On April 8, 2022 Orum Therapeutics, a private biotechnology company pioneering the development of tumor-directed targeted protein degraders (TPDs), reported that preclinical data for ORM-5029, a potential first-in-class TPD therapy for HER2-positive cancers, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting 2022 (Press release, Orum Therapeutics, APR 8, 2022, View Source [SID1234611750]). ORM-5029 is one of two lead programs from the company’s Antibody neoDegrader Conjugate (AnDC) platform based on its Dual-Precision Targeted Protein Degradation (TPD²) approach.
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ORM-5029 is designed to selectively deliver catalytic GSPT1 protein degraders to HER2-expressing tumor cells via antibody targeting. Orum developed a proprietary class of GSPT1 degrader molecules, paired them with a HER2-targeting antibody, pertuzumab, and screened numerous candidate conjugates to identify a molecule with the desired therapeutic profile. The data presented at AACR (Free AACR Whitepaper) 2022 describes initial preclinical evaluation of potency, efficacy, and pharmacodynamic (PD) response of ORM-5029.
"Targeted protein degradation holds much therapeutic promise, but classic TPD approaches face clinical development hurdles, including optimizing potency, exposure, and tolerability," said Peter U. Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. "We believe that we can fulfill the promise of TPD by developing novel small molecule degraders combined with the precise cellular delivery mechanism of antibodies. Compared to either small molecule GSPT1 degraders or standard-of-care antibody drug conjugates, ORM-5029 exhibited superior in vitro and in vivo potency, robust efficacy in low-HER2 settings, and dose-dependent efficacy. These data provide compelling evidence to support our unique approach to targeted protein degradation and continue development of ORM-5029."
Key data takeaways:
ORM-5029 displays robust efficacy both in vitro and in vivo compared to other small molecule GSPT1 degraders and approved antibody drug conjugates (ADCs)
ORM-5029 exhibits potent activity in HER2-low models both in vitro and in vivo
Dose-dependent efficacy of ORM-5029 correlates with robust and rapid PD modulation of tumor GSPT1 protein levels
Orum’s proprietary payload, SMol006, is a potent degrader with high selectivity for GSPT1 and is compatible with any ADC linker and conjugation technologies.
AACR 2022 is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans from April 8-13. The poster presentation titled, "ORM-5029: A first-in-class targeted protein degradation therapy using antibody neodegrader conjugate (AnDC) for HER2-expressing breast cancer," will be available for viewing to registered attendees from Friday, April 8, through Wednesday, July 13, on the AACR (Free AACR Whitepaper) Annual Meeting 2022 website. The poster (abstract # 3933) will be presented in person on April 13 from 9:00 am to 12:30 pm in Session PO.ET06.06 – Emerging New Anticancer Agents in Exhibit Halls D-H, Poster Section 22, Poster Number 7.
The poster is available on request; please email us at [email protected].
About Orum’s AnDC Platform
Orum’s Antibody neoDegrader Conjugate (AnDC) platform uses the Company’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders (TPD) combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class cell-specific TPD 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, neoDegraders are designed to be delivered specifically to cancer cells and degrade the intracellular target protein and cause tumor cell death.