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
to commence
on-going study


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.

Clinical Rationale

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-002 with a Hedgehog Pathway Inhibitor (HHPI)

The combination regimen is being developed as an effective treatment for Locally Advanced Basal Cell Carcinoma. Basal cell carcinoma is a common skin cancer, with 3-4 million cases arising annually in the US. About 2% of these patients progress to advanced disease (about ~60,000 per yr. in the US). LA BCC comprise unresectable lesions, recurrent (multiple recurrences) lesions and lesions on anatomically difficult surgical sites that would result in significant functional damage upon resection.

Clinical Rationale

The HHPI (Hedgehog pathway inhibitors, e.g., vismodegib and sonidegib) are FDA-approved agents for use in LA BCC when surgery and radiotherapy are not suitable. Of the estimated that of 60,000 LA BCC patients, only a small subset use HHPIs. The primary reason for HHPI’s low adoption rate is the low Complete Response (CR) rate observed. HHPIs are effective at shrinking the majority of LA BCC but a quiescent population of residual BCC persist even while ongoing treament. Combining, SP-002 with an HHPI can improve clinical outcomes via complementary and synergistic mechanisms of action. SP-002, as an add-on to standard of care (SOC) HHPI, vismodegib, is anticipated to improve both CR rate and durability of response.

Rationale for add-on of SP-002 to HHPIs

HHPI Monotherapy – major ‘debulking’ of large BCCs

BCCs are heterogeneous with respects to HHPI responsiveness

BCCs are heterogeneous with respects to HHPI responsiveness 1-3

HHPI highly effective in majority of BCCs

HHPI highly effective in majority of BCCs 1-3

HHPI resistant residual BCC can lead to relapse ~CR~20-30%

HHPI resistant residual BCC can lead to relapse ~CR~20-30% 5

Quiescent residual BCCs express LGR5 cancer stem cell marker 1-3

HHPI & SP-002 Combination Therapy – ‘debulking’ and removal of HHPI resistant residual populations

BCCs are heterogeneous with respects to HHPI responsiveness

HHPI highly effective in majority of BCCs


HHPI  plus SP-002

HHPI plus SP-002

Interferon – γ ablating residual BCCs (Interferon – γ reported to induce cell death in LGR5 stem cells) 4

Complete Responses
Targeting CR >40-50%

1 Eberl et al, Cell 2018 33, 229

2 Biels et al, Nature 2018 562:429

3 Sánchez-Danés, Nature 2018 562:434

4 Takashima, et al Sci Immunol 2019 4:42

5 vismodegib product information sheet


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.

Scientific Rationale

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

SPREE Platform

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.