On December 10, 2022 -Orum Therapeutics, a private biotechnology company pioneering the development of tumor-directed targeted protein degraders (TPDs), reported the presentation of positive preclinical data for ORM-6151, a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for acute myeloid leukemia (AML), at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2022) Annual Meeting & Exposition taking place December 10-13 in New Orleans and virtually (Press release, Orum Therapeutics, DEC 10, 2022, View Source [SID1234625062]). ORM-6151 is the second drug candidate from Orum’s Dual-Precision Targeted Protein Degradation (TPD2 TM) approach, which combines the catalytic mechanism of TPDs with the precision of tumor-targeting therapeutic antibodies.
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"These data demonstrate we can increase the therapeutic index to improve the efficacy and tolerability of targeted protein degrader therapies with our ‘TPD-squared’ approach"
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The data show that ORM-6151 has picomolar potency and efficacy superior to clinically equivalent doses of CC-90009, a small-molecule GSPT1 degrader, or Mylotarg, an FDA-approved treatment for AML, in CD33-expressing cell lines and primary relapsed/refractory AML patient blasts. In a clinically relevant animal model of AML, a single treatment of ORM-6151 at doses as low as 1 mg/kg, compared to a clinically equivalent dose of CC-90009, demonstrated superior tumor growth inhibition and correlated with the degree and duration of GSPT1 depletion. ORM-6151 also had robust activity in Mylotarg-resistant cell lines and exhibited minimal cytotoxic activity to healthy hematopoietic progenitor cells compared to CC-90009 or Mylotarg.
"These data demonstrate we can increase the therapeutic index to improve the efficacy and tolerability of targeted protein degrader therapies with our ‘TPD-squared’ approach," said Peter U. Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. "We believe that ORM-6151 via targeted tumor delivery has the potential to provide an improved therapeutic option in AML that appropriately balances efficacy with safety and tolerability of a clinically validated GSPT1 degradation mechanism. We look forward to continuing development of ORM-6151 with a goal of filing an Investigational New Drug application in the first half of 2023."
The poster can be viewed in the poster hall and via the virtual meeting platform for registered attendees. Details of the presentation are as follows, and the abstract can be viewed by clicking here.
Title: ORM-6151: A First-in-Class, Anti-CD33 Antibody-Enabled GSPT1 Degrader for AML
Publication Number: 1319
Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster I
Session Date: Saturday, December 10
Presentation Time: 5:30 PM to 7:30 PM CST
Location: Ernest N. Morial Convention Center, Hall D
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. The company 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.