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<span class="legendSpanClass">New data highlights the potential of neoantigen-producing ERAP1 inhibitors to drive differentiated T cell responses, leading to tumor growth suppression</span>
<span class="legendSpanClass">The proprietary new antigen generation technology platform represents a potential new pillar of tumor therapy</span>
Oxford, United Kingdom, November 12, 2021 /PRNewswire/ - The biotechnology company Gray Wolf Therapeutics pioneered the use of new targeted neoantigen generation-driven immuno-oncology new treatments and today announced the company’s promising preclinical In vivo data at the 36th Annual Meeting of the Society for Cancer Immunotherapy (SITC) is a leading ERAP1 inhibitor. At the SITC meeting held in November, the results were featured in a poster presentation (#553) titled "ERAP1's first-class inhibitors change the cancer immune peptide group, drive differentiated T cell response leading to tumor growth inhibition" October 2021 On the 14th in Washington, DC, and virtual.
Gray Wolf Therapeutics' first immuno-oncology method focuses on significantly increasing the visibility of tumors so that the body's immune system can recognize and destroy them. This is achieved by targeted inhibition of endoplasmic reticulum aminopeptidase (ERAP1 and ERAP2), which leads to the production and presentation of new antigens to the surface of tumor cells. The appearance of these new antigens lifted the veil of tumor cells, illuminated them for the immune system, and initiated a powerful, differentiated T cell response against tumors. Importantly, this unique approach is orthogonal to a wide range of other cancer treatments, including but not limited to immunotherapy.
The findings announced at the SITC meeting provided convincing evidence for several key elements of the company's hypothesis that ERAP1 inhibits the treatment of cancer. These include the company's ERAP1 inhibitor's ability to drive neoantigen production, differentiated T cell responses, and tumor growth inhibition.
The main highlights of the company introduction include:
The researchers emphasized the results of the study, demonstrating that ERAP1 inhibition triggers the definite production of new antigens in vitro and in vivo, as well as increased expression of existing new antigens, which are present in various species, cell types, and genetic backgrounds. For example, targeted ERAP1 inhibition in the HCT116 colorectal cancer cell line resulted in increased surface expression of key cancer antigens including MAGE3 and PBK, as well as the production of completely new neoantigens (ATAD2) in the tumor. It is believed that the production of this new antigen makes the tumor more visible to the immune system, thereby generating the required differentiated T cell response.
The presented findings highlight three different data sets that support the ability of ERAP1 to inhibit the T cell response that drives differentiation.
First, the results showed that in the CT26 tumor model, after treatment with ERAP1 inhibitors and anti-PD-1 antibodies, T cell receptor (TCR) diversity increased significantly over a series of time points. Second, the data showed that in the CT26 model, the combination of an ERAP1 inhibitor and anti-PD-1 resulted in a significant increase in T cell infiltration into the tumor and an increase in granzyme in the tumor. Finally, the treatment combination resulted in a significant increase in a broad range of translation-related immune markers that have been shown to be related to the patient's response to anti-PD-1 therapy, including CXCL9, CXCL10, IFNg, and IL-7R.
It is important to note that this effect on immune markers is tumor-specific because it is only observed inside the tumor, not at the periphery, indicating that ERAP1 inhibition is driving a new, cancer-specific reaction.
The ability of ERAP1 to inhibit T cell responses that drive neoantigen production and subsequent differentiation has a meaningful impact on tumor growth. The presented research results show that compared with the carrier, multiple homologous mouse models have obvious tumor growth inhibitory effects and improved overall survival rates after the combined treatment of ERAP1 inhibitors and anti-PD-1 antibodies. It is worth noting that in the CT26 syngeneic mouse model, every discovery that proves that differentiated T cell responses (that is, changes in TCR repertoire, T cell infiltration, and up-regulation of translation-related immune markers) are related to tumor growth inhibition, which is new Anti-tumor growth driven by antigen production provides convincing evidence. -Tumor response.
"All of these data provide convincing support for our belief that the production of new neoantigens through targeted inhibition of ERAP1 represents a promising new approach in the field of oncology drug development. Although we have previously shown us The potential of ERAP1 inhibitors to generate new antigens that drive the anti-tumor response, and these new data provided today clearly show that the anti-tumor response is due to a new and differentiated T cell response,” said Peter Joyce, PhD, CEO of Gray Wolf Therapeutics Said. "Although these promising results have been achieved by combining our ERAP1 inhibitors with anti-PD-1 antibodies, it is important to note that we believe our unique approach will be orthogonal to a wide range of other cancer treatments, Including, but not limited to, immunotherapy. Based on these data, we continue to advance our main ERAP1 inhibitor drug candidates through preclinical development, with the goal of entering the clinic in the second half of 2022."
Gray Wolf Therapeutics is developing a series of ERAP inhibitors, which it believes represents the first application of direct neoantigen generation in cancer treatment. GRWD5769 is the company's main ERAP1 inhibitor development candidate and is expected to enter the clinic in the second half of 2022.
Gray Wolf Therapeutics is a UK-based drug discovery biotechnology company that pioneered a new immuno-oncology therapy driven by targeted neoantigen generation. The company's first immuno-oncology method focuses on significantly increasing the visibility of tumors so that the human immune system can recognize and destroy them. Based on this approach, the company is developing a series of first-class small molecules that inhibit endoplasmic reticulum aminopeptidase (ERAP1 and ERAP2) and play a key role in the antigen presentation pathway. The company's main development candidate drug GRWD5769 is an ERAP1 inhibitor, which is expected to enter the clinic in the second half of 2022. The second project focused on ERAP2 inhibition is advancing preclinical development through early detection work.
For more information, please visit: www.greywolftherapeutics.com
Contact: Gray Wolf Therapeutics Peter Joyce CEO 44 (0) 01865 292 038 enquiries@gwt.bio
Vida Strategic Partner (Representing Gray Wolf Therapeutics) Tim Brons (Media) 415-675-7402 tbrons@vidasp.com
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