Amendment No. 1 to Form 8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K/A

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported) March 26, 2012

 

 

A.P. Pharma, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-33221   94-2875566

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

123 Saginaw Drive

Redwood City CA

  94063
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code (650) 366-2626

N/A

(Former name or former address, if changed since last report)

 

 

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))

 

 

 


EXPLANATORY NOTE

The purpose of this amendment to the Current Report on Form 8-K of A.P. Pharma, Inc. (the “Company”), as filed with the Securities and Exchange Commission on March 26, 2012, (the “Original Filing”), is to file a corrected Exhibit 99.1. On Slide number 23, the slope was corrected from -0.19 to -0.019. All of the other Items in the Original Filing are unchanged.

 

ITEM 8.01 Other Events.

A.P. Pharma, Inc. (the “Company”) will deliver a corporate presentation at meetings with investors during the week of March 26, 2012. The slides from the presentation are attached hereto as Exhibit 99.1. The attached materials have also been posted on the Company’s website at www.appharma.com. The Company does not undertake to update this presentation.

 

ITEM 9.01 Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit
No.

  

Description

99.1    Corporate Presentation, dated March 2012


SIGNATURE

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.

 

        A.P. Pharma, Inc.
Date: March 26, 2012    

/s/ John B. Whelan

    John B. Whelan
    President and Chief Executive Officer
Corporate Presentation, dated March 2012
Company Overview
OTCBB: APPA
March 2012
Exhibit 99.1


Legal Disclaimer
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.
2
This presentation contains "forward-looking statements" as defined by the Private
Securities Litigation Reform Act of 1995.  These forward-looking statements
involve risks and uncertainties, including uncertainties associated with timely
development, approval, launch and acceptance of new products, satisfactory
completion of clinical studies, establishment of new corporate alliances, progress
in research and development programs and other risks and uncertainties identified
in the Company's filings with the Securities and Exchange Commission.  Actual
results may differ materially from the results expected in our forward looking
statements.  We caution investors that forward-looking statements reflect our
analysis only on their stated date.  We do not intend to update them except as
required by law.


Company:
A.P. Pharma, Inc.
Ticker:
OTCBB: APPA.OB
Stock Price:
$0.33 (3/23/12)
Market Capitalization:
$111.2 million
1
Cash:
$18.0
million
2
Debt:
$1.57 million
2
Stock Summary
3
1
Based on 394.5 million fully diluted, as-converted common shares assuming the full
conversion of convertible debt outstanding or subject to purchase rights and 80 million
warrants using treasury stock method; not including options
2
As of December 31, 2011
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


John B. Whelan
President, CEO & CFO
Raven Biotechnologies
Eos Biotechnology
Hewlett Packard/Agilent
Michael A. Adam,
Ph.D.
Senior Vice President &
Chief Operating Officer
Spectrum Pharmaceuticals
Pfizer
Bristol-Myers Squibb
Thomas Ottoboni,
Ph.D.
Vice President,
Pharmaceutical Development
Talima Therapeutics
Point Biomedical
InSite Vision
Kristin Ficks*
Head of Commercial Operations
Gemini Healthcare
Celgene
Eisai/MGI Pharma
Management
4
*Ms. Ficks is an employee of Gemini Healthcare, LLC, and a consultant to A.P. Pharma
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


A.P. Pharma Highlights
5
Lead product candidate, APF530, is long-acting, injectable
product for chemotherapy-induced nausea and vomiting (CINV)
Incorporates
widely
used
5-HT3
anatgonist -
granisetron
(Kytril
®
)
5-day delivery profile
Reduces both acute-
and delayed-onset CINV with single injection
APF530
shown
to
be
non-inferior
to
market
leader
Aloxi
®
1,341-patient, randomized, controlled, Phase 3 study
Presented at ASCO 2009
Company is addressing issues raised in Complete Response
Letter
End-of-review meetings held in 1Q 2011
Resubmission planned for mid-2012
APF530 targets a $900 million market opportunity in US alone
Could be second, long-acting, injectable product on market
A.P. Pharma has the potential to leverage its Biochronomer™
drug delivery technology into other opportunities
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Important APF530 Milestones
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.
6
Milestone
Timing
Status
Successful end-of-review meetings
with FDA
1Q 2011
$24M New Funding
2Q 2011
Successful Completion of Thorough
QT Study
1Q 2012
Successful Completion of
Metabolism Study
1Q 2012
Human Factors Validation Study
2Q 2012*
Complete CMC Activities
2Q 2012*
Resubmit NDA
Mid-2012*
Expected NDA Approval Decision
~Year-end 2012*
* Indicates expected milestone timing


Clinical Summary
7
©
2012. A.P. Pharma, Inc. All rights reserved.


APF530 Pivotal Phase 3 Study Overview
Randomized, controlled, multi-center study
1,341 patients in primary efficacy population
Two doses of APF530 (5 mg and 10 mg granisetron)
compared to the approved dose of Aloxi
Patients stratified by type of chemotherapy regimen
(moderately or highly emetogenic)
Primary end point compared complete response between
groups in both the acute (day 1) and delayed (days 2-5)
phase
Complete response defined as no emesis and no rescue medications
A ±15% margin was used to establish non-inferiority
8
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


APF530 Phase 3 Study Design
APF530
(10mg)
APF530
(5mg)
APF530
(5mg)
Aloxi
APF530
(10mg)
APF530
(5mg)
Aloxi
APF530
(10mg)
APF530
(5mg)
APF530
(10mg)
Cycle 1
Cycles
2 to 4
Patient Stratification
(n = 1,341)
Moderately Emetogenic
(n = 634)
Highly Emetogenic
(n = 707)
9
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Primary Efficacy Results: Complete Response
Patients Receiving Moderately
Emetogenic Chemotherapy
10
Acute
Delayed
APF530 5mg
APF530 10mg
Acute
Delayed
Acute
Delayed
Difference in Complete Response
APF530-Aloxi (97.5% CI)
-15
-10
-5
0
5
10
15
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


Primary Efficacy Results: Complete Response
Difference in Complete Response
APF530-Aloxi (98.33% CI)
-15
-10
-5
0
5
10
15
Acute
Acute
Delayed
Delayed
APF530 5mg
APF530 10mg
Patients Receiving Highly
Emetogenic Chemotherapy
11
Acute
Delayed
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.
80.7
77.7
81.3
66.4
64.6
68.3
0
10
20
30
40
50
60
70
80
90
100


Safety Summary
1
Pulmonary embolism in morbidly obese patient on day 16
2
>90% of injection site reactions were reported as mild; one patient discontinued due to
Reported in Cycle 1
12
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.
N
%
N
%
N
%
Drug
Related
Serious
Adverse
Events
1
0.2
0
0
0
Discontinued Due to Adverse Event
1
0.2
1
0.2
0
0
Frequent Adverse Events
Gastrointestinal disorders
Constipation
Diarrhea
Abdominal pain
62
49
21
13.4
10.6
4.5
72
44
13
15.4
9.4
2.8
62
39
28
13.4
8.4
6.0
Nervous System
Headache
31
6.7
47
10.0
45
9.7
Injection Site
2
Placebo (NaCl)
Bruising
Erythema (redness)
Nodule (lump)
Pain
78
33
22
16
16.8
7.1
4.7
3.4
93
51
50
33
10.9
10.7
7.1
14
3
5
8.9
3.0
0.6
1.1
0
19.9
41
APF530 5 mg
APF530 10 mg
Aloxi 0.25 mg
injection site reaction
1


APF530’s Efficacy with Difficult Chemo Regimens
13
Treatment
Chemotherapeutic Regimen
APF530 10 mg
Aloxi 0.25 mg
Moderately
Emetogenic
Acute
Cyclophosphamide/Doxorubicin
70.7%
65.7%
All other regimens
84.4%
85.0%
Delayed
Cyclophosphamide/Doxorubicin
47.4%
46.3%
All other regimens
72.9%
70.0%
Highly
Emetogenic
Acute
Cisplatin regimens
81.1%
75.5%
Carboplatin/Paclitaxel
85.4%
89.8%
All other regimens
75.4%
67.6%
Delayed
Cisplatin regimens
66.0%
60.4%
Carboplatin/Paclitaxel
70.8%
71.4%
All other regimens
65.2%
57.4%
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


APF530’s Sustained Efficacy in Cycles 2-4
14
* Sakai et al (Annals of Oncology, Vol. 19 Sept. 2008)
Complete Response Rates for Delayed-onset CINV in Patients Receiving
Highly Emetogenic Chemotherapy
351
315
254
117
100%
90%
72%
33%
240
169
129
94
100%
70%
54%
39%
N =
% of Cycle 1
APF530 10mg
Aloxi 0.75mg*
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012
68.3
76.3
79.1
87.2
58.7
54.3
62.2
65.0
0
10
20
30
40
50
60
70
80
90
100
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Cycle 1
Cycle 2
Cycle 3
Cycle 4


Summary of APF530 Phase 3 Results
One of the largest, randomized, controlled clinical studies
conducted in the CINV setting
Non-inferiority to Aloxi was demonstrated
For both acute-
and delayed-onset CINV
With both moderately and highly emetogenic chemotherapy
APF530 was safe and well-tolerated
Incidence of adverse events comparable to Aloxi
High response rates were observed in difficult
chemotherapy regimens
A high level of efficacy was maintained through multiple
cycles of chemotherapy
15
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Regulatory Status
16
©
2012. A.P. Pharma, Inc. All rights reserved.


APF530 NDA Status
Submitted NDA in May 2009
Received Complete Response Letter in March 2010
FDA raised issues in three main areas:
Dosing system
Two-syringe system
Chemistry, Manufacturing, and Controls (CMC)
Sterilization
Characterization
Clinical/statistical
Specific studies
Presentation of data
Held end-of-review meetings with FDA in 1Q 2011
No additional clinical efficacy studies requested
Implementing plan to resubmit NDA in mid-2012
17
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Progress of NDA Resubmission
Dosing System
Change to single-syringe system –
completed
Enhanced
dosing
instructions
completed
Overall, simpler and more convenient
Formative,
non-clinical
human
factors
study
completed
Validation protocol under review by FDA
Chemistry, Manufacturing, and Controls
Change
from
bulk
to
terminal
irradiation
feasibility completed
Additional specifications and assays for raw materials, polymer and drug
product –
in progress
Manufacturing
runs
incorporating
these
changes
in progress
Clinical/Statistical
Thorough QT study –
completed
Metabolism study –
completed
Phase 3 clinical data presentation revision –
in progress
18
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Thorough QT Study Background
19
Prolongation of the QT/QTc interval is associated with
increased susceptibility to fatal cardiac tachyarrhythmias
Thorough QT studies are intended to determine whether a
drug has a threshold pharmacologic effect on cardiac
repolarization
Thorough QT studies are now routinely required by the
FDA prior to drug approval
The QT interval represents
the amount of time the
heart’s electrical system
takes to repolarize after
each beat
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Cardiac Safety Concerns in 5-HT3 Antagonist Class
20
“Anzemet causes a dose-dependent prolongation in the QT, PR, and QRS
intervals on an electrocardiogram (ECG) …
Anzemet injection should no
longer be used to prevent nausea and vomiting associated with initial and
repeat courses of emetogenic cancer chemotherapy.”
-
FDA Drug Safety Communication, Dec. 17, 2010
“Ondansetron (Zofran) may increase the risk of developing abnormal changes
in the electrical activity of the heart, which can result in a potentially fatal
abnormal heart rhythm.”
-
FDA Drug Safety Communication, Sept. 15, 2011
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


APF530 Thorough QT Study Design
Double-blind, single-site
Four-way crossover
56 healthy male and female subjects
Study Arms
SC APF530 1 g (granisetron 20 mg) –
2x therapeutic dose
IV Granisetron 50µg/kg over 3 minutes –
5x therapeutic dose
Oral Moxifloxacin 400 mg (Avelox®) –
positive control
Placebo 0.9% Normal Saline 0.84 mL
Primary endpoint: the upper bound of the one-sided 95%
confidence interval for placebo-adjusted, baseline-
subtracted QTcF being less than 10 milliseconds at all
time points
21
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


APF530 Thorough QT Study Results
Primary Endpoint Achieved in Both Granisetron Dose
Groups
Both
APF530
and
IV
granisetron
dose
groups
did
not
approach
or
exceed
the upperbound of 10 ms at any time point
The primary end point was met irrespective of heart-rate correction
methodology –
QTcF, QTcI, QTcB
PK/PD relationship was flat –
also showing no QTc signal
Valid Study
Moxifloxacin positive control group showed expected change –
assay
sensitivity reached
22
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


Granisetron Thorough QT PK/PD Results
23
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.
Plasma Concentration (ng/ml)
ddQTcF vs. Granisetron Plasma Concentration
Slope = -0.019


Metabolism Study
24
Protocol reviewed by FDA prior to starting study
Single blind, single site
14 healthy male and female subjects
Gather and analyze plasma and urine samples for metabolic products
Results corroborated in humans the metabolism data
previously observed in preclinical animal studies
Study results will be included in NDA resubmission
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


Commercial Opportunity
25
©
2012. A.P. Pharma, Inc. All rights reserved.


U.S. Market Opportunity for APF530
More than 7 million cycles of chemotherapy administered
each year
~27% are highly emetogenic
~46% are moderately emetogenic
Significant unmet medical need for additional therapies to
address delayed-onset CINV
5-HT3 antagonists are standard-of-care for CINV
Recommended in treatment guidelines –
NCCN, ASCO, ONS
An injectable 5-HT3 antagonist is co-administered with more than 90% of
moderately and highly emetogenic regimens
APF530 targets a $900
million market opportunity in the
US alone
In 2010, there were 5.14 million vials of injectable 5-HT3 antagonists
administered for CINV
The average selling price for market leader Aloxi is $175
Sources: Company-sponsored survey and analysis and Wolters Kluwer
26
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


1
st
Generation 5-HT3 Antagonist Study Results
27
Moderately
Emetogenic
Chemotherapy
-
Ondansetron
Gralla
Eisenberg
50%
34%
Highly Emetogenic Chemotherapy
Ondansetron
Granisetron
Aapro
Emend Label Studies
Emend
Label
Saito
25%
43%
52%
43%
33%
40%
Average Overall Complete Response* rates
Moderately Emetogenic Chemotherapy ~ 42%
Highly Emetogenic Chemotherapy ~ 39%
Overall Complete Response rates by study:
*Overall Complete Response defined as no emesis and no rescue
medications during 0 to 120 hours following chemotherapy
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Aloxi Study Results
28
Moderately Emetogenic Chemotherapy
Eisenberg
Gralla
Grunberg
Hajdenberg
APPA Ph 3
46%
69%
59%
59%
52%
Highly Emetogenic Chemotherapy
Aapro
APPA Ph 3
41%
62%
Average Overall Complete Response rates
Moderately Emetogenic Chemotherapy ~ 57%
Highly Emetogenic Chemotherapy ~ 51%
Overall Complete Response rates by study:
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Antiemetic Treatment Patterns
29
Most chemotherapy patients will undergo 4 to 15 cycles of
chemotherapy
Doctors prefer to administer antiemetics on-site for
moderately and highly emetogenic chemotherapy
Patient compliance is a significant concern
Average cost per CINV event ranges from $4,000 to $5,300
Issues controlling CINV typically appear during the first few
cycles
If the initial prevention regimen is not effective, drugs are
added and/or changed to address CINV in subsequent
cycles
No long-acting injectable alternative to Aloxi is available to prevent
delayed-onset CINV
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


©
2011. A.P. Pharma, Inc. All rights reserved.
30
March 2012
CINV Market Dynamics
Injectable Drugs for the Prevention of CINV
Number of Package Units Sold by Quarter
* US Oncology data added starting Q1'09.
Source: Wolters Kluwer
Usage in CINV estimated based on vial size


Aloxi Market Performance
31
Pricing
Average Selling Price = $175
Medicare Reimbursement = $186
Wholesale Acquisition Cost ~ $300 -
$330
Orange Book Patent Exclusivity
One patent expires April 2015
Three patents expire January 2024
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012
Zofran went
generic
Aloxi Sales
2004
2005
2006
2007
2008
2009
2010
0
50
100
150
200
250
300
350
400
450


CINV Market Dynamics: Conclusions
Aloxi has gained market share over last 3 years despite
availability of generics for acute-onset CINV
From 48% in 2008 to 56% in 2Q 2011
Kytril
was
widely
used
prior
to
Zofran
®
going
generic
High physician acceptance of granisetron
Aloxi dipped 30% when Zofran went generic but then
regained 100% of its lost share two quarters later
NK1 antagonists typically are only used as an adjunct to 5-
HT3 antatgonists
Injectable
Emend
®
units
sold
less
than
10%
of
injectable
units
sold
for
CINV prevention
32
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


APF530’s Potential Competitive Positioning
33
Provides 5 days of prevention against chemotherapy-
induced nausea and vomiting with a single injection
Second, long-acting, injectable product on market
Lack of complete effectiveness of available antiemetics
indicates need for additional products to prevent CINV
Most patients undergo 4 to 15 cycles of chemotherapy
Product
Effective for Delayed-
onset CINV
Cardiac Safety
Aloxi
Yes
Clean tQT results
Anzamet
No
QT effect –
contraindicated for CINV
Zofran/ondansetron
No
Warning added to label
Kytril/granisetron
No
-
AFP530
Yes
Clean tQT results
March 2012
©
2012. A.P. Pharma, Inc. All rights reserved.


APF530 Commercialization Strategy
A.P. Pharma owns worldwide rights to APF530
APF530 can be commercialized with a compact
commercial infrastructure targeting oncologists
Company evaluating partnering opportunities
34
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Financial Summary
35
Completed $24MM PIPE in July 2011
Current resources expected to fund Company into 2013
Summary Statement of Operations
(In thousands, except per share data)
Year Ended
December 31, 2011
Revenue
$      646
Operating expenses
11,708
Other
income
(expenses)
1
(752)
Net loss
$ (11,814)
Net
loss
per
share
2
$   (0.10)
Condensed Balance Sheet Data
(In thousands)
December 31, 2011
December 31, 2010
Cash and cash equivalents
$ 17,974
$ 2,109
Working capital
$ 14,547  
$    941
Total assets
$ 19,445
$ 2,911
Total stockholders’
equity
$ 15,752
$ 1,316
1
Includes discontinued operations
2
Based on 120.3 million weighted average common shares outstanding
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


A.P. Pharma Highlights
36
Lead product candidate, APF530, is long-acting, injectable
product for chemotherapy-induced nausea and vomiting (CINV)
Incorporates
widely
used
5-HT3
antagonist
-
granisetron
(Kytril
®
)
5-day delivery profile
Reduces both acute-
and delayed-onset CINV with single injection
APF530 shown
to
be
non-inferior
to
market
leader
Aloxi
®
1,341-patient, randomized, controlled, Phase 3 study
Presented at ASCO 2009
Company is addressing issues raised in Complete Response
Letter
End-of-review meetings held in 1Q 2011
Resubmission planned for mid-2012
APF530 targets a $900 million market opportunity in US alone
Could be second, long-acting, injectable product on market
A.P. Pharma has the potential to leverage its Biochronomer™
drug delivery technology into other opportunities
©
2012. A.P. Pharma, Inc. All rights reserved.
March 2012


Thank You
A.P. Pharma, Inc.
OTCBB: APPA
March 2012
37
©
2012. A.P. Pharma, Inc. All rights reserved.