Carol G. Gallagher, Pharm.D. President and CEO · 2011-02-23 · Carol G. Gallagher, Pharm.D. President and CEO J.P. Morgan Healthcare Conference January 11, 2011

Carol G. Gallagher, Pharm.D.President and CEO

J.P. Morgan Healthcare Conference

January 11, 2011

January 2011 | © 2011, Calistoga Pharmaceuticals, Inc. All rights reserved. Slide 2

Forward-Looking Statements

This presentation contains forward‐looking statements, including statements about the development of CAL‐101, other selective PI3K inhibitors and the efficacy, potency and utility of our product candidates in the treatment of cancer and inflammatory diseases. Various factors could cause actual results to differ materially from those projected in forward‐looking statements, including those predicting the commencement, duration and timing or availability of clinical trials and analyses of the trial results; efficacy, safety and clinical benefit of product candidates; ability to secure and timing of regulatory clearances; timing of product launches; retention and performance of third parties, including key personnel; the potential market for our product candidates; and the ability to effectively market our products. Although the Company believes that the forward‐looking statements contained herein are reasonable, it can give no assurance that the Company’s expectations are correct. The Company does not undertake any obligation to publicly update its forward‐looking statements based on events or circumstances after the date hereof.

January 2011 | © 2011, Calistoga Pharmaceuticals, Inc. All rights reserved.Slide 3

Indolent NHL (iNHL) and CLL Are Incurable Diseases Often Affecting Older Patients

Patients sufferfrom recurrent:Lymph node swellingSweatsChillsFatigueLife‐threatening infections


**Source: Synovate 2009

patients require drug treatmentfor iNHL and CLL annually in the US and EU5**

thousandthousand

OverOver


iNHL and CLL Regimens Have Substantial Toxicity and Become Less Effective with Recurrent Treatment

CHOP/R, CVP/R, BR, R, FCR

REMISSIONDURATION

Unmet MedicalNeed Increases

RESPONSE

2nd line1st line

Quality and Durability of Response Decline over Time

3rd line 4th line 5th line 6th 7th


Recurrent, Progressive Lymphoid Malignancy Alters Patient Lives


Opportunity to:• Improve current regimens• Establish new standard of care

without chemotherapy

Opportunity to:• Improve current regimens• Establish new standard of care

without chemotherapy

Novel Targeted Therapies Are Needed to Safely Provide More Durable Responses


PI3K Delta Inhibition Offers a Novel Targeted Therapy in B-Cell Malignancies

T308 S473AKTNF‐Bpathway

mTOR

BTK

PLC2

PKC GSK‐3

p70s6k elf4E

BCR

PI3KDelta

CD40

STAT

JAKTRAF6 JAK

LYN

SYK LYN/SYK

T‐cell Signalingstimulus

gp130 gp130

STAT BTK

PLC2

Malignant B‐cell membrane

T308 S473AKTNF‐Bpathway

mTOR

BTK

PLC2

PKC GSK‐3

p70s6k elf4E

PI3K Delta InhibitorPI3K Delta Inhibitor

PI3K Delta Inhibition CausesProliferationApoptosisStromal survival signals

CXCR5BAFFR

Stromal cell

IL‐6RCXCL13BAFFIL‐6


Calistoga PharmaceuticalsThe Leader in Delta-Isoform-Selective PI3K Inhibitors

• First company to demonstrate clinical benefit of delta‐isoform‐selective PI3K inhibitor in patients with hematologic cancers

• CAL‐101 is first‐in‐class PI3K delta inhibitor with compelling single‐agent and combination activity‒ Initiating full‐development registration program that supports potential U.S. commercialization in late 2013

• Worldwide rights owned on broad portfolio of molecules‒ Opportunities in hematologic malignancies, solid tumorsand inflammatory diseases

• Proven management team

• Well‐financed company with top‐tier investors


Calistoga Pharmaceuticals Has a Proven Management Team

Carol Gallagher, PharmD, President and CEO Metastatix, Anadys, CancerVax, Biogen Idec, Pfizer, Agouron

Albert Yu, MD, Chief Medical OfficerIcos Corporation

Roger Ulrich, PhD, Chief Development OfficerMerck & Co., Abbott, Pharmacia & Upjohn, Upjohn

Clifford Stocks, Chief Business Officer Icos Corporation, Booz Allen & Hamilton, University of Chicago

Langdon Miller, MD, EVP, Research and DevelopmentPTC Therapeutics, Pharmacia, National Cancer Institute

Andrew Guggenhime, Chief Financial OfficerFacet Biotech, PDL BioPharma, Neoforma, Merrill Lynch, Wells Fargo


Calistoga Pharmaceuticals Has the Support of Top-Tier Investors


CAL-101 Is a First-in-Class PI3K Delta Inhibitor

ADVANCINGinto Registration Trials

FAVORABLEPatient Tolerability

DURABLETumor Control

COMPELLINGAntitumor Activity

WW EXCLUSIVITYThrough 2024

CONVENIENTOral Therapy

SELECTIVEInhibitor of PI3K Delta

NOVELMechanism of Action


Patients with previously treated hematologicmalignancies

Phase 1 Dose‐Ranging Study

CAL‐101 50 mg to 350 mg BIDContinuous oral dosing (28‐day cycles)

48 weeks

Extension Study

Therapy continues as long as patient is benefitting

Early Development Program Evaluated Single-Agent CAL-101 in Patients with Hematologic Malignancies

References: NHL – Kahl, ASH 2010, #1777; CLL – Furman, ASH 2010, #55; PK/PD – Webb, ASH 2010, #1774


Characteristic iNHL(N=30)

CLL (N=54)

Age, median[range], years

61.5[32‐85]

62.5[37‐82]

Bulky disease, % 50 81

Adverse genetics (del 17p), % ‐‐ 36

Prior therapies, median [range], n

4[1‐10]

5[2‐15]

Prior therapy type, %

Rituximab 100 98

Alkylating agent 87 87

Anthracycline/anthracenedione 50 ‐‐

Purine analog 30 100

Alemtuzumab ‐‐ 31

Patients in Single-Agent CAL-101 Study Had Unfavorable Prognostic Characteristics and Multiple Prior Therapies


CAL‐101 Plasma Exposureby Dose Level

0

5000

10000

15000

0

1000

2000

3000

4000CmaxAUC

50 (n

=10)

100 (

n=22

)15

0 (n=

26)

200 (

n=26

)

350 (

n=14

)

Ctrough

Dose (mg/dose BID)

Mean AU

C 0‐6h 95

% CI (ngh

our/mL) M

ean Cmax &

Ctrough 95%

CI (ng/mL)

Best Lymph Node Changeby CAL‐101 Dose Level

‐100

‐75

‐25

0

50 (n

=9)

100 (

n=22

)15

0 (n=

12)

200 (

n=20

)

350 (

n=11

)

‐50*

*Criterion for lymph node response [Hallek 2008]

Dose (mg/dose BID)

Mea

n Ch

ange in SPD

95

% CI, (%

)Dose‐response relationship indicates that mean nodal shrinkage is >50% in

almost all patients at doses ≥150 mg BID

Dose‐exposure relationships indicate little exposure gain at doses of >150 mg BID

Activity Was Observed at All Doses (50 to 350 mg BID);Data Support 150-mg BID Dose for Future Trials


Best On‐Treatment Change in Tumor Size(ITT Analysis, N=30)

‐100

‐75

‐25

0

‐50*

+25

+50

+75

+100

Inevaluable (patients without a follow‐up tumor assessment; includes 2 patients with LPL with no adenopathy)

* Criterion for response [Cheson 2007, Hallek 2008]

% Cha

nge in Lym

ph Nod

e Area

Single-Agent CAL-101 Resulted in Tumor Shrinkage in Nearly All Patients with iNHL


iNHLTumor Control Endpoints

0 2 4 6 8 10 120

20

40

60

80

100

Cyclesb

% Progression

‐Free

In iNHL, Single-Agent CAL-101 Delivered a High Response Rate and Durable Tumor Control

Median DOR = 9 cyclesMedian PFS >12 cycles

Duration of Response (N=19)Progression‐Free Survival (N=30)0

20

40

60

80

100

iNHL (N=30)

63%

ITT Re

spon

se Ratea [E

xact Binom

ial 95%

CI] %

a Cheson 2007 criteria b Each cycle = 28 days


CAL-101 Activity Compares Favorably with Approved and Investigational Agents in Relapsed/Refractory iNHL

Slide 18

Bendamustine – Friedberg. J Clin Oncol 2008; 26:204; Kahl, Cancer 2010; 116:106CAL‐101 – Kahl. ASH 2010; # 1777.Rituximab – McLaughlin. J Clin Oncol 1998; 16:2825PCI‐32786 – Pharmacyclics press release 2010

Lenalidomide – Witzig. J Clin Oncol 2009; 27:5404Fostamatinib – Friedberg. Blood 2010; 115:2578Bortezemib – Di Bella. Blood 2010; 115:475

Bortezomib (N=60)

Fostamatinib (Syk inhibitor) (N=25)

Lenalidomide (N=43)

PCI‐32765 (Btk inhibitor) (N=20)

Rituximab (N=166)

Bendamustine (N=123)

CAL‐101 (N=30)

12%

Prior Therapies(median)

4

4

3

3

2

2

3

12%

23%

30%

48%

75%

63%

ITT Response Rate [Exact Binomial 95% CI], %

OVERALL RESPONSE RATEiNHL


CAL-101 Activity in Patients with CLL Showed a Rapid Lymph Node Reduction with a Lymphocyte Redistribution

Lymph node activity: Patients had a rapid, substantial, and sustained reduction in lymph node size

Lymphocyte redistribution: A subset of patients (58%) had an asymptomatic increase in circulating lymphocytes that was maximal during the first 2 cycles and usually decreased thereafter

Lymph Nodes

0 (49

)1 (

49)

2 (42

)4 (

30)

6 (22

)8 (

18)

10 (1

3)12

(10)

‐100

‐75

‐50

‐25

0

Cycle (N)

Mean SEM (%

Cha

nge)

Lymphocyte Counts

Pre (

50)

1 (50

)2 (

49)

4 (37

)6 (

29)

8 (27

)10

(19)

12 (1

4)

0

20

40

60

80

100

Cycle (N)

Mean SEM (K

/L)


Single-Agent CAL-101 Resulted in Tumor Shrinkage in All Evaluable Patients with CLL, Including Those with del (17p)

Best On‐Treatment Change in Tumor Size(ITT Analysis, N=54)

‐100

‐75

‐25

0

‐50*

+25

+50

+75

+100

Inevaluable (patients without a follow‐up tumor assessment)Patients with del (17p)

* Criterion for response [Hallek 2008]

% Cha

nge in Ly

mph

Nod

e Area


CLL Tumor Control Endpoints

0 2 4 6 8 10 120

20

40

60

80

100

Cyclesc

% Progression

‐Free

In CLL, Single-Agent CAL-101 Delivered a High Nodal Response Rate and Durable Tumor Control

Slide 21

0

20

40

60

80

100

OverallaResponse

80%

26%

Lymph NodebResponse

CLL (N=54)

ITT Re

spon

se Rate [Exact Binom

ial 95%

CI] %

All medians >11 cycles

Duration of Response (N=14)Duration of Nodal Response (N=44)Progression‐Free Survival (N=54)

C Each cycle = 28 daysa IWCLL response criteria b Decrease by 50% in the nodal SPD Hallek, Blood June 2008


0 25 50 75 100

ALT/AST

Pneumonia

Anorexia

Diarrhea

Fatigue

Neutropenic fever

Neutropenia

Thrombocytopenia

Anemia

NHLa(N=51)

CLL(N=54)

100 75 50 25

27%

10%

2%

6%

6%

6%

24%ba

4% 7%

4%

24%8%

Grade 3‐4 Events(All Events with 5% Incidence)

(All Dose Levels)

2% 7%

10% 0%

8% 4%

Incidence (%)

Single-Agent CAL-101 Has Been Well Tolerated, with Adverse Events Influenced by Underlying Disease Type

CAL‐101 shows no pattern of drug‐related symptoms (e.g., fatigue, nausea, neuropathy) seen with other cancer therapies

a Includes patients with MCL (N=21) and iNHL (N=30)b Pneumonia rate of 0.04 events/patient/month with CAL‐101 in CLL compares withthe expected rate of 0.06 events/patient/month [Perkins, Cancer 2002; Cancer 94:2033]


0

25

50

75

100

Grade 3Grade 4

ALT/AST Elevation

Week of CAL‐101 Treatment

Initial In

cide

nce, %

Grade 3-4 Serum Transaminase Changes in Patients with NHL Occur Early in Therapy and Are Monitorable and Reversible

Most patients continue CAL‐101 without recurrence

Recovers within 2‐6 weeks during temporary drug holiday

WeekN

‐151

0 1 2 3 446

6 836

1227

1621

2414

3215

409

486

2026


CAL-101 Is Being Studied Together with Bendamustine or Rituximab in iNHL and CLL Patients

Patient Characteristics

Total N=20

iNHL(N=12)

CLL(N=8)

B(N=6)

R(N=6)

B(N=3)

R(N=5)

Age, median [range], years

67[53‐80]

63.5 [63‐73]

64 [55‐74]

66 [56‐85]

Bulky adenopathy, n 3 3 3 2

Relapsed/refractory disease, n 3/3 6/0 1/2 3/2

Prior therapies, median[range], n

2 [1‐3]

3.5 [1‐9]

3 [1‐6]

3 [1‐8]

Prior therapy type, %

Rituximab 100 83 100 100

Alkylating agent 100 83 67 80

Purine analog 50 50 100 100

Anthracycline/anthracenedione 67 83 0 40


Almost All Patients with iNHL or CLL Receiving B + CAL-101 or R + CAL-101 Have Experienced Reductions in Nodal Size

‐100

‐75

‐25

0

‐50*

+25

+50

+75

+100

B(N=6)

R(N=6)

iNHL(N=12)

B(N=3)

R(N=5)

CLL(N=8)

* Criterion for response [Cheson 2007, Hallek 2008]Inevaluable (patients without a follow‐up tumor assessment]

Best On‐Treatment Change in Tumor Size(ITT Analysis)

% Cha

nge in Ly

mph

Nod

e Area

The pattern of adverse events has been consistent with the known safety profiles of the individual agents


Single‐Agent CAL‐101

Pre (5

0)1 (

50)

2 (49

)4 (

37)

6 (29

)8 (

27)

10 (1

9)12

(14)

0

20

40

60

80

100

Cycle (N)

ALC (K/uL)

CombinationB or R + CAL‐101

Pre (

8)1 (

8)2 (

7)3 (

5)4 (

4)5 (

2)6 (

2)

0

20

40

60

80

100

Cycle (N)ALC (K/uL)

Combination Therapy with Either B + CAL-101 or R + CAL-101 Results in Rapid Lymphocyte Clearance in Patients with CLL

Flinn, ASH 2010; #2832Furman, ASH 2010; #55


CAL-101 Has the Attributes of a Successful Oncology Product with Multi-Billion Dollar Revenue Potential

First‐in‐class Novel mechanism High single‐agent response rates Favorable tolerability Lack of overlapping toxicities with standard agents Adds efficacy to combination regimens (studies ongoing) Opportunity for chronic/maintenance dosing

(dosing until progression in current studies)


0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 50

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

Efficacy Efficacy

Safety

Safety

iNHL(N=14)

CLL(N=14)

Bortezomib

LenalidomideLenalidomide

PCI‐32765PCI‐32765

CAL‐101

Navitoclax

Fostamatinib

CAL‐101

CAL-101 Efficacy and Safety Scored High Marks Among Key Opinion Leaders Attending ASH 2010

100% of these KOLs wish to conduct future CAL‐101 clinical studies

Calistoga‐sponsored market research conducted by Bio Connections LLC at ASH 2010; 3 of 14 KOLs surveyed had prior CAL‐101 clinical study experience


CAL-101 Has Made the Transition from Early Development to Full Development

Healthy Volunteer Trials• Dose‐ranging

• Metabolism

Hematologic Cancer Trials• Single‐agent

• Combination

Full Development2011‐2013*

Early Development2008‐2010

Phase 2 single‐agent study

Phase 3 combination study

iNHLAcceleratedApproval

iNHLFull

Approval

Phase 3 combination study CLLFull

Approval

Investigator‐initiated study program MarketExpansion

*2013 potential first approval


Calistoga Pharmaceuticals Has a Broad Portfolio ofIsoform-Selective PI3K Inhibitors

CAL‐101(PI3K‐

(single agent)Hematologic malignancies

(with rituximab)CLL

Solid tumors

Inflammation

CAL‐263(PI3K‐

CAL‐120(PI3K‐‐

CAL‐129(PI3K‐

CAL‐253 & others(PI3K‐‐

ONCO

LOGY

INFLAM

MATION

INFLAM

/ONCO

PRECLINICAL CLINICAL

(with bendamustine/rituximab)iNHL, CLL


Calistoga PharmaceuticalsThe Leader in Delta-Isoform-Selective PI3K Inhibitors

• First company to demonstrate clinical benefit of delta‐isoform‐selective PI3K inhibitor in patients with hematologic cancers

• CAL‐101 is first‐in‐class PI3K delta inhibitor with compelling single‐agent and combination activity‒ Initiating full‐development registration program that supports potential U.S. commercialization in late 2013

• Worldwide rights owned on broad portfolio of molecules‒ Opportunities in hematologic malignancies, solid tumorsand inflammatory diseases

• Proven management team

• Well‐financed company with top‐tier investors


CAL-101 Is Already Making a Difference in the Lives of Patients with Lymphoid Malignancies

Pretreatment With CAL‐101 Treatment

2101 Fourth Ave, Suite 1960Seattle, WA 98121

www.calistogapharma.com

Documents

Carol G. Gallagher, Pharm.D. President and CEO · 2011-02-23 · Carol G. Gallagher, Pharm.D. President and CEO J.P. Morgan Healthcare Conference January 11, 2011