FDA’s Orphan Drug Status Granted to LNS8801 for Metastatic Uveal Melanoma

The FDA granted Orphan Drug Designation to the novel GPER agonist, LNS8801, for the treatment of patients with metastatic uveal melanoma.

The FDA granted Orphan Drug Designation to the novel GPER agonist, LNS8801, for the treatment of patients with metastatic uveal melanoma, according to a press release issued by Linnaeus Therapeutics, Inc.

"We are extremely pleased to have received Orphan Drug Designation for metastatic uveal melanoma from the FDA. This is an important milestone that has emerged from the very promising data we have seen in patients with metastatic uveal melanoma during dose escalation," commented Patrick Mooney, MD, chief executive officer of Linnaeus, in a statement

The use of LNS8801 as treatment of metastatic uveal melanoma is being explored in a phase 1/2 adaptive-design clinical trial (NCT04130516). The dose-escalation portion of the trial was recently completed. The study followed a 3+3 design aiming to determine both the maximum-tolerated dose and the recommended phase 2 dose of LNS8801. The study protocol also allows for pharmacokinetics and pharmacodynamics to be further evaluated in 8 to 10 patients.

In the study, LNS8801 is evaluated as monotherapy and in combination with the monoclonal antibody pembrolizumab (Keytruda) in patients who had previous clinical benefit from immune checkpoint inhibitors but then experienced disease progression.

Patients were eligible to enroll in the dose-escalation phase if they have histopathologically confirmed that was measurable per RECIST v1.1 criteria. All patients were required to be at least 18 years of age with an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ and bone marrow function.

Thus far, treated with LNS8801 in the first-in-human, multicenter study has been safe and well-tolerated by patients. Although early on in the course of the study, the agent has already shown target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancer. Based on the study signals, the company plan to include 2 additional cohorts of patients with metastatic uveal melanoma to test both LNS8801 and the agent in combination with pembrolizumab. The company also plans to present the phase 1/2 results in a peer-reviewed setting sometime in 2021.

Research around LNS8801 in the preclinical setting showed that the agent can lead to potent anti-tumor activity in multiple tumor types. The agent also demonstrated the ability to rapidly shrink tumors and enable immune memory. LNS8801 works by activating GPER

to quickly decrease c-Myc protein levels. Its effects on c-Myc protein levels has shown to be durable.

"We look forward to further exploring the preliminary results with LNS8801 alone and also in combination with pembrolizumab when we open additional cohorts soon,” Mooney stated, in the press release.

With an Orphan Drug status from the FDA, LNS8801 may eventually reach underserved communities or serve an unmet medical need in the skin cancer field. An Orphan Drug Designation allows an agent to have market exclusivity upon FDA approval as well as exemption from payment of application fees, and receipt tax credits for qualified clinical trials.


Linnaeus Therapeutics granted Orphan Drug Designation for LNS8801 for the treatment of patients with metastatic uveal melanoma. News release. March 10, 2021. Accessed March 10, 2021. https://bit.ly/30yyhfr