UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 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): July 14, 2011

 

 

Marina Biotech, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   000-13789   11-2658569

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

3830 Monte Villa Parkway, Bothell, Washington     98021
(Address of principal executive offices)     (Zip Code)

Registrant’s telephone number, including area code: 425-908-3600

N/A

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:

 

¨ 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 5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.

Amendment of 2008 Stock Incentive Plan

At the 2011 Annual Meeting of Stockholders (the “Annual Meeting”) of Marina Biotech, Inc. (the “Company”) held on July 14, 2011, the Company’s stockholders approved an amendment to the Company’s 2008 Stock Incentive Plan (as amended, the “2008 Plan”). The amendment was previously adopted by the Company’s Board of Directors on May 24, 2011. Pursuant to the amendment, the total number of shares of common stock, par value $0.006 per share, of the Company (“Common Stock”) that may be subject to the granting of awards under the 2008 Plan was increased from 2,125,000 shares to 8,125,000 shares.

Additional information regarding the 2008 Plan is summarized under the heading “Proposal No. 6 – Approval of an Amendment to our 2008 Stock Incentive Plan to Increase the Number of Shares Available Thereunder from 2,125,000 to 8,125,000” in the Company’s Definitive Proxy Statement on Schedule 14A in connection with the Annual Meeting (the “Proxy Statement”), which was filed with the Securities and Exchange Commission (the “SEC”) on June 7, 2011, and is incorporated herein by reference. The description of the 2008 Plan set forth in the Proxy Statement and in this Current Report on Form 8-K are qualified in their entirety by reference to the text of the 2008 Plan, which is filed as Exhibit 10.1 hereto and is incorporated herein by reference.

Amendment of Employee Stock Purchase Plan

At the Annual Meeting, the Company’s stockholders approved an amendment to the Company’s 2007 Employee Stock Purchase Plan (as amended, the “ESPP”). The amendment was previously adopted by the Company’s Board of Directors on May 24, 2011. Pursuant to the amendment, the total number of shares of Common Stock available for issuance under the ESPP was increased from 150,000 shares to 650,000 shares.

Additional information regarding the ESPP is summarized under the heading “Proposal No. 5 – Approval of an Amendment to our 2007 Employee Stock Purchase Plan to Increase the Number of Shares Available for Issuance Thereunder from 150,000 to 650,000” in the Proxy Statement, which was filed with the SEC on June 7, 2011, and is incorporated herein by reference. The description of the ESPP set forth in the Proxy Statement and in this Current Report on Form 8-K are qualified in their entirety by reference to the text of the ESPP, which is filed as Exhibit 10.2 hereto and is incorporated herein by reference.

Election of R. John Fletcher

On July 14, 2011, the Board of Directors of the Company, upon recommendation of the Nominating and Corporate Governance Committee of the Board, acting pursuant to Article II, Section 5 of the Amended and Restated By-Laws of the Company, elected R. John Fletcher to fill the vacancy in the Board of Directors created by the expiration of the term of Chiang J. Li, M.D., effective immediately, with a term expiring at the annual meeting of stockholders to be held in 2012. Mr. Fletcher was also appointed to serve as a member of each of the Board’s Audit Committee and Compensation Committee. Mr. Fletcher will be compensated as a director pursuant to the Company’s general compensation policy for non-employee directors. The Company announced the appointment of Mr. Fletcher in a press release dated July 18, 2011, which is attached hereto as Exhibit 99.1.

Item 5.03 Amendments to Articles of Incorporation or Bylaws; Change in Fiscal Year.

On July 18, 2011, the Company filed a Certificate of Amendment (the “Certificate of Amendment”) to the Restated Certificate of Incorporation of the Company (the “Restated Certificate”) with the Secretary of State of the State of Delaware to increase the number of authorized shares of Common Stock from 90,000,000 to 180,000,000. The holders of a majority of the outstanding shares of the Company’s capital stock approved the amendment to the Restated Certificate at the Annual Meeting pursuant to Section 242 of the Delaware General Corporation Law. A copy of the Certificate of Amendment is filed as Exhibit 3.1 hereto.

Item 5.07. Submission of Matters to a Vote of Security Holders.

The Company held its Annual Meeting on July 14, 2011. Proxies were solicited for each of the six (6) proposals set forth below pursuant to the Proxy Statement. Each share of Common Stock was entitled to one vote with respect to matters submitted to a vote of stockholders, and the voting results reported below are final. Abstentions had the same effect as “Against” votes for all proposals except Proposal No. 1.

PROPOSAL No. 1

Stockholders elected five (5) persons to the Board of Directors, each to hold office until the 2012 annual meeting of stockholders and until their respective successors shall have been duly elected or appointed and qualified, as shown below. This proposal required the affirmative vote of a plurality of the votes cast.

 

Nominee

 

Votes “FOR”

 

Votes WITHHELD

 

Broker Non-Votes

J. Michael French

  14,795,159   1,218,992   26,764,529

James M. Karis

  14,855,231   1,158,920   26,764,529

Peter D. Parker

  14,848,992   1,165,159   26,764,529

Gregory Sessler

  14,861,371   1,152,780   26,764,529

Michael D. Taylor, Ph.D.

  14,854,759   1,159,392   26,764,529

PROPOSAL No. 2

Stockholders ratified the appointment of KPMG LLP as the Company’s independent registered public accounting firm for the fiscal year ending December 31, 2011, as shown below. This proposal required the affirmative vote of a majority of the shares present at the Annual Meeting, either in person or by proxy, and entitled to vote.

 

Votes “FOR”

 

Votes AGAINST

 

Votes ABSTAINED

 

Broker Non-Votes

41,447,945

  926,904   403,831   -0-

PROPOSAL No. 3

Stockholders approved an amendment to the Restated Certificate to increase the number of authorized shares of Common Stock from 90,000,000 to 180,000,000, as shown below. This proposal required the affirmative vote of a majority of the issued and outstanding shares of Common Stock entitled to vote as of the record date.

 

Votes “FOR”

 

Votes AGAINST

 

Votes ABSTAINED

 

Broker Non-Votes

34,635,588

  7,788,108   354,984   -0-

PROPOSAL No. 4

Stockholders approved an amendment to the Restated Certificate to effect a reverse stock split, at a time in the future, and in such ratio between a one-for-two and one-for-ten reverse stock split, to be determined by our Board of Directors, to be in the best interest of the Company, as shown below. This proposal required the affirmative vote of a majority of the issued and outstanding shares of Common Stock entitled to vote as of the record date.

 

Votes “FOR”

 

Votes AGAINST

 

Votes ABSTAINED

 

Broker Non-Votes

34,878,303

  7,802,041   98,336   -0-

PROPOSAL No. 5

Stockholders approved an amendment to the Company’s 2007 Employee Stock Purchase Plan to increase the number of shares available for issuance thereunder from 150,000 to 650,000, as shown below. This proposal required the affirmative vote of a majority of the shares present at the Annual Meeting, either in person or by proxy, and entitled to vote.

 

Votes “FOR”

 

Votes AGAINST

 

Votes ABSTAINED

 

Broker Non-Votes

13,862,551

  2,053,716   97,884   26,764,529

PROPOSAL No. 6

Stockholders approved an amendment to the Company’s 2008 Stock Incentive Plan to increase the number of shares available for issuance thereunder from 2,125,000 to 8,125,000, as shown below. This proposal required the affirmative vote of a majority of the shares present at the Annual Meeting, either in person or by proxy, and entitled to vote.

 

Votes “FOR”

 

Votes AGAINST

 

Votes ABSTAINED

 

Broker Non-Votes

12,024,030

  3,889,210   100,911   26,764,529

Item 8.01 Other Events.

Exercises of Series B Warrants

During the period beginning on June 7, 2011 and ending on July 12, 2011, holders of 22,293,500 Series B Warrants, each to purchase one unit consisting of one share of Common Stock and one Series A Warrant to purchase one share of Common Stock, exercised their Series B Warrants, resulting in aggregate gross proceeds to the Company of approximately $3.1 million. The Company issued the Series B Warrants on May 20, 2011 in connection with the underwritten public offering of the Company’s securities effected pursuant to that certain Underwriting Agreement, dated May 17, 2011, between the Company and Roth Capital Partners, LLC, as representative of the underwriters named therein. The remaining 25,000 Series B Warrants expired by their terms on July 12, 2011.

Investor Presentation

Attached to this Current Report on Form 8-K as Exhibit 99.2, and incorporated herein by reference, is a copy of a presentation about the Company that it used at the Annual Meeting.

Item 9.01. Financial Statements and Exhibits

(d) Exhibits:

 

Exhibit No.

 

Description

  3.1   Certificate of Amendment.
10.1   2008 Stock Incentive Plan (filed as Appendix A to the Company’s Definitive Proxy Statement on Schedule 14A filed on April 29, 2008, and incorporated herein by reference).**
10.2   2007 Employee Stock Purchase Plan (filed as Exhibit 10.1 to the Company’s Registration Statement on Form S-8, File No. 333-146183, and incorporated herein by reference).**
99.1   Press release of Marina Biotech, Inc. dated July 18, 2011.
99.2   Investor Presentation of Marina Biotech, Inc.

 

** Indicates management contract.

SIGNATURES

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.

 

              Marina Biotech, Inc.
July 18, 2011               By:  

/s/ Peter S. Garcia

              Name:   Peter S. Garcia
              Title:   Chief Financial Officer

EXHIBIT INDEX

 

Exhibit No.

 

Description

  3.1   Certificate of Amendment.
10.1   2008 Stock Incentive Plan (filed as Appendix A to the Company’s Definitive Proxy Statement on Schedule 14A filed on April 29, 2008, and incorporated herein by reference).**
10.2   2007 Employee Stock Purchase Plan (filed as Exhibit 10.1 to the Company’s Registration Statement on Form S-8, File No. 333-146183, and incorporated herein by reference).**
99.1   Press release of Marina Biotech, Inc. dated July 18, 2011.
99.2   Investor Presentation of Marina Biotech, Inc.

 

** Indicates management contract.

CERTIFICATE OF AMENDMENT

OF THE

RESTATED CERTIFICATE OF INCORPORATION

OF

MARINA BIOTECH, INC.

Pursuant to Section 242 of the

Delaware General Corporation Law

The undersigned, a duly authorized officer of Marina Biotech, Inc. (the “ Corporation ”), a corporation organized and existing under the General Corporation Law of the State of Delaware (the “ DGCL ”), does hereby certify in accordance with the provisions of the DGCL as follows:

1.        The name of the Corporation is Marina Biotech, Inc. The Corporation was originally incorporated under the name Nastech Pharmaceutical Company Inc. The original Certificate of Incorporation of the Corporation (the “ Original Certificate ”) was filed with the Secretary of State of the State of Delaware on September 23, 1983, and the Original Certificate was amended and restated in its entirety by the filing of a Restated Certificate of Incorporation of the Corporation (the “ Restated Certificate ”) with the Secretary of State of the State of Delaware on July 20, 2005.

2.        This Certificate of Amendment amends the provisions of the Restated Certificate as set forth herein, and was adopted by the Corporation’s Board of Directors and authorized by a majority of the holders of the outstanding shares of common stock entitled to vote thereon at an annual meeting of stockholders pursuant to Section 242 of the DGCL.

3.        Article FOURTH, paragraph (a) of the Restated Certificate is hereby deleted and replaced in its entirety to read as follows:

“(a) The total number of shares of stock which the Corporation shall have authority to issue is 180,000,000 shares of Common Stock, $0.006 par value per share, and 100,000 shares of Preferred Stock, $0.01 par value per share.”

IN WITNESS WHEREOF, the undersigned, being the Secretary and Chief Financial Officer of the Corporation, does hereby execute this Certificate of Amendment as of July 18, 2011.

 

             

/s/ Peter S. Garcia

                Name:   Peter S. Garcia
                Title:   Secretary and Chief Financial Officer

Exhibit 99.1

Marina Biotech Announces Changes to Board of Directors

Appoints John Fletcher to Board of Directors and James Karis as Chairman

Bothell, WA, July 18, 2011 – Marina Biotech, Inc. (Nasdaq: MRNA), a leading nucleic acid-based drug discovery and development company, today announced that R. John Fletcher was elected to the Company’s Board of Directors effective July 14, 2011, replacing Board member Chiang Li, Ph.D., M.D., who announced his retirement from the Marina Biotech board prior to the 2011 annual meeting of shareholders. The Company also announced the appointment of James Karis, who has served as a Board member since 2009, as Chairman of the Board, effective July 14, 2011, replacing co-chairmen Gregory Sessler and Peter Parker, both of whom will continue as board members of Marina Biotech.

“I am pleased to welcome John Fletcher to Marina Biotech’s Board of Directors,” stated James Karis, Chairman of the Board of Directors of Marina Biotech. “John brings extensive corporate strategy and financing experience that is characterized by a strong understanding of the commercial potential of new technologies and the options for developing, funding, and acquiring new businesses. We would also like to thank Dr. Li for his service to our company and his contributions to our wholly owned subsidiary, Cequent Pharmaceuticals. In addition, I want to thank Greg and Peter for their outstanding efforts as co-Chairmen in effectively integrating the MDRNA and Cequent Boards and then leading the new Marina Biotech Board throughout this past year.”

Mr. Fletcher is an independent director for purposes of the Sarbanes Oxley Act of 2002 and NASDAQ stock exchange regulations. He is a Founding Partner of Fletcher Spaght Ventures, a venture capital firm investing in emerging growth healthcare and high technology companies. He also serves as the CEO of Fletcher Spaght Inc., a management consulting firm he founded to provide strategy and financing assistance to new companies. Mr. Fletcher has over twenty-five years providing strategy and financing assistance to new companies. Prior to launching Fletcher Spaght Inc. in 1983, he served as a Senior Manager at The Boston Consulting Group, managing client relationships in healthcare and high technology companies. Mr. Fletcher attended the Wharton School of Business at the University of Pennsylvania and completed all coursework for a Ph.D. He holds an MA in International Finance from Central Michigan University, an MBA from Southern Illinois University, and a BBA from George Washington University. He is a current or past board member for many companies, including Axcelis, GlycoFi and Spectranetics.

“I’m very excited to join the board of Marina Biotech and look forward to contributing strategically to the Company as it works to develop and commercialize therapeutic products based on RNA interference,” said Mr. Fletcher.

With the resignation of Dr. Li and the addition of Mr. Fletcher, there remain six members on the Marina Biotech Board of Directors.

About Marina Biotech, Inc.

Marina Biotech is a biotechnology company, focused on the development and commercialization of RNA interference- (RNAi) and RNA-based therapeutics. The Marina Biotech pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs — in bladder cancer and malignant ascites. Marina Biotech entered into an exclusive agreement with Debiopharm Group for the development and commercialization of the bladder cancer program. Marina Biotech’s goal is to improve human health through the development of RNAi and RNA-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Additional information about Marina Biotech is available at http://www.marinabio.com .

Forward-Looking Statements

Statements made in this news release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of Marina Biotech to obtain additional funding; (ii) the ability of Marina Biotech to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) the ability of Marina Biotech and/or a partner to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) the ability of Marina Biotech and/or a partner to obtain required governmental approvals; and (v) the ability of Marina Biotech and/or a partner to develop and commercialize products that can compete favorably with those of competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in Marina Biotech’s most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. Marina Biotech assumes no obligation to update and supplement forward-looking statements because of subsequent events.

Contact:

Marina Biotech, Inc.

Peter Garcia

Chief Financial Officer

(425) 908-3603

pgarcia@marinabio.com

Annual Shareholders Meeting
Company Update
14 July 2011
Exhibit 99.2

Forward Looking Statement
Statements made in this presentation may be forward-looking statements within the
meaning of Federal Securities laws that are subject to certain risks and uncertainties and
involve factors that may cause actual results to differ materially from those projected or
suggested. Factors that could cause actual results to differ materially from those in
forward-looking statements include, but are not limited to: (i) the ability of Marina Biotech to
obtain
additional
funding;
(ii)
the
ability
of
Marina
Biotech
to
attract
and/or
maintain
manufacturing, research, development and commercialization partners; (iii) the ability of
Marina
Biotech
and/or
a
partner
to
successfully
complete
product
research
and
development, including preclinical and clinical studies and commercialization; (iv) the ability
of Marina Biotech and/or a partner to obtain required governmental approvals; and (v) the
ability of Marina Biotech and/or a partner to develop and commercialize products that can
compete favorably with those of competitors. Additional factors that could cause actual
results to differ materially from those projected or suggested in any forward-looking
statements are contained in Marina Biotech’s most recent periodic reports on Form 10-K
and Form 10-Q which are filed with the Securities and Exchange Commission. Marina
Biotech assumes no obligation to update and supplement forward-looking statements
because of subsequent events.
2

Broad Nucleic Acid-Based Platform
Provides a Superior Drug Discovery Engine
Appropriate
therapeutic
approach
to
targets
not
typically
suited
to
small
molecule or monoclonal antibody therapeutics
Capitalizes on distinct endogenous intracellular processes for protein
down-regulation
Allows for a scientific and risk adjusted pursuit of a specific nucleic acid-
based therapeutic modality
Established regulatory path through FDA and EMA
Multiple nucleic acid-based therapeutics are in clinical development
Two such therapeutics have been approved
3

4
Pfizer and Nucleic Acid-based Therapeutics
Tacere
shRNA
(TT-033):  Three separate, expressed RNAi elements targeting the
conserved regions of the Hepatitis C virus entrapped in an AAV protein coat
$145 MM deal (upfront and milestone payments have been made through Feb
2010)
Quark
siRNA
(PF-04523655):  Chemically-modified, unformulated siRNA compound
targeting proprietary target, RTP-801, for the treatment of wet age-related
macular degeneration (wet-AMD) and diabetic macular edema (DME)
Terms
not
disclosed
but
Pfizer
upped
milestone
payments
in
March
2011
to
support extended Phase II trials
Santaris
:
LNA
chemistry
for
single-stranded
RNA-targeted
therapies
$17 MM upfront (included $10 MM in equity) in 2010; $14 MM in 2011 and up
to $600 MM in downstream milestones
ssRNA

Nucleic Acid Therapeutic “Toolbox”
Constructs
Dicer length siRNA
RISC length siRNA
microRNA mimetics
microRNA antagonists
miniRNAs
Single-stranded RNA/DNA
5
Chemistries
UNA –
Non-nucleotide acyclic
monomers –
greater flexibility
CRN –
nucleotide analogs with a
linker connecting the C2’
and C4’
Delivery
DiLA
2
–
Combinations of amino acid head-groups, spacers, and
alkyl chains (tails)
SMARTICLES –
Combinations of anionic and cationic lipids
E. Coli –
Non-pathogenic bacteria engineered to produce, deliver
and release interfering RNA mediators (shRNA) to targeted tissue
Conjugation –
Peptides, etc. (phage display library)

Critical Needs for a Broad Nucleic Acid-
Based Therapeutics Discovery Engine
Multiple
chemistries to construct single and double-stranded
oligonucleotides with suitable affinity, stability and minimization of off-
target activity
Unlocked Nucleotide Analogs (UNA)
Conformationally Restricted Nucleotides (CRN)
With
multiple
delivery
approaches
Multiple carriers ranging from saline to bacteria to liposomal
(DiLA
2
/SMARTICLES
®
)
Multiple routes of administration (oral, local and systemic)
Leading to multiple nucleic acid-based therapeutic approaches
Double-stranded RNAi-based therapeutics
Single-stranded oligonucleotide therapeutics
MicroRNA-based therapeutics
6

RNAi
RDNA+
/chi
Marina Biotech’s Nucleic Acid-based
Therapeutic Platform
7
“undruggable target”
for a specific
indication
ssRNA/DNA
dsRNA
antagomir
mimetic
CRN/RNA
+ delivery
CRN/RNA
UNA/CRN
+ delivery
CRN/RNA
+ delivery
CRN/RNA
Plasmid +
bacteria
UNA +
delivery
Molecular Target
Local/Systemic
Oral
mRNA
microRNA
tk
tau
mu RNA / mu RNA+
RNAi
RDNA
RNA
RNA+
chi

/ mu
mu
Selection of a Nucleic Acid-based
Therapeutic Approach
Target, indication and patient phenotype determine the most appropriate
combination of technologies and thus the specific nucleic acid-based
modality(ies) to pursue in preclinical proof-of-concept
Determine target and intended biology
Specific mRNA(s) to down-regulate a specific protein(s)
microRNA to up-/down-regulate multiple mRNAs/proteins
For down-regulation, use a mimetic
For up-regulation, use an antagomir
Select delivery approach based on construct and site (tissue/organ)
tk RNAi
tau RNAi
DNA+
–
delivery
of
ssDNA/RNA
A
When appropriate, multiple technologies can be evaluated to determine
the best approach
8
–
delivery
of
shRNA
to
mucosal
epithelium
RNAi
–
delivery
of
dsRNA
in
a
liposomal
formulation
RNAi
RDNA
RNA+
–
delivery
of
ssDNA/RNA
or
dsRNA
RNA
/ mu
RDNA+
–
delivery
of
ssDNA/RNA
chi
/chi
mu

transKingdom
RNAi Platform
9
“undruggable target”
for a specific
indication
Molecular Target
mRNA
(protein)
ssDNA/RNA
dsRNA
antagomir
mimetic
microRNA
CRN-RNA
+ delivery
CRN-RNA
UNA/CRN
+ delivery
CRN-RNA
+ delivery
CRN/RNA
Plasmid +
bacteria
UNA +
delivery
Local/Systemic
Oral
tk
RNAi

About transKingdom
RNA interference ( tk RNAi™)
10
Non-pathogenic bacteria engineered to produce, deliver and release
interfering RNA mediators (shRNA) to targeted tissue
Efficient delivery to the epithelium of the gastrointestinal tract via oral
administration
Safe
and
well
tolerated
daily
dosing
of
up
to
10
11
cfu
(colony
forming
units) in non-human primates for 9 months
Phase 1b/2a clinical trial to treat Familial Adenomatous Polyposis
(FAP) –
a genetic pre-cancerous polyposis disease with orphan drug
status
Exclusive worldwide license from Beth Israel Deaconess Medical
Center/Harvard

Familial Adenomatous Polyposis (FAP)
Rare hereditary disease
Mutation in Adenomatous Polyposis Coli (APC) gene
Causes
dysregulation
and
accumulation
of
-catenin
Results in numerous colon polyps appearing in early
adolescence with potential for rapid disease progression
Clinical
drug
product,
CEQ508,
targets
-catenin
oncogene
Unmet medical need
~80,000 worldwide (orphan status)
Near 100% risk of colon cancer if untreated
Treatment options:
Surgical intervention (colectomy) is the only available treatment
to prevent colon cancer progression
No generally accepted pharmaceutical approach is available
U.S. FAP Market Potential: >$100 MM
Opportunities to expand into sporadic CRC, other polyposis syndromes and other
GI cancers
Potential for 4Q2014 launch and first RNAi drug to market
11

Actual and Potential Clinical, Regulatory
and Commercial Timelines
12
December 2009 –
IND granted in U.S.
September 2010 –
Patent grant in the EP protecting tkRNAi
December 2010 –
Received FDA Orphan Drug Designation
January 2011 –
Completed LTT study in Non-Human Primates
June 2011 –
Completed dosing in Cohort 1
1Q2012 –
Complete dose escalating phase of 1b/2a
Delayed dosing of Cohort 2 until 4Q2011
Remedying GMP-related issues not a safety issue
Informed the FDA of our decision to delay dosing
2Q2012 –
Complete stable dose phase of 1b/2a
4Q2013 –
Complete Pivotal Phase 2
3Q2014 –
Expedited/accelerated FDA review and approval
4Q2014 –
Launch –
first RNAi drug to market

RNAi Platform
13
“undruggable target”
for a specific
indication
ssDNA/RNA
dsRNA
mRNA
antagomir
mimetic
microRNA
CRN/RNA
+ delivery
CRN/RNA
UNA/CRN
+ delivery
CRN/RNA
+ delivery
CRN/RNA
Plasmid +
bacteria
UNA +
delivery
Molecular Target
RNA i
tau
Local/Systemic
Oral
tau

About tau RNA interference ( tau RNAi)
14
Combination of highly active UsiRNA constructs and liposomal
delivery systems
UsiRNA –
Substitution of unlocked nucleobase analogs (UNA) within
siRNA; therapeutic use proprietary to Marina Biotech
DiLA
-
Di-Alkylated
Amino
Acids
for
liposomal-based
delivery;
novel
compounds proprietary to Marina Biotech
Smarticles -
Lipid-based amphoteric liposomes for oligonucleotide delivery
(in Phase I Clinical Trial by ProNAi via systemic delivery)
Pairing of the UsiRNA with the most appropriate liposomal delivery
system provides greater efficacy and specificity for RNAi
2

Publications on UsiRNAs and Systemic
and
Local
Delivery
with
DiLA
15
Mol Ther. 2011 Apr 19. (PMID:21505423)
An Amino Acid-based Amphoteric Liposomal Delivery System for Systemic Administration of
siRNA.
Adami RC, Seth S, Harvie P, Johns R, Fam R, Fosnaugh K, Zhu T, Farber K, McCutcheon M, Goodman TT, Liu Y, Chen Y, Kwang E,
Templin MV, Severson G, Brown T, Vaish N, Chen F, Charmley P, Polisky B, Houston ME Jr.
Marina Biotech, Inc., Bothell, Washington, USA.
Nucleic Acids Res. 2011 Mar 1;39(5):1823-32.
Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs.
Vaish N, Chen F, Seth S, Fosnaugh K, Liu Y, Adami R, Brown T, Chen Y, Harvie P, Johns R, Severson G, Granger B, Charmley P,
Houston M, Templin MV, Polisky B.
Marina Biotech Inc., 3830 Monte Villa Parkway, Bothell, WA 98021, USA
Mol Ther. 2011 Mar 1. (PMID: 21364537)
RNAi-based Therapeutics Targeting Survivin and PLK1 for Treatment of Bladder Cancer.
Seth
S,
Matsui
Y,
Fosnaugh
K,
Liu
Y,
Vaish
N,
Adami
R,
Harvie
P,
Johns
R,
Severson
G,
Brown
T,
Takagi
A,
Bell
S,
Chen
Y,
Chen
F,
Zhu T, Fam R, Maciagiewicz I, Kwang E, McCutcheon M, Farber K, Charmley P, Houston Jr ME, So A, Templin MV, Polisky B.
Discovery Research and Pharmaceutical Development, Marina Biotech Inc., Bothell, Washington, USA
2

Marina Biotech/Debiopharm:
Bladder Cancer R&D Collaboration
Exclusive agreement for the research, development and
commercialization of Marina Biotech’s pre-clinical program
in bladder cancer
First agreement to license an RNAi-based therapeutic,
delivered with a lipid-
or liposomal-based formulation, to a
pharma company
Debiopharm is responsible for development and
commercialization of any products
Debiopharm will pay:
All research and development costs for the program
Up to $24 million based on predefined research and development
milestones
Royalties on sales of products
16

ssDNA/RNA Technology
17
“undruggable target”
for a specific
indication
ssDNA/RNA
dsRNA
mRNA
antagomir
mimetic
microRNA
CRN/RNA
+ delivery
CRN/RNA
UNA/CRN
+ delivery
CRN/RNA
+ delivery
CRN/RNA
Plasmid +
bacteria
UNA +
delivery
RDNA/     RDNA+
Molecular Target
Local/Systemic
Oral
chi
chi

Conformationally Restricted
Nucleotides (CRN)
CRNs
are
nucleotide
analogs
with
a
linker
connecting
the
C2’
and
C4’
carbons of ribose
CRN and LNA lock the ribose ring into a stable conformation and increase
the hybridization affinity to the mRNA or microRNA target
Distinguished
from
LNA
by
a
longer
linker
and
different
location
of
the
oxygen atom
Places the oxygen in an optimal position for stability and affinity
RNA                                        CRN               
LNA
18

CRN-Substitution Results in Less
Ribose Ring Puckering
19
CRNs are distinguished by a linker whose length results in less ribose
ring puckering
Conformation of CRN more closely resembles that found in RNA
CRN
LNA
Puckering of the ribose
ring at the 2’
carbon

Less Ribose Ring Puckering May Result
in Lower Structural Distortion
20
CRN substitution within an oligo may result in lower structural distortion
when hybridized to a complementary mRNA
Figure Adapted from Eichert et al .,
Nucleic Acid res. 2010 Oct 1 38(19):6729-36
RNA/CRN
Distortion of
Duplex Structure
The rigid structure imparted by multiple
LNA
substitutions
“stretches”
the
duplex
CRNs have greater flexibility by virtue of
the longer linker and would be expected
to maintain an overall structure similar to
an all-RNA structure
Therefore CRN substituted single-
stranded RNA/DNA may have promising
drug-like properties

Therapeutic Approaches Using CRN
Technology
21
mRNA Translational Blockers
Substitute CRN at ends of DNA-RNA hybrid compounds thus preserving
DNA in the interior and allowing interaction with RNAse H
microRNA Antagonists
Substitute CRN throughout strand to maximize hybridization affinity
Additional modifications (e.g., 2’O-methyl) can be included within the
construct for increased affinity and greater nuclease stability
= CRN

Advantages of CRN Technology
22
Increased affinity with CRN substitution maintains structural orientation
thus allowing for variable lengths
Standard 19-
to 22-mers
Greater number of substitutions in 14-
to 16-mers
Fully substituted 7-
to 9-mers targeting microRNA seed region
Delivery can be achieved with multiple formulations
Simple formulations (e.g., saline) can be used in many situations (liver,
lung, kidney, some tumors)
If
appropriate,
encapsulation
within
a
liposomal
formulation
for
systemic
or
local administration to certain tissues/organs

CRN-Related Therapeutic Modalities
Aptamers
Therapeutics
Diagnostics
Delivery/cell surface ligands
Exon skipping oligonucleotide
Minor/Major Groove Binders/Triplex forming oligonucleotides
Ribozymes
Splice junction inhibitors
Steric blockers
tRNA/tRNA suppressors
bridge (adapter molecule) between the mRNA and the protein
“Suppress”
the phenotypic effect of a coding mutation
23

Other Uses for CRN technology
Primer/Probes for PCR
qRT-PCR
5’
and 3’
RACE
Single, multiplex and allele specific PCR
Capture Probes
In
situ
hybridization/Fluorescence
in
situ
hybridization
SNP genotyping
Expression analysis
Monitor/identify exon skipping
Monitor/identify splice variants
Research/Diagnostics agents
Aptamers
Bacterial strain/virus identification
Single cell miRNA analysis
24

microRNA (miRNA) Technology
Local/Systemic
Oral
“undruggable target”
for a specific
indication
microRNA
mimetic
antagomir
UNA/CRN
+ delivery
CRN-RNA
+ delivery
CRN/RNA
mRNA
dsRNA
ssDNA/RNA
Plasmid +
bacteria
UNA +
delivery
CRN-RNA
+ Delivery
CRN-RNA
25

microRNA Mimetic Approach
Molecular Target
Local/Systemic
Oral
“undruggable target”
for a specific
indication
microRNA
mimetic
antagomir
UNA/CRN
+ delivery
CRN-RNA
+ delivery
CRN-RNA
mRNA
dsRNA
ssDNA/RNA
Plasmid +
bacteria
UNA +
delivery
CRN-RNA
+ delivery
CRN-RNA
26
mu
RNA+

microRNA Mimetic using UNA & CRN
27
MicroRNA mimetic -
dsRNA
Substitute with UNA and CRN
UNA –
increase nuclease resistance and decrease cytokine induction;
inhibition of passenger strand activity
CRN –
increase hybridization affinity; nuclease resistance
Additional modifications (e.g., 2’O-methyl) can be included within the
construct for nuclease stability
Duplex
construct
–
likely
to
require
delivery
for
most
indications
DiLA
2
-based
liposomes
or
Smarticles
(amphoteric
liposomes)
= CRN
= UNA

Delivery of a miR-34 Mimetic in a Smarticles
Formulation Inhibits Tumor Growth
Inhibition of Liver Cancer Biomarker
Alpha Feto Protein Levels
Inhibition of Tumor Growth
Tumor Weight (g)
miR-NC
miR-34
Untreat. Cont.           miR-NC                  miR-34
Smarticles
formulation
provided
effective
delivery
to
orthotopic
liver
tumors
Significant reduction in tumor growth and liver tumor specific biomarker
28

Local/Systemic
Oral
Molecular Target
“undruggable target”
for a specific
indication
microRNA
mimetic
antagomir
UNA/CRN
+ delivery
CRN-RNA
+ delivery
CRN/RNA
mRNA
dsRNA
ssDNA/RNA
Plasmid +
bacteria
UNA +
delivery
CRN-RNA
+ delivery
CRN-RNA
29
mu
RNA/
mu
RNA+

microRNA Antagonist using CRN
30
MicroRNA antagonists (Antimir) therapeutics
Substitute CRN throughout the strand to maximize the hybridization affinity
between antimir and the target microRNA
Allows for use of shorter length sequences
Additional modifications (e.g., phosphorothioate and 2’O-methyl) can be
included within the construct for nuclease stability and increase affinity
Delivery formulation
Simple formulations (e.g., saline) can be used as the vehicle for and can
be used as the vehicle in many situations
Encapsulation within a liposomal formulation for systemic or local
administration may be required for some tissues/organs
= CRN

CRNs Increase Antimir Activity
CRN substitution increases the activity of an Antimir with >90%
inhibition of luciferase activity
No activity against a scrambled target sequence (not shown)
31
Dual luciferase assay; Average of triplicate; HeLa cells co-transfected with psiCHECK2-miR21plasmid
% Luciferase (Renilla) Activity Remaining
Construct
0%
20%
40%
60%
80%
100%
miR-21
Antimir-21
Unmodified
Antimir-21
(CRN)
Antimir-21
(LNA)
5 nM
25 nM
5 nM
25 nM
5 nM
25 nM
5 nM
25 nM

Antimir Conc. (nM)
CRN-substituted Antimir
LNA-substituted Antimir
Unmodified Antimir
CRN-substituted
Antimir
is
highly
potent,
with
an
IC
50
of
0.2
nM
Similar potency for CRN-
and LNA-substituted versions
50% Inhibition
Dual luciferase assay; HeLa cells co-transfected with psiCHECK2-miR21plasmid;
Unmodified Antimir all RNA; CRN-substituted Antimir has DNA and P=S backbone
CRNs Increase Antimir Potency
32

Molecular Target
Local/Systemic
Oral
“undruggable target”
for a specific
indication
microRNA
mimetic
antagomir
UNA/CRN
+ delivery
CRN/RNA
+ delivery
CRN/RNA
mRNA
dsRNA
ssRNA/DNA
Plasmid +
bacteria
UNA +
delivery
CRN/RNA
+ delivery
CRN/RNA
Marina Biotech’s Nucleic Acid-based
Therapeutic Platform
33
tk
RNAi
tau
RNAi
chi
RDNA/
chi
RDNA+
mu
RNA+
mu
RNA/

Resourcing a Broad Discovery Engine
–
Funded
by
Marina
Biotech
Includes funding CEQ508 Phase 1b/2a Trial
–
Funded by outside sources
siRNA in liposomal delivery for local administration funded by Debiopharm
(Marina Biotech UsiRNA and liposomal delivery)
–
Funded
by
Marina
Biotech
and
outside
sources
ssDNA in liposomal delivery for systemic administration funded by ProNAi (ProNAi DNA
decoy in Marina Biotech delivery)
ssRNA/DNA in saline/liposomal delivery for systemic administration funded by Marina
Biotech
–
Funded
by
Marina
Biotech
and
outside
sources
microRNA mimetic in liposomal delivery for systemic administration funded by
Mirna Therapeutics (Mirna mimetic in Marina Biotech delivery)
microRNA antagonists in saline for systemic administration funded by Marina
Biotech
34
tk
RNAi
tau
RNAi
chi
RDNA/
chi
RDNA+
mu
RNA/
mu
RNA+

2010-2011 Achievements
Initiated patient dosing in an FAP Phase 1b/2a Clinical Trial and
completed dosing the first cohort
Established first ever partnership around a liposomal delivered
RNAi compound with Debiopharm for the development and
commercialization a bladder cancer therapeutic
Established use of CRNs within single-stranded oligonucleotides
including microRNA antagonists
Established broadest single-company nucleic acid-based drug
discovery engine in the industry
Published three scientific manuscripts in peer-reviewed journals
describing UsiRNA platform, DiLA2 delivery technology and pre-
clinical data from the bladder cancer program
35

Thank You
36