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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
AVIGEN, INC.
(Exact name of registrant as specified in its charter)
DELAWARE
(State or other jurisdiction of incorporation or organization)
0-28272 13-3647113
(Commission File No.) (I.R.S. Employer Identification No.)
1201 HARBOR BAY PARKWAY, SUITE 1000
ALAMEDA, CALIFORNIA 94502
(Address of principal executive offices and zip code)
(510) 748-7150
(Registrant's telephone number, including area code)
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Item 5. Other Matters
In December 1998, Avigen completed a successful private placement of its
common stock and common stock warrants, raising approximately $5.8 million. In
the private placement Avigen issued an aggregate of 1,477,170 shares of its
common stock in multiple closings at the closing Nasdaq National Market price on
the respective date of issuance. The closing prices ranged from $2.25 to $4.875
per share. For every five shares purchased, each investor also received a
five-year warrant to purchase one share of the Company's common stock at a
twenty-five percent premium to the respective closing price.
In addition, Avigen has reported certain events in press releases,
including but not limited to the completion of the above transaction and the
issuance of patents, copies of which are attached hereto as exhibits and are
incorporated by reference herein.
Item 7. Exhibits
Exhibit 1. Press Release Dated November 10, 1998.
Exhibit 2. Press Release Dated December 9, 1998.
Exhibit 3. Press Release Dated January 11, 1999.
Exhibit 4. Press Release Dated January 13, 1999.
Exhibit 5. Press Release Dated January 19, 1999.
2.
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SIGNATURES
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.
AVIGEN, INC.
DATE: January 29, 1999 By: /s/ Thomas J. Paulson
--------------------------------
Thomas J. Paulson
Vice President, Finance and
Chief Financial Officer
3.
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INDEX TO EXHIBITS
Exhibit 1. Press Release Dated November 10, 1998.
Exhibit 2. Press Release Dated December 9, 1998.
Exhibit 3. Press Release Dated January 11, 1999.
Exhibit 4. Press Release Dated January 13, 1999.
Exhibit 5. Press Release Dated January 19, 1999.
4.
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EXHIBIT 1
Avigen Reports the Filing of the First IND for Gene
Therapy Treatment Of Hemophilia B
Researchers at Children's Hospital of Philadelphia Hope to Begin Human Clinical
Trials Soon
ALAMEDA, Calif. and PHILADELPHIA, Nov. 10 /PRNewswire/ -- Avigen, Inc., working
in conjunction with a research team at The Children's Hospital of Philadelphia,
announced today the filing of an Investigational New Drug (IND) application with
the FDA seeking approval of their gene therapy approach to the treatment of the
genetic disease, Hemophilia B, using Avigen's proprietary AAV vector delivery
system.
Avigen's gene therapy technology uses an AAV vector, a modified form of a
common, harmless human virus, to deliver genetic material to target cells that
will then produce the missing protein implicated in inherited and acquired
genetic disorders.
The IND is in effect an application to conduct human clinical testing; the
application must be approved by the FDA before the company can commence use of
the drug in humans. "When approved, Avigen's study will be the first clinical
trial of gene therapy in patients with hemophilia B," said Avigen President and
CEO John Monahan, Ph.D. "Our AAV vector has performed outstandingly in animal
studies," he said, "and we are anxious to replicate those same results in
humans."
Preparations are under way for the proposed Phase I trial at The Children's
Hospital of Philadelphia in collaboration with Katherine High, M.D., Director of
Research of the Hematology Division at The Children's Hospital of Philadelphia
and Associate Professor of Pediatrics at the University of Pennsylvania. The
study protocol calls for using AAV vectors to deliver the gene for Factor IX in
10 to 20 patients with hemophilia B. The protocol has already been approved by
hospital's Institutional Review Board and also by its Institutional Biosafety
Committee, essential steps prior to undertaking human trials.
According to Dr. High, who is respected throughout the world for her expertise
in both the basic science and clinical aspects of hemophilia, "AAV provides a
new way to fundamentally treat this disease. We're very excited about its
potential as a novel and greatly improved approach to treating hemophilia."
Jeanne Lusher, M.D., Chair of the Medical and Scientific Advisory Council of the
National Hemophilia Foundation said, "This is an exciting time for those of us
interested in a cure for hemophilia. One of the goals of the National Hemophilia
Foundation's CAMPAIGN FOR A CURE is to support the work of Dr. High, and others
as well, as they develop innovative approaches for the treatment of hemophilia."
Investigators will look for adverse effects associated with increasing doses,
and characterize the agent's pharmacokinetics and pharmacological actions in
humans.
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Following the successful completion of the Phase I trial, the next step will be
Phase II trials in a larger number of hemophilia patients to evaluate the
agent's effectiveness, to determine optimal dosage and dosage tolerances, and to
further identify any adverse effects or safety risks.
In preclinical studies in both small and large animal models of hemophilia B,
Dr. High and Avigen scientists have demonstrated that delivery of the gene for
Factor IX to muscle using AAV vectors significantly reduced blood clotting times
after intramuscular injection of vector. Dr. High and Avigen collaborative
researchers will update their findings in presentations to the American Society
of Hematology meeting scheduled for December 4th through the 8th in Miami Beach,
Florida.
Hemophilia B is a bleeding disorder caused by the absence or deficiency of a
blood clotting protein called Factor IX. According to the World Hemophilia
Foundation, one in 10,000 males born worldwide has hemophilia. There are two
major types of Hemophilia, called A or B. Hemophilia A, due to a lack of a blood
clotting protein called Factor VIII, is more common, with an A-to-B ratio of
four to one (4:1). Avigen later intends to extend its vector system to also
treat Hemophilia A. Existing treatment for hemophilia is both imperfect and
expensive. Currently, the estimated replacement clotting factor market size for
Hemophilia B is $200 million, and over $1 billion for Hemophilia A.
Based in the San Francisco Bay Area, Avigen, Inc., is a biotechnology company
involved in the development of gene therapy products derived from
adeno-associated virus for the treatment of inherited and acquired diseases. The
company's proposed gene therapy products are designed for in vivo administration
to achieve the production of therapeutic proteins within the body.
Except for the historical information contained herein, this news release
contains forward-looking statements that involve risks and uncertainties. The
company's actual results may differ materially from those discussed herein.
Factors that could cause or contribute to such differences include, but are not
limited to, those discussed in this press release, as well as other risks
detailed from time to time in documents filed by Avigen with the SEC, including
the report on Form 10K for the year ended June 30, 1998.
6.
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EXHIBIT 2
Avigen Issued Patent on Erythropoietin Gene Therapy
ALAMEDA, Calif., Dec. 9 /PRNewswire/ -- Avigen, Inc., (Nasdaq: AVGN - news)
today announced that the company has been issued a patent from the United States
Patent Office covering all uses for erythropoietin (EPO) delivered using
adeno-associated virus (AAV) ectors. "We are very pleased with the breadth of
the patent claims that issued," says Avigen's President and CEO, John Monahan,
Ph.D. "The broadest claim covers AAV vectors carrying the EPO gene -- regardless
of the method used to make the vector, where the vector is administered, or even
what disease is being treated."
EPO is a human protein that stimulates red blood cell production. Recombinant
EPO is commonly prescribed to patients on dialysis who suffer from anemia
associated with chronic kidney failure. Annual sales of recombinant EPO were in
excess of $1.2 billion in calendar 1997. The advantage of Avigen's AAV gene
delivery system is that a single administration provides sustained expression of
EPO, obviating the need for frequent EPO injections.
"This is just one example of Avigen's strong and growing patent position in AAV
gene delivery," says Monahan, "Our rapidly growing patent portfolio includes
commercially significant patents in AAV vector production, tissue
administration, formulations, and disease indications."
Based in the San Francisco Bay Area, Avigen, Inc., is a biotechnology company
involved in the development of gene therapy products derived from
adeno-associated virus for the treatment of inherited and acquired diseases. The
company's proposed gene therapy products are designed for in vivo administration
to achieve the production of therapeutic proteins within the body.
Except for the historical information contained herein, this news release
contains forward-looking statements that involve risks and uncertainties. The
company's actual results may differ materially from those discussed herein.
Factors that could cause or contribute to such differences include, but are not
limited to, those discussed in this press release, as well as other risks
detailed from time to time in documents filed by Avigen with the SEC, including
the report on Form 10K for the year ended June 30, 1998.
7.
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EXHIBIT 3
Avigen Announces Completion of Private Placement
ALAMEDA, Calif., Jan. 11 /PRNewswire/ -- Avigen, Inc. (Nasdaq: AVGN - news)
today announced the completion of an approximately $5.8 million private
placement of its common stock and warrants with a group of investors from the
United States, Europe, and Hong Kong.
In the private placement, the investor group purchased the shares of common
stock in multiple closings at per share purchase prices equal to the closing
prices on the Nasdaq National Market on the respective days of closing. For
every five shares purchased, each investor also received a five-year warrant to
purchase one share of common stock at a twenty-five percent premium to the
respective closing price.
The shares of common stock, the warrants and the shares of common stock
underlying the warrants have not been registered under the Securities Act of
1933 and may not be offered or sold in the United States without such
registration or an applicable exemption from such registration requirements.
Under the terms of the transaction, the Company has agreed to file a
registration statement with respect to the shares within sixty days.
Based in the San Francisco Bay Area, Avigen, Inc., is a biotechnology company
involved in the development of gene therapy products derived from
adeno-associated virus (AAV) for the treatment of inherited and acquired
diseases. The Company's proposed gene therapy products are designed for in vivo
administration to achieve the production of therapeutic proteins within the
body.
Except for the historical information contained herein, this news release
contains forward-looking statements that involve risks and uncertainties. The
Company's actual results may differ materially from those discussed herein.
Factors that could cause or contribute to such differences include, but are not
limited to, those risks detailed from time to time in documents filed by Avigen
with the SEC, including the report on Form 10-K for the year ended June 30,
1998.
8.
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EXHIBIT 4
Avigen Receives Broad Patent for Muscle Delivery of
AAV Gene Therapy
Encompasses Delivery to All Muscle Types, including Skeletal, Smooth And Cardiac
ALAMEDA, Calif., Jan. 13 /PRNewswire/ -- Avigen, Inc. (Nasdaq: AVGN - news)
today announced the issuance of U.S. Patent No. 5,858,351 to Avigen and Johns
Hopkins University covering the in vivo administration of any gene into
skeletal, smooth, or cardiac muscle tissue using adeno-associated virus (AAV)
vectors, regardless of the method used to make the vector, how the gene is
regulated, or even what disease is being treated. The research underlying the
patent was developed through the collaborative effort of scientists from Avigen
and Johns Hopkins University.
"Because of the advantages of AAV over alternative gene delivery approaches, AAV
has emerged as a leading delivery vehicle for gene therapy," said Avigen's
President and CEO, John Monahan, Ph.D. "We believe that this is a very
significant patent because it encompasses so many disease indications where
muscle could serve as a primary or preferred site of administration -- including
blood diseases such as hemophilia and anemia, cardiovascular diseases such as
restenosis, and metabolic storage diseases," he said. "Muscle administration of
the AAV vector is a simple, yet elegant and straight-forward approach to gene
therapy, as opposed to the more invasive method of injecting the vector into an
organ, such as the liver."
In the case of hemophilia for example, patients are missing the protein factor
IX that causes blood to clot. Avigen scientists have reported long-term
expression of clotting factor IX in an animal model of hemophilia B following a
single intramuscular (IM) administration of the gene for factor IX utilizing AAV
gene therapy, showing therapeutic levels of factor IX more than a year after the
initial treatment.
Although the clotting factor is normally produced in the liver, this research
indicates that muscle tissue is capable of producing the protein following IM
administration of AAV-factor IX gene therapy. "This is a significant advance,"
according to hemophilia researcher Mark Kay, M.D., Ph.D., "because it
demonstrates multiple approaches to treating the same disease, and IM
administration is a simpler treatment than infusion into the liver." Dr. Kay is
Director of the Program in Human Gene Therapy and Associate Professor in the
Departments of Pediatrics and Genetics at Stanford University School of Medicine
and a member of Avigen's Scientific Advisory Board.
This is the second patent relating to adeno-associated virus (AAV) Avigen has
been issued in the past six weeks and complements its recently issued Patent No.
5,846,528, broadly covering erythropoietin gene therapy. "The muscle patent
nicely complements our recently issued EPO patent," says Monahan. "For example,
Avigen's intellectual property now posses at least two barriers to anyone
wishing to commercialize intramuscular administration of EPO using AAV --
regardless of how it is made, used or regulated."
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Avigen scientists have observed long-term expression of erythropoietin following
a single administration of AAV erythropoietin into skeletal muscle of normal and
anemic mice. Nearly two years after administration, the mice are exhibiting
therapeutic levels of EPO.
EPO is a protein produced by the kidney that stimulates cells in the bone marrow
to produce red blood cells; it is also involved in the production of hemoglobin.
In inherited disorders such as sickle cell anemia and beta-thalassemia, the body
produces inadequate levels of, or abnormal, hemoglobin molecules. Acquired
anemias occur in patients with renal failure, AIDS, and in those receiving
chemotherapy for cancer, when the body's production of red blood cells is
inadequate. "Treating such patients through Avigen's AAV-EPO gene therapy
approach has potential value both clinically and economically," said Dr.
Monahan. The Company estimates that hundreds of thousands of patients with these
anemias are potential candidates for AAV-EPO therapy.
Based in the San Francisco Bay Area, Avigen, Inc. is a biotechnology company
involved in the development of gene therapy products derived from
adeno-associated virus for the treatment of inherited and acquired diseases. The
Company's proposed gene therapy products are designed for in vivo administration
to achieve the production of therapeutic proteins within the body.
NOTE: Except for the historical information contained herein, this news release
contains forward-looking statements that involve risks and uncertainties. Actual
results may differ materially from those discussed herein. Factors that could
cause or contribute to such differences include, but are not limited to, those
discussed in this press release, as well as other risks detailed from time to
time in documents filed by Avigen with the SEC, including the report on Form
10-K for the year ended June 30, 1998. In particular, the foregoing discussion
of the effect of patents issued involves risks and uncertainty, including the
risks: that third parties may be successful in challenging the patents; or that
new technologies will be developed that are superior in treating the diseases
targeted by the Company. In addition, the statements above regarding the
potential for gene therapy using AAV for treating humans with inherited or
acquired disorders is subject, in addition to the above, to the following risks
and uncertainties: success of gene therapy in animal models does not guarantee
that the same results will be obtained with humans; and other risks and
uncertainties inherent in the development of gene therapy products.
10.
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EXHIBIT 5
Avigen Receives Patent Covering TVI Gene Therapy
Novel System Provides Stable and Predictable Genome Integration
ALAMEDA, Calif., Jan. 19 /PRNewswire/ -- Avigen, Inc. (Nasdaq: AVGN - news)
today announced the issuance of United States Patent No. 5,843,742 covering its
targeted vector integration (TVI) technology with applications in many gene
therapy platforms. The broadest claim covers methods of integrating or inserting
genes in a stable manner into the genome of any mammalian host cell. TVI is
important since it is capable of imparting sustained long-term expression to
many gene therapy platforms.
This is the third patent relating to adeno-associated virus (AAV) issued to
Avigen in the past two months. On December 8, 1998, Avigen was issued United
States Patent No. 5,846,528 covering erythropoietin gene therapy using AAV. On
January 12, 1998, Avigen and Johns Hopkins University were issued United States
Patent No. 5,858,351 covering any muscle delivery of AAV gene therapy. "This is
an additional platform with novel properties adding to Avigen's strong and
growing patent position in gene therapy." said John Monahan, Ph.D., President &
CEO of Avigen, Inc.
TVI takes advantage of AAV's inherent ability to predominantly integrate itself
into a specific location within the human genome believed to be harmless,
thereby achieving long term expression. Moreover, it is believed that any
potential risk of tumor formation caused by the random integration of the virus
into a vital region of the host's genome is reduced.
TVI can be applied to any DNA or viral system.
"We believe that our TVI technology has utility in a wide range of gene therapy
applications where stable integration of atherapeutic gene is desired for
sustained long-term expression, and potentially adds an additional layer of
safety to many genetherapy platforms currently being used by reducing the risks
associated with random gene integration," said Dr. Monahan.
Based in the San Francisco Bay Area, Avigen, Inc., is a biotechnology company
involved in the development of gene therapy products derived from
adeno-associated virus for the treatment of inherited and acquired diseases. The
Company's proposed gene therapy products are designed for in vivo administration
to achieve the production of therapeutic proteins within the body.
NOTE: Except for the historical information contained herein, this news release
contains forward-looking statements that involve risks and uncertainties. Actual
results may differ materially from those discussed herein. Factors that could
cause or contribute to such differences include, but are not limited to, those
discussed in this press release, as well as other risks detailed from time to
time in documents filed by Avigen with the SEC, including the report on Form
10-K for the year ended June 30, 1998. In particular, the foregoing discussion
of the effect of patents issued involves risks and uncertainty, including the
risks: that third parties may be successful in challenging the patents; or that
new technologies will be developed that are superior in treating the diseases
targeted by the Company.
11.
