On March 22, 2022 Tollys, a biopharmaceutical company developing TL-532, the first anti-cancer immunotherapy based on a new generation of synthetic toll-like receptor 3 (TLR3) specific agonist, reported that it will release the latest preclinical developments of TL-532 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Tollys, MAR 22, 2022, View Source [SID1234610532]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The preclinical data included in the poster identified TL-532 as the spearhead of a new rationally designed TLR3-agonist family. In monotherapy, it demonstrated substantial tolerance and promising anti-cancer and auto-vaccinal activity, which included unrelated cancers. TL-532 also demonstrated its remarkable ability to overcome Immune Checkpoint Inhibitor (ICI) tumorresistance, thus increasing the clinical landscape for ICI combination treatment.

Further key highlights from the poster, titled ‘The specific TLR3-agonist TL-532 induces lifelong anti-tumor auto-vaccination, cross-immunity against unrelated cancers and reverses resistance to immune checkpoint inhibitors’:

 In vivo activity of TL-532 led to substantial tumor growth inhibition (88%) and delay (370%), translating into 35% Complete Response (CR) rate and 5.3-fold median survival benefit
 Interestingly, among these CRs, 62% (13/21) showed life-long tumor auto-vaccination after three consecutive rechallenges at 3, 10 and 30 months
 Remarkably, 54% (6/11) of the mice autovaccinated against bladder cancer also demonstrated cross-immunity against an unrelated and poorly immunogenic, syngeneic osteosarcoma cancer cell model (LM8)
 TL-532 treatment appeared to decrease the expression of the immune checkpoint PD-L1 on tumor cells ex-vivo and in cDCs in vivo and demonstrated a remarkable ability to reverse the anti-PD-L1 tumor-resistance when combined with the ICI leading to doubling of CR rate
 Ex vivo and in vivo, the tumor cell death by apoptosis induced by TL-532 was associated with a tumor microenvironment switch, evidenced by increases in antitumor biomarker secretion (IFN-α, IFN-λ1, IFN-γ, CCL5, CXCL9, CXCL10, CX3CL10), decreases in protumor biomarkers CCL22 and sFAS, and was associated in vivo with the recruitment and activation of conventional Dendritic Cells (cDCs) and Cytotoxic T-Lymphocytes (CTLs) at the tumor site.

Abstract title: ‘The specific TLR3-agonist TL-532 induces life-long anti-tumor autovaccination, cross-immunity against unrelated cancers and reverses resistance to immune checkpoint inhibitors’ Authors: Marc Bonnin, Saïd Ourfali, Mathilde Boucard-Jourdin, Clémence Perret, Chloé Renoux, Nelly Vey, Marc Colombel, Bettina Werlé, Sylvain Thierry. Tollys SAS, Lyon, France, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
Session category: Immunology Session title: Inflammation, Immunity and Cancer
Session date and Time: Tuesday Apr 11, 2022, 1:30 PM-5:00 PM
Location: New Orleans Convention Center, Exhibition Halls D-H, Poster Section 39
Poster board number: 2
Abstract number: 2085

The complete abstract can be accessed on the AACR (Free AACR Whitepaper) annual meeting website.

About TL-532
TL-532 is the first synthetic specific TLR3 agonist with a proprietary defined doublestranded RNA sequence. As such, TL-532 has the potential to be the best-in-class and firstto-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells-not in normal cells-, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) a switch of the tumor microenvironment by producing cytokines and chemokines which are unfavorable to tumor development. The result is the immunogenic cell death of tumor cells, accompanied by an auto-vaccination preventing the recurrence of cancer