Heat Biologics is developing dual-acting immunotherapies, therapeutic vaccines, and costimulatory antibodies against cancer, and now a vaccine against COVID-19.

Leveraging A Natural Molecular Warning System

Within the human immune system, the heat shock protein gp96 serves as a natural molecular warning system. It is a potent mucosal immune memory inducer and serves as a chaperone to deliver antigens (pathogen or tumor) to the immune system and activate B cell and T cell responses. Gp96 functions as a potent immune adjuvant that induces immunity against necrotic cells and is normally released only during necrosis or cell death.

Clinical-stage biotechnology company Heat Biologics has developed a proprietary gp96 platform that leverages gp96’s role as a natural molecular warning system based on research initially conducted at the University of Miami. Heat Biologics’ proprietary gp96 vaccine platform reprograms live cells to continually secrete antigens of interest bound to gp96, thus activating a robust immune response against those antigens. The allogeneic (off-the-shelf) cell therapies are produced using a robust, scalable manufacturing process and have broad applications in both cancer treatment and vaccines for infectious diseases..

Dual-Acting Cancer Cell Therapies

The company’s Immune Pan-Antigen Cytotoxic Therapy (ImPACT) platform genetically engineers cells to deliver gp96-chaperoned cancer testis antigens to activate a patient’s immune system. The technology provides targeted panantigen (known and unknown) delivery to antigen-presenting cells (APCs) in vivo selectively via MHC-1 molecules. The result is cross-presentation of specific antigens to cytotoxic CD8+ T cells with exclusive cytotoxic killer CD8⁺ T cell activation. Synchronous/linked delivery of the antigen and Antigen-specific adjuvant has a potent effect without causing unwanted immune system stimulation.

Our Combination Pan-Antigen Cytotoxic Therapy (ComPACT) platform is a dual-acting immunotherapy designed to deliver T cell activation and co-stimulation in a single product. ComPACT utilizes localized delivery of OX40 ligand fusion protein (OX40L-Fc) co-stimulation to ensure safety and contribute to the induction of long-lasting memory responses. As ComPACT is designed to deliver the gp96-chaperoned antigens and co-stimulatory fusion protein (OX40L) in a single cell line, it has the potential to provide the benefits of combination immunotherapy without the need for multiple, independent biologic products. 

Cell Therapy for Non–Small Cell Lung Cancer

Heat Biologic’s lead candidate HS-110 (viagenpumatucel-L) is an off-the-shelf cell-based therapy for the treatment of non–small cell lung cancer (NSCLC) based on our ImPACT technology. In clinical trials, HS-110 demonstrated a broad activation of T cell–mediated immune response in cancer patients.

Currently, we are evaluating the safety and efficacy of HS-110 in combination with Bristol-Myers Squibb’s checkpoint inhibitor nivolumab (Opdivo^®) or Merck’s checkpoint inhibitor pembrolizumab (Keytruda^®) in a multicenter phase II clinical trial with approximately 120 patients. Positive interim top-line data is highly encouraging.

First Allogeneic Cell Therapy That Delivers Localized Ox40-Mediated Co-Stimulation

HHS-130 is the first allogeneic, off-the-shelf cell therapy that delivers localized OX40-mediated co-stimulation. Improved efficacy and safety were demonstrated in multiple preclinical cancer models using OX40L-Fc via cell-based delivery, compared with systemic administration of an OX40 agonist antibody in combination with HS-110. A phase I clinical trial has been initiated for HS-130 in combination with HS-110 for patients with advanced solid tumors refractory to standard of care. The first patient was dosed in early 2020.

Covid-19 Vaccine Development 

Our proprietary gp96 platform has been shown to activate the human immune system to combat infectious diseases. Collaborators of Heat Biologics’ have laid a strong foundation on engineering different pathogenic antigens into our platform.

The gp96 platform has been rigorously tested in designing vaccines against SIV/HIV, malaria, Zika, and other infectious diseases in numerous National Institutes of Health (NIH)- and Department of Defense (DOD)-funded mouse and primate trials. These studies demonstrated that these vaccines stimulated a robust systemic immune response, culminating in humoral and cell-mediated responses in different organs, including the gut, reproductive tract, and liver.

Based on these results, Heat decided to initiate a COVID-19 vaccine collaboration with the University of Miami in March 2020. A program was formally launched within the wholly owned subsidiary Zolovax, Inc., to develop a vaccine using its immune-activating gp96 vaccine platform for preventing infection from the SARS-CoV-2 coronavirus that causes COVID-19.

Heat’s COVID-19 vaccine program focuses on leveraging our gp96 platform to deliver multiple SARS-CoV-2 antigens. This approach is designed to induce T cell and B cell responses at the point of viral entry (the mucosal site) to protect against SARS-CoV-2 virus across diverse human populations. Such design has the potential to generate long-term immune responses without the disadvantages of possible genomic integration of foreign DNA or viral vector instability.

The vaccine will be developed at the University of Miami Miller School of Medicine under the direction of Natasa Strbo, M.D., D.Sc., research assistant professor of microbiology and immunology, who has spent many years advancing the gp96 platform in designing vaccines against HIV, malaria, zika, and other infectious diseases. Heat Biologics has also formed a COVID-19 Advisory Board (CAB).