Shares of Trevena Inc ( TRVN ) are trading lower on Thursday, with a session volume of 23.65 million, as per data from Benzinga Pro.

The company released preclinical data from two separate research collaborations.

The first studies examined the cellular mechanism of analgesic effects of TRV045, a novel S1P1 receptor modulator, in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN).

The second set of studies was from a separate, ongoing collaboration with the NIH-supported Epilepsy Therapy Screening Program (ETSP), which studied the use of TRV045 in three different preclinical models, examining its potential effects on acute seizure protection and its potential ability to modify seizure development, or epileptogenesis.

In this study, TRV045 did not cause S1P1R functional desensitization or S1PR1 protein reduction despite repeated dosing over 14 days.

In contrast, Novartis AG’s Gilenya (fingolimod), an approved S1PR modulator, demonstrated significant S1P1R functional desensitization and protein reduction in this model.

Repeated fingolimod (1 mg/kg, once a day for 14 days) dosing decreased such 35SGTPgS binding by approximately 70% compared with vehicle, while repeated TRV045 oral dosing (10 mg/kg, once a day for 14 days) had no effect.

S1PR1 protein expression indicated that repeated fingolimod treatment caused an approximately 30% reduction in S1P1R protein in the spinal cord, while repeated TRV045 treatment had no effect.

Similar effects were seen in the region of the periaqueductal gray; both regions play important roles in pain transmission.

A validated model of seizure induction in mice was used in a preclinical study.

At the 30mg/kg dose, TRV045 demonstrated a statistically significant increase in time to the first myoclonic (whole-body) twitch (31.6 seconds TRV045 vs 26.0 seconds vehicle, p=0.02).

This dose of TRV045 also demonstrated an increase in the time to generalized clonus (33.9 seconds TRV045 vs. 28.7 seconds vehicle, p=0.056).

A separate study used a validated model of acute anti-seizure effect in rats. A dose-dependent protection was observed across the dose range, reaching 7 of 8 rats protected at the 30 mg/kg dose level and an estimated effective dose for 50% of the population (ED50) of 18 mg/kg.

The NIH-supported Epilepsy Therapy Screening Program plans to initiate additional studies of the anti-seizure potential of TRV045.

Although the initial assessment of the potential anti-epileptogenic effect of TRV045 did not demonstrate a statistically significant difference on the outcomes studied here, these results will assist in subsequent considerations of other dose and treatment duration in future seizure prevention studies.

Price Action: TRVN shares are down 33.7% at $0.2349 at last check Thursday.