Orum Therapeutics Unveils New Program at AACR 2023, Highlighting Cbl-b Inhibitor-PD-1 Conjugate, and Presents New Data Supporting Clinical Development of Two GSPT1 Programs Orum’s new program in immuno-oncology achieves simultaneous blockade of PD-1
19 Apr 2023
Phase 1AACRClinical Result
BOSTON, MA, USA & DAEJEON, South Korea I April 18, 2023 IOrum Therapeutics, a clinical-stage private biotechnology company pioneering cell-specific targeted protein degradation (TPD² ™) and targeted protein stabilization (TPS² ™), today announced new preclinical data for three of Orum’s therapeutic programs: ORM-5029, which is a proprietary GSPT1 degrader conjugated to HER2-targeting antibody pertuzumab; ORM-6151, which delivers GSPT1 degrader to CD33+ tumorsCD33+ tumors; and its new immuno-oncology program for a Cbl-b inhibitorCbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody pembrolizumab. The data were presented in three posters at the 2023 American Association for Cancer Research (AACR) Annual Meeting.
“We are pleased to present new data supporting clinical development of two programs from our TPD² GSPT1 Degrader Platform, which was developed to improve the therapeutic window and realize the full potential of GSPT1 degraders through precision delivery to cancer cells via antibody drug conjugates,” said Peter Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. “We are also excited to unveil at AACR our new TPS² platform, which has the potential to achieve the full promise of Cbl-b inhibitorsCbl-b inhibitors through T cell-specific delivery. With this novel approach, we show that we can limit unwanted systemic exposure, including the risk of toxicity associated with c-Cbl inhibition, prolong the activation of exhausted PD-1+ T cells, and provide resistance to negative environmental cues such as TGF-β or regulatory T cells. We believe our approach of harnessing the power of protein degraders and stabilizers with the precision of antibody targeting will improve the treatment of cancer for more patients.”
Details of the data presented are as follows:
Title: A novel antibody-enabled Dual-precision Targeted Protein Stabilization (TPS²) that augments anti-tumor immune response by targeting Cbl-b inhibitor to exhausted T cells while blocking checkpoint molecule, PD-1
Presenter: Joanne Lim, Ph.D.
Abstract Number: 4436
Summary: Cbl-b inhibition results in stabilization of intracellular proteins downstream of the T cell activation pathways. Using a murine model well-established to be refractory to anti-PD-1 antibodyPD-1 antibody treatment, we demonstrated that anti-PD-1-Cbl-b inhibitor approach increased effector T cell markers in the tumor and delayed tumor growth.
Presented Data:
Title: ORM-6151: A first-in-class CD33-antibody enabled GSPT1 degrader for AML
Presenter: James Palacino, Ph.D.
Abstract Number: 2700
Summary: ORM-6151 shows robust single-dose efficacy, both in vitro and in vivo with superiority or comparability to standard of care (SOC) agents. In addition, in vitro testing demonstrated superior tolerability to healthy bone marrow progenitor cells, suggesting better tolerability. Responses in representative TP53 wild-type and mutant AML models demonstrated comparable activity, indicating the potential for responses in a large percentage of AML patients with poor treatment options.
Presented Data:
Title: Development of RNAscope multiplex-based assay for exploratory pharmacodynamic biomarkers assessment in breast cancer patients from Phase I clinical trial of ORM-5029, a potent GSPT1 degrader
Presenter: Shikha Saini, Ph.D.
Abstract Number: 2118
Summary: To fulfill the need to develop pharmacodynamic biomarkers as predictors of efficacy to support clinical development of ORM-5029, Orum identified a novel GSPT1 antibody for detection of depletion following treatment with ORM-5029. GSPT1 depletion and subsequent activation of the integrated stress response are both seen following in vitro or in vivo treatment with ORM-5029. Degree of pharmacodynamic (PD) change correlates with depth and duration of in vivo response. Orum is currently developing a multiplexed (IF/ISH/ISH) assay to track PD responses in patients, with an aim to better predict responses and efficacious doses.
Presented Data:
The posters are available to download through the links below:
PD-1-Cbl-bi TPS² preclinical poster: https://docsend.com/view/enn7dddfbbn74sr2
ORM-6151 preclinical poster: https://docsend.com/view/gkrqtx49dwmthe28
ORM-5029 predictive biomarker poster: https://docsend.com/view/dqym6ks36t73qz7k
About Orum’s TPS² Approach
Orum’s Dual-precision Targeted Protein Stabilization (TPS²) approach combines novel payloads with the precise cell delivery mechanism of antibodies to increase the levels of intracellular target proteins in a cell-type-specific manner for oncology and immuno-oncology. The first program applying the TPS² approach is a Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody. By delivering Cbl-bi specifically to exhausted T cells, the conjugate is designed to restore effector T cell function, where PD-1 checkpoint blockade alone is insufficient, while also enabling T cells to overcome the immunosuppressive mechanisms in a tumor microenvironment.
About Orum’s GSPT1 Platform Using the TPD² Approach
Orum’s GSPT1 platform uses the company’s unique Dual-precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class, cell-specific TPDs for the treatment of cancer. Orum has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to cancer cells and degrade the intracellular target protein GSPT1 and cause tumor cell death.
About Orum Therapeutics
Orum Therapeutics is a private, clinical-stage biotech pioneering the development of tumor-directed targeted protein degraders (TPD²) and stabilizers (TPS²) with the precision of antibody targeting to improve cancer treatment for more patients. The first therapeutic candidates from the TPD² GSPT1 platform, ORM-5029 and ORM-6151, are in clinical development for the treatment of solid tumors and hematologic cancers, respectively. The first program applying the TPS² approach is a Cbl-b inhibitorCbl-b inhibitor conjugated to anti-PD-1 antibody. Orum is located in Boston, US, and Daejeon, South Korea. For more info, visit www.orumrx.com.
SOURCE: Orum Therapeutics
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