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8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): January 12, 2015

 

 

Idera Pharmaceuticals, Inc.

(Exact Name of Registrant as Specified in Charter)

 

 

 

Delaware   001-31918   04-3072298

(State or Other Jurisdiction

of Incorporation)

  

(Commission

File Number)

   (IRS Employer
Identification No.)

 

167 Sidney Street

Cambridge, Massachusetts

   02139
(Address of Principal Executive Offices)   (Zip Code)

Registrant’s telephone number, including area code: (617) 679-5500

(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))

 

 

 

Item 7.01. Regulation FD Disclosure.

Idera Pharmaceuticals, Inc. (the “Company”) has included on its website an updated corporate slide presentation, which it intends to present and/or distribute to the investment community and utilize in various industry and other conferences. The corporate slide presentation is accessible in the Investors and Media section of the Company’s website at www.iderapharma.com and is attached hereto as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.

The information furnished pursuant to Item 7.01 of this current report, including Exhibit 99.1, shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934 or otherwise subject to the liabilities of that Section. As such, this information shall not be incorporated by reference into any of the Company’s reports or other filings made with the Securities and Exchange Commission. The furnishing of the information in this current report is not intended to, and does not, constitute a determination or admission by the Company that the information in this current report is material or complete, or that investors should consider this information before making an investment decision with respect to any security of the Company.

 

Item 9.01 Financial Statements and Exhibits.

 

(d) Exhibit

The following exhibit is furnished as part of this current report on Form 8-K:

 

Exhibit 99.1 —   Solving Unmet Patient Needs with Strong Scientific Foundations – Idera Pharmaceuticals – January 2015

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

    Idera Pharmaceuticals, Inc.

Date: January 12, 2015

     By:   /s/ Louis J. Arcudi, III
     

Louis J. Arcudi, III

Senior Vice President of Operations,
Chief Financial Officer, Treasurer and Secretary

Exhibit Index

 

Exhibit No.

   

Description

99.1    Solving Unmet Patient Needs with Strong Scientific Foundations – Idera Pharmaceuticals – January 2015
EX-99.1
IDERA
PHARMACEUTICALS
JANUARY
2015
Solving
Unmet
Patient
Needs
with
Strong
Scientific
Foundations
Exhibit 99.1

Forward
looking
statements
Any
statements
that
we
may
make
in
this
presentation
about
future
expectations,
plans
and
prospects
for
the
Company
constitute
forward-looking
statements
for
purposes
of
the
safe
harbor
provisions
under
The
Private
Securities
Litigation
Reform
Act
of
1995.
Actual
results
may
differ
materially
from
those
indicated
by
these
forward-looking
statements
as
a
result
of
various
important
factors,
including
whether
Idera’s
cash
resources
will
be
sufficient
to
fund
the
Company’s
continuing
operations
and
the
further
development
of
the
Company’s
programs;
whether
results
obtained
in
preclinical
studies
and
clinical
trials
such
as
the
results
described
in
this
presentation
will
be
indicative
of
the
results
that
will
be
generated
in
future
clinical
trials;
whether
products
based
on
Idera’s
technology
will
advance
into
or
through
the
clinical
trial
process
when
anticipated
or
at
all
or
warrant
submission
for
regulatory
approval;
whether
such
products
will
receive
approval
from
the
U.S.
Food
and
Drug
Administration
or
equivalent
foreign
regulatory
agencies;
whether,
if
the
Company’s
products
receive
approval,
they
will
be
successfully
distributed
and
marketed;
whether
the
Company’s
collaborations
will
be
successful;
and
such
other
important
factors
as
are
set
forth
under
the
caption
“Risk
Factors”
in
the
Company’s
Quarterly
Report
on
Form
10-Q
for
the
quarter
ended
September
30,
2014.
Idera
disclaims
any
intention
or
obligation
to
update
any
forward-looking
statements.
2

Our goal is to translate scientific breakthroughs into
important medicines for patients
Leading scientific discovery in
immunotherapy & gene silencing
Focused on serious unmet needs in
oncology & rare diseases
Committed to advancing patient care
3

Scientific platforms support broad pipeline opportunities
4
SERIOUS UNMET PATIENT NEEDS
Genetically defined forms
of B-cell lymphoma
Immuno-oncology
Rare autoimmune and
inflammatory diseases
Multiple targets in
cancer and rare
diseases
TOLL-LIKE RECEPTOR
IMMUNE MODULATION
GENE SILENCING
OLIGONUCLEOTIDES

Idera is a pioneer of immunotherapy and gene silencing
technologies
5
THIRD GENERATION
CHEMISTRY
Gene silencing oligonucleotides
IMMUNE BLOCKADE
Toll-like receptor antagonism
SECOND GENERATION
CHEMISTRY
Modified RNA-DNA hybrid structure;
Most successful to date,
but limitations persist
ANTISENSE
CONCEPT
FIRST GENERATION
CHEMISTRY
IMMUNE ACTIVATION
Toll-like receptor agonism
Idera scientists were
early pioneers

Understanding of TLR biology has informed development
of immunotherapy and gene silencing technologies
Toll-like Receptors (TLRs)
•
Discovered in the 1990s; subject of Nobel Prize in 2011
•
Play central role in the innate immune system
•
Initiate signaling cascades that activate inflammation and
adaptive immune responses
•
Nucleic acids are ligands for endosomal TLRs 7, 8 and 9
Therapeutic Implications
TLR
immune
modulation
exploits
TLR-nucleic
acid
interaction
to
stimulate
or
block
TLR-mediated
signaling
Gene
silencing
oligonucleotides
are
specifically
designed
to
avoid
activation
of
TLRs,
thereby
enabling
enhanced
gene
silencing
activity
6

Idera has developed two leading nucleic acid chemistry-
based platforms
7
TOLL-LIKE RECEPTOR
IMMUNE MODULATION
GENE SILENCING
OLIGONUCLEOTIDES
TECHNOLOGY
BIOLOGICAL
TARGET
BIOLOGICAL
IMPACT
Oligonucleotide-based
Third generation
oligonucleotide chemistry
Toll-like receptors
RNA
Activate or inhibit
immune activity
Silence
disease-related genes

Idera’s growing pipeline
B-CELL LYMPHOMA –
IMO-8400
Waldenström’s macroglobulemia
Diffuse large B-cell lymphoma (MYD88 L265P+)
RARE DISEASES –
IMO-8400
Dermatomyositis
Duchenne muscular dystrophy
DEVELOPMENT PROGRAM
PRECLINICAL
PHASE 1
PHASE 2
PIVOTAL
Planning underway
IMMUNO-ONCOLOGY –
IMO-2125 / IMO-2055
Intratumoral combination with CPI
Planning underway
Planning underway
GENE SILENCING OLIGONUCLEOTIDES
Undisclosed targets
Major Anticipated 2015 Milestones:
•
Results from Phase 1/2 Waldenström’s trial in 4Q
•
Immuno-oncology, Dermatomyositis and Duchenne programs advance into or toward clinical trials
•
Selection of first GSO development candidates for development
8
AUTOIMMUNE DISEASES
Undisclosed targets

Idera’s future is bright: long-term value drivers
•
Immunotherapy
and
gene
silencing
platforms
are
the
foundation
for
potentially
transformational
therapies
for
cancer
and
rare
diseases
•
Genetically
defined
B-cell
lymphoma
programs
are
progressing
in
the
clinic
•
New
immuno-oncology
program
offers
opportunity
to
enhance
emerging
class
of
checkpoint
inhibitors
and
improve
outcomes
for
cancer
patients
•
Rare
disease
programs
focus
on
serious
unmet
medical
needs
in
collaboration
with
strong
advocacy
communities
•
Enhanced
executive
management
team
has
track
record
of
success
and
expertise
to
build
the
business
9

B-cell lymphoma programs
10
Leading scientific discovery in
immunotherapy & gene silencing
FOCUSED ON SERIOUS UNMET NEEDS
IN ONCOLOGY & RARE DISEASES
Committed to advancing patient care

B-cell lymphomas characterized by the MYD88 L265P
mutation are rare and have limited treatment options
Waldenström’s Macroglobulinemia (WM)
•
Rare
and
slow-growing
form
B-cell
lymphoma
1
•
~1,000-1,500
new
cases
diagnosed
annually
in
US
1
•
Currently
incurable
with
no
FDA
approved
therapies
1
•
90%
carry
MYD88
L265P
mutation
2
•
Serious
complications
include
anemia,
retinopathy
and
peripheral
neuropathy
1
Diffuse Large B-Cell Lymphoma (DLBCL)
•
Fast
growing
and
potentially
lethal
form
of
B-cell
lymphoma
1
•
~20,000
new
cases
diagnosed
annually
in
US
3
•
10%
carry
MYD88
L265P
mutation
4,5
•
Data
show
poor
prognosis
in
MYD88
L265P+
population
6
MYD88
L265P
mutation
also
present
in
chronic
lymphocytic
lymphoma
(5-10%)
7
,
splenic
marginal
zone
lymphoma
(13%)
8
,
primary
CNS
lymphoma
(36%)
9
,
and
other
cancers
11
1
American
Cancer
Society;
Treon
SP,
et
al.
N
Engl
J
Med.
2012.;
3
Cultrera
JL,
et
al.
Cancer
Control.
2012.;
4
Wang,
et
al.
Bood
Lymph
Canc
2013.
5
Rosenwald
A,
et
al.
N
Engl
J
Med.
2002.
6
Fernandez-Rodriguez
C,
et
al.
Leukemia.
2014.
7
Puente,
et
al.
Nature.
2011.
8
Yan,
et
al.
Haematologica.
2011.
9
Montesinos-Rongen,
et
al.
Acta
Neuropathol.
2011.
Time (Months)
Survival is impaired in
MYD88 L265P+ DLBCL patients
6
2

Targeted therapy for B-cell lymphoma patients carrying
oncogenic mutation in TLR signaling pathway
Graphic adapted from Cancer Res. 2013,73 Suppl. 1.2332. IMO-8400 data presented at AACR 2014.
IMO-8400 inhibits
tumor cell viability
IMO-8400 suppresses
tumor-associated cytokines
0
50
100
150
200
250
10
20
30
-
IMO-8400 (
M)
WM Cells
WM Cells
IMO-8400 (
M)
0
10
20
30
40
60
80
100
12

IMO-8400 has demonstrated tolerability and evidence
of clinical activity
•
IMO-8400 is a synthetic oligonucleotide-based
antagonist of TLRs 7, 8 and 9
•
Activity observed in preclinical models of
autoimmune diseases and lymphoma
•
Evidence of TLR antagonism
established in human clinical trials in psoriasis
•
IMO-8400 generally well tolerated in ~85
patients and healthy subjects with >550 doses
administered to date
IMO-8400 blocks TLR
signaling and immune
system activation
13

Following safety review, enrollment initiated in third dose
cohort of Phase 1/2 Waldenström’s trial
0.6 mg/kg weekly
4 weeks
Cohort 1
20 weeks
1.2 mg/kg weekly
Cohort 2
4 weeks
20 weeks
2.4 mg/kg weekly
Cohort 3
4 weeks
20 weeks
•
Positive data review committee (DRC) recommendation to
advance to 2
nd
dose cohort*
•
Enrollment initiated
Study objectives: demonstrate safety, clinical activity and optimized dosing regimen; Target enrollment: up to ~30 patients
•
Positive DRC recommendation to
advance to 3
rd
dose cohort*
•
Received FDA orphan drug designation for IMO-8400 in Waldenström’s in December 2014
•
Trial results expected in 4Q 2015
14
*DRC recommendations on dose escalation based on 4-week safety data from cohorts 1 and 2, respectively

Additional B-cell lymphoma program updates
•
Completed initial development of prototype CDx under collaboration with Abbott Molecular
•
Activated
multiple
clinical
sites
and
expanded
patient
screening
in
Phase
1/2
DLBCL
trial
•
Presented abstracts at ASH 2014 included:
–
Safety of IMO-8400 in Phase 1 and 2 clinical trials in healthy volunteers and psoriasis patients
–
Preclinical activity of IMO-8400 in combination with rituximab
IMO-8400 + rituximab
inhibited tumor growth
15
IMO-8400 + rituximab
improved tumor histology
Rituximab
alone
IMO-8400
+ rituximab
Data from ABC-DLBCL MYD88 L265P+ OCI-Ly10 xenograft model. Presented at ASH 2014.

Immuno-oncology program
16
Leading scientific discovery in
immunotherapy & gene silencing
FOCUSED ON SERIOUS UNMET NEEDS
IN ONCOLOGY & RARE DISEASES
Committed to advancing patient care

Cancer immunotherapy with intratumoral TLR 9 agonist
and checkpoint inhibitors
Therapeutic Rationale
Emerging class of checkpoint inhibitors (CPIs) represents a significant
advance in cancer immunotherapy
Intratumoral administration of TLR 9 agonists have demonstrated
immunostimulatory activity in preclinical models of cancer
Opportunity
Combination of complementary cancer immunotherapy agents may 
increase the duration and durability of clinical responses
17
–
Designed to block pathways that inhibit anti-tumor immune responses
–
PD-1 and CTLA-4 inhibitors are FDA approved for the treatment of
melanoma; clinical development in additional cancer types is ongoing

Intratumoral TLR 9 agonist stimulates immune response
while CPI inhibits tumor defense against immune attack
18
Modulation of the
Tumor Microenvironment
•
Intratumoral TLR 9 agonist
stimulates dendritic cell
maturation and T-cell
activation;
induces
interferon-
•
CPIs block inhibitory pathways
enabling activation of CD4+
and CD8+ T-cell responses
•
Dying tumor cells release
antigens enabling T-cell
memory, systemic anti-tumor
immune responses

IMO-2125 & IMO-2055 are clinical-stage TLR 9 agonists
•
IMO-2125 and IMO-2055 are synthetic
oligonucleotide-based agonists of TLR 9
•
Completed trials involving systemic administration
of IMO-2125 and IMO-2055 included:
–
80 patients with hepatitis C
–
300 patients with various types of cancer
•
Idera’s TLR 9 agonists have demonstrated
evidence of anti-tumor activity in multiple settings
–
Clinical trial in non-small cell lung cancer
•
Smith, et al. Cancer Immunol Immunother 2014.
–
Preclinical models
•
Damiano, et al. Clin Cancer Res 2006.
•
Damiano, et al. PNAS 2007.
•
Damiano, et al. Clin Cancer Res 2009.
•
Rosa, et al. Clin Cancer Res 2011.
19
IMO-2125 and IMO-2055
stimulate TLR signaling to
induce an immune
response

Intratumoral IMO-2055 and anti-CTLA-4 mAb demonstrated
potent and systemic anti-tumor activity in preclinical models
Inhibited growth of treated tumors
Induced systemic anti-tumor immune response
•
AH1 antigen presented in locally treated tumors
•
ß-gal antigen presented in disseminated lung metastases
Data from CT26 colon carcinoma model. Presented at AACR Tumor Immunology 2014.
Anti-CTLA-4
IMO-2055 + Anti-CTLA-4
Anti-CTLA-4
IMO-2055 +
Anti-CTLA-4

Priorities for immuno-oncology program
•
Rapidly advance a combination regimen with an intratumoral TLR 9
agonist
and a CPI into clinical development
•
Complete ongoing preclinical studies to characterize potential combination
regimens with various CPIs
21
Intratumoral TLR 9 agonism has the potential to enhance
cancer immunotherapy regimens with CPIs

Idera’s growing pipeline
B-CELL LYMPHOMA –
IMO-8400
Waldenström’s macroglobulemia
Diffuse large B-cell lymphoma (MYD88 L265P+)
RARE DISEASES –
IMO-8400
Dermatomyositis
Duchenne muscular dystrophy
DEVELOPMENT PROGRAM
PRECLINICAL
PHASE 1
PHASE 2
PIVOTAL
Planning underway
IMMUNO-ONCOLOGY –
IMO-2125 / IMO-2055
Intratumoral combination with CPI
Planning underway
Planning underway
GENE SILENCING OLIGONUCLEOTIDES
Undisclosed targets
Major Anticipated 2015 Milestones:
•
Results from Phase 1/2 Waldenström’s trial in 4Q
•
Immuno-oncology, Dermatomyositis and Duchenne programs advance into or toward clinical trials
•
Selection of first GSO development candidates for development
22
AUTOIMMUNE DISEASES
Undisclosed targets

SUDHIR AGRAWAL, D.Phil.
President, Research
PETE WOLF
SVP, General Counsel
LOU ARCUDI
SVP, Chief Financial Officer
LOU BRENNER, M.D.
SVP, Chief Medical Officer
KATE HAVILAND
VP, Rare Diseases
LIZ EBERHARDT
VP, Oncology Team
Enhanced executive management team has a track record
of success across the industry
23
VIN MILANO
Chief Executive Officer
BOB DOODY
VP, Investor Relations and
Corporate Communications

Financial overview
COMMON SHARES OUTSTANDING
85.8M as of 9/30/14
RECENT CLOSING PRICE
$4.96 as of 1/8/15
TRADING VOLUME
~1.7M shares daily (90 day average)
MARKET CAPITALIZATION
~$425.6M as of 1/8/15
CASH & INVESTMENTS
~$58M as of 9/30/14
24

Idera’s future is bright: long-term value drivers
•
Immunotherapy
and
gene
silencing
platforms
are
the
foundation
for
potentially transformational therapies for cancer and rare diseases
•
Genetically
defined
B-cell
lymphoma
programs
are
progressing
in
the
clinic
•
New
immuno-oncology
program
offers
opportunity
to
enhance
emerging
class
of checkpoint inhibitors and improve outcomes for cancer patients
•
Rare
disease
programs
focus
on
serious
unmet
medical
needs
in
collaboration
with strong advocacy communities
•
Enhanced
executive
management
team
has
track
record
of
success
and
expertise to build the business
25

Solving Unmet Patient Needs with
Strong Scientific Foundations
APPENDIX

B-cell lymphoma programs
27
Leading scientific discovery in
immunotherapy & gene silencing
FOCUSED ON SERIOUS UNMET NEEDS
IN ONCOLOGY & RARE DISEASES
Committed to advancing patient care

Oncogenic MYD88 L265P signaling requires TLRs 7 and 9
Time (Days)
28
TLR and MYD88 Knockdown
“…Here we show that the MYD88 L265P
oncoprotein binds constitutively to two
members of the Toll-like receptor family,
TLR7 and TLR9, thereby amplifying signals
that emanate from these receptors.
Knockdown of TLR7 or TLR9 potently
suppressed
NF-
B
activity
in
ABC-DLBCL
cell lines and promoted apoptosis…
These new insights into the oncogenic
mechanisms of MYD88 mutants provide a
rationale for targeting of TLR7 and TLR9
signaling for the therapy of ABC-DLBCL.”
Lim, Barton, Staudt. AACR 2013.

Rare disease programs
29
Leading scientific discovery in
immunotherapy & gene silencing
FOCUSED ON SERIOUS UNMET NEEDS
IN ONCOLOGY & RARE DISEASES
Committed to advancing patient care

Duchenne muscular dystrophy is a rare and universally fatal
neuromuscular disorder
Therapeutic Rationale
Muscle cell damage caused by lack of functional dystrophin protein
TLR 7 significantly over-expressed, even in pre-symptomatic infants
Corticosteroids are standard of care, but have limited efficacy and serious side effects
~15-20k patients in U.S.
Opportunity
TLR antagonism has the potential to reduce muscle inflammation and slow disease progression
Immune modulation may potentiate dystrophin restoration therapies such as exon skipping by
inducing immunologic tolerance to dystrophin
Graphic adapted from McDonald C, et al. Muscle & Nerve, 2013; Bushby K, et al. Lancet, 2010
DELAYS IN DEVELOPMENT
PROBLEMS STANDING
PROBLEMS WALKING
FULL-TIME WHEELCHAIR USE
LIMITED USE OF ARMS
VENTILATION
DEATH
30
MMWR 2009; Chen, et al. Neurology 2005; Henriques-Pons, et al. Hum Mol Gen 2014.

Dermatomyositis is a rare and disabling inflammatory
muscle disease with skin involvement
31
Therapeutic Rationale
•
Cell damage may be caused by stress, injury or infection
•
TLR 9 and mRNA for MYD88 significantly over-expressed
•
Onset typically occurs between ages 40-60 years
•
Symptoms can be severely disabling, and include:
–
Muscle weakness, skin rash and/or calcinosis, joint pain, and
difficulty swallowing
•
Corticosteroids and immunosuppressive drugs have limited
efficacy and serious side effects
•
~25k patients in U.S.
Opportunity
•
TLR antagonism may disrupt the autoimmune cycle of tissue
damage to improve disease symptoms
Data provided by The Myositis Association. Rayavarapu, et al. Skeletal Muscle 2013.

Scientific rationale for TLR antagonism in
dermatomyositis and Duchenne muscular dystrophy
TLR
ANTAGONIST
INHIBITS
SIGNALING
CASCADE
Damaged cells release self DNA, self
RNA and other molecules to form
Damage Associated Molecular
Patterns (DAMPs).
DAMPs stimulate TLR signaling to
promote inflammation.
Inflammation causes additional
cellular damage, thereby propagating
the diseases process.
32
Damaged or Dying Cells
Adapted from Rayavarapu, et al. Skeletal Muscle 2013.

Rare disease programs are advancing toward clinical
development
Duchenne Muscular Dystrophy
•
Collaborating with Parent Project Muscular Dystrophy
•
Conducting
additional
preclinical
studies
in
well-established
mdx
mouse
model
•
Evaluating potential clinical trial design options with disease experts, including population
and endpoint selection
Dermatomyositis
•
Collaborating with The Myositis Association
•
Organized advisory board of expert clinicians to inform design of Phase 2 clinical trial
•
Finalizing clinical trial plan with IMO-8400; anticipate pre-IND meeting with FDA in 1H 2015
33

Gene silencing oligonucleotide program
34
LEADING SCIENTIFIC DISCOVERY
IN IMMUNOTHERAPY &
GENE SILENCING
Focused on serious unmet needs in
oncology & rare diseases
Committed to advancing patient care

Novel Gene Silencing Oligonucleotides (GSOs)
overcome limitations of current antisense technologies
THIRD GENERATION
SECOND GENERATION
FIRST GENERATION
Chemistry
•
Single-stranded structure with
phosphorothioate backbone
Clinical Activity
•
Severe off-target immune
activation limited clinical utility
Chemistry
•
Modified RNA-DNA hybrid
structure pioneered by Idera
•
Most successful antisense
chemistry to date
Clinical Activity
•
Immune activation,
immunotoxicity, injection site
reactions
•
Hepatic toxicity with chronic dosing
•
Limited therapeutic index
Chemistry
•
Novel structure discovered by Idera
•
19-
to 21-mer length is optimal for gene silencing
•
No 5’-prime ends abrogates immune activation
•
Accessible 3’-prime ends improves degradation and
clearance
•
Issued U.S. patent
Activity in Preclinical Models
•
Reduced immunotoxocity
•
Decreased hepatic toxicity
•
Improved potency
•
Increased therapeutic index
In vivo proof-of-concept established against
multiple gene targets
Bhagat, et al. J Med Chem 2011.

Evaluate targets based on scientific merit and technical feasibility
Validate targets in preclinical models
Initiate development plans based on strategic prioritization
Assessment of potential GSO targets in oncology and
rare diseases is underway
Assess clinical feasibility and commercial potential
36
PRIORITIZATION OF
GSO TARGETS FOR
CLINICAL DEVELOPMENT