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Message: U.S. Listing

Golfyeti,

Great post. What I love about this forum is the different perspectives that others bring that compliment my own very science-centric views. I completely forgot about the potential for the imminent US listing in my Tick Tock post from yesterday. Regarding the timing of the US listing.....I think some kind of news has to break first that gets Resverlogix some serious attention before the US listing occurs. For example, a news release formally announcing that 250 events has been reached, dosing has ended, patient follow ups have begun and adjudication has begun. A final DSMB report and publication of BETonMACE trial design, rationale and baseline data in major journal would help too. Once these happen (could be anytime between now and end of January in my opinion), we could see the increased attention and valuation that facilitate the US listing. I do anticipate the US listing to occur before top-line data reveal. It could be a wild month and a half coming up. All just my opinion. DYODD.

What I also enjoy about this forum are the topics that posters like you bring up now and then that allow us to contextualize Resverlogix and bromodomain technology to other exisiting or up and coming fields. Between Amarin and Moderna, I would say the closer comparator is Amarin but still not the best comparison. Amarin is a company with a single drug, Vascepa, with groundbreaking CVOT results with the hopes of expaning into additional indications and patient populations. Unlike Amarin/Vascepa, Resverlogix (and Zenith) have an entire platform of bromodomain inhibitors that could very well lead to additional drugs and indications beyond the reach of apabetalone. As described below, Moderna is more of a platform technology not a single drug. 

As for Moderna......I love their ticker symbol MRNA. The Cramer video was great. He did a good job of putting their tech into layman's terms. Moderna is based upon mRNA. DNA sequence in the nucleus of the cell carries the "blueprint" of nucleotide sequences for tens of thousands of genes. This DNA is read by RNA polymerase and other transcriptional machinery in the cell nucleus to synthesize messenger RNA (mRNA). Each mRNA is a transient molecule that contains the nucleotide information for a single gene. After the mRNA is synthesized, it is exported from the nucleus and recognized by the ribosomes in the cell that then translate the mRNA nucleotide sequence into an amino acid containing protein. DNA --> mRNA --> protein. Central dogma. When one refers to a gene or mRNA being up-regulated or down-regulated, or refer changes in gene expression, one is referring to changes in the actual number of transcribed mRNA molecules for a particular gene.

There are many competing technologies that intervene somewhere in the DNA-->RNA-->protein spectrum including, but not limited to, manipulating the DNA genome (i.e. CRISPR gene editing), promoting specific mRNA degradation or interfering with mRNA translation (i.e. IONIS antisense oligonucleotide platform or RNA interference technologies), increasing or decreasing mRNA expression by providing an activator or inhibitor of a transcription factor (i.e. PPARalpha or PPARgamma agonists) or epigenetic component (i.e. BET inhibitor), restoring gene expression via a viral vector (i.e. adeno-associated viruses expressing a specific mRNA/protein), or providing an already made protein therapeutic to a patient (i.e. enzyme replacement therapies, antigen to promote immune response).

Moderna's mRNA approach takes mRNA already synthesized in the lab and delivers it to the patient. The patient's cells then translate this mRNA into the corresponding protein. Because there are tens of thousands of genes encoded by the human genome (including multiple common and rare variants), as well as thousands and thousands of foreign (non-human) genes/proteins, this mRNA "platform" enables them to potentially deliver a wide array of protein-encoding mRNAs to the patient. There are many different applications that Moderna is chasing after, which you can read about on the "modalities" and "pipeline" pages. Most of their programs are pre-clinical still. A number of programs for vaccines and immuno-oncology are in Phase 1. In my opinion, these vaccine/immuno-oncology applications of Moderna's mRNA tech are very promising. Moderna only has one single program in Phase 2 (with Astrazeneca) for delivery of genetic instructions to spur the production of vascular endothelial growth factor (VEGF-A) via epicardial injection in patients undergoing Coronary Artery Bypass Grafting (CABG) surgery.

"Early-stage?  Completely untested and Unproven?  Years and years before knowing?  And the market this week assigns a valuation of $6 Billion US ??"

Yes, early stage. Not completely untested/unproven. Applications already in the clinic like vaccines, immuno-oncology, and others requiring local and transient expression of a protein encoded by a specific mRNA hold a lot of promise. However, I do have concerns about the likelihood of the current pre-clinical applications for Systemic Secreted Therapeutics and Systemic Intracellular Therapeutics making their way into humans. Do they have delivery systems advanced enough to get their mRNA therapeutics into the required tissue(s)? It's easy to get things into the liver, but what about other tissues? How long will the administration of a single systemic mRNA therapy (presumably by intravenous injection) last? How often will patients need to come back to the clinic for a repeat dose? These are likely going to be very expensive therapies like the PCSK9 antibodies and the Ionis anti-sense oligonucleotides. So delivery, frequency of dosing and cost may pose challenges for some of these systemic secreted/intracellular therapeutic programs.

BearDownAZ

 

 

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