LNS8801 / Linnaeus Therap - LARVOL DELTA

Prenatal activation of the G protein-coupled estrogen receptor (GPER) improves placental oxygenation and enhances offspring cardiac function in preeclampsia. (AHA 2025) - "In utero GPER activation enhances placental oxygen saturation and extends cardiovascular benefits at least 10 weeks into postnatal life in offspring exposed to PE. These findings highlight GPER-targeted interventions as a promising strategy to reduce the intergenerational impact of this obstetric disease."

Cardiovascular • Gynecology • Hypertension • Obstetrics

Pregnancy-Dependent Cardioprotection via GPER Activation in Dahl Salt-Sensitive Rats with Superimposed Preeclampsia. (PubMed, Am J Physiol Heart Circ Physiol) - " This study highlights the importance of pregnancy-specific adaptations on the cardiovascular effects of GPER activation. While LNS8801 demonstrated cardioprotective and antihypertensive benefits in pregnant Dahl SS/Jr rats, its effects were absent in virgin animals."

Journal • Preclinical • Cardiovascular • Gynecology • Hypertension • Nephrology • Renal Disease

A Trial of LNS8801 With or Without Pembrolizumab in Patients With Refractory Melanoma (clinicaltrials.gov) - P2/3 | N=135 | Recruiting | Sponsor: Linnaeus Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2030 ➔ Feb 2031 | Initiation date: Nov 2024 ➔ Aug 2025 | Trial primary completion date: Aug 2028 ➔ Feb 2029

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Cutaneous Melanoma • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

LNS-8801 as a therapeutic agent for aggressive lymphomas: ROS-induced cytotoxicity and synergy with existing therapies. (PubMed, Blood Adv) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Oncology

Pregnancy-Dependent Cardioprotection via GPER Activation in Dahl Salt-Sensitive Rats. (PubMed, bioRxiv) - "While LNS8801 demonstrated cardioprotective and antihypertensive benefits in pregnant Dahl SS/Jr rats, its effects were absent in virgin animals, underscoring the influence of the physiological and hormonal environment on GPER-mediated responses. These findings provide a foundation for further exploration of GPER as a therapeutic target for pregnancy-associated cardiovascular dysfunction and preeclampsia, reinforcing the need for pregnancy-specific approaches in drug development."

Journal • Preclinical • Cardiovascular • Gynecology • Hypertension • Renal Disease

Linnaeus Therapeutics Awarded Its Fourth Competitive SBIR Award by the National Cancer Institute Bringing Total SBIR Funding to $8.3 Million (PRNewswire) - "Linnaeus Therapeutics, Inc...announced it has been awarded its fourth competitive Small Business Innovation Research ('SBIR') Award by the National Cancer Institute ('NCI') of the National Institutes of Health ('NIH'). This $2,000,000 SBIR award was granted to the company after yet another highly competitive peer-review process. The award will help fund the clinical development of its lead compound, LNS8801, which targets a G protein-coupled receptor (GPER), for the treatment of metastatic cutaneous melanoma as a monotherapy in patients who cannot tolerate immunotherapy....Linnaeus anticipates initiating a randomized controlled clinical trial in unresectable, treatment refractory cutaneous melanoma in Q2 of this year."

Financing • New trial • Cutaneous Melanoma

Linnaeus Therapeutics Announces Publication of Seminal Paper on LNS8801 in Cancer Research Communications (PRNewswire) - "Linnaeus Therapeutics, Inc...announced that seminal data describing Linnaeus's clinical candidate, LNS8801, was published in Cancer Research Communications...In preclinical models, LNS8801 demonstrated potent, oral, GPER-dependent anticancer effects. This study also demonstrates that a common genetic variant of GPER may influence patient response, offering a potential mechanism-linked biomarker for patient selection and personalized therapy. These findings complement the data generated in ongoing clinical trials of LNS8801 for cancer....Linnaeus anticipates initiating a randomized controlled clinical trial testing LNS8801 in unresectable, treatment-refractory, cutaneous melanoma patients this year. This study will randomize 135 biomarker-positive patients to receive either LNS8801 monotherapy, LNS8801 in combination with pembrolizumab, or physician's choice therapy. The study will assess progression-free survival and overall survival between the groups."

New trial • Preclinical • Cutaneous Melanoma • Melanoma

LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development. (PubMed, Cancer Res Commun) - "In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response."

Journal • Oncology • ER

LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development (Cancer Res Commun) - "Using preclinical models, we show that LNS8801 suppresses cancer in a GPER-dependent manner and that LNS8801 is efficacious when administered orally. Further, we show that GPER is widely, but not ubiquitously, expressed in both normal and malignant human tissues."

Preclinical • Oncology

KEYNOTE-B47: Study Assessing MTD, Safety, Tolerability, PK and Anti-tumor Effects of LNS8801alone and with Pembrolizumab (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Linnaeus Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Dec 2027 | Trial primary completion date: Mar 2024 ➔ Dec 2026

IO biomarker • Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MYC • PD-L1

LNS8801: An enantiomerically pure agonist of the G protein-coupled estrogen receptor suitable for clinical development. (PubMed, bioRxiv) - "In addition, an attenuated response to LNS8801 is observed in a common germline coding variant in human GPER. These findings support ongoing human cancer trials with LNS8801 and suggest that the germline GPER genotype may serve as a predictive biomarker of therapeutic response."

Journal • Oncology • ER

A Trial of LNS8801 with or Without Pembrolizumab in Patients with Refractory Melanoma (clinicaltrials.gov) - P2/3 | N=135 | Not yet recruiting | Sponsor: Linnaeus Therapeutics, Inc. | Phase classification: P3 ➔ P2/3

Phase classification • Cutaneous Melanoma • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

Effect of LNS8801 (with or Without Pembrolizumab) on Melanoma (clinicaltrials.gov) - P3 | N=135 | Not yet recruiting | Sponsor: Linnaeus Therapeutics, Inc.

New P3 trial • Cutaneous Melanoma • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

An In Vivo Study of LNS8801, a GPER Agonist, in a Spontaneous Melanoma-Prone Mouse Model, TGS. (PubMed, Pigment Cell Melanoma Res) - "Over the course of the 32-week experiment, visible images were taken by the small animal imaging IVIS system to track tumor progression, and blood and tissue samples were collected for molecular analyses. Results showed that sex-biased effects were observed in the efficacy of LNS8801 and that LNS8801 shows a UV-protective influence in both male and female TGS mice."

Journal • Preclinical • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

Efficacy of LNS8801 in melanoma patients with prior immune-related adverse events from immune-checkpoint inhibitors (ESMO 2024) - P1/2 | "LNS8801 is safe and tolerable and demonstrates encouraging activity in patients with ICI treatment-refractory CM and prior irAEs. Consensus germline GPER is a promising predictive biomarker for benefit and continues to be associated with improved outcomes in patients treated with LNS8801. These data support further development of LNS8801 as a therapy for patients with CM who can no longer tolerate ICI therapy."

Adverse events • Checkpoint inhibition • Clinical • IO biomarker • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CTLA4 • MYC • PD-1

Linnaeus Therapeutics Announces Presentation of Positive Clinical Data of LNS8801 in Metastatic Melanoma at 2024 ESMO Annual Meeting (PRNewswire) - P1/2 | N=200 | NCT04130516 | Sponsor: Linnaeus Therapeutics, Inc. | "Linnaeus Therapeutics...announced the presentation of clinical data at the 2024 ESMO...from its dose-expansion cohort of LNS8801 as a monotherapy in patients with metastatic cutaneous melanoma...LNS8801 monotherapy treatment resulted in a disease control rate of 100% in biomarker-positive patients, with a preliminary progression-free survival of over 6 months. This includes a patient that has been on treatment for over 4.5 years with resolution of all soft-tissue lesions and no evidence of active disease in the residual bone-associated target lesion or elsewhere....Linnaeus anticipates initiating a randomized controlled clinical trial in unresectable, treatment-refractory cutaneous melanoma in Q4 of this year. This study will randomize 135 biomarker-positive patients to receive LNS8801 monotherapy; LNS8801 and pembrolizumab; or physician's choice therapy."

New trial • P1/2 data • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor

Linnaeus Therapeutics Announces Issuance of Composition of Matter Patent for LNS8801 by the European Patent Office (PRNewswire) - "Linnaeus Therapeutics, Inc...today announced that on March 6, 2024, the European Patent Office (EPO) issued EP patent 3,823,617 ('617 patent) covering the pharmaceutical composition of matter for the company's lead compound, LNS8801....Based on promising data from the phase 1/2 study, Linnaeus plans to initiate a potentially pivotal, randomized controlled trial in patients with metastatic cutaneous melanoma who have had confirmed progression on immune checkpoint inhibitors."

New trial • Patent • Cutaneous Melanoma • Oncology • Solid Tumor

Ovariectomy-Induced Arterial Stiffening Differs From Vascular Aging and Is Reversed by GPER Activation. (PubMed, Hypertension) - P1/2 | "This study enhances our understanding of the impact of estrogen loss on vascular health in a murine model and warrants further studies to examine the ability of LNS8801 to improve vascular health in menopausal women. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04130516."

Journal • Cardiovascular

The effect of LNS8801 in combination with pembrolizumab in patients with treatment-refractory cutaneous melanoma (SITC 2023) - P1/2 | "Consensus germline GPER is a promising predictive biomarker, and continues to be associated with improved outcomes in patients treated with LNS8801. These data support further development of LNS8801 in combination with pembrolizumab as a therapeutic approach to treat refractory CM patients."

Clinical • Combination therapy • IO biomarker • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CTLA4 • MYC • PD-1

The effect of LNS8801 in combination with pembrolizumab in patients with treatment-refractory cutaneous melanoma (ESMO 2023) - P1/2 | "Consensus germline GPER is a promising predictive biomarker, and is associated with improved outcomes in patients treated with LNS8801. These data support further development of LNS8801 in combination with pembrolizumab treat advanced CM patients."

Clinical • Combination therapy • IO biomarker • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CTLA4 • MYC • PD-1

LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway. (PubMed, Cancer Res Commun) - "Previous work demonstrated that LNS8801 inhibits cancer via GPER activation, especially in solid tumors. Here we show that LNS8801 inhibits AML via GPER-independent mechanisms that include ROS induction and ER activation."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Melanoma • Oncology • Solid Tumor

The effect of LNS8801 alone and in combination with pembrolizumab in patients with metastatic uveal melanoma. (ASCO 2023) - P1/2 | "LNS8801 alone and in combination with pembrolizumab is tolerable without unanticipated toxicities and demonstrates encouraging anti-tumor activity in patients with mUM. The hypofunctional germline GPER variant appears over-represented in this cohort compared to the normal population, suggesting a potential significant role for GPER in the development of mUM. These data support further development of LNS8801 alone and in combination with pembrolizumab as a therapeutic approach to treat mUM patients, especially for patients with consensus germline GPER."

Clinical • Combination therapy • IO biomarker • Metastases • Eye Cancer • Fatigue • Immune Modulation • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • MYC

Linnaeus Therapeutics Announces Presentation of Positive Clinical Data of LNS8801 in Metastatic Uveal Melanoma at 2023 ASCO Annual Meeting (PRNewswire) - P1/2a | N=200 | NCT04130516 | Sponsor: Linnaeus Therapeutics, Inc. | "Linnaeus Therapeutics, Inc...announced the presentation of clinical data from its phase 1 dose-expansion study of LNS8801 as a monotherapy and in combination with pembrolizumab in metastatic uveal melanoma at the 2023 ASCO Annual Meeting....LNS8801 alone and in combination with pembrolizumab was tolerable without unanticipated toxicities. LNS8801 demonstrated encouraging anti-tumor activity in patients with metastatic uveal melanoma, overall 50% of patients had disease control. These data support further development of LNS8801 alone and in combination with pembrolizumab as a therapeutic approach to treat metastatic uveal melanoma patients."

P1 data • Eye Cancer • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

The GPER Agonist LNS8801 Induces Mitotic Arrest and Apoptosis in Uveal Melanoma Cells. (PubMed, Cancer Res Commun) - "Here, we demonstrate that the GPER agonist LNS8801 induced both GPER-dependent and GPER-independent effects and elicited potent anticancer activities in vitro and in vivo. Our results complement and support the ongoing clinical trial of LNS8801 in advanced uveal melanoma."

Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CDKN1A • GPER1 • TP53

Study Assessing MTD, Safety, Tolerability, PK and Anti-tumor Effects of LNS8801alone and With Pembrolizumab (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Linnaeus Therapeutics, Inc. | Trial primary completion date: Oct 2023 ➔ Mar 2024

Metastases • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1