COMPANY OVERVIEW (as of 8/14/2017)
We are an immuno-oncology company developing novel therapies designed to activate a patient’s immune system against cancer utilizing
an engineered form of the protein, gp96, a potent immune response stimulator and the basis of our core technology. Our platform
technologies are designed to turn “cold” tumors “hot” by increasing the ability of tumor infiltrating lymphocytes (TILs) to attack the tumor.
We do this by addressing two distinct, but synergistic mechanisms-of-action: robust activation and proliferation of CD8+ T cells, or
“killer” T cells and T cell co-stimulation. Heat’s highly specific T cell-stimulating therapeutic platform technologies, ImPACT® (Immune
Pan-Antigen Cytotoxic Therapy) and ComPACT™ (Combination Pan-Antigen Cytotoxic Therapy), are intended to activate and, in the case
of ComPACT™, also co-stimulate “killer” T cells. Most recently, we acquired two additional T cell co-stimulators through the acquisition
of Pelican Therapeutics, Inc. (“Pelican”), broadening our pipeline and strengthening our portfolio in the emerging T cell activation space.
Through our ImPACT® platform technology, we have developed product candidates that consist of live, allogeneic “off-the-shelf”
genetically-modified, irradiated human cancer cells. These cells are intended to secrete a broad spectrum of Cancer Testis Antigens (CTA)
together with the gp96 protein. The secreted antigen gp96-Ig-CTA complexes are designed to activate a patient’s adaptive, T cell mediated
immune system to recognize and kill cancer cells. Gp96 has been shown to assist in tumor rejection by delivering multiple, mutated tumor
proteins to immune cells to stimulate a CD-8+ immune response against a patient’s cancer cells. Our ImPACT® technology achieves this by
reprogramming live tumor cells to secrete gp96, along with their chaperoned tumor antigens; thereby, transforming the allogeneic cells into
machines that activate a robust “killer” CD8+ T cell immune attack against a patient’s cancer.
Our ComPACT™ platform technology, currently in preclinical development, is a dual-acting immunotherapy, combining a pan-antigen T
cell activator and a T cell co-stimulator in a single product, offering the potential benefits of combination immunotherapy without the need
for multiple, independent biologic products. The platform has been engineered to incorporate various fusion proteins targeting costimulatory
receptors (OX40, ICOS, GITR, TL1A, etc.) into the gp96-Ig expression vector, enabling the combination of two
immunotherapy pathways into a single therapy.
Using our ImPACT® platform technology, we developed the product candidate, HS-110 (viagenpumatucel-L), as a potential treatment for
patients with non-small cell lung cancer (“NSCLC”). We are conducting a Phase 2 clinical trial evaluating HS-110 in combination with
nivolumab (Opdivo®), a Bristol-Myers Squibb anti-PD-1 checkpoint inhibitor, to treat patients with NSCLC whose cancers have
progressed after first-line therapy. Our multicenter, open-label trial is expected to initially enroll 18 patients evaluable for baseline biopsy
and is designed to accommodate cohort expansion up to 30 patients per arm (approximately 60 patients). Primary and secondary trial
endpoints include safety and tolerability, immune response, overall response rate, and progression-free survival. Trial enrollment is
currently ongoing.
On March 21, 2017, we reported positive interim results for our NSCLC trial, indicating a favorable safety profile, low toxicities and robust
immune response. At that time, 15 patients had been treated with the HS-110/nivolumab combination, and 12 of these 15 patients were
evaluable for ELISPOT analysis. ELISPOT results suggest that HS-110 plays an integral role in tumor reduction and may enhance efficacy
of checkpoint inhibitors in lung cancer patients. Immune responses to HS-110 were observed in all five patients that exhibited tumor
reductions. No tumor reductions were observed in patients that did not mount an immune response to HS-110. The timing of immune
response to HS-110 corresponded to the timing of observed clinical responses, and those responses appear to be sustained. Furthermore, at
that time, five patients had been enrolled in the low tumor infiltrating lymphocytes (TIL) cohort. Three of the five patients (60%)
experienced significant tumor reduction, which is higher than the 10% response rate of low TIL patients reported for existing data on
nivolumab alone.
On April 28, 2017, we completed the acquisition of 80% of Pelican’s common stock. Pelican is a biotechnology company focused on the
development and commercialization of monoclonal antibody and fusion protein-based therapies that are designed to activate the immune
system. PTX-25, Pelican’s lead product candidate targeting the T cell co-stimulator, TNFRSF25, combined with immunotherapies,
including ImPACT and ComPACT, may have the ability to activate memory CD8+ cytotoxic T cells and eliminate tumor cells in patients.
PTX-25 is designed to harness the body's natural tolerance mechanisms to reprogram the immune system and provide a long-term, durable
effect after a short course of therapy. PTX-15, Pelican’s second product candidate, is a human TL1A-lg fusion protein designed to stimulate
the specific proliferation of Treg cells in vivo to provide precise control of the regulatory arm of our immune system, and can be used in
immuno-oncology and other disorders. We believe this is important because many leading global pharmaceutical companies are focused on
T cell co-stimulators to enhance the effectiveness of their existing immune-oncology therapies.
On June 1, 2016, Pelican was awarded a $15.2 million Cancer Prevention Institute of Texas (CPRIT) grant to support further development
of PTX-25 and fund a large Phase 1 clinical trial to examine the benefits it may provide to patients with several types of cancers, such as
lung, lymphoma, prostate, pancreatic and ovarian. The CPRIT grant is subject to customary CPRIT funding conditions.
Our wholly-owned subsidiary, Zolovax, Inc. (“Zolovax”), is in pre-clinical studies to develop therapeutic and preventative vaccines to treat
infectious diseases based on our gp96 vaccine technology, with a current focus on the development of a Zika vaccine in collaboration with
the University of Miami. Other infectious diseases of interest include HIV, West Nile virus, and Dengue and yellow fever.
We continue to evaluate other potential indications for our ImPACT® and ComPACT™ platform technologies. Specifically, with
ComPACT™, we have developed cell lines for several other cancers, with the first product candidate being a second-generation therapy for
NSCLC (HS-120). Our decision to further pursue these or any additional product candidates, other than our lead product candidate, will be
based in part upon available funding and partnering opportunities. Although we are no longer pursuing our HS-410 bladder cancer program,
pursuant to regulatory requirements, we continue to monitor the patients from the bladder cancer Phase 2 clinical trial.
AI
