SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned,
thereunto duly authorized.
Novogen Limited
(Registrant)
Kate Hill
Kate Hill
Company Secretary
Date 15 March 2017
ASX:NRT
NASDAQ:NVGN
Novogen Ltd
(Company)
ABN 37 063 259 754
Capital Structure
Ordinary Shares on issue:
483 M
Board of Directors
Mr John O’Connor
Chairman
Non-Executive Director
Mr Bryce Carmine
Deputy Chairman
Non-Executive Director
Dr James Garner
Chief Executive Officer
Managing Director
Mr Ian Phillips MNZM
Non-Executive
Director
Mr Iain Ross
Non-Executive Director
Mr Steven Coffey
Non-Executive Director
MARKET RELEASE
15 March 2017
NOVOGEN PRESENTS AT ROTH
CONFERENCE
Sydney, 15th March 2017 – Novogen Ltd (ASX: NRT; NASDAQ: NVGN), an Australian oncology-focused biotechnology company, is pleased to
release the presentation that CEO, Dr James Garner will be presenting at the 29th Annual ROTH Conference being held in Laguna Niguel, California.
Dr
James Garner will be presenting at the The Ritz Carlton Hotel, Dana Point on Tuesday 14th March at 4 pm local time.
[ENDS]
|
|
|
|
|
Media and Investor Relations
|
|
Investor Relations (US)
|
|
Glen Zurcher
E:
glen.zurcher@irdepartment.com.au
T: +61 420 249 299
|
|
Robert Kennedy
E:
robert.kennedy@novogen.com
T: +1 212 519 9832 / +1 646 662 3574
|
About Novogen Limited
Novogen Limited (ASX: NRT; NASDAQ: NVGN) is an emerging oncology-focused biotechnology company, based in Sydney, Australia. Novogen has a portfolio of four
development candidates, diversified across three distinct technologies, with the potential to yield
first-in-class
and
best-in-class
agents across a range of oncology indications.
The lead program is
GDC-0084,
a small molecule inhibitor of the PI3K / AKT / mTOR pathway, which is being developed to treat glioblastoma multiforme. Licensed from Genentech in late 2016,
GDC-0084
is anticipated to enter phase II clinical trials in 2017. Three further molecules have been developed
in-house
from two proprietary drug discovery platforms
(superbenzopyrans and anti-tropomyosins) to treat ovarian cancer and a range of solid tumours. Cantrixil, the most advanced of these, commenced a
first-in-human
clinical
study in patients with ovarian cancer in late 2016, while Anisina and Trilexium are in preclinical development.
For more information, please visit:
www.novogen.com
Novogen Limití
Presentation to 29th Annual ROTH Conference
Dr James
Garner Dana Point, CA
Chief Executive Officer 14 March 2017
james.garner@novogen .com
Version 1.0
Forward-Looking Statements
This presentation contains “ forward-looking statements ” within the meaning of the “ safe-harbor ” provisions of the Private Securities
Litigation Reform Act of 1995. Such statements involve known and unknown risks, uncertainties and other factors that could cause the actual results of the Company to differ materially from the results expressed or implied by such statements,
including changes from anticipated levels of customer acceptance of existing and new products and services and other factors. Accordingly, although the Company believes that the expectations reflected in such forward-looking statements are
reasonable, there can be no assurance that such expectations will prove to be correct. The Company has no obligation to sales, future international, national or regional economic and competitive conditions, changes in relationships with customers,
access to capital, difficulties in developing and marketing new products and services, marketing existing products and services update the forward-looking information contained in this presentation.
1
COMMERCIAL IN CONFIDENCE
Novogen is a biotech company dedicated to driving sustainable, long-term growth in shareholder value
Focus on unmet medical need
Robust pipeline of novel therapies,
targeting oncology patients poorly
served by existing treatment options
Financially sound
Listed on ASX and NASDAQ, with
cash runway for continuing operations
Clinical stage
Two clinical stage programs: GDC-
0084 and Cantrixil, with rich flow of
milestones over next
12-18
months
Strong management
and Board
Lean team of internationally-
experienced pharma executives,
overseen by seasoned Board
2
COMMERCIAL IN CONFIDENCE
2016 has been a transformative year for Novogen
3Q 2016
Submission of Cantrixil
2Q 2016 IND4Q 2016
1Q 2016
Granting of patent for ATM Appointment
of ScientificLicensing of
GDC-0084
Appointment of CEO technology Advisory Boardfrom Genentech
Granting of patent for SBP Conclusion of CanTx joint Recruitment of seniorInitiation of Cantrixil phase
technology venture managementI study
COMMERCIAL IN CONFIDENCE 3
Novogen is listed on ASX and NASDAQ, and is well-
funded
Share Price (US$)
3.00 Cash at Bank*Debt
NVGN~US$ 17 millionNil
NASDAQ Biotech Index
2.50
Market CapitalisationUS$ 27 million
2.00
ASX:NRT
ListingNASDAQ:NVGN (1:25
1.50 ratio)
Average Daily VolumeASX:0.1% /day
1.00 NASDAQ:0.2% /day
0.50 Shares on
Issue483 million
(35% US, 65% Australia)
0.00
Outstanding~60 million
Mar-16 Jun
-16
Sep-16Dec-16Mar-17Options
/ Warrants
Last
reported as at 31 December 2016. Includes value of Australian R&D Tax Rebate.
4
COMMERCIAL IN CONFIDENCE
Novogen has focused on oncology, with a clear strategy for building and managing a high-value portfolio
PartnersTightly focused on
oncology, with a
weighting to solid
tumours
Un-proven
programs
Assets
in-licensed
Significantly
de-risked
taken from
preclinical Open-minded as to
from external partners molecules partnered
or early stage with pharma / largetechnology (e.g.
development
to biotech for completionbiologics vs small
completion of clinical of Phase IIImolecules)
trials that substantially development,
de-risk
the program registration, or
and provide a clear Precise development
commercialisation
Assets from internal path to registration plan guided by
discovery
engines understanding of
biology and biomarkers
Early
consideration of
commercial value
drivers in program
planning & design
5
COMMERCIAL IN CONFIDENCE
Novogen has built a strong management team with international experience in big pharma
Dr James Garner
Chief Executive Officer & Managing Director
Physician / MBA; Extensive pharma drug development experience
Dr Gordon Hirsch
Chief Medical Officer
Physician / MBA; Twenty years of pharmaceutical industry experience
Dr Peng Leong
Chief Business Officer
Eighteen years of business development and investment banking experience
Kate Hill
Company Secretary
Chartered accountant, and former audit partner at Deloitte
COMMERCIAL IN CONFIDENCE 6
Our newly-appointed Scientific Advisory Board brings global expertise and experience to Novogen
Professor Sir Dr Karen ProfessorProfessor
Murray
Brennan Ferrante Peter GunningAlex Matter
COMMERCIAL IN CONFIDENCE 7
Novogen now has a well-diversified portfolio of assets, stretching from preclinical to
mid-stage
clinical
LeadPreclinicalIND-EnablingPhase
IPhase IIPatent
OptimisationProof-of-ConceptTox &
CMCClinical TrialsClinical TrialsExpiry
PI3K GDC-0084
GlioblastomaPhase II2032
2017
SBP TRXE-002-1
Ovarian Cancer2035
Cantrixil
ATM ATM-3507
Solid TumorsIND2035
Anisina 2017
SBP TRXE-009
Solid Tumors2035
Trilexium
Brain -penetrant PI3K inhibitor with some mTOR activity,
targeting PI3K / Akt / mTOR pathway, which is
PI3K Technology shown to be upregulated in majority of GBM cases and many other tumor types
First-in
-class program targeting cancer-specific tropomyosin isoform in cytoskeletal microfilaments of
ATM Technology cancer cells, leading to apoptosis
First-in
-class program based onearlier clinically-validated isoflavone chemotype (e.g. phenoxidiol, MEI
SBP
Technology Pharma), but with distinct IP space and greater preclinical activity
8
COMMERCIAL IN CONFIDENCE
GDC-0084
Glioblastoma Multiforme (GBM) is the most common form of primary brain cancer
Presentation
Usually presents with non—specific symptoms (e.g. headaches, nausea)
Rapid clinical progression to permanent neurological defect and coma
Source:
GLOBOCAN 2012
Epidemiology
Approximately 12,500 incident cases per annum in
United States
Limited understanding of causes and risk factors
Generally more
common in people >50 years of age, and slightly more common in males
COMMERCIAL IN CONFIDENCE
Prognosis
Median survival following diagnosis =
12-15
months with best available treatment (~3 months without treatment)
5-year
survival rate =
3-5%
Limited improvement in prognosis over last 15
-20
years
9
Current GBM standard of care is ineffective in
GDC-0084
~65% of
patients
Standard
of
Care Debulking surgery Radiotherapy +Temozolomide
(‘Stupp where possible temozolomidemaintenance therapy
Regimen’)
6 weeks4w6 x
28-day
cycles
Temozolomide is clearly efficacious… …but only in ~35% of patients who are
sensitive
Source: ME Hegi,
A-C
Diserens, T Gorlia, et al. (2005). N Engl J Med
352:997-1003
10
COMMERCIAL IN CONFIDENCE
The PI3K / Akt / mTOR pathway isupregulated in
GDC-0084
the vast majority of
GBM cases
Select PI3K
inhibitors Growth factor
receptors
Taselisib
(Genentech) PI3K upregulated, or
PTEN
PI3K knocked out, in ~85% of GBM
Buparlisib cases
(Novartis)
PIP2 PIP3PI3K dysregulation associated with
worse
prognosis
GDC-0084
2-Year
Survival Rate
30%
mTORC 24%
2 Akt
20%
everolimus
mTORC
1 10%
+ -+0%
0%
Protein synthesis SurvivalCell cycle &pAkt positivepAkt negative
& cell growth proliferation
11
COMMERCIALIN CONFIDENCE
GDC-0084
GDC-0084
shows single-agent activity in preclinical models of glioblastoma
Illustrative Dose-Dependent Activity in U87 Model General Findings
)
3
(mm Widespread activity in a range of PDX
Vehicle models; appears unaffected by MGMT
0.03
mg/kg promotor status
0.45 mg/kg
Volume 2.2 mg/kg
4.5
mg/kg Clear dose—PI3Kinhibition—response
9 mg/kg relationship seenin most experiments
Tumor 13 mg/kg
18 mg/kg
GDC-0084
even moderately active in
GS2 intracranial
model (intact BBB, no
PI3K dysregulation) which is resistant to
other test
articles
Day
12
COMMERCIAL IN
CONFIDENCE
PI3K inhibitors are well-validated, with one
GDC-0084
marketed product and
extensive clinical data
Zydelig (idelalisib) on market Other PI3K inhibitors in clinical trials
Idelalisib (and programs such as Infinity Therapeutics and TG
Therapeutics) specifically target the d isoform of PI3K, which is Few PI3K inhibitors are able to cross the blood-brain barrier
associated with hematological malignancies
13
COMMERCIAL IN CONFIDENCE
GDC-0084
shows consistent penetration of
GDC-0084
blood-brain barrier in multiplespecies
100 100100100
GDC-0084 MALDI
MS/MS
(15 mg/kg)
0 000
U87 orthotopic
GBM model Cresyl Violet
Free
Brain-to-
Brain-to- CSF-to-Free
Species Free Plasma
Plasma
Ratio Plasma Ratio
Ratio
Mouse 1.3 0.40-
Rat 2.4 0.681.5
Dog 2.2 0.451.03Postmortem samples from
Human > 1.54 > 0.511 trial patient (45mg dose)
confirmed animal data
14
COMMERCIAL IN CONFIDENCE
GDC-0084
GDC-0084
is among the most advanced PI3K inhibitors in active development for
GBM
212 17340
100%
Non-
Oncology
(39)
Discontinued
80% / No
Development
(79)
60% Other
Oncology
Indications
(35)
Oncology
40% (173) Discovery
(54)
20% Ph I (17)
Marketed
Ph II (15)(1)Glioblastoma
Ph III (7)(5)
0%
PI3K Inhibitors OncologyClinical
Completed P1 in
GBM (n=47)
GDC-0084
P1/2a in GBM due
to complete in Oct
buparlisib 2016
Single-site P2 in
GBM underway;
PQR-309 read-out
in Jan
‘18
Discontinued
sonolisib
Discontinued
voxtalisib
Source: Thomson Reuters Cortellis Competitor Intelligence
15
COMMERCIAL IN CONFIDENCE
Genentech’s phase I study established a
GDC-0084 dose
of 45mg and demonstrated acceptable
safety
Phase I Study
Population in phase I study (recurrent patients) had significantly more advanced disease than that proposed for phase II study (first-line patients)
47 patients enrolled at 4 centers (MD Anderson, UCLA, Dana- Farber, and Vall d’Hebron )
Patients were grade 3 or 4 gliomas with at least one (and in most cases, several) lines of prior therapy
Planned MTD expansion cohort to explore efficacy signals in pure GBM population was not performed due to budgetary restrictions
45mg established as Maximally Tolerated Dose (MTD) for phase II study
Pharmacokinetic profile
consistent with daily dosing
Safety profile consistent with other PI3K inhibitors, with hyperglycemia and mucositis / stomatitis the most common adverse events
Promising signals of pharmacodynamic response on
FDG-PET,
an exploratory radiological marker
COMMERCIAL IN CONFIDENCE
Rationale for Externalization
GBM currently not considered a strategic priority for Genentech, following mixed success with Avastin in recurrent disease
GBM market is relatively small (~12,500 cases per annum in US), and larger opportunities exist in Genentech / Roche portfolio
Rich late-stage portfolio in
Genentech creates higher funding hurdles for early-stage projects
such as
GDC-0084
Large pharma overheads make economics of
GDC-0084
less promising;
lean biotech model offers opportunity to externalise and
re-
acquire after clinical proof
-of-
concept
16
GDC-0084
Time on study exceeded historical controls (~1 month) for the majority of patients
Taal et al,
Lancet Oncology, 2015 shows one month survival in comparable lomustine-treated cohort
COMMERCIAL IN CONFIDENCE 17
Response rate was consistent witha
GDC-0084
primarily
cytostatic mode of action
from lesions
change of target
Best % baseline
CR / PR: 0
SD: 15 (35%)
PD: 27 (63%)
18
COMMERCIAL IN CONFIDENCE
On
FDG-PET,
7/27 patients (26%)hada
GDC-0084
metabolic partial
response
Tumor
mean
in Lesion
Response Enhancing
in
Best Overall SUVmax
Normal Brain Tissue
in Brain
Response Normal
Overall SUV in
Best Median
19
COMMERCIAL IN CONFIDENCE
GDC-0084
Brain metastases from
non-CNS
tumors represent long-term upside potential
Overview Example: Breast Cancer
Estimated
100,000—200,000
~30-44%
of metastatic HER2-
cases/year in US positive
metastatic breast cancer
patients have brain metastases
~10-25%
adult cancer patients
develop symptomatic brain mets Brain metastases
represent the
cause of death in ~50% of HER2-
Lung, breast and
melanoma positive breast cancer patients
represent the majority of brain mets
~40-50%
of breast cancer brain
Frequency of brain mets
increasing metastases have disordered PI3K
with better systemic control and pathway
longer survival
Therapies that are effective for the
Few (if any) drugs available to treat primary tumor (e.g. Herceptin) are
brain metastasis often ineffective for brain metastases
Source: E Lim & N Lim (2012). Oncology.
26(7):652-9;
PK Brastianos, SL Carter, S Santagata, et al. (2015).
Discovery 5:1164
COMMERCIAL IN CONFIDENCE
Next Steps
Use GBM as a ‘gateway indication’, with the potential to explore registration post-phase II via accelerated approval / breakthrough designation, subject to clinical
results
Meanwhile, conduct preclinical exploration of brain metastases in partnership with identified researchers to demonstrate preclinical proof
-of-concept
and augment economic value of the asset
20
Ovarian cancer remains a disease of high
Cantrixil
unmet medical need
High Incidence Poor Prognosis with Existing TherapiesGrowing and Evolving Market
Five-Year SurvivalMarket Size (US$ ,000)
Lung 1,200
0%50%100%
Ovarian Cancer
1,000
17th most common Breast Stage 1$1,100M
tumour worldwide
7th most common 800
tumour in women Stage 2
~240,000
new Colorectal 600
cases per annum
1.7% of all new Stage 3$454M
cancer
cases Prostate 400
Overall lifetime risk Stomach
is 1.6% for women Stage 4200
Genetic cause (BRCA1 or BRCA2) in ~10% of
cases
More common in women who have not borne children 0
80% of cases occurring in women >50 years of age 20102020
Anthracyclines
Antimetabolites
Folate Receptor Targeting Agents
Other Cytotoxics
PARP Inhibitors
Platinum Agents
Taxanes
Source: GLOBOCAN; Holschneider & Berek (2000), Sem Surg Onc
19(1):3-10;
Decision Resources
21
COMMERCIAL IN CONFIDENCE
Phase I study is designed to establish safety
Cantrixil
and tolerability, and
explore potential efficacy
Trial Sites Patient Population Study DesignCompletion
~6 hospitals in United Women with Standard dose Forecast 18 month
States and Australia confirmed ovarian escalation to establishstudy duration
cancer maximally tolerated
Investigators are
dose (MTD) Actual duration will
generally specialist Resistant or refractory depend on how many
gynaecological to at least one prior Expansion phase atdose cohorts are
oncologists with line of therapy MTD to explorerequired to establish
clinical trial (generally a platinum signals of clinicalMTD
experience compound) activity
Study performed under Investigational New
Drug (IND)
application with United States Food & Drug Administration
(FDA) – provides careful validation and supports eventual
product
approval in United States
In addition to standard efficacy measures (via CT scan),
study will measure exploratory biomarkers to seek signals of
clinical activity
22
COMMERCIAL IN CONFIDENCE
2017 will be an important year for Novogen, with a rich series of value-driving events
Key Milestones for 2017
Initiation of
GDC-0084
phase
II study
Full recruitment of Cantrixil phase I study
Stage-up
of Anisina for IND submission and phase I study
Further progression of early-stage pipeline as appropriate
Commencement of work on ‘next generation ATM’
program, following receipt of $3M
grant from Australian
Government
23
COMMERCIAL IN CONFIDENCE
Novogen now has a diversified portfolio and is
positioned for growth
Focus on unmet need: pipeline of novel therapies, targeting oncology patients, poorly served by existing treatment options
Building a sustainable model: leveraging oncology expertise, developing commercially attractive,
in-house
and external assets
Diversified portfolio:
Multiple assets in various stages of development – from
pre-clinical
through to phase
II-ready
Across technologies / development platforms
Strong management and board: lean team of internationally-experienced pharma executives
Financially sound: listed on ASX and NASDAQ, with cash runway
News flow: rich series of
value-driving milestones over
12-18
months
24
COMMERCIAL IN CONFIDENCE
Novogen