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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: John McCarthy who wrote (11417)11/19/1997 12:04:00 AM
From: Henry Niman  Read Replies (1) | Respond to of 32384
 
John, I think that JNJ has spent closer to $150 million with AMLN and the light at the end of the tunnel just got dimmer. I agree its a huge market and I would rate rexinoids well above Pramlintide for market size and market share.



To: John McCarthy who wrote (11417)11/19/1997 12:13:00 AM
From: Henry Niman  Read Replies (1) | Respond to of 32384
 
John, Here's LGND's press release on the stellar clinicals for oral Targretin for CTCL:
PHASE II/III Data Are Favorable for Ligand's Targretin(TM) Capsules

Multicenter Interim Findings Presented at
European Society for Dermatologic Researchers Meeting

SAN DIEGO, Sept. 29 /PRNewswire/ -- Ligand Pharmaceuticals Inc.
(Nasdaq: LGND) announced that a leading dermatologist reported on Sunday that
41 percent of early and advanced stage cutaneous T-cell lymphoma (CTCL)
patients who had been refractory or intolerant to prior therapy and then
received higher dose Targretin(TM) Capsules (LGD1069) achieved a complete or
partial response. For the group of early stage CTCL patients, 37 percent who
received higher dose Targretin Capsules achieved complete or partial response
compared to none of the patients who received a lower dose of Targretin
Capsules. Findings for patients with advanced stage CTCL who received higher
dose Targretin Capsules showed 43 percent partial response. None of the
advanced stage patients received lower dose Targretin Capsules. The interim
findings for the first 36 patients enrolled in these two multicenter Phase
II/III trials were based on the Physicians' Global Assessment of Response
provided in the protocol. CTCL is a debilitating cancer characterized
primarily by skin lesions that can affect more than 50 percent of a person's
skin surface, making day-to-day living painful and difficult.
According to Madeleine Duvic, MD, Chief of Dermatology at The University
of Texas M. D. Anderson Cancer Center and Professor of Dermatology at The
University of Texas -- Houston Medical School, who presented the interim
findings, "Targretin is very active in CTCL with an acceptable safety profile.
The oral and topical routes of administration offer advantages over parenteral
administration, and are appropriate for both limited topical disease and more
advanced stages of CTCL. Receptor selective retinoids offer patients new
therapeutic alternatives that may be disease specific."
Dr. Duvic presented the findings during a keynote address, "Novel
Therapeutic Approaches to CTCL," at the European Society for Dermatologic
Research Cutaneous Lymphoma meeting in Berlin Sunday, Sept. 28.
The interim findings of the Phase II/III trials included two groups of
patients with refractory or persistent CTCL. The first group included
15 patients with early stage CTCL, seven of whom received low doses
(6.5 mg/m2/day) of Targretin Capsules, and eight who received higher doses
(500 to 650 mg/m2/day). The second group included 21 patients with advanced
stage CTCL who received the higher doses of Targretin Capsules.
Among the eight early stage patients on higher dose Targretin Capsules,
one patient (12 percent) attained complete response (no clinical evidence of
disease); two patients (25 percent) attained partial response (defined as
greater than 50 percent improvement); four patients (50 percent) showed
stabilization of disease; none of the patients showed progressive disease; and
one patient had been treated less than four weeks and was not yet evaluable
for response. Of the seven early stage patients receiving lower doses of
Targretin Capsules, there were no complete or partial responses; one patient
(14 percent) showed stabilization of disease; five patients (71 percent)
showed progression of disease; and one patient was not yet evaluable for
response.
Findings for the 21 patients with advanced stage CTCL who received higher
dose only Targretin Capsules showed nine patients (43 percent) with partial
response; seven (33 percent) who attained disease stabilization; two
(10 percent) who had progression of disease; and three patients who had been
treated less than four weeks and had not yet been evaluated for response.
Patients in both the early and advanced stage groups who received higher
dose Targretin Capsules included one (3 percent) with complete response;
11 (38 percent) with partial response; 11 (38 percent) with stabilization of
disease; two (7 percent) with progression of disease; and four patients not
yet evaluable for response. No responses were noted in patients with the
lower dose, suggesting a dose response.
Two-thirds of the responses were noted to have begun by the time of the
first response assessment, which occurred at week four of treatment. All of
the patient responses to Targretin Capsules are ongoing, with the exception of
one partial response patient who relapsed.
"Although a number of the higher dose patients have required dose
modifications for related side effects, Targretin Capsules have been
reasonably well-tolerated in the study population," according to Richard
Yocum, MD, Medical Director of Clinical Research at Ligand. "The majority of
the higher dose drug-related adverse events consisted of reversible
neutropenia (a reduction of white blood cells) without infectious
complications and elevation of serum triglycerides," Dr. Yocum said.
Targretin is a synthetic retinoid analogue discovered by Ligand scientists
which selectively activates a subclass of retinoid receptors called retinoid X
receptors (RXRs) which play an important role in several cellular activities.
One of the most important of these activities is called programmed cell death,
or "apoptosis," a natural process by which the body rids itself of unwanted
cells. This activity makes Targretin a potentially valuable anti-cancer
agent.
Approximately 1,700 patients are newly diagnosed with CTCL each year in
the U.S. The Company estimates that the prevalence of CTCL in the U.S. is
between 11,000 and 14,000 patients. Currently, patients with refractory or
advanced stages of CTCL commonly undergo cytotoxic chemotherapy or receive
interferon in attempts to control the disease.
An interim assessment of Phase I/II clinical trials for Targretin Topical
Gel in March 1997 showed that 43 percent of CTCL patients achieved clinically
significant improvement for signs and symptoms of the disease, with no related
serious adverse events. The study included 48 patients.
Phase II/III clinical trials for Targretin Capsules in CTCL are being
conducted at approximately 35 study centers and will enroll approximately
120 evaluable patients throughout the U.S., Canada, Europe and Australia. The
Company anticipates filing new drug applications (NDAs) for Targretin Capsules
and Topical Gel upon successful completion of the Phase III studies in the
second half of 1998.
Since 1989, Ligand Pharmaceuticals Inc. has established a leadership
position in gene transcription technology, particularly intracellular receptor
(IR) technology and Signal Transducers and Activators of Transcription
(STATs). Ligand applies IR and STATs technology to the discovery and
development of small molecule drugs to enhance therapeutic and safety profiles
and to address major unmet patient needs in cancer, women's and men's health
and skin diseases, as well as osteoporosis, cardiovascular, inflammatory and
metabolic diseases.
This press release may contain certain forward-looking statements by
Ligand and actual results could differ materially from those described as a
result of certain risks and uncertainties, including, without limitation (a)
that interim results may not be predictive of any final results; (b) that
these or any new products under development by Ligand or any of its partners
may not receive approval from the U.S. Food and Drug Administration or other
authorities to market any of these products; (c) that, there may not be a
market for the drugs, if, in fact, the drugs are approved for marketing. The
Company undertakes no obligation to update these statements for events or
circumstances occurring after the date hereof.
Targretin is the trademark of Ligand Pharmaceuticals Inc.

SOURCE Ligand Pharmaceuticals Inc.

CONTACT: Susan Atkins, Vice President, Corporate Communications
of Ligand Pharmaceuticals, 619-550-7687



To: John McCarthy who wrote (11417)11/19/1997 12:18:00 AM
From: Henry Niman  Read Replies (1) | Respond to of 32384
 
Here's the press release that launched this thread:
Ligand Reports On New Indications For Targretin(TM) (LGD1069)

Preclinical studies in mouse models indicate RXR-selective retinoid may have
utility in treatment of diabetes and prevention/treatment of breast cancer

SAN DIEGO, Sept. 12 /PRNewswire/ -- Scientists from Ligand Pharmaceuticals
Inc. (Nasdaq: LGND) today reported preclinical study results at the Bear
Stearns conference in New York that indicate Targretin(TM) (LGD1069), one of
Ligand's lead retinoid therapeutics, may have utility in treating human type
II diabetes and in the treatment or prevention of breast cancer. The
preclinical data demonstrated Targretin's (LGD1069) ability to significantly
decrease blood glucose, triglyceride and insulin levels in mouse models of
human type II diabetes and human obesity. In addition, in a rat model of
mammary carcinoma, Targretin (LGD1069) reduced incidence and tumor frequency
at least as well as tamoxifen, without the undesirable reduction in mean body
weight produced by tamoxifen.
"The ability of Targretin (LGD1069) to provide therapeutic benefits in
preclinical animal models of diabetes and breast cancer reinforces the concept
that retinoid-based drugs may play a major role in treating a variety of
diseases susceptible to intervention through intracellular signaling
pathways," according to Andres Negro-Vilar, MD, Ph.D., Ligand Senior Vice
President, Research, and Chief Scientific Officer. "We will evaluate
Targretin (LGD1069) for treatment of these new indications because they
address the needs of large patient populations with few optimal therapeutic
alternatives."
Commenting on data presented at the conference, Dr. Richard Heyman, Ligand
Director, Retinoid Research, explained: "Our molecular approach to drug
discovery, coupled with our extensive understanding of retinoid action, has
led us to the identification of an unexpected and novel class of compounds
that have promise in new indications."

Preclinical Data In db/db and ob/ob Mouse Models of Diabetes
Data presented by Dr. Heyman indicate Targretin(TM) (LGD1069) may be
useful in the treatment of human type II diabetes. Using two mouse models of
human type II diabetes (the db/db mouse, and the ob/ob mouse), Targretin
(LGD1069) was compared to treatment with a thiazolidinedione (TZD), a member
of a new class of investigational antidiabetes drugs, and a control group (15
animals in each treatment group). Animals were treated daily at 3 doses for
14 consecutive days, and glucose, triglycerides and insulin levels were
monitored throughout the duration of the treatment.
* Targretin (LGD1069) significantly decreased the levels of blood glucose
by 40%, triglycerides by 30% and insulin by 20%, at the termination of the
study.
* Targretin (LGD1069) maintained the antidiabetic activity during the
course of therapy.
* Targretin (LGD1069), as a single agent, was as effective as TZD.
* Targretin (LGD1069) demonstrated additive therapeutic effects when
administered with TZD.
* Targretin (LGD1069) was well tolerated throughout the treatment period.

Non-insulin dependent diabetes mellitus (NIDDM or type II diabetes) is a
metabolic disorder affecting primarily adult individuals and is characterized
by profound changes in glucose homeostasis 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.
Targretin (LGD1069) acts as an insulin sensitizer leading to a significant
reduction in hyperglycemia, hypertriglyceridemia and hyperinsulinemia in
animal models of NIDDM.
"This suggests that these agents may be effective in the treatment of type
II diabetes," according to Dr. Heyman. "Since a key event in the actions of
Targretin (LGD1069) is the activation of RXR, this raises the intriguing
possibility that these receptors are the molecular target for the antidiabetic
action for this class of compounds.
"The translation of these animal models into the human clinical setting is
promising based on the observation by others that another class of insulin
sensitizer, the thiazolidinediones, decreased hyperglycemia, hyperinsulinemia
and hypertriglyceridemia in animal models of NIDDM and appears to be effective
in recently conducted early stage human clinical trials of type II diabetes."

Preclinical Data From NMU Rat Model of Mammary Carcinoma
Other data presented by Dr. Heyman indicate Targretin(TM) (LGD1069) may be
useful in the treatment or prevention of human breast cancer. In a
preclinical study, Targretin (LGD1069) was examined in a carcinogen-induced
(i.e. NMU) rat mammary carcinoma model system. Targretin (LGD1069) treatment
was compared to treatment with tamoxifen and a control group (15 animals in
each group) to determine the retinoid's ability to reduce tumor incidence and
tumor frequency. Palpation measurement from week five through week 12 of the
study indicated:

* Targretin (LGD1069) decreased incidence of breast tumor formation in
Sprague-Dawley rats at least as well as tamoxifen. Animals treated with
Targretin (LGD1069) experienced a 90% reduction in breast tumor incidence
versus controls. "Incidence" is the percentage of animals which form tumors
after administration of the carcinogen. By comparison, tamoxifen reduced
tumor incidence by up to 85%.
* Targretin (LGD1069) decreased the number of NMU-induced tumors per
animal at least as well as tamoxifen. Control animals had 3.0 tumors per
animal. Targretin (LGD1069) reduced the mean number of tumors per animal by
85%. Tamoxifen reduced the mean number of tumors per animal by 75%.
* Targretin (LGD1069) treatment had no dose limiting toxicities, while
tamoxifen treatment at higher doses resulted in some dose limiting toxicity
including undesirable reduction in mean animal body weight versus control
animals.
Targretin (LGD1069) is a small organic compound discovered by Ligand
scientists which selectively activates a subclass of retinoid receptors called
RXRs which play an important role in several cellular activities. One of
these activities is called programmed cell death or "apoptosis," a natural
process by which the body rids itself of unwanted cells. Targretin (LGD1069)
is being developed by Ligand in both topical and oral formulations. Topical
Targretin (LGD1069) is entering pivotal Phase III clinical trials for the
treatment of cutaneous T-cell lymphoma (CTCL). In addition, Targretin
(LGD1069) oral formulation is entering pivotal Phase II/III trials for the
treatment of CTCL and is in Phase II trials in lung cancer, head and neck
carcinoma, Kaposi's sarcoma, ovarian cancer, prostate cancer and renal cell
cancer.
Ligand Pharmaceuticals Inc., founded in 1987, is a leader in gene
transcription technology, particularly intracellular receptor (IR) technology
and Signal Transducers and Activators of Transcription (STATs), Ligand applies
IR and STATs technology to the discovery and development of small molecule
drugs to enhance therapeutic and safety profiles and to address major unmet
patient needs in cancer, women's health and skin diseases, as well as
osteoporosis, cardiovascular and inflammatory disease.
This statement contains certain forward looking statements by Ligand 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 that: (a) human clinical trials will result from the preclinical
studies discussed herein; (b) that the preclinical results described herein
will be observed in human patients; (c) that these or any new products under
development by Ligand or any of its partners will receive approval from the
U.S. Food and Drug Administration or other authorities to market any of these
products; (d) that, if approved, there will be a market for the drugs; or (e)
that preclinical results will be predictive of any final results.
Targretin (LGD1069) is the trade mark of Ligand Pharmaceuticals Inc.
If you would prefer to receive Ligand press releases via email, please
inform Ligand at investors@ligand.com and request to be placed on the priority
email list.

SOURCE Ligand Pharmaceuticals. Inc.

CONTACT: Susan E. Atkins of Ligand Pharmaceuticals, 619-550-7687


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