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Exhibit 99.1
FOR IMMEDIATE RELEASE
CONTACTS:
Amgen Guilford Pharmaceuticals
Denise Powell (investor) Angela Webber
(805) 447-4346 (410) 631-6449
David Kaye (media) Brad Miles (media)
(805) 447-6692 Jonathan Fassberg (investor)
BMC/The Trout Group
(212)-477-9007
AMGEN ACQUIRES RIGHTS FROM GUILFORD PHARMACEUTICALS FOR BREAKTHROUGH
NEUROTROPHIC AGENTS
BALTIMORE, MD and THOUSAND OAKS, CA, August 21, 1997 -- Guilford
Pharmaceuticals Inc. (NASDAQ:GLFD) and Amgen (NASDAQ:AMGN) today announced that
they have entered into an agreement granting Amgen worldwide rights for
Guilford's FKBP-neuroimmunophilin ligands, a novel class of small molecule
neurotrophic agents that may represent a new approach in the treatment of
neurodegenerative disorders.
Neuroimmunophilin ligands are a novel class of small molecule orally active
neurotrophic agents, which are being developed to promote nerve regeneration
and repair in neurodegenerative disorders.
Under the terms of the agreement, Amgen will receive worldwide rights to
FKBP-neuroimmunophilin compounds for all human therapeutic and diagnostic
applications. Amgen will conduct and pay for all clinical development and
manufacturing of products, and will market products worldwide.
Under the terms of the agreement, Amgen will pay Guilford in several phases.
Guilford will receive a total of $35 million in rights payments upon closing,
in the form of a $15 million cash signing payment, $15 million for purchase of
Guilford equity, plus a $5 million purchase of 700,000 warrants exercisable at
150% of the purchase price.
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Amgen Acquires Neuroimmunophilin Neurotrophic Agents from Guilford
Pharmaceuticals
August 21, 1997
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Amgen will also provide $13.5 million over three years to support research
activities at Guilford on the neuroimmunophilin program. The agreement
contemplates milestone payments for up to in ten specified indications, seven
neurological (Parkinson's Disease; Alzheimer's Disease; Stroke; Peripheral
Neuropathies; Traumatic Brain Injuries; Traumatic Spinal Cord Injuries; and
Multiple Sclerosis), and three non-neurological indications. Guilford would
receive development milestone payments for each indication and could receive up
to $392 million in milestone payments if all ten indications are successfully
developed to approval.
Guilford will also receive royalties on product sales. Guilford also has the
option in the future to conduct Phase I and Phase II clinical development of
one product in one indication, and to co-promote one product in the U.S., for
which certain costs would be paid by Amgen. If Amgen elects to exercise its
warrants this would represent an additional equity investment of approximately
$25 million in Guilford.
"We are extremely pleased and enthusiastic to collaborate with Guilford on the
development and commercialization of this important class of potential
neurological medicines," Said Gordon Binder, Amgen's Chairman and Chief
Executive Officer. "The science supporting Guilford's work holds the promise of
yielding breakthrough treatments for a variety of neurological disorders and
complements Amgen's expertise and commitment to neuroscience and small molecule
drug research and development programs," he said.
"This is another major milestone for Guilford. Amgen is a leader in the
development of innovative therapies for neurological disorders. We believe that
our neuroimmunophilin ligands could potentially be one of the most important
new developments in the treatment of neurodegenerative disorders in many years.
If we are able to substantially slow the rate of or reverse the progression of
neurodegenerative disorders in patients, this would represent a major
breakthrough in the treatment of these serious diseases", commented Dr. Craig
R. Smith, President and Chief Executive Officer of Guilford.
"We received a great deal of interest from many companies for our
neuroimmunophilin program. We chose Amgen because we were impressed with their
commitment to the area, and their demonstrated capability in pre-clinical and
clinical development. We appreciate being able to work with such an outstanding
partner in the development of innovative neurological products", continued Dr.
Smith.
Amgen is a global biotechnology company that discovers, develops, manufactures
and markets human therapeutics based on advances in cellular and molecular
biology.
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Amgen Acquires Neuroimmunophilin Neurotrophic Agents from Guilford
Pharmaceuticals
August 21, 1997
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Guilford Pharmaceuticals Inc. is a biopharmaceutical company engaged in the
development of polymer-based therapeutics for cancer, and novel products for
the diagnosis and treatment of neurological diseases, including Parkinson's
disease, Alzheimer's disease, stroke, severe head trauma, spinal cord injuries,
multiple sclerosis, peripheral neuropathies, and cocaine addiction.
###
This press release contains forward-looking statements that involve risk and
uncertainties, including those described in the section entitled "Risk Factors"
from Guilford Pharmaceuticals registration statement on Form S-3, declared
effective April 7, 1997, that could cause the Company's actual results and
experience to differ materially from anticipated results and expectations
expressed in these forward-looking statements. Among other things, there can be
no assurance that any of the compounds which are the subject of this
collaboration will earn milestone payments or that such compounds can be
successfully developed into safe and effective FDA-approved drugs, and
consummation of this transaction is subject to compliance with
Hart-Scott-Rodino requirements.
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Background Information - Neuroimmunophilin Ligands
August 21, 1997
Guilford Pharmaceuticals, Inc. discovered a novel class of compounds, the
neuroimmunophilin ligands, that may be capable of regenerating nerves damaged
by injury and neurodegenerative diseases such as Alzheimer's Disease and
Parkinson's Disease. These neuroimmunophilin ligands consist of small organic
molecules which have activity that is comparable or superior to NGF, BDNF, and
other protein neurotrophic factors, but are active following oral
administration.
Neuroimmunophilin ligands appear to have several advantages over previous
nerve-regeneration compounds. NGF, BDNF and other neurotrophic factors are
proteins, very large molecules that cannot pass into the brain. They cannot be
taken orally as a pill, and therefore must be administered by injection
directly into the brain. Guilford's small molecule neuroimmunophilin ligands
can be administered orally and are capable of going from the bloodstream into
the brain. Their mechanism of action appears to specifically target damaged
nerve cells while leaving healthy cells alone, making it likely that these new
compounds should have fewer side effects than earlier generations of drugs.
Immunosuppressive drugs such as cyclosporin A and FK-506 are known to bind to
intracellular proteins called immunophilins. Starting in 1990, scientists at
Guilford and Johns Hopkins University, under Dr. Solomon Snyder, Director of
the Department of Neuroscience, made the seminal discovery that immunophilin
binding proteins are enriched at up to 50-fold higher concentrations in the
brain than in immune tissue. In addition, it was discovered that drugs that
bind to immunophilin binding proteins, such as FK-506 and cyclosporin A, widely
used immune suppressive drugs used by organ transplant recipients, can produce
nerve growth in vitro (in test tube experiments) and in vivo (in animal
experiments) (i.e. they are neurotrophic). Guilford scientists, utilizing
state-of-the-art structure-based drug design techniques, synthesized a series
of novel small molecule neuroimmunophilin ligands which possess the
neurotrophic activity of FK-506, but are devoid of the undesired
immunosuppressive activity of FK-506.
Parkinson' s Disease Experimental Models
Some of Guilford's work in this area was published earlier this year
(Proceedings of the National Academy of Sciences, Volume 94 pp. 2019-2024,
March 1997; Nature
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Background Information - Neuroimmunophilin Ligands
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Medicine, Volume 3, Number 4 pp. 421-428, April 1997), presentations at the
American Academy of Neurology and American Chemical Society meetings in April
1997, and other scientific abstract presentations in 1995. These studies showed
that one of Guilford' s novel compounds, GPI-1046, promoted both morphologic
and functional recovery in animal models of both peripheral nerve injury and
Parkinson' s disease. The studies showed that in a mouse model of Parkinson's
disease, GPI-1046 showed potent neuroprotective and regenerative effects on the
nigral-striatal dopamine system, an area of the brain damaged in Parkinson's
disease.
In these studies, the neurotoxin MPTP was administered to severely damage
nigral-striatal dopamine neurons and mimic the damage caused by Parkinson's
disease, simultaneously with GPI-1046. Compared with the MPTP/control group,
GPI-1046 protected more than 80% of the nigral-striatal dopamine neurons.
The studies went one step further in an attempt to more accurately model human
Parkinson's disease by administering GPI-1046 after damage of the
nigral-striatal dopamine neurons had taken place. This "modeling" was
accomplished by administering two different neurotoxins, either MPTP or
6-hydroxydopamine. In these experiments, GPI-1046 was administered up to one
month after striatal dopamine neurons were destroyed by the neurotoxin.
GPI-1046 significantly increased the number of functional dopamine terminals in
the striatum at doses a low as 4 mg/kg. Administration of GPI-1046 was also
shown to significantly improve both neuronal dopamine levels and turnover,
indicating physiological recovery. Furthermore, administration of GPI-1046 was
also shown to significantly improve functional behavior in the rats, as
measured by apomorphine or amphetamine induced rotational behavior.
Guilford has conducted studies which have looked at other neurological models
in addition to Parkinson's Disease, and found protective and regenerative
effects using GPI-1046. In animals whose sciatic nerves were crushed, GPI-1046
accelerated functional recovery of the damaged nerves. The compound was able to
regenerate the myelin sheath over the nerves, a characteristic critical to
nerve re-growth, and functional recovery.
Potent Neurotrophic Effects
Very low doses of these neuroimmunophilin ligands have been shown to markedly
stimulate nerve growth, repair, and re-myelination in a wide variety of cell
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Background Information - Neuroimmunophilin Ligands
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culture and animal models. The compounds have been shown to be both orally and
systemically active and to cross the blood brain barrier. Guilford has made
major breakthroughs in chemistry, and has successfully synthesized small
molecule neurotrophic factors with low picomolar or even femtomolar potency
(GPI-1046 in vitro ED50=53 pM; GPI-1216 in vitro ED50 = 0.25 pM).
Potential Clinical and Commercial Applications
The neuroimmunophilin program is conducting research to explore the potential
utility of these compounds in a number of potential applications of serious and
life-threatening neurodegenerative disorders:
Alzheimer's Disease
Parkinson's Disease
Multiple sclerosis
Peripheral neuropathies - i.e. diabetic neuropathy; cancer chemotherapy
induced neuropathy, hereditary sensory and motor neuropathies; motor
neuron disorders such as ALS Traumatic head injuries
Traumatic spinal cord injuries
Stroke - aiding recovery following stroke or other cerebral ischemic
events.
There are also several non-neurological potential applications which are being
studied with the neuroimmunophilin ligands.
Guilford has filed over 20 composition of matter and use patents covering
five distinct chemical structural series of novel neuroimmunophilin compounds.
One patent has been issued in the U.S., and several others published in Europe.
Several extremely potent series of compounds have been identified, including
GPI-1234, GPI-1305, GPI-1308, GPI-1312, GPI-1216, GPI-1152, and GPI-1046, which
are under pre-clinical development.
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Background Information - Neuroimmunophilin Ligands
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Contacts:
Amgen Guilford
Denise Powell (investor/media) Angela Webber
(805) 447-4346 (410) 631-6449
Jeanne Flynn, Pharm. D. (patients) Brad Miles (media)
(805) 447-3390 Jonathan Fassberg (investor)
BMC/The Trout Group
(212) 477-9007