THE WT1 IMMUNOTHERAPY ENGINEERED FOR A BROAD SPECTRUM OF CANCER INDICATIONS
The Company’s lead product candidate, galinpepimut-S, targets malignancies and tumors characterized by an overexpression of the WT1 (Wilms Tumor Protein) antigen. The WT1 antigen is one of the most widely expressed cancer antigens in multiple malignancies. It has been ranked by the National Cancer Institute (NCI) as the Number 1 target for cancer immunotherapy. SELLAS’ WT1 immunotherapy is comprised of four peptide chains, two of which are modified chains that induce a strong innate immune response (CD4+/CD8+) against the WT1 antigen and access a broad range of HLA types. When administered to a patient, the induced immune response recognizes and kills cancerous cells and also provides ongoing support and memory to the immune system so that it can continue to target and kill recurring tumors and residual cancerous cells.
This efficacy along with an attractive safety profile gives galinpepimut-S the potential to be a highly effective approach to prolonging survival by delaying or preventing relapse and recurrence in patients in complete remission or with minimal residual disease.
WT1: #1-Ranked Cancer Antigen by the National Cancer Institute
Source: Cheever CCR 2009
Why Target WT1?
WT1 is widely over-expressed in a broad range of cancers
Source: Memorial Sloan Kettering Cancer Center data (based on review of literature and multiple studies)
Galinpepimut-S: Key Differentiators
Patients with AML, mesothelioma, MM and other types of cancers show relapse rates in excess of 80% or more. Although most patients get into complete remission with currently available treatments, the majority of those patients, unfortunately, relapse thereafter. Thus, SELLAS’ WT1 immunotherapy can target over 25 cancers that over-express WT1 and, due to its potent T-cell immune response, it is designed to prevent/prolong relapses and prolong survival in these patients as illustrated in Phase 1 & 2 clinical trials performed.
WT1 IMMUNOTHERAPY DEVELOPMENT
The WT1 (Wilms Tumor Protein) antigen is a transcription factor that is not generally expressed in normal adult cells, but appears in a large number of cancers, as well as in certain cancer stem cells (CSCs). Previously, WT1 has not been drugable by traditional approaches, but it can be targeted by the immune system, in particular by CD4 T-cells and CD8 T-cells. Specifically, a number of different peptide sequences from the WT1 antigen have been identified as immunogenic and capable of stimulating cytotoxic T-cells that will target and kill WT1-expressing cancer cells. Studies also have shown that WT1 does not provoke tolerization and that patients’ T-cells can remain reactive to the antigen over time.
WT1 is the #1 ranked antigen by the National Cancer Institute as target for immunotherapy approaches. The WT1 antigen is expressed broadly across a range of cancers enabling galinpepimut-S to address multiple tumor types. It is potentially applicable to over 25 types of cancers worldwide.
The WT1 immunotherapy, originally developed by Memorial Sloan Kettering Cancer Center (MSKCC) and licensed to SELLAS, incorporates a set of immunogenic peptides that have been shown to stimulate both CD4 and CD8 T-cells. In addition, key amino acids from some of these peptides have been modified to improve their immunogenicity. SELLAS is working with MSKCC on an immunotherapy and is further optimizing the manufacturing process towards a lyophilized formulation.
WT1 immunotherapy is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target. Initial studies have been conducted in patients with acute myeloid leukemia and thoracic cancers, such as lung cancer and mesothelioma. Based on encouraging results in these initial studies, additional Phase 2 trials were launched in hematopoietic cancers and solid tumors. Results of these initial studies have shown that SELLAS’ WT1 immunotherapy is well-tolerated and capable of inducing a robust immune response to the antigen. Patients enrolled in the acute myeloid leukemia and mesothelioma trials have shown prolonged survival following vaccination.
In patients with advanced cancers over-expressing WT1, SELLAS’ immunotherapy is designed to prevent relapses and potentially improve survival rates of patients, while maintaining their quality of life. Clinical studies conducted at MSKCC have shown strong proof of concept, including compelling survival findings, and a positive safety and tolerability profile.
Acute Myeloid Leukemia (AML)
Initial clinical studies of galinpepimut-S were conducted in AML due to the high levels of WT1 expression observed in the tumor type and the deep institutional experience of Memorial Sloan Kettering Cancer Center with AML.
– Phase I and Phase II studies were conducted with 9 and 22 patients, respectively. Of these total 31 patients 16 (52%) remain alive with a median OS of the Phase II study patients of 61.8 months.
– Galinpepimut-S was further independently validated at the Moffitt Cancer Center (MCC) in a more severe AML population after they reached their second complete remission (CR2), where it showed statistically significant clinical benefit with a historical site comparison of a median survival of 16.5 months vs. 5.5 months with best standard treatment. Disease free survival was 10.6 months vs 4.4 months with standard treatment.
– The Phase III clinical trials for Acute Myeloid Leukemia are scheduled to begin in H1 2017.
AML Patients with Intermediate Risk with Best Standard Therapy (N=968)
Source: Appelbaum F R et al. Blood 2006;107:3481
Galinpepimut-s phase 2: Overall Survival in AML Patients in CR1
Galinpepimut-S -> 1855 d (5.08 years; 61.8 mo)
Best Standard Therapy (BST) -> ~525 d (1.44 yrs; 17.5 mo)
Source: Walter RB, et al. J Clin Oncol. 2010; 28:1766-71.
Malignant Pleural Mesothelioma (MPM)
MPM was also chosen as a clinical trial setting due to the high levels of expression of WT1 in patients with this tumor type.
– A 40-patient Phase II, double-blind, randomized study at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center, co-sponsored by the Department of Defense, showed a positive impact on survival.
– Median OS of 24.8 months in galinpepimut-S arm vs. 16.6 months in the control group.
– The Phase III clinical trials for MPM are targeted to begin in H2 2017.
Malignant Pleural Mesothelioma (n=40)
Median Overall Survival (From Start of Treatment)
Galinpepimut-s 24.8 m (8.5-39.4)
Control 16.6 m (10.2-28.1)
Source: Zauderer et.al., Study 10-134 (Abst # 8519, ASCO 2016)
Multiple Myeloma (MM)
19 patients enrolled; 17/18 evaluable patients still alive.
– 86% actuarial OS at 18 months and median OS not reached yet.
– Median PFS has not been reached as of yet, but is poised to be greater than 18 months.
– 15/18 patients with high-risk cytogenetics at diagnosis, as well as additional unfavorable clinical characteristics: typically, extremely poor prognosis with PFS of 12-15 months after transplant with best standard treatment in this population.
– A Phase I study in Ovarian Cancer aiming to enroll 10-15 patients has been initiated in May 2016 to assess the safety and efficacy of galinpepimut-S plus BMS’s PD-1 antibody, nivolumab (Opdivo®). The ongoing Phase I study data is expected by H1 2017.
– Further studies have been planned for Chronic Myelogenous Leukemia (CML) and Glioblastoma Multiforme, which are expected to be initiated in 2017.
For more information on the WT1 program, please see Publications and Presentations.