Curis (CRIS) 8-K Regulation FD Disclosure

0

NASDAQ: CRIS

Corporate Overview

January 13, 2014

Exhibit 99.1

1

Forward Looking Statements

This

presentation

contains

statements

about

Curis’

future

expectations,

plans

and

prospects

that

constitute

forward-looking

statements

for

purposes

of

the

safe

harbor

provisions

of

the

Private

Securities

Litigation Reform Act of 1995. Actual results or events could differ materially from the expectations, plans

and prospects disclosed in the forward-looking statements that the Company makes due to a number of

important factors, including risks related to: the Company’s ability to satisfactorily respond to the FDA’s

request for additional data and analysis regarding CUDC-427 with respect to the partial clinical hold and its

ability to conduct future preclinical or clinical studies involving CUDC-427 if the FDA or other regulatory

agencies

continue

to

express

safety

concerns

even

if

the

hold

is

lifted;

Genentech

and

Roche’s

ability

to

successfully

develop

and

commercialize

Erivedge;

the

Company’s

and

its

collaborators’

ability

to

successfully research, obtain regulatory approvals for, develop and commercialize products based upon the

Company’s technologies; the Erivedge royalty-collateralized loan transaction entered into by the Company’s

wholly-owned subsidiary, including the risk that it may not receive sufficient levels of royalty

revenue

from

sales

of

Erivedge

to

satisfy

the

debt

obligation

or

may

otherwise

lose

its

rights

to

royalties

and

royalty

related

payments

as

a

result

of

a

foreclosure

of

the

loan;

the

Company’s

ability

to

obtain

and

maintain

proprietary

protection

for

its

technologies

and

product

candidates;

competitive

pressures;

the

Company’s ability to raise additional funds to finance its operations; and those risk factors discussed in the

Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, and other reports

that it files with SEC.

The forward-looking statements included in this presentation represent our views as of the date of this

presentation. We anticipate that subsequent events and developments will cause our views to change.

While we may elect to update these forward-looking statements in the future, we specifically disclaim any

obligation to do so. These forward-looking statements should not be relied upon as representing our

views

as of any date subsequent to the date of this presentation.

2

HDAC/PI3K

Indications

Indications

Market

Market

NSCLC

Lymphomas and

Multiple Myeloma

Target

Target

Program

Program

Preclinical

Preclinical

Phase 1

Phase 1

Phase 2 

Phase 2 

Phase 3

Phase 3

CUDC-907

Debio 0932

Clinical Pipeline

Novel, Targeted Cancer Therapeutics

Renal Cancer

Advanced Basal Cell

Carcinoma

Operable Basal Cell

Carcinoma

Erivedge®

AML and MDS

Proprietary Programs

Partnered Programs

Hsp90

Hedgehog

IAP

CUDC-427

Breast, Ovarian,

Lymphomas, and

Other Cancers

Phase 1*

Phase 1

Approved in US, AUS, EU & Others

Phase 2

Phase 1b/2

Phase 1

Phase 1/2

* CUDC-427 is currently on an FDA partial clinical hold.

3

CUDC-907:

Potent Inhibitor of HDAC and PI3K Enzymes

4

Oral, first-in-class highly potent and selective inhibitor of HDAC and PI3K

enzymes

Preclinical highlights

Hematological indications clinical highlights

Clinical testing in solid tumor indication(s) anticipated in late 2014

CUDC-907 Summary

Inhibition of PI3K, MAPK and JAK/STAT pathways in hematologic tumor models

Potential

biomarkers predicting CUDC-907 sensitivity

Phase 1 dose escalation study ongoing in lymphoma and multiple myeloma patients

Side

effect

profile

consistent

with

target

inhibition

–

thrombocytopenia,

diarrhea,

fatigue

Preliminary evidence of anti-tumor activity based on 1 PR & 7 SD out of 13 patients

Dose escalation phase projected for completion in mid 2014

Dose

expansion

phase

(DLBCL

&

MM)

projected

for

initiation

in

2H

2014

Phase 2 testing in hematological indication(s) anticipated late 2014

5

CUDC-907: Dual Activity against HDAC & PI3K

M2

•

~ 80% PI3K activity as

compared to parent

•

No HDAC activity

M1

•

~ 30% PI3K activity as

compared to parent

•

No HDAC activity

PI3K

IC50 (nM)

Alpha

Delta

Beta

Gamma

19

39

54

311

HDAC

IC50 (nM)

1

2

3

6

10

4, 5, 7, 8, 9

1.7

5.0

1.8

27

2.8

>200

CUDC-907

•

Full HDAC activity

•

Full PI3K activity

H

2

N

O

R

R

R

H

O

O

R

HDACi Moiety

PI3Ki Moiety

6

CUDC-907 & M2 Tissue Distribution in Mouse

Informs Clinical PK Model

Mouse 25 mg/kg Single Dose, PO

Differential kinetics & distribution of CUDC-907 & M2 metabolite

M1 & M2 levels higher in plasma than CUDC-907 levels

CUDC-907 is predominantly distributed to tissues

CUDC-907

M2

7

CUDC-907: Phase 1 Clinical Design

Phase 1 dose-escalation monotherapy study

Relapsed/refractory lymphoma or multiple myeloma patients

MSKCC (Anas Younes, MD), SCRI (Jesus Berdeja, MD), MDACC (Yasuhiro Oki, MD)

3+3 design

1

o

Objective

Determination of MTD and recommended Phase 2 dose (RP2D)

2

o

Objectives

Safety & tolerability

Pharmacokinetics and biomarkers of CUDC-907 activity

Anti-cancer activity

21-day cycles testing 3 different administration schedules (oral dosing)

Daily:  MTD reached

BIW (Mon/Thu):  dose escalation ongoing

TIW (Mon/Wed/Fri):  dose escalation ongoing

8

CUDC-907: Phase 1 Clinical PK

Plasma levels of CUDC-907 & Metabolites

Apparent increase in exposure with higher doses

Differential kinetics of CUDC-907 & metabolites

Higher M1 & M2 levels compared to CUDC-907 in plasma samples

•

Model: metabolites are generated from tissue-distributed CUDC-907

Potential

accumulation

of

metabolites

with

daily

dosing

–

supports

intermittent

dosing

Anticipate higher CUDC-907 exposure in tissue vs. plasma

Day 1

D8

Day 15

Day 1

Day 15

D8

Day 1

Day 15-17

D8

9

CUDC-907: Phase 1 Clinical Safety

Daily dosing schedule

Intermittent dosing schedules (BIW, TIW)

Common side effects consistent with target modulation –

thrombocytopenia,

diarrhea and fatigue

MTD at 30mg dose level

•

Treatment-related AEs & dosing interruptions for thrombocytopenia and/or

neutropenia

2 DLTs (G3 diarrhea & G4 hyperglycemia) in 1 subject at 60mg dose level

No treatment related adverse events observed thus far –

60 mg cohort

10

11 subjects were evaluable for

response (i.e.,    1 post-treatment

response assessments)

1 subject with mixed FL/DLBCL

achieved PR (70% reduction in target

lesion) in Cycle 4 (30mg daily dose

level)

7 subjects achieved SD

4 subjects with   

4 cycles of study

treatment (to date)

1 subject is currently in Cycle 15 of

study treatment (MM)

*Note: Concurrent PD documented as new lesions

CUDC-907: Phase 1 Best Tumor Response

Observed to-Date (Study Ongoing)

Younes A, Flinn IW, Oki Y, et al.  A First-In-Man Phase 1 Study Of CUDC-907, a First-In-Class Chemically-Designed Dual

Inhibitor Of PI3K and HDAC In Patients With Refractory Or Relapsed Lymphoma and Multiple Myeloma.  American Society

of Hematology Annual Meeting and Exposition, 7-10 December 2013, Abstract No. 4363

11

CUDC-907 Summary

Inhibitor of PI3K alpha, delta, beta and key HDAC enzymes

Exclusive worldwide rights

Potent activity in lymphoma and multiple myeloma models

Phase 1 dose escalation completion projected mid 2014

Clinical PK as predicted from animal model studies

Improved tolerability with intermittent schedule (2x or 3x weekly)

•

Expected to permit higher doses than daily schedule

Preliminary evidence of clinical activity in 11 patients –

1 PR, 7 SD

Expansion cohorts in 2H 2014 (DLBCL, MM)

Phase 2 testing projected for late 2014

Clinical testing in solid tumor indication(s) anticipated in late 2014

12

CUDC-427:

Antagonist of IAP (Inhibitor of Apoptosis) Proteins

13

CUDC-427:  Antagonist of IAP Proteins

In-licensed from Genentech, Nov. 2012

Exclusive, worldwide license

No “call-back”

or “reach-through”

provisions

Oral small molecule, monovalent SMAC mimetic drug candidate

Targets and inhibits IAP proteins –

cIAP1, cIAP2, XIAP, ML-IAP

Synergy with chemotherapy or TNF demonstrated

Genentech completed Phase 1 dose-escalation clinical trial

42 patients with solid tumors or lymphoma

Well tolerated using 14 days on and 7 days off administration schedule

Significant biomarker activity starting at ~ 90mg dose

Complete responses (n=2)

Disease stabilization > 3 months observed (n=4)

•

Liver enzyme increases and rash observed at higher doses ( > 450mg dose)

14

CUDC-427 and Apoptosis Induction

TNF

Caspase-8

Caspase-9

Caspase-3, -7

Bid

Bax/Bak

Cytochrome C

Smac

Extrinsic

Intrinsic

NF-kB

Mitochondria

Apoptosis

Non-

canonical

Pathway

Canonical

Pathway

CUDC

CUDC

427

CUDC

CUDC

427

Oral small molecule drug

Monovalent SMAC mimetic

Synergy with apoptosis-

inducing agents:

chemotherapy or TNF

cIAPs

cIAPs

ML-IAP

XIAP

15

CUDC-427 Phase 1 Trial Summary

Phase 1 monotherapy trial executed by Genentech

Design

Dose-escalation study in patients with refractory solid tumors or lymphoma

42 patients in 11 cohorts

5mg to 600mg once daily dosing, 14 days “on”

and 7 days “off”

schedule

Results

Dose proportional PK with no evidence of drug accumulation

MTD not determined

Rapid down-modulation of cIAP target in circulating PBMC and tumor biopsies

2 patients with complete responses (CR)

8

patients

with

stable

disease

(SD,

4

of

which

lasted

3

months)

16

CUDC-427 Phase 1 Trial –

Clinical Activity

Two patients had complete response

MALT

lymphoma

(300

mg):

CR

by

PET

let

in

Cycle

5

(off

study

–

patient

choice)

Ovarian cancer (450 mg): CR end of Cycle 2 (off study due to AE,

rash)

Sustained

CR per imaging

Feb 2013

July 31, 2012

April 18, 2012

17

CUDC-427 Clinical Development Status

Curis-initiated Phase 1 study using monotherapy continuous bi-daily

administration

schedule

–

July

2013

1 patient

death

due

to

liver

failure

–

October

2013

FDA

partial

clinical

hold

–

November

2013

Response to FDA in final preparation; submission shortly

Further

development

–

contingent

on

FDA

lift

of

partial

clinical

hold

Capecitabine combination Phase 1b/2 trial in HER-2 negative breast cancer

Monotherapy in patients with genetic alterations in IAP pathway components

•

Potential indications: MALT lymphoma

•

Trial start dependent on development of genetic screening assay

Other combination treatment trials pending results of preclinical

studies

Chemotherapy

Targeted therapies

18

CUDC-427 Summary

Potent antagonist of IAP proteins

Exclusive worldwide rights

Orally available small molecule drug

Preclinical efficacy and synergy with chemotherapy or TNF

Phase 1 monotherapy studies

Discontinuous daily regimen well tolerated –

(formal MTD not reached)

•

Clinical benefit observed in patient with IAP pathway genetic alteration

MALT lymphoma with cIAP2 gene amplification:  300mg / 5 cycles

CR

Continuous bi-daily treatment not well tolerated

Combination therapy

CUDC-427 + capecitabine Phase 1b/2 trial planned

–

contingent on FDA lifting

partial clinical hold

Additional combination trials projected based on preclinical data

•

TNF inducers, apoptosis inducing agents, biologics

19

Erivedge

®

:

First-in-class

Hedgehog Pathway Inhibitor

20

Erivedge

®

Developed Under Collaboration

Genentech and Roche

Erivedge (vismodegib)

Oral inhibitor of Hedgehog signaling pathway

Discovered under broad pathway collaboration formed in 2003

Approved for treatment of advanced basal cell carcinoma (BCC)

Genentech/Roche-sponsored trial completed in less severe, operable BCC

Genentech/Roche-sponsored trial initiated in AML and MDS

Several investigator-sponsored studies are ongoing in other cancers

Milestone and royalty-based revenue stream for Curis

Potential for $115 million in development & regulatory milestones

•

$56 million received to-date

Royalties on global net sales

21

Marketed in the U.S. for the treatment of advanced BCC

Roche recorded ~ $51 million net sales first 9 months 2013

•

32% growth 3Q ($21.4 million) vs. 2Q ($16.2 million)

Anticipated continued sales growth in 2014

Near-term Erivedge royalties primarily fund non-recourse loan from

Pharmakon, subject to quarterly caps (estimated full repayment early 2017)

Expand

global

marketing

–

Roche

Approved in U.S., Australia, European Union and multiple other countries

Reimbursement discussions ongoing in Ex-US territories

Filed with health authorities in many other countries

Genentech

plans

to

present

operable

BCC

Phase

2

trial

results

in

1Q

2014

Erivedge

®

Launched in Multiple Countries

Genentech and Roche

22

Initiated Phase 1b/2 study of Erivedge in patients with AML and

high-risk MDS in October 2013

Study design

Approx. 60 patients across 2 cohorts

Primary endpoint: ORR after 8 weeks of treatment

Secondary endpoints: ORR rate at any time during treatment, duration of

response, OS and safety and PK

Roche Continues to Invest in Erivedge

•

Cohort 1: 150 mg Erivedge daily

•

Cohort 2: 150 mg Erivedge daily + cytarabine for 10 days

23

Debio 0932:

Second Generation, Oral HSP90 Inhibitor

Phase 1/2

DebioPharm

24

Second generation oral small molecule Hsp90 inhibitor

Exclusive worldwide license with Debiopharm

$90 million in potential payments ($13 million received to-date)

Royalties on net sales; share of certain sublicensing payments

Clinical

development

status

–

Debiopharm

Completed Phase 1 Study –

50 subjects

•

Of 8 NSCLC patients:  1 PR (mut KRAS), 4 SD

Phase 1 portion of Phase 1/2 HALO study in Stage IIIb/IV NSCLC patients

•

In combination with chemotherapy, front line and previously treated patients

•

Debiopharm

anticipates

Phase

2

initiation

in

mid

2014

(milestone

payment)

Initiated Phase 1 study in renal cell carcinoma in 2013

•

In combination with everolimus

•

Debiopharm anticipates Phase 2 initiation in 2H 2014 (milestone payment)

Debio 0932

Oral Small Molecule Hsp90 Inhibitor

25

CUDC-101: EGFR/Her2 and HDAC inhibitor

Strong preclinical evidence of synergistic inhibition of multiple signaling

pathways

Phase 1 and Phase 1b studies completed using intravenous administration

•

71 patients as monotherapy –

activity in liver cancer patients

•

12

patients

in

combination

with

chemoradiation

–

activity

in

SCCHN

patients

•

Intravenous administration not feasible to maintain recommended exposure levels

Phase

1

study

conducted

using

oral

administration

–

captisol

formulation

•

3 patients treated –

study halted due to low drug exposure

•

Efforts to develop an new oral formulation of CUDC-101 with adequate bioavailability

have been unsuccessful

Curis will not invest further in CUDC-101 without securing a partnership

Discovery research

Ongoing

efforts

focused

on

backup

compounds

and

third

generation

EGFR

inhibitor chemical scaffolds

CUDC-101 and EGFR Discovery Program

26

September 30, 2013

(000’s)

Cash, cash equivalents, investments (1)

$

67,100

Erivedge®

secured debt (non-recourse to Curis)

$

30,600

Basic shares outstanding

84,100

Fully-diluted shares outstanding (2)

96,000

Net loss through September 30, 2013

$

(8,100)

(1)

Curis

received

an

additional

$6.8

million

in

net

proceeds

through

the

sale

of

1.56

million

shares

under

its

at-the-market

sales agreement, which settled in early October.

(2)

Comprised

of:

(i)

84.1

million

shares

outstanding,

(ii)

warrants

to

purchase

1.4

million

shares

at

$3.55

per

share,

and

(iii) options to purchase 10.5 million shares at a weighted average exercise price of $2.86 per share.

Summary Financial Data

27

NASDAQ: CRIS