Forward-Looking Statements This presentation contains forward-looking statements including, but not limited to, statements related to the

process and timing of anticipated future development of AcelRx's product candidates, including Zalviso and ARX-04;

anticipated results and timing of the completion of the SAP302 study for ARX-04; AcelRx's plans to seek a pathway

forward towards gaining approval of Zalviso in the United States, including the anticipated timing, design and results

of the additional clinical trial for Zalviso; the anticipated resubmission of the Zalviso NDA to the FDA; statements

related to the timing and success of commercial launch of Zalviso in Europe; ability to fund ARX-04 development

from the contract with the Department of Defense; the status of the Collaboration and License Agreement with

Grunenthal, including potential milestones and royalty payments under the Grunenthal CLA; anticipated cash

balance at year-end 2015 and cash forecasts. These forward-looking statements are based on AcelRx's current

expectations and inherently involve significant risks and uncertainties. AcelRx's actual results and the timing of

events could differ materially from those anticipated in such forward-looking statements as a result of these risks

and uncertainties, which include, without limitation, risks related to: any delays or inability to obtain and maintain

regulatory approval of its product candidates, including Zalviso and ARX-04; its ability to timely and successfully

design and complete the additional clinical study requested by the FDA to support resubmission of the Zalviso NDA;

its ability to timely resubmit the Zalviso NDA to the FDA and to receive regulatory approval for Zalviso; the fact that

the FDA may dispute or interpret differently positive clinical results obtained to date from the pivotal Phase 3

SAP301 ambulatory surgery study of ARX-04; its ability to complete Phase 3 clinical development of ARX-04;

inability to successfully manufacture Zalviso to meet the requirements of Grunenthal and potential delays in the

timing of the European launch; the success, cost and timing of all product development activities and clinical trials,

including the SAP302 ARX-04 trial; and other risks detailed in the "Risk Factors" and elsewhere in AcelRx's U.S.

Securities and Exchange Commission filings and reports, including its Quarterly Report on Form 10-Q filed with the

SEC on November 3, 2015. AcelRx undertakes no duty or obligation to update any forward-looking statements

contained in this release as a result of new information, future events or changes in its expectations.

2

Who We Are

We are a specialty pharmaceutical company focused on the

development and commercialization of innovative therapies for

the treatment of acute pain

Sublingual Sufentanil

Platform Formulation for Pain

Two Phase 3 Programs

EU Approval

Strong Financial Position

3

Sublingual Sufentanil Platform

ARX-04 completing Phase 3 and preparing NDA ER study is enrolling, with results expected Q1:16

Pre-NDA meeting is scheduled for December 2015

NDA submission is planned for H1:16

Zalviso™ New U.S. Study Commencing and EU Commercial Launch Submitted protocol to FDA for open label study in moderate-to-severe pain

EU approval received; Commercial Launch Commencing

Cash of over $100mm Completed EU royalty monetization $65M

EU approval milestone $15M

DoD support up to $17M

4

Targeting Acute Pain

High Therapeutic Index

Lipophilicity

No Active Metabolites

Rapid Uptake Across BBB

505(b)(2) NDA filing

IV formulation (generic) approved in

US & EU ZalvisoTM ARX-04

Sublingual Sufentanil Intended to Treat Pain in

Hospital and Multiple HCP Settings

5

Intended for Healthcare Professional Administration Intended for Patient Administration in Hospital

US Market Opportunities

Zalviso Market Potential

ARX-04 Market Potential

Product Opportunities for Sublingual Sufentanil Tablets

$1.3B2

ER Departments

Ambulatory Surgery Centers

InPatient Surgeries

Interventional Procedures

$445.5M1

InPatient Post Surgery

1 Recent Zalviso analyst estimates

2 ZS Associates 2014 and Millennium 2010 6

Why Sublingual Sufentanil?

Molecular Properties

Lipophilic –1500 times more fat-soluble than morphine

20% non-ionized at physiological pH (fentanyl only 8%)

Fat-soluble, non-ionized molecules = Fast Brain Penetration

7

Longer duration of action compared to IV

Consistent plasma levels

Fast transit time to the brain

Oral bioavailability of sufentanil is low

Sufentanil Transit Time to the Brain

Commonly used IV opioids have a delayed equilibration time

between plasma and CNS

Morphine

Hydromorphone

Sufentanil rapidly penetrates the CNS

due to its very high lipophilicity

Sufentanil

2.8

46

1 Lotsch et al., Anesthesiol 95:1329-38, 2001

2 Shafer et al., Geriatric Anesthesiology. 2nd ed. New York, NY: Springer; Chapter 15:209–28, 2007

3 Scott et al., Anesthesiol 74:34-42, 1991

Blood Brain

Barrier

8

Plasma versus Brain Morphine Concentrations

1 IV PCA dosing frequency based in IAP309 Phase 3 study; plasma and brain concentrations modelled from published plasma and CNS equilibration values by Fisher - consultant to AcelRx

Delayed brain uptake leads to disconnect between IV dosing and effect1

0

100

80

60

40

20

0

2 4 6

Time (hours)

8 10 12

Cp

/ C

e (n

g/m

l)

Morphine + M6G* Plasma Effect Site

Morphine/M6G in brain

* Assumes equipotency of morphine and M6G; other potency ratios achieved similar results

Plasma concentrations with IV morphine dosing

9

Sufentanil Concentrations

Sublingual sufentanil plasma and brain concentrations shown to track together

0

100

80

60

40

20

0

2 4 6 8 10 12

Time (hours)

Cp

/ C

e (n

g/m

l)

Plasma Effect Site

1 Plasma and brain concentrations modelled from SSTS PK data and from published CNS equilibration values D. Fisher - consultant to AcelRx

Uptake of sublingual sufentanil leads to potential for real-time tracking between dosing and effect1

Sufentanil

10

PK of Opioid Brain Concentrations

11

Clinical Data Overview

Results of Phase 2 dose ranging counted as pivotal

Positive Phase 3 SAP301 in Abdominal Surgery

SAP302 Emergency Room (ER) study underway (supplements safety database in key setting)

ARX-04 Program

Zalviso Program

Positive Phase 3 studies IAP 309,310,311

abdominal/orthopedic surgeries

Head-to-head vs. IV PCA morphine (IAP 309) as

measured by PGA and onset of pain relief,

showed superiority

12

ARX-04: Sublingual Sufentanil (30mcg)

Healthcare Professional Administered

13

Intended for treatment of moderate-to-severe acute pain in a medically

supervised setting

Single tablet dosage strength – 30 mcg

Administered, per patient’s request, every 60 minutes

Tablet pre-loaded in a single-dose applicator (SDA) within a foil pouch

making it suitable for field/trauma use

ARX-04: Potential Market

175M Patients Annually

5,000 Emergency Departments (ER)

Data on file. In-house commissioned market research. Millennium Research Group “US Market Opportunity Study for Sublingual Sufentanil” Study dated March 24, 2010

5,300 Ambulatory Surgery Center (ASC)

23M Surgeries Performed at ASC’s Annually

Moderate-to-Severe

Pain Patients

Other ASC ER

51.38M 12.02M Total 76.3M

Data on file. In-house commissioned market research. ZS Associates “Opportunity Assessment, US & EU” Study dated August 8, 2014 Ambulatory Surgery Center Association and Ambulatory Surgery Foundation, History of ASCs, www.advancingsurgicalcare.com Emergency Medicine Network, National Emergency Department Inventory, www.emnet-usa.org

12.9M

14

ARX-04: Phase 3 Abdominal Surgery Study Design

Postoperative ambulatory surgery patients following

abdominal surgery

Open herniorrhaphy

Abdominoplasty

Any laparoscopic abdominal surgery

Primary endpoint: Sum of the pain intensity difference to

baseline over the first 12 hours (SPID12)

Study completed at 24 hours after first dose

15

Randomized 2:1

Study randomized 163 patients

ARX-04 Superior to Placebo on Primary Endpoint

16

25.8

13.1

0

5

10

15

20

25

30

ARX-04 Placebo

SPID12

SPID12

(p<0.001)

• Difference in pain scores superior for ARX-04 at first time measure (15 minutes) p=0.002

• ARX-04 also positive on secondary endpoints • AE’s reported in the study were typical of opioid therapy (nausea,

headache, vomiting) with no statistical difference between ARX-04 and placebo

SPID Over First Hour of Treatment

0

0.2

0.4

0.6

0.8

1

1.2

0 15 30 45 60

Placebo

ARX-04

***

**

***

***

** p<0.01 *** p<0.001

Minutes 17

Statistical Separation at 15

minutes

ARX-04: ER Study Design

Exclusions Pregnancy

Opioid-tolerant (taking more than 15 mcg oral morphine equivalent daily)

Dependent on supplemental oxygen

Primary efficacy endpoint: SPID1 Summed pain intensity difference to baseline over first hour after receiving ARX-04

Key safety endpoints Six-Item Screener (cognitive impairment test): pre-dose and one-hour post-dose

Adverse events

Vital signs

ARX-04 single-dose treatment, open label, evaluating safety and efficacy

in patients presenting to the ER with trauma or injury associated with

moderate-to-severe pain

18

ARX-04: Anticipated Timeline

Pre-NDA Meeting Dec 2015

NDA Submission H1 2016

ER Study Results Q1 2016

NDA PDUFA Date H1 2017

19

Zalviso: Sublingual Sufentanil (15mcg)

Patient Controlled Analgesia (PCA)

Single Tablet Dosage – 15mcg

Pre-programmed Delivery – Designed to Avoid Nurse Errors

No IV-Eliminates IV Related Infection Risk

Intended for Treatment of Acute Pain

20

Tablets pre-loaded in delivery device designed to dispense sublingual tablets (20-minute lock out)

Zalviso: Delivery Device Design and Features

21

Non-invasive (sublingual) delivery

Eliminates IV infection risk

May enhance ambulation

Pre-programmed delivery

Factory set 20-minute lockout period

Fixed drug and dose (15 mcg sufentanil) eliminate end-

user programming error risk associated with PCA pumps

Investigational drug and delivery system not FDA

approved for commercial use Design safety features

Priming cap, RFID cartridge provides full inventory loop tracking of sufentanil tablets

Single tablet delivery on patient demand

RFID thumb tag co-located to device helps reduce unauthorized dosing

HCP-controlled access, device tether reduces risk of product loss

Battery power for 72-hour function even in the event of power outage

Zalviso: Market Potential

22

EU5 Opportunity US Opportunity

20.1M

Non-Surgical

31.7M

Surgical

7.4 M

Moderate

To Severe

7.6M

Moderate

To Severe

9.3M

Eligible

Patients

13.6M

Moderate

To Severe

5.8M

Mild to

Moderate

Inpatient

Procedures

19.4M

Total

Inpatients

51.8M

Zalviso Phase 3 Data-Placebo Studies

23

Tim

e-W

eig

hte

d S

PID

Time (Hours)

IAP 310 - Abdominal

p=0.001

Placebo Zalviso

120

100

80

60

40

20

0

Tim

e-W

eig

hte

d

SP

ID

Time (Hours)

IAP 311 - Orthopedic

p<0.001

Placebo Zalviso

-20

100

80

60

40

20

0

Zalviso: Regulatory Status

24

FDA teleconference held and meeting minutes received

FDA requested additional study on device error

Protocol submitted, awaiting FDA feedback

Prepared to initiate in Q1:16 pending FDA feedback

All comers, single arm, various surgical settings, SPID12

Collecting data on device performance and dropped tabs

Zalviso: Grunenthal Collaboration

Commercial rights to European Union

Collaboration Details

$30M upfront received

$5M on MAA filing received

$15M on MAA approval received

$28.5M in R+D milestones remain

$166M commercial milestones remain (20% of first four worth

$44.5M in total retained as part of PDL deal)

Royalties from mid teens to mid twenties expected over life of

agreement (25% retained as part of PDL deal)

Peak revenues in EU expected to be $150M

25

Intellectual Property

IP Strategy

Drug-device combination allows

for broad patent coverage

Integrated IP and regulatory

strategy designed to minimize

ANDA exposure

IP Portfolio

11 US patents issued on NanoTab

7 US patents issued on Devices

Coverage through 2027 - 2031

3 EU patents issued on NanoTab

2 EU patents issued on Device

Coverage through 2027 - 2029

19 issued patents in other territories

11 US applications plus 30+ foreign

applications in late stage prosecution

26

Financial Summary

27

Cash on hand at September 2015

EU approval milestone (received Q4 2015)

Projected cash balance Dec 31, 2015

Outstanding Loan Amount

Shares Outstanding

$104 million

$15 million

$100+ million

$23 million

45 million

Cash sufficient to mid-2017

Milestones

28

ARX-04 DoD Contract Executed

CHMP Positive Opinion

ARX-04 SAP301 Topline Data

Completed $65M Royalty Deal

Zalviso MAA Approval

May 2015

July 2015

Sept 2015

Sept 2015

Sept 2015

ARX-04 Pre NDA Meeting

ARX-04 ER Study Results

ARX-04 NDA Submission

Zalviso single arm study commencing

Zalviso EU Commercial launch

Dec 2015

Q1 2016

H1 2016

Q1 2016

H1 2016

Upcoming:

Completed:

29