Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Enemem, If a 40% baseline variability is acceptable, a patient could have a wide range in AHI baseline readings - say 50 and 70 on nights 1 and 2. What they'll probably do is average those (60) and call that the baseline. Having only 2 data points for the baseline and one data point with drug onboard isn't ideal, but that's what we've got.
Again, so long as the drug has a consistent effect, and the variability is random, the trend could be detectable. In this case, the SD of the control data would be large, but the SD of the drug condition would be small. The trial could fail to reach statistical significance, but a trend could be apparent.
The more general point is that without a more complete picture of the data, it isn't very useful to speculate about outcomes.
Concerning a placebo effect, being a psychological effect, wouldn't one expect less placebo effect in a trial where the subject is asleep than in a trial where the subject is awake?
Placebo effects routinely have been shown to affect physiological variables that are outside of our conscious control. SA could plausibly be attenuated due to placebo effect, especially because subjects know the expected outcome of the drug treatment.
>>> If a patient has a 40% variability between baseline readings on nights 1 and 2, you have to show a really large drug effect before it even 'counts'
You don't necessarily need a large effect, just a consistent effect. The goal here isn't statistical significance, but a trend in the data.
I'm more concerned about placebo effect.
First they have to get the FDA's approval.
The problem I see is that in the short term, we're close to being back in the same trap we thought we had gotten out of: assuming good trial results and/or IND approval, by the time it comes in late summer/early fall, corx will have operating funds for under a year. Share-price is going to be about where it is now, since concern about liquidity is going to cap any substantial upward movement.
The only hope here is more than one interested party for SA and/or ADHD. Otherwise, once again counterparties will wait to get the most favorable terms. In this regime, corx is once again going to have to raise funds.
If Samyang is the institution that provides the funds, this might not be too bad. In light of this, I think that an important indicator of corx's future prospects is whether or not Samyang opts for shares rather than cash. If they opt for shares, it will suggest that they maintain interest in the IP and the company, and thus perhaps would consider a second financing. If they choose cash, corx's prospects would appear dimmer.
Everything I've written assumes pretty smooth sailing. Bad trial results and/or slippage, and/or problems with the FDA will make this bad situation considerably worse.
I think we're in for more pain and waiting here.
Respir Physiol Neurobiol. 2009 Aug 31;168(1-2):125-32. Epub 2009 Mar 21.
PHOX2B in respiratory control: lessons from congenital central hypoventilation syndrome and its mouse models.
Amiel J, Dubreuil V, Ramanantsoa N, Fortin G, Gallego J, Brunet JF, Goridis C.
a b s t r a c t
Phox2b is a master regulator of visceral reflex circuits. Its role in the control of respiration has been
highlighted by the identification of heterozygous PHOX2B mutations as the cause of Central Congenital
Hypoventilation Syndrome (CCHS), a rare disease defined by the lack of CO2 responsiveness and of breathing
automaticity in sleep. Phox2b27Ala/+ mice that bear a frequent CCHS-causing mutation do not respond
to hypercapnia and die in the first hour after birth from central apnoea. They are therefore a reliable
animal model for CCHS. Neurons of the retrotrapezoïd nucleus/parafacial respiratory group (RTN/pFRG)
were found severely depleted in these mice and no other neuronal loss could be identified. Physiological
experiments show that RTN/pFRG neurons are crucial to driving proper breathing at birth and are necessary
for central chemoreception and the generation of a normal respiratory rhythm. To date, the reason
for the selective vulnerability of RTN/pFRG neurons to PHOX2B protein dysfunction remains unexplained.
One genetic component that could contribute to this is errors in the phox2b transcription factor, which leads to CCHS (chronic congenital hypoventilatory syndrome). Patients with this condition don't have a chemosensory arousal response, so once they go into apnea, they stay there for a while. Because this mutation has variable penetrance, it's possible that people with mild CCHS and mild obesity have off-the-charts OSA.
I remember that during the RD study they showed evidence of either prevention or recovery of opioid induced sleep apnea.
You're right, and this is clinically significant since people using opioids for pain management have big SA problems. I wrote Varney with the suggestion that they run trials targeting this population only, since there's a large patient population using opioids chronically for pain management. I think the observed efficacy is due to ampakine's effects on opioid-induced respiratory depression, which is likely an important causal factor behind these subjects' SA. As such, the findings need to be interpreted carefully.
The muscle tone data is what I see as most promising for the broader population of OSA patients. I remain pessimistic about ampakines generically being a treatment for OSA, because there are so many ways to get to OSA, and there are so many interacting regulatory systems that are likely out of whack in OSA patients.
I don't know how instrumented the subjects participating in the trial were, so I don't know how unambiguously central SA and OSA can be differentiated.
The SA trial is largely out of corx's hands. The IND submission isn't. I very much hope they are moving forward on that. My fear is that they've trimmed back their staffing to a point where the necessary work takes longer to complete, or worse still, isn't completed properly (with only upper management left, I worry...).
They have to get it right.
>>Ampakines can disrupt sleep patterns... tend to cause insomnia
Well that'll take care of the SA!
Although this has always struck me as a basic problem, there may be a dosage window where airway patency is restored, but insomnia is not induced.
More narrowly, because the trial participants will only be exposed to ampakine treatment for one night, the insomnia effect will mitigated by the accumulated sleep debt of people with chronic SA. If there were a second night involved, the risk of insomnia would likely be higher.
The issues you raise are the basis for my skepticism about ampakines in SA. Physiologically, it is an incredibly complicated condition, influenced by lung volume (affected by obesity), adipose tissue (a consequence of obesity), carotid body feedback gain, central chemosensation feedback gain, strength/weakness of adaptive responses in the cerebral vasculature, and efficacy of efferent drive to the various muscle groups involved with airway patency.
This doesn't mean that I think ampakines will be useless; I think it's likely that ampakines will improve drive to motoneurons, which in turn will improve airway patency, but all the other pieces of this homeostatic regulatory circuit need to be affected in a coordinated manner. What matters here is not whether ampakines will work, but whether they will generate a positive trend in the incredibly slow, expensive, and inconclusive clinical trial that corx has undertaken.
I remain long, but I've come to see that corx's business model is not really viable. Their indication-based outlicencing strategy is problematic, since once a compound is outlicenced for one indication, it becomes much less attractive as an outlicencing candidate for other indications; it can't generate enough money from an outlicencing deal to shepherd another compound to late stage, and limited funds also preclude developing compounds in parallel, which eats away at patent life. Basically, I don't think that they can generate the funds that will allow them to enter a regime of sustained profitability.
Unfortunately, I don't take their word for it. I remember a shareholder meeting where Stoll stated that the problems with CX-717 had been laid to rest, and on the strength of that share price rose steeply... except that the FDA didn't buy it.
Even if Varney is being truthful that cx-1739 meets the tox standards that cx-717 failed to meet, and even though Laughren supposedly told Stoll that if corx brought them a compound that met all of the tox standards that were set for cx-717, he would approve the IND, I'm not counting on anything; the process is too opaque and arbitrary.
That said, I'm more confident about the IND than I am about the SA trial. I also think the IND is more important: if the approval comes through, the FDA will have given the green light for a trial using an ampakine for an indication requiring chronic use. If we get that approval, whether or not the drug shows efficacy in ADHD (I'm pretty confident about that too, since I think low impacts will act generically as cognitive enhancers), this approval will remove the taint associated with ampakines since the cx-717 debacle.
>> CX-1739 is clean
That's an assumption.
It's important that they do this soon then, but it is much more important that they do it right. If they don't get the approval, this company's survival is in doubt.
A succesful IND is the most important event confronting corx IMO.
>>IND acceptance by FDA (Psychiatric/Laughren), allowing the ADHD trial to start
Does anyone have any ideas about how close we are to corx submitting its request?
I think the RD process was an outlier. Macro factors and corx's own dire straits subverted the outcome. I don't think SA will work, although the weak trial that corx set up may generate a spurious positive result.
I don't see how this is going to work out, but that's fine with me. I'm in because to exit now would recoup ~15% of what I put in. I'm ready to risk loosing what little I have left on the chance of a good outcome. The science is good, so at least this is possible.
preparing to initiate a Phase IIa trial with CX1739
I take it this means submitting a request to the FDA. My recollection is that the FDA has 90 days to provide a decision.
All this leads me to believe that there will be no news until the fall, at the earliest.
I'm also curious to see if they in fact have the top-of-line results for SA by late summer. More conservative and more accurate predictions about their timelines would be a welcome development.
As I said, I have doubts about Iggs. A few weeks ago, she (?) stated her intention to go, so this is another opportunity to link the virtual and real worlds. It's useful to identify bashers, because then they can just be shunned out of existence.
The only person who has committed to show up is Iggs. if a seriously pissed-off woman starts chewing out corx management, then that's her.
People here (myself included) have had doubts about whether iggs is legit or a basher. Given her stated commitment to show up at the meeting, this will be a useful test.
I like the decision to keep posts away from tit-for-tat personal attacks, or even worse self-important bloviation about personal righteousness, etc.
Obviously, there would be less of this if something were actually happening with corx. Because of the nature of the business, most of the time, nothing will be. In the tedium between events, I am very happy to get a glimpse at the sector via other posters' OT messages. I hope they are retained.
Over the past few years, a person could have made a substantial amount of money shorting cor(x), aided perhaps by half-way decent bashing skills.
I don't think R&R plays a role in this, nor Samyang, since with current trading volumes and prices, an institutional investor could easily manipulate share-price.
I think what was going on was a short trade timed to come due in this pricing period. Iggs' pain is real.
I take the stability of cor share-price through the Samyang option financing window as a very good sign about corx's new partners.
This dog-that-didn't-bark situation stand in contrast to the iggnoble R&R shennanigans that have accompanied past financing deals.
The question is, why at this price? Samyang could have driven shareprice down to $0.15 without any difficulty at all, and recouped the volume of shares traded many times over because of the resulting price difference.
Based on what I've come to consider standard operating procedure in this sector, this is surprising. Does anybody have any theories about why Samyang didn't take advantage of the situation?
I am thinking they were the one sitting on 0.23-0.24 range
If you're right that they're clamping the price, it begs the question of why they don't drive the price down further. At these trading volumes, selling 300K shares would drive the price down appreciably.
The more interesting possibility is that they aren't doing anything to manipulate share price to their advantage. This is perhaps to maintain their reputation as a good partner, with an eye on facilitating future deals. If this holds up, it's a nice change from R&R.
I don't find it very surprising that we haven't seen much of an increase in share price, even though immediately after the deal I got silly. An ongoing trial is ridiculously overdue, cor is at the mercy of another FDA ruling, and everything else is currently way to vague to motivate investors. I'm guardedly optimistic, but I can understand why others aren't.
no, but it doesn't appear to have happened yet. It might create a small buying opportunity for optimists.
Let's see if Samyang decides to depress shareprice over the next few days. It would be easy, and could substantially increase their stake in the company.
There's no "FDA" in "should". Remember the 8' box?
Of the 3 events, the most important one in my estimation is the OK from the FDA. The ampakine platform was tainted by the cx-717 hold. if corx is cleared to go forward with ADHD, investors can have some confidence that a similar approval will be granted for any SA trials that would follow on the current POC trial.
Even if SA comes out positive, I think people will be waiting for evidence that the FDA is willing to consider ampakines for chronic use.
This gives us a ball-park on Samyang's conversion price, ~$0.15 assuming we stay at or near $0.18.
It will be interesting to see if shares are dumped to lower share price as the April 15 conversion deadline arrives. At these volumes, a pretty substantial reduction in share-price would be easy.
We are a penny stock now folks. That's not much to hang your hat on to get people interested. And one success by management after a series of failures is not enough to convince the masses that Cortex is back in the hunt.
The silver lining to this is that it gives the small investor a chance to buy into a company with valuable IP. This stock is cheap enough to allow someone to get a substantial number of shares without putting much money at risk. Until the BAM and other shares are cleared, share price will remain low.
All in all, this is the best buying opportunity I've seen since I've been in cor. The company is on sounder financial footing by selling IP to a highly regarded mid-cap; it has reduced its overhead by firing half its staff (not the best way to reduce overhead, but that's life); the compound it is bringing the FDA does not have the problems identified with CX717, and corx is much more aware of the risks associated with FDA submissions; it has an extraordinarily rich IP portfolio; it might even get lucky with SA; corx management have collectively had a near-death experience, and based on the last two deals they've completed, have raised their game.
Too bad I'm broke.
The most important task for corx at this point is submitting a package to the FDA that gets through. An FDA hold or an FDA rejection will do perhaps irreversible damage to the platform. An FDA approval, irrespective of trial outcome, will reassure investors about the key issue of ampakine safety. Further, because of their similar effect in animals, and because they are closely related compounds, established CX717 efficacy in ADHD predicts CX1739 efficacy as well.
They need to hire a competent consultant to ensure that lines of communication are established early in the process, and that FDA concerns are addressed. They probably have a good idea of the issues they need to address, but should take the most proactive and robust approach to this filing possible.
I think we'll end the week above $0.50
Does the current deal complicate subsequent outlicencing deals? Is there a precedent for a single compound being outlicenced to different entities for different indications?
I think there is a decent chance you'll end up a very rich man on this one. My position is about 1/10 of yours, but it's all I've got, so I'm paying attention. The irony is that at this share price, the dollar amount of my investment would have bought me 300K shares.
I just hope that some of what I've learned here helps me in the future.
Most importantly, to invest in this sector, greed and fear have to be replaced by dilligence and patience. In the last 3 months there have been 2 events where some people doubled their money with no risk. It just takes learning, watching, and waiting... lots of waiting.
Does volume reflect demand, or the limited bandwidth of OTC trading?
Is there a path back to getting listed?
another obvious benefit of these developments is that samyang's holdings will be smaller than anticipated, giving corx more options.
Amen Hallelujah
I think we're going to be alright here.
While we stagnate here, another company has shown efficacy in treating OSA:
http://ir.vivus.com/releasedetail.cfm?ReleaseID=434788
It's not necessarily so stupid to buy corx at this point. If I wasn't holding corx stock, and had money that I was willing to loose on a long-shot, I'd be buying here based on the potential upside: at least a double on a sale, and considerably higher if things start going right for the company. Thus, this surprising uptick may just reflect the actions of one or two optimistic gamblers.
That said, it's an interesting signal, since common sense and good judgement would suggest that in the absence of news this stock should drift downwards.