Here's info on the retinoids slated to enter the clinic next year:
Allergan Ligand Retinoid Therapeutics, Inc. Announces Three Potential New Clinical
Candidates
Presentations Today At Hambrecht & Quist
SAN FRANCISCO, Jan. 7 /PRNewswire/ -- Allergan Ligand Retinoid
Therapeutics, Inc. (ALRT) (Nasdaq: ALRIZ) presented scientific information
today on three advanced preclinical compounds from the ALRT pipeline at least
two of which are expected to be designated as clinical candidates during 1997.
"ALRT268 (an RXR selective agonist), an RAR alpha agonist, and an RAR
antagonist are all advancing swiftly through advanced pre-clinical evaluation,
and we expect to make decisions selecting at least two of the three compounds
this year to go into human trials in 1998," according to Marvin E. Rosenthale,
Ph.D., ALRT President, who presented today at the 15th Annual Hambrecht &
Quist Healthcare Conference.
Scientists previously have discovered that there are six retinoid
receptors in two subfamilies. The Retinoic Acid Receptors (RARs), alpha,
beta, and gamma, are intracellular receptors (IRs) that mediate a variety of
critical cellular activities, including cell proliferation and
differentiation. The RXRs (Retinoid X Receptors) are IRs that also mediate a
variety of critical cellular activities, including regulation of programmed
cell death called apoptosis and regulation of metabolism. Compounds which can
selectively stimulate specific subsets of retinoid receptors have been shown
to have promise as potential therapeutics that can deliver significant
clinical benefits.
"Based on results from animal studies, we believe ALRT268 has potential in
non-insulin dependent diabetes mellitus (NIDDM or human type II diabetes),"
Dr. Rosenthale said.
Using two mouse models of NIDDM (the db/db mouse and ob/ob mouse), ALRT268
was compared to treatment with a thiazolidinedione (TZD) which is a member of
a new class of investigational anti-diabetes drug and a control group (15
animals in each group.)
The animals were treated daily with ALRT268 over 14 consecutive days, and
glucose, triglycerides and insulin levels were monitored throughout the
duration of the treatment.
* ALRT268 significantly decreased the levels of blood glucose by 40%,
triglycerides by 45% and insulin by 60%, at the termination of the study.
* ALRT268 maintained the antidiabetic activity during the course of
therapy.
* ALRT268, as a single agent, was as effective as a second generation
TZD.
* ALRT268 demonstrated additive therapeutic effects when administered
with TZD.
* ALRT268 was well tolerated throughout the treatment period.
NIDDM is a metabolic disorder affecting primarily adult individuals and is
characterized by profound changes in glucose regulation and a cascade of
associated hormonal and metabolic disturbances. Elevated levels of glucose
(hyperglycemia) and triglycerides (hypertriglyceridemia) as well as increases
in insulin (hyperinsulinemia) levels due, at least in part, to the ensuing
insulin resistance are part of the metabolic profile seen in these patients.
ALRT268 acts as an insulin sensitizer leading to a significant reduction in
hyperglycemia, hypertriglyceridemia and hyperinsulinemia in animal models of
NIDDM.
"This quarter, ALRT will also decide on the clinical potential of a
topical RAR antagonist which is a potential compound for use as treatment or
prevention of systemic retinoid induced mucocutaneous toxicity," Dr.
Rosenthale said. "We have a good lead candidate which functions as a potent
antagonist to RAR agonist activity. This is important because the most
notable side effects of currently marketed retinoids with sales in excess of
$400 million such as all-trans retinoic acid (ATRA), 13 cis-retinoic acid etc.
appear to be associated with activating the RAR subfamily.
"Finally, ALRT expects to make a decision during 1997 about the human
clinical potential of an RAR alpha selective agonist. In vitro studies have
indicated that the RAR alpha compound has a high degree of selectivity for
receptors inhibiting proliferation in human leukemias and breast cancer cell
lines. This compound does not stimulate other receptor subtypes (RAR
beta/gamma) which are responsible for undesirable side effects such as
mucocutaneous and bone toxicity," Dr. Rosenthale explained.
These three compounds are ALRT's proprietary retinoid-based compounds.
Allergan Ligand Retinoid Therapeutics, Inc. was formed in 1994 to discover and
develop drugs based on retinoids. Retinoids have a broad range of biological
actions, and evidence suggests they may be useful in the treatment of a
variety of cancers including leukemias and certain metabolic, skin and eye
diseases. The Company's lead product, topical Panretin(TM) Gel (ALRT1057), a
retinoid receptor pan-agonist, is in pivotal Phase III clinical trials for the
treatment of cutaneous Kaposi's sarcoma (KS). Pivotal Phase II/III clinical
trials for the treatment of acute promyelocytic leukemia are being launched
for oral Panretin Capsules. International Phase II clinical trials for the
treatment of various cancers, including renal cell carcinoma (in Canada and
the U.S. in combination with interferon alpha), non-Hodgkin's lymphoma,
multiple myeloma, prostate cancer, ovarian cancer, KS, and breast cancer as
well as myelodysplastic syndrome are also being conducted with Panretin
Capsules. Phase II trials are also being conducted for benign indications in
psoriasis and proliferative vitreoretinopathy (PVR) with Panretin Capsules.
This press release contains certain forward looking statements by ALRT and
actual results could differ materially from those described as a result of
factors including, but not limited to, the following. There can be no
assurance: (a) that the preclinical results described herein will be observed
in patients; (b) that these or any new products under development by ALRT will
receive approval from the U.S. Food and Drug Administration or other
authorities to market any of these products; or (c) that, if approved, there
will be a commercial market for the products.
NOTE: If you would prefer to receive Ligand's press releases via email,
please inform us at investors@ligand.com and request to be placed on our
priority email list.
SOURCE ALRT
CONTACT: Susan E. Atkins, Vice President, Corporate
Communications and Investor Relations of Ligand Pharmaceuticals,
619-550-7687 |
