April 18, 2023，Data of InnoCare’s robust oncology pipelines were presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting.

Oral Presentation:

ICP-490 is a highly potent and selective IKZF1/3 degrader with robust anti-tumor activities against multiple myeloma and non-Hodgkin’s lymphoma

Abstract Number: 3427

In various multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) tumor models, ICP-490 demonstrates superior tumor killing activities, including overcoming lenalidomide resistance. ICP-490 is now in phase I clinical trial.

Cell viability assays reveal robust in vitro efficacies of ICP-490 against various MM and NHL(including DLBCL) cell lines with nanomolar IC50. It also exhibits potent anti-proliferative activity in lenalidomide-resistant cell lines. In contrast to its tumor killing effect, ICP-490 shows no cytotoxicity against normal human cells. In vivo efficacy studies have further confirmed the effectiveness of ICP-490 against various MM and DLBCL xenografts.

The immune modulation activity of ICP-490 has also been illustrated in a combinatory treatment with monoclonal antibody, where low dose of ICP-490 leads to robust induction of IL-2 and granzyme B, and much improved efficacy of anti-CD38 mAbs in MM; in NHL, ICP-490 demonstrates synergistic tumor killing effects when combined with BTK inhibitor orelabrutinib.

ICP-490 has overall favorable pharmacokinetic parameters with high oral bioavailability.

Poster Presentation 1:

Combination of BTK inhibitor orelabrutinib, anti-CD19 antibody tafasitamab, and IMiD lenalidomide for the treatment of B cell malignancies

Abstract Number: 4013

R-CHOP has been widely recognized as effective first-line treatment for DLBCL. However, 30-50% of the patients are either refractory or eventually develop relapsed diseases (r/r DLBCL). Multiple clinical trials of orelabrutinib are being carried out for the treatment of DLBCL, including the first-line treatment of MCD subtype of DLBCL. An exploratory study to evaluate the safety and efficacy of orelabrutinib, tafasitamab and lenalidomide combinations in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL) is ongoing.

The highly selective BTK inhibitor orelabrutinib is a superior combinatory partner with antibody therapeutics whose mechanism of action is highly dependent on ADCC. Orelabrutinib is a highly selective BTK inhibitor with no inhibition effect on T cells, which confers its ability to enhance or retain the ADCC activity of tafasitamab. Combination of orelabrutinib with tafasitamab and/or lenalidomide also leads to synergistic tumor lysis activity, with or without the presence of immune effector cells. Confirmation of the synergistic effects of orelabrutinib with tafasitamab and lenalidomide in various preclinical models has provided scientific rationales for testing the combinatory treatment in clinical studies.

Poster Presentation 2:

Preclinical development of SHP2 allosteric inhibitor ICP-189

Abstract Number: 4012

ICP-189 is a novel allosteric inhibitor of SHP2 with broad-spectrum anti-tumor activities as a single agent or in combination with other targeted or immune modulating anti-cancer therapeutics. ICP-189 is now in phase I clinical trial in China and United States.

In a phosphatase profiling assay, ICP-189 efficiently inhibits the catalytic activity of SHP2, with no significant effects on 21 other tested tyrosine and serine/threonine phosphatases, indicating its high selectivity for SHP2. ICP-189 has demonstrated robust in vitro efficacies in a panel of tumor cell lines bearing activated RTK, RAS, NF1 loss-of-function, or BRAF class III mutations. It has also exhibited synergistic tumor killing effects in combination with EGFR, KRASG12C, MEK and CDK4/6 inhibitors.

The in vivo efficacy of ICP-189 is well accompanied by pharmacodynamic modulations, where ICP-189 exposure levels correlate with reduced p-ERK and DUSP6 mRNA levels in tumors.

The pharmacokinetic parameters of ICP-189 are overall favorable, with high oral bioavailability.

Detailed abstracts can be found at AACR official website.

About InnoCare

InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancer and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and United States.