Product and Pipeline
More effective combination treatments for cancer
Cancers are complex dynamic and adaptive diseases with the tumor micro-environment comprising many different cell types, matrix proteins and secreted molecules.
The interplay between these elements impacts the responsiveness to therapy and whether there is continued tumor survival and progression, even in the face of continued treatments. We believe that remodelling of the tumor microenvironment and taking a multi-pathway and multi-target approach offers an opportunity to significantly improving response rates and durability of response.
|Product||Indication||Preclinical||Phase 1||Phase 2||Status|
|SP-002: Phase 2A||Multi-lesional Basal Cell Nevus Syndrome||On-going and to complete in 2023|
|SP-002: Phase 2B||Locally Advanced BCC||Commence in 2H, 2023|
|SP-002: Phase 1/2A||Squamous Cell Carcinoma||Commence in 1H, 2024|
|SP-002: Phase 1/2A||Cutaneous Breast Cancer||Commence in 1H, 2024|
|SP-105||Optimization and Clinical Trial enabling Studies||On-going IND enabling Studies|
SP-002 is a human adenovirus 5 vector encoding Interferon-γ
SP-002 is an adenoviral vector (serotype 5, Ad5) encoding the therapeutic cytokine Interferon-γ. The vector has been engineered to be replication-deficient so it can transduce cells and produce Interferon-γ but not new viral particles (a safety feature not present in oncolytic viruses, which may also replicate in non-cancer cells). Interferon-γ has shown superior potency against tumors compared with Interferon-⍺, however, its successful clinical application in cancer has been hampered by its narrow therapeutic window. The main advance of SP-002 is a wide-therapeutic window where transduced tumors release local sustained IFN-γ allowing for a therapeutically effective dose to be delivered without causing significant systemic toxicities. Interferon-γ is a central orchestrator of an immune response (both adaptive and innate response), can induce programmed cell death in tumors, and restricts neo-vasculature supporting tumor growth.
It is being developed as an effective, durable non-surgical intra-lesional treatment for treating multiple Basal Cell Carcinomas in Basal Cell Nevus Syndrome patients.
SP-105 comprises SP-002 in combination with a controlled-release cox-2 inhibitor to enable the local release profile that can provide a wider therapeutic window.
Cox-2 Inhibitors and SP-002 both promote adaptive immune responses and direct anti-tumor effects through complementary pathways.1, 2 A key part of the regulatory feedback that dampens the cellular inflammatory response driven by Interferon-γ signalling, is the induction of Cox-2 expression which suppresses cellular immunity.3 Cyclooxygenase-2 expression within the tumour stroma enhances PDL1 expression in tumour-associated macrophages and myeloid-derived suppressor cells (the PD1/PDL1 nexus is a major regulatory checkpoint that can shut-down T cell responses elicited by Interferon-γ signalling).4, 5 A second major negative regulator of T cell responses elicited by Interferon-γ signalling are regulatory T cells (Tregs).6 Cox-2 expression has been shown to be potent inducers of regulatory T cells.7
Preclinical IND enabling studies.
1. Zuo et al, Exp. Cell Res. 2015: 333(2):316
2. Nakanishi et al Carcinogenesis 2011: 32(9):1333
3. Ren et al Drug Design, Development and Therapy 2014: 8:1527
4. Sharma et al Journal of Immunology 2005: 175(2):813
5. Gobel et al Cell Death and Disease 2014: 5, e1568
6. Li et al, ONCOIMMUNOLOGY 2016: 5(2):e1074374
7. Sharma et al (2), Cancer Res. 2005: ;65(12):5211
A viral vector designed to be administered intralesionally to remodel the disease microenvironment to become more permissive to small-molecule, biological and cellular therapies by altering the stromal and extra-cellular matrix components.
Lead candidate optimization studies.