InMune Bio Announces Clinical and Preclinical Data for Two Novel Drug Candidates, HPK1 Inhibitor PRJ1-3024 and Cbl-b Inhibitor YF550-C1, at ASCO 2024

May 30, 2024 10:40 CST Updated 10:40

MingMed

Innovative Drug Developer

▎WuXi AppTec Content Team Report

On May 29, MingMed announced that its subsidiary, Xi'an Yufan Biotechnology Co., Ltd., will present a poster at the ASCO Annual Meeting to be held in the United States from May 31 to June 4, 2024.Phase 1 Clinical Data in China for HPK1 Small Molecule Inhibitor PRJ1-3024andPreclinical Data of Cbl-b Small Molecule Inhibitor YF550-C1。

HPK1 (Hematopoietic Progenitor Kinase 1), located upstream of the PD1 pathway, is a key kinase expressed in immune cells. It negatively regulates the functions of various immune cells through feedback and also controls the expression of PD-1 in T cells, making it a potential next target for immunotherapy.PRJ1-3024 is one of the HPK1 inhibitors that entered clinical stage relatively early., which entered the Phase 1 clinical trial stage in the United States and China in November 2021 and February 2022, respectively, to evaluate the safety, tolerability, preliminary efficacy, and pharmacokinetic data of PRJ1-3024 for the treatment of advanced solid tumors.MingMed announced the relevant data of the Phase 1 clinical trial in the United States for PRJ1-3024 at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2023) in November 2023.

The results of the Phase 1 clinical trial in China announced at the ASCO Annual Meeting included dose groups of 80mg, 160mg, 300mg, 320mg, 500mg, and 700mg.A total of 30 patients with advanced solid tumors (the majority of whom had received PD-1 treatment)The LatestNumberAccording to, The results showed:

As of May 15, 2024,A subject with acral melanoma who has received more than 11 months of treatment achieved sustainedPartial Remission (PR）, and treatment is still ongoing.; All target lesions of the patient have reached clinical recovery, one of the two non-target lesions has disappeared, and the other pathological lymph node lesion is continuously shrinking, with the hope of further achieving clinical recovery of all lesions in subsequent treatments.Four additional subjects achieved stable disease (SD)., including one case of non-small cell lung cancer, one case of squamous cell carcinoma of the head and neck, and two cases of triple-negative breast cancer participants.
In the PRJ1-3024 monotherapy dose escalation study, among the 30 subjects enrolled, no dose-limiting toxicity events were reported, and no irAEs or treatment-related deaths occurred in any of the dose groups.PRJ1-3024With good safety, tolerability, preliminary efficacy, and pharmacokinetic properties。
Preliminary pharmacokinetic results suggest that within the dose range of 300-500mg once daily (QD), the plasma concentration can reach therapeutic levels and maintain a steady state; among two acral melanoma patients with clinical benefit, one has been confirmed as PR in subsequent CT scans.

In addition, at this ASCO meeting,Yufan Biotechnology will also present its research data on the Cbl-b inhibitor YF550-C1.Casitas B-lineage lymphoma b (Cbl-b) is one of the ligases in the E3 ubiquitin family, primarily expressed in mature hematopoietic cells, including T cells and NK cells. Even without the co-stimulation of CD28, knocking out Cbl-b will upregulate the secretion of IL-2 and IFN-γ during TCR activation. In addition to T cells, Cbl-b also plays an important role in NK cells.

Preclinical in vivo studies have shown that:

Knocking out Cbl-b promotes cytokine release, enhances T cell activation, strengthens the killing ability of T cells and NK cells, and inhibits tumor growth in mice.
YF550-C1 demonstrated robust T cell activation, alleviation of T cell immunosuppression, NK cell activation, and exhibited anti-tumor activity in multiple preclinical tumor models.
YF550-C1 is a clinical candidate compound,Can be used as a single therapy or in combination with PD-1/PD-L1 antibodies in tumor immunotherapy.。

References:

[1]2024 ASCO丨MingMed to Present Clinical Data of HPK1 Inhibitor PRJ1-3024 and Preclinical Data of Cbl-b Inhibitor. Retrieved May 29, 2024. From https://mp.weixin.qq.com/s/PFB7p-Wrcpkv2hJmrAR5SA

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