| To: Miljenko Zuanic who wrote (103) | 11/20/2002 2:01:28 PM | | From: scaram(o)uche | | | | J Pharmacol Exp Ther 2002 Dec 1;303(3):1189-1198
SSR182289A, a Novel, Orally Active Thrombin Inhibitor: In Vitro Profile and ex Vivo Anticoagulant Activity.
Berry CN, Lassalle G, Lunven C, Altenburger JM, Guilbert F, Lale A, Herault JP, Lecoffre C, Pfersdorff C, Herbert JM, O'Connor SE.
Sanofi-Synthelabo Research, Cardiovascular-Thrombosis Department, Chilly-Mazarin and Toulouse, France.
SSR182289A competitively inhibits human thrombin (K(i) = 0.031 +/- 0.002 &mgr;M) and shows good selectivity with respect to other human proteases, e.g., trypsin (K(i) = 54 +/- 2 &mgr;M), factor Xa (K(i) = 167 +/- 9 &mgr;M), and factor VIIa, factor IXa, plasmin, urokinase, tPA, kallikrein, and activated protein C (all K(i) values >250 &mgr;M). In human plasma, SSR182289A demonstrated anticoagulant activity in vitro as measured by standard clotting parameters (EC(100) thrombin time 96 +/- 7 nM) and inhibited tissue factor-induced thrombin generation (IC(50) of 0.15 +/- 0.02 &mgr;M). SSR182289A inhibited thrombin-induced aggregation of human platelets with an IC(50) value of 32 +/- 9 nM, but had no effect on aggregation induced by other platelet agonists. The anticoagulant effects of SSR182289A were studied by measuring changes in coagulation markers ex vivo after i.v. or oral administration in several species. In dogs, SSR182289A (0.1-1 mg/kg i.v. and 1-5 mg/kg p.o.) produced dose-related increases in clotting times. After oral dosing, maximum anticoagulant effects were observed 2 h after administration with increases in thrombin time, 2496 +/- 356%; ecarin clotting time (ECT), 1134 +/- 204%; and activated partial thromboplastin time (aPTT), 91 +/- 20% for the dose of 3 mg/kg p.o., and thrombin time, 3194 +/- 425%; ECT, 2017 +/- 341%; and aPTT, 113 +/- 9% after 5 mg/kg p.o. Eight hours after administration of 3 or 5 mg/kg SSR182289A, clotting times were still elevated. SSR182289A also showed oral anticoagulant activity in rat, rabbit, and macaque. Hence, SSR182289A is a potent, selective, and orally active thrombin inhibitor. |
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| To: scaram(o)uche who wrote (109) | 11/21/2002 8:30:06 PM | | From: Miljenko Zuanic | | | | 3Q-10Q file:
5. Debt
During the first quarter of 2002, the Company repaid a $5.0 million short-term note. During the first nine months of 2002, the Company entered into a series of loans totaling $7.9 million, payable over 36 to 48 months with interest rates of 11.12% to 11.84%, to finance the purchase of capital equipment and leasehold improvements.
Why they need loan at 12% interest? Is $75 MM too small for their appetite?
Cut the salary, work for free! Suckers! Until you have something to show.
<< We expect that substantially all of our revenue for the foreseeable future will come from corporate collaborations, license agreements, government grants, and interest earned on our cash balances.>>
Will see about that?
They added new collaboration with BMS in 08-02. Hope this one can generate clinical candidate.
<< In August 2002, we entered into a collaborative discovery and lead optimization agreement with BMS, which expires in July 2003. Under the August 2002 agreement, we agreed to assist one another in the optimization of certain BMS compounds. The Company and BMS agreed to allocate and, from time to time, reallocate research funding between the July 2000 agreement and the August 2002 agreement so that the aggregate amount of research funding committed to by BMS through July 2003 under both agreements remains unchanged. Also under the terms of the August 2002 agreement, we are eligible to receive from BMS, depending on whether stipulated milestones are met, aggregate milestone payments of up to $5.0 million for the first product developed, and are eligible to receive additional milestones if subsequent products are developed. We are entitled to receive royalties on sales of products developed pursuant to the agreement.>> |
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| To: Findit who wrote (113) | 11/26/2002 11:00:44 AM | | From: Findit | | | | Up 22% on only 18K shares traded. Those MM's sure know how to play the game. Not that I am complaining. Been waiting for this one to move for quite a while.
Jim |
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| To: Harold Neely who started this subject | 12/6/2002 12:08:51 PM | | From: scaram(o)uche | | | | OK, it's time to start weeding.......
NOMINATION AND ELECTION OF DIRECTORS
The Company's Ninth Restated Certificate of Incorporation and Bylaws provide
that the Board of Directors shall be classified, with respect to the time for
which the directors severally hold office, into three Classes: Class I, Class
II, and Class III, as nearly equal as possible in numbers of directors, as
determined by the Board of Directors. The Board is empowered to increase or
decrease the total number of directors as well as the number of directors in
each class, provided that each class continues to consist, as nearly as
possible, of an equal number of directors. The Board of Directors has currently
fixed the size of the Board at nine (9) Directors. The term of office of one
class of Directors expires each year and at each annual meeting the successors
to the Directors of the class whose term is expiring in that year are elected
to hold office for a term of three (3) years and until their successors shall
be elected and qualified.
The three directorships expiring this year are presently filled by Dr. F.
Raymond Salemme, Mr. Joshua Ruch, and Dr. William Claypool. Dr. F. Raymond
Salemme, Mr. Joshua Ruch, and Dr. William Claypool have stated that they will
stand for re-election as Directors. Upon the recommendation of the Nominating
Committee, the Board has nominated for election at this Annual Meeting Dr.
Raymond Salemme, Mr. Joshua Ruch, and Dr. William Claypool as nominees for the
class of Directors whose term expires in 2005. If the nominees are elected at
this Annual Meeting, the Board of Directors shall consist of nine (9) Directors
divided into three (3) classes of three (3) Directors each.
Dr. Salemme, Mr. Ruch, and Dr. Claypool have informed the Company that they
are willing to serve for the term to which they are nominated if they are
elected. If a nominee for director should become unavailable for election or is
unable to serve as a Director, the shares represented by proxies voted in favor
of that nominee will be voted for any substitute nominee as may be named by the
Board of Directors. |
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| To: scaram(o)uche who wrote (115) | 12/6/2002 12:11:13 PM | | From: scaram(o)uche | | | | Dr. William Claypool, 51................................................................ 2002 2005
Dr. William Claypool joined us as a director in January 2002. Dr. Claypool has
served as the CEO of Phoenix Data Systems, Inc. since June 2001. Dr. Claypool also
served as CEO of the GI Company from January 2001 to June 2001. From 1991 to
December 2000, Dr. Claypool held a number of key management positions of
increasing responsibility with SmithKline Beecham Pharmaceuticals. Most notably,
he was Senior Vice President and Worldwide Medical Director, Clinical Research
and Development from November 1998 to December 2000. Prior to his tenure with
SmithKline Beecham, Dr. Claypool was employed with G.D. Searle & Co. in
Clinical Research. Prior to beginning his career in industry, Dr. Claypool held
academic positions at the University of Pennsylvania School of Medicine, the
University of Pittsburgh School of Medicine, and the University of Illinois at
Chicago College of Medicine. He has been an active member of many organizations
including the American Thoracic Society, the American College of Chest
Physicians, the American Federation for Clinical Research, the Chicago Thoracic
Society, and the American Physiology Society. He has been published in many
highly regarded pharmaceutical publications as well. Dr. Claypool earned a B.S.
from the University of Notre Dame and an M.D. from the University of Connecticut
School of Medicine. He did his residency and fellowship at the Hospital of the
University of Pennsylvania.
Mr. Joshua Ruch, 52..................................................................... 1997 2005
Mr. Joshua Ruch has been a director with us since March 1997. Mr. Ruch is the
Chairman and Chief Executive Officer of Rho Capital Partners, Inc., an international
investment management firm which he co-founded in 1981. Prior to founding Rho
Capital Partners, Inc., Mr. Ruch was employed in investment banking at Salomon
Brothers and Bache Halsey Stuart, Inc. Mr. Ruch received a B.S. degree in electrical
engineering from the Israel Institute of Technology (Technion) and an MBA from
the Harvard Business School. Mr. Ruch also serves on the Board of Directors of
Diacrin, Inc., a public company, as well as several private companies in the
technology sector.
Dr. F. Raymond Salemme, 57.............................................................. 1993 2005
Dr. F. Raymond Salemme founded the Company in 1993, and has served as a
director since February 1993. Dr. Salemme currently serves as President and Chief
Scientific Officer, positions he has held since June 1998 and June 1996,
respectively. Dr. Salemme was Chairman of the Company from June 1996 to June
1998, and served as President and Chief Executive Officer from February 1993 to
June 1996. Dr. Salemme is co-inventor on 14 US patents covering our
DirectedDiversity(R) chemi-informatics process control technology and our
ThermoFluor assay technology. Prior to founding our company, Dr. Salemme
established drug discovery groups specializing in structure-based drug design,
biophysics, and computational chemistry at Sterling Winthrop Pharmaceuticals and
DuPont Merck Pharmaceuticals, Inc. Dr. Salemme also worked in Central Research
and Development at DuPont, where he led research in protein X-ray crystallography
and engineering, developed computational methods for crystallography and drug
design, and conducted large-scale computational simulations of proteins and
polymer systems. In 1983, Dr. Salemme founded the Protein Engineering Division
of Genex Corporation, among the first companies to use X-ray crystallography and
molecular modeling for genetically engineering proteins. From 1973 to 1983, Dr.
Salemme was Professor of Biochemistry at the University of Arizona and published
extensively in the areas of molecular structures of redox proteins, the theory of
biological electron transfer and protein architecture. Dr. Salemme received a B.A. in
Molecular Biophysics from Yale University (with exceptional distinction) and a
Ph.D. in Chemistry from the University of California, San Diego, where his Ph.D.
thesis solved one of the first high-resolution 3-D protein structures by X-ray
crystallography. In addition to duties at 3DP, Dr. Salemme serves on several
corporate scientific and academic advisory boards, as well as federal advisory
committees on advanced technology and biotechnology, including the National
Institute of Science and Technology (NIST) Visiting Committee on Advanced
Technology and advisory committees for the National Institutes of Health. |
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