Vaccinex, Inc. (VCNX) is a clinical-stage biotechnology company that has been pioneering a differentiated approach to treating neurodegenerative diseases, cancer, and autoimmune disorders through the inhibition of Semaphorin 4D (SEMA4D). The company's lead product candidate, pepinemab, has shown promising results in clinical trials for Alzheimer's disease and head and neck cancer.
Business Overview and History Vaccinex was incorporated in Delaware in April 2001 and is headquartered in Rochester, New York. The company has been engaged in the discovery and development of targeted biotherapeutics to treat serious diseases and conditions with unmet medical needs. Since its inception, Vaccinex has devoted substantially all of its efforts toward product research, manufacturing and clinical development, and raising capital.
In 2017, Vaccinex entered into a research collaboration and license option agreement with Surface Oncology, Inc. to identify and select antibodies against two target antigens. This agreement provided the company with an upfront technology access fee as well as milestone payments. In 2019, Surface Oncology exercised an option and the companies entered into an exclusive research tool license agreement.
The company has developed multiple proprietary platform technologies, including its SEMA4D antibody platform and ActivMAb antibody discovery platform, to identify and develop potential product candidates. Vaccinex's lead product candidate, pepinemab, is currently in clinical development for the treatment of Alzheimer's disease, head and neck cancer, pancreatic cancer, and breast cancer.
In 2021, Vaccinex initiated a randomized, placebo-controlled, multi-center phase 1b/2 clinical study of pepinemab in Alzheimer's disease, known as the SIGNAL-AD trial. This trial is based on evidence from the company's previous SIGNAL clinical trial in Huntington's disease, which showed that treatment with pepinemab reduced cognitive decline and induced a sharp increase in glucose metabolism in the brain during disease progression. In April 2023, Vaccinex reached its enrollment target for the SIGNAL-AD study, and in June 2024, the last patient completed their final visit.
Vaccinex has also been evaluating pepinemab in combination with immune checkpoint inhibitors, such as KEYTRUDA, for the treatment of head and neck cancer. In 2023, the company analyzed interim data from the first 36 patients in the open-label, single-arm, Phase 2 KEYNOTE B-84 study, which showed that pepinemab in combination with KEYTRUDA resulted in an approximately 2x increase in objective responses and median progression-free survival in patients with PD-L1-low tumors, compared to historical response rates for immune checkpoint inhibitor monotherapy in this population.
In addition to its work in Alzheimer's disease and cancer, Vaccinex previously evaluated pepinemab for the treatment of Huntington's disease in its Phase 2 SIGNAL trial. While the study did not meet its prespecified primary endpoints, it provided important new information, including evidence of cognitive benefit and a reduction in brain atrophy and increase in brain metabolic activity in patients with manifest disease symptoms.
Financial Overview Vaccinex has not yet generated any revenue from the sales of its product candidates. The company has relied on public and private sales of equity and debt financing, as well as capital contributions from noncontrolling interests and limited service revenue from collaboration agreements, to fund its operations.
For the fiscal year ended December 31, 2023, Vaccinex reported a net loss of $20.25 million, with total revenue of $570,000 and total operating expenses of $23.45 million. The company's net cash used in operating activities was $17.23 million, and its free cash flow was -$17.30 million.
In the most recent quarter, Vaccinex reported revenue of $52,000 and a net loss of $5.73 million. The decrease in revenue and net loss compared to the prior year quarter was primarily due to the winding down of the SIGNAL-AD trial, a pause in enrollment for the head and neck cancer trial, and less drug manufacturing costs.
Vaccinex operates solely in the United States and does not report performance by geographic markets.
Liquidity As of September 30, 2024, Vaccinex had cash and cash equivalents of $2.91 million and total current assets of $4.80 million, which the company has projected will be insufficient to sustain its operations through one year following the date that the financial statements were issued. The company is actively exploring partnership opportunities and pursuing various financing strategies, including the public or private sale of equity, debt financing, or other capital sources, to fund its continued operations and development efforts.
Vaccinex's debt-to-equity ratio stands at -0.04, indicating a relatively low level of debt compared to equity. The company's current ratio and quick ratio are both 0.77, suggesting potential liquidity challenges in meeting short-term obligations.
Positive Data from SIGNAL-AD Trial in Alzheimer's Disease In July 2024, Vaccinex reported positive topline results from its randomized, double-blind, phase 1b/2 SIGNAL-AD study of pepinemab in Alzheimer's disease. The trial met its primary endpoint, demonstrating that treatment with pepinemab resulted in a statistically significant increase in FDG-PET signal, a measure of brain metabolic activity, in the medial temporal cortex of patients with mild cognitive impairment due to Alzheimer's disease. This finding is consistent with pepinemab's previously observed ability to prevent disease-related decline of brain metabolic activity in Huntington's disease, a neurodegenerative disorder that shares important pathological features with Alzheimer's disease.
Although the SIGNAL-AD study was not sufficiently powered to detect cognitive effects or changes in additional secondary endpoints with statistical significance, the company believes the results support the continued development of pepinemab in Alzheimer's disease, particularly in the early stages of the disease, such as mild cognitive impairment. Vaccinex plans to pursue a development partnership for pepinemab in Alzheimer's disease going forward.
The SIGNAL-AD study enrolled 50 participants with mild cognitive impairment (MCI) or mild dementia due to AD. As of June 30, 2024, all participants completed 12 months of treatment, and topline data from the study was reported in July 2024.
Collaborations and Partnerships Vaccinex has established several collaborations and partnerships to advance the development of its product candidates and platform technologies. In addition to the company's collaboration with Merck for the evaluation of pepinemab in combination with KEYTRUDA in head and neck cancer, Vaccinex has entered into an agreement with Merck KGaA, EMD Serono in the U.S. to evaluate pepinemab in combination with Bavencio (avelumab) for the treatment of pancreatic cancer.
Furthermore, Vaccinex has signed several proprietary project agreements with pharmaceutical companies, including Amgen, Merck, Chugai, Absci, Gigagen (Grifols), Merus, Soleil, ThirdArc, and Incyte, to employ the company's ActivMAb® technology for antibody discovery against complex antigen targets.
Challenges and Risks Vaccinex faces several challenges and risks common to early-stage biotechnology companies, including the need to continue demonstrating the safety and efficacy of its product candidates, obtaining regulatory approvals, and securing sufficient funding to support its ongoing operations and development efforts.
The company's recurring net losses and negative cash flows from operations have raised substantial doubt about its ability to continue as a going concern. Vaccinex will need to secure additional financing, either through public or private sales of equity, debt financing, or other capital sources, to fund its operations and advance the development of its product candidates.
Additionally, Vaccinex was recently notified by Nasdaq that it no longer complies with the exchange's continued listing standards, and the company's common stock may be subject to delisting. Vaccinex has appealed this determination, and its common stock is expected to remain listed on Nasdaq through at least December 2024, pending the outcome of the appeal.
Conclusion Vaccinex is a clinical-stage biotechnology company that has been pioneering a differentiated approach to treating neurodegenerative diseases, cancer, and autoimmune disorders through the inhibition of SEMA4D. The company's lead product candidate, pepinemab, has shown promising results in clinical trials for Alzheimer's disease and head and neck cancer, and Vaccinex is actively pursuing partnership opportunities and financing strategies to support the continued development of its pipeline.
Despite the challenges and risks facing the company, Vaccinex's unique approach and the positive data from its SIGNAL-AD trial in Alzheimer's disease suggest that pepinemab may have the potential to address significant unmet medical needs in various therapeutic areas. Investors should closely monitor the company's progress as it navigates the development and commercialization of its product candidates.