Pharmaceuticals Develops First Novel Oral Compounds Which Demonstrate
Regenerative Activity In Animal Models of Parkinson's Disease Three posters
to be presented today ..

Source: PR Newswire

BALTIMORE, Md., Nov. 18 /PRNewswire/ via Individual Inc. -- Guilford
Pharmaceuticals Inc. (Nasdaq: GLFD) reported that it will present data today
at the Society for Neuroscience Meeting in Washington D.C. on a novel class
of orally active small molecule compounds the company has discovered, the
neuroimmunophilins, which for the first time demonstrate a potent
regenerative effect in rodent models of Parkinson's Disease.

"Parkinson's Disease is considered to be one of the most debilitating
neurodegenerative disorders, and is believed to affect over 800,000
Americans. Previously, protein-based neuronal growth factors, such as NGF
and GDNF, have been shown to increase neuronal cell growth in animal
experiments of Parkinson's Disease. However, proteins and peptides are very
difficult to administer for neurodegenerative disorders, because they are
not orally active, and do not get into the brain," commented Dr. Peter
Suzdak, Vice President of Research at Guilford Pharmaceuticals.

The animal models of Parkinson's Disease studied by Guilford involve
administration of one of two neurotoxins, either MPTP or 6-hydroxydopamine,
to rats or mice. These neurotoxins selectively destroy the parts of the
brain which deteriorate in Parkinson's Disease, and are thus used as animal
models to study the effects of potential therapeutic drugs for Parkinson's
Disease.

The first of Guilford's presentations, scheduled for 1:00 p.m. today, will
show the effects of a novel, orally active Guilford compound, GPI-1046, in
various experiments administering either MPTP to mice or 6-hydroxydopamine
to rats. The experiments were conducted in two ways.

First, with simultaneous administration of GPI-1046 with a neurotoxin, to
evaluate the neuroprotective effect, and second, administration of GPI-1046
some time after the neurotoxin, to evaluate the neurotrophic, or
regenerative effect. In all experiments, GPI-1046 was administered
systemically, including by oral administration.

The results of the first series of experiments showed that simultaneous oral
administration of GPI-1046 with MPTP produced approximately an 85%
neuroprotective effect. "To our knowledge, these results are the most
significant neuroprotective effect ever demonstrated in this animal model of
Parkinson's Disease, and appear to be much greater than has been previously
demonstrated with protein growth factors," commented Dr. Suzdak.

The second series of experiments involved administering GPI-1046 some period
of time after either MPTP or 6-hydroxydopamine, also including with oral
administration. The significance of these experiments is that Guilford's
neuroimmunophilin compound was given for the first time after the
degeneration in the brain had occurred. In the first set of this series,
GPI-1046 was administered to mice 8 days after MPTP, and produced an
approximately 45% regeneration of dopaminergic neurons. In the second set of
experiments, GPI- 1046 was given to rats either one week or one month after
6-hydroxydopamine. 6-hydroxydopamine is a very potent neurotoxin, which
experimentally results in an extremely severe lesion and destruction of
almost all of the nigro-striatal dopaminergic neurons in the rat brain. The
results of these experiments showed that GPI-1046 produced approximately a
40% regeneration of dopaminergic nerve terminals in the striatum in the
brain, regardless of whether it was given one week or one month after the
6-hydroxydopamine.

Furthermore, GPI-1046 was also able to improve the functional recovery of
the rats. In assessments of various behavioral effects of 6-hydroxydopamine,
GPI-1046 appeared to produce near-normal behavior.

"The results obtained with GPI-1046 are to our knowledge unprecedented and
the first ever demonstration of a nerve regenerative effect with an orally
active small molecule," commented Dr. Suzdak. "I know of nothing which has
previously demonstrated both such a potent regenerative effect on damaged
brain neurons, and a near-normalization of animal behavior, as we have shown
with GPI-1046. These results may have potentially significant implications
for the treatment of neurodegenerative disorders such as Parkinson's Disease
and Alzheimer's Disease in people. If we are able to demonstrate a similar
regenerative effect in humans, for the first time ever we may be able to
slow the deterioration, or even reverse some of the effects and restore
functioning, to patients with these debilitating degenerative disorders.
Some of our newer series of neuroimmunophilin compounds, all synthesized by
Guilford, are even more potent and appear significantly more effective in
animal models than GPI-1046."

Guilford Pharmaceuticals and its academic collaborators has been conducting
research with the neuroimmunophilins since the early 1990's, beginning with
the observations of neurotrophic effects with some commonly used
immunosuppressive compounds, such as FK-506 and cyclosporin. In May 1996,
Guilford made the first public presentation of scientific data on the
neuroimmunophilins at the IBC Neurotrophin Meeting in London, England. At
that meeting, Guilford disclosed that it had discovered the novel mechanism
of action responsible for the neurotrophic effects of the
neuroimmunophilins, a cascade of events initiated by inhibition of FKBP-12
mediated rotamase (peptidyl-prolyl isomerase) enzyme activity. Guilford also
disclosed at that meeting that its scientists had discovered and
demonstrated for the first time a separation of the neurotrophic and
immunosuppressive effects of this class of compounds.

The second of Guilford's three posters to be presented at the Society for
Neuroscience Meeting will show experimental data on GPI-1046 in a cell
culture model designed to assess the potency of the compound. In this
experiment, using chick dorsal root ganglia cells (sensory neurons),
GPI-1046 demonstrated an ED50 (effective dose to achieve a 50% maximal
effect) of 53 picomolar. "These results show that not only are our compounds
very effective in animal models, but they are also extremely potent -- even
more so than protein neuronal growth factors such as NGF, which in our
experiments has an ED50 of approximately 300 picomolar", continued Dr. Suzdak.

The third of Guilford's poster presentations will describe the discoveries
first made by Guilford scientists in separating the neurotrophic from
immunosuppressive effects of compounds such as FK-506, and the discovery of
FKBP-12 mediated rotamase inhibition as the novel mechanism of action that
produces the neuronal growth effects.

"Guilford is committed to the development of novel, orally active
neurotrophic agents for a wide range of neurodegenerative disorders," said
Dr. Craig Smith, Guilford's President and C.E.O. "In studies over the past
several years, we previously demonstrated the neurotrophic and
neuroprotective activity of our novel compounds in a variety of other
earlier animal models, such as the sciatic nerve crush in rats, a model of
peripheral nerve injury. In these studies, our compounds appeared to produce
a near-complete restoration of both nerve structure and behavioral function.
We also demonstrated for the first time a potent effect of our compounds to
restore myelin levels, which are necessary for normal functioning of
neurons. Other experiments we performed showed that our compounds have
regenerative effects on other types of brain neurons, such as serotonergic
and other neurons. We also have an extensive intellectual property
portfolio, with numerous patent applications dating back to the early
1990's. Based on our promising results, we are moving forward with further
research and development of our novel neuroimmunophilin compounds for
Parkinson's Disease, Alzheimer's Disease, multiple sclerosis, peripheral
neuropathies, traumatic head and spinal cord injuries, and stroke. We now
have a library of several hundred active compounds, and are currently
conducting studies in primates. We intend to initiate clinical studies with
the first of our neuroimmunophilin ligands by the end of 1997 or early 1998."

Guilford Pharmaceuticals Inc. is a biopharmaceutical company engaged in the
development of polymer-based therapeutics for brain and other cancers, and
novel products for the diagnosis and treatment of neurological diseases,
including Parkinson's disease, Alzheimer's disease, stroke, 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 Company's most recently
filed SEC documents, such as the Forms 10-K and 10-Q and its current report
on Form 8-K filed on September 24, 1996, that could cause the Company's
actual results and experience to differ materially from anticipated results
and expectations expressed in these forward-looking statements. In
particular, the pre-clinical results are based on a limited number of animal
models, and there can be no assurance that the company will be able to
successfully develop one or more of its compounds into a safe and effective
FDA-approved drug. While the company has filed numerous patent applications
in the U.S. and abroad, the patentability, validity, enforceability, and
non-infringement of claims made in such applications cannot be assured.

Guilford Pharmaceuticals press releases available through Company News On-
Call by fax, 800-758-5804, ext. 112882, or at http://www.prnewswire.com

SOURCE Guilford Pharmaceuticals

/CONTACT: Angela Webber of Guilford Pharmaceuticals Inc., 410-631-6449; or
Brad Miles (media) of Ted Klein & Company; or Jonathan Fassberg (investor)
of The Trout Group, 212-477-9007/ (GLFD)

[11-18-96 at 13:34 EST, PR Newswire]