Announcement • Jun 21

Trevena, Inc. 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

Trevena, Inc. announced preclinical data from two separate research collaborations. The first from a series of experiments conducted in collaboration with scientists at Virginia Commonwealth University and presented at the recent annual meeting of the American Society for Pharmacology and Experimental Therapeutics in May 2024. These 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. This newly reported preclinical data, presented as a poster at the recent annual meeting of the American Society for Pharmacology and Experimental Therapeutics in May 2024, provides further insight into TRV045’s mechanism of action and its potential as a differentiated long-term therapeutic for neuropathic pain. 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, unlike other S1PR modulators, such as fingolimod, that demonstrate initial agonism but long-term functional antagonism due to S1PR desensitization and protein reduction. In this new study, S1PR1 functional desensitization was measured by S1PR1 stimulated 35SGTPgS binding in membrane homogenates of spinal cord prepared from drug treated mice. 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 measured by Western immunoblotting indicated that repeated fingolimod treatment caused an approximately 30% reduction in S1P1R protein in spinal cord while repeated TRV045 treatment had no effect. Similar effects were seen in the region of the periaqueductal gray; both of these regions play important roles in pain transmission. The company believe these studies indicate that, unlike fingolimod, TRV045 does not cause S1PR1 protein reduction or S1PR1 functional desensitization, suggesting that sustained TRV045 agonism is the underlying mechanism for its analgesic effects. 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). These effects were present after acute single dose administration of TRV045 in both male and female mice and after repeated treatment (once daily for 7 days). Trevena has previously observed that TRV045, unlike other known S1P-targeted compounds, exerted these analgesic effects in the absence of any reduction in circulating peripheral lymphocytes, suggesting that TRV045’s analgesic effects may not be due to receptor down-regulation. In a preclinical study using a validated model of seizure induction in mice, known as the intravenous Pentylenetetrazol (ivPTZ) Seizure Threshold Test, one of four doses of TRV045 (5, 10, 20 or 30mg/kg) or vehicle was orally administered to ten mice per dosage level. At one hour after test drug administration, 0.5% PTZ solution, a known seizure-inducing compound, was administered via iv infusion. Outcome measures included time to the first myoclonic (whole-body) twitch, and time to generalized clonus (seizure). At the 30mg/kg dose, TRV045 demonstrated a statistically significant increase in time to first myoclonic twitch (31.6 seconds TRV045 vs 26.0 seconds vehicle, p=0.02). This dose of TRV045 also demonstrated an increase in 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, the maximal electroshock (MES) model. In this test, 60 Hz of alternating current (150 mA) is delivered for 0.2 sec by corneal electrodes after application of local anesthesia. Protection from MES-induced seizures is shown by abolition of the hindlimb tonic extensor component of the seizure episode. Rats (N=8 per group) were tested at four doses of TRV045, administered by intra-peritoneal (IP) injection (10, 15, 20 and 30 mg/kg). There was a dose-dependent protection 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. Finally, TRV045 was screened in a preliminary study to evaluate the potential for TRV045 to exert an antiepileptogenic effect, or to prevent the emergence of epilepsy. In this model, rats underwent repeated low-dose IP injection of kainic acid to induce status epilepticus (SE), which leads to the development of spontaneous recurring seizures weeks later. Administration of test compounds immediately after the induction of SE, and before the development of spontaneous seizures, provides insight into the potential disruption of the process of seizure development, or epileptogenesis.

Announcement • Jun 27

Trevena, Inc. Announces New Topline OLINVYK Data Highlighting Reduced Cost Per Admission from Artemis Real-World Outcomes Study

Trevena, Inc. announced new topline OLINVYK data from the ARTEMIS study. The ARTEMIS study was an electronic medical records (EMR) based assessment focused on clinical and health resource utilization outcomes at Cleveland Clinic and Wake Forest Baptist Health. The study reviewed OLINVYK-treated patients in the ~200 patient VOLITION study with comparable surgical patients (matched patients) treated with other IV opioids, at the same institutions and during the study period. New topline data includes data from OLINVYK-treated patients (n=105) and matched patients (n=525) at Cleveland Clinic, as well as measures of cost per admission at both Wake Forest Baptist Health and Cleveland Clinic for OLINVYK-treated and matched patients. Initial ARTEMIS data from Wake Forest Baptist Health was previously announced based on OLINVYK-treated patients (n=96) compared to matched patients (n=457) at that site. ARTEMIS (EMR-Based) Topline Results: Overall Data from Cleveland Clinic and Wake Forest Baptist Health. OLINVYK-treated patients (n=201) had a $8,756 (19%) reduction in average cost per admission (p<0.0001) and 1.4-day (20%) reduction in average overall hospital length of stay (p<0.0001) compared to matched patients (n=982) treated with other IV opioids. Based on the data company have to date, there was not a statistically significant difference in the average duration of time in the post-anesthesia care unit (PACU) between OLINVYK-treated and matched patients. Cleveland Clinic Results. OLINVYK-treated patients (n=105) had a $7,102 reduction in average cost per admission (p=0.00043) and a 0.9-day reduction in average overall hospital length of stay (p=0.0181) compared to matched patients (n=525) treated with other IV opioids at Cleveland Clinic. Wake Forest Baptist Health Results. OLINVYK-treated patients (n=96) had a $10,339 reduction in average cost per admission (p<0.0001) compared to matched patients (n=457) treated with other IV opioids at Wake Forest Baptist Health. The Company previously announced that OLINVYK-treated patients at this site had a 1.6 day reduction in average overall hospital length of stay compared to matched patients treated with other IV opioids (p<0.0001). ARTEMIS Study Details: ARTEMIS is an electronic medical record (EMR) based analysis that compared the health outcomes of VOLITION study patients with a matched population of patients, who underwent similar surgical procedures but were treated with other IV opioids, at the same institutions and during the same general time period as VOLITION. Matching was conducted with a greedy matching algorithm, using a propensity scoring method with eight different demographic and clinical characteristics including age, sex, type and duration of surgery, measures of overall surgical and medical morbidity, and type of hospital insurance. Cost weights were calculated using a national dataset, and data was controlled for relevant covariates. The Company previously announced initial topline ARTEMIS data from Wake Forest Baptist Health (n=96 OLINVYK-treated patients; n=457 matched patients treated with other IV opioids). New topline data is now available from Cleveland Clinic (n=105 OLINVYK-treated patients; n=525 matched patients treated with other IV opioids), as well as for cost per admission for both Wake Forest Baptist Health and Cleveland Clinic. While an EMR analysis does not provide definitive data of group differences as seen in a prospectively randomized study, company believe EMR data bring a unique perspective to an understanding of how drugs may perform in the real world. VOLITION Study Details: VOLITION is a real-world, open-label, multi-site, post-approval clinical outcomes study in 203 adult patients undergoing major non-cardiac surgery. IV OLINVYK was dosed as the first-line analgesic during post-operative care, with a 1.5mg loading dose of OLINVYK at surgical closure, and 0.35mg to 0.5mg of OLINVYK, as needed, administered with a PCA device, with a 6-minute lockout period. Additional boluses (=1 mg) of OLINVYK were available if needed as soon as 15 minutes after the initial 1.5 mg loading dose. The average age of patients in VOLITION was 57.1 years (range 19 to 89), with approximately equal representation of men and women. Approximately 85% of patients underwent an abdominal surgical intervention, such as partial or total colectomy, enterotomy or other open abdominal procedures. A majority of patients had significant morbidity at the time of surgery as reflected by ASA status, and their respiratory risk was intermediate to high risk, graded using the PRODIGY risk score. The average duration of the surgery was 4.7 hours (range of 1.2 to 12.6 hours).

Total Shareholder Yield	n/a
Future Dividend Yield	n/a
Dividend Growth	n/a
Next dividend pay date	n/a
Ex dividend date	n/a
Dividend per share	n/a
Payout ratio	n/a

Segment	Dividend Yield
Company (TRVN)	n/a
Market Bottom 25% (US)	1.3%
Market Top 25% (US)	4.2%
Industry Average (Biotechs)	2.3%
Analyst forecast (TRVN) (up to 3 years)	n/a

Data	Last Updated (UTC time)
Company Analysis	2026/07/08 01:22
End of Day Share Price	2026/06/26 00:00
Earnings	2024/09/30
Annual Earnings	2023/12/31

Package	Data	Timeframe	Example US Source ^*
Company Financials	10 years	Income statement Cash flow statement Balance sheet	SEC Form 10-K SEC Form 10-Q
Analyst Consensus Estimates	+3 years	Forecast financials Analyst price targets	Analyst Research Reports Blue Matrix
Market Prices	30 years	Stock prices Dividends, Splits and Actions	ICE Market Data SEC Form S-1
Ownership	10 years	Top shareholders Insider trading	SEC Form 4 SEC Form 13D
Management	10 years	Leadership team Board of directors	SEC Form 10-K SEC Form DEF 14A
Key Developments	10 years	Company announcements	SEC Form 8-K

Analyst	Institution
Ying Huang	Barclays
Ritu Baral	Canaccord Genuity
Brandon Folkes	Cantor Fitzgerald & Co.

Trevena Dividends and Buybacks

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Key information

Recent dividend and buyback updates

Recent updates

Trevena, Inc. announced delayed annual 10-K filing

Trevena, Inc. Appoints Katrine Sutton as Principal Financial Officer and Principal Accounting Officer

Trevena, Inc.(OTCPK:TRVN) dropped from S&P TMI Index

Trevena, Inc.(OTCPK:TRVN) dropped from NASDAQ Composite Index

Trevena Announces Receipt of Nasdaq Delisting Notification

Trevena Regains Compliance with the Minimum Bid Price Requirement from Nasdaq

New major risk - Share price stability

New major risk - Revenue and earnings growth

Second quarter 2024 earnings released: US$0.23 loss per share (vs US$0.69 loss in 2Q 2023)

Trevena, Inc. 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

First quarter 2024 earnings released: US$0.36 loss per share (vs US$0.81 loss in 1Q 2023)

Nasdaq Hearings Panel Grants Trevena an Extension Until August 28, 2024 to Regain Compliance with the Nasdaq Continued Listing Requirements, Including the Minimum Bid Price Requirement and Equity Standard Requirement

Trevena, Inc., Annual General Meeting, Jun 13, 2024

New major risk - Revenue and earnings growth

Full year 2023 earnings: EPS and revenues miss analyst expectations

No longer forecast to breakeven

New major risk - Market cap size

Trevena, Inc. Promotion of Barry Shin to the Position of Executive Vice President and Chief Operating Officer

Trevena, Inc. announced that it expects to receive $1.945934 million in funding

Trevena, Inc. Announces Acceptance of Abstract Examining the Use of Olinvyk in Patients with Acute Burn Injuries

New major risk - Revenue and earnings growth

Consensus EPS estimates fall by 28%, revenue upgraded

Trevena, Inc. Announces Board Changes

Trevena, Inc. to Report Q3, 2023 Results on Nov 14, 2023

New major risk - Revenue and earnings growth

Trevena, Inc. Announces Completion of Initial Analysis of Olinvyk Continuous Respiratory Monitoring Data from Volition Study

Trevena, Inc. Announces Retirement of Michael Dougherty as A Member of the Board of Directors and as A Member of the Audit Committee, Effective as of September 14, 2023

Trevena, Inc. Announces Preliminary TRV045 Data from Two Proof-Of-Concept Studies Evaluating S1pr Mechanism of Action and CNS Target Engagement

Trevena Receives Non-Compliance Notice From Nasdaq Stock Market

Consensus revenue estimates increase by 725%

New major risk - Market cap size

Trevena, Inc. Appoints Mark Corrigan to Board of Directors

Trevena, Inc. Announces New Topline OLINVYK Data Highlighting Reduced Cost Per Admission from Artemis Real-World Outcomes Study

New major risk - Market cap size

Trevena Regains Compliance with the Minimum Bid Price Requirement under Nasdaq Listing Rule 5550(a)(2)

Trevena, Inc. to Report Q1, 2023 Results on May 15, 2023

Price target decreased by 39% to US$17.00

Trevena Announces Publication of OLINVYK Respiratory Physiology Study in ANESTHESIOLOGY

Trevena, Inc. Enrolls First Subject in TRV045 Proof-of-Concept Trial Evaluating S1PR Mechanism of Action and Target Engagement

Price target decreased to US$28.67

Insufficient new directors

Consensus forecasts updated

Second quarter 2022 earnings: EPS exceeds analyst expectations while revenues lag behind

Trevena Q2 2022 Earnings Preview

Trevena slides on $2M preferred stock offering

Trevena (NASDAQ:TRVN) Will Have To Spend Its Cash Wisely

Consensus revenue estimates fall by 36%

First quarter 2022 earnings: EPS and revenues miss analyst expectations

Insufficient new directors

Consensus forecasts updated

Is Trevena (NASDAQ:TRVN) In A Good Position To Deliver On Growth Plans?

Price target decreased to US$4.67

Insufficient new directors

Trevena Offers An Enticing Risk-Reward At These Prices

Trevena: Remaining Patient After A Disappointing Q2 Earnings

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