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BREMNER
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Company Update 1 Effie Tsotsani
Tekmira Pharmaceuticals (TKMR US) — Investment Stance: Positive PT C$67 March 2014
Company overview:
Tekmira Pharmaceuticals is a leading RNA interference (RNAi) Therapeutics Company with more than
14 years of industry experience. The Company has good revenue potential via its pipeline of product
candidates in development to treat serious human diseases such as cancer and viral infections like
Hepatitis B and Ebola. Tekmira is advancing the development of novel drugs in areas where there is a
significant unmet medical need and commercial opportunity and it also licences its leading RNAi
delivery technology to partners around the world advancing their own pipeline of developmental
drugs.
(1) RNA interference (RNAi) is considered one of the most important discoveries in the field of
biomedical science in the last decade as it has the potential to generate a new class of safer
therapies that are more specific and effective. It takes advantage of the body's own natural
processes to silence genes and treat serious human diseases that often rely on the production
of certain proteins at the genetic level. This method of treatment is not currently available
with conventional drugs. In the cell, DNA carries the genetic info required to make each
specific protein, genes are first copies or transcribed into RNA which is translated into protein.
Most diseases are by caused either the absence or over-production of a specific protein. RNAi
products can silence or eliminate the production of disease-causing proteins, creating
opportunities for therapeutic interventions that are not possible with conventional drugs.
One method to target disease-causing proteins involves developing small interfering RNA
(siRNA) molecules that are developed to suppress the production of proteins through the RNAi
mechanism. siRNA-based therapeutics can bind to a target protein mRNA with great specificity
resulting into suppressing this specific protein for long periods of time.
(2) To realise the therapeutic potential effective delivery is critical. The Company's proprietary
LNP Delivery Platform makes possible the successful delivery and enablement of RNAi as
well as mRNA drugs. Tekmira's Lipid Nanoparticle (LNP) technology represents the most
widely adopted RNAi delivery technology to date, as it allows drugs to be encapsulated in tiny
particles made of lipids which travel through the bloodstream to target tissues. LNPs are
designed to stay in the circulation long enough to accumulate at disease sites and through a
process called endocytocis, cells take up the LNPs which allows them to migrate into the cell.
The LNPs then undergo an interaction within the cell and the siRNA drug is released mediating
RNAi. This technology has a series of benefits that improve effectiveness of delivery. While it
minimizes immunotoxicity and other undesired side effects. The Company has licenced its
technology to Alnylam and Merk&Co with the former providing royalty bearing access to some
of its partners. TKMR has an ongoing research relationship with Bristol-Myers Squibb
Company, etc outside the field of RNAi they have a legacy licencing agreement with Spectrum
Pharmaceuticals. In addition to RNAi Tekmira's LNP delivery technologies can be used for
mRNA molecules. The mRNA molecules are large, fragile and easily degrade they do not
readily cross plasma membranes to enter target cells and so a delivery solution is required.
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Tekmira Pharmaceuticals March 2014
Tekmira's third generation LNP technology demonstrates significant improvements over
previous generations and potent mRNa delivery is readily achieved.
(3) Tekmira has a number of drugs in its pipeline that are focusing on delivering drugs for rare
diseases where the molecular target is found in the liver though their third generation liver
centric LNP. TKM-PLK1 is currently in phase II trial and is targeting three different forms of
cancer, while TKM-Ebola specialises in the Zaire species of Ebola virus. The Company has two
areas of particular interest in its future research; glycogen storage diseases and rare forms of
hypertriglyceridemia and is expecting to be in a position to identify another development
candidate in 2014.
TEKMIRA PROGRAMS Research Preclinital Phase I Phase II Phase III APPROVED Time
Pha so I started in Jan/II. Phase II in Aug 13.
TKM- P11(1. Oncology
Pha sole HCC trial In HI/14. GI.Net Phase II data in 2H14
TICM-Ebola (bola Virus Infection
TICM-HBV Hepatitis B IHBV) PM soI lo stan1l4/15
UM -ALONE filcher Use Disorder Proof of concept near complete:it 2H14
1)(M-Marburg Marburg Virus Infection
Rare Forms of Hypertriglycerfdemia
Glycogen Storage Disorder Type IV
• TKM-PLK1: PLK1 is an abbreviation for Polo Like Kinase 1 which is enzyme that in humans is
encoded by the PLK1 gene and is being studied as a target for cancer drugs. Inhibition of
PLK1 expression prevents the tumour cell from completing cell division, resulting in cell cycle
arrest and death of the cancer cell. By using an RNAi approach and exploiting its naturally
occurring mechanism of action, Tekmira can potentially overcome the limitations of other
approaches and effectively silence PLK1. The clinical trials have been conducted with patients
who have Gastrointestinal Neuroendocrine Tumours (GI-NET), Adrenocortical Carcinoma
(ACC) and will soon begin a Hepatocellural Carcinoma (HCC).
▪ GI-NET — Refers to a group of usual and complex cancers that neuroendocrine cells
arising in the gastrointestinal tract. It is estimated that there has been a four-fold
increase in the incidence of NETs between 1973 and 2004. Approximately 55k people
are living with GI-NET in the US. There is poor prognosis for advanced metastatic NETs,
with 25% of patients surviving less than a year. Treatment of patients with GI-NET
remains a challenge, and currently there are no approved anti-tumour drug
treatments indicated specifically for GI-NET.
✓ HCC — Primary liver cancer, or hepatocellular carcinoma is one of the most common
cancers worldwide, with more than 630,000 people diagnosed each year. HCC
represents a major unmet medical need and is associated with one of the poorest
survival rates in oncology. This is in part because only 10-20% of hepatocellular
carcinomas can be removed completely using surgery.
• ACC — Is a rare cancer that forms in the outer layer of tissue of the adrenal gland. The
adrenal gland is on top of each kidney that makes steroid hormones, adrenaline and
noradrenaline to control heart rate, blood-pressure and other body functions. In most
cases patients that have undergone treatment will develop recurrence because of the
underlying tumor biology, so at the moment there is a lack of effective systemic
therapies.
For the purpose of our analysis we assume that the cost of the PLK1 treatment could be up
to $20k annually and we expect the drug to hit the market no earlier than 2018.
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• TKM-Ebola: The Zaire species of Ebola virus, a highly contagious and lethal human infectious
disease, has been associated with periodic outbreaks of haemorrhagic fever in human
populations with mortality rates reaching 90% making it one of the most feared infectious
diseases. At the moment there are no known cures or vaccines available. In March St" 2014
the FDA announced they granted Fast Track designation for the development of TKM-Ebola,
an anti-Ebola viral therapeutic. The drug is being developed under a $140mn contract with
the US. Department of Defense's Medical Countermeasure Systems BioDefense Therapeutics
(MCS-BDTX) Joint Product Management Office. The FDA ascribed a fast track status to this
drug as it is targeting an unmet medical need since there are no therapies available for acute
Ebola infection. Additionally the haemorrhagic fever that Ebola infection confers is usually
fatal and there have been tangible clinical benefits. The Fast Track status of this drug is
highlighting its importance and confidence on future success but in no way does it guarantee
approval status irrespectively of the clinical trial results. However, based on the results of
preclinical studies on animals where the result was 100% protection from an otherwise
lethal dose of the virus, we are confident that the results of the human clinical trial will
assess the safety and effectiveness of the treatment. The Ebola virus is transmitted from
person to person through bodily fluids, humans first got the virus through contact with the
bodily fluids of infected animals. According to WHO (World Health Organisation) fruit bats are
considered natural hosts for Ebola. The mortality rate of the Ebola fever is up to 90% as
infected individuals usually experience both internal and external bleeding as blood vessels
start to leak, and is a matter of few days. However, what causes death is not intense bleeding
but form viremia (virus enters the bloodstream and gains access to the rest of the body).
For the purpose of our analysis we assume that the cost of such treatment could be up to
$100k annually and we expect the drug to hit the market in 2016.
• TKM-HBV is focused on addressing Hepatitis B virus (HBV) surface antigen expression in
chronically infected patients. This therapy could prove to be a significant opportunity for
the Company given the size of the addressable market. Currently there are more than
350mn people infected globally with Hepatitis B Virus with the US having c.1.4mn
chronically infected individuals. Small molecule nucleotide therapy is rapidly becoming the
standard care for chronically infected HBV patients but many of them continue to express a
viral protein called surface antigen. This protein can cause inflammation of the liver, leading
to cirrhosis and some cases to hepatocellular cancer. TKM-HBV is designed to block the
surface antigen and may also allow these patients the potential to raise their own antibodies
against the virus, which could lead to a functional cure for the infection. TKM-HBV is
developed as a multi-component RNAi therapeutic that targets different sites on the HBV
genome and will employ a liver-centric- LNP formulation that is more potent than any LNP
currently in clinical development. The Company is expecting to file an Investigational New
Drug (IND) application in the second half of 2014, and also advance the therapy to chronically
infected HBV patients. For the purpose of our analysis we assume that the cost of such
treatment could be up to $5k annually and we expect the drug to hit the US market in 2020
and China approximately one year later.
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• TKM — ALDH2 is a unique application of RNAi and is designed to knockdown the Aldehyde
dehydrogenase 2 (ALDH2) enzyme to induce long term sensitivity to ethanol. By silencing
this enzyme the levels of acetaldehyde are higher and that results into adverse physiological
effects that cause individuals to avoid alcohol consumption. The Company has developed an
extremely potent siRNA trigger combined with a third generation LNP. Although an ALDH2
inhibition drug already exists (Disulfiram) it has to be taken daily, while TKM-ALDH2 is
expected to prolong ethanol sensitivity and overcome the limitations of patient compliance.
The Company is expecting to complete preclinical work and file for IND in the second half of
2014, and hope for Phase 1 clinical trial data available in 2015. The drug will be developed in
order to target patient population consisting of individuals who have moderate-to-severe
alcohol use disorder and are pursuing treatment. Currently there are approximately 18mn
people with an alcohol use disorder in the US, out of which 2mn seek treatment and c350th
receive pharmacotherapy for alcohol use disorder.
For the purpose of our analysis we assume that the cost of such treatment could be up to
$5k annually and we expect the drug to hit the market not before 2018.
Apart from the pipeline products we described above the Company has o series ofpartnered products
which we present on the table below:
PARTNER PROGRAMS Research Prechnical Phase I Phase II Phase III APPROVED
Marqibo - Adults Relapsed Leukemia (Spectrum) J launched by Spectrum Pharma in 3O13
AIN -TTRO2 - TTRArnyloidosis (Alnylam) II = Phase III trial started in dQ13
ALN - VSP - Liver Cancer (Alnynam) Al Phase II testing in China in 2H13
AIN - PCS - High Cholesterol (Alnylam)
BIAS - Target Selection
Marqibo, is a liposomal formulation for the treatment of adult patients with relapsed Leukaemia
(second or greater relapse) or whose disease has progressed following two or more anti-leukaemia
therapies. The drug received accelerated approval from the FDA in 2012 and in 2013 Sprectrum
launched Marqibo through its existing haematology sales force. Tekmira is entitled to royalty
payments based on the drug's commercial sales.
Alnylam's LNP-Enabled Therapeutics; There are currently three LNP-based products in clinical
development ALN-TTR02, ALN-VSP, and ALN-PCS02 targeting amyloidosis, liver cancer and high
cholesterol respectively. Anlylam has a licence to use Tekmira's intellectual property to develop and
commercialise products and can also grand access to their LNP Delivery Technology to its partners as
part of a product sublicense. As a result Anlylam will pay low single digit royalties as the drugs are
developed and commercialised.
For the purpose of our analysis we assume that the vast majority of Alnylam's drugs will hit the
market approximately on 2018.
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Intellectual property
Tekmira has developed a series of expertise and in addition the Company owns a portfolio of patents
and patent applications specific to LNP inventions, formulation and manufacturing of LNP-based
pharmaceuticals, chemical modification of RNAi molecules and RNAi drugs and processes directed at
particular disease indications. The Company has a portfolio of approximately 95 patent families in the
US and abroad that are directed to various aspects of LNPs and LNP formulations. The portfolio
includes approximately 72 issued US patents, 71 issued non-US patents and 229 pending patent
applications.
Liquidity
The Company successfully completed a capital raising in March 2014 ($56.9mn net proceeds) that
secure the financing of a number of research projects that the Company has in early clinical and
preclinical phase. Post the Capital
Competitors
The main direct competitors of Tekmira are listed below, the majority of these companies are active
on the siRNA sector and have drugs mainly in early stages of clinical trials.
• Dicema (DRNA US) - the Company provides biopharmaceutical products. The Company
discovers and develops ribonucleic acid interference drugs for the treatment of rare inherited
diseases involving the liver and for cancers that are genetically defined. The Company
recently (total proceeds of $92.9mn) and is a siRNA formulation developer.
• Arrowhead Research Corporation (ARWR US) - is conducting research projects in the area of
the development of nanotechnologies and applications with the California Institute of
Technology. The Company is also a siRNA developer.
• Silence Therapeutics (SLN LN) - the Company has developed a proprietary short interfering
RNA (siRNA modecule). Silence also has developed a proprietary systematic delivery system
to deliver molecules to targeted disease tissues and cells. The Company is lead drug partner
with Quark & Pfizer and is on Phase I for PKN3-targeted cancer siRNA.
• Alnylam Pharmaceuticals Inc (ALNY US) - is an early stage therapeutics company. The
Company is developing technology that can specifically and potently silence disease-causing
genes. The Company has a number of siRNA drugs and uses Tekmkira's LNP delivery patents.
• Opko Health (OPK US) - the Company is involved in the discovery, development, and
commercialization of pharmaceuticals products, vaccines and diagnostic products. Their
siRNA pipeline still focused on AMD.
• Isis Pharmaceuticals (ISIS US) - the Company discovers and develops novel human
therapeutic compounds and at the moment it has various compounds in clinical trials for a
variety of diseases such as Crohn's disease, psoriasis, asthma and cancer. Their research
programs support efforts in both antisense and small molecule drug delivery.
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Valuation and risks
For the purposes of this analysis we factor into our numbers the proceeds coming from that are
currently on preclinical/clinical phase with the majority of the revenues occurring from 2016 onwards.
We value the company with a DFC model, we assume a WAAC of 12.7% and LTG of 2.3% which lead
to a target price of C$67.
Discounted Cashflows
Free Cash Flow
2014E 2015E 2016E 2017E 2018E 2019E 2020E 2021E 2022E 2023E
Free Cash Flow -8 -9 33 38 57 97 122 169 217 222
PV of cashflows -8 26 27 35 54 60 74 84 76
PV of terminal Value 741
Long term growth 2.30%
WACC 13%
Enterprise Value C$1,169
Net Debt 0
Esti mated Market price C$1,169
Estimated value per sh. C$67
Current Share price C$27
upside / downside 150%
Risks that could drive the share price lower are (1) delay on the clinical trials compared to our
estimates, (2) not satisfactory outcome of clinical trials for the therapies that are currently undergoing
this process (3) development and commercialization of pipeline products.
Tekmira @current 11(MR US I $23.50 I $505.5 E $23.50
Oicerna Pharma DRNA US $32.20 $564.4 $32.20
Arrowhead Research Corp ARWR US $16.37 $728.3 $16.37
Silence Therapeutics PLC SLN LN $4.40 $222.5 $4.40
Avg RNAi (early stage) $505.07
AI nylam Pharma ALNY US $63.97 $4,088.8 $63.97
Opko Health OPK US $9.08 $3,652.0 $9.08
Isis Pharma ISIS Us $42.90 $4,873.8 $42.90
Avg RNAi (late stage) $4204.87
Avg Total $2,355
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Ownership — shareholder structure
The main shareholders of the group are listed below:
Major Shareholders
Name No. Shares Change Date
Frankl in Resources 9.41% 2,022,400 2,022,400 31/12/2013
Newby Steven 5.61% 1,206,000 262,000 14/02/2014
BMO Financial Corp. 3.49% 749,599 -49,270 31/12/2013
Sabby Management 2.42% 519,200 519,200 31/12/2013
Growthworks Canadian Fund 2.33% 500,550 -413,253 31/12/2012
Baker Bross Advisors LLC 2.33% 479,755 500,000 31/12/2013
Jewell Donald 2.23% 348,000 1,600 07/08/2013
Pointstate Capital 1.62% 245,562 348,000 31/12/2013
Summary of Financial Statements
Our financial assumptions are based on the fact that all products that are on Tekmira's pipeline and
are in a process of clinical trials are going to be approved. We use the Company's guidance with
regards to royalty rates etc.
Revenue From IMMO Pipeline 2011E 2015E 2016E 2012E 2018E 2019E 2020E 2021E 2022E 2023E
7KM. PU(1. Oncology $0 $0 50 50 510 540 553 $67 587 5107
7KM-Ebola • (bola Virus infection 50 $0 531 $32 533 533 534 $35 536 $37
TXM-1188 Hepatitis B (118V) SO SO $0 $0 50 SO $5 539 566 $94
D(M -ALDIl 2 Al chol Use Disorder SO $0 $0 $0 $3 $8 $13 518 524 $30
TKMII Revenue (USCnn) SO $0 $31 $32 $45 $81 $105 $160 $212 $267
TKMII Revenue (CDmn) SO $0 $35 $36 $51 $91 $118 $179 $238 $300
Revcrur tom Krtrct PrcgrJ 2011E 2015E 2016E 2012E 2018E 20191 2020E 2021E 2022E 2023E
Ala roibo Adults Relapsed Look* $1.24 $1.91 $3.46 $3.5S $3.64 $3.73 $3.82 $3.91 $4.01 $4.10
ALN •TTRO2 TTR Amyl oi dos i s (Alr $0.00 $0.00 $0.00 $0.91 $3.56 $4.87 $7.49 $10.23 $13.10 $16.11
ALN -V5P. Liver Cancer (illnynarnl $0.00 $0.00 $0.00 $0.00 $0.68 $2.62 $3.59 $4.60 $5.65 $6.76
ALN Nish Cholesterol lAlnyl $0.00 $0.00 $0.00 $0.00 $0.00 $1.15 $4.40 56.02 59.25 $11.06
TKM11 Partner Revenue (USDmn) $1.24 $1.91 $3.46 54.48 $7.88 $12.37 $19.29 $24.75 $32.01 $38.04
TKM11 Partner Revenue (CDmn) $1.39 $2.14 $3.88 $5.01 $8.83 $13.85 $21.61 $27.73 $35.86 $42.61
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Income Statement (C$mn) 2011 2012 2013 2014E 2015E 2016E 2017E 2018E 2019E 2020E 2021E 2022E 2023E
AMR Product Pipeline 0 0 0.0 0 0 34.69 35.55 5024 90.91 118.03 178.72 237.75 299.62
Partner Products 0.0 1.39 2.14 3.88 5.01 823 13.85 21.61 27.73 3526 42.61
Collaborations and Contracts • 16.1 • 12.1 10.4 10.4 15.4 15.6 16.6 190 19.0 19.0 19.0 19.0 19.0
UcencIng fees and milestone payme, 0.5° 2 5.0 5.0 5.0 6.0 7.0 7.0 7.0 7.0 7.0 7.0 7.0
Total Revenue 16.6 v 141 15.5 16.9 22.6 60.2 642 85.7 130.8 165.6 232.4 299.6 3682
Expenses -27.1 -27 -27.6 -30.1 -37.3 -32.2 -31.1 -34.7 -39.9 -50.5 -70.9 -91.4 -112.3
o/ts.= -19.9 -18 -21.5 -23.4 -28.25 -24.07 -22.47 -23.13 -22.23 -28.16 -3932 -50.93 -61.6
o/tv G&A -63 -8.1 -5.5 -6.04 -8.106 -722 -7.70 -1028 -15.69 -19.88 -27.89 -35.95 -44.19
o/IsM -1 -0.9 -0.6 -0.67 -0.896 -0.90 -0.96 -1285 -1.961 -2.485 -3.487 -4.494 -5.523
o/tv Loss on purchase & senlement r 0 0' 0.0 0 0 0 0 0 0 0 0 0 0
Other Income (loss) 0.60 42.6 -1.91 0 0 0 0 0 0 0 0 0 0
Net (loss) Income -9.9 29.7 -141 -132 -14.7 28.0 331 51.0 90.9 115.1 161.5 2082 255.9
EDS -0.87 2.164 -0.92 -0.76 -024 1.61 1.90 2.92 5.21 6.61 9.27 11.95 14.68
EDS fully dll -0.87 2.074 -0.92 -0.76 -024 1.61 1.90 292 5.21 6.61 9.27 11.95 14.68
Adj. Net Income -9.9 -12.9 -122 -132 -14.7 28.0 331 51.0 90.9 1151 161.5 2082 255.9
Adj. EPS -0.87 -0.94 -0.79 -026 -024 1.61 1.90 292 5.21 6.61 9.27 11.95 14.68
Adj. EPS fully di I -0.87 -0.9 -0.79 -026 -024 1.61 1.90 292 5.21 6.61 9.27 11.95 14.68
Number of Shares 11.32 13.73 15.3 17.43 17.43 17.43 17.43 1743 17.43 17.43 17.43 17.43 17.43
Number of Shares (debuted) 11.32 14.32 15.3 17.43 17.43 17.43 17.43 17.43 17.43 17.43 17.43 17.43 17.43
EEIIDA -8.9 -12 ' -11.5 -12.6 -13.8 28.9 34.0 523 92.8 117.6 165.0 212.7 261.4
Morgan 96 -54% -85% -75% -75% -61% 48% 53% 61% 71% 71% 71% 71% 71%
Disclaimer
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