SG-3-06686 / Second Genome - LARVOL DELTA

Preclinical evaluation of SG-3-06686, a positive allosteric modulator of CXCR3 (ESMO 2022) - "Conclusions CXCR3 pathway modulation is a well validated and exciting immunotherapy approach to potentially enhance effector cell recruitment and amplify anti-tumor activity. Additionally, CXCR3 ligands CXCL9 and CXL10 are upregulated in response to certain established cancer treatments such as radiotherapy and chemotherapy and contribute to their efficacy, providing a strong rationale for combination strategy with SG-3-06686."

Preclinical • Oncology • CD4 • CD8 • CXCL9 • CXCR3

Targeting the CXCR3 pathway with a novel peptide drug candidate mobilizes the immune system to enhance anti-tumor immunity (AACR 2022) - "The CXCR3 chemokine system is instrumental in effector cell recruitment to the tumor and augments intratumoral CD8+ T cell proliferation and function, which are key mechanisms driving anti-tumor immunity and responses to ICI therapy.We used our proprietary peptide discovery platform to identify a unique microbiome-derived peptide, SG-3-00802, from bacterial strains associated with response to anti-PD1 inhibitors in patients with melanoma...Supporting this concept, we demonstrated that SG-3-00802DC showed anti-tumor activity in pre-clinical mouse tumor models, alone and in combination with anti-PD-1, improved overall survival and increased recruitment of CXCR3+ effector cells into the tumor microenvironment.Numerous strategies are currently undergoing clinical evaluation to improve long-lasting disease control in broader patient populations by combining ICIs with approved and novel therapeutic agents and procedures. SG-3-00802DC, with its well validated and unique..."

Melanoma • Oncology • Solid Tumor • CD8 • CXCL10 • CXCL11 • CXCL9 • CXCR3

Second Genome Presents New Preclinical Data at AACR 2022 Demonstrating that SG-3-06686, a CXCR3 Chemokine Receptor Modulator, Induces Migration of Immune Effector Cells, Inhibits Tumor Growth as Monotherapy and Boosts Anti-Programmed Death Protein-1 (PD-1) Activity (PRNewswire) - "'We look forward to submitting an investigational new drug (IND) application for SG-3-06686, a potential first in class CXCR3 immune modulator, in early 2023'...SG-3-06686 is a potent CXCR3 chemokine receptor engager that acts as a positive allosteric modulator to increase receptor activity to the three known ligands (CXCL9/10/11). It has demonstrated to increase the activity of CXCL11 on CXCR3 activation by greater than 10-fold from a nM to a pM range with similar effects on CXCL9 and CXCL10. This activity in turn drives strong antitumor activity in several preclinical cancer models."

IND • Preclinical • Oncology

A novel microbiome-derived peptide reverses resistance to anti-PD-1 therapy (SITC 2021) - "Microbiome-derived peptides identified by Second Genome’s discovery platform sg4sight modulate innate immune cells e.g. dendritic cells to promote anti-tumor immunity. SG-3-00802 peptide has the greatest potential to impact subjects who are potentially going to be non-responders to anti-PD-1 or have derived inadequate response to ICI therapies."

Oncology • CXCL10 • TNFA

Second Genome Presents Preclinical Data at SITC 2021 Demonstrating that a CXCR3-Positive Allosteric Modulator, SG-3-00802, Targets a Key Mechanism Required for Efficacious Immunotherapy (PRNewswire) - " Second Genome...presented preclinical data demonstrating that the Company's CXCR3-positive allosteric modulator, SG-3-00802, can reverse resistance to anti-programmed death protein-1 (PD-1) therapy, illustrating that the microbiome directly interacts with the human immune system to enhance immunity and impact antitumor activity. The data (E-Poster #569) were presented at the Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting, held virtually and in Washington, D.C. November 10-14."

Preclinical • Oncology

[VIRTUAL] A novel microbiome-derived peptide, SG-3-00802 reverses resistance to anti-programmed death protein-1 (PD-1) therapy (ESMO 2021) - "In summary, we showed that the microbiome directly interacts with the human immune system to impact antitumor immunity. SG-3-00802 shows great potential to improve responses in ICI-resistant patients and potentially acts as a CXCR3 receptor sensitizer by increasing CXCR3 activation in response to its ligands CXCL9/10/11, leading to recruitment of effector cells to mount a robust immune response."

Oncology • CCR7 • CD8 • CXCL10 • CXCL11 • CXCL9 • CXCR3 • CXCR4 • IFNG • IL12A

Second Genome Presents Preclinical Data at ESMO 2021 Demonstrating that a Novel Microbiome-Derived Peptide, SG-3-00802, Reverses Resistance to Anti-Programmed Death Protein-1 (PD-1) Therapy (PRNewswire) - “’We look forward to advancing SG-3-00802 into the clinic, with an IND submission on track for 2022’…The mechanism of action by which SG-3-00802 exerted its anti-tumor effects demonstrated to be CXCR3 dependent. Receptor activation and immune cell recruitment assays demonstrated that SG-3-00802 enhanced the activity of CXCR3 in the presence of its endogenous ligands, resulting in increased lymphocyte migration, validating CXCR3 as the functional target. These observations were confirmed in vivo, as CXCR3 inhibition decreased the anti-tumor activity of SG-3-00802 alone and in combination with anti-PD1.”

IND • Preclinical • Oncology