February 2015 Exhibit 99.1 |
Forward Looking Statements 2 This presentation contains forward-looking statements, including, but not limited to, statements related to future financial results, potential proceeds under the Grunenthal agreement, the process and timing of anticipated future development of AcelRx’s product candidates, including Zalviso, the NDA submission and the CRL, the Type A meeting held with the FDA to discuss the CRL, AcelRx’s plans to address the issues raised in the CRL, and anticipated resubmission of the Zalviso NDA to the FDA, including the scope of the resubmission and the timing of the resubmission and FDA review time, the impact, if any, of the FDA’s review of the amendments to the Zalviso NDA that were not previously reviewed, planned initiation of the Phase 3 clinical trial for ARX-04, and the therapeutic and commercial potential of AcelRx Pharmaceuticals' product candidates, including Zalviso. These forward-looking statements are based on AcelRx Pharmaceuticals' current expectations and inherently involve significant risks and uncertainties. AcelRx Pharmaceuticals' 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: AcelRx Pharmaceuticals' ability to receive regulatory approval for Zalviso; any delays or inability to obtain and maintain regulatory approval of its product candidates, including Zalviso, in the United States and Europe; AcelRx's ability to build an effective commercial organization; its ability to receive any milestones or royalty payments under the Grunenthal agreement; its ability to obtain sufficient financing to commercialize Zalviso and proceed with clinical development of ARX-04; the success, cost and timing of all product development activities and clinical trials, including the planned Phase 3 ARX-04 trial; the market potential for its product candidates; the accuracy of AcelRx’s estimates regarding expenses, capital requirements and needs for financing; and other risks detailed in the "Risk Factors" and elsewhere in AcelRx Pharmaceuticals' U.S. Securities and Exchange Commission filings and reports, including its Quarterly Report on Form 10-Q filed with the SEC on November 10, 2014. AcelRx Pharmaceuticals 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. |
3 AcelRx–Working to Improve Acute Pain Management Zalviso TM profile from Phase 3 studies Efficacy: Demonstrated in two placebo controlled studies, 1 active comparator study Adverse events: Most common related AE’s were nausea, vomiting, O 2 desaturation, itching High patient satisfaction and nurse ease of care reported Grünenthal partnership to commercialize Zalviso in EU & Australia established Upcoming regulatory catalysts in US and EU US: NDA resubmission targeted Q1 2015 EU: Day 120 submission planned for Q1 2015 Strong balance sheet with $75 million cash on hand December 31, 2014 (unaudited) Terms: $250M upfront and potential milestones, mid-teens to mid-twenties % royalty Other Territories: Continue to seek additional partnerships in Asia & South America CE Mark: Received December 2014 MAA filed in Switzerland |
4 AcelRx Update Q1 2015 Zalviso resubmission • Received FDA comments on bench testing • • • – Healthy volunteers study completed at risk, testing successful – Post-op patient study initiated Zalviso EU Day 120 Response • • • Expected submission in Q1 ARX-04 • Discussion with DoD continues, funding targeted for H1 2015 • Pivotal Phase 3 study to be initiated in Q1 without DoD funding Bench testing initiated, anticipated completion end of February Awaiting FDA comments on Human Factors protocol Proposed HF study to FDA in two populations: healthy volunteers, post-op patients All questions to be addressed and in process of preparing a response CE mark approved and to be included as part of response |
Major items in CRL: System errors were noted in the clinical setting at a single digit rate Did not appear to impact Phase 3 safety and efficacy results Improvements have been made to reduce error rate Formal bench testing in process to confirm error rate reduction 15 misplaced tablets of ~30,000 doses IFU modified to address this issue HF studies underway to confirm IFU/GUI changes are adequate Data to be provided to support 24 month dating 5 Zalviso NDA Status-CRL received July 25, 2014 Demonstration of a reduction in the incidence of system errors Changes to the Instructions for Use (IFU) to address inadvertent dosing Support for shelf life (not approvability issue) |
Proposed Indication: Management of Moderate to Severe In-Hospital Acute Pain Investigational drug and delivery system not FDA approved for commercial use 6 Clinical Data |
Invasive route of delivery IV infiltration causes analgesic gaps IV connection restricts patient mobility Risk of IV site infection Programming errors 1/9 harmful hospital errors due to IV PCA 2 IV PCA – Current Standard of Care 7 In-hospital, post-operative moderate to severe pain control Higher Patient satisfaction when patients control their own pain IV-PCA 1. FDA / AAMI Summit Meeting held October 2010; http://www.aami.org/infusionsummit/AAMI_FDA_Summit_Report.pdf 2. Calculated from “The rate and costs attributable to intravenous patient-controlled analgesia errors.” Brian Meissner et al, Hospital Pharmacy April 2009 Infusion pumps large source of morbidity / mortality 1 |
Zalviso: Leveraging Sufentanil High Therapeutic Index Opioid In animal studies High Lipophilicity 6 minute brain:plasma equilibration No active metabolites OPIOID THERAPEUTIC INDEX Morphine 71 1 Hydromorphone 232 2 Fentanyl 277 1 Sufentanil 26,716 1 8 Sublingual Sufentanil Delivery May reduce IV peaks & troughs Small size may minimize swallowed drug May result in high bioavailability Helps with goal of consistent dose delivery Supplied in cartridge of 40 Tablets 2 days for average patient 1. Mather, Clin Exp Pharmacol Physiol 1995; 22:833. 2. Kumar, Eur J Pharmacol 2008; 597:39 (ED50) and Purdue Pharma MSDS, 2009 (LD50) Enables rapid transmucosal uptake |
9 9 Zalviso: Delivery Device Design and Feature Set Non-invasive (sublingual) delivery Eliminates IV infection risk May enhance ambulation Pre-programmed delivery Factory set 20-minute lockout period Addresses end-user programming error risk Design safety features Set-up tablet, RFID cartridge provides full inventory loop tracking of sufentanil tablets RFID thumb tag co-located to device helps reduce proxy dosing HCP controlled access, device tether reduces risk of product loss Battery power ensures 72-hour function even in the event of power outage Investigational drug and delivery system not FDA approved for commercial use |
Zalviso Phase 3 Program 10 Surgery Type Study Type Sites N Data Primary Endpoint Results Abdominal & Orthopedic Surgery (IAP309) Open-label, Active-comparator 1 o EP: Patient Global Assessment of Method of Pain Control over 48 hrs 26 359 1:1 Nov 2012 Zalviso non-inferior to IV PCA (p<0.001) Zalviso also demonstrates superiority to IV PCA (p=0.007) Abdominal Surgery (IAP310) Double-blind, Placebo-controlled 1 o EP:Sum of Pain Intensity Difference over 48 hrs 13 178 2:1 Mar 2013 Sufentanil treatment superior to placebo p=0.001 Orthopedic Surgery (IAP311) Double-blind, Placebo-controlled 1 o EP:Sum of Pain Intensity Difference over 48 hrs 34 426 3:1 May 2013 Sufentanil treatment superior to placebo p<0.001 |
IAP310 & IAP311 Primary Endpoint: SPID-48 – ITT Population 11 p=0.001 p<0.001 Time (hrs) Time (hrs) Zalviso Zalviso 0 20 40 60 80 100 120 IAP 310 – Abdominal Placebo -20 0 20 40 60 80 100 IAP 311 - Orthopedic Placebo |
12 Time from first dose of study drug (hours) Zalviso: Studies Indicate Rapid Ability to Control Moderate to Severe Acute Pain 0 1 2 3 0 0.25 0.5 0.75 1 2 3 4 5 6 Zalviso 309 Zalviso 310 Zalviso 311 IV PCA MS 309 |
Adverse Reactions >2% in Placebo Studies 13 * Significantly Different between Zalviso and Placebo (p<0.05) Possibly or Probably Related Adverse Reactions Zalviso N=429 Placebo N=162 Nausea 29.4% 22.4% Vomiting 8.9% 4.9% Oxygen Saturation Decreased 6.1% 2.5% Itching* 4.7% 0% Dizziness 4.4% 1.2% Constipation 3.7% 0.6% Headache 3.3% 3.7% Insomnia 3.3% 1.9% Hypotension 3.0% 1.2% Confusional State 2.1% 0.6% |
Proposed Indication: Management of Moderate to Severe In-Hospital Acute Pain Investigational drug and delivery system not FDA approved for commercial use 14 Commercial Opportunity |
Target Market Potential 15 1. Rosetta, 2009 Inpatient sample 2. Decision Resources, Pain Management Study, Acute Pain, October 2014 • The potential market for Zalviso is defined as: • Acute moderate-to-severe pain population in the hospital setting • Includes post-operative as well as non-surgical pain • The market size for Zalviso is characterized by hospital in-patient sampling that demonstrates 15M patients annually 1 • 7.6M patients post-op • 7.4M patients non post-op 2013 U.S. Acute Pain Market $6.7B 2 • 43% of which represents post-op pain • 20% of which represents other acute pain (non post-op) 1 |
Anticipated Formulary Adoption after FDA Approval Earliest – 2 Months; Typical – 8-10 Months 16 42% Very Likely to Approve 42% Quite Likely to Approve 16% Early Approval Unlikely might be swayed by additional, independent clinical literature assume product expensive, might accept favorable cost-benefit analysis looking for relevant experts to champion the product unsure of cost, looking for favorable cost-benefit analysis convinced by the clinical benefit demonstrated assume ability to demonstrate economic benefit or set cost aside ZS Associates Qualitative Survey Among 45 P&T Committee Members, Fall 2013, sponsored by AcelRx Pharmaceuticals, Inc. |
Strong Positive Reaction to Zalviso Clinical Profile Market Research Among Hospital Specialists (n=244) Predicted Zalviso Share of Procedural Volume * Size of bubble is representative of size of Zalviso opportunity in Specialty 0 10% 20% 30% 40% 50% 60% 17 Orthopedic Surgeons Cardiothoracic Surgeons General Surgeons Hospitalist Anesthesiologist OB / GYN 1. ZS Associates Quantitative Survey Among Hospital Specialists, Winter 2013, sponsored by AcelRx Pharmaceuticals, Inc. 1 |
Current Cost of IV PCA 18 Data from Premier Database, 2010-12 Data for post surgical pain management involving IV PCA in total knee/hip replacement and abdominal surgery Costs for pumps, tubing, carrier saline and drug range from $200-240 for 2 days Zalviso may add value: Addresses programming errors Elimination of PCA IV site infection risk Supports early ambulation Enhanced patient satisfaction 1. COST OF INTRAVENEOUS PATIENT-CONTROLLED ANALGESIA (IV PCA) EQUIPMENT AND OPIOID MEDICATION FOR ORTHOPEDIC AND ABDOMINAL SURGERIES IN US HOSPITALS 0 50 100 150 200 250 300 Opioids via PCA/ Other Tubing / Carrier Saline IVPCA / Carrier Infusion Pump Total Knee Total Hip Abdominal Xiang (Jay) Ji, MS, Jennifer Stephens, PharmD, Pamela Palmer, MD, PhD. Poster presented at ISPOR meeting, June 2014 |
US Customer-focused Organization Planned Build 80% of relevant procedure volume identified in top 1,400 accounts 65 sales territories planned Estimated cost/rep $250K Estimated salesforce cost around $16.5M per annum 19 Medical Affairs 8 MSL’s in place Commercial 7 RBD’s (6 hired) 65 Account Managers to be hired |
20 Zalviso Publication Strategy Peer Reviewed Manuscripts in Process A Phase 3 Study of a Sufentanil Sublingual Microtablet System for the Management of Postoperative Pain Following Major Orthopedic Surgery (IAP-311 Primary); Anesthesiology - Submitted Peer-Reviewed Manuscripts Available Cost of Opioid Intravenous Patient-controlled Analgesia: Results From a Hospital Database Analysis and Literature Assessment. (Palmer et al.) Clinicoeconomics and Outcomes Research www.dovepress.com/getfile.php?fileID=20509 Pharmacokinetics of Sublingual Sufentanil Tablets and Efficacy and Safety in the Management of Postoperative Pain (Minkowitz et al.) Reg Anesth Pain Med 2013;38: 131-139. Sufentanil Sublingual Microtablet System versus Intravenous Patient-Controlled Analgesia with Morphine for Postoperative Pain Control: A Randomized, Controlled Trial (IAP309 Primary); Pain Practice; http://onlinelibrary.wiley.com/doi/10.1111/papr.12238/full • A Phase 3 Study of Sufentanil Sublingual Microtablet System for the Management of Postoperative Pain Following Open Abdominal Surgery (IAP-310 Primary); Reg Anesth Pain Med – http://journals.lww.com/rapm/Abstract/onlinefirst/Sufentanil_Sublingual_Tablet_System_for_the.99572.aspx |
Investigating Moderate to Severe acute pain treatment in medically supervised settings Investigational drug and delivery system not FDA approved for commercial use 21 ARX-04 HCP Administered Single 30mcg dose Sufentanil Tablet |
ARX-04 – Short Term Acute Pain Management 22 End of Phase 2 Meeting held Dec. ‘13 505(b)(2) submission 500 patient safety database , 100 multiple dose, 400 single dose Single & repeat dose PK study - completed Phase 3 placebo-controlled study Abdominal surgery, SPID-12 primary, follow for 48 hours Results expected H2 2015 Small safety study in ER patients planned - results expected H2 2015 Will count as pivotal trial -0.5 0 0.5 1 1.5 2 2.5 0 15 30 45 60 Minutes after Dose 30 mcg 20 mcg placebo * ** ** *p<0.01 **p<0.001 Successful Phase 2 Bunionectomy Study |
ARX-04 – PK Study Results 23 Demonstration of Bioequivalence of 2 x 15 mcg and 1 x 30 mcg sublingual sufentanil tablets Bioavailability: 30 mcg 57.6% 2 x 15 mcg 60.9% Proposed to FDA that demonstration of bioequivalence for 2 x 15mcg dosed 20 mins apart and single 30mcg dose would enable use of Zalviso database to support ARX-04 In Phase 3 Zalviso studies, 323 patients dosed at t=0 and between t=20-25mins later 0.0 10.0 20.0 30.0 40.0 50.0 60.0 0 100 200 300 400 Time (minutes) One 30 mcg tablet 2 x 15 mcg tablet BA for 30 mcg 57.6% BA for 2 x 15 mcg 60.9% |
ARX-04 – Commercial Opportunity 24 Market Research Suggests Broad Opportunity in Moderate to Severe Acute Pain* ER Department 51MM patients annually 2 doses per patient on average Inpatient Surgery 8MM patients annually 2-9 doses per patient Outpatient Surgery 13MM patients annually 3 doses per patient on average Non-surgical Acute Pain 4MM patients annually 8 doses per patient on average ZS Associates US Opportunity Sizing, September 2014; Includes only patients 18+ years of age. Sponsored by AcelRx Pharmaceuticals, Inc. 0% 20% 40% 60% 80% Physician Stated Share |
25 Scientific Conference Schedule - 2015 Minimally Invasive Surgery Symposium (MISS) February 25-28; Las Vegas, NV – poster presentation (ARX- 04) American Academy of Orthopedic Surgeons (AAOS) March 24-28; Las Vegas, NV – Booth & Symposium American Society of Peri-Anesthesia Nurses (ASPAN) April 26-30; San Antonio, TX – Booth & Symposium American Congress of Obstetricians (ACOG) May 2-6; San Francisco – Booth & Symposium International Conference on Emergency Medicine (ICEM) American Society of Pain Management Nursing (ASPMN) September 16-19; Atlanta, GA – Booth & Symposium American College of Surgeons (ACS) October 4-8; Chicago, IL – Booth & Symposium American Society of Anesthesiologists (ASA) October 24-28; San Diego, CA – Booth & Symposium American Society of Regional Anesthesia and Pain Management (ASRA) November 19-21; Miami, FL – 1 Booth & Symposium American Society of Health System Pharmacists (ASHP) December 6-10; New Orleans, LA – Booth & Symposium May 11-12; Montreal, Quebec – Podium Presentation (ARX-04) February 25-28; Las Vegas, NV – poster presentation (ARX-04) |
Financial Summary 26 Cash position at September 30, 2014: $85 million $10 million drawn June 2014 under debt facility $5 million received August 2014 from Grünenthal for MAA submission Currently available cash resources fund operations through launch Assumes timely regulatory approval of Zalviso in the US in 2015 Supports execution of all planned US pre-commercial launch efforts Q3 2014 cash usage of ~$12 million Headcount at December 31, 2014: 50 Cash balance December 31, 2014 $75 million (unaudited) 44 million shares outstanding at December 31, 2014 |
Future Catalysts 27 Event Timing 120 day question response to Zalviso MAA review Q1 2015 Zalviso NDA resubmission (pending protocol approval) Q1 2015 ARX-04 DOD contract finalized H1 2015 Zalviso NDA decision Q3 2015 Zalviso MAA decision Q3 2015 ARX-04 Phase 3 data H2 2015 |
28 AcelRx–Working to Improve Acute Pain Management Zalviso TM profile from Phase 3 studies Efficacy: Demonstrated in two placebo controlled studies, 1 active comparator study Adverse events: Most common related AE’s were nausea, vomiting, O 2 desaturation, itching High patient satisfaction and nurse ease of care reported Grünenthal partnership to commercialize Zalviso in EU & Australia established Upcoming regulatory catalysts in US and EU US: NDA resubmission targeted Q1 2015 EU: Day 120 submission planned for Q1 2015 Strong balance sheet with $75 million cash on hand December 31, 2014 (unaudited) MAA filed in Switzerland CE Mark: Received December 2014 Other Territories: Continue to seek additional partnerships in Asia, South America Terms: $250M upfront and potential milestones, mid-teens to mid-twenties % royalty |