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SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF
THE SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported) November 10, 1998
NEOTHERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Delaware 000-28782 93-0979187
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(State or other jurisdiction (Commission (IRS Employer
(of incorporation) File Number) Identification No.)
157 Technology Drive, Irvine, California 92618
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(Address of principal executive offices) (Zip Code)
Registrant's telephone number, including area code:(949) 788-6700
Not Applicable
(Former name or former address, if changed since last report)
(Telephone area code changed from (714) to (949)
Page 1 of 9
Exhibit Index on Page 3
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ITEM 5. OTHER EVENTS
Reference is made to the press releases issued to the public by the
Registrant on November 10, 1998, November 11, 1998 and November 12, 1998, the
text of which are attached hereto as Exhibits 99.1, 99.2 and 99.3 for a
description of the events reported pursuant to this Form 8-K.
ITEM 7. EXHIBITS
EXHIBIT:
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99.1 PRESS RELEASE DATED NOVEMBER 10, 1998.
99.2 PRESS RELEASE DATED NOVEMBER 11, 1998.
99.3 PRESS RELEASE DATED NOVEMBER 12, 1998.
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934,
the Registrant has duly caused this report to be signed on its behalf by the
undersigned thereunto duly authorized.
NEOTHERAPEUTICS, INC.
Date: November 12, 1998 By: /s/ Samuel Gulko
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Samuel Gulko
Chief Financial Officer
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EXHIBIT INDEX
EXHIBITS DESCRIPTION
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99.1 Press Release dated November 10, 1998
99.2 Press Release dated November 11, 1998
99.3 Press Release dated November 12, 1998
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EXHIBIT 99.1
CONTACTS:
INVESTMENT COMMUNITY: MEDIA:
Carol Gruetter John Lockhart
NeoTherapeutics, Inc. Halsted Communications, Inc.
Tel: (949) 788-6700 Tel: (800) 600-7111 x.224
e-mail: [email protected] (213) 957-3111 x.224
e-mail: [email protected]
Margaret Wyrwas and Christine Seketa
Hill and Knowlton, Inc.
Tel: (212) 885-0544 or (212) 885-0350
e-mail: [email protected]
[email protected]
NEOTHERAPEUTICS ANNOUNCES RESULTS FROM FIRST U.S. CLINICAL TRIAL OF AIT-082
PRESENTED TODAY AT SOCIETY FOR NEUROSCIENCE MEETING IN LOS ANGELES
Los Angeles -- November 10, 1998--NeoTherapeutics, Inc. (Nasdaq: NEOT, NEOTW)
and the Alzheimer's Disease Cooperative Study (ADCS), a clinical research
group directed by Dr. Leon Thal and funded by the National Institute on
Aging, announced today at the 28th Annual Meeting of the Society for
Neuroscience in Los Angeles results from a Phase 1 clinical trial on
NeoTherapeutics' drug compound AIT-082 (NEOTROFIN-TM-, leteprinim potassium).
The presentation entitled "A Phase 1 Study of AIT-082 in Healthy Elderly
Volunteers" was co-authored by Dr. Michael Grundman and his colleagues at
the ADCS. The ADCS conducted a Phase 1 study of AIT-082, which represented
the first U.S. clinical trial for this drug, in eight healthy elderly
volunteers at two clinical sites. After initial treatment with a placebo, six
subjects were treated with rising doses of AIT-082 on a weekly basis. Two
volunteers received placebo throughout this double-blind trial. The study
participants tolerated the drug well without significant side effects.
Subjects tended to perform better on tests of memory and concentration when
they received AIT-082 than when they received placebo. Due to the small
number of people in this study, further testing will be required before the
effects of AIT-082 on memory can be established.
AIT-082 is a novel small molecule that, in animals, crosses the blood-brain
barrier to regenerate nerve function by increasing levels of neurotrophic
growth factors and causing nerve sprouting in the brain. Pre-clinical studies
in animals have demonstrated that AIT-082 improves memory in aged animals and
in animals with neurological deficits. Dr. Leon Thal of the University of
California, San Diego and Director of the Alzheimer's Disease Cooperative
Study commented "The unique manner in which AIT-082 acts was the basis for
the interest of the ADCS in evaluating this compound. While we are very
encouraged with the preliminary results from this limited trial, additional
larger studies are required before any
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definitive conclusion can be made regarding the efficacy of AIT-082 for the
treatment of Alzheimer's disease. The ADCS is pleased to be collaborating in
the evaluation of this drug."
Dr. Neil Buckholtz, Chief of the Dementias of Aging Branch of the National
Institute on Aging (NIA), a division of the National Institutes of Health,
said: "The NIA is very encouraged that AIT-082 proved safe in this small
group of people. We look forward to additional data from larger clinical
trials. The progress on AIT-082 reflects the accomplishments that can be
made through a productive cooperation between government and the
pharmaceutical industry."
The ADCS has recently begun its second study with AIT-082. Thirty-six
patients with mild to moderate Alzheimer's disease will participate in this
second Phase 1 study in which the participants will receive AIT-082 or a
placebo daily for seven days. The study is predominately designed to measure
safety parameters but will also look at memory improvement in the patients.
"As the first drug in human clinical trials which could promote regeneration
of nerve function in patients with Alzheimer's disease, we are very
encouraged by these positive results," said Dr. Alvin Glasky, President and
Chief Scientific Officer of NeoTherapeutics. "Based upon the clinical
results observed in this study, as well as in our other Phase 1 clinical
trials, we have accelerated the clinical development program for the use of
NEOTROFIN" (AIT-082) in Alzheimer's disease." AIT-082 is also being
evaluated in a Phase 2 clinical trial of patients with mild to moderate
Alzheimer's disease.
The Alzheimer's Disease Cooperative Study (ADCS) is a consortium of
approximately 35 academic medical centers funded by the National Institute on
Aging for the purpose of conducting clinical trials in Alzheimer's disease.
In addition to AIT-082, the ADCS has conducted clinical trials with vitamin
E, prednisone, melatonin, and estrogen. Alzheimer's disease affects
approximately four million people in the United States alone.
The National Institute on Aging has provided support to this drug through
Small Business Innovative Research grants, contracted services for drug
manufacturing (with the National Institute of Mental Health) and toxicity
testing as well as funding the ADCS clinical trials.
NeoTherapeutics' research program is focused on designing and developing
small molecules capable of promoting nerve regeneration and repair for a
range of neurological diseases and conditions such as Alzheimer's and
Parkinson's diseases, stroke and spinal cord injury. Additional compounds in
NeoTherapeutics' product pipeline address other health issues such as
migraine and depression. For additional Company information, visit the
NeoTherapeutics web site at WWW.NEOTHERAPEUTICS.COM.
This press release contains forward-looking statements regarding future
events and the future performance of NeoTherapeutics that involve risks and
uncertainties that could cause actual results to differ materially. These
risks include, but are not limited to, the early stage of product
development, the need for additional funding, the initiation and completion
of clinical trials and dependence on third parties for clinical testing,
manufacturing and marketing. These risks are described in further detail in
the Company's reports filed with the Securities and Exchange Commission.
#######
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EXHIBIT 99.2
CONTACTS:
INVESTMENT COMMUNITY: MEDIA:
Carol Gruetter John Lockhart
NeoTherapeutics, Inc. Halsted Communications, Inc.
Tel: (949) 788-6700 Tel: (800) 600-7111 x.224
e-mail: [email protected] (213) 957-3111 x.224
e-mail: [email protected]
Margaret Wyrwas and Christine Seketa
Hill and Knowlton, Inc.
Tel:(212) 885-0544 or (212) 885-0350
e-mail: [email protected]
[email protected]
FOR IMMEDIATE RELEASE
- ----------------------
NEOTHERAPEUTICS ANNOUNCES AIT-082 PREVENTS EXCITOTOXIC BRAIN DAMAGE
PRESENTED TODAY AT SOCIETY FOR NEUROSCIENCE MEETING IN LOS ANGELES
Los Angeles, November 11, 1998 -- NeoTherapeutics, Inc. (Nasdaq: NEOT;
NEOTW) announced today new and important findings on AIT-082 (NEOTROFIN-TM-,
leteprinim potassium) that may open a novel therapeutic approach to the
treatment of brain injury and stroke. The research, presented in two
presentations by Drs. Francesco Caciagli and Patrizia DiIorio and colleagues
of the University of Chieti, Italy and by Dr. Bernhard Juurlink and
colleagues of the University of Saskatchewan, describes the ability of
AIT-082 to reduce or prevent brain damage due to neuroexcitotoxins. This type
of damage contributes to the long-lasting disabling effects of stroke as well
as spinal cord and brain injuries. These reports are among seven presented
on AIT-082 at the 28th Annual Meeting of the Society for Neuroscience, held
in Los Angeles.
Dr. Juurlink's presentation - entitled "The Hypoxanthine Analogue AIT-082
Promotes Neurite Formation and Regeneration in Hippocampal Neurons,"
describes the abilities of AIT-082 to enable neurons to better withstand
normally damaging levels of glutamate, a naturally occurring neurotoxin. It
also promotes better recovery from glutamate-induced damage. It seems as if
AIT-082 might improve nerve metabolism by influencing the function of
mitochondia, the cell structures responsible for producing energy. The
results suggest that AIT-082 might be used therapeutically for the
establishment, maintenance and regeneration of synaptic connections in the
diseased central nervous system.
Dr. Juurlink said: "These encouraging results illustrate an important aspect
of the action of AIT-082. Energy is essential for all cells to function
properly, in particular cells of the brain. This action of AIT-082 could
serve as a basis for the drug's protective action seen when nerve cells are
subjected to neurotoxic injury as seen in stroke and brain trauma."
Dr. Caciagli's presentation - entitled "The Hypoxanthine Derivative AIT-082
Protects Against Neurotoxicity In Vitro and In Vivo," describes a series of
experiments which were designed to look at the protection of neurons both in
tissue culture and in the brains of animals from damage due to excitotoxic
molecules. AIT-082 enhanced the ability of neurons to withstand this type of
damage. One of the mechanisms by which AIT-082 effects this protection is by
the natural production of protective neurotrophic factors, such as nerve
growth factor. The effects of AIT-082 in these animals were confirmed by
magnetic resonance imaging (MRI) of the brain of the experimental animals.
The MRI scans showed the therapeutic effect of the drug; those animals who
were given AIT-082 showed less brain damage.
Professor Francesco Caciagli, Chairman of the Department of Biomedical
Sciences at the University of Chieti, Italy said: "These very encouraging
results can serve as the justification of evaluating AIT-082 as a therapeutic
agent from the treatment of stroke as well as traumatic brain and spinal cord
injury."
Dr. Alvin Glasky, President and Chief Scientific Officer of NeoTherapeutics,
based in Irvine, CA, stated: "We are very pleased that these exciting
experimental results from Canada and Italy have extended our knowledge about
the action of AIT-082. While our clinical program of testing AIT-082 for the
treatment of Alzheimer's disease continues at an accelerated rate, we must
give consideration to initiating clinical trials with other neurodegenerative
conditions."
NeoTherapeutics' research program is focused on designing and developing
small molecules capable of promoting nerve regeneration and repair for a
range of neurological diseases and conditions such as Alzheimer's and
Parkinson's diseases, stroke and spinal cord injury. Additional compounds in
NeoTherapeutics' product pipeline address other health issues such as
migraine and depression. For additional Company information, visit the
NeoTherapeutics web site at www.neotherapeutics.com.
###
This press release contains forward-looking statements regarding future
events and the future performance of NeoTherapeutics that involve risks and
uncertainties that could cause actual results to differ materially. These
risks include, but are not limited to, the early stage of product
development, the need for additional funding, the initiation and completion
of clinical trials and dependence on third parties for clinical testing,
manufacturing and marketing. These risks are described in further detail in
the Company's reports filed with the Securities and Exchange Commission.
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EXHIBIT 99.3
CONTACTS:
INVESTMENT COMMUNITY: MEDIA:
Carol Gruetter John Lockhart
NeoTherapeutics, Inc. Halsted Communications, Inc.
Tel: (949) 788-6700 Tel: (800) 600-7111 x.224
e-mail: [email protected] (213) 957-3111 x.224
e-mail: [email protected]
Margaret Wyrwas and Christine Seketa
Hill and Knowlton, Inc.
Tel:(212) 885-0544 or (212) 885-0350
e-mail: [email protected]
[email protected]
FOR IMMEDIATE RELEASE
- ----------------------
NEOTHERAPEUTICS DEMONSTRATES NOVEL ACTIONS FOR AIT-082 ON CENTRAL NERVOUS SYSTEM
PRESENTED AT SOCIETY FOR NEUROSCIENCE MEETING IN LOS ANGELES
Los Angeles, November 12, 1998 -- NeoTherapeutics, Inc. (Nasdaq: NEOT;
NEOTW) announced new and important findings on AIT-082 (NEOTROFIN-TM-,
leteprinim potassium) that may shed light on the novel mechanism of action of
this compound. The research, presented at the 28th Annual Meeting of the
Society for Neuroscience in Los Angeles, describes experiments undertaken to
understand the novel mechanism of action of AIT-082. AIT-082 is currently in
clinical development for Alzheimer's disease.
Researchers presented a total of seven reports on AIT-082 at the meeting.
Among these reports, "Effect of AIT-082 on Brain NGF mRNA Levels and
Transport of AIT-082 Across the Blood-Brain Barrier" describes the rapid
entry of AIT-082 into the brain after injection into animals. While the drug
remains in the brain for only a few minutes, the length of time is sufficient
for AIT-082 to trigger the nerve cells to produce natural neurotrophic
factor. This short time in the brain prevents accumulation, which helps
explain the absence of toxic side effects. When AIT-082 reaches the neurons
in the brain, it acts by rapidly turning on the gene for nerve growth factor,
the effect of which is seen by two hours. These data confirm and extend
NeoTherapeutics' claims as to the rapid and unique nature of AIT-082's
actions in the central nervous system.
In another report, "The Effects of AIT-082 on Memory in Young and Aged Mice"
confirms that AIT-082 has different actions on the central nervous system
than other drugs in development for Alzheimer's disease. Many other
experimental memory-enhancing drugs act in concert with corticosteroid
hormones to improve memory. These experiments demonstrate that AIT-082's
memory-enhancing activities are independent of these hormones. The results
of time-dependent portions of this activity point to three actions of
AIT-082. Within 30 minutes after administering AIT-082, there are minor
improvements in motor coordination and sensitivity to pain that may be
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dependent on corticosteroid hormones. Two distinct memory effects, a
short-term effect and a long lasting effect, may be due to the presence of
increased levels of neurotrophic growth factors that are not affected by
these corticosteroid hormones.
The results from these two presentations emphasize AIT-082's uniqueness and
potential for use in a variety of neurodegenerative diseases. AIT-082 is
currently in clinical development for Alzheimer's disease. NeoTherapeutics
is exploring the possibility of this compound's use in other
neurodegenerative diseases.
Dr. Michelle Glasky, Vice President for Scientific Affairs of
NeoTherapeutics, said: "These new results provide additional evidence of the
unique action of AIT-082 to produce its memory enhancing activity by
potentially causing nerve regeneration or new nerve connections called
synapses. This action could explain the difference between AIT-082 and the
other therapeutic approaches which merely increase neurotransmitters. If
nerve connections are destroyed during degeneration, increasing levels of
neurotransmitter at dead connections will have little benefit. We are
hopeful that this beneficial action seen in animal studies can be extended to
the human trials currently in progress and planned for the future."
NeoTherapeutics' research program is focused on designing and developing
small molecules capable of promoting nerve regeneration and repair for a
range of neurological diseases and conditions such as Alzheimer's and
Parkinson's diseases, stroke and spinal cord injury. Additional compounds in
NeoTherapeutics' product pipeline address other health issues such as
migraine and depression. For additional Company information, visit the
NeoTherapeutics web site at www.neotherapeutics.com.
###
This press release contains forward-looking statements regarding future
events and the future performance of NeoTherapeutics that involve risks and
uncertainties that could cause actual results to differ materially. These
risks include, but are not limited to, the early stage of product
development, the need for additional funding, the initiation and completion
of clinical trials and dependence on third parties for clinical testing,
manufacturing and marketing. These risks are described in further detail in
the Company's reports filed with the Securities and Exchange Commission.
9
