wisconsin alumni research foundation
Business Development
and Licensing Opportunities
Vitamin D Technologies
business development and technology licensing opportunities
vitamin D technologies
Vitamin D Research at UW–Madison
WARF and UW–Madison have a long history of outstanding work with
vitamin D. The licensing and commercial development of a vitamin
D discovery made by UW–Madison biochemist Harry Steenbock is
WARF’s first success story.
Steenbock founded WARF as a result of his 1923 breakthrough
discovery that irradiating foods with ultraviolet light increased their
vitamin D content. He knew his discovery had the potential to
eliminate rickets, a crippling bone disease of children caused by
vitamin D deficiency.
WARF’s first licensee, Quaker Oats, used the technology to fortify its
cereals. WARF licensed subsequent Steenbock discoveries to other
companies to enrich milk and bread, and to develop pharmaceutical
preparations of vitamin D. Thanks to the ready availability of vitamin
D-fortified foods, by the time Steenbock’s patent expired in 1945
rickets had all but disappeared.
vitamin D
Hector DeLuca, Steenbock’s last graduate student, continued his
mentor’s pioneering work in vitamin D. His research showed that
vitamin D itself is not active in the body but must metabolize to
more active forms. Not only did this work reveal the underpinnings
of the endocrine system used to regulate calcium metabolism,
but it enabled the development and use of vitamin D analogs in
pharmacotherapy. DeLuca’s research has been instrumental in the
development of drugs such as Alfarol®, Calcijex®, Rocaltrol®, Hectorol®
and Zemplar®, which treat kidney disease and bone loss.
Rocaltrol
C alc i j e x
O n e - A l p ha / al p hacalc i dol
H e ctorol
Z e m p lar
On average, the DeLuca laboratory discovers eight to ten new
compounds each year. These discoveries are analogs of vitamin
D with targeted biologic activities that could be useful in treating
human diseases, including autoimmune disorders like multiple
sclerosis and diabetes; proliferative diseases, such as psoriasis and
cancer; metabolic bone diseases, including osteoporosis and renal
osteodystrophy/secondary hyperparathyroidism; and inflammatory
diseases, such as irritable bowel syndrome and rheumatoid arthritis.
The team also has discovered vitamin D analogs that possess
targeted biologic activities but have minimal effect on calcium
mobilization from the skeleton or intestine—a central goal in
contemporary vitamin D research.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Novel Anabolic Treatments
for Osteoporosis and Related
Bone Disorders
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF)
is seeking commercial partners interested in developing
novel compounds for the treatment of osteoporosis
and related bone disorders.
OVERVIEW
Osteoporosis is a debilitating disease in which bones become fragile
and more likely to break. According to the 2004 Surgeon General’s
report on bone health and osteoporosis, more than 1.5 million people
in the United States suffer fractures as a result of osteoporosis each
year. Osteoporosis causes 2.6 million visits to the doctor’s office,
800,000 trips to the emergency room, 500,000 hospitalizations and
180,000 nursing home placements, and costs for treating fractures
resulting from osteoporosis exceed $18 billion each year.
The normal process of bone remodeling involves carefully balanced
rates of bone resorption and bone synthesis. Osteoporosis occurs when
accelerated rates of bone resorption and declining rates of new bone
synthesis alter the mineral content, density and structure of bone. This
problem is particularly pronounced in post-menopausal women when
declining levels of estrogen accelerate bone resorption rates while
advancing age decreases the rate of bone synthesis. The decrease in
bone mineral density is usually associated with an increased incidence
of fracture, particularly in the weight bearing areas of the skeleton.
Hormone replacement therapy (HRT) was once the main treatment
for osteoporosis in post-menopausal women because it effectively
balanced bone resorption and new bone synthesis, critical processes
essential for healthy bone remodeling. Bisphosphonate compounds
have largely replaced HRT due to concerns that HRT may increase the
risk of cancer. Bisphosphonates are designed to conserve bone mineral
density and reduce fracture risk by slowing the rate of bone resorption;
however, they do not stimulate new bone synthesis. Despite evidence
of improved bone mineral density and a reduction in fractures rates,
fractures continue to occur in treated patients. Therefore, a need exists
for treatments that will improve the quality and strength of the bone
that is preserved with anti-resorption treatments.
APPLICATIONS
n
Osteoporosis
n
Osteopenia
n
Bone Repair
KEY BENEFITS
n
ddresses the need for osteoporosis
A
therapies with anabolic activity that may
lead to greater bone strength and fracture
resistance.
n
ffers a fresh approach for gaining access
O
to the osteoporosis therapeutics market.
n
Provides an opportunity to leverage or
expand existing therapeutic franchises
through development of single agent treatments or combination product treatments
with existing bone resorption inhibitor
products.
n
inimal development time required —
M
early pre-clinical screening studies
completed; late stage/GLP pre-clinical and
clinical evaluations may be available.
n
Innovative licensing and/or development
terms are ­available.
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
A Novel Treatment Approach: Anabolic analogs
of calcitriol with high selectivity for bone and more
favorable safety profiles.
UW–Madison researchers are investigating new treatments
for osteoporosis that focus on improving bone quality and
increasing bone strength by stimulating bone synthesis,
in addition to blocking bone resorption. In recent years,
analogs of the hormonally active form of vitamin D, known
as calcitriol or 1,25 dihydroxyvitamin D3, have emerged as a
promising focus for the development of anabolic osteoporosis
therapies. Calcitriol has been shown to slow bone loss and
reduce the risk of fractures, particularly when taken with
calcium. However, bone synthesis has been only weakly
observed at very high concentrations, and the concentration
of calcitriol required to achieve observable levels of bone
growth cannot be safely sustained due to excessive
mobilization of intestinal calcium and the occurrence of doselimiting hypercalcemia.
Researchers at the University of Wisconsin are designing
and studying promising new analogs of calcitriol that can
stimulate new bone synthesis with little evidence of calcium
mobilization in the intestine. These compounds could prove
useful as bone strengthening agents for osteoporosis,
either as monotherapy or in combination with anti-resorptive
treatments.
BUSINESS OPPORTUNITY
n
steoporosis is a growing market and under-diagnosed
O
disease in the United States. In 2009 it is estimated that
11 million people and 18% of the US population over the
age of 50 have osteoporosis. This number is expected to
exceed 14 million by 2021.
n
T he U.S. osteoporosis market generated revenues of $4.7
billion in 2008 and is expected to generate $6.5 billion by
2021.
n
lmost 90% of the treatments currently marketed for
A
osteoporosis do not provide anabolic bone formation
activity as their mechanism of action.
n
clear need exists for new products that can improve
A
current approaches to reducing fracture risks by forming
new bone as well as preserve existing bone.
n
Extensive intellectual property rights may already
be established in major market areas.
vitamin D technologies
t the present time, a significant late stage commercialization
A
opportunity is available through our Licensee, Deltanoid Pharmaceuticals. For further
information, please contact our office.
STAGE OF DEVELOPMENT
The analogs offered in this portfolio have been subjected to
in vitro/in vivo models for evaluations of receptor binding,
cell proliferation, cellular differentiation, calcium mobilization
and blood calcium levels. In some cases, Good Laboratory
Practice (GLP)-rated pre-clinical and clinical data may be
available for evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
ADDITIONAL INFORMATION
For more information about the inventor(s),
see http://discoveryportal.org
n
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Non-Calcemic Vitamin D Analogs
for Treating Prostate Cancer
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF)
is seeking commercial partners interested in developing
novel compounds for the treatment of prostate cancer.
OVERVIEW
According to the Centers for Disease Control and Prevention, nearly
200,000 men in the United States were diagnosed with prostate
cancer in 2005. The occurrence of undiagnosed forms of prostate
cancer suggests the actual population of men affected with the
disease may be substantially underestimated since as many as 40
percent of men over 50 have a “clinically silent” form of the cancer.
The American Cancer Society reports that nearly 29,000 men will die
annually from this disease.
Like many other cancers, prostate cancer often can be treated
successfully if it is diagnosed at an early stage; however, the standard
treatment, surgery to remove the prostate and nearby lymph nodes or
radiation to kill tumor cells, can result in impotence or incontinence.
Effective treatments for prostate cancer are actively being sought,
particularly for advanced, androgen-independent prostate cancer.
In recent years, analogs of the hormonally active form of vitamin D,
known as calcitriol or 1,25 dihydroxyvitamin D3, have emerged as a
promising focus for the development of prostate cancer therapies.
Calcitriol has been shown to promote tumor cell differentiation
and inhibit proliferation of malignant cells. While promising, the
concentrations of calcitriol required for effective prostate cancer
treatment can be toxic as effective therapeutic concentrations elevate
blood calcium to dangerous levels.
APPLICATIONS
n
Treatment for all forms of prostate cancer.
n
uitable as an oral or intravenous
S
formulation.
KEY BENEFITS
n
proven biologically active compound that
A
stops growth of prostate cancer cells.
n
Provides a safer, less calcemic compound
than the natural hormone calcitriol.
n
ffers a fresh therapeutic approach for
O
gaining access to the cancer therapy
market.
n
Provides a drug development opportunity
in a growing market space.
n
Innovative licensing and development
terms available.
A Novel Solution May Be Possible: Non-calcemic analogs
of calcitriol
UW–Madison researchers are designing non-calcemic analogs of
calcitriol with anti-cancer effects on prostate cancer cells. The
anti-cancer effects are attributed to mechanisms that stop cancer
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
cell growth, including apoptosis, differentiation and antiangiogenesis. These analogs may provide the solution to
the dose limitations of calcitriol by providing the ability to
administer higher concentrations of a vitamin D analog with
much lower potential for causing hypercalcemia and its
complications.
BUSINESS OPPORTUNITY
n
Prostate cancer is a growing market worldwide.
n
need remains unmet for non-invasive treatments
A
and fewer treatment-related side effects.
n
major gap in the market exists, offering high commercial
A
potential for second line treatment of hormone refractory
prostate cancer (HRPC).
STAGE OF DEVELOPMENT
The analogs offered in this portfolio have been subjected to
in vitro/in vivo models for early-stage pre-clinical evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
ADDITIONAL INFORMATION
For more information about the inventor(s),
see http://discoveryportal.org
n
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Vitamin D Analogs
Provide a Novel Approach
for the Treatment of Acne
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF)
is seeking commercial partners interested in developing
novel compounds for the treatment of acne.
OVERVIEW
Acne, a chronic inflammatory disease, is the most common skin
condition in the United States, affecting approximately 85 percent
of teenagers and 20 percent of adults. Acne occurs when pores in
the skin are clogged by sebum, an oily substance secreted by the
sebaceous glands. It is characterized by the presence of pimples or
“zits” on the face, neck, chest, back and/or upper arms.
Although acne is not caused by bacteria, bacteria can make acne
worse. The bacterium Propionibacterium acnes, which is normally
present on skin, feeds on sebum. When a pore is clogged with sebum,
P. acnes bacteria can grow and produce chemicals that irritate and
inflame the skin. The inflamed blemishes often result in scarring.
Vitamin D was first proposed as a treatment for acne in 1938 by Dr.
Merlin Maynard, who found it to be a satisfactory therapy for more
than 75 percent of his patients. Analogs of the hormonally active
form of vitamin D, known as calcitriol or 1,25 dihydroxyvitamin D3, act
on the immune system to reduce inflammation. In addition, calcitriol
supports the production of antimicrobial peptides in the skin and may
help provide an effective defense against the bacteria that can lead to
severe acne.
APPLICATIONS
n
Prevention or treatment of acne.
KEY BENEFITS
n
ffers a fresh therapeutic approach for
O
gaining access to the skin care market.
n
Provides a drug development opportunity in
a growing market space.
n
trong intellectual property rights and
S
development incentives are available.
While promising, the concentrations of calcitriol required for effective
treatment of acne can be toxic. The hormone mobilizes calcium from
bones and increases intestinal absorption of dietary calcium. Effective
therapeutic concentrations can lead to hypercalcemia; a condition
characterized by elevated blood calcium levels, alterations in mental
status, muscle weakness and calcification of soft tissues and organs
such as the heart and kidneys. Therefore, a need exists for noncalcemic compounds that provide desirable therapeutic effects without
causing dose-limiting hypercalcemia.
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
STAGE OF DEVELOPMENT
Many of the analogs offered in this portfolio have been
subjected to in vitro/in vivo models for evaluations of receptor
binding, cell proliferation, cellular differentiation and bone
and intestinal calcium mobilization. In some cases, Good
Laboratory Practice (GLP)-rated pre-clinical and clinical data
also may be available for evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
ADDITIONAL INFORMATION
For more information about the inventor,
see http://discoveryportal.org
n
A Novel Treatment: Non-calcemic analogs of calcitriol
Researchers at the University of Wisconsin are designing noncalcemic analogs of calcitriol. These analogs may provide the
solution to the dose limitations of calcitriol by offering a wider
dose range and lower potential for causing hypercalcemia
and its complications. They show significant ability to reduce
inflammation at concentrations that do not cause bone
calcium mobilization, intestinal calcium transport or increase
blood calcium to dangerous levels.
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
WARF maintains a robust and growing portfolio of low and
non-calcemic analogs of calcitriol. Intellectual property
rights for commercialization in the acne space are currently
available.
BUSINESS OPPORTUNITY
n
0 million Americans have active acne, and one quarter
6
of those individuals have acne severe enough to cause
scars.
Illustration courtesy of Don Bliss, National Cancer Institute
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Psoriasis Treatments with Next
Generation Vitamin D Analogs
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF)
is seeking commercial partners interested in developing
novel compounds for the treatment of psoriasis.
OVERVIEW
According to the National Institutes of Health, approximately 7.5 million
people in the United States have psoriasis, an incurable and painful
skin disorder in which affected individuals develop thick, scaly areas
on their skin. This disease ranges from minor localized patches on the
skin to debilitating full body coverage.
Psoriasis occurs when the immune
system sends out faulty signals that
cause skin cells to grow too fast. Many
treatments, including topical products,
systemic medications and phototherapy,
are available to control the symptoms
of psoriasis, but these treatments may
cause adverse side effects or may not
be effective in many individuals.
Analogs of the hormonally active form of vitamin D, known as
calcitriol or 1,25 dihydroxyvitamin D3, have been recognized for years as
a promising focus for the development of psoriasis therapies. Calcitriol
encourages skin cells to stop proliferating and start differentiating,
reducing their growth rate to near normal levels. In addition, calcitriol
acts on the immune system to reduce itching and inflammation.
While promising for the treatment of mild cases, the concentrations
of calcitriol required for effective treatment of severe psoriasis can
be toxic. The hormone mobilizes calcium from bones and increases
intestinal absorption of dietary calcium. Effective therapeutic
concentrations can lead to hypercalcemia; a condition characterized
by elevated blood calcium levels, alterations in mental status,
muscle weakness and calcification of soft tissues and organs such
as the heart and kidneys. Therefore, a need exists for non-calcemic
compounds that provide desirable therapeutic effects without causing
dose-limiting hypercalcemia.
APPLICATIONS
n
Mild psoriasis
n
Severe psoriasis
KEY BENEFITS
n
proven biologically active compound
A
that slows the growth of skin cells with
minimal potential for raising calcium levels.
n
ay enable less frequent dosing and
M
increase in size of treatment areas.
n
Early pre-clinical screening studies
completed; later stage pre-clinical and
clinical GLP evaluations may be available.
n
ffers a fresh therapeutic approach for
O
gaining access to the growing psoriasis
and skin therapy market.
n
Innovative licensing and/or development
terms available.
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
A Novel Treatment:
Non-calcemic analogs of calcitriol
Researchers at the University of Wisconsin are designing noncalcemic analogs of calcitriol. These analogs may provide the
solution to the dose limitations of calcitriol by offering a wider
dose range and lower potential for causing hypercalcemia and
its complications. They show significant ability to slow the
growth of skin cells at concentrations that do not cause bone
calcium mobilization, intestinal calcium transport or increase
blood calcium to dangerous levels.
WARF maintains a robust and growing portfolio of low and
non-calcemic analogs of calcitriol. Intellectual property rights
and special development incentives for commercialization in
the psoriasis space are currently available.
STAGE OF DEVELOPMENT
The analogs offered in this portfolio have been subjected to
in vitro/in vivo models for evaluations of receptor binding,
cell proliferation, cellular differentiation, calcium mobilization
and blood calcium levels. In some cases, Good Laboratory
Practice (GLP)-rated pre-clinical and clinical data may be
available for evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
ADDITIONAL INFORMATION
For more information about the inventor(s),
see http://discoveryportal.org
n
BUSINESS OPPORTUNITY
n
T hrough 2006, the prevalence of psoriasis was estimated
to be 17 million people worldwide.
n
atamonitor reports $1.95 billion in sales of psoriasis
D
treatments in 2005.
n
y 2015 the market for psoriasis treatments will exceed
B
$2.3 billion in the U.S., $832 million in the E.U. and $354
million in Japan.
n
n increasing demand exists for safer therapeutics that
A
control symptoms with greater efficacy, longer duration
and improved quality of life.
n
Providers view vitamin D analog treatments as first line
options versus steroids due to safety concerns and also
over biologic treatments as payers carefully scrutinize riskbenefit and cost-benefit ratios.
n
ext generation vitamin D treatments are needed to
N
replace older products with narrow therapeutic indexes.
vitamin D technologies
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Novel Drug Candidates for
Secondary Hyperparathyroidism
(SHPT) and Renal Osteodystrophy
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF) is seeking
commercial partners interested in developing novel compounds
for the treatment of SHPT and renal osteodystrophy.
OVERVIEW
Renal osteodystrophy is a debilitating bone disease found in patients
suffering from chronic kidney disease (CKD). It occurs when the
kidney loses its ability to maintain the proper balance of calcium and
phosphorous in the blood. A healthy kidney filters toxins and excess
nutrients from the blood. It also stimulates intestinal absorption of
calcium and phosphate by synthesizing calcitriol, the active form of
vitamin D.
But in patients with CKD, calcitriol cannot be synthesized, resulting
in hypocalcemia. In addition, nutrients, particularly phosphorous,
accumulate in the blood. Hypocalcemia and excess phosphorous
stimulate the secretion of parathyroid hormone (PTH), which causes
the resorption of calcium and phosphorus from bone. Left untreated,
hyperplasia of the parathyroid glands can occur. Prolonged exposure to
elevated levels of PTH can lead to excessive demineralization of bone
and weakening of the skeleton.
To suppress PTH, synthetic forms of calcitriol are used to restore blood
calcium to acceptable levels. However, these compounds stimulate
calcium and phosphorus absorption in the intestine, potentially causing
dose-limiting hypercalcemia and hyperphosphatemia.
New Treatments: Improved non-calcemic analogs of calcitriol
APPLICATIONS
n
ral and intravenous treatments
O
for management of SHPT and renal
osteodystrophy in CKD patients.
KEY BENEFITS
n
Proven biologically active compounds
selected to target and suppress PTH levels.
n
Provide safer, less calcemic and less
phosphatemic compounds than the natural
hormone calcitriol or currently marketed
treatments.
n
ffers a fresh therapeutic approach for
O
gaining access to the kidney disease
market.
n
Provides a drug development opportunity
in a growing market space.
n
trong intellectual property rights and
S
development incentives are available.
Currently approved products for use in renal osteodystrophy and
SHPT were discovered by researchers at the University of Wisconsin
(Calcijex©, Rocaltrol©, Hectorol© and Zemplar©), and research continues
to identify analogs that can more effectively suppress PTH and further
reduce dose-limiting hypercalcemia and hyperphosphatemia. New
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
ADDITIONAL INFORMATION
thyroid gland
For more information about the inventor(s),
see http://discoveryportal.org
n
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
parathyroid gland
compounds that have been discovered are showing great
promise for further advancing the efficacy and safety of SHPT
treatments. Early stage in vivo data suggests these new
compounds provide wide therapeutic indexes, making them
excellent development candidates for SHPT treatments.
BUSINESS OPPORTUNITY
n
The market for vitamin D analogs used to treat SHPT and
renal osteodystrophy in the US was estimated to be worth
more than $800 million at the end of 2008.
n
T he U.S. Renal Data Service (USRDS) estimated
approximately 330,000 people received dialysis treatment
for stage 5 CKD in 2006 and that the U.S. CKD population
is expected to increase 60% by 2020.
n
Improving treatment outcomes relating to bone and
mineral disorders is a central theme in CKD patient
management strategies.
STAGE OF DEVELOPMENT
Many of the analogs offered in this portfolio have been
subjected to in vitro/in vivo models for evaluations of receptor
binding, cell proliferation, cellular differentiation, bone
and intestinal calcium mobilization. In some cases, Good
Laboratory Practice (GLP)-rated pre-clinical and clinical data
may also be available for evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Type 1 Diabetes — A Novel
Drug Development Opportunity
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF) is seeking
dedicated partners focused on translational research into
therapeutics for treatment of type 1 Diabetes using novel
vitamin D analogs.
OVERVIEW
According to the Juvenile Diabetes Research Foundation, more than
three million people in the United States have type 1 diabetes. Type
1 diabetes is an autoimmune disease that results when the immune
system destroys insulin-producing beta cells in the pancreas. It can
lead to serious complications, including blindness, cardiovascular
disease, kidney damage and lower-limb amputations.
Treatment consists of daily insulin injections. There is no cure, and no
clinically useful means of preventing this disease currently exists.
While the cause of type 1 diabetes is still not fully understood, available
evidence suggests analogs of the hormonally active form of vitamin D,
known as calcitriol or 1,25 dihydroxyvitamin D3, could play an important
role in understanding the disease and possible therapeutic solutions.
Vitamin D is essential for normal insulin secretion, and vitamin D
receptors have been described in pancreatic beta cells.
In addition, current research into therapeutic solutions focuses on
immune modulation and protection of beta cells, two characteristics of
calcitriol. Therefore, it is believed that these compounds may play an
important role as therapeutics that can be used to preserve islet cell
function and/or prevent diabetes. In nonobese diabetic (NOD) mouse
models, calcitriol has been shown to prevent the development
of diabetes.
APPLICATIONS
n
Prevention of type 1 diabetes in humans
and other animals.
KEY BENEFITS
n
proven biologically active compound
A
with beneficial effects on beta cell and
immune function.
n
Provides a safer, less calcemic compound
than the natural hormone calcitriol.
n
ffers a fresh therapeutic approach for
O
gaining access to the diabetes market.
n
Provides a drug development opportunity
in a growing market space.
n
Innovative licensing and/or development
terms available.
To modulate the immune system and protect insulin-producing beta
islet cells, vitamin D analogs can target antigen presenting dendritic
cells (DCs) and inhibit their differentiation and maturation. These
analogs cause DCs to become tolerogenic by selectively decreasing
the T-effector “attack” cells (T helper 1 cells) that can destroy islet
cells and/or by stimulating T-regulatory cells (T helper 2 cells), which
suppress the generation and function of T-effector cells.
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
While promising, the concentrations of calcitriol required
for effective diabetes prevention can be toxic. The hormone
mobilizes calcium from bones and increases intestinal
absorption of dietary calcium. Effective therapeutic
concentrations can lead to hypercalcemia; a condition
characterized by elevated blood calcium levels, alterations
in mental status, muscle weakness and calcification of soft
tissues and organs such as the heart and kidneys.
A Novel Approach to Prevention and Treatment:
Non-calcemic analogs of vitamin D
UW–Madison researchers are designing non-calcemic analogs
of calcitriol. These analogs may provide the solution to
the dose limitations of calcitriol by offering a wider dose
range and lower potential for causing hypercalcemia and its
complications. They show significant ability to preserve islet
cell function and prevent diabetes at concentrations that
do not cause bone calcium mobilization, intestinal calcium
transport or increase blood calcium to dangerous levels.
vitamin D technologies
STAGE OF DEVELOPMENT
The analogs offered in this portfolio have been subjected to
in vitro/in vivo models for early-stage pre-clinical evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
ADDITIONAL INFORMATION
For more information about the inventor(s),
see http://discoveryportal.org
n
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
WARF maintains a robust and growing portfolio of low and
non-calcemic analogs of calcitriol. Intellectual property rights
and special development incentives for commercialization in
the type 1 diabetes space are currently available.
BUSINESS OPPORTUNITY
n
iabetes affects 246 million people worldwide and nearly
D
8% of the U.S. population. By 2025 experts predict 380
million people will be afflicted with diabetes.
n
In 2007, the five countries with the largest numbers of
people with diabetes were India (40.9 million), China
(39.8 million), United States (19.2 million), Russia (9.6
million) and Germany (7.4 million).
n
lobal diabetes treatment market was valued at over $21
G
billion in 2006.
n
T he Juvenile Diabetes Research Foundation estimates
there are over 3 million people in the US with T1D and
nearly 15,000 new cases of T1D diagnosed yearly.
n
ultiple source funding is available for diabetes
M
translational research.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Non-Calcemic Vitamin D
Analogs for Multiple Sclerosis
INVENTOR
n
Hector DeLuca
The Wisconsin Alumni Research Foundation (WARF) is seeking
commercial partners interested in developing novel compounds
for the prevention or treatment of multiple sclerosis.
OVERVIEW
Multiple sclerosis (MS) is a complex and unpredictable disease of the
central nervous system. MS is thought to be an autoimmune disease
in which the immune system attacks and destroys the myelin that
insulates the nerves in the brain and spinal cord. When myelin is
damaged, the transmission of messages between the brain, spinal cord
and body is slowed or blocked, leading to diminished or lost function.
No cure for MS has been developed. Several therapies, including
anti-inflammatory steroids, naturally occurring antiviral proteins known
as interferons and immunosuppressive agents, have shown some
promise for the treatment of MS symptoms. However, these treatments
are associated with adverse side effects and are not effective for all
patients.
The hormonally active form of vitamin D, known as calcitriol or 1,25
dihydroxyvitamin D3, has shown some ability to prevent experimental
autoimmune encephalomyelitis (EAE) in mice, a chronic relapsing brain
and spinal cord disease that resembles MS. While promising, the
concentrations of calcitriol required to achieve this therapeutic effect
are likely to cause dose-limiting hypercalcemia and are not suitable for
long-term use.
A Novel Approach for Prevention and Treatment:
Non-calcemic analogs of calcitriol
APPLICATIONS
n
Prevention and treatment for MS
KEY BENEFITS
n
proven biologically active compound that
A
may reduce the risk of developing MS or
slow the progression of the disease.
n
Provides a safer, less calcemic compound
than the natural hormone calcitriol.
n
ffers a fresh therapeutic approach for
O
gaining access to the MS therapy market.
n
Provides a drug development opportunity
in a growing market space.
n
Innovative licensing and development
terms available.
At UW–Madison, promising research is underway with several noncalcemic vitamin D analogs that show efficacy in the EAE mouse model.
These analogs may provide the solution to the dose limitations of
calcitriol by offering a wider dose range and lower potential for causing
hypercalcemia and its complications.
Continued on next page >
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
ADDITIONAL INFORMATION
For more information about the inventor(s),
see http://discoveryportal.org
n
Hector DeLuca
CONTACT INFORMATION
Please contact our licensing team at [email protected]
or 608.262.4924 to explore and discuss innovative
development pathways that are available to qualified
development interests.
Image printed courtesy of HowStuffWorks.com
BUSINESS OPPORTUNITY
n
Cure for MS is a large and unmet medical need.
n
More than 350,000 individuals in the U.S. are affected.
n
200 new cases are diagnosed each week.
n
Annual cost of MS in the U.S. is in the billions of dollars.
STAGE OF DEVELOPMENT
The analogs offered in this portfolio have been subjected to
in vitro/in vivo models for early-stage pre-clinical evaluation.
Please contact our office for updates as study data sets may
be evolving with compounds under development.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
Inventor Bios
HECTOR DELUCA
Hector DeLuca is the world’s foremost vitamin D researcher, with more than 1,500
patents and 1,120 papers to his name. He began his career in 1951 under the tutelage
of the esteemed Dr. Harry Steenbock, who brought the world vitamin D-fortified foods.
DeLuca made the critical discovery that vitamin D is a prohormone that is converted in
the body to a hormonal form. His group further elucidated the vitamin D endocrine system
based in the kidney. His lab continues to make significant academic and commercial
contributions to the vitamin D field, including the development of drugs such as Alfarol®,
Calcijex®, Rocaltrol®, Hectorol® and Zemplar®. DeLuca currently serves as the CEO and
president of Deltanoid Pharmaceuticals, a company he co-founded in 2001 to focus on
early stage development of therapies derived from vitamin D-based compounds.
MARGARET CLAGETT-DAME
Margaret Clagett-Dame is a professor of biochemistry and pharmaceutical sciences
at UW–Madison. She holds more than 70 patents and is known for her considerable
experience working with vitamins A and D. Her research focuses on the molecular action
of vitamin A in embryonic and neuronal development, as well as the discovery of synthetic
analogs of vitamin A for cancer prevention and treatment. Clagett-Dame received her B.S.
and M.S. from Pennsylvania State University, followed by her Ph.D. in biochemistry from
UW–Madison. She co-founded Deltanoid Pharmaceuticals and currently serves as vice
president and chief scientific officer.
Deltanoid Pharmaceuticals is a drug development company involved in breakthrough
treatments for diseases including osteoporosis, renal osteodystrophy and psoriasis,
among others. Vitamin D research at UW–Madison led to the formation of Deltanoid
Pharmaceuticals by DeLuca and Clagett-Dame, who wanted to ensure the development
of promising technologies with the potential to improve human health. The company’s
continued focus is to develop selected therapies through the early phases of the
drug development process and seek partners for later stage development and
commercialization. Deltanoid Pharmaceuticals specializes in designing advanced vitamin
D analogs, and several of its vitamin D-based therapies are already being tested in
human clinical trials.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org
business development and technology licensing opportunities
vitamin D technologies
The UW–Madison / WARF Advantage
The University of Wisconsin and WARF — A Single Location to
Accelerate Translational Development of New Drugs
The University of Wisconsin–Madison has the integrative capabilities to complete
many key components of the drug development cycle, from discovery through
clinical trials. As one of the top research universities in the world, and one of the
two best-funded universities in the country, UW-Madison offers state-of-the-art
facilities unmatched by most public universities.
These include the Small Molecule Screening Facility at the UW Comprehensive
Cancer Center; the Zeeh Pharmaceutical Experiment Station, which provides
consulting and laboratory services for developing formulations and studying
solubility, stability and more; the Waisman Clinical Biomanufacturing Facility; the
Wisconsin Institute for Medical Research, which provides UW–Madison with a
complete translational research facility; and soon, the Wisconsin Institutes for
Discovery, made up of innovative private and public interdisciplinary biomedical
research institutes. The highly qualified experts at these facilities are ready to
work with you to create a library of candidates for drug development.
WARF: A Leader in Technology Transfer Since 1925
Since its founding as the patenting and licensing arm of the UW–Madison, WARF
has been working with business and industry to transform university research into
products that benefit society. WARF intellectual property managers and licensing
staff members are leaders in the field of university-based technology transfer.
They are familiar with the intricacies of patenting, have worked with researchers
in relevant disciplines, understand industries and markets, and have negotiated
innovative licensing strategies to meet the individual needs of business clients.
About WARF
WARF was established in 1925 as the world’s first university-based technology
transfer office. It is a private, nonprofit supporting organization to UW–Madison,
one of the top-ranked public research universities in the U.S. WARF supports
world-class research at the university by protecting the intellectual property of
its faculty, staff and students, and licensing their discoveries to companies for
commercial use to benefit humankind. Through WARF’s work, university research
benefits the public by bringing resources back to the university to continue the
cycle of investment, research and invention.
Wisconsin Alumni Research Foundation | 614 Walnut Street, 13th Floor | Madison, WI 53726 | [email protected] | www.warf.org