development or potential failure of these assets could have a severe impact on the company’s future prospects.
Additionally, Calithera’s financial position remains precarious, with limited cash resources and a need to secure additional funding or strategic partnerships to sustain its operations. The company’s ability to execute on its business plan and navigate the competitive landscape in precision oncology will be crucial to its long-term success.
Calithera is currently evaluating all options for its programs, including strategic collaborations, licensing agreements, and the potential sale of certain programs, in order to extend its cash runway. The company believes its existing cash and cash equivalents will be sufficient to fund its current operating plan into the second quarter of 2023. However, if Calithera is unsuccessful in its efforts to secure additional funding or further delays occur, the company may need to terminate its programs and consider a wind down of its operations.
Conclusion
Calithera Biosciences is a clinical-stage biopharmaceutical company with a dedicated focus on developing targeted small molecule therapies for cancer. The company’s acquisition of the Takeda Programs, sapanisertib and mivavotinib, has strengthened its precision oncology pipeline, though the company faces significant challenges in advancing these assets and securing its financial future. Investors should closely monitor Calithera’s progress in its clinical trials, regulatory milestones, and strategic initiatives as the company navigates the competitive and capital-intensive world of oncology drug development.
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