Orum Therapeutics discloses preclinical results of AML drug candidate at ASH

Orum Therapeutics said on Monday that its acute myeloid (AML) drug candidate, ORM-6151, demonstrated superior safety and efficacy compared to competing drugs in preclinical trials, at the American Society of Hematology (ASH) in New Orleans, the U.S.

ORM-6151 is the second candidate material to utilize Orum's dual-precision targeted protein degradation (TPD2) platform. It combines an antibody targeting the over-expressed CD33 antigen on the surface of cancer cells with a G1 To S Phase Transition 1 (GSPT1) protein-coding gene.

This novel candidate drug combines a catalytic mechanism of TPD with an antibody that selectively treats undruggable target proteins in cancer cells, according to the company.

The preclinical study showed the drug candidate’s superior safety and efficacy at clinically equivalent doses in CD33 expression cell lines and patient-derived AML cells compared to GSPT1 degrader molecule CC-90009 and Pfizer’s AML treatment, Mylotarg (ingredient: gemtuzumab ozogamicin).

Additionally, mouse experiments showed strong tumor growth inhibition after a single treatment of ORM-6151 with a dose as low as 1 mg/kg compared to competitor candidate substances. ORM-6151 also showed strong activity in Mylotarg-resistant cell lines and minimal cytotoxic activity compared to CC-90009 or Mylotarg in healthy hematopoietic stem cells.

According to the American Cancer Society, there were more than 20,000 new AML patients in the United States as of 2022, and more than half of them have died.

Currently, the most widely used treatment is Abbvie's Venclexta (venetoclax) which gives patients aged 75 or older, an overall survival rate of 15 months or less. Besides this, Pfizer's FDA-approved Mylotarg also targets CD33 expressed in more than 90 percent of AML patients but is limited due to safety concerns. Meanwhile, Bristol Myers Squibb (BMS) has ongoing clinical trials for its novel E3 ligase modulator CC-90009 but the demand is still high for alternative treatments.

"The data shows that our TPD² platform technology can broaden the therapeutic index of targeted proteolytic agents," said Peter U. Park, Chief Scientific Officer of Orum Therapeutics. "We will strive to continue providing clinically effective treatment options for AML patients."

Consequently, Orum said they plan to apply for an Investigational New Drug (IND) to the U.S. FDA in the first half of next year.