OTX-2002 Receives Orphan Drug Designation From the FDA for HCC

Patients with hepatocellular carcinoma may benefit from treatment with OTX-2002, a first-in-class epigenomic controller designed to downregulate c-Myc that recently received orphan drug designation from the FDA

The FDA has given orphan drug designation to OTX-2002 for the treatment of patients with hepatocellular carcinoma (HCC), according to a press release from Omega Therapeutics.

The safety, tolerability, and preliminary antitumor activity of the first-in-class epigenomic controller that was designed to downregulate c-Myc (MYC) is currently being assessed as part of the phase 1/2 MYCHELANGELO 1 trial (NCT05497453). OTX-2002 will be evaluated as both a single agent and in combination with other standard of care therapies in a population of patients with relapsed/refractory HCC and other solid malignancies associated with the MYC oncogene. The first patient on the trial was recently dosed.

“HCC is a devastating illness that often develops resistance to current standard of care therapeutics. The FDA’s decision to grant orphan drug designation for OTX-2002 underscores the need for novel therapies to address HCC and the potential of epigenomic programming to transform the treatment landscape,” Mahesh Karande, president and chief executive officer at Omega Therapeutics, said in the press release. “We look forward to continuing to work with clinical investigators, patients, and the FDA as we advance our MYCHELANGELO clinical program and evaluate the potential of OTX-2002 to bring a new treatment option to the liver cancer patient community.”

mRNA product OTX-2002 is delivered through lipid nanoparticles and downregulates MYC expression pre-transcriptionally by epigenetic modulation and simultaneously circumventing autoregulation.

The study has an estimated enrollment of 190 patients who will receive either OTX-2002 monotherapy, OTX-2002 plus a tyrosine kinase inhibitor, or OTX-2002 plus a checkpoint inhibitor. Primary end points for the trial include dose-limiting toxicities, incidence of treatment-emergent adverse effects, overall response rate, and duration of response.

The trial will include patients with metastatic, advanced, or recurrent solid malignancies who have relapsed on or after or are refractory to standard of care therapies. Patients are required to have Barcelona Clinic Liver Cancer stage B or C, Child-Pugh A disease and be ineligible for or refractory to locoregional therapy. Moreover, patients needed to be 18 years or older. Those with chronic hepatitis B were required to have been treated with antiviral therapy 12 weeks prior to enrolling. An ECOG performance status of 0 or 1 was also required.

Those who have mixed histology cholangiocarcinoma and HCC or a fibrolamellar HCC variant are not eligible to enroll. Other exclusion criteria include having 50% or higher liver occupation, clear bile duct invasion, portal vein invasion with Vp4, active or untreated central nervous system metastases, a history of ascites requiring paracentesis within 3 months, esophageal or gastric variceal bleeding in the last 3 months, or hepatic encephalopathy within 3 months.


Omega Therapeutics receives orphan drug designation for OTX-2002 for the treatment of hepatocellular carcinoma. News release. Omega Therapeutics. November 2, 2022. Accessed November 2, 2022. http://bit.ly/3fqiafd