Core Insights - Vaccinex, Inc. is presenting new data on pepinemab, a monoclonal antibody targeting SEMA4D, which enhances immune responses in neoadjuvant settings for head and neck cancer [2][5][6] - The upcoming presentation at the ASCO conference will detail how pepinemab treatment correlates with improved pathologic responses by inducing mature lymphoid structures [4][6] Company Overview - Vaccinex, Inc. is focused on innovative treatments for cancer and neurodegenerative diseases through the inhibition of SEMA4D [8] - The lead drug candidate, pepinemab, is designed to block SEMA4D, which is implicated in immune cell infiltration and activation in tumors [7][9] Clinical Research and Development - Pepinemab is being evaluated in combination with other immunotherapies, such as KEYTRUDA and BAVENCIO, in various clinical trials for head and neck cancer and pancreatic adenocarcinoma [9][10] - Previous studies indicate that pepinemab can enhance immune cell interactions and improve treatment outcomes in patients with "cold" tumors, which are typically resistant to standard immunotherapy [5][6] Upcoming Events - The ASCO conference presentation is scheduled for June 1, 2025, focusing on the neoadjuvant biomarker trial of pepinemab in resectable head and neck cancer [4][5]

Core Insights - Pepinemab, a Semaphorin 4D blocking immunotherapy, shows promise in enhancing immune responses and improving survival in patients with metastatic melanoma and head and neck cancer [1][2][4][5]. Company Overview - Vaccinex, Inc. is a clinical-stage biotechnology company focused on innovative treatments for cancer and Alzheimer's disease through the inhibition of Semaphorin 4D [2][8]. - The lead drug candidate, pepinemab, is designed to block SEMA4D, which is believed to prevent immune cell infiltration in tumors and trigger inflammation in neurodegenerative diseases [8]. Clinical Data and Presentations - New data on pepinemab's mechanism to enhance immune responses will be presented at the 2025 AACR Annual Meeting, highlighting its role in improving clinical outcomes in combination with immune checkpoint therapies [2][3]. - Previous studies indicate that pepinemab enhances the maturity of tertiary lymphoid structures (TLS), correlating with longer recurrence-free survival in metastatic melanoma patients [5][6]. Mechanism of Action - Pepinemab facilitates immune cell interactions by blocking SEMA4D's inhibitory signal to dendritic cells, promoting the formation of organized immune centers (TLS) that amplify T cell responses [3][4][5]. - The presence of TLS has been associated with better clinical outcomes and responses to immune checkpoint therapy, making pepinemab a potential solution for "cold" tumors [4][5]. Ongoing Research - Evaluation of pepinemab in the neoadjuvant setting for head and neck cancer is ongoing, with results expected to be reported at upcoming scientific meetings [6].

Core Insights - Pepinemab, a Semaphorin 4D blocking immunotherapy, shows promise in enhancing immune responses and improving survival in patients with metastatic melanoma and head and neck cancer [1][2][4] Company Overview - Vaccinex, Inc. is a clinical-stage biotechnology company focused on innovative treatments for cancer and Alzheimer's disease through the inhibition of Semaphorin 4D [2][8] - The lead drug candidate, pepinemab, is designed to block SEMA4D, which is believed to prevent immune cell infiltration in tumors and trigger inflammation in neurodegenerative diseases [7][8] Clinical Data and Presentations - New data on pepinemab's mechanism to enhance immune responses will be presented at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) [2][3] - Pepinemab has been shown to enhance the maturity of tertiary lymphoid structures (TLS) and correlate with longer recurrence-free survival when combined with immune checkpoint inhibitors in metastatic melanoma patients [5][6] Mechanism of Action - Pepinemab facilitates immune cell interactions within organized centers of immunity, known as tertiary lymphoid structures, by blocking the SEMA4D inhibitory signal to dendritic cells [3][4] - The presence of TLS has been associated with clinical benefits and positive responses to immune checkpoint therapy, making pepinemab a potential solution for inducing TLS in "cold" tumors [4][5] Ongoing Studies - Evaluation of pepinemab in the neoadjuvant setting for head and neck cancer is ongoing, with results expected to be reported at upcoming scientific meetings [6]

Drug Development and Clinical Trials - The company is focused on developing pepinemab, a humanized monoclonal antibody targeting SEMA4D, for Alzheimer's disease (AD) and other cancers, with over 650 patients treated in Phase 1 and 2 clinical trials as of December 31, 2024[24]. - The SIGNAL-AD study for pepinemab in AD reached its enrollment target in April 2023, with all 50 participants completing 12 months of treatment by June 30, 2024[28]. - The SIGNAL-AD Phase 1b/2 study for Alzheimer's disease reached its enrollment target in April 2023, with topline data reported on July 31, 2024[54]. - The SIGNAL Phase 2 clinical trial enrolled 265 subjects, with 179 in early manifest disease and 86 in late prodromal stages, randomized to receive either pepinemab or placebo for 18 months[99]. - The study did not meet pre-specified co-primary endpoints, but significant treatment effects were observed in cognitive assessments, particularly in patients with more advanced disease[100]. - The Phase 1 clinical trial of pepinemab in MS patients demonstrated no dose-limiting toxicity across doses ranging from 1 to 20 mg/kg, with an estimated half-life of approximately 20 days[72]. - Pepinemab was well-tolerated in a Phase 1/2 trial for children with recurrent solid tumors, although the frequency and duration of objective responses did not support further development as a single agent[49]. - The company has paused its cancer research efforts but previously studied pepinemab in advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC)[29]. - Clinical trials related to cancer have been paused, following the completion of a Phase 1 trial and the initiation of the CLASSICAL–Lung trial[118]. Mechanism of Action and Therapeutic Potential - Pepinemab demonstrated a 21.1% objective response rate (ORR) and a median progression-free survival (PFS) of 5.79 months in patients with low PD-L1 tumors, nearly double the historical response rates for immune checkpoint inhibitor monotherapy[33]. - Pepinemab's mechanisms of action include blocking SEMA4D signaling, which promotes immune cell infiltration and reduces immune suppression in tumors[26]. - Pepinemab is designed to block SEMA4D signaling, which regulates immune cell migration and activation, potentially enhancing immune responses in cancer and neurodegenerative diseases[41]. - The mechanism of action of pepinemab includes inhibiting the activation of inflammatory cells and promoting the repair of damaged tissues[53]. - SEMA4D is implicated in neuroinflammatory and neurodegenerative diseases, affecting the activation of microglia and astrocytes, which are critical in Alzheimer's disease pathology[55]. - SEMA4D impacts the pathology of Alzheimer's Disease through multiple mechanisms, making it a promising target for therapeutic development[78]. - Pepinemab treatment in preclinical studies showed substantial reductions in neuroinflammatory processes in a mouse model of multiple sclerosis[86]. - Pepinemab treatment in YAC128 mice resulted in a significant reduction in cortical and white matter volume loss, indicating potential neuroprotective effects[90]. - Behavioral assessments showed that pepinemab-treated YAC128 mice exhibited no significant difference in anxiety-like behavior compared to wild type control mice, suggesting a reduction in anxiety[91]. - In cognitive tests, pepinemab improved spatial memory in YAC128 mice, restoring memory performance to levels comparable to wild type controls[92]. Funding and Financial Support - The company received a funding grant of $750,000 from the Alzheimer's Association and up to $3 million from the Alzheimer's Drug Discovery Foundation to support the SIGNAL-AD study, with two-thirds of the funding received in 2020 and the remainder in Q3 2023[27]. Partnerships and Collaborations - The company has entered into antibody discovery agreements with third parties for the use of the ActivMAb platform, enhancing its partnership opportunities[23]. - The collaboration with Merck Sharp & Dohme for the KEYNOTE-B84 trial involves testing pepinemab in combination with pembrolizumab for R/M HNSCC patients[45]. - The company has entered into multiple investigator-sponsored trial agreements to further evaluate pepinemab in various cancer indications[50]. - The company has entered into collaborations for using ActivMAb to express complex antigens for antibody discovery under fee-for-service arrangements[187]. Intellectual Property and Competitive Advantage - The company believes it is the only entity targeting SEMA4D for potential treatments of neurodegenerative diseases, cancer, or autoimmune disorders, providing a competitive advantage[196]. - The intellectual property portfolio includes several issued U.S. and foreign patents for the SEMA4D antibody platform and pepinemab, with expiration dates projected between 2030 and 2038[204]. - The company wholly owns ten additional pepinemab-related patent families, with various projected expiration dates, including methods for treating cancer and neuroinflammatory disorders[205]. - The ActivMAb platform is protected by two patent families and a provisional patent application, along with granted U.S. and foreign patents licensed from the University of Rochester[212]. - The University of Rochester granted an exclusive, worldwide, sublicensable license to commercialize patents related to the ActivMAb antibody discovery platform, with low single-digit royalties on sales and milestone payments upon specific regulatory submissions[213]. Safety and Efficacy Observations - The company has observed no concerning safety signals with the combination of pepinemab and avelumab, with only one grade 3 pulmonary embolism reported[171]. - Pepinemab has shown potential as a single-agent therapy, with higher levels of circulating B and T cells correlating with longer progression-free survival in patients with solid tumors[133]. - Approximately 59% of subjects in the CLASSICAL-Lung trial experienced a halt or reversal of tumor progression after treatment with pepinemab plus avelumab[168]. - Among 21 evaluable immunotherapy naïve patients, the disease control rate (PR plus SD) was approximately 81%[169]. - The combination of pepinemab and KEYTRUDA™ resulted in an objective response rate (ORR) of 21.1% and a median progression-free survival (PFS) of 5.79 months in patients with PD-L1-low tumors[172]. Market Context and Disease Statistics - An estimated 6.9 million Americans aged 65 and older are living with Alzheimer's in 2024, projected to grow to 12.7 million by 2050 without medical breakthroughs[76]. - There are over 30,000 clinically diagnosed Huntington's Disease patients in the U.S., with an additional 250,000 at risk of inheriting the mutated allele[81]. - The American Cancer Society estimates that in 2024, approximately 2 million Americans will be diagnosed with cancer, with 611,720 expected to die from the disease[146]. Preclinical and Research Insights - Anti-SEMA4D treatment shifts the balance of cytokines and chemokines in the tumor microenvironment, enhancing secretion of tumoricidal cytokines (IFN γ, TNF α) while reducing immunosuppressive chemokines[136]. - In preclinical models, SEMA4D produced in tumors obstructs the activation of tumor-inhibiting immune cells, suggesting that targeting SEMA4D could enhance immune responses in various cancers[154]. - Pepinemab has demonstrated single-agent efficacy in PLXNB1 and ErbB-2 double positive tumors, indicating its potential as a therapeutic strategy for HER2+ cancers[156]. - The combination treatment with anti-CTLA-4 and anti-SEMA4D in colorectal tumor models demonstrated an average tumor regression of approximately 80%, with some cases achieving 100% regression[136].

Core Viewpoint - Vaccinex, Inc. has decided to delist its common stock from Nasdaq following a suspension of trading since December 18, 2024, due to a notice from the Nasdaq Hearings Panel [1][2] Company Overview - Vaccinex, Inc. is a clinical-stage biotechnology company focused on treating neurodegenerative diseases and cancer by inhibiting SEMA4D, which is believed to trigger damaging inflammation [1][4] - The company's lead product, pepinemab, is designed to block SEMA4D and is being evaluated for Alzheimer's disease and various cancers [4][7] Delisting Details - The company plans to file a Form 25 with the Securities and Exchange Commission around March 17, 2025, to officially remove its common stock from Nasdaq [2] - The decision to delist follows a notice from Nasdaq regarding the delisting of the company's securities [2] Product Development Focus - Vaccinex aims to continue the development of pepinemab through partnerships, grants, and other financing avenues [3] - Pepinemab has been studied in clinical trials for Alzheimer's disease and is also being evaluated in combination therapies for cancer, including studies with KEYTRUDA® and BAVENCIO® [4][5]

Core Viewpoint - Vaccinex, Inc. has received a notice from Nasdaq indicating that its shares will be delisted due to non-compliance with continued listing standards, specifically failing to maintain a minimum of $2.5 million in stockholders' equity [1]. Company Overview - Vaccinex, Inc. is a clinical-stage biotechnology company focused on treating neurodegenerative diseases and cancer by inhibiting SEMA4D, which is believed to trigger damaging inflammation [3]. - The lead drug candidate, pepinemab, is designed to block SEMA4D and has shown promise in clinical trials for Alzheimer's Disease and Huntington's disease [3][6]. - Pepinemab is also being evaluated in oncology settings, including studies in combination with KEYTRUDA® and BAVENCIO® for various cancers [3][4]. Recent Developments - The trading of Vaccinex's common stock on Nasdaq will be suspended effective December 18, 2024, and the company expects its stock to be quoted on the OTC Markets Group under the existing symbol "VCNX" [2].

Core Viewpoint - Vaccinex, Inc. is actively exploring partnerships to advance the development of its lead drug candidate, pepinemab, for Alzheimer's disease, following promising clinical trial results that indicate its potential to slow cognitive decline in patients with Mild Cognitive Impairment and Mild Dementia [1][2][4]. Financial Results - As of September 30, 2024, the company reported cash and cash equivalents of $2.9 million, an increase from $1.5 million as of December 31, 2023 [7]. - The comprehensive loss for the quarter ended September 30, 2024, was $5.7 million, with a net loss per share of $(2.83), compared to a comprehensive loss of $4.9 million and a net loss per share of $(15.25) for the same period in 2023 [11][28]. - Research and development expenses for the quarter were $3.2 million, down from $4.4 million in the comparable period in 2023 [10]. Clinical Development - The SIGNAL-AD clinical trial demonstrated that treatment with pepinemab slowed the expression of key biomarkers associated with Alzheimer's disease progression, including GFAP and p-tau 217 [2][4]. - Pepinemab treatment showed a consistent trend of slowing cognitive decline as measured by established cognitive assessments, particularly in patients with early signs of cognitive deficits (MMSE 22-26) [3][4]. - The findings from the SIGNAL-AD study are consistent with previous studies in Huntington's disease, indicating a potential broader application of pepinemab in neurodegenerative diseases [4]. Partnership and Funding - The company is encouraged by the results from its clinical trials and is pursuing discussions for partnerships to expedite further development of pepinemab [4]. - The SIGNAL-AD study received funding from the Alzheimer's Drug Discovery Foundation and a grant from the Alzheimer's Association, highlighting external support for its research initiatives [4]. Stockholder Equity and Compliance - On October 7, 2024, the company received a notice from Nasdaq regarding non-compliance with continued listing standards related to stockholders' equity, prompting the company to submit a compliance plan [12][13].

Core Insights - Vaccinex, Inc. has signed multiple proprietary project agreements with major pharmaceutical companies, leveraging its ActivMAb® technology for antibody discovery [1][2] - The ActivMAb® platform is designed to express complex proteins, enabling the development of various antibody-based therapies targeting difficult membrane proteins [2][4] - The company is actively presenting its research at the Society for Immunotherapy of Cancer's 29th Annual Meeting, showcasing successful antibody discovery campaigns [2][3] Company Overview - Vaccinex is focused on treating neurodegenerative diseases and cancer through the inhibition of semaphorin 4D (SEMA4D), with its lead drug candidate, pepinemab, currently in clinical trials [5][6] - Pepinemab is being evaluated in combination with KEYTRUDA® and BAVENCIO® for various cancer indications, including recurrent head and neck cancer and metastatic pancreatic adenocarcinoma [5][6] - The company holds global commercial and development rights to pepinemab and collaborates with Merck Sharp & Dohme Corp. for the KEYNOTE-B84 study [6] Technology and Innovation - The ActivMAb® technology allows for the discovery of antibodies specific to complex membrane antigens, which are often challenging for traditional drug development [2][4] - The platform has already led to the identification of a clinical candidate, CHS-114, which is in development for cancer immunotherapy [4] - Vaccinex's technology is positioned to address high-value targets that have shown low efficacy or high toxicity with small molecule drugs [4]

Core Insights - Vaccinex, Inc. announced new biomarker data indicating that neoadjuvant treatment with pepinemab enhances the clinical activity of immune checkpoint inhibitors in poorly immunogenic, HPV-negative head and neck cancer [1][2] - The data will be presented at the Society for Immunotherapy of Cancer's Annual Meeting on November 8, 2024, highlighting findings from the Phase 2 KEYNOTE-B84 study and an independent study on resectable HNSCC [1][2] Group 1: Pepinemab and Its Mechanism - Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which is involved in inhibiting immune responses by affecting dendritic cells and astrocytes [3][4] - The treatment with pepinemab has shown to induce the formation of mature lymphoid aggregates in tumors, correlating with improved immune interactions and durable responses [2][4] Group 2: Clinical Trials and Studies - Over 600 patients have been enrolled in various clinical trials for pepinemab, which appears to have a favorable safety profile [3] - Pepinemab is being evaluated in combination with KEYTRUDA® in the Phase 1b/2 KEYNOTE-B84 study for recurrent or metastatic head and neck cancer and in combination with BAVENCIO® for metastatic pancreatic adenocarcinoma [4][5] Group 3: Company Overview - Vaccinex, Inc. focuses on innovative treatments for cancer and neurodegenerative diseases through the inhibition of SEMA4D [4] - The company holds global commercial and development rights to pepinemab and collaborates with Merck Sharp & Dohme Corp. for the KEYNOTE-B84 study [5]

Core Insights - Vaccinex has reported positive results from its SIGNAL-AD Phase 1b/2 trial of pepinemab in early stages of Alzheimer's disease, focusing on its potential to intervene early and block astrocyte activation and inflammation [2][3][7] Group 1: Clinical Findings - The study demonstrated that pepinemab treatment inhibits the increase of plasma GFAP and p-tau 217 biomarkers during Mild Cognitive Impairment (MCI), which is the earliest stage of Alzheimer's disease [3][4] - Pepinemab treatment may slow cognitive decline in patients progressing to mild dementia, as indicated by strong treatment trends across various cognitive measures [3][4] - A proteomic analysis of cerebrospinal fluid showed that several proteins associated with normal Alzheimer's progression were inhibited by pepinemab treatment, supporting its potential benefits [4] Group 2: Mechanism of Action - Pepinemab has been shown to inhibit or reverse damage caused by toxic aggregates of alpha synuclein, which are linked to various neurodegenerative diseases, including Alzheimer's [5][7] - The company plans to focus on treating patients with MCI or mild dementia due to Alzheimer's with pepinemab to slow disease progression [7] Group 3: Future Development - Vaccinex aims to continue discussions for partnerships to further develop pepinemab for Alzheimer's, Huntington's disease, and potentially other neurodegenerative diseases [7]