DPC: Take a look at management credentials at MCRB, the most advanced public company working on the microbiodine as a way to cure disease. Some very interesting stuff they are doing. What do you think?
I was thinking the same thing. We are so ahead of the pack. I did not read it fully yet, but it does not contain much we did not know. It just goes to show the market is not efficient.
Deep sequencing shows that HBV basal core promoter and precore variants reduce the likelihood of HBsAg loss following tenofovir disoproxil fumarate therapy in HBeAg-positive chronic hepatitis B
Results NGS analysis of HBV sequences from 157 patients infected with genotypes A to D showed the frequency of variants in the basal core promoter (BCP) and precore (PC) regions varied by genotype and that these mutations were associated with the absence of HBsAg loss. This was the case even when mutations were present at frequencies below the threshold of detection by population sequencing. Increased viral diversity across the HBV genome as determined by NGS was also associated with reduced likelihood of HBsAg loss.
Conclusion Patients with detectable BCP and/or PC variants and higher viral diversity have a lower probability of HBsAg loss during long-term NA therapy. Strategies to achieve functional cure of HBV infection through combination therapy should consider using NGS to stratify patients according to BCP/PC sequence. Consideration should also be given to earlier initiation of therapy prior to the emergence of BCP/PC variants.
Cerulean Pharma’s lead nanotech cancer drug has run into another stone wall in the clinic. The Waltham, MA-based biotech $CERU says that CRLX101 combined with Avastin flubbed a Phase II study, failing to provide evidence of an improvement in progression-free survival when compared against standard of care therapies for renal cell carcinoma.
Cerulean’s shares were slammed on the news, plunging 62% and wiping out the lion’s share of its $75 million market cap.
The drug combo group actually performed worse than the control arm, with investigators reporting a 3.7 month median PFS for Cerulean’s drug compared with 3.9 months for standard of care. The objective response rate was even worse: 5% for the CRLX101 combination against 14% for standard of care.
I think they have talked about possible open label data so many times that they have created an expectation that there will be an open label release. I expect one when we might least expect it. Is that a contradiction?
When you talk about "execution" what are you referring to? Do you believe that a science inquiry into what drug works on a disease is susceptible to the kind of execution that delivers precise timing of results? Or do you give the science a chance to find solutions when you see they are on the right track?
Do you look at the recent money raise, with impressive institutions that understand biotech, just in time as good "execution"? How about the AD data of 99% KD? or the rapid development and proof of concept with 521 to show the impact of iDNA? was that good "execution"?
What about the development of animal models for ARWRs preclinical pipeline, that gets ARWR on the SubQ path and the extrahepatic path? Good execution?
What do you think of the expansion facility next door to Roche? good execution?
I know you like their chances to get something done that is important in the field of HBV, and I think you understand they are in the important new sector of gene modifying activities that likely will yield an entire group of new drugs. Do you like the way DPC is "executing" to deliver triggers? How about how they "execute" to get KD without SAE? Good execution?
Should I keep going?
You might be right that he does not want to dilute at these prices, as that is what I think he was saying about needing to balance interests of shareholders into the mix. The rest of what you said, I disagree, especially about those comments on 521, which I think they are learning may not even be needed as 520 is working with both cases of eAG+ and eAG-, at least that is my take on his "backup" comment.
I also think he is buying the time he knows he needs to do the collaboration deal with DPC. What I am worried about is whether that deal will bring in money. We will have to see what sort of deal and how far along it is. He seem to be open to a number of deals.
Not 6 cents any more, it is up to 39 cents on 7+ M shares, or $2.7 M in profit for the "Smart Money". See what they are call smart?
Both drug resistance and disease mutations are big issues for HBV treatment!
Another study that may help ARWR define "end points" that could gain approval of ARC-520
NEW YORK (Reuters Health) - Patients with chronic hepatitis B virus (HBV) infection who are receiving long-term treatment with entecavir had lower than expected hepatocellular carcinoma (HCC) rates in a recent retrospective study.
The risk of HCC in chronic hepatitis B patients ranges from
These authors think,
course of disease, HBV e antigen (HBeAg) seroconversion, defined by the loss of
HBeAg and the development of the antibody anti-HBe, forecasts a favorable
long-term outcome. HBeAg seroconversion is usually followed by the sustained
suppression of HBV DNA, normalization of alanine aminotransferase (ALT) levels,
and long-term remission of hepatic inflammation confirmed by liver biopsy [Chen et
al., 2006; Bortolotti et al., 2006; Hui et al., 2007]. Without antiviral treatment, HBeAg
may seroconvert spontaneously at a rate of 5%–10% per year in HBeAg-positive
CHB patients in the immune clearance phase [Hui et al., 2007; Liaw et al., 2010]. It is
very significant to recognize CHB patients who are prone to spontaneous HBeAg
seroconversion as early as possible, to prevent unnecessary prescription and
corresponding financial burden, and more importantly drug-induced adverse reactions.
Additionally, antiviral treatment should be prescribed immediately for CHB patients
without spontaneous HBeAg seroconversion."
I am not confident that this is the current state of thinking, but perhaps it would be different if there were a fast way to achieve FC and risks of progression could be overcome.
This 2011 article talks about the 4 phases of cHBV infection but may be out of date with current thinking. It is interesting in that it discusses the so called "immune tolerant phase" in children and identifies a period of long immune inactivity. It also discusses what the authors think are the importance of "spontaneous HBeAg seroconversion group" for treatment and may form another basis for how ARC-520 could help a patient get to a potential regulatory "end point", to wit, spontaneous HBeAg seroconversion group.
" Antiviral medication is dispensed at the hospital pharmacy
with a single copayment (between $5 and $30 USD) per 60 tablets or
approximately 2 months of supply with some limited dispensing occurring
in community pharmacies.25 In Australia, the majority of 10 000
prescriptions annually are from public hospital specialists.26,27"
" Single, daily dosing of oral medication
that has a good safety and side effect profile in CHB promotes
adherence.21 However, CHB is usually asymptomatic and individuals
may not perceive the benefit of medication taking. Communicating the
need for adherence is complex in a condition spanning decades, with
treatment only recommended for a minority of patients with active
viral replication and ongoing liver injury or established cirrhosis.22"