Targovax is developing immunotherapies to enable the immune system to kill cancer cells. They have two platforms: oncolytic viruses and peptide vaccines. Their peptide vaccine TG01 showed encouraging 2-year survival data in a Phase I/II trial in pancreatic cancer patients, with a survival rate higher than historical controls. Their oncolytic virus ONCOS-102 is in a Phase I trial in CPI-refractory melanoma patients to see if it can activate the immune system and make those patients responsive to checkpoint inhibitors again. Targovax has multiple clinical readouts expected in 2017 and 2018 that could be value inflection points.
Targovax is developing two complementary and highly targeted approaches to cancer immunotherapy: a peptide-based targeted immunotherapy platform for patients with RAS-mutated cancers and a virus-based oncolytic immunotherapy platform based on engineered oncolytic viruses armed with potent immune-stimulating transgenes for patients with solid tumors.
Targovax is developing two complementary and highly targeted approaches to cancer immunotherapy: a peptide-based targeted immunotherapy platform for patients with RAS-mutated cancers and a virus-based oncolytic immunotherapy platform based on engineered oncolytic viruses armed with potent immune-stimulating transgenes for patients with solid tumors.
Download Global cancer immunotherapy market outlook 2020KuicK Research
\"Global Cancer Immunotherapy Market Outlook 2020\" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
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Marketed Cancer Vaccines: 12 Vaccines
Global cancer immunotherapy market outlook 2020KuicK Research
"Global Cancer Immunotherapy Market Outlook 2020" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
Targovax Next generation immune activators for solid tumorsRoarFredriksen1
Targovax (OSE:TRVX) is a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors. Targovax’s focus is to activate the patient’s immune system to fight cancer, and to bring benefit to cancer patients with few available treatment alternatives. Targovax is developing its product candidates in different cancer indications, including melanoma, mesothelioma, and multiple myeloma, and has demonstrated a favorable safety and tolerability profile.
Targovax’s lead clinical candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has been engineered to selectively infect cancer cells and activate the immune system against the tumor. Following very encouraging clinical data in several indications, both as monotherapy and in combinations, ONCOS-102 is progressing into a randomized phase 2 trial in melanoma patients resistant to PD-1 checkpoint inhibitor treatment.
Building on successful clinical studies which have provided deep mechanistic insights into the tumor biology and the human immune systems, Targovax is researching circular RNA (circRNA) as novel cancer medicines. In addition, Targovax has a KRAS immunotherapy program, with lead cancer vaccine candidate, TG01, expected to enter the clinic in an enhanced format in the second half of 2022. Together this provides Targovax with a rich pipeline of innovative future immunotherapy product candidates to follow ONCOS-102.
2. www.targovax.com
Important notice and disclaimer
This report contains certain forward-looking statements based on uncertainty, since they relate to events and
depend on circumstances that will occur in future and which, by their nature, will have an impact on the results of
operations and the financial condition of Targovax. Such forward-looking statements reflect the current views of
Targovax and are based on the information currently available to the company. Targovax cannot give any assurance
as to the correctness of such statements.
There are a number of factors that could cause actual results and developments to differ materially from those
expressed or implied in these forward-looking statements. These factors include, among other things, risks or
uncertainties associated with the success of future clinical trials; risks relating to personal injury or death in
connection with clinical trials or following commercialization of the company’s products, and liability in connection
therewith; risks relating to the company’s freedom to operate (competitors patents) in respect of the products it
develops; risks of non-approval of patents not yet granted and the company’s ability to adequately protect its
intellectual property and know-how; risks relating to obtaining regulatory approval and other regulatory risks relating
to the development and future commercialization of the company’s products; risks that research and development
will not yield new products that achieve commercial success; risks relating to the company’s ability to successfully
commercialize and gain market acceptance for Targovax’s products; risks relating to the future development of the
pricing environment and/or regulations for pharmaceutical products; risks relating to the company’s ability to secure
additional financing in the future, which may not be available on favorable terms or at all; risks relating to currency
fluctuations; risks associated with technological development, growth management, general economic and
business conditions; risks relating to the company’s ability to retain key personnel; and risks relating to the impact of
competition.
2
3. www.targovax.com
Enables the immune system to kill cancer cells:
o Oncolytic viruses
• Release cancer antigens
• Imlygic, ONCOS-102
o Peptide vaccines
• Mimic cancer antigens
• TG01, TG02
o Cell therapies
• Load T-cells with antigen receptors
• Chimeric antigen receptors, CARs
o Checkpoint inhibitors
• General upgrade of immune system
• Yervoy, Keytruda, Opdivo, Tecentriq
3
Immunotherapy – enables the immune system to kill cancer cells
Surgery
Chemo
Radio-
therapy
Targeted
therapies
Traditional cancer treatment New approach - Immunotherapy
4. www.targovax.com
The goal is to make cancer a chronic disease by combining
immuno-oncology therapies
4
o Yervoy started the revolution
in cancer treatment in 2011
o Due to immuno-oncology
combination the number of
addressable cancers is
expected to increase to at
least 60%
Untreated
Time from treatment
Proportionalive
Long term survival
Long term survival
Chemotherapy / TKI
Immunotherapy
combination
Immunotherapy
monotherapy
5. www.targovax.com
Checkpoint inhibitors show signs of “curing” some cancers
- example of Yervoy treated melanoma
5
Week 108: complete remissionWeek 72: complete remission
1 year20 weeks 8 months
Prior to Yervoy 4 weeks 8 weeks
6. www.targovax.com 6
Response rate to checkpoint inhibitors (CPIs)
ONCOS-102 can
potentially activate
non-responders to
become susceptible
to CPI's
~80%
~84%
~80%
~70%
~70%-80%
~40%
Head and Neck
Lung Carcinoma (NSCLC)
Triple Negative Breast
Renal Cell carcinoma
Melanoma
Large unmet need for checkpoint inhibitor refractory patients
Non-respondersResponders
Bladder
7. www.targovax.com
ONCOS-102: CPI refractory melanoma trial details
7
Setting
Background
Key endpoints
Advanced malignant melanoma patients not responsing to CPIs
Immune activate CPI non-responders with ONCOS-102, then re-
challenge with a CPI (Keytruda)
No standard of care for patients not responding to CPI
Safety
Immune activation and clinical response data
Correlation of immune activation and clinical response data
Cohorts
Six patients with prior PD1 monotherapy
Six patients with prior PD1 plus Yervoy combination therapy
Sequence ONCOS-102 – 3 weeks Keytruda – 5 months
Yervoy – generic name: ipilimumab
Keytruda – generic name: pembrolizumab
8. www.targovax.com 8
At the tumor:
Virus injected directly into tumor,
replicates, lyses cells and releases
antigens. Immune system picks up
antigens
At the lymph node:
Immune system starts production
of tumor specific T-cells
At the tumor lesions:
T-cells find tumor lesions with
corresponding tumor antigens
and kill the cancer cells
Lymph node
How does ONCOS-102 work?
9. www.targovax.com
Adaptive immune system (biopsy) Anti-tumor immune response (blood)Innate Immune System (biopsy)
Initial ONCOS-102 trial showed strong T-cell response
9
OvCa.
patient
(FI1-19)
o Increase in T-cell infiltration into tumors
(including CD8+ killer T-cells) in 11 out
of 12 patients
o Observation in one non-injected distant
metastasis
o Induction of proinflammatory cytokines
+ fever (all patients)
o Infiltration of innate immune cells into
tumors in 11 out of 12 patients
o Systemic induction of tumor-specific
CD8+ T-cells
Correlation between post-treatment
increase in innate immune cells and OS
Associated with clinical benefit
Correlation between post-treatment
increase in CD8+ T-cells and OS
(p=0.008, R=0.74)
Evidence that immune system
recognizes tumor threat
Evidence that T-cells find the
tumor and are cell killing
Evidence of production of tumor
antigen specific T-cells
Mesothelioma patient:
MAGE-A3 specific CD8+ cells
Ovarian patient:
NY-ESO-1, MAGE-A1, MAGE-A3, and
Mesothelin specific CD8+ cells
Overall survival
Scatterplot of ranks
IncreaseinCD68+
cellspost-treatment
p=0.0004, R=0.86
10. www.targovax.com
Six shots on goal
10
Cancer
indication
Combined
with
ONCOS-102
Melanoma CPI
Mesothelioma Chemo* Orphan ind.
Ovarian &
Colorectal
CPI
Orphan ind.
Sponsor**: Ludwig
Prostate DC therapy Sponsor: Sotio
TG
Resected
Pancreatic
Chemo* Orphan ind.
Colorectal CPI
4 readouts
2017
5 readouts
2018
2017 2018
H1 H2 H1 H2
2019
H1
Phase l
Phase l/ll
Phase l
Phase lb/ll
Phase I/II
Phase Ib
Interim data Clinical, immune and
safety data
* In combination with Standard of Care Chemoterapy. Pemetrexed/cisplatin for
Mesothelioma and Gemcitabine for Resected Pancreatic
12. www.targovax.com
Encouraging survival rate and “signal” of efficacy in TG01 trial
68% (13 of 19) of the patients in cohort 1 were alive two years after the resection
– Published historical rate 30-53% suggests a signal of clinical efficacy for TG011
Abstract submitted to ASCO 2017 (June) from this 1st cohort
– Efficacy, safety, immune activation
In summary: encouraging survival rate and “signal” of efficacy
1 J Neoptolemos 2010, J van Loethem 2010, H Oettle 2013, M Sinn 2015, K Uesaka 2016 (In these reported studies overall survival is measured
either from surgery or treatment randomization).
CT TG01-01; A Phase I/II Trial of TG01 and Gemcitabine as Adjuvant Therapy for
Treating Patients with Resected Adenocarcinoma of the Pancreas
13. www.targovax.com
TG – background: “reasons to believe”
13
1 Weden et al, 2011, Oettle et al, JAMA 2007 and 2013
2 Gjertsen et al 2001, Data on file
120 patients treated with TG peptides in 1990’s
10 year follow up of resected pancreas cancer patients showing twice the survival rate
to historical control Immune activation and clinical response data1
Advanced pancreatic cancer patients vaccinated with TG peptides with a positive
immune response (DTH, proliferative T cells) showed longer overall survival compared
to patients without a positive immune response2
Potential conversion of immunologically cold RAS positive tumors to hot tumors
responsive to CPIs
14. www.targovax.com
How is the Targovax peptide vaccine approach different?
14
CD4+ and CD8+
T-cells
Knowing the
target
Both necessary for establishing a clinical effective cellular response
Our TG peptides designed to active and stimulate both
Most failed peptide vaccines designed to only activate CD8+ T-cells
We target RAS mutations that are known neo-antigens
RAS mutations cause abnormal cell growth - definition of cancer
Most other peptide vaccine studies have not known the cancer antigens
Right adjuvant
We use the right type of adjuvant – GM-CSF
Well known, effective, non-depot forming
Other have used depot forming adjuvants – T-cells not attracted to tumor
15. www.targovax.com
Multiple near term value inflection points
15
2015 2016 2017 2018H1 H2
phase ll initiated
TG01
Immune activation
and MoA demo
ONCOS-102
Interim data
pancreas
TG01 (1st cohort)
Immune activation
pancreas
TG01 (2nd cohort)
2-year survival
pancreas
TG01 (1st cohort)
2-year survival
pancreas
TG01 (2nd cohort)
Initiate phase l/ll
mesothelioma
ONCOS-102
Initiate phase l
prostate
ONCOS-102
Initiate phase l/ll
melanoma
ONCOS-102
Interim data
ovarian /colorectal
ONCOS-102
phase l/ll data
melanoma
ONCOS-102
Interim data
melanoma
ONCOS-102
Interim data
mesothelioma
ONCOS-102
Initiate phase Ib in
colorectal
TG02
Interim data
colorectal
TG02 (mono)
Initiate phase l
Ovarian/colorectal
ONCOS-102
Interim data
prostate
ONCOS-102
phase I data/
colorectal
TG02 (combo)
H1 H2
Listing on OSE main list
Oslo Stock Exchange
16. www.targovax.com
Financial summary
Operations
Cash NOK 172m USD 20m
Annual run rate NOK 110m USD 13m Last four quarters
Annual opex NOK 120m USD 14m Last four quarters
16
The share OSE: TRVX
Daily liquidity NOK 9m USD 1m Last two month’s avg.
Market Cap NOK ~1 bn USD 123m At share price NOK ~24
Debt NOK 40m USD 5m EUR 6m conditional
No. of shares 42.2m 44.9m fully diluted
Analysts DNB, ABG Sundal Collier, Arctic, Redeye,
Norske Aksjeanalyser
17. www.targovax.com 17
Clinical trials
TG
ONCOS
1
2
3
Six shots on goal
Encouraging top line two-year survival data
Important proof of concept trial in CPI refractory melanoma
Data in 2H17
Arming the patient’s immune system to fight cancer