Galena Biopharma (NASDAQ: GALE) is focused on developing and commercializing targeted oncology treatments to address major unmet medical needs and advance cancer care. The company’s peptide vaccine immunotherapies harness the patient’s own immune system to identify and destroy cancer cells. Utilizing peptide immunogens has many clinical advantages, including an excellent safety profile and long-lasting protection through immune system activation and convenient delivery.
GALE’s lead product, NeuVax™, is currently midway through a pivotal Phase 3 trial under a Special Protocol Assessment (SPA) from the FDA. In completed Phase 1/2 trials of NeuVax, patients who exhibited robust immunologic response had a significant benefit in reduction recurrence with minimal toxicity. Neuvax is being developed a targeted therapy for breast cancer patients whose cancers express the HER2 protein at the IHC 1+/2+ levels, for which there is no current targeted therapy. It is also undergoing a Phase 2 combination trial with Herceptin (trastuzumab) on HER2-overexpressed (IHC 3+) patients.
The company’s second product candidate, GALE-301, is based on the Folate Binding Protein (FBP), is a highly immunogenic peptide that can stimulate the immune system to recognize and destroy preclinical FBP-expressing cancer cells. The FBP peptide immunotherapy has demonstrated excellent safety, robust immunologic responses, and preliminary efficacy in ovarian and endometrial patients in a Phase 1/2a trial.
The company is actively seeking commercialization partners for its current clinical programs in selected regions of the world and welcomes ideas and proposals for strategic alliances, including in-licensing opportunities for commercial and late stage oncology products.
The most recent corporate presentation (4/8/2016) can be found here: http://s2.q4cdn.com/425283004/files/doc_presentations/2016/Galena-Presentation-8-Apr-16.pdf
NeuVax is currently undergoing Phase 3 clinical trial for the adjuvant (after-surgery) treatment of early-stage HER2/neu-expressing breast and prostate cancer. Each year, approximately 230,000 people in the U.S. are diagnosed with breast cancer.
NeuVax has been developed to bolster the immune response in breast cancer patients. The trial, entitled PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) is being conducted under an FDA-approved Special Protocol Assessment (SPA). The therapy targets the 50% to 60% of patients with tumors that express HER2 in low-to-intermediate amounts and achieve remission with current standard of care, but who have no available HER2 targeted adjuvant treatment options to maintain their disease-free status. NeuVax can be used to help the body target and kill undetected cancer cells before they grow into metastatic tumors.
NeuVax may also be developed to treat other types of solid tumors.
GALE-301/302 (Folate Binding Protein-E39)
The company’s second product candidate, Folate Binding Protein (FBP), is a highly immunogenic peptide that can stimulate the immune system to recognize and destroy preclinical FBP-expressing cancer cells. FBP is over-expressed in more than 90% of ovarian and endometrial cancers, as well as 20%-50% of breast, lung, colorectal, and renal cell carcinomas. This vaccine is currently in a Phase 1/2 trial in two gynecological cancers: ovarian and endometrial adenocarcinomas.
Ovarian cancer occurs in more than 22,000 patients per year in the U.S. and is the most lethal gynecologic cancer. Despite the incidence of ovarian cancer being only approximately 20% that of breast cancer, the number of patients that die from ovarian cancer is nearly 50% that of breast cancer. Due to the lack of specific symptoms, the majority of ovarian cancer patients are diagnosed at later stages of the disease. These patients are routinely surgically debulked to minimal residual disease, and then treated with platinum-basd and/or taxane-based chemotherapy. While most patients respond to this treatment regime and become clinically free of disease, the majority of these patients will relapse, and once the disease recurs, the treatment options and successes drop dramatically.
Endometrial cancer is the most common gynecologic cancer and occurs in over 46,000 women, with over 8,000 deaths, in the U.S. annually. There are two basic types of endometrial cancer: endometriod and papillary serous. The latter has a much more aggressive clinical course and the majority of these patients will die of this form of the disease.
Each year, nearly 1.6 million new cases of cancer are diagnosed in the United States, excluding skin cancer diagnosed annually. Cancer is the second leading cause of death (after heart disease) in the United States, expected to account for about 572 thousand deaths. There are more than 100 different varieties of cancer, which can be divided into six major categories.
This year, one in four deaths in the US is expected to be due to cancer. For all forms of cancer combined, the 5-year relative survival rate is 64%. Despite the fact that the cancer mortality rate in the U.S. has risen steadily for the past 50 years, scientific advances appear to have begun to turn the tide. According to the National Center for Health Statistics, 2003 was the first year since 1930 annual cancer deaths declined - the start of what researchers hope will be a long-term decline in cancer mortality.
A cancer vaccine (cancer immunotherapy) is designed to target and therapeutically fight cancer cells. The vaccine could contain cells, parts of cells or pure antigens. There is also broad variability of potential vectors for delivering the “vaccine.” The goal of the vaccine is to increase the immune response against cancer cells that are already present in the body. Cancer immunotherapy is considered active immunotherapy because substances injected into the body are meant to trigger the patient’s immune system to respond.
Immunotherapy is a form of therapy that uses the patient’s own immune system to fight disease. This type of treatment works in two ways: education and stimulation of the immune system to work smarter, or the introduction of additional immune system components that help the immune system work more effectively. The first is generally known as active immunotherapy and the latter is generally known as passive immunotherapy.
NeuVax works by turning on the immune system. NeuVax recruits the main components of the cellular immune system to fight cancer by presentation of a T-cell peptide epitope in the context of the peptide-HLA-T-cell receptor complex. When NeuVax is administered, the E75 peptide, a well-established T-cell epitope discovered on HER2, binds to the HLA-A2 and HLA-A3 molecules on the surface of tumor cells and Antigen Presenting Cells (APCs). The peptide sends a signal to the immune system by binding in the HLA-peptide-T-cell receptor complex. Circulating T-cells recognize the peptide bound to HLA though T-cell receptors (TCRs) on their surfaces and the T-cells become “educated” and “activated” to target HER2-expressing tumor cells exhibiting the E75 epitope bound to HLA. Furthermore, activation of these T-cells leads to clonal expansion and proliferation of E75-specific “killer T-cells” that circulate through the body, identify and destroy cancer cells that are processing HER2.
Tumor cells are differentiated from healthy cells by the expression of tumor-associated proteins, also known as “tumor antigens.” HER2/neu is a well-established tumor-associated antigen found at various expression levels on the membrane surface of many types of human cancer cells. The human immune system is constantly surveying the body for foreign invaders (foreign proteins) or abnormal self proteins. To aid in this immune surveillance, cellular proteins such as HER2/neu and others are routinely digested or broken down inside the cell into short fragments called peptides and the small peptides are then “displayed” on the cell surface as a means of communicating with the immune system. Differences between the pool of peptides from a tumor cell and a normal cell are revealed on the outside of the cell. Peptides that are presented on or from tumor cells, but that are absent (or present to a far lesser extent) on healthy cells are called tumor-associated peptides (TAPs).
Unlike existing monoclonal antibody therapy which requires frequent, ongoing, intravenous (I.V.) infusion, NeuVax can produce continuing activation of the immune system and therapeutic levels of Killer T-cells with a once monthly intradermal (under the skin) dosing schedule that is less expensive and more convenient for both the patient and physician.
Neuvax (Nelipepimut-S) Phase 2 trial results: http://www.ncbi.nlm.nih.gov/pubmed/24907636
Disease-free survival. (A) All assessable patients; (B) patients with HER2 1+ or 2+ disease. (C) By dosing group (*P
value compares optimally dosed group to control group); (D) evaluating optimally boosted patients (*P
value compares optimally boosted group to control group).
Quote: GALE-301/302 Phase 1/2a trial results: https://globenewswire.com/news-release/2016/04/19/830247/0/en/Galena-Biopharma-Presents-GALE-301-GALE-302-Clinical-Booster-Data-at-the-American-Association-for-Cancer-Research-AACR-Annual-Meeting.html
RESULTS: Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%).
CONCLUSION: The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.
SAN RAMON, Calif., April 19, 2016 (GLOBE NEWSWIRE) -- Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of targeted oncology therapeutics that address major unmet medical needs, today announced that data from the booster phase of the Company’s GALE-301/GALE-302 Phase 1/2a clinical trial was presented at the American Association for Cancer Research (AACR) Annual Meeting.
The poster, entitled, “Comparing an attenuated booster (E39’) vs. E39 booster to potentiate the clinical benefit of the folate binding protein (FBP)-derived vaccine (E39 + GM-CSF) in a phase I/IIa trial to prevent recurrence in endometrial (EC) and ovarian cancer (OC) patients,” was presented today by Dr. Doreen Jackson from the San Antonio Military Medical Center. In the Phase 2a portion of the trial, patients were randomized to two different boosters: E39 (GALE-301), versus E39’ (GALE-302). The purpose of the study was to evaluate the immune responses and determine which booster, if either, would provide a sustained immune response and potentially longer disease free survival (DFS) rates.
The use of the wildtype peptide (GALE-301/E39) demonstrated the same tolerable safety profile as the attenuated peptide (GALE-302/E39’) with only Grade 1 local reactions and minimal Grade 2 toxicities. Importantly, the percentage of patients who received two booster inoculations and remained disease free was significantly better in the drug treatment arm, versus the control arm (p=0.02), regardless of which booster was used. At median follow up of 16 months, the boosters demonstrated equivalent efficacy after two booster inoculations with an estimated, two-year DFS rate of 66.7% (GALE-301 n=7, GALE-302 n=7) in each booster arm versus 36% (n=22) in the control arm.
“In our GALE-301 Phase 2a trial, we randomized patients to determine an optimal boosting strategy and to see if there was an observable difference between boosting patients with GALE-301 versus the attenuated version of the peptide, GALE-302,” stated Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. “The results show that both boosters were effective with no measurable difference between them, and we will consider this as we continue to evaluate the best path forward for our compounds targeting FBP. The primary analysis of this trial will be presented at the upcoming American Society of Clinical Oncology meeting in June.”
A total of 51 patients were enrolled in the Phase 1/2a trial with 29 HLA-A2-positive patients in the vaccine group (VG) and 22 HLA-A2-negative patients in the control group (CG). Six monthly intradermal inoculations of GALE-301 plus 250mcg GM-CSF were administered to the VG to complete the primary vaccine series (PVS). Patients were then randomized to receive two booster inoculations of 500mcg of GALE-301 or GALE-302 plus 250mcg GM-CSF at six and twelve months post-PVS. Seventeen patients continued onto the booster series and were randomized with 14 receiving two boosters. There were no significant demographic or baseline differences between groups, no difference in toxicities were observed, and there were no Grade 3 or 4 toxicities in either group.
Relevant Analysis http://seekingalpha.com/article/3809756-neuvax-vaccine-matter-signal-integrity http://seekingalpha.com/article/3837936-neuvax-vaccine-matter-signal-integrity-part-2 http://seekingalpha.com/article/3959991-neuvax-vaccine-matter-signal-integrity-addendum