Resverlogix October 2018 events

...We Welcome You To The Resverlogix HUB withIn The AGORACOM COMMUNITY!

Dear Agoracom Family,

I want to thank all of you for your patience with us over the past 48 hours and apologize for what was admittedly a botched launch of our new site.

As you can see, we have reverted back to the previous version of the site while we address multiple forum functionality flaws that inexplicably made their way into the launch.

To this end:

1.We have identified 8 fundamental but easily fixable flaws that will be corrected in the coming week, so that you can continue to use the forums exactly as you've been accustomed to.

2.Additionally we will also be implementing a couple of design improvements to "tighten up" the look and feel of the forums.

Sincerely,

George et al

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BearDownAZ

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Resverlogix October 2018 events

in response to

Re: Resverlogix H2 2018 events

BearDownAZ

posted on Oct 08, 2018 05:35PM

Busy day on Oct 17th at BIO Investor Forum in San Francisco. All times Pacific. Resverogix on the podium at 3 PM, Zenith at 3:30 PM and our friends at BiOasis at 2 PM.

Also, abstract now available for Resverlogix's poster presentation at ASN Kidney Week October 26th in San Diego. Abstract appears somewhat similar to the abstract for the May ERA-EDTA poster.

ABSTRACT: FR-PO132

Apabetalone Downregulates Factors and Pathways Associated with Vascular Calcification

BACKGROUND: Apabetalone, an oral small molecule BET inhibitor, reduced the incidence of major adverse cardiac events (MACE) in patients with CVD and improved eGFR in a subgroup with CKD in phase 2 trials. Because vascular calcification (VC) is associated with MACE, effects of apabetalone on processes associated with VC were examined.

METHODS: Plasma proteomics was conducted in CVD patients receiving apabetalone in the 3 month (ASSERT) and 6 month (SUSTAIN & ASSURE) phase 2 trials, as well as patients with stage 4/5 CKD that received a single 100mg dose. Coronary artery VSMCs were used to examine effects of apabetalone on transdifferentiation & calcium deposition.

RESULTS: Apabetalone significantly reduced circulating levels of VC markers in CVD patients in phase 2 trials, including alkaline phosphatase, osteopontin and osteoprotegerin. Plasma proteomics of CKD patients (n=8) indicated activation of molecular pathways driving VC including IL-6 signaling, BMP-2 signaling & RANK signaling in osteoclasts. Downregulation of these pathways by apabetalone was predicted in the CKD cohort 12hrs post-dose.

In VSMCs cultured in osteogenic conditions, apabetalone opposed induction of transdifferentiation markers & inhibited calcium deposition. BRD4 is a transcriptional regulator & target of apabetalone. ChIP-seq showed transdifferentiation of VSMCs to a calcifying phenotype promoted re-distribution of BRD4 on chromatin, resulting in fewer BRD4-rich enhancers (118 in osteogenic, 288 in basal). 38 genes were uniquely associated with BRD4-rich enhancers in osteogenic vs basal conditions; several of the genes have been linked to calcification. Apabetalone reduced BRD4 on many of these enhancers, which correlated with decreased gene expression. Bioinformatics indicated BRD4 may cooperate with specific transcription factors to promote calcification.

CONCLUSION: Involvement of BRD4 in VSMC transdifferentiation & calcification is a novel discovery. Further assessment of apabetalone as a therapeutic for VC is warranted. The impact of apabetalone on biomarkers, renal function & CVD outcomes in patients with impaired kidney function is being evaluated in a subgroup of the phase 3 BETonMACE trial.

That same week,

CTAD 2018 (11TH Clinical Trials on Alzheimer's Disease) October 24-27, 2018; Barcelona, Spain

Poster presentation "Apabetalone, a BET bromodomain inhibitor, suppresses inflammatory mediators in microglia and vascular endothelial cells that contribute to neurodegenerative disease." Abstract not available.