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Created: 10/12/2012 12:00:47 AM - Followers: 23 - Board type: Free - Posts Today: 0
Resverlogix Corp., a biotechnology company, engages in the development of novel therapies for cardiovascular disease (CVD), cancer, and fibrotic diseases. The company's development programs include NexVas Plaque Regression, a technology platform, which is in two Phase 2b clinical trials with RVX-208 for the development of drugs that increase ApoA-I to reduce the risk of CVD; and IL-6 and IL-17, which are cytokine mediators for the treatment of autoimmune diseases, as well as technology for the development of drugs in the areas of multiple sclerosis and rheumatoid arthritis. Its development programs also include NexVas Alzheimer's Disease that focuses on the effects of ApoA-I production on cognition; memory; and both plasma and cerebrospinal fluid biomarkers, such as Amyloid Beta 40, 42, tau, and P-tau; and ReVas, a research stage technology for the development of therapeutics to be used with medical devices for the treatment of cardiovascular diseases. The company is headquartered in Calgary, Canada.


CARDIOVASCULAR DISEASE & ATHEROSCLEROSIS
Atherosclerosis is the key underlying cause of cardiovascular disease (CVD) which is responsible for more than 18 million deaths per year worldwide. Atherosclerosis burden results from the accumulation of fat and cholesterol in the artery wall, leading to plaque that causes narrowing and hardening of the arteries, resulting in a loss of elasticity and function. The projected direct and indirect medical costs of CVD in the U.S. will grow from $500 billion in 2012 to $1.2 trillion by 2030 and the largest percentage of this cost is associated with the treatment of atherosclerosis.
The image below illustrates the progression of atherosclerosis in CVD patients. As the disease progresses, the patient develops more severe coronary artery disease (CAD) resulting in increased risk of morbidity and death.


 

APOA-I, HDL AND REVERSE CHOLESTEROL TRANSPORT

APOA-I AND HDL

Please mouse over the interactive image to learn about the ApoA-I/HDL Particle.
 

The most abundant protein in HDL is ApoA-I and it serves as the building block for high-density lipoprotein (HDL or the "good cholesterol") particles. Increased production of ApoA-I protein will result in the synthesis of new HDL particles. These newly synthesized HDL particles are more' functional' because of their ample capacity to remove cholesterol from atherosclerotic plaques. The efflux of cholesterol from the plaque to HDL is called reverse cholesterol transport (RCT). The goal of enhanced RCT with newly synthesized HDL is to remove cholesterol from plaque in the arteries, subsequently regressing atherosclerosis. ApoA-I production therapeutics are the only technologies to date to efficiently remove and regress atherosclerotic plaque in high risk CVD patients.

REVERSE CHOLESTEROL TRANSPORT

Reverse cholesterol transport (RCT) is the natural process within the body that describes how HDL removes cholesterol from atherosclerotic plaques found in the wall of arteries. Cholesterol removed from the plaque is transported on the HDL particle to the liver for excretion from the body in the bile. Newly synthesized HDL particles are flat and empty and thus have the most function in mediating RCT.

 

RVX-208 & MOA

RVX-208

RVX-208 is a first-in-class, small molecule that inhibits BET bromodomains. It is currently being evaluated in a phase 2b clinical trial for its ability to reverse and/or stabilize atherosclerotic disease. RVX-208 acts to increase the production of ApoA-I protein which in turn is used to make new high-density lipoprotein (HDL) particles. These functional HDL particles are flat and empty and can efficiently remove plaque via reverse cholesterol transport (RCT), the natural process through which atherosclerotic plaque is transported out of the arteries and removed from the body by the liver.

MECHANISM OF ACTION

RVX-208 acts via an epigenetic mechanism leading to enhanced activity of the ApoA-I gene resulting in increased production of the protein. RVX-208 works by binding to a target called a BET protein. Within the BET protein there are two specialized regions known as bromodomains. Each bromodomain can recognize and bind to an acetylated lysine. This modified amino acid is found in histones bound to DNA. When a BET protein, through the actions of a bromodomain, finds an acetylated lysine and binds to it, this epigenetic process is called 'reading'. When RVX-208 binds to the BET protein, it triggers a cascade of events leading to increased ApoA-I gene transcription and eventually production of the protein. RVX-208 is the first in this class of compounds to enter into clinical development. Clinical experience with RVX-208 demonstrates that BET inhibitors can be both safe and efficacious when given chronically.

 

CLINICAL DEVELOPMENT

RVX-208 has successfully completed a Phase 2b clinical trial 'SUSTAIN' and a second Phase 2b trial 'ASSURE' is ongoing.

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.

ASSURE

ASSURE is a Phase 2b clinical trial that will evaluate the ability of RVX-208, to regress atherosclerotic disease versus placebo using intravascular ultrasound (IVUS) technology in patients with high-risk CVD. ASSURE is a 26-week, multi-center, double-blind, randomized, parallel group, placebo-controlled clinical trial. The primary trial endpoint will be the change in percent atheroma volume from baseline to 26 weeks measured by IVUS. Secondary objectives for ASSURE are evaluating the safety and tolerability of RVX-208 and effects of RVX-208 on HDL and non-HDL lipid parameters. IVUS technology will also be used to evaluate the changes in plaque stability, an important factor affecting risk of myocardial infarction. Over 310 patients have been enrolled of which 25% will receive placebo and 75% given 100 mg of RVX-208 twice daily.

ASSURE enrollment was completed September 2012. Data is expected in the first half of 2013.

All clinical trials are led by the Cleveland Clinic.

FUTURE DEVELOPMENT OF RVX-208

Following the phase 2b program, phase 3 clinical outcomes trials are planned. They will encompass high risk patients with coronary artery disease and with low baseline HDL. In addition, these patients will have at least one more risk factor such as diabetes, smoking or high blood pressure. These trials are often designed with a certain number of events to be observed such as cardiovascular death, non-fatal myocardial infarction, stroke or re-vascularization.



Apabetalone (RVX-208) is a first-in-class small molecule that inhibits BET bromodomain proteins. The Phase 3 clinical trial BETonMACE is advancing with a primary endpoint of time to first occurrence of Major Adverse Cardiac Events (MACE) in high-risk cardiovascular disease (CVD) patients with type 2 diabetes mellitus and low high-density lipoprotein (HDL).

 
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#1085 Anyone have any idea what this company is big orange 07/16/2020 01:32:26 PM
#1084 With all that has been shown in the cabel 04/21/2020 11:01:14 AM
#1083 I think the only plan is survival. noretreat 04/21/2020 10:45:10 AM
#1082 Any news about the future plans for this company? big orange 04/21/2020 10:37:04 AM
#1081 69 cents. tempting, but holding off on noretreat 03/12/2020 03:18:24 PM
#1080 some will use this pop as an exit noretreat 02/03/2020 11:17:21 AM
#1079 Yes! Much quicker than expected! cabel 02/03/2020 08:44:11 AM
#1078 BRIEF-Resverlogix Receives US FDA Breakthrough Therapy Designation For Apabetalo noretreat 02/03/2020 07:40:17 AM
#1077 But it doesn’t really matter what the analyst noretreat 02/02/2020 02:33:37 PM
#1076 As far as I can tell so far noretreat 02/02/2020 02:33:00 PM
#1075 What do analysts say about the secondary analysis? big orange 02/01/2020 04:57:08 PM
#1074 Seeing a "clear path to commercialization" at the jstiltz22 01/13/2020 12:19:24 PM
#1073 Interesting secondary analysis released today noretreat 01/13/2020 10:39:19 AM
#1072 The sad truth is that BetOnMace was a noretreat 12/13/2019 05:48:47 PM
#1071 The statement in this release was optimistic to noretreat 12/11/2019 04:38:59 PM
#1070 This one’s down about 40% the last couple noretreat 12/11/2019 04:37:45 PM
#1069 Resverlogix Announces Change to its Board of Directors CALGARY, Phoenix300 12/11/2019 08:32:47 AM
#1068 cognitive results pres. noretreat 12/06/2019 08:50:49 AM
#1067 ambiguous but holy cow!!! noretreat 12/05/2019 08:51:07 PM
#1066 Thanks. Time will tell. big orange 12/01/2019 01:59:04 PM
#1065 Shop themselves to anyone with cash? If noretreat 12/01/2019 06:41:51 AM
#1064 Any ideas what their plans are for the big orange 11/30/2019 09:29:10 PM
#1063 Not good. Here's hoping somebody buys them out. big orange 11/18/2019 08:43:34 PM
#1062 They missed their primary endpoint and have to noretreat 11/18/2019 08:02:29 PM
#1061 Then why did the bottom fall out? big orange 11/18/2019 07:18:23 PM
#1060 from another board noretreat 11/18/2019 04:49:23 PM
#1059 My concern is that there will need to big orange 11/02/2019 12:35:12 PM
#1058 I fully expect all remaining data on endpoints noretreat 10/30/2019 06:40:33 AM
#1057 NR, so are you all out of RVX,... cabel 10/27/2019 07:09:34 PM
#1056 Why should any of the rumors be true? noretreat 10/26/2019 07:46:17 PM
#1055 Shorting onto news? noretreat 10/26/2019 07:44:59 PM
#1054 My concern with the dramatic drop in pps big orange 10/25/2019 02:54:47 PM
#1053 I am more looking forward to hearing about cabel 10/25/2019 12:24:10 PM
#1052 arfxf All the rumors of "just missed it" and noretreat 10/25/2019 12:09:39 PM
#1051 NR, While we are waiting for more Data cabel 10/25/2019 11:14:08 AM
#1050 And the FDA did agree to the protocol. noretreat 10/12/2019 01:32:12 PM
#1049 Don't know what the protocol was for what big orange 10/12/2019 01:08:52 PM
#1048 not making any big bets on it, but noretreat 10/10/2019 04:03:01 PM
#1047 Hope you are right big orange 10/10/2019 09:23:35 AM
#1046 Not necessarily as it is one of the noretreat 10/10/2019 08:36:29 AM
#1045 Would require a stage three clinical trial before big orange 10/09/2019 09:52:49 AM
#1044 May work better with Crestor than Lipitor. That noretreat 10/08/2019 09:01:45 PM
#1043 Maybe to discuss the potential for this compound. big orange 10/07/2019 11:06:11 PM
#1042 The 64k question is, why would AHA put biopa 10/05/2019 12:55:58 AM
#1041 OTOH, there is much more information to come noretreat 10/03/2019 10:28:43 AM
#1040 The facts are easy. It missed its primary noretreat 10/03/2019 09:53:29 AM
#1039 What facts and rumors? big orange 10/02/2019 09:50:12 PM
#1038 Endpoint not met. Very little cash. Facts. Rumors abound noretreat 10/02/2019 07:46:20 PM
#1037 Why coming back so strong? Thought that big orange 10/02/2019 06:30:06 PM
#1036 Fun times. Almost halfway back noretreat 10/02/2019 06:10:36 PM
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