Ariad patents molecule for treatment of Parkinson Disease

March 2014 Patent re use of ponatinib for PD


[0064] In pharmacokinetic experiments in rodents, We have
found that the potent multi-kinase inhibitor, ponatinib, can
actually accumulate in brain to levels betWeen tWo- and three
foldhigher than inblood. This Was an unexpectedly fortuitous
?nding. The very favorable accumulation of ponatinib in
brain combined With its signi?cant inhibitory potency against
kinases such as Abl, permits delivery of pharmacologically
relevant concentrations of drug to the brain, e.g., at levels
effective to inhibit the phosphorylation of parkin in brain
Which has been associated With the development of PD. This
noW makes compounds of Formula I such as ponatinib very 
attractive agents for treating PD.


[0065] As discussed herein, this disclosure provides a 
method for treating PD by administering to a patient in need 
thereof an effective amount of a compound of Formula I such 
as ponatinib or a pharmaceutically acceptable salt thereof. 

Therapy
[0068] Therapy according to the invention may be provided
at home, the doctor’s of?ce, a clinic, a hospital’s outpatient
department, or a hospital. Treatment generally begins at a
hospital so that the doctor can observe the therapy’s effects
closely and make any adjustments that are needed. The dura
tion of the therapy depends on the age and condition of the
patient, the stage of the patient’s Parkinson’s disease, and
hoW the patient responds to the treatment. Additionally, a
person having a greater risk of developing Parkinson’s dis
ease (e.g., a person Who is genetically predisposed) may 
receive ponatinib therapy to inhibit or delay symptoms of the 
disease.

etc., as illustrated beloW.
[0174] For example, White opaque capsules Were prepared 
containing nominally 2 mg of ponatinib free base, provided as
the hydrochloride salt, With no excipients. White opaque cap
sules Were also prepared containing 5 mg, 15 mg, or 20 mg of
ponatinib free base, provided as the hydrochloride salt, mixed
With conventional excipients.

Applicant’s oWn WO 2007/075869, Which is hereby
incorporated herein by reference for all purposes, discloses
certain compounds that inhibit inter alia Abl. One notable Abl
inhibitor is ponatinib, Which is currently the subject of a
clinical trial to determine the e?icacy of ponatinib in patients
With chronic myeloid leukemia (CML) in chronic phase (CP),


Korean Patent Info

Open Letter to Ariad Investor Relations about the next molecule, aka "The God Molecule"

Investors: IF YOU AGREE with this open letter, PLEASE SEND Kendra Adams of Ariad Investors Relations (Kendra.adams@ariad.com) a message 

Dear Ms. Adams,

For quite some time now, Dr. Berger and others in Ariad management have been talking about the imminent announcement of a  Best in Class" new molecule for an "unmet medical need." Yet, in spite of multiple promises for nearly a year, we've heard absolutely nothing. Not a word, not a peep, not a clue.  And in the meantime, the share price of Ariad continues to plummet leaving many if not most small investors under water.  

So the question that all small  investors are asking, and the one I believe we deserve an answer to without further delay, is when will the "Mystery Molecule" be revealed?

With kind regards,

Trading Cyclist

New patent for our old friend pona?

Ariad applied for a patent in 2013, and was awarded same on July 15th 2014.   What follows here, after a brief commentary, are excerpts from the full patent record which can be found at  US Patent no. 8,778,942.   My layman's take away from this patent award is that ponatinib (Iclusig)  is better than we think, and is a  a potential replacement for Gleevec  - up to 10X more powerful, and with applications for a wide variety of cancers (including lung and pancreatic cancer).   Read the patent and draw your own conclusions.    

-------------------------------------------------
5. Uses, Formulations, Administration 

Pharmaceutical Uses; Indications 

This invention provides compounds having biological properties which make them of interest for treating or ameliorating diseases in which kinases may be involved, symptoms of such disease, or the effect of other physiological events mediated by kinases. For instance, a number of compounds of this invention have been shown to inhibit tyrosine kinase activity of Src and abl, among other tyrosine kinases which are believed to mediate the growth, development and/or metastasis of cancer. A number of compounds of the invention have also been found to possess potent in vitro activity against cancer cell lines, including among others K-562 leukemia cells. Observed potencies have been as much as 10-fold more powerful than Gleevec in conventional antiproliferation assays with K562 cells. 

Such compounds are thus of interest for the treatment of cancers, including both primary and metastatic cancers, including solid tumors as well as lymphomas and leukemias (including CML, AML and ALL), and including cancers which are resistant to other therapies, including other therapies involving the administration of kinase inhibitors such as Gleevec, Tarceva or Iressa. 

Such cancers include, among others, cancers of the breast, cervix, colon and rectum, lung, ovaries, pancreas, prostate, head and neck, gastrointestinal stroma, as well as diseases such as melanoma, multiple myeloma, non-Hodgkin's lymphoma, melanoma, gastric cancers and leukemias (e.g., myeloid, lymphocytic, myelocytic and lymphoblastic leukemias) including cases which are resistant to one or more other therapies, including among others, Gleevec, Tarceva or Iressa. 

Resistance to various anticancer agents can arise from one or more mutations in a mediator or effector of the cancer (e.g., mutation in a kinase such as Src or Abl) which correlate with alteration in the protein's drug binding properties, phosphate binding properties, protein binding properties, autoregulation or other characteristics. For example, in the case of BCR-Abl, the kinase associated with chronic myeloid leukemia, resistance to Gleevec has been mapped to a variety of BCR/Abl mutations which are linked to a variety of functional consequences, including among others, steric hindrance of drug occupancy at the kinase's active site, alteration in deformability of the phosphate binding P loop, effects on the conformation of the activationloop surrounding the active site, and others. See e.g. Shah et al, 2002, Cancer Cell 2, 117-125 and Azam et al, 2003, Cell 112, 831-843 and references cited therein for representative examples of such mutations in Bcr/Abl which correlate with drug resistance.   

Again, we contemplate that compounds of this invention, both as monotherapies and in combination therapies, will be useful against leukemias and other cancers, including those which are resistant in whole or part to other anticancer agents, specifically including Gleevec and other kinase inhibitors, and specifically including leukemias involving one or more mutations in BCR/Abl, within or outside the kinase domain, including but not limited to those noted in any of the foregoing publications. See in particular Azam et al. and references cited therein for examples of such mutations in BCR/Abl, including, among others, mutations in the drug binding cleft, the phosphate binding P loop, the activation loop, the conserved VAVK of the kinase beta-3 sheet, the catalytic alpha-1 helix of the small N lobe, the long alpha-3 helix within the large C lobe, and the region within the C lobe downstream of the activation loop.

Cliff Notes Guide to Ariad Message boards: intro for new investors

New to ARIA? Cruising the bulletin boards?   Here's everything you need to know to stay sane, and not take any of it too seriously...

Yahoo: 75% adolescent potty humor, 15% pumping and bashing, and 10% absolute gems of investing insight (thank you Bart H. , SullyinFL and MikiesBack). Problem is you have to wade through (or try to block) all the potty humor and pumping and bashing, and that gets incredibly tiring.  That said, in spite of the grotesque potty humor, there's something unmistakably honest about this place, which is why I keep going back. At the end of the day, we're just gamblers, however clever we think we are or how many degrees we might have. All that's quite clear on Yahoo.

StockTwits: Good folks, nobody gets emotional, or pathological... There is a  fair amount of pumping and bashing (which you'll find anywhere), but also genuine camaraderie whatever your viewpoint might be.  People share good intel, links, and it's a fun place to spend some time.  Down side is that posts are limited to 140 characters...which, as you'll see in a minute, might actually be an upside.  I'm migrating back there, as it's a good, comfortable, smart place to respectfully trade ideas about your investment.

iHub: Just, absolutely...amazing. And infuriating. The site is dominated by two bashers (former longs), sir 2da and Dr. BiotechResearcher (aka, BR) who, like the worst broken record on the planet, play their mournful, pompous laments about the stupidity of Ariad management (in particular its MD CEO) and the futility of investing in Ariad  again and again and again. And again.  I don't know who these guys are in real life, but I imagine them to be prune like, bitter old white guys whose lives (and investments) have not turned out as they hoped.  They are bitter, that much is clear...and they need to move on.  That said, there are also some extremely intelligent, insightful and well researched posts (thank you Jesspro, STOCKSEEK and Amplekind) that are must reads for any new investor.  I'd just recommend that you put the bitter old white guys on "ignore" from the get go -  you'll have a much better experience.

Good luck to all.

TC