Amarantus
Provides Business
Overview
New York, NY -- May 11,
2018 -- InvestorsHub NewsWire -- Amarantus Bioscience Holdings,
Inc. (OTC
Pink: AMBS) (the "Company," or AMBS), a US-based JLABS-alumnus
biotechnology holding company, developing first-in-class orphan
neurologic, regenerative medicine and ophthalmic therapies and
diagnostics through its subsidiaries, today provided a business
update to the financial community regarding the business operations
of the Company and its subsidiaries.
Overview of
Amarantus Operations
In April 2017, Amarantus
Bioscience Holdings ("AMBS" or the "Company") made the strategic
decision to house our various assets in individual subsidiaries to
raise focused capital in order to move the assets forward. The
Company formed wholly-owned subsidiaries Elto Pharma, Inc. to house
intellectual property (IP) rights to Eltoprazine which is moving
into Phase 2b clinical development for the treatment of Parkinson's
disease levodopa dyskinesia (PD-LID) and MANF Therapeutics, Inc. to
house IP rights to mesencephalic astrocyte-derived neurotrophic
factor ("MANF") which is moving into IND-enabling studies for the
treatment of orphan ophthalmological diseases. The formation of
Elto Pharma and MANF Therapeutics added to the already established
wholly-owned subsidiary Cutanogen Corporation which is developing
Engineered Skin Substitute (ESS) initially for the treatment of
life-threatening pediatric severe burns. Taken together, these
three subsidiaries of AMBS are developing orphan therapeutic assets
that are in areas of neurology, regenerative medicine and
ophthalmology where competition is limited, and where each program
has the potential to become 'standard of care' for multiple
indications.
In addition, on April
6th, 2018, AMBS announced that it
reacquired rights to Alzheimer's Blood Diagnostic LymPro
Test and MS diagnostic MSPrecise, and subsequently on
May
4th, 2018 entered into an exclusive option
agreement with Leipzig University to gain access to additional IP
and data rights surrounding the use of LymPro Test with amyloid PET
imaging for the diagnosis of Alzheimer's disease. The
Company is evaluating the formation of a neuro-diagnostics
subsidiary to raise capital to move those diagnostic assets
forward. As a result, the four primary assets of the Company are
being positioned to move forward independently within their
subsidiary, attract executive talent, and raise capital on their
own to advance the programs, with Amarantus' primary focus being on
protecting and growing the value of the shares AMBS holds in each
of those subsidiaries. As these opportunities mature, become
further de-risked and gain traction in the market, AMBS will
evaluate the return of capital to Amarantus shareholders to drive
AMBS's value and reward shareholder loyalty.
As the Company continues
to work on the financing plan for each subsidiary, one of the
primary reasons for raising capital into the subsidiaries is to
limit AMBS's need for dilutive capital on an ongoing basis at the
parent level. Going forward, each subsidiary is being populated
with key executives and product development teams that have the
experience and skillsets to drive these programs towards milestones
that will improve their individual value as they achieve FDA
milestones with guidance of AMBS' Chief Regulatory
Advisor Brian Harvey. The companies will in turn have
greater demand for partnering or acquisition from larger
organizations with distribution capabilities. The quality of the
slate of Chief Medical Advisors (CMAs) recently appointed to
Elto Pharma
(Paula Trzepacz, MD), Cutanogen
Corporation (Richard Kagan, MD) and LymPro
(Michael Ropacki, PhD) speaks to the soundness of the
scientific and medical approach to each of these programs, and
gives AMBS confidence that each subsidiary will be able to attract
additional expertise, as well as the capital necessary to advance
the programs. We believe executing this strategy provides the best
opportunity for shareholder value creation.
Capital Raising
Strategy for AMBS
AMBS is focused on
utilizing regulations created under the JOBS Act to raise equity
capital that will allow it to complete its recapitalization plan
and focus on the business of managing its portfolio. The Company is
in active discussions with key advisors and investment banking
firms to advance this effort. In March, the Company completed the
Tender Exchange which restructured outstanding securities that
previously inhibited the Company's ability to raise equity capital,
and in April retained counsel experienced in negotiating with
accounts payable (AP) creditors to complete the AP settlement
requirements under the Tender Exchange agreement, thereby releasing
the liens on the Company's assets. Going forward, the Company is
looking at the next equity raise under the JOBS Act as the turning
point that will allow it to emerge from the recapitalization phase
and return to normal business operations.
Alzheimer's Blood
Diagnostic LymPro Test
Update
Amarantus continues to
believe in LymPro. The feedback the Company received in 2015-16
surrounding the use of LymPro in clinical trials was quite positive
as it related to the cell-cycle hypothesis of Alzheimer's that
underpins LymPro, and the clinical data produced as of that time.
However, prospective collaborators noted that what was missing from
our initial dataset was the use of a reference standard that
incorporated newly available biomarkers, such as PET imaging.
In
presenting final LP-002 LymPro data at the
Alzheimer's Association International Conference (AAIC)
in 2015, the Company showed equivalence between
LymPro and the clinical diagnosis-only reference standard in
distinguishing patients diagnosed with dementia of the Alzheimer's
type from healthy controls, based on clinical diagnosis alone.
Thereafter, Amarantus worked closely with Leipzig to design a
clinical study that would overcome those previous shortcomings by
evaluating LymPro's ability to discriminate patients with dementia
of the Alzheimer's type from patients who suffer from other forms
of dementia using clinical diagnosis in addition to various
biomarkers, such as amyloid PET imaging. The Company is grateful to
Leipzig for having financed the entirety of that study (LymPro PET
1), and for initiating a second, confirmatory study (LymPro PET 2)
that is currently enrolling. For Amarantus shareholders, this means
that while AMBS was unable to advance the LymPro asset over the
last 3 years, LymPro was continuing to move forward at Leipzig and
AMBS is now positioned to become the beneficiary of those efforts.
A recent statement from Merck (below) in the New England Journal of
Medicine conceded the widely held hypothesis of amyloid's causative
role in Alzheimer's disease may itself be flawed, bringing even
greater importance to the scientific hypotheses behind LymPro,
which sit 'up-stream' to amyloid plaque:
"This suggests that
once dementia is present, disease progression may be independent of
A production or, alternatively, that the amyloid hypothesis of
Alzheimer's disease may not be correct."
-
N Engl J Med 2018;
378:1691-1703
Given the continued high
failure rates in Alzheimer's clinical trials, major uncertainties
emerging regarding the amyloid therapeutic hypothesis of
Alzheimer's disease, and the wealth of scientific data continuing
to emerge that supports the cell-cycle hypothesis of Alzheimer's
disease (https://www.spandidos-publications.com/etm/15/1/103),
the Company believes LymPro puts Amarantus squarely back in the
center of emerging technologies that have the potential to make a
significant impact in the development of new treatment paradigms
for Alzheimer's. AMBS intends to bring in seasoned management to
build a business around LymPro.
Elto Pharma
Update
Based upon an independent
3rd party valuation of the PD-LID indication in the US and Europe
alone, Eltoprazine is the most valuable asset in the Amarantus
portfolio as measured by risk-adjusted net present value (rNPV),
with a robust 9-figure valuation. This rNPV is primarily driven by
the fact Eltoprazine:
- Is in Phase 2b clinical
development, with strong initial
Phase 2a data;
Is being developed to enter a growing market with little
competition;
Is treating a significant orphan drug-designated patient population
(180,000+ in the US alone);
Has recently approved competitive medicines in PD-LID that are
beginning to demonstrate value to the payor
community.
As a result, Amarantus is
laser-focused on ensuring that Elto Pharma attracts long-term
focused capital that will allow it to fulfill its initial mission
to advance the PD-LID indication through Phase 2b. If successful,
Elto Pharma could see secondary indications such as Agitation in
Alzheimer's disease and Adult ADHD dramatically increase the
program's rNPV as they re-enter mid-stage clinical development
based on the strength of their initial Phase 2
data.
Based on this information,
Elto Pharma is preparing to initiate a private round of financing,
followed by preparations for a traditional initial public offering
(IPO) that has seen comparable companies command valuations in the
hundreds of millions. We believe that capital raising around Elto
Pharma could drive the value of the Amarantus shares, based upon
our then ownership position in that entity. The Company has begun
working with domestic (NYSE or NASDAQ) and international advisors
(Hong Kong, or others) to determine the best jurisdiction to list
Elto Pharma. The Company intends to provide updates on Elto Pharma
to Amarantus shareholders as progress is made.
Cutanogen
Corporation Update
It is clear, based upon
the data published in the Journal of Burn Care and Research in
2017, that Cutanogen's ESS has tremendous potential to dramatically
improve the standard of care in the treatment of acute pediatric
burns, as measured by a number of key trial
endpoints:
- Reducing mortality vs.
historical control;
Reducing time to wound closure vs. historical control;
Improving function post-treatment vs. historical
control.
Based upon the strength of
the data seen to date, the Company believes Cutanogen is ready to
move into a pivotal study to bring this life-saving orphan
treatment to market, making pediatric burns the first indication
for which Cutanogen will be seeking approval for ESS. The
opportunity for ESS, however, expands far beyond the treatment of
acute pediatric burns.
ESS is a cell & gene
therapy skin platform technology that has a multitude of possible
use cases in the medical field. Two examples of potential uses of
this technology that have already been used in humans
include:
- Re-grafting/revision
surgeries covering large body surface areas;
Giant Congenital Melanocytic Nevus management.
As Cutanogen builds out
the commercial plan for ESS, and assesses the collective rNPV of
each use case, it becomes clear that ESS could become a standard
tool in acute treatment settings, but also in elective treatments
where skin harvesting can be scheduled to meet a pre-defined
timeline. Recent data published in Nature regarding the use of gene
therapy on epidermal skin grafts for the treatment of an
epidermolysis bullosa patient (https://www.nature.com/articles/nature24753)
clearly points to the potential use of gene therapy with the ESS
platform, which opens up the potential use of ESS to a wide range
of rare pediatric skin diseases. Cutanogen has IP rights to the use
of ESS in combination with gene therapy.
Beyond the use cases for
ESS noted above, recent data published on improvements made to ESS
(https://onlinelibrary.wiley.com/doi/full/10.1111/pcmr.12609)
have added the potential to match the skin color of the graft to
the skin color of the patient via the addition of melanocytes in
the next generation version of the product (ESS 2.0). Consequently,
the ESS 2.0 platform can expand beyond the treatment of acute
catastrophic and rare pediatric conditions, and expand into
cosmetic applications, significantly opening the market potential
for this product. Taken together, the potential uses for the
current ESS, ESS 2.0 and further generations of ESS have the
potential to significantly drive the rNPV of the product based upon
its fundamental scientific and medical
characteristics.
What could further drive
rNPV for ESS is the Rare Pediatric Disease Designation (RPDD)
program at the FDA that provides incentives, in the form of
Priority Review Vouchers (PRVs), to companies that develop
treatments for rare diseases that primarily affect children. The
Company believes ESS is likely to qualify for one or more RPDDs
over time. As such, the key focus for Cutanogen is now on raising
private financing so that it can prepare for its own IPO as a cell
& gene therapy platform technology company that is moving into
pivotal studies as a life-saving treatment option in a potential
rare pediatric condition, for which few adequate treatment options,
if any, exist.
MANF
Therapeutics
MANF Therapeutics
continues to amass a tremendous portfolio of intellectual property
covering the use of MANF in the treatment of a range of disorders.
While still in pre-clinical development, the next major step for
this program is the appointment of a Chief Medical Advisor who can
help finalize the selection of the initial indication for
first-in-man studies with MANF, and drive the program towards the
clinic. There is significant reason to believe that successful
first-in-man studies with MANF could have a dramatic impact on the
rNPV of the MANF asset, as positive efficacy in one indication
likely increases the potential of a positive outcome in other,
potentially larger, indications. Amarantus has continued to work
with key groups, including the Snow Foundation focused on
developing new treatments for Wolfram's Syndrome, to advance the
science underpinning MANF so that upon proper capitalization this
asset can be swiftly moved to complete IND-enabling studies in
preparation for first-in-man. Amarantus continues to believe that
MANF is potentially the most valuable asset in the Amarantus
portfolio and the Company will continue to invest in the IP
underpinning MANF until such time that MANF Therapeutics can
independently finance its development. With
potential disease-modifying applications in Glaucoma, Parkinson's
disease, Alzheimer's disease, myocardial infarction and diabetes,
human proof of concept with MANF in an orphan indication
would significantly drive the rNPV for
MANF by establishing a reasonable risk adjusted discount
to its value in the event of success in these
larger indications.
Summary
While certain risks remain
as we complete the recapitalization of AMBS and the capital
formation process for our subsidiaries, the Company has made
tremendous progress in the last 6 months towards bringing these
important scientific and medical breakthroughs back into
development following a prolonged period of inactivity. The new
members of the team have injected significant insight and energy to
our efforts. Going forward, Amarantus is focused on completing the
capitalization of the parent via the JOBS Act, privately
capitalizing its subsidiaries, and then facilitating the
advancements of our subsidiaries to build value for AMBS and its
shareholders.
About
Elto Pharma, Inc.
Elto Pharma, Inc. is
developing eltoprazine, an oral small molecule 5HT1A/1B partial
agonist in clinical development for the treatment of Parkinson's
disease levodopa-induced dyskinesia (PD-LID), aggression in
Alzheimer's disease and adult attention deficit hyperactivity
disorder (adult ADHD). Eltoprazine has been evaluated in over 680
human subjects to date, was well-tolerated and showed promising
efficacy results in both cognitive and movement disorders.
Eltoprazine has received orphan drug designation (ODD) from the US
FDA for the treatment of PD-LID.
Eltoprazine was originally
developed by Solvay (now Abbvie) for aggression-related
indications. The eltoprazine program was out-licensed to
PsychoGenics, Inc. (PGI). PGI licensed eltoprazine to Amarantus in
2014 after a successful proof-of-concept trial in
PD-LID.
In April 2017, Amarantus
incorporated the wholly-owned subsidiary Elto Pharma, Inc. for the
purpose of raising capital to finance the further clinical
development of eltoprazine.
About Cutanogen
Corporation
Engineered Skin Substitute
(ESS) is a tissue-engineered skin prepared from autologous
(patient's own) skin cells. It is a combination of cultured
epithelium and a collagen-dermal fibroblast implant that produces a
skin substitute which contains both epidermal and dermal
components. This model has been shown in preclinical studies to
generate a functional skin barrier. Most importantly, because ESS
is composed of a patient's own cells, it is less likely to be
rejected by the immune system of the patient, unlike porcine or
cadaver grafts in which immune system rejection is a possibility. A
non-GMP version ESS has been used in investigator-initiated and
compassionate-use clinical study settings in over 150 human
subjects, primarily pediatric patients, for the treatment of severe
burns up to 95% of total body surface area. The non-GMP version has
also been used in the treatment of two patients with Giant
Congenital Melanocytic Nevi (GCMN).
In July 2015, Amarantus
acquired Lonza Walkersville's wholly-owned subsidiary Cutanogen
Corporation, the sole licensor of intellectual property rights to
ESS from Cincinnati's Shriners Hospitals for Children and the
University of Cincinnati. Cutanogen Corporation is a wholly-owned
subsidiary of Amarantus.
About MANF
Therapeutics, Inc.
MANF
(mesencephalic-astrocyte-derived neurotrophic factor) is believed
to have broad potential because it is a naturally-occurring protein
produced by the body to reduce/prevent apoptosis (cell death) in
response to injury or disease, via the unfolded protein response.
By administering exogenously produced MANF the body, Amarantus is
seeking to use a regenerative medicine approach to assist the body
with higher quantities of MANF when needed. Amarantus is the
frontrunner and primary holder of intellectual property around
MANF, and is initially focusing on the development of MANF-based
protein therapeutics.
In April 2017, Amarantus
incorporated the wholly-owned subsidiary MANF Therapeutics, Inc. to
focus on the preclinical and clinical development of MANF. MANF's
lead indication is retinitis pigmentosa, and additional indications
including Parkinson's disease, diabetes and Wolfram's syndrome are
envisioned. Further applications for MANF may include Alzheimer's
disease, traumatic brain injury, myocardial infarction,
antibiotic-induced ototoxicity and certain other orphan
diseases.
About LymPro
Test
The Lymphocyte
Proliferation Test (LymPro Test) is a diagnostic blood test that
determines the ability of peripheral blood lymphocytes (PBLs) and
monocytes to withstand an exogenous mitogenic stimulation that
induces them to enter the cell cycle. It is believed that certain
diseases, most notably Alzheimer's disease, are the result of
compromised cellular machinery that leads to aberrant cell cycle
re-entry by neurons which then leads to apoptosis. LymPro is unique
in the use of peripheral blood lymphocytes as a surrogate for
neuronal cell function, suggesting a common relationship between
PBLs and neurons in the brain.
About Amarantus
Bioscience Holdings, Inc.
Amarantus Bioscience
Holdings (AMBS) is a JLABS alumnus biotechnology company developing
treatments and diagnostics for diseases in the areas of neurology,
regenerative medicine and orphan diseases through its subsidiaries.
AMBS' wholly-owned subsidiary Elto Pharma, Inc. has
development rights to eltoprazine, a Phase 2b-ready small molecule
indicated for Parkinson's disease levodopa-induced dyskinesia,
Alzheimer's aggression and adult attention deficit hyperactivity
disorder, commonly known as ADHD. AMBS acquired the rights to the
Engineered Skin Substitute program, a regenerative medicine-based
approach for treating severe burns with full-thickness autologous
skin grown in tissue culture that is being pursued by AMBS'
wholly-owned subsidiary Cutanogen Corporation. AMBS'
wholly-owned subsidiary MANF Therapeutics, Inc. owns key
intellectual property rights and licenses from a number of
prominent universities related to the development of the
therapeutic protein known as mesencephalic astrocyte-derived
neurotrophic factor ("MANF"). MANF Therapeutics, Inc.
is developing MANF-based products as treatments for brain and
ophthalmic disorders. MANF was discovered by the Company's Chief
Scientific Officer John Commissiong, PhD. Dr. Commissiong
discovered MANF from AMBS' proprietary discovery engine PhenoGuard.
The Company also re-acquired rights to the Alzheimer's blood
diagnostic LymPro Test , MSPrecise and NuroPro.
For further information
please visit www.Amarantus.com, or connect with the Amarantus on Facebook,LinkedIn,Twitterand Google+.
Amarantus
Investor and Media Contact:
Howard
Gostfrand
American Capital Ventures,
Inc.
Office:
305-918-7000
Email: hg@amcapventures.com
Source: Amarantus
Bioscience Holdings, Inc.