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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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« What Really Makes a Biopharma Hub? | Main | Open Access For ACS Articles? »

March 5, 2013

TauRx's Funding Is Odd

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Posted by Derek

I still get inquiries about TauRx and their work on Alzheimer's. There's an awful lot of pent-up demand in that field, and it's getting worse every year. The latest is that the company has ten million more dollars in a follow-on investment option from the Dundee Corporation of Toronto.

Who they? That's what I wondered, too, and the press release occasions more questions than it answers:

Dundee Corporation is a Canadian independent publicly traded asset management company listed on the Toronto Stock Exchange (“TSX”) under the symbol “DC.A”. Asset management activities are focused in the areas of the corporation’s core competencies and include resources, real estate and infrastructure, and more recently, the agriculture sector.

What, then, are they doing investing in biopharma? You can lose your shirt over here, guys, and you can most especially lose it in Alzheimer's. TauRx also has major funding from the Genting Burhad group. And you may well ask "Who they?", too, because they're a large Malaysian company whose core business is casinos and resorts. Now, they're also into cruise ships, and oil and gas, and power generation and (perforce) real estate, but biotech would seem to be rather far down the list.

This is a. . .unique funding setup for a biopharma company. I have to think that there's a reason for it, but I'm not quite sure what the reason is. Speculation, anyone? Thanks to John Carroll of FierceBiotech on Twitter, who doesn't understand what's going on, either.

Comments (16) + TrackBacks (0) | Category: Alzheimer's Disease | Business and Markets


COMMENTS

1. Anonymous on March 5, 2013 1:52 PM writes...

Someone in the top management of Dundee Corporation was recently diagnosed with Alzheimer's?

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2. johnnyboy on March 5, 2013 3:35 PM writes...

I'm no cognoscenti in such things, but large companies or investment groups might be making these investments knowing full well that they'll never make any money, and using them as a tax write-off. They might be getting R&D tax credits for it as well, which in Canada are pretty generous.

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3. John Spevacek on March 5, 2013 3:45 PM writes...

The Toronto Stock Exchange has a reputation for being a bit "crazy".

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4. Anonymous on March 5, 2013 4:14 PM writes...

The funding source is as straightforward as the mechanism of action. See the following:

Akoury E, Pickhardt M, Gajda M, Biernat J, Mandelkow E, Zweckstetter M. Mechanistic Basis of Phenothiazine-Driven Inhibition of tau Aggregation. Angew Chem Int Ed Engl. 2013 Feb 11. PMID: 23401175

Crowe A, James MJ, Lee VM, Smith AB 3rd, Trojanowski JQ, Ballatore C, Brunden KR.Aminothienopyridazines and Methylene Blue affect Tau Fibrillization via Cysteine Oxidation.
J Biol Chem. 2013 Feb 26. PMID: 23443659

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5. Polymer Bound on March 5, 2013 4:39 PM writes...

Delaying Alzheimer's progression by 5-10 years would be great for the casino business...

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6. gippgig on March 6, 2013 12:50 AM writes...

Casinos and Alzheimer's drugs both involve a lot of gambling.

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7. newnickname on March 6, 2013 6:49 AM writes...

I'm thinking back to a now defunct biotech that was founded, funded and folded after 10-12 years as a wholly owned subsidiary of another publicly traded company that had nothing to do with biotech or pharma. As I recall, the academic lab boss whose "technology" formed the basis of the biotech was closely related to the family with a controlling interest in the public company. So I guess the public company sort of funded his academic research and his company as an "investment" (read: gift). Although the biotech did develop collaborations and deals with Big Pharma, I think it was another scam operation, disguising crappy results as Holy Grail.

I guess it's a good thing THAT doesn't happen anymore, huh!

Permalink to Comment

8. Rico on March 6, 2013 7:10 AM writes...

Could it be Dundee is just be a Canadian shell company for Genting?...maybe for some obscure tax reason, they hope (assume?) to take a writedown on the TauRx investment against profits from another part of the business.

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9. Chemist Turned Hedgie on March 6, 2013 8:16 AM writes...

Dundee is certainly not a shell company, having a market cap of C$1.7bn. They are an asset management company so this looks like a simple, early investment rather than a tax trade- if it fails, the fund loses money. However, it does look like a bit of a departure from their usual focus so #1 might well be right.

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10. Liz Moench on March 6, 2013 8:33 AM writes...

There's far too much speculation going on here when the evidence is already in the public domain! Consider that despite 18 failed Beta Amyloid studies clinical research still continued to focus on beta amyloid plaques rather than tau tangles. Even though evidence of the link to tau tangles was confirmed by Sir Martin Roth, Cambridge University 1968. In 2000, Lancet, researchers at Southampton University confirmed that when plaque was removed from patients' brains via beta amyloid therapies, cognitive decline continued due to the presence of tangles in the brain. In 2008, TauRx released the Phase 2 results at ICAD in Chicago. These results were significant. Even so, the medical community and traditional pharma investors still focused on beta amyloid plaque theory despite the many failed beta amyloid studies. This required TauRx to raise its money from alternative sources. They have had no choice. Without their innovative persistence in seeking funding, the company would not have been able to fund its global Phase 3 studies now underway, even in the light of more than 2 decades of peer reviewed published articles about tau tangles and Alzheimer's. TauRx's studies are possibly the most important ones currently being conducted in Alzheimer's today. They will be the first studies to confirm the effectiveness of a tau aggregation inhibitor. We applaud the efforts of TauRx. Follow the company on Facebook or at their corporate website www.TauRx.com it's the best way to stay informed and avoid nebulous speculation. Congratulations to the TauRx team please continue your great work!

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11. Liz Moench on March 6, 2013 8:33 AM writes...

There's far too much speculation going on here when the evidence is already in the public domain! Consider that despite 18 failed Beta Amyloid studies clinical research still continued to focus on beta amyloid plaques rather than tau tangles. Even though evidence of the link to tau tangles was confirmed by Sir Martin Roth, Cambridge University 1968. In 2000, Lancet, researchers at Southampton University confirmed that when plaque was removed from patients' brains via beta amyloid therapies, cognitive decline continued due to the presence of tangles in the brain. In 2008, TauRx released the Phase 2 results at ICAD in Chicago. These results were significant. Even so, the medical community and traditional pharma investors still focused on beta amyloid plaque theory despite the many failed beta amyloid studies. This required TauRx to raise its money from alternative sources. They have had no choice. Without their innovative persistence in seeking funding, the company would not have been able to fund its global Phase 3 studies now underway, even in the light of more than 2 decades of peer reviewed published articles about tau tangles and Alzheimer's. TauRx's studies are possibly the most important ones currently being conducted in Alzheimer's today. They will be the first studies to confirm the effectiveness of a tau aggregation inhibitor. We applaud the efforts of TauRx. Follow the company on Facebook or at their corporate website www.TauRx.com it's the best way to stay informed and avoid nebulous speculation. Congratulations to the TauRx team please continue your great work!

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12. Lane Simonian on March 6, 2013 12:38 PM writes...

I would like to hear more from Liz on the link between tau tangles and Alzheimer's disease. Does tau hyperphosphorylation interfere with neurotransmissions and/or is it something else?

I agree with Liz that it is foolish to focus on amyloid plaques after so many failed trials. And it is not a matter of just starting earlier. Some of the finidings regarding amyloid plaques is that they are not toxic in themselves,that the transition metals in amyloid plaques damage but do not kill neurons, and that the chelation of metals out of plaques does not stop the peroxynitrite-mediated killing of neurons. Amyloid plaques are both a symptom and partially cause of Alzheimer's disease but not the main cause (the main cause is likely the p38 MAPK generation of peroxynitrites).

What can be said of amyloid plaques can also be said of hyperphosphorylated tau proteins, though. Not only do peroxynitrites through the oxidation of g-protein coupled receptors and nitration of tyrosine kinase receptors contribute to the hyperphosphorylation of tau proteins they also mediate the nitration of tau proteins themseleves which prevents them from being reconstituted (just as the peroxynitrite-mediated nitration of amyloid plaques contributes to their aggregation and limits their clearance).

http://www.ncbi.nlm.nih.gov/pubmed/16816118
http://www.ncbi.nlm.nih.gov/pubmed/21903077

As far as I know targeting tau tangles, does nothing to stop the peroxynitrite-mediated nitration of NMDA receptors which results in the efflux of glutamate which causes inflammation or the influx of calcium which kills neurons. Nor does it reverse the oxidation of g-protein coupled receptors involved in sleep, mood, alertness, smell, social recognition, and short-term memory.

Tau tangles are probably a more important target than amyloid plaques but this does not address the totality of the disease. Peroxynitrite scavengers do.

Permalink to Comment

13. Anonymous on March 6, 2013 2:38 PM writes...

http://www.theglobeandmail.com/globe-investor/news-sources/?date=20130304&archive=prnews&slug=PH70448

Liz Moench is their media contact...

Permalink to Comment

14. Lane Simonian on March 6, 2013 3:26 PM writes...

Thank you for this information.

Permalink to Comment

15. matt on March 7, 2013 12:09 AM writes...

@Liz Moench: the evidence you cited was a general rah-rah for TauRX, while the post was about how and why those two particular backers came to be associated with TauRX.

For myself, I hope TauRX closes their Phase III early with positive results. I don't buy the argument that traditional pharma investors have completely fixated on amyloid, though. Even Nativis gets funding from people, and focusing on the tau pathology seems perfectly respectable and even perhaps less risky than tackling the same amyloid target the big guys are going after.

Are there risks to profitability from other companies exploiting the knowledge that TauRX's candidate was derived from methylene blue?

TauRX is based in Singapore, so a big Malaysian investor doesn't seem unusual. Wasn't there just a post about venture capital being nearby a biopharma hub? Maybe that happens elsewhere, but the venture capital just looks different from American sources. [I recall the Saudi Arabian sheikh that saved Apple's bacon, so to speak, at one low point.]

If TauRX's LMTX fails in Phase III, well, that's not a surprise for any drug these days. But IF it succeeds, perhaps the question will be "Why didn't the biopharma-focused investing community put money into this?" Perhaps they will need to do the finance equivalent of some of the soul-searching this blog does about whether good candidates are being ignored (by Lipinski rules, "ugly" functional groups or fragments, bad animal models, etc).

Whether LMTX succeeds or fails, though, there will surely be tau-targeted drugs coming.

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16. Dylan on March 7, 2013 10:33 AM writes...

We used to do business with Dundee Securities, a Canadian broker who provided a lot of investment research on Canadian biotech companies. I think there biotech analyst left and formed his own company a couple of year ago, but I think up until then they actively invested in small biotechs. I assume they are part of the same group?

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