“These findings further support the biological rationale that both of our lead product candidates, SRF388 and SRF617, promote increased proinflammatory activity within the tumor microenvironment in the hopes of ultimately providing novel treatment options to patients with cancer,” said
The e-poster website will be launched at 8:30 a.m. ET on Saturday, April 10, and will remain available for viewing through Monday, June 21. The two e-posters will also be viewable on the
Presentation Type: e-poster (Abstract: 1802)
Title: CD39 inhibition shapes the transcriptional landscape of myeloid cells and induces proinflammatory states in the CT26 syngeneic tumor model
Lead Authors: Devapregasan Moodley, Ph.D. and
- SRF617 is a potent inhibitor of CD39 enzymatic activity both in vitro and in vivo.
- Increased activity of CD39 results in significant reductions in extracellular ATP and subsequent accumulation of adenosine, contributing to tumor immune escape, induction of angiogenesis and metastatic progression.
- Immunological mechanisms associated with CD39 blockade reveal major changes to immunocyte transcriptional landscapes, including upregulation of several proinflammatory genes.
- CD39 inhibition predominantly shaped the transcriptional landscape of myeloid cells and dendritic cells, and generally induced proinflammatory conditions.
- These findings indicate that CD39 blockade induces proinflammatory responses, supporting future clinical studies of SRF617 for treating patients with cancer.
Presentation Type: e-poster (Abstract: 1607)
Title: IL-27 signaling serves as an immunological checkpoint for NK cells to promote hepatocellular carcinoma in multiple murine models
Lead Author: Turan Aghayev
- IL-27 signaling suppresses natural killer (NK) cells within the tumor microenvironment, promoting hepatocellular carcinoma (HCC) development in vivo.
- Elevated IL-27RA expression in cancer tissue and elevated EBI3 serum levels are associated with poor prognosis in patients with HCC.
- Inhibiting IL-27 signaling leads to tumor growth inhibition and suppressed HCC development in a non-alcoholic steatohepatitis (NASH)-driven HCC model with concomitant enhancement of NK cell activity.
- These findings indicate that IL-27 blockade regulates NK cell-mediated control of HCC and is a promising therapeutic target in liver cancer.
SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. A substantial body of research supports a role for CD39 in allowing cancer to evade immune responses. For example, pancreatic cancer stromal cells within the tumor micro-environment express high levels of CD39 which may inhibit anti-cancer immune responses. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents.
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immuno-suppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.
About Surface Oncology:
Surface Oncology is an immuno-oncology company developing next-generation antibody therapies focused on the tumor microenvironment. Its pipeline includes two wholly-owned clinical-stage programs targeting CD39 (SRF617) and IL-27 (SRF388), as well as a preclinical program focused on depleting regulatory T cells via targeting CCR8 (SRF114). In addition, Surface has two partnerships with major pharmaceutical companies: a collaboration with Novartis targeting CD73 (NZV930; Phase 1) and a collaboration with GlaxoSmithKline targeting PVRIG (SRF813; preclinical). Surface’s novel cancer immunotherapies are designed to achieve a clinically meaningful and sustained anti-tumor response and may be used alone or in combination with other therapies. For more information, please visit www.surfaceoncology.com.
Cautionary Note Regarding Forward-Looking Statements:
Certain statements set forth in this press release constitute “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by terms such as “believes,” “expects,” “plans,” “potential,” “would” or similar expressions, and the negative of those terms. These forward-looking statements are based on Surface Oncology’s management’s current beliefs and assumptions about future events and on information currently available to management.
Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Surface Oncology’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, risks and uncertainties related to Surface Oncology’s ability to successfully develop SRF388 and SRF617 and its other product candidates through current and future milestones or regulatory filings on the anticipated timeline, if at all, the therapeutic potential of Surface Oncology’s product candidates, the risk that results from preclinical studies or early clinical trials may not be representative of larger clinical trials, the risk that Surface Oncology’s product candidates, including SRF388 and SRF617, will not be successfully developed or commercialized, the risks related to Surface Oncology’s dependence on third-parties in connection with its manufacturing, clinical trials and preclinical studies, and the potential impact of COVID-19 on our clinical and preclinical development timelines and results of operations. Additional risks and uncertainties that could affect Surface Oncology’s future results are included in the section titled “Risk Factors” in our Annual Report on Form 10-K for the year ending December 31, 2020, which is available on the Security and Exchange Commission’s website at www.sec.gov and Surface Oncology’s website at www.surfaceoncology.com.
Additional information on potential risks will be made available in other filings that Surface Oncology makes from time to time with the Securities and Exchange Commission. In addition, any forward-looking statements contained in this press release are based on assumptions that Surface Oncology believes to be reasonable as of this date. Except as required by law, Surface Oncology assumes no obligation to update these forward-looking statements, or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements.
Source: Surface Oncology, Inc.