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Lyvgen Announces First in Human Dosing of LVGN7409 CD40 Agonist Monoclonal Antibody in a Phase 1 Clinical Trial for the Treatment of Advanced or Metastatic Malignancy in the US

January 26, 2021
Lyvgen, a clinical-stage biotechnology company, today announced first-in-human (FIH) dosing of its xLinkAb product LVGN7409 (CD40 agonist), a bi-functional monoclonal antibody optimally activating CD40 upon FcγRIIB-mediated cross-linking.
“LVGN7409 is Lyvgen wholly owned product candidate and a potential best-in-class agonist for CD40, an attractive IO target studied clinically for nearly sixteen years,” said Jieyi Wang, Ph.D., Chief Executive Officer of Lyvgen. “In preclinical studies, LVGN7409 demonstrated superior anti-tumor activity and safety as compared to other clinical CD40-targeted antibodies. Based on its bi-functional design to leverage FcγRIIB enriched in tumor microenvironment and the excellent preclinical activity and safety profile, we expect to achieve a larger therapeutic window of LVGN7409 in the clinic and believe it offers a promising option for patients who do not respond well to PD-1 based therapies.”
This is an open-label, non-randomized, two-stage, FIH Phase 1 study, utilizing an accelerated dose escalation followed by a traditional 3 + 3 dose escalation algorithm to identify the recommended phase 2 dose of LVGN7409 as a single agent (monotherapy) and in combination with anti-PD-1 antibody and/or CD137 agonist. Initial clinical data from the trial are expected in the second half of 2021. In addition, Lyvgen plans to explore biomarkers and evaluate LVGN7409 in combination with other therapeutic agents in specific cancers.

Encouraging progress of targeting CD40 as cancer treatment leads to LVGN7409
A substantial body of evidence in humans and animals indicates that activating CD40 have the potential to be an important therapeutic option for converting tumor from “cold” to “hot” and as a promising IO treatment especially for non-inflamed immune desert tumors.[1-10]
Besides LVGN7409, there are other clinically studied CD40 agonist candidates including Selicrelumab (ROCHE), APX005M (Apexigen), YH003 (Eucure Biopharma), Mitazalimab (Alligator Bioscience), CDX1140 (Celldex Therapeutics Inc), SL172154 (Shattuck Labs), GEN1042 (Genmab), ABBV927 (AbbVie), and the preclinical stage candidates such as MP0317 (Molecular Partners AG). 
Despite the recognized promise of anti-CD40-agonist therapy, some of the anti-CD40 mAbs were limited because of their toxicity or low activity.

About LVGN7409
LVGN7409 is xLinkAb anti-CD40 agonist mAb that has been designed to activate CD40 optimally in tumor microenvironment by targeting both CD40 and FcγRIIB. LVGN7409 strikes a balance between antitumor efficacy and safety by agonizing CD40 only in the presence of FcγRIIB, which is expressed on immune cells enriched in the tumor microenvironment, including B cells, dendritic cells and granulocytes.

About Lyvgen
Lyvgen is a biopharmaceutical company focused on developing innovative immuno-oncology therapeutics. Lyvgen uses its xLinkAb™ platform to generate IgG agonist antibodies targeting co-stimulatory receptors with selectivity for tumor microenvironment. Lyvgen’s most advanced programs include LVGN7409 and LVGN6051, a third generation CD137(4-1BB) agonist antibody, in combination with KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy, in a Phase 1 study in adult patients with advanced malignancy including lung cancer, melanoma, gastrointestinal cancer with MSI-high or DMMR, and lymphoma.

Contact
Luyan Liu
BD Director
Lyvgen Biopharma
Luyan.liu@lyvgen.com

Reference
1. Richards, D.M., et al., Concepts for agonistic targeting of CD40 in immuno-oncology. Hum Vaccin Immunother, 2020. 16(2): p. 377-387.
2. Tang, T., et al., Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint. Pharmacol Ther, 2020: p. 107709.
3. Vonderheide, R.H., CD40 Agonist Antibodies in Cancer Immunotherapy. Annu Rev Med, 2020. 71: p. 47-58.
4. Bajor, D.L., et al., Immune activation and a 9-year ongoing complete remission following CD40 antibody therapy and metastasectomy in a patient with metastatic melanoma. Cancer Immunol Res, 2014. 2(11): p. 1051-8.
5. O'Hara, M.H., et al., CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol, 2021. 22(1): p. 118-131.
6. Morrison, A.H., et al., Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity. Proc Natl Acad Sci U S A, 2020. 117(14): p. 8022-8031.
7. Diggs, L.P., et al., CD40-mediated immune cell activation enhances response to anti-PD1 in murine intrahepatic cholangiocarcinoma. J Hepatol, 2020.
8. Baumann, D. and R. Offringa, Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy. Cell Stress, 2020. 4(10): p. 248-251.
9. Ma, H.S., et al., A CD40 Agonist and PD-1 Antagonist Antibody Reprogram the Microenvironment of Nonimmunogenic Tumors to Allow T-cell-Mediated Anticancer Activity. Cancer Immunol Res, 2019. 7(3): p. 428-442.
10. Vonderheide, R.H., The Immune Revolution: A Case for Priming, Not Checkpoint. Cancer Cell, 2018. 33(4): p. 563-569.

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