On May 16, 2022 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, reported financial results for the first quarter ended March 31, 2022, and provided a corporate update on key events since the start of 2022 (Press release, Vaccinex, MAY 16, 2022, View Source [SID1234614593]).
"I am pleased to report that Vaccinex’s clinical programs for oncology and neurodegenerative disease have made substantial progress this year. In oncology, we were gratified to report promising Phase Ib safety results and to observe two complete responses (CRs) in the first three patients enrolled in the open label, Phase 1b/2 KEYNOTE-B84 trial. The trial is evaluating the use of pepinemab in combination with KEYTRUDA (pembrolizumab) as first-line treatment for patients with advanced recurrent or metastatic head and neck cancer. We are hopeful that, with continued positive results, this combination may represent a novel option for patients with head and neck cancer, including those whose tumors express low levels of the PD-L1 biomarker and who have limited treatment choices," said Maurice Zauderer, Ph.D., President and Chief Executive Officer of Vaccinex.
Dr. Zauderer continued, "In neurodegenerative disease, enrollment in the Phase 1/2a SIGNAL-AD trial in mild Alzheimer’s Disease continues to progress, and we plan to soon publish the results of the SIGNAL Huntington’s Disease study that we believe showed promise of slowing or preventing cognitive decline."
Dr. Zauderer continued, "Looking ahead, we expect to complete enrollment in the KEYNOTE-B84 and SIGNAL-AD trials in 2022. Data read outs are planned from the KEYNOTE-B84 during H2:2022 and topline data from the SIGNAL-AD trial are expected in H2:2023. These data will help to guide the regulatory and product development path for pepinemab. We look forward to continue to update the clinical community and investors on our progress."
Pepinemab Clinical Updates and Upcoming Milestones:
Oncology: Head and Neck Cancer
Enrollment is underway in the Phase 1b/2 clinical trial evaluating pepinemab in combination with Merck’s anti-PD-1 immune checkpoint therapy KEYTRUDA (pembrolizumab) in recurrent or metastatic head and neck cancer.
Multiple prior studies1-3 suggest that inhibition of SEMA4D increases immune infiltration and alters the balance of cytotoxic and immunosuppressive cells in the tumor microenvironment. As SEMA4D is highly expressed in head and neck cancer, there is strong rationale for development in this indication.
In January 2022, Vaccinex reported two complete responses in the first three patients enrolled. Vaccinex reported further details of these patient responses (Abstract CT-11) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2022) on Monday, April 11, 2022.
The KEYNOTE-B84 study is planned to enroll up to 65 subjects across 18 U.S. trial sites and will assess whether combination immunotherapy with pepinemab and pembrolizumab can improve responses in this population. Key endpoints of the study will include objective response, progression free survival and overall survival.
Next Data and Trial Completion: Data read-outs are expected in H2:2022. Enrollment is expected to be completed and topline data presented in H1:2023.
ASCO Abstract Publication: An abstract of the Phase 1b segment of the study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84) will be published with the ASCO (Free ASCO Whitepaper) proceedings on May 26, 2022.
Vaccinex has exclusive global commercial and development rights to pepinemab and is sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp. Additional information about the study is available: here.
Other Trials. Pepinemab is also being evaluated in multiple investigator-sponsored trials (ISTs) being conducted by the Winship Cancer Institute of Emory University to evaluate pepinemab in combination with checkpoint inhibitors in "Window of Opportunity" biomarker studies of head and neck cancer and melanoma.
Alzheimer’s Disease. Enrollment continues in the Phase 1/2a SIGNAL-AD trial of pepinemab in early Alzheimer’s disease which is being funded in part by the Alzheimer’s Drug Discovery Foundation and by a grant from the Alzheimer’s Association under its 2020 Part the Cloud Program. Additional information about this study is available here.
The randomized, double-blind, placebo-controlled, multi-center safety and biomarker study of pepinemab in early AD is planned to enroll 40 subjects across 15 U.S. trial sites.
Next Data and Trial Completion: Enrollment is expected to be completed by year-end 2022 and topline data are expected in H2:2023.
Huntington’s disease. The Phase 2 double-blind, placebo-controlled SIGNAL trial of pepinemab in patients with early manifest Huntington’s disease (HD) has been completed and we believe the program is Phase-3 ready.
While the Phase 2 study did not meet the prespecified primary endpoints, pre-specified exploratory and post-hoc analyses supports the potential cognitive benefit of treatment with pepinemab in HD patients, particularly those with mild cognitive deficits:
Highly significant improvement (p=0.007) in the (Huntington’s Disease Cognitive Assessment Battery (HD-CAB) Composite score
Significant benefit in reducing apathy severity (p=0.017, 1-sided)
Reduced atrophy (p=0.017) in caudate region of striatum
A striking increase in brain metabolic activity as measured by FDG-PET in most brain regions
Next Steps: The company intends to publish the results of the SIGNAL study in mid-2022. In addition, Vaccinex is in ongoing discussions with potential partners on plans to advance pepinemab into a Phase 3 HD trial.
As previously announced, we have entered into several collaborations with pharmaceutical and biotechnology companies employing the unique capabilities of our ActivMAb antibody discovery platform to address difficult to drug G-protein Coupled Receptors (GPCRs) and ion channels known to be strongly associated with diseases.
In April, 2022, Vaccinex announced presentation of an abstract at the 18th Annual PEGS Boston Conference & Expo, May 2-3, 2022, related to ActivMAb’s successful expression and selection of antibodies against multi-pass receptors and its potential application as a tool for drug discovery and development projects.
In January 2022, the Company sold 8,747,744 shares of the Company’s common stock at a purchase price of $1.11 per share raising aggregate gross proceeds of approximately $9.7 million. In addition, during the first quarter, the company received $3.5 million of net proceeds from the Open Market Sale Agreement by selling 3,115,197 shares of the Company’s common stock at a weighted average price of $1.16 per share.
Financial Results for the Three Months Ended March 31, 2022:
Cash and Cash Equivalents and Marketable Securities. Cash and cash equivalents and marketable securities on March 31, 2022 were $16.8 million, as compared to $8.6 million as of December 31, 2021.
Research and Development Expenses. Research and development expenses for the quarter ended March 31, 2022 were $3.0 million as compared to $5.5 million for the comparable period in 2021.
Research and Development expenses are lower in 2022 compared to 2021 primarily attributed to reduced clinical trial costs as a result of the completion of the CLASSICAL-Lung and SIGNAL studies, partially offset by setup expenses for the KEYNOTE B84 and SIGNAL-AD studies as well as a large production run of pepinemab completed in Q1:21.
General and Administrative Expenses. General and administrative expenses for the quarter ended March 31, 2022 were $1.6 million as compared to $1.6 million for the comparable period in 2021.
Essentially flat level of general and administrative expenses reflects careful cost control measures in light of inflationary pressures.
Comprehensive loss/Net loss per share. The Comprehensive Loss and Net loss per share for the quarter ended March 31, 2022 was $4.6 million and $0.12, respectively, compared to $6.6 million and $0.26 for the comparable period in 2021.
Full financial tables are included below. For further details on Vaccinex’s financials, refer to its Form 10-Q filed May 16, 2022, with the Securities and Exchange Commission
Shafique MR, Fisher TL, Evans EE, Leonard JEE, Pastore DRE, Mallow CL, Smith E, Mishra V, Schroder A, Chin KA, Beck JT, Baumgart MA, Govindan R, Gabrial NY, Spira AI, Seetharamu N, Lou Y, Mansfield AS, Sanborn RE, Goldman JW, Zauderer M. A Phase Ib/2 Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer. Clin Cancer Res 2021, doi: 10.1158/1078-0432.CCR-20-4792
Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith ES, Zauderer M, Evans EE, Allen CT. Semaphorin4D inhibition improves response to immune checkpoint blockade via attenuation of MDSC recruitment and function. Cancer Immunol Res. 2019 Feb;7(2):282-291
Evans EE, Jonason AS Jr, Bussler H, Torno S, Veeraraghavan J, Reilly C, Doherty MA, Seils J, Winter LA, Mallow C, Kirk R, Howell A, Giralico S, Scrivens M, Klimatcheva K, Fisher TL, Bowers WJ, Paris M, Smith ES, Zauderer M. Antibody blockade of semaphorin 4D promotes immune infiltration into tumor and enhances response to other immunomodulatory therapies. Cancer Immunol Res. 2015 Jun;3(6): 689-701. View Source
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates the actin cytoskeleton of cells that plays an important role in tumor immunity and cell interactions in the brain. Preclinical and clinical data show that pepinemab promotes infiltration/activation of dendritic cells and CD8+ T-cells and reverses immunosuppression within the tumor microenvironment. Pepinemab is being evaluated in several studies in oncology and neurodegenerative disease.
Vaccinex has developed a proprietary mammalian cell-based antibody discovery platform with unique multi-pass membrane target capabilities. The ActivMAb technology now has four main applications: complex membrane antigen presentation, antibody or antigen discovery, and protein optimization. Vaccinex has entered into an antibody license with Surface Oncology (Cambridge, MA) and into Material Transfer Agreements for drug discovery or process development with major pharmas utilizing this technology. Vaccinex seeks partnering opportunities for co-development or licensing of existing antibodies in our pipeline, discovery of new antibodies and/or applications for this powerful technology.