UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 12, 2015
ACELRX PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
| DELAWARE | 001-35068 | 41-2193603 | ||
| (State of incorporation) | (Commission File No.) | (IRS Employer Identification No.) |
351 Galveston Drive
Redwood City, CA 94063
(Address of principal executive offices and zip code)
Registrant’s telephone number, including area code: (650) 216-3500
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Item 2.02 Results of Operations and Financial Condition.
AcelRx Pharmaceuticals, Inc. (the “Company” or “AcelRx”) will be providing financial information about the Company’s cash and investment balances as of December 31, 2014 in the Company’s presentation handout to be utilized in various meetings with securities analysts and investors during the J.P. Morgan Healthcare Conference from January 12, 2015 through January 15, 2015. The aforementioned financial information is included on slides #3, #27 and #29 of the presentation handout, as furnished in Exhibit 99.1 to this Current Report and is incorporated herein by reference.
The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 to this Current Report shall be deemed to be “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 to this Current Report shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission under the Securities Act or the Exchange Act made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 7.01. Regulation FD Disclosure.
AcelRx will participate in various meetings with securities analysts and investors during the J.P. Morgan Healthcare Conference from January 12, 2015 through January 15, 2015 and will utilize a presentation handout during those meetings. The presentation handout, together with a slide setting forth certain cautionary language intended to qualify the forward-looking statements included in the presentation handout, are furnished as Exhibit 99.1 to this Current Report and are incorporated herein by reference. The presentation handout will also be made available in the “Investor Relations” section of AcelRx Pharmaceuticals, Inc.’s website, located at www.acelrx.com.
The information contained in this Item 7.01 and in the accompanying Exhibit 99.1 to this Current Report shall be deemed to be “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that Section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying Exhibit 99.1 to this Current Report shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission under the Securities Act or the Exchange Act made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit Number |
Description | |
| 99.1 | Slide presentation entitled, “AcelRx Pharmaceuticals, Inc. January 2015” | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: January 13, 2015 | ACELRX PHARMACEUTICALS, INC. | |||||
| By: | /s/ Timothy E. Morris | |||||
| Timothy E. Morris | ||||||
| Chief Financial Officer | ||||||
INDEX TO EXHIBITS
| Exhibit Number |
Description | |
| 99.1 | Slide presentation entitled, “AcelRx Pharmaceuticals, Inc. January 2015” | |
| Exhibit 99.1
|
January 2015
|
|
Forward Looking Statements
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 recent 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.
2
|
|
AcelRx–Working to Improve Acute Pain Management
ZalvisoTM 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, O2 desaturation, itching High patient satisfaction and nurse ease of care reported
Grünenthal partnership to commercialize Zalviso in EU & Australia established
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
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) 3
|
|
Zalviso NDA Status-CRL received July 25, 2014
Major items in CRL:
Demonstration of a reduction in the incidence of optical system errors
Optical 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 Additional bench testing to be completed to confirm error rate reduction
Changes to the Instructions for Use (IFU) to address inadvertent dosing
15 misplaced tablets of ~30,000 doses IFU modified to address this issue
HF studies will be required to confirm IFU/GUI changes are adequate
Support for shelf life (not approvability issue)
Data to be provided to support 24 month dating
| 4 |
|
|
|
Zalviso NDA Resubmission Plan
Type A meeting with FDA to clarify CRL issues held
Modifications to dispenser completed IFU modifications completed
Protocols for bench testing and HF study submitted to FDA
Shelf life data available and to be included in resubmission FDA to review and comment on protocols
Bench testing and HF work to be completed Expected to refile by end of Q1 2015
Type II submission (6 month review)
5
|
|
Proposed Indication: Management of
Moderate to Severe In-Hospital Acute Pain
Investigational drug and delivery system not FDA approved for commercial use
6
|
|
IV PCA – Current Standard of Care
In-hospital, post-operative moderate to severe pain control Higher Patient satisfaction when patients control their own pain
Invasive route of delivery
IV infiltration causes analgesic gaps IV connection restricts patient mobility Risk of IV site infection
Programming errors
Infusion pumps large source of morbidity / mortality1 1/9 harmful hospital errors due to IV PCA2
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
7
|
|
Zalviso: Leveraging Sufentanil
OPIOID
THERAPEUTIC
INDEX
Morphine
711
Hydromorphone
2322
Fentanyl
2771
Sufentanil
26,7161
High Lipophilicity
Enables rapid transmucosal uptake 6 minute brain:plasma equilibration
No active metabolites
1. Mather, Clin Exp Pharmacol Physiol 1995; 22:833.
2. Kumar, Eur J Pharmacol 2008; 597:39 (ED50) and Purdue Pharma MSDS, 2009 (LD50)
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
8
|
|
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
9
|
|
Zalviso Phase 3 Program
Primary Endpoint
Surgery Type Study Type Sites N Data
Results
Open-label, Zalviso non-inferior to IV PCA
Abdominal & (p<0.001)
Active-comparator 359 Nov
Orthopedic 1o EP: Patient Global 26 Zalviso also demonstrates
1:1 2012
Surgery (IAP309) Assessment of Method of superiority to IV PCA
Pain Control over 48 hrs (p=0.007)
Double-blind, Sufentanil treatment
Abdominal Placebo-controlled 178 Mar
13 superior to placebo
Surgery (IAP310) 1o EP:Sum of Pain Intensity 2:1 2013
Difference over 48 hrs p=0.001
Double-blind, Sufentanil treatment
Orthopedic Placebo-controlled 426 May
34 superior to placebo
Surgery (IAP311) 1o EP:Sum of Pain Intensity 3:1 2013
Difference over 48 hrs p<0.001
10
|
|
IAP310 & IAP311 Primary Endpoint:
SPID-48 – ITT Population
Time-Weighted SPID
IAP 310 – Abdominal
120 100 80 60 40 20 0
0.25 0.75 2 6 10 16 24 32 40 48
Time (hrs)
Sufentanil NanoTab Placebo
p=0.001
Time-Weighted SPID
IAP 311—Orthopedic
Time afterTime first (hrs) study drug dosing
(hrs)
Sufentanil NanoTab Placebo
100 80 60 40 20 0 -20
0.25 0.75 2 6 10 16 24 32 40 48
11
|
|
Zalviso: Studies Indicate Ability to Control Moderate to Severe Acute Pain
Patient Pain Intensity
Difference
Zalviso 309 Zalviso 310 Zalviso 311 IV PCA MS 309
3 2 1 0
0 0.25 0.5 0.75 1 2 3 4 5 6
Time from first dose of study drug (hours)
12
|
|
Adverse Reactions >2% in Placebo Studies
Possibly or Probably
Zalviso
Placebo
Related Adverse Reactions
N=429
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%
13
|
|
* Significantly Different between Zalviso and Placebo (p<0.05)
Proposed Indication: Management of
Moderate to Severe In-Hospital Acute Pain
Investigational drug and delivery system not FDA approved for commercial use
14
|
|
Moderate-to-Severe Pain in US Hospital Settings1,2
Hospital in-patient, moderate-to-severe acute pain, post-operative
12M procedures per annum, Zalviso potentially usable in ~95% cases
Hospital in-patient, moderate-to-severe acute pain, not post-operative
7.4M patients per annum, Zalviso potentially usable in ~66-80% cases IV push opioid is current standard for acute non-post-op pain, not IV PCA Physicians reported Zalviso may be supplementary to IV push
Hospital Hospice in-patient, moderate-to-severe acute pain
300k patients per annum, Zalviso potentially usable in ~40% cases Zalviso is a potential replacement for liquid morphine
1. Rosetta Mini-quant Survey fielded to 29 physicians (15 hospitalists and 14 anesthesiologists) in Winter 2011.
2. Rosetta Qualitative Interviews, Fall 2011.
15
|
|
Anticipated Formulary Adoption after FDA Approval
Earliest – 2 Months; Typical – 8-10 Months
42% Very Likely to Approve
convinced by the clinical benefit demonstrated
assume ability to demonstrate economic benefit or set cost aside
42% Quite Likely to Approve
looking for relevant experts to champion the product
unsure of cost, looking for favorable cost-benefit analysis
16% Early Approval Unlikely
might be swayed by additional, independent clinical literature
assume product expensive, might accept favorable cost-benefit analysis
ZS Associates Qualitative Survey Among 45 P&T Committee Members, Fall 2013, sponsored by AcelRx Pharmaceuticals, Inc.
16
|
|
Strong Positive Reaction to Zalviso Clinical Profile
Market Research Among Hospital Specialists (n=244)1
Total Relevant Procedure Volume
0
10% 20% 30% 40% 50% 60%
Orthopedic Surgeons
General Surgeons
Cardiothoracic Surgeons OB / GYN
Hospitalist
Anesthesiologist
* Size of bubble is representative of size of Zalviso opportunity in Specialty
Predicted Zalviso Share of Procedural Volume
1. ZS Associates Quantitative Survey Among Hospital Specialists, Winter 2013, sponsored by AcelRx Pharmaceuticals, Inc.
17
|
|
Current Cost of IV PCA
Cost per patient for 2 days ($)1
0 50 100 150 200 250 300
Total Knee Total Hip Abdominal
IVPCA / Carrier Infusion Pump
Tubing / Carrier Saline
Opioids via PCA/ Other
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
Xiang (Jay) Ji, MS, Jennifer Stephens, PharmD, Pamela Palmer, MD, PhD. Poster presented at ISPOR meeting, June 2014
18
|
|
US Customer-focused Organization Planned Build
Medical Affairs
Commercial 8 MSL’s in place 7 RBD’s (6 hired)
65 Account Managers to be hired
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
|
|
Zalviso Publication Strategy
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
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
20
|
|
ARX-04
HCP Administered Single 30mcg dose Sufentanil Tablet
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 – Short Term Acute Pain Management
Phase 2: 30mcg sufentanil tablet Rapid onset of effect demonstrated
Pain Intensity Difference (LS Mean)
2.5 2 1.5 1 0.5 0
-0.5 0
15 30 45 60
Minutes after Dose
30 mcg 20 mcg placebo
*p<0.01 **p<0.001
End of Phase 2 Meeting held Dec.
Proposed Clinical Development
Pathway
505(b)(2) submission
500 patient safety database , 100 multiple dose, 400 single dose
Phase 3 placebo controlled study
Abdominal surgery, SPID-12 primary, follow for 48 hours
Results expected H2 2015
Single & repeat dose pk study
In addition, a small ER study is planned
Results expected H2 2015
22
|
|
ARX-04 – PK Study Results
Demonstration of Bioequivalence of 2x15mcg and 1x30mcg 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
Bioavailability of 1x30mcg and 2x15mcg sublingual sufentanil tablets
60.0
(pg/mL) 50.0
40.0
30.0
Concentration 20.0 Plasma 10.0
0.0
0 100 200 300 400
BA for 30 mcg 57.6% BA for 2 x 15 mcg 60.9%
One 30 mcg tablet
2 x 15 mcg tablet
Time (minutes)
23
|
|
ARX-04 – Commercial Opportunity
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
Physician Stated Share
80%
60%
40%
20%
0%
Emergency Room Inpatient Surgery Outpatient Surgery Non-surgical Impatient
ZS Associates US Opportunity Sizing, September 2014; Includes only patients 18+ years of age.
Sponsored by AcelRx Pharmaceuticals, Inc.
24
|
|
Zalviso – ARX-04 Commercial Synergy
Duration of moderate-severe pain
24+ hrs 12 hrs 1-6 hrs
Inpatient Surgery Emergency Room
Outpatient Surgery/ASC
Non-surgical Acute Pain
Zalviso ARX-04
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)
May 11-12; Montreal, Quebec – Podium Presentation (ARX-04)
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
26
|
|
Financial Summary
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
27
|
|
Future Catalysts
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
Q1
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
ZalvisoTM 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, O2 desaturation, itching High patient satisfaction and nurse ease of care reported
Grünenthal partnership to commercialize Zalviso in EU & Australia established
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
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)
29