Trevena : TRV045 Product Overview

INNOVATING FOR PATIENTS

Nasdaq TRVN I January 2023

Forward-Looking Statements

To the extent that statements contained in this presentation are not descriptions of historical facts regarding Trevena, Inc. (the "Company" or "we"), they are forward-looking statements reflecting management's current beliefs and expectations. Forward-looking statements are subject to known and unknown risks, uncertainties, and other factors that may cause our or our industry's actual results, levels of activity, performance, or achievements to be materially different from those anticipated by such statements. You can identify forward-looking statements by terminology such as "anticipate," "believe," "estimate," "expect," "intend," "may," "might," "plan," "objective," "predict," "project," "suggest," "target," "potential," "will," "would," "could," "should,"

"continue," "ongoing," or the negative of these terms or similar expressions. Forward-looking statements contained in this presentation include, but are not limited to, (i) statements regarding

the timing of anticipated clinical trials for our product candidates; (ii) the timing of receipt of clinical data for our product candidates; (iii) our expectations regarding the potential safety, efficacy, or clinical utility of our product candidates; (iv) the size of patient populations targeted by our product candidates and market adoption of our potential drugs by physicians and patients; (v) the timing or likelihood of regulatory filings and approvals; and (vi) our cash needs.

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the commercialization of any approved drug product, the status, timing, costs, results and interpretation of our clinical trials or any future trials of any of our investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including our assessment of the discussions with the FDA or other regulatory agencies about any and all of our programs; uncertainties related to the commercialization of OLINVYK; available funding; uncertainties related to our intellectual property; uncertainties related to the ongoing COVID-19 pandemic, other matters that could affect the availability or commercial potential of our therapeutic candidates; and other factors discussed in the Risk Factors set forth in our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings we make with the SEC from time to time. In addition, the forward-looking statements included in this presentation represent our views only as of the date hereof. We anticipate that subsequent events and developments may cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, except as may be required by law.

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Trevena Overview

	Focused on Innovative Medicines
	For CNS Disorders
	Detailed in Following Slides
Olinvyk IV*	S1P Modulator Program
Approved NCE for the	Novel S1P1R modulator
management of acute	with differentiated MOA
pain in adults*	(lead asset: TRV045)
Proven track record of Trevena	Initiated POC study for
internal discovery and	CNS disorders
development through approval

Innovative CNS Pipeline

Based on Nobel-prize winning biased ligand technology

NCEs addressing acute / neuropathic pain, epilepsy, acute migraine, OUD

• OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Please see Important Safety Information including BOXED WARNING at the end of presentation. Full Prescribing Information at www.OLINVYK.com.

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TRV045: Innovative Clinical-Stage S1P1R Modulator

TRV045:	S1PR: Validated target for multiple blockbusters (fingolimod / siponimod / ozanimod / ponesimod)
Selective S1PR Modulator	TRV045: Unique profile (S1P1R specific, receptor recycling, no lymphopenia) for new indications
Large Addressable	Initial investigation for orphan / non-orphanepilepsy and non-opioidchronic pain
Target Indications	Broad potential application in CNS disorders, autoimmune disease and inflammatory disease
Strong MOA	Nonclinical models demonstrated positive efficacy outcomes, avoiding known S1PR safety issues
Support	NIH collaboration: Epilepsy Therapy Screening Program & Preclinical Screening Pain Platform
Novel Family of	New chemical entity; potent and selective for subtype 1; developed in-house with strong IP
S1PR Modulators	Platform of S1PR backup opportunities for longer term value creation
Near-Term	CNS target engagement POC study - enrollment completion expected mid-2023
Value Drivers

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S1P1 Receptor - Novel Target for CNS Indications

S1P1 receptors are highly expressed on key CNS cells involved in neuroinflammation

Potential therapeutic role in seizures, epileptogenesis and pain signaling

Epilepsy		Neuropathic pain
•	Neuroprotective effects3		•	Inhibits pain sensation1
•	Modulates BBB permeability,		•	Inhibits excitatory neuronal signaling2
	anti-inflammatory effects4,5

Existing S1PR-targeted drugs, however, are ill-suited for CNS indications due to known:

Lymphopenia	Pulmonary AEs
Cardiac AEs	Ophthalmologic AEs

1)	Sim-Selley et al., Journal of Pharmacology & Experimental Therapeutics, 2018. 2) Sim-Selley et al, Journal of Neurochemistry, 2008. 3) Gol et al., European Journal of Pharmaceutical Sciences, 2017.	5
4)	Leo et al, CNS & Neurological Disorders - Drug Targets, 2017. 5) Choi, et al. PNAS 2011.