Orally active in the Rat with no sleepiness or dizziness. A reasonable dose of 375 BID in human models ...Say Bye bye to lyrica and Neurontin these are junk in comparison. I don't think we are grasping how good a drug ZLCS is sitting on.
Animal pain studies don't always translate into clinical results for humans. But we have a somewhat unusual situation here that's very good for a biotech investor.
If a drug works in rats and then later in man, what you have is proof not only that your drug manipulates a biological pathway as intended, but that it was also bio-available in man and that this manipulation of your targeted pathway translates into an effective treatment in man for some indication.
Z160 is an N-type calcium channel blocker. The rat studies showed that blocking this pathway reduces pain on a level with morphine. In rats. Good so far.
But theoretically it's entirely possible (if we had no other data) for the effect of blocking this pathway in man, even with good bio-availability, to be... well, null, nothing. There could be a redundant pathway in man that takes over for it. Lots of possible reasons for this strategy not to work in man.
EXCEPT there's Prialt (Ziconotide) out there already. It's an N-type calcium channel blocker too. And it works in man. So we don't have to worry about whether the process itself translates into man. It does. The strategy itself works. We have proof.
We just need to know that the pharmacokinetics and safety of Z160 are good. The ADME/tox, in other words. Absorption, Distribution, Metabolism, Excretion and Toxicity. And we have those data from PI and preclinical studies. And they look great.
Bottom line--a lot of the X-factors that can #$%$ up going from animals to humans and even from PI to PII have been reduced or entirely eliminated here for what could be a blockbuster, game-changing drug.
You don't get a chance like this very often in biotech investing.
Sentiment: Strong Buy
Nicely composed. Such a chance to become involved in some way in the future of pain management - thanks to market inefficiency , or whatever the reason for this price level... I hope few will quibble about the relative pennies of risk.
Rul6t2, one other thing worth noting is that even in the previously failed Phase 2 trial, there were some patients--as noted by Merck--on the previous formulation who experienced analgesia (pain relief), despite the overall lack of bioavailability. In other words, the bioavailability was enough for some patients at that time; just not most. The fact that the drug is now clearly active bodes very well for the prospects of Z160.
Isn't the rat's "no sleepiness or dizziness" we've been exposed to about 160 funny to hear in the face of the other science reported? Maybe those rats had Ben level communication skills :)
Zalicus is pretty much betting the farm on Z160. I think it will pay off BIG TIME. When Merck decided to walk away some years ago they did note that there were no adverse effects from the compound being used. Things have really moved along nicely since then and it appears as though there are still no adverse effects. I think Novartis will be eating Merck for lunch.
Sentiment: Strong Buy
In bioequivalence studies, the maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. Cmax is highly correlated with the area under the curve (AUC) contrasting blood concentration with time. Therefore, use of the Cmax/AUC ratio is recommended for assessing the equivalence of absorption rates. The ratio is independent of both intrasubject variations and possible differences in the extent of absorption and reflects only the contrast between the absorption and disposition rate constants (ka/k).
Preclinical data for Z160 is suggestive of efficacy on par with ziconotide, gabapentin, and morphine. The data is from a spinal serve ligation (Chung) model, one of the most commonly used neuropathic pain models for preclinical testing. Zalicus has confirmed that Z160 exposure in humans exceeds the minimum efficacy levels for this neuropathic pain model.
The mechanism of action for Z160 has been validated by ziconotide, marketed by Jazz Pharmaceuticals as Prialt. Prialt has well-documented clinical efficacy. The product is the only non-opioid analgesic (synthetic peptide) approved for the management of severe chronic pain in patients who are intolerant of or refractory to other treatment options. The problem with Prialt is that it must be given through intrathecal injections. The key difference between Z160 and Prialt, is that Z160 is an oral tablet with proposed dosing at around 375 mg BID; that’s less than half of the dose that Merck noted was well-tolerated without conveying serious adverse events in previous clinical studies. Prialt is also an irreversible binder of Cav2.2, whereas Z160 is state-dependent – meaning it is designed to only target and modulate those neurons transmitting pain signals.
Back in March 2006, Merck licensed the compound (originally named NMED-160) from Neuromed for $25 million upfront and potentially as much as $450 million in milestones and royalties on sales. Unfortunately, Merck returned the rights to NMED-160 back to Neuromed in August 2007 because phase 2 clinical studies, “Did not demonstrate the ideal pharmaceutical characteristics considered necessary to advance the compound further into development.” Interestingly enough, Merck did note that no serious adverse events with NMED-160 were observed in clinical trials testing the safety and effectiveness even at doses as high as 1600 mg per day. We knew from a post hoc analysis, that the Merck study had some patients who had over 400ng/mL; they had analgesia.Despite Merck walking from the collaboration, scientists at Neuromed knew they had an effective drug if they could improve the formulation. That is exactly what Zalicus has spent the past several years doing. Phase 1 data was released in March 2012. The data shows a greater than 8-fold improvement in CMax and 5-fold improvement in AUC for the new formulation of Z160 vs. the old NMED-160 compound that Merck previously believed was a blockbuster drug.