TRV045 / Trevena - LARVOL DELTA

TMS and EEG Pharmacodynamic Effects of a Selective Sphingosine-1-Phosphate Subtype 1 Receptor Agonist on Cortical Excitability in Healthy Subjects. (PubMed, Clin Pharmacol Ther) - "These findings show that TRV045 has central nervous system activity with evolving effects following repeated dosing. These data support further studies to elucidate the mechanism of action of TRV045 and its potential anti-epileptic effects."

Clinical • Journal • PK/PD data • CNS Disorders • Epilepsy • Multiple Sclerosis

Trevena Announces Preclinical TRV045 Data Providing Insight Into Novel Mechanism of Analgesic Effect in Chronic Neuropathic Pain Model and Demonstrating Statistically Significant Anti-Seizure Activity in Epilepsy Models (GlobeNewswire) - "Trevena, Inc...announced today preclinical data from two separate research collaborations....In this study, TRV045 did not cause S1P1R functional desensitization or S1PR1 protein reduction despite repeated dosing over 14 days. In contrast, fingolimod, an approved S1PR modulator, demonstrated both significant S1P1R functional desensitization and protein reduction in this same model. As a result, the Company believes TRV045 may represent a differentiated mechanism to provide sustained S1P1R agonism and analgesic effect....Trevena has previously reported that, in a validated mouse model of CIPN, oral administration of TRV045 (1 mg/kg, 3 mg/kg, and 10 mg/kg) reduced mechanical and cold stimulus-evoked nociception in a statistically significant, dose-related manner (at the 3 mg/kg and 10 mg/kg doses only)."

Preclinical • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

TRV045, a Novel and Selective S1P1 Receptor Modulator is Efficacious in Acute, Chronic and Prevention in Mouse Models of Chronic Neuropathy, Without Causing Lymphopenia (ACNP 2023) - "At Day 15, mice were treated with TRV045 (0.1, 0.3, 3, 10 mg/kg, p.o.) or fingolimod (1 mg/kg, p.o.) or vehicle. Oral administration of TRV045 reduced the stimulus-evoked nociception in a dose-related manner in a mouse model of chemotherapy-induced peripheral neuropathy. Our experiment in the preventive paradigm suggests TRV045 may have potential disease or pathology-modifying effects on pain transmission processes detectable by the cold hypersensitivity test, with the reasonable assumption that at 168 hours, no detectable levels of TRV045 remain in circulation. Whether the efficacy seen at 24 hours was attributable to residual tissue TRV045 or results of disease prevention remains to be determined."

Lymphopenia • Preclinical • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain • S1PR1

Trevena Announces TRV045 Presentation at the American College of Neuropsychopharmacology 62nd Annual Meeting (GlobeNewswire) - "Trevena....today announced a poster presentation at the 62nd Annual Meeting for the American College of Neuropsychopharmacology (ACNP). The conference is being held from December 3rd to 6th, 2023....The poster discussed the potential utility of TRV045 for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) using an established nonclinical model....In addition, the Company is currently collaborating with the National Institutes of Health (NIH) to evaluate TRV045 for the potential treatment of epilepsy and as a nonopioid treatment for pain."

Preclinical • CNS Disorders • Pain • Peripheral Neuropathic Pain

Trevena Reports Favorable TRV045 Topline Safety and Tolerability Data from Proof-of-Concept Studies (GlobeNewswire) - P1 | N=104 | "There were no drug-related adverse events reported in either POC study, and no serious adverse events were reported in either POC study. Of the adverse events, 98% (102 of 104) were reported as mild in the Target Engagement POC study, and 99% (79 of 80) were reported as mild in the TMS POC study. The most common adverse events reported were headaches, somnolence, dizziness and fatigue...Laboratory results also showed no clinically significant reduction in total lymphocyte count, no clinically significant changes in heart rate or blood pressure, and no clinically significant changes in ECG interval measures (including no prolongation of PR or QTcF intervals)."

P1 data • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Trevena Announces Preliminary TRV045 Data from Two Proof-of-Concept Studies Evaluating S1PR Mechanism of Action and CNS Target Engagement (GlobeNewswire) - P1 | N=NA | "Trevena, Inc...announced preliminary topline data from two Phase 1 proof-of-concept studies of TRV045, a novel sphingosine-1-phosphate receptor modulator selective for the S1P receptor subtype 1....Data from both studies demonstrated CNS penetration and target engagement, as well as plasma exposures in the anticipated active dose range, supporting the therapeutic potential of TRV045. In a capsaicin-induced neuropathic pain model, a validated model of neuropathic pain, TRV045 showed a statistically significant, dose-dependent treatment effect. In the transcranial magnetic stimulation (TMS) proof-of-concept study, TRV045 demonstrated statistically significant changes in the power spectral density in several bands."

P1 data • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Trevena Initiates Targeted Proof-of-Concept Study to Evaluate TRV045 as a Potential Treatment for Epilepsy and Other CNS Disorders (GlobeNewswire) - "Trevena, Inc...announced the initiation of a Phase 1 proof-of-concept study of TRV045, a novel sphingosine-1-phosphate receptor modulator selective for the S1P receptor subtype 1....'We look forward to reporting topline data from both of our Phase 1 proof-of-concept studies later this year to help inform our future development path for TRV045'....The study is expected to complete enrollment by mid-2023."

Enrollment status • P1 data • Trial status • CNS Disorders • Epilepsy

Trevena Enrolls First Subject in TRV045 Proof-of-Concept Trial Evaluating S1PR Mechanism of Action and Target Engagement (Yahoo Finance) - "New Phase 1 clinical study designed to build on nonclinical evidence of anti-inflammatory signaling and potential disease-modifying effect of TRV045 in the treatment of epilepsy and other CNS disorders...The first subject in the trial was dosed in December 2022 and the study is expected to complete enrollment by mid-2023."

Enrollment status • CNS Disorders • Diabetic Neuropathy • Epilepsy • Pain • Peripheral Neuropathic Pain

"$TRVN Trevena Enrolls First Subject in TRV045 Proof-of-Concept Trial Evaluating S1PR Mechanism of Action and Target Engagement https://t.co/WbdswE86nw" (@stock_titan)

Trevena Announces Poster Presentations of TRV045 Nonclinical Epilepsy Data, and OLINVYK Clinical Neurocognitive and GI Data, at Recent Medical Meetings (Yahoo Finance) - "TRV045 data reflected reduced seizure burden in nonclinical models of acute epilepsy presented at American College of Neuropsychopharmacology (ACNP) Annual Meeting...Trevena, Inc...announced that three abstracts related to the Company’s commercial and clinical pipeline were presented at medical meetings in December."

Preclinical • CNS Disorders • Epilepsy • Pain

Trevena Announces Completion of Phase 1 Study for TRV045, Novel S1P Receptor Modulator (Yahoo Finance) - P1 | N=89 | "TRV045 demonstrated a favorable tolerability profile with no reported SAEs and no lymphopenia; Nonclinical study showed anti-inflammatory signaling, suggesting a potential disease-modifying effect of TRV045 in the treatment of epilepsy, based on astrocyte cell culture study; PK profile supports anticipated once daily dosing."

P1 data • CNS Disorders • Epilepsy • Pain • Peripheral Neuropathic Pain

TRV045, a Novel, Selective S1P Receptor subtype-1 Modulator that Does Not Cause lymphopenia, Is Efficacious in Acute and Chronic Rodent Epilepsy Models (ACNP 2022) - "Fingolimod, a nonselective S1PR modulator but with high potency for S1PR1, has shown anti-epileptic effects in a diverse range of preclinical epileptic models, possibly through anti-inflammatory mechanisms as well as preservation of neuronal and blood brain barrier integrity. The S1PR1 modulator TRV045 prevented generalized seizures in the CK mouse and rat MES models and reduced seizures in the KA-SRS chronic spontaneous seizure model, indicating that it is a viable candidate for human research in the treatment of epilepsy."

Lymphopenia • Preclinical • CNS Disorders • Epilepsy • S1PR1

Trevena Reports Second Quarter 2022 Results and Provides Business Update (GlobeNewswire) - "Trevena, Inc...reported its financial results for the second quarter ended June 30, 2022 and provided an overview of its recent operational highlights....Phase 1 study of TRV045, in development for diabetic neuropathic pain, remains on track for completion in 2H 2022. Phase 1 study has continued to progress with full enrollment in the single ascending dose and food effect segments of the study. The Company expects to complete the remaining multiple ascending dose portion later this year."

Trial completion date • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Trevena Reports First Quarter 2022 Results and Provides Business Update (BioSpace) - "Continued progress of Phase I study for TRV045, novel S1P receptor modulator, for use in diabetic neuropathic pain (DNP)...Trevena, Inc...today reported its financial results for the first quarter ended March 31, 2022 and provided an overview of its recent operational highlights....Advanced Phase 1 study of TRV045, our novel S1P receptor modulator, for diabetic neuropathic pain."

Trial status • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Trevena Announces Advancement of TRV045 Into Clinical Development for Diabetic Neuropathic Pain (GlobeNewswire) - "Trevena, Inc...today announced it is advancing TRV045 into clinical development, following receipt of a notification from the U.S. Food and Drug Administration (FDA) that the study may proceed....The Company will initiate a three-part Phase 1 single ascending dose (SAD), food effect, and multiple ascending dose (MAD) trial. The primary objective of the study is to evaluate the safety and tolerability of TRV045 in healthy adult subjects. The study will also assess the pharmacokinetics (PK) of TRV045 and determine whether TRV045 is associated with changes in lymphocyte counts, hemodynamic function, and QTcF interval..."

New P1 trial • CNS Disorders • Pain

Trevena, Inc. Reports Fourth Quarter and Full Year 2020 Results (Trevena Press Release) - "Commenced partnership with NIH to evaluate TRV045 for epilepsy and chronic neuropathic pain; IND filing on track for 1H 2021...This differentiated formulation could extend the Company’s market exclusivity an additional five years to 2041. The Company has initiated IND-enabling activities with this oral dosage form, which it believes offers significant advantages for exploring multiple CNS disease states."

Commercial • IND • Licensing / partnership • CNS Disorders • Epilepsy • Pain

Trevena, Inc. Provides Update on Commercial Launch Activities for OLINVYK and Announces Anticipated Pipeline Catalysts (GlobeNewswire) - "Trevena...today provided an update on the U.S. commercial launch for OLINVYK (oliceridine) injection and announced anticipated milestones for 2021...All three vial presentations of OLINVYK (1 mg/1 mL and 2 mg/2 mL single-dose vials; 30 mg/30 mL single-patient-use vials for patient-controlled analgesia) are now available for ordering….The health economic model, which highlights OLINVYK versus IV morphine cost information, is expected to be published in 1H 2021."

HEOR • Launch US • CNS Disorders • Epilepsy • Pain

[VIRTUAL] TRV045, a Novel, Selective S1P1 Receptor Modulator, is Efficacious in Reversing Neuropathic Pain Without Affecting Lymphocyte Trafficking (ACNP 2020) - "Lymphocytes counts were determined in male C57BL/6 mice (n=6-12/group) following 3 consecutive days of dosing with vehicle, 3.7 mg/kg TRV045 s.c. (approximately 25-fold higher dose compared to the calculated ED50 dose in the mouse CIPN assay) or 0.03 mg/kg fingolimod p.o. Lymphocyte counts were also determined in male cynomolgus monkeys (n=3) following oral dosing with vehicle or 60 mg/kg TRV045...Paw withdrawal latency was 7.1 ± 0.5 sec in vehicle-treated animals and 16.7 ± 1.3 sec in gabapentin-dosed animals (p<0.001 vs vehicle)... TRV045 is a selective S1P1 receptor modulator that is an effective analgesic in rodent models of neuropathic pain. TRV045 differentiates from other non-selective S1P receptor modulators in that it does not cause lymphopenia. Therefore, TRV045 may provide a new therapeutic option for the treatment of neuropathic pain."

Alzheimer's Disease • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

[VIRTUAL] TRV045, a Novel, Selective S1P1 Receptor Modulator is Efficacious in Rodent Models of Epilepsy, Without Affecting Lymphocyte Trafficking (ACNP 2020) - "FTY720 has also been shown to demonstrate antiepileptogenic effects in both the rat lithium-pilocarpine model of status epilepticus and the pentylenetetrazole (PTZ)-induced kindling mouse model. We have shown that the S1P1R¬selective compound TRV045 prevented generalized seizures in a rat MES model and demonstrated anti-convulsant activity in a corneal kindled mouse model. These data suggest that the novel mechanism of action of TRV045 may provide a new therapeutic option for the treatment of epilepsy."

Preclinical • Alzheimer's Disease • CNS Disorders