HERON THERAPEUTICS, INC. /DE/ - FORM 8-K - EX-99.1 - CORPORATE PRESENTATION

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8-K - FORM 8-K - HERON THERAPEUTICS, INC. /DE/	d323470d8k.htm

Company Overview

OTCBB: APPA

March 2012

Exhibit 99.1

Legal Disclaimer

March 2012

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

Cash:

$18.0

million

Debt:

$1.57 million

Stock Summary

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

As of December 31, 2011

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

*Ms. Ficks is an employee of Gemini Healthcare, LLC, and a consultant to A.P. Pharma

March 2012

A.P. Pharma Highlights

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

non-inferior

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

March 2012

Important APF530 Milestones

March 2012

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

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

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)

March 2012

Primary Efficacy Results: Complete Response

Patients Receiving Moderately

Emetogenic Chemotherapy

Acute

Delayed

APF530 5mg

APF530 10mg

Acute

Delayed

Acute

Delayed

Difference in Complete Response

APF530-Aloxi (97.5% CI)

-15

-10

-5

March 2012

Primary Efficacy Results: Complete Response

Difference in Complete Response

APF530-Aloxi (98.33% CI)

-15

-10

-5

Acute

Delayed

APF530 5mg

APF530 10mg

Patients Receiving Highly

Emetogenic Chemotherapy

Acute

Delayed

March 2012

80.7

77.7

81.3

66.4

64.6

68.3

100

Safety Summary

Pulmonary embolism in morbidly obese patient on day 16

>90% of injection site reactions were reported as mild; one patient discontinued due to

Reported in Cycle 1

March 2012

Drug

Serious

Adverse

Events

0.2

Discontinued Due to Adverse Event

0.2

Frequent Adverse Events

Gastrointestinal disorders

Constipation

Diarrhea

Abdominal pain

13.4

10.6

4.5

15.4

9.4

2.8

13.4

8.4

6.0

Nervous System

Headache

6.7

10.0

9.7

Injection Site

Placebo (NaCl)

Bruising

Erythema (redness)

Nodule (lump)

Pain

16.8

7.1

4.7

3.4

10.9

10.7

7.1

8.9

3.0

0.6

1.1

19.9

APF530 5 mg

APF530 10 mg

Aloxi 0.25 mg

injection site reaction

APF530’s Efficacy with Difficult Chemo Regimens

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

APF530’s Sustained Efficacy in Cycles 2-4

* 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

100%

70%

54%

39%

N =

% of Cycle 1

APF530 10mg

Aloxi 0.75mg*

March 2012

68.3

76.3

79.1

87.2

58.7

54.3

62.2

65.0

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

March 2012

Regulatory Status

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

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

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

March 2012

Thorough QT Study Background

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

March 2012

Cardiac Safety Concerns in 5-HT3 Antagonist Class

“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

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

March 2012

APF530 Thorough QT Study Results

Primary Endpoint Achieved in Both Granisetron Dose

Groups

Both

APF530

and

granisetron

dose

groups

did

not

approach

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

March 2012

Granisetron Thorough QT PK/PD Results

March 2012

Plasma Concentration (ng/ml)

ddQTcF vs. Granisetron Plasma Concentration

Slope = -0.19

Metabolism Study

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

Commercial Opportunity

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

March 2012

Generation 5-HT3 Antagonist Study Results

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

March 2012

Aloxi Study Results

Moderately Emetogenic Chemotherapy

Eisenberg

Gralla

Grunberg

Hajdenberg

APPA Ph 3

46%

69%

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:

March 2012

Antiemetic Treatment Patterns

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

March 2012

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

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

March 2012

Zofran went

generic

Aloxi Sales

2004

2005

2006

2007

2008

2009

2010

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

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%

injectable

units

sold

for

CINV prevention

March 2012

APF530’s Potential Competitive Positioning

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

QT effect –

contraindicated for CINV

Zofran/ondansetron

Warning added to label

Kytril/granisetron

AFP530

Yes

Clean tQT results

March 2012

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

March 2012

Financial Summary

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)

(752)

Net loss

$ (11,814)

Net

loss

per

$ (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

Includes discontinued operations

Based on 120.3 million weighted average common shares outstanding

March 2012

A.P. Pharma Highlights

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

non-inferior

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

March 2012

Thank You

A.P. Pharma, Inc.

OTCBB: APPA

March 2012

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