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/	d462570d8k.htm

Company Overview

OTCBB: APPA

January 2013

Exhibit 99.1

Legal Disclaimer

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.

January 2013

Company:

A.P. Pharma, Inc.

Ticker:

OTCBB: APPA.OB

Stock Price:

$0.60 (1/4/13)

Market Capitalization:

$280.3

million

Cash:

$60.0

million

Debt:

$4.7

million

Stock Summary

Based on 499.0 million fully diluted, as-converted common shares assuming the full conversion of

convertible debt outstanding and 80 million warrants using treasury stock method; not including

options

As of September 30, 2012

January 2013

John B. Whelan

President & CEO

Raven Biotechnologies

Eos Biotechnology

Hewlett Packard/Agilent

Michael A. Adam, Ph.D.

Senior Vice President &

Chief Operating Officer

Spectrum Pharmaceuticals

Pfizer/Agouron

Bristol-Myers Squibb

Mark Gelder, M.D.

Senior Vice President &

Chief Medical Officer

GE Healthcare

Bayer Healthcare

Wyeth

Robert Rosen

Senior Vice President &

Chief Commercial Officer

Bayer Healthcare

Sanofi-Synthèlabo

Imclone

Senior Management

January 2013

A.P. Pharma Highlights

January 2013

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

Patent coverage into 2024

APF530

shown

non-inferior

market

leader

Aloxi

1,341-patient, randomized, controlled, Phase 3 study

FDA PDUFA Action Date of March 27, 2013

Resubmitted NDA for APF530 in September 2012

Addressed issues raised in Complete Response Letter

Product launch planned for 2H 2013

APF530 targets a $900 million market opportunity in US alone*

Recent competitive setbacks could enhance commercial uptake

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

*Branded market estimate using 2011 units based on Wolters Kluwer and Aloxi ASP

Important APF530 Milestones

Milestone

Timing

Status

Successful End-of-Review Meetings with

FDA

1Q 2011

Successful Completion of Thorough QT

and Metabolism Studies

1Q 2012

Completed $53.6MM PIPE Financing

3Q 2012

Successful Completion of Human Factors

Validation Study

3Q 2012

Successful Completion of CMC Activities

3Q 2012

Resubmitted NDA

Sept 2012

Key Commercial Organization Hires

4Q 2012

FDA PDUFA Action Date

March 27, 2013

Target Product Launch

2H 2013*

* Indicates expected milestone timing

January 2013

Clinical Summary

January 2013

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

January 2013

5-Day Profile: APF530 Pharmacokinetics

January 2013

Granisetron is released rapidly following injection of APF530 and continues to be released

over a 5-day period.

120

144

168

Time after Dosing (h)

All subjects (n= 18)

mean ±

SEM

Primary Efficacy Results: Complete Response

Patients Receiving Moderately

Emetogenic Chemotherapy

Acute

APF530 10mg

Acute

Delayed

Difference in Complete Response

APF530-Aloxi (97.5% CI)

-15

-10

-5

January 2013

Delayed

75.0

76.9

57.2

58.5

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

80.0

90.0

100.0

Primary Efficacy Results: Complete Response

Difference in Complete Response

APF530-Aloxi (98.33% CI)

-15

-10

-5

Patients Receiving Highly

Emetogenic Chemotherapy

Acute

Delayed

January 2013

Acute

Delayed

APF530 10mg

Safety Summary

APF530 5 mg dose studied in separate arm of the phase 3 study; one pulmonary embolism in

morbidly obese patient on day 16 (0.2%); one dyspepsia event (0.2%)

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

reaction

Reported in Cycle 1

January 2013

APF530 10 mg

Aloxi 0.25 mg

Drug

Serious

Adverse

Events

Discontinued

Due

Adverse

Event

0.2

Frequent Adverse Events

Gastrointestinal Disorders

Constipation

Diarrhea

Abdominal pain

15.4

9.4

2.8

13.4

8.4

6.0

Nervous System

Headache

10.0

9.7

Injection Site

Placebo (NaCl)

Bruising

Erythema (redness)

Nodule (lump)

Pain

19.9

10.9

10.7

7.1

8.9

3.0

0.6

1.1

Efficacy through Multiple Chemotherapy Cycles

January 2013

Overall Complete Response defined as no emesis and no rescue medications during 0 to 120 hours

following chemotherapy

Moderately Emetogenic

Chemotherapy

Highly Emetogenic

Chemotherapy

Overall

Complete

Response

Rates

for

APF530

53.8

58.8

61.7

100

Cycle 1

Cycle 2

Cycle 3

Cycle 4

63.3

73.7

76.9

82.1

100

Cycle 1

Cycle 2

Cycle 3

Cycle 4

62.0

January 2013

Overall Complete Response defined as no emesis and no rescue medications during 0 to 120 hours

following chemotherapy. Protocol criteria may vary across studies.

MEC

HEC

Ondansetron

Granisetron

Gralla

Eisenberg

Aapro

Emend Label Studies

Emend

Label

Saito

50%

34%

25%

43%

52%

43%

33%

40%

MEC

HEC

Eisenberg

Gralla

Grunberg

Hajdenberg

APPA Ph 3

Aapro

APPA Ph 3

46%

69%

59%

52%

41%

62%

Aloxi –

Second Generation

First Generation 5-HT3 Antagonists

Overall

Complete

Response

Rates

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%

Data from post-hoc analysis. Not statistically significant.

January 2013

Summary of APF530 Phase 3 Results

One of the largest, randomized, controlled clinical studies

conducted in the CINV setting

Bioerodible polymer technology releases granisetron to

prevent CINV over 5 days

Non-inferiority to Aloxi was demonstrated at 10 mg

For both acute-

and delayed-onset CINV

With both moderately and highly emetogenic chemotherapy

APF530 was well-tolerated

Incidence of adverse events comparable to Aloxi

Good response rates were observed in difficult

chemotherapy regimens

Efficacy was maintained through multiple cycles of

chemotherapy

January 2013

Regulatory Status

January 2013

APF530 NDA Status

Submitted NDA in May 2009 under 505(b)(2) filing pathway

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

Resubmitted NDA in September 2012

PDUFA Action Date of March 27, 2013

January 2013

Addressed Complete Response Letter Issues

Dosing System

Change to single-syringe system

Enhanced dosing instructions

Successfully evaluated in a Human Factors study

Chemistry, Manufacturing, and Controls

Change from bulk to terminal irradiation

Additional specifications and assays for raw materials, polymer and drug

product

Three registration lots completed implementing these changes

Clinical/Statistical

Thorough QT study

Metabolism study

Phase 3 clinical data presentation revision

January 2013

Improved Dosing System

January 2013

New Single-syringe System

Original Two-syringe System

Thorough QT Study Background

Prolongation of the QT/QTc interval is associated with increased

susceptibility to fatal cardiac tachyarrhythmias

Thorough

studies

are

intended

determine

whether

drug

has

threshold pharmacologic effect on cardiac repolarization

Thorough QT studies are now routinely required by the FDA prior to

drug approval

FDA has raised QT cardiac safety concerns with 5-HT3 antagonists

The QT interval represents

the amount of time the

heart’s electrical system

takes to repolarize after

each beat

January 2013

Zofran Use in CINV Restricted

Most widely used generic 5-HT3 now restricted

FDA issued a Drug Safety Communication June 29, 2012

“The

use

single

intravenous

dose

ondansetron

should

avoided. New information indicates that QT prolongation occurs in a

dose-dependent manner, and specifically at a single intravenous dose of

32 mg.”

“No single intravenous dose of ondansetron should exceed 16 mg due to

the risk of QT prolongation.”

“The lower dose intravenous regimen of 0.15 mg/kg every 4 hours for

three doses may be used in adults with chemotherapy-induced nausea

and vomiting.”

Results of Zofran tQT study

32 mg IV dose causes 20 ms increase in QTcF

8 mg IV dose causes 6 ms increase in QTcF

FDA removed 32 mg dose from market December 4, 2012

Impact on sales may be significant

January 2013

Anzemet in CINV Previously Removed

FDA issued a Drug Safety Communication Dec. 17, 2010

“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.”

Anzemet label changed to remove CINV indication

IV Anzemet sales fell to near zero in one quarter

January 2013

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 50 µg/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

January 2013

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

January 2013

Granisetron Thorough QT PK/PD Results

ddQTcF vs. Granisetron Plasma Concentration

Slope = -0.019

Plasma Concentration (ng/ml)

January 2013

ddQTcF vs PlCon

LME Regression Line

90% Upper Confidence Interval

90% Lower Confidence Interval

Corr = 0.02 (p>0.32)

100

-60

-50

-40

-30

-20

-10

Metabolism/Fate of Polymer Study

FDA requested study at end-of-review meeting in 1Q 2011

Purpose of study is to demonstrate fate of polymer in

human subjects

Confirm polymer breaks down into same hydrolytic end-products as seen

in animals

Confirm lack of other detectable polymer-related metabolites

Protocol reviewed by FDA prior to initiating study

Single blind, single site

14 healthy male and female subjects

Gather and analyze plasma and urine samples for metabolic products

Study objectives achieved

Confirmed polymer breaks down into same hydrolytic end-products as in

animals

Confirmed lack of other detectable polymer-related metabolites

January 2013

Human Factors Study

January 2013

Assess the Instructions-for-Use and usability of APF530 in

simulated oncology setting

Follows June 2011 FDA guidance: “Applying Human Factors and Usability

Engineering to Optimize Medical Device Design”

Initial risk assessment followed by iterative process of formative studies

Validation study completed following formative studies

New single-syringe design improves overall usability

All subjects successfully followed instructions

Average injection time reduced by 45%

Previous Syringe

Current Syringe

Ease

3.1

8.3

Comfort

5.2

9.4

Control

7.7

9.5

–

very

difficult,

–

very

easy

Mean Usability Scores

Commercial Opportunity

January 2013

Continuing Unmet Need in CINV

Need for long-acting antiemetic

therapies

Delayed CINV (days 2-5) remains

particularly challenging to manage

Significant portion of patients fail to

respond to Aloxi

Need for antiemetic therapies with

sustained efficacy

CINV risk increases over multiple

chemotherapy cycles

Available at: http://www.cancer.gov/cancertopics/pdq/supportivecare/nausea/HealthProfessional/page6#Section_183

“Despite the use of both first-generation

and second-generation 5-HT

receptor

antagonists, the control of acute CINV, and

especially delayed nausea and vomiting,

suboptimal,

and

there

considerable

opportunity for improvement

with either

the addition or substitution of new agents in

current regimens.”

NCI Statement On The Existing

Unmet

Need

CINV

January 2013

Addressing Debilitating Effects of CINV

January 2013

More than 7 million cycles of

chemotherapy administered each

year

~27% are highly emetogenic

~46% are moderately emetogenic

Most chemotherapy patients will

undergo 4-15 cycles of

chemotherapy

5-HT3 antagonists are standard-

of-

care for CINV

Recommended in ASCO, NCCN

and ONS guidelines

NK-1 antagonists are only indicated

in combination with 5-HT3

antagonists

An Injectable 5-HT3 antagonist is

co-administered with more than

90% of MEC and HEC regimens

If initial regimen is non-effective,

drugs are added or changed to

address CINV in subsequent cycles

5-HT3 Antagonists Have Made a Substantial Impact

The use of high-dose

metoclopramide

Introduction of first-generation

5-HT3 antagonists (short-acting)

Approval of second-generation

5-HT3 antagonist (long-acting)

Approval of first

NK-1 antagonist

Adapted from Hawkins et al, Clinical Journal

of Oncology Nursing 2009, Volume 13, Number 1

FDA withdrawal of Anzemet and 32 mg dose of

ondansetron (Zofran) due to QT prolongation risk

5-HT3 receptor antagonists approved for CINV

January 2013

2003

2006

2011

1990s

1980s

Chemotherapy

Acute CINV

Delayed CINV

Highly

Emetogenic

granisetron

(Kytril)

ondansetron

(Zofran)

Aloxi

None

Moderately

Emetogenic

granisetron

(Kytril)

ondansetron

(Zofran)

Aloxi

U.S. CINV Market Dynamics

Source: Wolters Kluwer

Usage in CINV estimated based on vial size

January 2013

~85% drop following tQT

FDA Safety Letter

~40% drop following FDA

32 mg dose warning

~35% drop and rebound

in 6-month period

100,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

Q2'06

Q4'06

Q2'07

Q4'07

Q2'08

Q4'08

Q2'09

Q4'09

Q2'10

Q4'10

Q2'11

Q4'11

Q2'12

Injectable Drugs for the Prevention of CINV

Number of Package Units Sold by Quarter

ALOXI

ANZEMET

KYTRIL

KYTRIL Generic (GRANISETRON)

ZOFRAN

ZOFRAN Generic (ONDANSETRON)

EMEND

* US Oncology data added starting 1/2009.

Aloxi Market Performance

Pricing

Average Selling Price = $175

Medicare Reimbursement = $186

Wholesale Acquisition Cost ~ $380

Orange Book Patent Exclusivity

One patent expires April 2015

Three patents expire January 2024

January 2013

100

150

200

250

300

350

400

450

2004

2005

2006

2007

2008

2009

2010

2011

Zofran went

generic

Aloxi Sales

~80% of Aloxi Is Used in Clinics

IMS Health and Source Healthcare Analytics (WKH) data and Eisai Co., Ltd. published sales figures

January 2013

U.S.

Aloxi

Units

Class

Trade

–

Months

Ending

June

2012

Hospital

Other

Clinics

2.2 million units

0.5 million units

0.1 million units

>90% of Aloxi Units Contracted Through GPOs

January 2013

2.2 Million Clinic Units

23%

48%

21%

Misc

Onmark

ION

USO

IMS Health and Source Healthcare Analytics (WKH) data and Eisai Co., Ltd. published sales figures

Clinic

Units

GPO

–

Months

Ending

June

2012

WKH Data Oct. 2012 –

Clinic Analysis

Aloxi Clinical Use Is Largely Concentrated

Cumulative Number of Accounts

1% accts

4% accts

161

7% accts

252

11% accts

500

22% accts

674

29% accts

904

39% accts

1246

54% accts

2305

100% accts

362

15% accts

80% of units (1.7M) comes from 39% of accounts (904)

50% of units (1.1M) comes from 15% of accounts (362)

January 2013

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2,000

2,200

No New Injectable 5-HT3 Drug on Horizon

*Company reports, Leerink Swann; **Clinical Trials.gov NCT01339260 FDC = Fixed Dose Combo; PDUFA date expected 12-15 months post P3 data

EUR-1025 development program uncertain (once-a-day oral modified-release formulation of ondansetron)

January 2013

APF530 FDA PDUFA Date

2012

2013

2014

2015

Rolapitant Oral

FDA Approval

Expected Q4 2014

Rolapitant IV

Study Data 1H 2014

FDC P3 Oral

Data Expected Q1 2013

FDC Oral

FDA Approval 1H 2014

Rolapitant P3

Oral Data

Expected 2H 2013

Rolapitant IV

FDA Approval

Expected 2H 2015

Candidate

Class

Indication

Sponsor

Possible Launch

APF530

5-HT3 Extended

release

Prevention

of CINV in MEC/HEC

A.P. Pharma

2H 2013

FDC**

FDC combines netupitant

(NK-1) with

palonosetron

(Aloxi) in a single oral tablet

Prevention of CINV in MEC/HEC

Eisai / Helsinn

Oral 2H 2014

Rolapitant*

Long-acting NK-1

Prevention

of CINV in MEC/HEC only

in combination with 5-HT3

Tesaro

Oral 2H 2014

2H 2015

APF530 Proposed Label

January 2013

Proposed indication submitted in NDA

INDICATIONS AND USAGE

1.1 Chemotherapy-Induced Nausea and Vomiting

APF530 is indicated for:

• Moderately emetogenic

cancer chemotherapy (MEC)-

prevention of acute and delayed nausea and vomiting

associated with initial and repeat courses

• Highly emetogenic

cancer chemotherapy (HEC)-

prevention of

acute nausea and vomiting associated with initial and repeat

courses

APF530 Planned Market Positioning

January 2013

Acute Onset

24 Hours)

Delayed Onset

120 Hours)

Moderately

Emetogenic

Highly

Emetogenic

Moderately

Emetogenic

Highly

Emetogenic

(0-

(24-

APF530

Aloxi

Kytril

Zofran

If approved by FDA, APF530 and Aloxi would be the only

“long acting”

5-HT3 antagonists approved for the

prevention of acute and delayed-onset CINV

APF530 and Aloxi Profiles

January 2013

Attribute

APF530

Aloxi

Indication

MEC –

acute and delayed CINV

HEC –

acute CINV

MEC –

acute and delayed CINV

HEC –

acute CINV

MOA

5-HT3 receptor antagonist

Dosing

SC injection once per cycle

IV once

per cycle

Long acting

agent

Bioerodible polymer technology releases granisetron

over 5 days

~ 40 hour half life

Efficacy

Non

-inferiority to Aloxi

Effective in difficult chemotherapy regimens

Demonstrated efficacy through multiple cycles in

MEC and HEC

Safety

Headache, constipation,

injection site bruising and

pain

Clean QT profile

Headache

and constipation

Clean QT profile

Summary

January 2013

$900 million market potential for injectable 5-HT3 antagonists*

APF530 demonstrated non-inferiority to the market share leader

Aloxi

APF530 product profile

5-day release PK profile

Good response in difficult chemotherapy regimens

Efficacy through multiple cycles of chemotherapy

Clean QT results

Current market dynamics are stale with minimal investment

providing opportunities to become the market leader

Competitive landscape creates opportunity with the removal of

Anzemet and Zofran 32mg

Greater than 80% of Aloxi sales are in the community setting

and highly concentrated consistent with other supportive care

products

*Branded market estimate using 2011 units based on Wolters Kluwer and Aloxi ASP

A.P. Pharma Product Lifecycle Considerations

APF530 covered by multiple patents

2 patents covering combination of polymer, excipients and drug expire in

2021

3 patents covering APF530 expire in 2024

Polymer-based injectable products are difficult to copy

independent of IP

ANDA FDA requirements for injectable products

Must have same inactive ingredients in the same concentration as

the

reference listed drug

Polymers are complex mixtures of varying-length molecules, making

characterization for “sameness”

very challenging

January 2013

Financial Summary

January 2013

Expect cash sufficient to fund commercial launch of APF530

Summary Statement of Operations

(In thousands, except per share data)

Year Ended

December 31, 2011

Nine Months Ended

September 30, 2012

Revenue

$ 646

$ –

Operating expenses

11,708

15,203

Other income (expenses)

(752)

(408)

Net loss

$ (11,814)

$ (15,611)

Net loss per share

$ (0.10)

$ (0.07)

Condensed Balance Sheet Data

(In thousands)

September 30, 2012

Cash and cash equivalents

$ 60,048

Total assets

$ 61,761

Total stockholders’

equity

$ 57,517

Based on 120.3 and 225.1 million weighted average common shares outstanding for the periods

ended December 31, 2011 and September 30, 2012, respectively

A.P. Pharma Highlights

January 2013

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

Patent coverage into 2024

APF530 shown to be non-inferior to market leader Aloxi

1,341-patient, randomized, controlled, Phase 3 study

FDA PDUFA Action Date of March 27, 2013

Resubmitted NDA for APF530 in September 2012

Addressed issues raised in Complete Response Letter

Product launch planned for 2H 2013

APF530 targets a $900 million market opportunity in US alone*

Recent competitive setbacks could enhance commercial uptake

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

*Branded market estimate using 2011 units based on Wolters Kluwer and Aloxi ASP

Thank You

A.P. Pharma, Inc.

OTCBB: APPA

January 2013

HERON THERAPEUTICS, INC. /DE/ - FORM 8-K - EX-99.1 - CORPORATE PRESENTATION - January 7, 2013

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