11/11/15 by BiotechInvestAXON (biotech scam, but valuable one because promise new Alzheimer's disease drug )
Axovant Sciences Ltd., a clinical-stage biopharmaceutical company, focuses on the acquisition, development, and commercialization of therapeutics for the treatment of neurodegenerative disorders. It develops RVT-101, a product candidate that plans to commence a Phase III pivotal program for the treatment of Alzheimer's disease and other forms of dementia. The company was formerly known as Roivant Neurosciences Ltd. and changed its name to Axovant Sciences Ltd. in March 2015. Axovant Sciences Ltd. was founded in 2014 and is based in Hamilton, Bermuda.
One my subscriber asked me how I know that some biotechs are scam but other ones are gems. Answer is simple: I'm using the combination of intuition and professions experience and knowledge to analyze the science that underlie each exact biotech company.
So, let's analyze AXON
Will not talk about Axovant founder - it's useless. Question is what kind of science underline new AD drug? What is RVT-101?
"RVT-101 is an orally administered neurotransmitter-targeted therapy with the potential to improve cognition, function, and behavior in patients with dementia. RVT-101 works by antagonizing the 5HT6 receptor in the brain, thereby enhancing the release of acetylcholine, a neurotransmitter, which is understood to have critical effects on cognition and function in patients with dementia."
Other source said:
"It’s true that RVT-101 missed its primary endpoint in not one but four clinical trials. The first three tested RVT-101 by itself, when most Alzheimer’s experts say RVT-101 would work best when used with an older drug like Aricept.
One explanation is that both RVT-101 and Aricept work by raising brain levels of a neurotransmitter critical for thinking, called acetylcholine. The older drugs do this by preventing acetylcholine from being cleared from the brain. Think of this as blocking a drain. RVT-101, they believe, makes more acetylcholine, like turning up a faucet. Unless the drain is blocked, the extra neurotransmitter just gets cleared away.
The fourth study, which included 683 patients, is more complicated. The Food and Drug Administration requires Alzheimer’s drugs to improve both how well patients think (called “cognition”) and how well they function (can they dress themselves, or brush their teeth?). In a 684-patient study, patients who received RVT-101 and Aricept simultaneously saw brain cognition decline 1.5 points less on a 70-point scale than those who got Aricept alone over 48 weeks. And they declined 2 points less on a 78-point scale that measured how well they functioned. But the trial failed because Glaxo researchers had named a different endpoint on function where the result was not statistically significant. Looking at the whole of the database, though, it really looks like the drug did have an effect on both cognition and function."
And another source said:
"Axovant’s RVT-101 is a serotonin-6 (5-HT6) receptor antagonist. GlaxoSmithKline’s (GSK) studies have shown that RVT-101 has some moderate improvements in cognitive function: “In one 576-subject trial, once-daily 15 and 30 mgSB-742457 each missed the co-primary endpoints of significantly improving Change plus Caregiver Input (CIBIC-plus) and ADAS-Cog scores from baseline to week 24 vs. placebo. In the second 684-subject trial, once-daily 15 and 35 mg SB-742457 as an add-on to donepezil each missed the co-primary end point of significantly improving Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores from baseline to week 24 vs. placebo. High-dose SB-742457 met the co-primary endpoint of significantly improving ADAS-cog scores from baseline to week 24 vs. placebo, but low-dose SB-742457 missed that endpoint. Similar results were observed at week 48. The results are in line with two previous Phase II trials of SB-742457.”
What this means to me is that, basically, GSK did not find the drug anything extraordinary. It won some, it lost some, and overall, it wasn’t worthwhile for GSK to pursue it. The year it was abandoned by GSK, the only moderately successful drug for AD, Aricept, had sales of $1.5bn. If GSK thought RVT-101 was even 1/10th as good as Aricept, that was $150 million at launch for the new drug. Today Aricept is available in at least 30 generic versions. So, if GSK is right and RVT-101 didn’t seem to have a fighting chance against Aricept then, it has even less chance against less expensive generic donepezil.
My position on RVT-101 is simply this: that of all the 100 or so trials ongoing in AD, it is just one, nothing special, and nothing to be valued so highly. It may win the FDA’s nod, and so may some others. If history is anything to go by, that is highly unlikely. The FDA, and everyone else, is now looking for a cure."
So, why "RA Capital and Visium both bought large stakes in Axovant, and agreed to a deal where they wouldn’t sell shares for 90 days? They were not insiders, so were not subject to the normal 180-day lockup for insider sales, but Axovant and its bankers wanted to prevent them from being able to sell immediately. Their positions are so large that it is unlikely that they would have been able to sell very much anyway without making the stock price drop dramatically. Mutual funds like Capital Growth and Janus also bought into the deal."
Top Institutional Holders
Holder Shares % Out Value* Reported
QVT Financial LP 75,000,000 75.64 1,528,499,925 Jun 30, 2015
Visium Asset Management 5,080,000 5.12 103,530,394 Jun 30, 2015
RA Capital Management, LLC 5,000,000 5.04 101,899,995 Jun 30, 2015
Capital Research Global Investors 4,000,121 4.03 81,522,461 Jun 30, 2015
Shaw D.E. & Co., Inc. 1,750,000 1.77 35,664,998 Jun 30, 2015
Franklin Resources, Inc 1,406,682 1.42 18,174,331 Sep 30, 2015
JANUS CAPITAL MANAGEMENT, LLC 1,395,435 1.41 28,438,963 Jun 30, 2015
FMR, LLC 1,258,781 1.27 16,263,450 Sep 30, 2015
Falcon Edge Capital, LP 1,000,000 1.01 20,379,999 Jun 30, 2015
Price (T.Rowe) Associates Inc 1,000,000 1.01 20,379,999 Jun 30, 2015
All these holders bought AXON at high $20-25 range. May be they just stupid? It's very unlikely. They want at lest 100-200% gain for their holdings.
Well, everybody knows that Costs of Alzheimer's disease could bankrupt Medicare
The U.S. Food and Drug Administration (FDA) has approved two types of medications — cholinesterase inhibitors
(Aricept, Exelon, Razadyne) and memantine (Namenda) — to treat the cognitive symptoms (memory loss, confusion, and problems with thinking and reasoning) of Alzheimer's disease.
As Alzheimer’s progresses, brain cells die and connections among cells are lost, causing cognitive symptoms to worsen. While current medications cannot stop the damage Alzheimer’s causes to brain cells, they may help lessen or stabilize symptoms for a limited time by affecting certain chemicals involved in carrying messages among the brain's nerve cells. Doctors sometimes prescribe both types of medications together. Some doctors also prescribe high doses of vitamin E for cognitive changes of Alzheimer's disease.
All of the prescription medications currently approved to treat Alzheimer’s symptoms in early to moderate stages are from a class of drugs called cholinesterase inhibitors. Cholinesterase inhibitors are prescribed to treat symptoms related to memory, thinking, language, judgment and other thought processes.
Cholinesterase inhibitors prevent the breakdown of acetylcholine
, a chemical messenger important for learning and memory. This supports communication among nerve cells by keeping acetylcholine levels high.
The drugs just delay worsening of symptoms for 6 to 12 months, on average, for about half the people who take them.
Are generally well tolerated. If side effects occur, they commonly include nausea, vomiting, loss of appetite and increased frequency of bowel movements.
Three cholinesterase inhibitors are commonly prescribed:
Donepezil (Aricept) is approved to treat all stages of Alzheimer's.
Rivastigmine (Exelon) is approved to treat mild to moderate Alzheimer's.
Galantamine (Razadyne) is approved to treat mild to moderate Alzheimer's.So, we don't have a serotonin-6 (5-HT6) receptor antagonist. May be AXON drug is absolutely new one and can cure AD? "Blockade of central 5-HT6 receptors has been shown to increase glutamatergic and cholinergic neurotransmission in various brain areas, whereas activation enhances GABAergic signaling in a widespread manner. Antagonism of 5-HT6 receptors also facilitates dopamine and norepinephrine release in the frontal cortex, while stimulation has the opposite effect."
Neurologically, cholinergic is the abbreviated term referring to acetylcholine. The parasympathetic nervous system, which uses acetylcholine almost exclusively to send its messages, is said to be almost entirely cholinergic. Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, the basal forebrain, and brain stem complexes are also cholinergic."
Thus, since Axovant’s RVT-101 is a serotonin-6 (5-HT6) receptor antagonist it just increase cholinergic neurotransmission in brain.
MINDSET is a Phase 3 international, multi-center, double blind, placebo-controlled clinical study designed to evaluate the safety, tolerability and efficacy of RVT-101 in patients with mild-to-moderate Alzheimer’s disease. The 24-week trial will compare 35-mg, once-daily oral doses of RVT-101 to placebo in approximately 1,150 patients with mild-to-moderate Alzheimer’s disease on a stable background of donepezil therapy. The primary efficacy evaluations are the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study – Activities of Daily Living scale (ADCS-ADL), each of which have been used as endpoints to obtain regulatory approval of currently-marketed Alzheimer’s disease treatments in the United States and Europe.
The MINDSET trial is designed to confirm the results of a 684-patient international, multi-center, double-blind placebo-controlled study in which patients on a stable background of donepezil therapy receiving 35 mg RVT-101 demonstrated statistically significant improvements on the ADAS-cog and ADCS-ADL as compared to patients receiving donepezil alone.And we already know that "in the second 684-subject trial, once-daily 15 and 35 mg SB-742457 (now RVT-101) as an add-on to donepezil each missed the co-primary end point of significantly improving Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores from baseline to week 24 vs. placebo. High-dose SB-742457 met the co-primary endpoint of significantly improving ADAS-cog scores from baseline to week 24 vs. placebo, but low-dose SB-742457 missed that endpoint. Similar results were observed at week 48."So, the combination of drug: SB-742457 - 35mg added to existing donepezil and donepezil 10 mg was successful in old trial. And now in "new" trial AXON is testing the combination of "experimental" 35 mg RVT-101 (old name SB-742457) as adjunct to 5 mg or 10 mg donepezil.Estimated Enrollment: 1150
Study Start Date: October 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
So, most probable results of this trial will be "significantly improving ADAS-cog scores from baseline to week 24 vs. placebo" i.e. AD patients that got RVT-101 and Aricept simultaneously will show brain cognition decline 1.5 points less on a 70-point scale than those who got Aricept alone.
First conclusion from all mentioned above data: AXON is STRONG BUY. Pps can easy reach $50-60 range in 2017 before trial results release and after success results can jump to $100.
Well, it's possible reason that funds/institutions are buying AXON now at $15-17 range.
So, AXON is not a scam but the hidden biotech gem?
It depends on understanding what is real AD drug. Will RVT-101 cure AD? Nope.
Are there any real AD drugs on market now? Nope
Will be any new and strong AD drugs on market in nearest future? May be yes. And very soon i.e. in 2016.
What will happen with AXON pps if new AD show much better results in With Mild to Moderate Alzheimer's Disease? Yep, just a crash to $1-2 level.
The drug is TRx0237.
In 2008 the company presented the results of a large Phase 2 clinical trial involving 321 patients with mild and moderate Alzheimer’s. This study was conducted in the UK and Singapore. It involved the first-generation TAI, rember®. The results were reported at the Alzheimer’s Association International Conference on Alzheimer's Disease Conference in 2008 (ICAD 2008) in Chicago, USA. These results showed that the rate of Alzheimer’s progression was reduced by 90% over a 2-year period.
Phase 3: Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease
Primary Outcome Measures:
Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 65 weeks ] [ Designated as safety issue: Yes ]
Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity
Secondary Outcome Measures:
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Other Outcome Measures:
Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [ Time Frame: 39 weeks and 65 weeks ] [ Designated as safety issue: No ]
Change in expected decline of whole brain volume as measured by brain MRI [ Time Frame: 39 weeks and 65 weeks ] [ Designated as safety issue: No ]
Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
Estimated Enrollment: 833
Study Start Date: February 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Will not talk a lot about TauRx science will only say that it is a real science. TRx0237 is Tau Aggregation Inhibitor (TAI). And in Phase 2 clinical trial rember® (now TRx0237) showed a significant reduction in the rate of
clinical decline: 80% by weeks 50 and 102 of this trial, relative to
controls, as measured using psychometric tools. Functional neuroimaging
results from the trial supported the psychometric data: in patients
taking rember®, the loss of function in the areas of the brain known to
be particularly affected by the Tau-tangle pathology of disease was
eliminated over 6 months. Functional brain scan benefits seen at 6
months were predictive of clinical benefit at 12 months.
And we know that cholinesterase inhibitors like Aricept just delay worsening of symptoms for 6 to 12 months, on average. Then they stop to work and AD progresses. RVT-101 is a serotonin-6 (5-HT6) receptor antagonist that just increase cholinergic neurotransmission in brain. It will also work no more than 12 months. But TRx0237 can reduce cognition decline by 80% even after week 102 (2 years).
For what AD drug insurance companies will pay, for RVT-101 or for TRx0237?
Final conclusion: AXON is scam biotech because RVT-101 is not real AD drug just another palliative drug that will slightly improve quality of life for both the patient and the family. AXON founder is bringing his family along for the ride: his mother and brother are both employees of Axovant Sciences and have received some 1 million stock options between them that carry an exercise price of 90 cents per share. “They are both physicians by training, one of them has been a geriatric physiatrist who has treated patients with Alzheimer’s disease for a couple of decades,” says Ramaswamy. “Like all of our employees they have received stock options.” Vivek’s mother, Geetha Ramaswamy, and his bother, Shankar Ramaswamy, were granted stock options for 262,500 shares and 750,000 shares respectively. In each case the exercise price is .90 per share. As of yesterday’s close that equates to a paper profit of $7.61 million and $21.75 million respectively. They each have an annual salary of $250,000 as well. As for himself, Vivek, along with his two partners, control 75% of the now $1.7 billion company - that’s an asset worth almost $1.3 billion.
So, the answer is clear: this family want to become super-rich by seeding a false hope for AD patients and their families.
So, how to trade AXON safely and avoid big losses if this scam is crashed?
I'll buy AXON now at price range $15-17 and hold before the release of Ph3 AD trial by TauRx. For double gain it's possible to short AXON before release of TRx0237 results for Mild to Moderate Alzheimer's Disease. If TRx0237 results are perfect, AXON pps can easy drop 70-80% in one day. In case if TRx0237 show results that are similar to RVT-101 (brain cognition decline 1.5 points less on a 70-point scale than those who got Aricept alone) AXON pps can drop only slightly. And third scenario is TRx0237 completely fails in Ph3: AXON pps will continue to grow and can easy reach $50-70 range before trial results release in 2017. And if RVT-101 show better results than Aricept FDA will approve and insurance companies will pay for this drug but not for Aricept and it's analogs. Billions annual sales...
02/23/16 by BiotechInvest
AXON death is coming:
"First results from the clinical trial "Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease" are expected in the first half of 2016. If the Phase 3 clinical trials confirm a level of efficacy and safety similar to that seen in the Phase 2 trial reported in the Journal of Alzheimer’s Disease (the beneficial effect was sustained to 50 weeks in both mild and moderate subjects at this dose, with 90-percent reduction in the rate of cognitive decline overall) a treatment targeting the Tau aggregation pathology of AD could be on the market as early as 2017.It's very unlikely that AXON fake AD drug can reduce the rate of cognitive decline even on 30% (if any). The simple prediction of AXON pps after TauRx success: <$1. 06/21/17 by BiotechInvest
Well, who is next in line for AD trial failure? Of course, it is AXON scam.
But look at analyst's opinion below:
Rigorous Trial Design, Nice Risk/Reward Keep Analyst Anxious For Avoxant's Phase 3 MINDSET Data
"Investors could potentially be rewarded with another upcoming catalyst in September with topline Phase 3 MINDSET results, analysts at HC Wainwright noted.
HC Wainwright's Andrew Fein maintained a Buy rating on Axovant's stock and $35 price target based on the company's upcoming results of intepirdine in mild-to-moderate Alzherimer's.
Related Link: Analyst: Neurotrope's Bryostatin-1 Trial Data Justifies Additional Studies
The analyst noted several developments that could "sweeten the deal on the upside" that could improve investor sentiment.
"The clinical pipeline matures with multiple readouts this year even sans MINDSET: HEADWAY-DLB study of intepirdine in 4Q (enrollment completed), phase 2 study of intepirdine on gait and balance, two phase 2 studies of nelotanserin, regulatory discussions for RVT-103, and plans for POC for RVT-104."
The appointment of "biotech superstar" David Hung as CEO serves as not only an "external validation" of the company's prospects but now gives the company ability to better execute on its pipeline.
Axovant remains well-financed with $213 million in cash on the balance sheet which could support its pipeline development in the medium term."
Primary Outcome Measures:
Change from baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 items (ADAS-Cog-11) [ Time Frame: 24 weeks ]
Change from baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale [ Time Frame: 24 weeks ]
A Phase 3, Double-blind, Randomized Study of RVT-101 Versus Placebo When Added to Existing Stable Donepezil Treatment in Subjects With Mild to Moderate Alzheimer's Disease
RVT-101 adjunct to 5 mg or 10 mg donepezil
once daily, oral, 35 mg tablets
Placebo Comparator: Placebo
Placebo adjunct to 5 mg or 10 mg donepezil
once daily, oral, pill manufactured to match RVT-101 35 mg tablet
RVT-101 + donepezil vs donepezil alone?
So, this analyst said "nice risk/reward" i.e. if you buy AXON now for $23-24 and Phase 3 fails to meet primary goals AXON pps will not be crashed to $5 and below because AXON already has "HEADWAY-DLB study of intepirdine in 4Q (enrollment completed), phase 2 study of intepirdine on gait and balance, two phase 2 studies of nelotanserin, regulatory discussions for RVT-103, and plans for POC for RVT-104."
But he forgot to say that with probability of Ph3 failure is >80% the majority of investors will lose >75% of invested money.
The intepirdine is a fake AD drug and can't compete even with donepezil. But AXON CEO was smart enough to fool funds/institutions that bough >90% AXON shares.
QVT Financial LP has 75,000,000 (Mar 30, 2017) or 75.63% AXON outstanding $1,101,749,968 and will lose >70% of investment in one day.
Who will win if Ph3 fail? Everybody who bought AXON below $20, use "run up" to $30 , make +50% then sold for gain and short AXON at $30 or higher. I already bough AXON for run up and will sell it before trial results release (October 2017). At some point I'm going to short AXON and wait for Ph3 trial results.