1. petros on December 20, 2012 9:37 AM writes...

Sad. So much for it being a top 10 CNS partnering opportunity!
http://www.prnewswire.com/news-releases/allon-selected-as-top-10-partnering-prospect-by-cns-experts-181353711.html

2. bradpalm1 on December 20, 2012 10:04 AM writes...

Another "Top Projects to Watch" in the neuroscience field at this TAP conference was Naurex's GLYX-13, an interesting tetrapeptide found to be a modulator of NMDA receptors and being currently studied for treatment-resistant depression, neuropathic pain and autistic spectrum disorders. It seems to have a ketamine-like MOA without the accompanying hallucinations and has recently some good market exposure. The trick, as always, is how to get these oligopeptides into the CNS without first being broken down in the GI tract.

3. Perdurabo on December 20, 2012 10:32 AM writes...

Quotes from the PR Newswire article are a bit ominous:
"strategic review [to] include all options for exploiting Allon's assets"
and
"The Company will also take immediate action to reduce its ongoing operating expenses including a reduction in staff."

4. RB Woodweird on December 20, 2012 10:45 AM writes...

Somebody got hosed, eh?

"Allon Therapeutics‘ target price was increased in a recent report by Neil Maruoka of Canaccord Genuity.

“We have taken this opportunity to update our assumptions ahead of key clinical data for davunetide. With a stronger balance sheet that should allow the company to reach pivotal data, we have increased our expected probability of success for this drug to 50% from 40%. We believe that this still represents a relatively high risk profile for a pivotal study; nonetheless, we recommend that risk-tolerant investors position themselves ahead of this key potential catalyst based on a solid risk-return profile,” said Maruoka. “We value Allon using an explicit NPV model of the global opportunity for davunetide in FTD. We have revised our 12-month target to C$1.00 (from C$0.65), which continues to support our SPECULATIVE BUY recommendation."

5. newnickname on December 20, 2012 12:03 PM writes...

Josh Chamot from the Parabon Press Release threads might want to look at the Allon Press Releases. (I've only looked at the two linked by Derek.) As biotech press releases go, there isn't very much hype. A "sad day for patients, family members, and caregivers ... so many of them held out great hope that these results would define a drug that has an impact on their disease ... we do believe that we designed the correct study and executed that study well." They didn't blame the poor results on too low a dose, an already sickened patient population, statistically insufficient data, Hurricane Sandy or anything else. They are NOT making any Big Promises about another trial with different endpoints, nothing about a 2nd generation version of the drug that will be 4x as potent or anything else. Veni, vidi, defecit.

6. NJBiologist on December 20, 2012 12:37 PM writes...

@2 bradpalm1: "The trick, as always, is how to get these oligopeptides into the CNS without first being broken down in the GI tract."

Actually, that's one of them, and it's a big one, but another equally big one will be sidestepping the minefield of CNS side effects that has accompanied pretty much every one of the numerous attempts to modulate the NMDA receptor in the past. This problem has been widespread enough that I'd ask for multiple successful phase II trials before dismissing side effect liabilities.

7. bradpalm1 on December 20, 2012 2:15 PM writes...

NJB: very true, although I would point to the relatively benign side effect profiles of amantadine and memantine, two structurally similar small molecule NMDA modulators which also demonstrate similar neuroprotective properties. Naurex's tetrapeptide, GLYX-13, apparently acts as a partial agonist of NMDAs receptor at the glycine binding site which is distinct from the NMDA glutamate binding site. Perhaps this helps explain its more benign profile in these Phase II trials.

I also find it intriguing that the growing recognition of NMDA modulators like amantadine and memantine (which have recently been repurposed as potential treatments for traumatic brain injury and concussions in the case of amantadine, and autism in the case of memantine) point the way to the future therapeutic potential of manipulating NMDA and AMPA receptors in these states. With the recent failure of Lilly's rigid glutamate analogs in clinical trials, elegant drugs like GLYX-13 could usher in a new exciting area of critically needed drug development.

8. Anonymous on December 20, 2012 4:46 PM writes...

Memantine binds in the pore, not the glycine binding site. Mind you so does ketamine; memantine just comes off easier and is use dependent.

Any reason why a peptide partial agonist of the glycine site would be any better than the small molecule ones that exist? If i had to guess maybe some unknown interaction at an GluN1 splice variant that may be distributed favourably.