Chimera Research Group

Chimera Research Group
Contributor since: 2009
Company: Chimera Research Group
Fascinating piece, appreciate the investigative approach.
Aetna has some good commentary on it here and references. I would say there needs to be more trials before making conclusions off of relatively small studies done thus far.
"Aetna considers fecal bacteriotherapy medically necessary for persons with Clostridium difficile infection, with infection confirmed by a positive stool test for C. difficle toxin, that has recurred following at least one course of adequate antibiotic therapy (10 or more days of vancomycin at a dose of greater than or equal to 125 mg four times per day or 10 or more days of metronidazole at a dose of 500 mg three times per day). Aetna considers fecal bacteriotherapy experimental and investigational for all other indications."
http://bit.ly/OgM9nF
Trial failed all real secondary endpoints. The company along with Dr Tanzi continue to spin the results.
The 'primary' efficacy endpoints was a measure composed of 7 different values, then they made up 3 different z-score tests. Only one was successful.
Quote:
There was a statistically significant improvement in performance on the Trail Making Test Part B (as illustrated in the graph), in the PBT2 250mg group compared to placebo at both 12 (p<0.001) and 26 weeks (p=0.042).
"Main Composite Cognition z-score and Exploratory Composite Cognition z-score. No statistically significant changes."
Read towards the bottom now on secondary endpoints, of which are legitimate endpoints. No effect on biomarkers either.
"No significant changes were seen in motor, functional, behavioural or global assessments in either PBT2 treatment group compared to placebo over the 26 week treatment period."
http://bit.ly/1gfabHi
Theyve been doing it since failed data with PBT1 in 2003. Pushed forward PBT2 even though there was little data suggesting it worked.
Good example of their hilarity. Shockingly, nothing ever came of these meetings.
"Prana Responds to Press Comments on Visits by Pharmaceutical Executives
MELBOURNE, AUSTRALIA -- (MARKET WIRE) -- 03/04/08 -- Prana Biotechnology Limited (NASDAQ: PRAN) (ASX: PBT), has become aware of certain comments which appeared in today's press which have followed on from the release of 26 February 2008 when Prana announced the successful outcome of its Phase IIa Clinical Trial of PBT2 in Early Alzheimer's Disease. The comments relate to a visit to Prana by pharmaceutical company executives and expressed the belief that Prana was engaged in confidential commercial discussions to fund further trials of PBT2."
Do some due diligence. Funny how the company than canned this "definitive" study to do a 40 patient study which is very far from definitive. Trial results will be ambiguous and executives will move forward regardless.
"Prana to Commence Phase IIb Trial on PBT2
525 Alzheimer's Disease Patients to Be Treated for 12 Months
NEW YORK, NY -- (Marketwire) -- 04/20/10 -- Prana Biotechnology (NASDAQ: PRAN) (ASX: PBT) today announced that it is finalising plans to commence a definitive Phase IIb trial of its lead Alzheimer's disease drug, PBT2, before the end of this year.
The Phase IIb trial will involve 525 patients with mild to moderate Alzheimer's disease. Treatment will be over a period of 12 months, with the key performance measure being cognition (including ADAS Cog* and Executive Function tests from the NTB*). The trial, a double blind placebo controlled study, will test the efficacy of 2 doses of PBT2 (250mg and 100mg). "We are excited by this protocol because we already know how patients benefited from a 250mg dose of PBT2 in just 12 weeks, so we are confident the benefit will be even stronger and more pronounced over a 12 month trial," said Mr. Kempler. "This trial is all about cognition and helping patients."
It missed on all endpoints(MMSE and ADAS-Cog).
Company mined one of the 6 components of the NTB.
$600 billion , why not $600 trillion? Actually market size is about $10-11B or 60 times smaller than you claim.
http://bit.ly/1eXthSZ
PBT2 will not change this either. Read some actual reviews of their data.
"In the second trial a successor compound, PBT2, was compared with placebo in 78 participants with mild Alzheimer's dementia; all were included in the intention-to-treat analysis. There was no significant difference in the Neuropsychological Test Battery (NTB) composite, memory or executive scores between placebo and PBT2 in the least squares mean change from baseline at week 12. However, two executive function component tests of the NTB showed significant improvement over placebo in the PBT2 250 mg group from baseline to week 12: category fluency test (2.8 words, 95% CI 0.1 to 5.4; P = 0.041) and trail making part B (-48.0 s, 95% CI -83.0 to -13.0; P = 0.009). In the executive factor Z score, the difference in least squares mean change from baseline at week 12 for PBT2 250 mg compared with placebo was 0·27 (0·01 to 0·53; p=0·042).There was no significant effect on cognition on Mini-Mental State Examination (MMSE) or ADAS-Cog scales. PBT2 had a favourable safety profile."
- See more at: http://bit.ly/1eXth5C
CEO Martin Shkreli posted a thoughtful response
http://bit.ly/1eZpDql
Guess we were right after all...
BRCA testing fee cut in half by Medicare, no error either. Now $1438 vs prior 3k.
Despicable behavior by management not confirming this weeks ago.
http://go.cms.gov/1bmX6KO
Trial fails on OS, p=0.58. Imagine a big surprise to the author?
The CMS just cut their reimbursement rate by ~50%. Not a positive development going forward.
Not sure batting 2/25 is a good outcome
Impressive they were able to turn this around. I do wonder how they will sell Vimovo with Nexium going generic in April'14.
Per your reference to the CC, here is Scarlett's quote
"John A. Scarlett - Chief Executive Officer, President and Director
Well, I'm not going to talk about the considerations in these data, but what I can say is that the IWG criteria for myelofibrosis is pretty clear. It's quite clear that CRs and PRs are intended to signify a disease modification and to achieve a CR, PR, clearly, you have to achieve other components of the response, the remission beyond pure bone marrow morphology, et cetera. So these are found in the blood paper in 2013 and include resolution of symptoms, spleen and liver not being palpable, and so forth. So I would just refer everyone to that paper."
Now, please read the actual criteria for CR's
"1. Complete remission (CR)
i. Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly.
ii. Peripheral blood count remission defined as hemoglobin level at least 110 g/L, platelet count at least 100 × 109/L, and absolute neutrophil count at least 1.0 × 109/L. In addition, all 3 blood counts should be no higher than the upper normal limit.
iii. Normal leukocyte differential including disappearance of nucleated red blood cells, blasts, and immature myeloid cells in the peripheral smear, in the absence of splenectomy.*
iv. Bone marrow histologic remission defined as the presence of age-adjusted normocellularity, no more than 5% myeloblasts, and an osteomyelofibrosis grade no higher than 1."
Taken from here
http://bit.ly/1be30Pl
Then read the abstract again, it says specifically
"Overall response rate was 44%. This included five (28%) patients who met the *BM* and *peripheral blood morphologic criteria* for CR (n=4) or PR (n=1) and 3 patients with clinical improvement, pending validation of response duration and resolution of drug-induced grade-1 thrombocytopenia. The four (22%) CR patients experienced reversal of BM fibrosis and recovery of normal megakaryocyte morphology. Two CR patients were transfusion-dependent at baseline and became transfusion-independent. Complete molecular responses were documented in 2 CR patients: one had U2AF1Q157P and 10% JAK2V617F and the other SF3B1K666E and 50% JAK2V617F. A third CR patient had a >50% reduction in U2AF1 469_insAGTATG mutation. Among 13 patients with leukocytosis, 10 (77%) normalized their count or had >50% reduction. *Eleven (61%) patients had complete or partial resolution of leukoerythroblastosis*"
You see no mention of "Complete resolution of disease-related symptoms and signs including palpable hepatosplenomegaly". Hence, it does not meet the official criteria for a CR yet.
Additionally, President and CEO of Moffit confirmed these are not true CR's.
http://onforb.es/1be315B
We think it could be a very promising therapeutic option. We want to see longer follow up data.
I shouldve clarified. More than doubled outstanding shares in 12 months.
They cancelled the breast cancer stuff. Anyone following the RNA space, knows oligos are not suited for solid tumors.
Company has already said they do not have any plans for the further development of imetelstat for multiple myeloma.
Certainly some short term pain.
How did it work out for you last time when the CEO diluted the company by 100%+?
We have no position, long or short. Actually think it is a promising program, but believed some clarification was needed. We will actually be at ASH, so we look forward to seeing the data.
Re dilution/funding - Imetelstat is a very expensive drug to produce(think SRPT eteplirsen) and if they intend on running a large follow up study, will need to scale manufacturing. Read their risk assessment on it. Just look at their burn rate for 2013! They arent even running any trials at all.
"We may not be able to manufacture imetelstat at costs or scales necessary to conduct our clinical trials or potential future commercialization activities.

Imetelstat is likely to be more expensive to manufacture than most other treatments currently available today or that may be available in the future. The commercial cost of manufacturing imetelstat will need to be significantly lower than our current costs in order for imetelstat to become a commercially successful product. Oligonucleotides are relatively large molecules produced using complex chemistry, and the cost of manufacturing an oligonucleotide like imetelstat is greater than the cost of making typical small-molecule drugs. Our present imetelstat manufacturing processes are conducted at a relatively modest scale appropriate for our ongoing Phase 2 clinical trials and investigator-sponsored trials for which we provide clinical drug supply. We may not be able to achieve sufficient scale increases or cost reductions necessary for successful commercial production of imetelstat. Additionally, given the complexities of our manufacturing processes, the resulting costs that we incur to conduct our clinical trials may be higher than for other comparable treatments, requiring us to expend relatively larger amounts of cash to complete our clinical trials, which would negatively impact our financial condition and could increase our need for additional capital."
A very odd world we live in when a drug like this does $26M in sales. Both of its components are generic. DUEXIS offers no benefit in dosing either.
Good job by the sales team. Sure surprised me.
The share price for Myriad has declined more precipitously than it's peers, which to us means that the price action has some fundamental basis outside of the macro-events in the biopharma sector.
We stand by our short-thesis, and at least in this short-term our thesis has been confirmed. We are not confident in Myriad's long-term prospects and our overall short-thesis remains.
An interesting entry point may be between 1.25 to 1.5 billion dollar market cap.
We hope our insights have helped you profit or at the least, helped with risk mitigation.
I wouldn't worry so much at AMBRY, or Gene-by-Gene, or Quest, or LabCorp, as if that wasn't enough competition. If I were an investor, I would worry about every academic center in the country.
Thanks for your comments.
Thanks for commenting. With all due respect, in what world do you think the ACA is a win for MYGN? I am very curious to the logic of that.
The ACA is a give away to insurance companies to RE-negotiate rates with providers and labs under the guise of "new coverage." In case you haven't noticed, LESS, not more, insurers are participating in these exchanges, and several more large insurers, like AETNA have announced that they aren't participating in certain states... It turns out the requirements of preventative care coverage and costs spend controls have made these exchanges not profitable.
No one is going to pay MYGN's exorbitant rates.
Also, the ACA will encourage the use of academic centers for specialty care. Remember, we said these are the people who can do the testing without MYGN's special database.
Further, all the diversification MYGN has done with the analysis business will take awhile to not suck costs.
jacosa, thanks for commenting. I totally disagree with you.
Totally underplays the bleeding risk with this drug as well.
Actually believe it was a lot more pills than 3 pills 3 times a day, think it was more like 4-6 pills 3 times a day.
It doesnt work. The PFS curves were identical.
Good luck to them with over a dozen companies launching competing BRCA testing.
Appreciate the comment. We strive to provide independent analysis.
Thermodox does not work. The company's recent claims don't fly with us.
Dr. Frost has been saying this for years... has yet to deliver on any of it.