Subject:
Alliance Pharmaceutical Corp. Update
Date:
Tue, 4 Aug 1998 18:06:11 -0700
From:
Gwen Rosenberg <owner-owner@allp.com>
Reply-To:
Gwen Rosenberg <GHR@allp.com>
August 4, 1998
UPDATE ON IMAGENT(R)...
We are pleased to report recent progress with Imagent, the ultrasound
contrast agent being developed by Alliance in conjunction with
Schering AG, Germany. In addition to the Phase III studies announced
previously, we have initiated new clinical (human) studies with the
product, for which Alliance will receive a $2 million milestone
payment from Schering. In the past few months we have also completed
construction of a commercial-scale manufacturing facility, extended
our patent portfolio, and presented data regarding Imagent studies at
a number of scientific conferences. A summary of these activities is
provided below.
CLINICAL DEVELOPMENT
Cardiology (Heart) Studies
Imagent is intended to increase the information provided by
conventional ultrasound examinations of the heart. More than 15
million echocardiology procedures are conducted in the United States
each year. Additional patients could potentially benefit from
ultrasound diagnosis of myocardial perfusion (blood flow in the heart
muscle), which is currently assessed by nuclear medicine imaging
tests.
Phase III Cardiology Function Studies - Enrollment is continuing in
the Phase III cardiology function studies initiated in March. These
multicenter trials are designed to demonstrate the use of Imagent to
aid in the evaluation of cardiac function as assessed by both ejection
fraction and endocardial border definition. Ejection fraction is an
indication of the amount of blood pumped by the heart, and
visualization of the endocardial border assists in the diagnosis of
heart wall motion irregularities.
Phase II Myocardial Perfusion Study - A Phase II feasibility study is
underway to investigate the use of Imagent for ultrasound assessment
of myocardial perfusion defects. Patients enrolled in this study
have a suspected myocardial infarct (blockage) or ischemic heart
disease (oxygen deficiency). The study is designed to evaluate the
ability of Imagent to enhance ultrasound images of perfused myocardium
in order to differentiate normal heart muscle from areas of ischemia
under stress conditions. The successful use of Imagent for this
indication could permit earlier detection of coronary abnormalities
before permanent damage has occurred.
General Sonography ("Radiology") Studies
More than 15 million ultrasound scans are conducted in the U.S. each
year to determine blood flow in the major organs, patency (openness)
of blood vessels, and vascularity of tumors. Malignant tumors,
however, are often surrounded by a disorderly network of small blood
vessels that are difficult to visualize using conventional ultrasound
techniques. By increasing detection of these vessels, Imagent could
help differentiate among normal, benign, and malignant tissues. The
ability of Imagent to enhance organ and blood vessel images obtained
during color Doppler, gray-scale, and harmonic ultrasound is being
investigated in several clinical studies.
Phase II Liver and Kidney Study - Enrollment has been completed in a
Phase II study in which Imagent was used to enhance visualization of
space-occupying lesions such as tumors and cysts in the liver and
kidney. The additional information obtained from contrast-enhanced
images could help distinguish healthy tissue from organ lesions,
thereby improving the early detection of abnormal masses.
Phase II Prostate Feasibility Study - A clinical study has been
initiated to assess use of Imagent to classify lesions in the
prostate. Patients included in this study have a high likelihood of
prostatic lesions as determined by abnormal prostate serum antigen
tests or digital rectal exams. Enhancement of ultrasound images using
Imagent could potentially help radiologists and urologists better
target areas for biopsy, enabling the physicians to make faster and
more accurate diagnoses and begin appropriate treatment sooner.
Phase II Breast Feasibility Study - A clinical study involving
patients with suspected breast lesions is underway. The primary
objective of this study is to evaluate the ability of Imagent to
enhance visualization of blood flow in mammographically detected
breast lesions in order to help classify the lesion as benign or
malignant. Better characterization of breast lesions could
potentially reduce the number of unnecessary biopsies conducted on
patients with atypical mammograms. This information may also assist
the physician in determining optimal management of follow-up
treatment.
PATENTS
Alliance is continuing to expand our ultrasound imaging patent
portfolio. We currently have eight United States patents, including
two new patents issued this year. A number of additional patent
applications are pending in the U.S. and elsewhere.
On March 31, 1998, Alliance was issued United States Patent No.
5,733,527, entitled "Methods for Harmonic Imaging with Ultrasound."
The issued claims, which complement Alliance's previous broad harmonic
imaging patent, cover the use of specific second generation ultrasound
contrast agents with harmonic imaging methods. In addition to
covering the use of Alliance's commercial embodiment of Imagent,
individual claims specify harmonic imaging methods using contrast
agents comprising perfluoropropane, perfluorobutane, perfluoropentane,
and sulfur hexafluoride, as well as mixtures of fluorinated and
nonfluorinated gases.
On February 24, 1998, Alliance was issued United States Patent No.
5,720,938, entitled "Systems for the Formation of Microbubbles." This
"article of manufacture patent" describes kits and systems used to
prepare microbubble ultrasound contrast agents. It broadly covers
systems capable of forming injectable ultrasound contrast agents
composed of microbubbles that contain fluorocarbon vapor. In addition
to covering Alliance's commercial embodiment of Imagent, various
claims cover ultrasound contrast agent kits incorporating other
fluorocarbon gases and powders, as well as fluorocarbon gases and
liquids.
SCIENTIFIC PRESENTATIONS
Alliance is continuing to support preclinical studies that explore
additional potential uses for Imagent. The following are results from
studies that have been published or presented at recent scientific
meetings:
* Three-Dimensional Harmonic Gray-Scale Ultrasound Visualization
of Vascular Anatomy
(American Institute of Ultrasound Medicine, March 1998)
Conclusions: High-resolution harmonic imaging with Imagent
provided superior vascular contrast compared to standard gray-scale,
color Doppler, and power Doppler imaging, and achieved near complete
suppression of background tissue signal. 3-D visualization allowed
clear appreciation of vascular anatomy, even for tortuous vessels.
* Gated Three-Dimensional Ultrasound Imaging of the Coronary
Arteries using Contrast and Harmonic Imaging
(American Institute of Ultrasound Medicine, March 1998)
Conclusions: High-resolution harmonic imaging with Imagent
and gated 3-D techniques offered a superior method for evaluating the
coronary artery anatomy and observing cardiac dynamics. The high
contrast and spatial resolution achieved with Imagent allowed
recognition of vessels with higher temporal resolution and without
blooming artifacts common with color/power Doppler.
* Flow Velocity Profile Estimation using B-mode Ultrasound and
Contrast
(American Institute of Ultrasound Medicine, March 1998)
Conclusions: It is difficult to assess blood flow in vessels
viewed in cross-section using standard Doppler techniques. The use of
Imagent in combination with B-mode imaging allowed visual assessment
as well as quantitative estimation of blood flow velocity profiles
across a vessel and potentially in a tissue cross-section.
* Vascular Echogenicity on B-mode High-Resolution Harmonic Imaging
as a Function of Velocity and Contrast Concentration
(American Institute of Ultrasound Medicine, March 1998)
Conclusions: High-resolution harmonic imaging with Imagent
displayed B-mode images that allow the differentiation of arteries
from veins, regardless of direction of blood flow.
* Myocardial Blood Volume Decreases Distal to a Stenosis during
Hyperemia: Basis for Stenosis Detection by Contrast
(American Institute of Ultrasound Medicine, March 1998)
Conclusions: Myocardial blood volume is decreased in the
region distal to stenosis (the tissue located downstream to a
blockage). The magnitude of the volume decrease, which is
proportional to the severity of the stenosis, can be detected by the
use of Imagent in conjunction with coronary vasodilators.
* Sonographic Ventriculography: A New Potential Use for Ultrasound
Contrast Agents in Neonatal Hydrocephalus
(Society for Pediatric Research, May 1998)
Conclusions: Sonographic ventriculography enhanced with
Imagent showed potential for identifying patency of cerebrospinal
fluid pathways in newborns with hydrocephalus (abnormal increase in
the amount of fluid in the cranial cavity).
* Evaluation of Dynamic Changes in Myocardial Blood Flow after
Ischemia-Reperfusion by Intravenous Myocardial Contrast
Echocardiography
(American Society of Echocardiography, June 1998)
Conclusions: Dynamic changes in myocardial blood flow have
been observed over time following reperfusion of occluded coronary
arteries. Serial changes in flow were accurately detected by
myocardial contrast echocardiography using Imagent. This approach has
potential applications in the evaluation and management of
post-ischemic reperfusion in humans.
* Assessment of Graded Coronary Stenoses Using Intravenous
Myocardial Contrast Echocardiography
(American Society of Echocardiography, June 1998)
Conclusions: Imagent correctly depicted the progressive
reduction of blood flow in the coronary arteries produced by graded
stenoses during vasodilation.
MANUFACTURING
Imagent is manufactured using Alliance's proprietary spray-drying
technology, which enables easy shipping and long-term storage of the
product. In May, major construction was completed on a new facility
in San Diego that will be used for commercial-scale manufacturing of
Imagent, as well as future manufacturing of additional products. The
56,000 sq. ft. building was designed in 1987 for electronic wafer
fabrication, and the similarities in industrial requirements for
microelectronics and pharmaceuticals provided a suitable production
facility for Alliance with minimal structural modification.
The new facility includes clean room areas that are designed to meet
Class 100 to Class 100,000 limits for non-viable particulate
contaminates (corresponding to European classes A, B, C, and D). The
versatile site will also be used for shipping and receiving, product
storage, and inspection/labeling/packaging operations, and it can
accommodate a number of laboratory activities.
CORPORATE & PRODUCT FACT SHEETS
Please visit Alliance's Internet web site at allp.com to view our
updated Alliance Corporate Fact Sheet. The Fact Sheet introduces
PulmoSpheres*, Alliance's new platform technology in early preclinical
development. PulmoSpheres are microscopic hollow/porous spheres that
contain a drug such as an antibiotic, steroid, or lung surfactant
stabilized within the shells of the spheres. The spheres are produced
by the same Alliance spray-drying technology that is used during
Imagent processing. The PulmoSpheres are then suspended in perflubron
or other fluorochemical for administration directly into the lungs via
liquid instillation (e.g. through a bronchoscope), nebulization, or
metered-dose inhalation.
A new Imagent Product Fact Sheet is also available on the web site.
This has been designed to provide "information at a glance" about the
product.
Thank you for your interest in Imagent and Alliance Pharmaceutical
Corp. Additional information about other Alliance products will be
forthcoming. If you would like to receive copies of the abstracts
cited above, and/or hardcopy color copies of the Corporate Fact Sheet
or Imagent Product Fact Sheet, please reply to this message with your
name, mailing address, and quantity of Fact Sheets requested.
Sincerely,
Gwen Rosenberg
Vice President, Corporate Communications
Except for historical information, the matters set forth in this
presentation are forward-looking statements that are subject to risks
and uncertainties that could cause actual results to differ materially
from those set forth herein. We refer you to cautionary information
contained in documents the Company files with the Securities and
Exchange Commission from time to time, including the last Form 10-K
and Form 10Q, and those risk factors set for in the recent
registration statement on Form S-3 (Registration Number 333-06739).
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