Haddonfield NJ, June 7, 2021–Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, today announced the presentation of clinical data from its phase 1 dose-escalation study of LNS8801 as a monotherapy and in combination with pembrolizumab at the 2021 ASCO Annual Meeting.
The poster was entitled, “Phase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies.”
In the phase 1 dose-escalation portion of the study, LNS8801 demonstrated exceptional safety and tolerability. With monotherapy, no dose-limiting toxicities (DLTs) or treatment-related serious adverse events were observed. The combination of LNS8801 and pembrolizumab was confirmed to be safe and tolerable with no DLTs observed. The recommended phase 2 dose (RP2D) of LNS8801 dosed alone or in combination with pembrolizumab has been identified as 125 mg daily.
Putative predictive, prognostic, and confirmatory biomarkers that correlate well with anticancer activity and clinical benefit have been identified. These biomarkers will aid in the selection of patients in future clinical studies and will continue to be validated in the phase 2a program.
During dose escalation, LNS8801 demonstrated provocative signals of monotherapy and combinatorial activity in multiple settings of high unmet medical need. With LNS8801 monotherapy, 32% of all patients and 78% of biomarker-identified patients dosed at or above the RP2D had disease control and stable disease by RECIST 1.1. In immune-checkpoint inhibitor intolerant cutaneous melanoma, significant reductions in tumor size and ongoing/prolonged disease control (62+ weeks) have been observed in 2 of 2 patients. In metastatic uveal melanoma, 80% of patients dosed at or above the RP2D had stable disease (26+ weeks). In combination with pembrolizumab, a 33% objective response rate and a 100% disease control rate were observed (n=3), including a partial response in a pembrolizumab-experienced non-small cell lung cancer patient.
“We are extremely pleased to showcase these data at ASCO,” commented Patrick Mooney, MD, CEO of Linnaeus. “The data from the phase 1 study clearly demonstrate that LNS8801 is extremely safe and well tolerated and shows very promising signs of clinical benefit and preliminary efficacy alone and in combination with pembrolizumab. We look forward to further exploring LNS8801 alone and in combination with pembrolizumab in the currently open phase 1b cohorts and when we soon open additional phase 2a expansion cohorts.”
Having completed the dose-escalation phase of the study, Linnaeus is currently testing LNS8801 in its phase 1/2a adaptive-design clinical trial as a monotherapy and in combination with KEYTRUDAÒ (pembrolizumab) in patients who had previous clinical benefit from immune checkpoint inhibitors and then subsequently progressed. This marks the first time any company has dosed a patient in a clinical trial specifically targeting the GPER in combination with pembrolizumab. Linnaeus is also evaluating LNS8801 in a monotherapy cohort in patients with metastatic cutaneous melanoma who are PD-1/L1 therapy intolerant.
Linnaeus intends to open phase 2a cohorts in the near term.
LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.
In the ongoing phase 1/2a study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancer.
Linnaeus Therapeutics, Inc. is a privately held biopharmaceutical company focused on the development and commercialization of novel, small molecule oncology therapeutics that target a novel G protein-coupled receptor, known as GPER, or GPR30. The company was launched through the UPstart incubator at the University of Pennsylvania’s Penn Center for Innovation (PCI) Ventures. Its lead molecule, LNS8801, is in the final stages of preclinical development. The Company expects to begin its phase 1 clinical program in the summer of 2019. In addition to developing GPER agonists, Linnaeus is also currently focusing on developing small molecules that activate other G protein-coupled receptors to engage tumor-suppressive cellular signaling pathways.
Chief Executive Officer