I haven't noticed that he's smart. I've noticed that he can increase the price of generics. I guess some might respect that. I definitely do not.
And it is so simple, pointing to crappy biotechs. I don't often short, maybe three times in twenty years. Have nothing against those who short crap, but it is just so easy.... can't imagine why you respect his calls, but, hey, floating boats.
I've never seen anything like the array of form 4s that we've seen from this price-raise shop, feel that CEOs should not day trade their own issue, and wouldn't be upset at all if SEC puts him away or permanently on shelf. Very simply and accurately put, he pumped and he dumped.
Have you noticed that he misses milestone guidance?
Regarding "scam".... here are recent publications from PTC, published in J. Med. Chem., Science, and Nature Medicine. Please feel free to show me what RTRX has going for it in the "respected science" file.
;-)
J Med Chem. 2014 Mar 13;57(5):2121-35. doi: 10.1021/jm401621g. Epub 2013 Dec 4.
Structure-activity relationship (SAR) optimization of 6-(indol-2-yl)pyridine-3-sulfonamides: identification of potent, selective, and orally bioavailable small molecules targeting hepatitis C (HCV) NS4B.
Zhang N1, Zhang X, Zhu J, Turpoff A, Chen G, Morrill C, Huang S, Lennox W, Kakarla R, Liu R, Li C, Ren H, Almstead N, Venkatraman S, Njoroge FG, Gu Z, Clausen V, Graci J, Jung SP, Zheng Y, Colacino JM, Lahser F, Sheedy J, Mollin A, Weetall M, Nomeir A, Karp GM.
1PTC Therapeutics, Inc. , 100 Corporate Court, South Plainfield, New Jersey 07080, United States.
A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the optimal combination of substituents at the indole N-1, C-5, and C-6 positions and the sulfonamide group to limit the potential for in vivo oxidative metabolism and to achieve an acceptable pharmacokinetic profile. Compound 4t has excellent potency against the HCV 1b replicon, with an EC50 = 2 nM and a selectivity index of >5000 with respect to cellular GAPDH. Compound 4t has an overall favorable pharmacokinetic profile with oral bioavailability values of 62%, 78%, and 18% in rats, dogs, and monkeys, respectively, as well as favorable tissue distribution properties with a liver to plasma exposure ratio of 25 in rats.
at Med. 2014 Jan;20(1):29-36. doi: 10.1038/nm.3418. Epub 2013 Dec 1.
Self-renewal as a therapeutic target in human colorectal cancer.
Kreso A1, van Galen P2, Pedley NM3, Lima-Fernandes E4, Frelin C5, Davis T6, Cao L6, Baiazitov R6, Du W6, Sydorenko N6, Moon YC6, Gibson L3, Wang Y3, Leung C3, Iscove NN7, Arrowsmith CH8, Szentgyorgyi E9, Gallinger S10, Dick JE11, O'Brien CA12.
Author information
11] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
2Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
31] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
4Structural Genomics Consortium, Toronto, Ontario, Canada.
51] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
6PTC Therapeutics, South Plainfield, New Jersey, USA.
71] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. [3] Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
81] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Structural Genomics Consortium, Toronto, Ontario, Canada. [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
9Department of Pathology, Toronto General Hospital, Toronto, Ontario, Canada.
101] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [2] Fred Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
111] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. [3].
121] Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. [2] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. [3] Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada. [4].
Abstract
Tumor recurrence following treatment remains a major clinical challenge. Evidence from xenograft models and human trials indicates selective enrichment of cancer-initiating cells (CICs) in tumors that survive therapy. Together with recent reports showing that CIC gene signatures influence patient survival, these studies predict that targeting self-renewal, the key 'stemness' property unique to CICs, may represent a new paradigm in cancer therapy. Here we demonstrate that tumor formation and, more specifically, human colorectal CIC function are dependent on the canonical self-renewal regulator BMI-1. Downregulation of BMI-1 inhibits the ability of colorectal CICs to self-renew, resulting in the abrogation of their tumorigenic potential. Treatment of primary colorectal cancer xenografts with a small-molecule BMI-1 inhibitor resulted in colorectal CIC loss with long-term and irreversible impairment of tumor growth. Targeting the BMI-1-related self-renewal machinery provides the basis for a new therapeutic approach in the treatment of colorectal cancer.
Science. 2014 Aug 8;345(6197):688-93. doi: 10.1126/science.1250127.
Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy.
Naryshkin NA1, Weetall M1, Dakka A1, Narasimhan J1, Zhao X1, Feng Z2, Ling KK2, Karp GM1, Qi H1, Woll MG1, Chen G1, Zhang N1, Gabbeta V1, Vazirani P1, Bhattacharyya A1, Furia B1, Risher N1, Sheedy J1, Kong R1, Ma J1, Turpoff A1, Lee CS1, Zhang X1, Moon YC1, Trifillis P1, Welch EM1, Colacino JM1, Babiak J1, Almstead NG1, Peltz SW3, Eng LA4, Chen KS4, Mull JL5, Lynes MS5, Rubin LL5, Fontoura P6, Santarelli L6, Haehnke D6, McCarthy KD4, Schmucki R6, Ebeling M6, Sivaramakrishnan M6, Ko CP2, Paushkin SV4, Ratni H6, Gerlach I6, Ghosh A6, Metzger F7.
1PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA.
2Section of Neurobiology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
3PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA. friedrich.metzger@roche.com speltz@ptcbio.com.
4SMA Foundation, 888 Seventh Avenue, Suite 400, New York, NY 10019, USA.
5Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
6Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland.
7Roche Pharmaceutical Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland. friedrich.metzger@roche.com speltz@ptcbio.com.
Spinal muscular atrophy (SMA) is a genetic disease caused by mutation or deletion of the survival of motor neuron 1 (SMN1) gene. A paralogous gene in humans, SMN2, produces low, insufficient levels of functional SMN protein due to alternative splicing that truncates the transcript. The decreased levels of SMN protein lead to progressive neuromuscular degeneration and high rates of mortality. Through chemical screening and optimization, we identified orally available small molecules that shift the balance of SMN2 splicing toward the production of full-length SMN2 messenger RNA with high selectivity. Administration of these compounds to ?7 mice, a model of severe SMA, led to an increase in SMN protein levels, improvement of motor function, and protection of the neuromuscular circuit. These compounds also extended the life span of the mice. Selective SMN2 splicing modifiers may have therapeutic potential for patients with SMA. |
