Galinpepimut-S (GPS) Therapy, Sellas Life Sciences

Our Therapy

SELLAS is partnering with Memorial Sloan Kettering Cancer Center to develop novel immunotherapies for a broad range of cancer indications

GPS Cancer Immunotherapy

GALINPEPIMUT-S

THE GPS IMMUNOTHERAPY ENGINEERED FOR A BROAD SPECTRUM OF CANCER INDICATIONS

SELLAS’ lead product candidate, galinpepimut-S, targets malignancies and tumors characterized by an overexpression of the WT1 antigen. The WT1 antigen is one of the most widely expressed cancer antigens in multiple malignancies. It has been ranked by the NCI as the top priority among cancer antigens for 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 has the potential to recognize and destroy cancer cells and provide ongoing support and memory to the immune system so that it can continue to target and destroy recurring tumors and residual cancer cells.

The Company’s lead product candidate, galinpepimut-S, targets malignancies 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 has the potential to recognize and destroy cancer cells. This efficacy along with a well-tolerated safety profile gives galinpepimut-S the potential to be a highly effective approach to prolonging survival by delaying or preventing relapse/recurrence in patients in complete remission or with minimal residual disease.

WT1: Top Priority Cancer Antigen by the National Cancer Institute

Source: Cheever CCR 2009

Patients with AML, MPM, MM and other types of cancers who undergo initial debulking front-line therapy have shown relapse rates in excess of 80% or more, as this upfront therapy rarely leads to complete eradication of the disease. Although most patients enter into complete remission with currently available treatments, the majority of those patients, unfortunately, relapse thereafter. Thus, SELLAS’ WT1 immunotherapy can target over 20 cancers that over-express WT1 and, due to its strong T-cell immune response, it is designed to prevent/delay relapses (by prolonging the progression-free interval) and eventually potentially prolong survival in these patients, which is evidenced by the positive results in Phase 1 & 2 clinical trials performed to date.

Tumor types pursued by SELLAS’ clinical program Other tumor types

AML: acute myelogenous leukemia MPM: malignant pleural mesothelioma

Source: Memorial Sloan Kettering Cancer Center data (based on review of literature and multiple studies)

GPS POISED TO BECOME AN EFFECTIVE immunotherapy

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 20 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.

GPS Immunotherapy Development

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 has the potential to recognize and destroy cancer cells. This efficacy along with a well-tolerated safety profile gives galinpepimut-S the potential to be a highly effective approach to prolonging survival by delaying or preventing relapse/recurrence in patients in complete remission or with minimal residual disease.

The WT1 immunotherapy, originally developed by 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 further optimizing the manufacturing process towards a lyophilized formulation with high stability features. The general principles of the mechanism of action of galinpepimut-S is schematically represented in the graphic below.

WT1 immunotherapy is administered in combination with an adjuvant and an immune modulator (GM-CSF) to improve the immune response to the target. Initial pilot clinical studies have been conducted in patients with AML and thoracic cancers, such as lung cancer and MPM. 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 AML and MPM trials have shown prolonged survival following active immunization with galinpepimut-S.

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 well-tolerated safety 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 this tumor type and the deep institutional experience of MSKCC with AML.

Phase 1 and Phase 2 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 2 study patients of 67.6 months.
Galinpepimut-S was further independently validated at the Moffitt Cancer Center (MCC) in a more severe AML population in patients who had 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.
A Phase 3 clinical trial for AML is currently being scheduled, pending funding availability.

Malignant Pleural Mesothelioma (MPM)

MPM was chosen as a clinical trial setting due to the high levels of expression of WT1 in patients with this tumor type.

A 41-patient Phase 2, double-blind, randomized study performed at MSKCC and MD Anderson Cancer Center and co-sponsored by the Department of Defense (DOD), demonstrated a well-tolerated safety profile.
The most recent analysis shows median OS was 22.8 months in the GPS arm vs. 18.3 months in the control arm, (HR: 0.79), with a median follow-up of 17.2 months.
A Phase 3 clinical trial for MPM is currently being scheduled, pending funding availability.

Multiple Myeloma (MM)

19 patients enrolled; 17/18 evaluable patients still alive.

88% actuarial OS at 18 months and median OS not reached yet.
Median PFS of 23.6 months.
15/18 patients with high-risk cytogenetics at diagnosis, as well as additional unfavorable clinical characteristics including all of them with Minimal Residual Disease (MRD) after successful Autologous Stem Cell Transplantation (ASCT); typically, extremely poor prognosis with PFS of 12-15 months after ASCT with best standard treatment (typically Immunomodulatory Drug [IMID] maintenance) in this population.

Additional Studies

A Phase 1 study in ovarian cancer aiming to enroll 10-15 patients was initiated in May 2016 to assess the safety and efficacy of galinpepimut-S in combination with the PD-1 antibody, nivolumab (Opdivo^®).
Further studies have been planned for chronic myelogenous leukemia (CML).

For more information on the WT1 program, please see Publications and Presentations.

Galinpepimut-S (GPS) Therapy

Our Therapy

GPS Cancer Immunotherapy

THE GPS IMMUNOTHERAPY ENGINEERED FOR A BROAD SPECTRUM OF CANCER INDICATIONS

GPS Immunotherapy Development

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