RE:RE:RE:RE:RE:RE:RE:Resverlogix Q&A From TodayHi jdstox. I've been trying to reply to your paragraph 3 of your post on Mar 9 at 10:45 p.m. but I have been having ongoing problems with the Stockhouse website of late.
I've finally been able to read todays posts and I believe most of my points have been made by others today but I stiil want to shre my thoughts.
Hi jdstox. I read your future post so I want to apologize up front and assure you that I won’t bother you in the future but I do value your perspective.
You indicated on a post that you have been around on RVX since 2004 and so you have seen much more than me.
I’ve been a shareholder for about 7 years and I have never sold a share. I have dollar cost averaged down over time because I believe in the potential of rvx-208.
I just wanted to give my perspective on your 3
rd paragraph from your 10:45 p.m. posting from March 9
th as follows:
Jdstox asked “Has there ever before been a drug that has failed so many trials and was yet approved for Phase 3 trials? Has anybody ever seen that?”
I must say that my observations about rvx-208 and RVX are the exact opposite of what yours appears to be. I guess it just goes to demonstrate how human perceptions can vary even when we are looking at the same data.
Since starting to pay detailed attention to RVX I have seen
nothing but a string of continuous successes on both the scientific side and the ability to raise funds and keep the ship afloat. Even though I have taken some gentle shots across Don’s bow I feel strongly
he has his hand firmly on the tiller and is steering a steady course and getting closer to his destination each day. Yes, I am a bit frustrated with communications (lack of) because my business is communications strategy and I understand the tremendous power of strong messaging. But in the end
Don has been at this successfully for 15 years and he is an effective leader and I believe he has strong empathy with his scientific team AND speaking of the scientific team I think it is absolutely remarkable the team he has assembled in Calgary.
So what I see in RVX is a long and continuing string of successes starting at the beginning of the company and getting stronger each passing month. Yes, there have been blips but this is science and any investor who does not understand at least the fundamentals of scientific discovery should not be in this stock unless you have strong advisors.
RVX started exploring the field of epigenetics I believe about 7 to 10 years ago, long before other pharma developers and thus
has developed significant intellectual properties advanced beyond others. As I understand it BP has only recently started to realize the huge potential of this field way beyond just CVD and extending into various cancers, CKD, inflammation diseases such as arthritis and on and on as well as individually tailored treatments.
Recently there have been postings that discussed competitors to rvx-208. One of the science posters, I believe it was fouremm (apologies in advance if I’m wrong) who felt it would be CETP inhibitors. Back around 2010-2012 or so clinical trials revealed CETP inhibitors yielded very significant increases in HDL but with no clinical effects. Also, there were also toxicity issues and yet these companies are back in the field with new trials on CETP inhibitors.
Rvx-208 is a BET inhibitor, which increases ApoA-1 and HDL. Fouremm responded in his/her post that
rvx-208 results in an increase in functional HDL. This may, indirectly be the basis of MACE reduction. (fouremm, I apologize for my explanation so please straighten me out here if I'm off base). I’m not a science person but this
functional stuff has significance to me because from what I’ve read proteins can become non-functional I believe through free radicals or inflammation (science folks help me here – I’m over stepping my bounds).
Trial Results SUSTAIN - In this Phase 2b clinical trial of 176 patients with established atherosclerotic CVD,
RVX-208 significantly increased HDL-C, the primary endpoint. SUSTAIN
also successfully met secondary endpoints, showed increases in levels of Apo-AI and large HDL particles, both believed to be important factors in enhancing reverse cholesterol transport activity. The SUSTAIN trial also
showed that RVX-208 was safe when given daily for 6 months and increases in alanine aminotransferase (ALT) reported in previous trials were infrequent and transient with no new increases observed beyond week 12 of the 24-week trial.
That looks like success to me.
ASSURE - was a 26-week, multi-center, double-blind, randomized, parallel group, placebo-controlled trial led by Cleveland Clinic. This trial assessed the early impact of atherosclerosis regression by treatment of RVX-208 in high-risk cardiovascular disease (CVD) subjects. There were 281 Patients that formed the Full Analysis Set (FAS) in which they each received two Intra-Vascular Ultrasound (IVUS) procedures which provided Grey-Scale images detailing plaque volume.
- Multiple secondary IVUS endpoints such as Total Atheroma Volume (TAV) and 10mm worst occluded TAV were met with high statistical significance with p<0.001 and p<0.001, respectively.
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- Additional secondary lipid biomarker endpoints such as HDL and ApoA-I were also met 10.73% p<0.001, 11.69% p<0.001, respectively.
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- The primary endpoint in ASSURE, -0.6% change in PAV was not met. The RVX-208 treated group had -0.4% median plaque regression (p=0.08).
So on the primary endpoint of PAV (adjusted percent atheroma volume) reduction the achieved regression was -0.4% at p=.08. So this means that there is
less than a 1 in 10 chance that this level of regression occurred by random chance. This is not good enough in science. This raises a question. Suppose that the same result of -0.4% PAV regression was statistically significant at p=0.001
then would BP consider this regression clinically significant. - I put this to the science posters and the answer was YES. In other words there would be significant health benefits achieved by -0.4% regression in 6 months (the length of the trial) and if this worked on a linear basis the plaque regression would be -0.8% in a year vs. potential plaque growth over that period.
Combined ASSURE/SUSTAIN Post Hoc Analysis RVX scientists combined the 2 trials and examined MACE events (major cardiovascular adverse events) within patients with diabetes mellitus and CVD. The control group received Crestor only and the test group received rvx-208 + Crestor. They found at day 210 a RRR (relative risk reduction) of 77% of MACE with p=.01 (i.e. less than 1 in 100 chance that this occurred by random chance as opposed to the effect of the treatment with rvx-208).
Phase 3 Trial. I consider it a "
very significant success" that RVX has moved directly to phase 3. Obviously this health issue is extremely significant to the FDA and health care providers. We know that obesity in America is growing and with it diabetes mellitus and these people have a much higher than average likelihood of MACE (21% at day 210 in the control sample of the combined trials vs. 5.1% in the group treated with rvx-208 + Crestor. I know I would want to be in the test group). Can you imagine a 1 in 5 chance of a MACE event in half a year if you were one of these people?
This is a huge market in the
USA alone none the less in Asians countries and around the world.
Emerald Logic FACET Analysis RVX now has at its disposal the power of the multivariate modeling of their full data sets. This could include virtually every trial they have done. This type of modeling is extremely powerful. Even the brightest scientists can really only deal with a few variables at any one time. Even meta-analysis (which brings together the findings of many studies on the same subject) is very difficult to achieve with current methods and it usually does it at the
macro data level. The Emerald multi-variate analysis brings together many variables (from the
raw data set) and analyses them with multiple approaches such as factor analysis, regression, automatic interaction detection (AID and THAID), non parametric statistics and many function fitting models and algorithms.
Add to this Emeralds experience across other disease and clinical trial studies and the knowledge benefits are huge.
To give even a simple an idea of the complexity of the variables they could be patient variables (age, weight, various medical conditions, fitness, sex, previous problems, genetic factors, etc) then there are treatment variables like dosages, time, other drugs, control vs. test, etc and then there are the dependent variables like MACE, PAV regression and various markers like ApoA-1, HDL, etc. So you can understand the extreme complexity of this type and the cause and effect factors. Thank heavens for Emerald.
The scientific benefits are very significant. Once the multivariate analysis is complete (and it is complete) the scientists can use the graphs and mathematical functions to help explain gaps in their understanding of the biochemical pathways. For example they should get a better understanding of the gaps between ApoA-1 increases, Crestor and MACE reduction. This is an important gap to fill in AND if filled it can create a powerful argument to BP.
So I’m long based on the science. Yes, I get frustrated but good science takes time. I’m guessing that Don knows how close he is and he can taste it. Let’s face it, it has been a long time for him.
No worries jdstox. I do apologize but felt a need to express my “rose coloured glasses” view.
Also, my apologies to other posters and readers for another long winded post, the ideas of which have already been mentioned by other posters today.
Thanks to the very insightful perspectives regarding valuation today and ove the past few days.
Hope this comes through. I've been having big problems with Stockhouse for the past few days about "temporary unavailable due to scheduled downtime". Who would do downtime during the trading week?????
Stay well. I won't bug you!
IMHO GLTA DYODD
Cheers
Toinv