SYDNEY, July 29, 2015 /PRNewswire/ -- US-Australian drug
discovery company, Novogen Limited (ASX: NRT; NASDAQ: NVGN) today
confirmed it is committed to progressing its ground-breaking
technology platforms to Phase 1 clinical trials as soon as
practicable and to ensure the Company delivers the best value for
shareholders.
Acting Chief Executive Officer, Iain
Ross, said the Company currently had an extensive program of
activities underway including the lead pre-clinical programs,
discovery programs and academic partnerships and initiatives, and
he was working with the newly evolved Board and incumbent
Scientific Management Team to review the Company's immediate
priorities with the intent of providing a shareholder update by
1 September 2015.
"We remain committed to exploiting and creating value from all
our technology platforms in order to build a sustainable,
international, biotech company. Whilst we do not rule out securing
third party collaborations and partnerships to further validate and
fund our programs, I can confirm there are no M&A plans," Mr
Ross said.
"Notwithstanding, it is clear that we cannot realistically
undertake and fully resource all our research and development
programs in parallel all the way through to market approval and
launch. These are new ground-breaking and first in class
technologies and it is critical that we understand which
indications, stage of disease and combinations with other oncology
agents will deliver the best outcome for patients and value for
shareholders."
"Accordingly I have initiated a Company-wide review and I am
working closely with the Board, Management and Company's scientific
advisers to review immediately the pre-clinical programs in detail,
including the targeted indications, route of patient
administration, product formulations, manufacturing scale-up and
regulatory requirements," Mr Ross continued.
"Whilst not wanting to pre-empt the outcome of the review I
anticipate we may have to re-prioritize some of the programs as
outlined in the PRODUCT UPDATE section below."
"One outcome from this process will be to focus our valuable
resources; set clear, realistic, scientific and commercial
priorities in order that we can execute and manage the business
effectively and report our on-going progress to our shareholders
against the priorities we have established. We know already we are
under-resourced in some areas and therefore I have commenced the
search for a world class CEO and authorized the immediate
recruitment of additional staff including a full time CMO, project,
and manufacturing management support.
"We operate in a highly competitive market place and we will
ensure as an organization we are fit for purpose."
"In summary Novogen is in an excellent situation. The Company is
in a solid financial position with a suite of promising drug
candidates. Novogen has world-class science, a scientific team of
the highest quality, and some strong academic partnerships. I am
delighted to be able to lead the Company through this period of
transition and intend to keep shareholders updated," Mr Ross
concluded.
PRODUCT UPDATE
Novogen has two drug technology platforms -- the Superbenzopyran (SBP) and
anti-tropomyosin (ATM) -- around
which the Company has established very strong patent positions. Our
medicinal chemistry programs have identified two promising drug
candidates (Cantrixil and Anisina), which the Company is
progressing down the translational development path in concert.
Cantrixil
Cantrixil is being developed by the Company's subsidiary company
CanTx (a joint venture between Yale
University and Novogen). Cantrixil has been designed to be
injected into the peritoneal cavity with the aim of treating both
differentiated cancer cells and cancer initiating cells, the cells
thought to be primarily responsible for cancer recurrence post
chemotherapy.
Our Yale collaborators have
demonstrated that Cantrixil modulates both the JNK and PKC pathways
resulting in caspase-mediated cell death. Yale researchers also demonstrated that Cantrixil
was active in a stringent, clinically relevant rodent model of
human ovarian cancer. Pending successful completion of our
toxicology program, an initial first-in-human clinical study
assessing the safety and tolerability of Cantrixil in late-stage
cancer patients is planned to commence in 2016.
At the Company's pre-IND meeting with the US Food and Drug
Administration (FDA), the agency agreed with our strategy on
manufacturing and toxicology evaluation. Subsequent to this
meeting, the Company has been able to produce both the active drug
substance and drug product that both meet Good Laboratory Practice
(GLP) standards. Critically the drug has shown an excellent
stability profile, all manufacturing processes have proven robust
and scalable. Novogen has commenced manufacture to Good
Manufacturing Practice (GMP) standards enabling the Company to meet
product demand for clinical trials.
The Company has commenced its Cantrixil toxicology evaluation
with the aim of gaining Investigational New Drug (IND) status with
the FDA. This evaluation will characterize the toxicology signals
associated with the experimental drug, and correlate any toxicities
with drug concentrations achieved in mammalian models. This
information will enable regulators, such as the FDA and clinical
investigators to assess the drug's safety, ascribe a starting dose
in humans and to establish monitoring of potential toxicities
encountered in humans.
Results to date indicate that the drug is associated with
gastrointestinal toxicity manifest as diarrhoea and some
haematological toxicity manifest as anaemia. Also, while not
uncommon for oncology drugs, preliminary studies suggest that
Cantrixil is associated with cardiovascular toxicity though this
observation is being assessed further. The Company anticipates
completing the Cantrixil toxicology evaluation by the end of
2015.
Novogen has assembled a Medical Study Committee for Cantrixil
and commenced writing the Phase I clinical trial protocol where the
Company will assess the safety and tolerability of Cantrixil in
late stage cancer patients. Novogen is also planning to conduct a
second trial in women with late-stage ovarian cancer who have
become unresponsive to standard of care therapy once the Company
has received IND status for Cantrixil from the FDA. The FDA
recently granted Cantrixil Orphan drug status for ovarian
cancer.
Progress and timing of these clinical studies will depend
upon the outcome of the toxicology program and therefore it is not
possible at this stage to be precise as to when clinical studies
will commence however the Company continues to aim to start the
trials in 2016.
Anisina
Anisina is an anti-tropomyosin (ATM) small molecule targeting a
protein component of the actin microfilaments, tropomyosin Tpm3.1
which is essential for tumor cell survival. In vitro studies
confirm that inhibition of Tpm3.1 function impacts the structural
integrity of the cancer cells cytoskeleton causing the cancer cell
to die. In addition to being an effective anti-cancer agent, these
ATM compounds are also novel in that when administered to animals
and used in combination they can enhance the killing effect of one
of the most widely used classes of chemotherapy drugs in cancer
-- the anti-microtubules.
Preclinical studies are underway to validate the effectiveness
of Anisina in animal models of adult (prostate and melanoma) and
pediatric (neuroblastoma) cancers both on its own, and in
combination with standard of care microtubule inhibitors.
Importantly, a proof of concept study done in an animal cancer
model as part of the Children's Oncology Drug Alliance (CODA) has
confirmed that Anisina is not only effective on its own in reducing
neuroblastoma tumor growth but also enhances the sensitivity of
cancer cells to microtubule targeting compounds.
The Company has successfully optimized the manufacturing process
of the Anisina Active Pharmaceutical Ingredient ("API") using a
process that is scalable and meets GLP standards. The process has
proven robust and as a consequence manufacturing programs were
completed 6 weeks ahead of schedule. The GMP manufacture of
material for clinical trials has been accelerated to commence in
August.
Novogen has identified the drug product that the Company intends
to use in the clinic. This has enabled the Company to initiate its
Anisina toxicology program with a view to filing an IND with the
FDA. The Company has assembled a Medical Advisory Board for Anisina
and, based on our pharmacology package, anticipates initially
taking Anisina through to the clinic as an IV delivered drug in
combination with taxanes or vinca alkaloids targeting prostate,
melanoma or neuroblastoma. Further studies are ongoing to identify
the Anisina adult cancer indication. The FDA recently granted
Anisina Orphan drug status for neuroblastoma.
Pending the outcome of our Anisina toxicology program and
discussions with the FDA, the first-in-human studies are predicted
to start in 2016.
TRXE-009 (Trilexium)
TRXE-009 is the Company's second lead SBP drug candidate.
Researchers have shown in animal models that Trilexium affects the
viability of cancer cells by increasing rates of cell death (via
caspase-mediated apoptosis) and reducing proliferation. This was
observed in cancer cells representative of Glioblastoma, melanoma
and prostate cancer. The Company has also demonstrated tumor growth
inhibition in several other animal models (flank models of
melanoma, prostate and GBM).
These findings combined with recently announced pre-clinical
in-vitro studies demonstrate that TRXE-009 is highly cytotoxic to
chemo-resistant pediatric brain cancers including Diffuse Intrinsic
Pontine Glioma (DIPG). Using a proprietary formulation, animal
studies have confirmed that TRXE-009 inhibits the proliferation of
prostate, melanoma, and GBM tumors grown subcutaneously (under the
skin).
A major hindrance to the use of chemotherapeutic agents for
brain tumors is the presence of the blood brain barrier, which
blocks drug access to the brain tumor. To counter this, the Company
has identified a micelle formulation that was able to deliver
potentially therapeutic concentrations of TRXE-009 to the brain
tissue of rodents. This finding represents a step forward in the
development of the drug with the next key step being to demonstrate
that this micelle drug product inhibits the growth of human brain
cancer cells growing in the brain of rodents (orthotopic model of
human brain cancer). Another key goal will be to demonstrate
anti-tumor efficacy of the micelle drug product in rodent models of
prostate cancer and melanoma.
Once Novogen has optimized the TRXE-009 formulation and
confirmed activity in the above key studies, the Company will
commence the requisite toxicology program required prior to the
conduct of a first-in-human trial in 2016/2017.
Jacob's Hope
Jacob's Hope is the name the Company has given to the
degenerative disease and regenerative medicine program that is
highly experimental and investigational. It is named after a very
brave young man called Jacob who has a disease known as Duchenne
muscular dystrophy (DMD). Jacob and thousands of children like him
around the world, is the reason we are running this program.
Jacob Hope consists of three
exploratory programs:
- Regenerative Medicine Program,
- Facioscapulohumeral muscular dystrophy (FSHD) program
and
- Lysosomal Storage Disorder (LSD) Program.
Regenerative Medicine
Studies in the test tube have demonstrated that SBP analogues
are able to promote the differentiation of neural progenitors into
functional neural cells. The Company has commenced a
medicinal chemistry program aimed at refining the SBP chemical
scaffolds with the intention of identifying lead compounds that can
be appraised in an appropriate model of brain injury such as stroke
and traumatic brain injury.
FSHD
The Company's initial evaluation of a panel of SBP analogues
in an in vitro model of FSHD using diseased embryonic stem cells
have demonstrated that discrete analogues may have a positive
effect on the phenotypic appearance of myotubes when compared with
the formation of myotubes with no treatment. This is an intriguing
finding as the screen may provide a tool by which a medicinal
chemistry program could identify potential lead analogues to
progress into in-vivo translational models of FSHD.
LSD
Contracts are in place with a world expert in LSD, where a
panel of SBP analogues will be assessed in human fibroblasts
isolated from patients with LSD. These fibroblasts are unable to
prevent the accumulation of intracellular heparan sulfate, which
leads to the death of the cell. The aim of this screening program
is to identify a subset of analogues that inhibit this accumulation
and thus rescue cell function.
Given the data achieved to date in the Regenerative Medicine
and FSHD programs, the Company intends to pursue patent protection
around the discrete SBP pharmacophores that are attributable to
either potentiating neurogenesis in the Regenerative Medicine
Program, or normalizing the myotube phenotype in the FSHD program.
The Company will also endeavor to protect any SBP pharmacophore
that is active in the LSD setting.
This patent protection strategy will increase the intrinsic
value of each program and establish a priority date from an
intellectual property perspective thereby enabling the Company to
re-visit each program that has promise when funds and time
permits.
About the Children's Oncology Drug Alliance
(CODA)
CODA's mission is to accelerate development of innovative new
therapeutic approaches to the treatment of childhood cancers and to
take account of the fact that childhood cancers are different from
adult cancers and the lifelong consequences of side-effects from
cytotoxic treatment can be far more devastating in a child than in
an adult. CODA unites the research and resources of five
organizations in Australia and the
US.
The Australian members are:
- The charity, The Kids' Cancer Project
- The originator of the anti-tropomyosin technology, the
University of New South Wales
and its commercial arm, New South Innovations
- Biotechnology company, Novogen Limited
The US member is the: Nationwide Children's Hospital,
Columbus, Ohio.
Novogen is providing access to both its anti-tropomyosin and
super-benzopyran drug technologies. Anisina is being evaluated for
its ability to complement the action of standard chemotherapies in
childhood cancers. TRXE-009 is being evaluated for its ability to
treat brain cancers in children.
Further information on CODA is available at
www.childrensoncologydrugalliance.org
About Novogen
Novogen is a public, Australian-US drug development company
whose shares trade on both The Australian Securities Exchange (NRT)
and NASDAQ (NVGN). The Novogen group includes US-based, CanTx Inc.,
a joint venture company with Yale
University. Novogen has two drug technology platforms [the
superbenzopyrans (SBPs) and anti-tropomyosins (ATMs)] yielding drug
candidates that are first-in-class with potential application
across a range of oncology and degenerative diseases. Given the
encouraging data from in vitro and in vivo pre-clinical
Proof-of-Concept studies in the field of Oncology, our immediate
focus is to advance our lead Oncology drug candidates pending
successful completion of their respective toxicology programs.
Ovarian cancer, colorectal cancer, malignant ascites, prostate
cancer, neural cancers (glioblastoma, neuroblastoma in children)
and melanoma are the potential clinical indications being pursued,
with the ultimate objective of employing both technologies as a
unified approach to therapy.
For more information, please visit www.novogen.com
Forward Looking Statement
This press release contains "forward-looking statements"
within the meaning of section 27A of the Securities Act of 1933 and
section 21E of the Securities Exchange Act of 1934. The Company has
tried to identify such forward-looking statements by use of such
words as "expects," "appear," "intends," "hopes," "anticipates,"
"believes," "could," "should," "would," "may," "target,"
"evidences" and "estimates," and other similar expressions, but
these words are not the exclusive means of identifying such
statements. Such statements include, but are not limited to any
statements relating to the Company's drug development program,
including, but not limited to the initiation, progress and outcomes
of clinical trials of the Company's drug development program,
including, but not limited to, Cantrixil, Anisina, Trilexium, and
any other statements that are not historical facts. Such statements
involve risks and uncertainties, including, but not limited to,
those risks and uncertainties relating to the difficulties or
delays in financing, development, testing, regulatory approval,
production and marketing of the Company's drug components,
including, but not limited to, Cantrixil, Anisina, Trilexium, the
ability of the Company to procure additional future sources of
financing, unexpected adverse side effects or inadequate
therapeutic efficacy of the Company's drug compounds, including,
but not limited to, Cantrixil, Anisina, Trilexium, that could slow
or prevent products coming to market, the uncertainty of patent
protection for the Company's intellectual property or trade
secrets, including, but not limited to, the intellectual property
relating to Cantrixil, Anisina, Trilexium, and other risks detailed
from time to time in the filings the Company makes with Securities
and Exchange Commission including its annual reports on Form 20-F
and its reports on Form 6-K. Such statements are based on
management's current expectations, but actual results may differ
materially due to various factions including those risks and
uncertainties mentioned or referred to in this press release.
Accordingly, you should not rely on those forward-looking
statements as a prediction of actual future results.
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SOURCE Novogen Ltd