Answer from Fred wrt Bloom Burton - straight from the horses (so to speak).
Fred was pretty miffed in his response that he needed to waste valuable time on these "ridiculous insinuations " by Bloom Burton. But he did so nevertheless at length in this response. Fred's responses are in red intersperced within a copy of the Bloom Burton report. I received this email from Fred earlier this evening around 6:00PM ET Wed. but I was at a wedding tonight, so I did not see it until about 1:00AM Thurs. morning when I returned home. Sorry for the delay. Here is Fred's definitive response to Bloom Burton: I will try to repost it again in the morning for those that miss it this late at night.
Glta, Stockman6767
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Subject: Hi Fred, could you please comment and respond to all the Bloom & Burton concerns reported below. - Regards, .........................
Bloom Burton and Co.: Hold rating and $2.00 target for PLI
According to Bloom Burton and Co.
https://www.bloomburton.com/research/PLI20161130.pdf
ProMetic Life Sciences Inc. (TSX:PLI, C$2.46)
Rating: HOLD
Risk: Above Average
12-month Price Target: $2.00 (was $2.30)
Missing Patients and PBI-4050 Structure.
Last week following ProMetic’s Analyst Day, we reiterated our opinion that the market is overvaluing ProMetic:www.bloomburton.com/research/PLI20161122.pdf. This is based on our view that numerous pre-clinical PBI-4050 data releases helped boost PLI stock starting in early 2013, however, the recent slate of phase 2 trials prove little about the drug, in our opinion.
They are entitled to their opinion, we obviously do not agree nor do we think their opinion is based on facts that are accurate. Our 3 open label studies were designed to provide early evidence of activity and efficacy translation from what we have seen in all our preclinical models to human patients and this is exactly what we have generated. It makes perfect sense to look for such confirmation in open label trials before committing more resources into placebo controlled trials. The fact that these trials were open label does not affect in any way shape or form the validity of the results we have generated, it actually provides us with greater comfort and confidence to actually proceed with placebo controlled trials. Placebo effects in both Metabolic syndrome and Type 2 diabetes and IPF are well known and documented and would not have changed anything to our results. We were looking to see if there would be translation of activity from our preclin models to human patients and this is exactly what we have seen
Recent press releases touting activity are drawing on results that may represent nothing more than placebo effect or artefact. We take this stance because we believe that trials were too small, too short, without placebo controls, and with endpoints that may be influenced by subjective factors.
Same response as above. An average reduction of -80 ml to -100 ml for the FVC in IPF patients cannot be an artefact or a coincidence. The fact that our studies did not have a placebo control arm does not change the fact that the large IPF studies did have placebo arms and they all produced the same decline trend in FVC or deaths rate. Our IPF study, albeit small in number of patients, hence our clear mention of early signs of efficacy, is suggesting that 2 cohorts provide an opportunity to show superiority to standard of care and could justify running a larger placebo control study. Have a look at Intermune preliminary data in their phase 2 with roughly 50 patients, it gave them a market cap at the time of US $800M and that was their only product and indication.
As for the metabolic syndrome trial, we ended up enrolling patients with an HbA1c that was not as high as what typical Type 2 diabetes enroll. We were interested in seeing whether or not there would be hypoglycemia episodes. Typically they enroll patients with an HbA1c that is higher than 7.5 or 8 %. This what we have used to benchmark our results and we have demonstrated efficacy in lowering in a material manner their HbA1c. Do not forget also that these patients are and were already on a cocktail of drugs (metformin and other drugs etc…) and yet we still reduced their HbA1c levels despite that fact. Placebo effect? I don’t think so. It is a well-known and documented fact that placebo effect in such trials are 0.13%
You should also pay close attention to the fact that we have also moved and significantly reduced many related and associated biomarkers in the right direction. This cannot all be a coincidence
Digging deeper, it also appears that groups of patients may have been excluded from several data presentations, which could lead to unwarranted enthusiasm for the results. .
The fact that the numbering of patients does not necessarily follow perfectly the numerical order is such a ridiculous argument that I will keep this very short. They get a number when screened - not when they are dosed. Dosing schedule may vary and we may get data from patients with higher numbers - and if numbers are skipped, it does not mean that previous numbers have been dosed and made it into the trial. We are reporting on the patients that have been dosed, each with their assigned number. For example, patient # 6 did not complete the 12 weeks treatment period, hence his exclusion from the reported data
We take this stance because we believe that trials were too small, too short, without placebo controls, and with endpoints that may be influenced by subjective factors.
Proof of concept trials are typically shorts to give a quicker early indication of activity before more resources get committed. The fact that we see biomarkers move significantly in a manner of weeks in metabolic syndrome and Alstrom patients is indicative and representative of the intended activity
We believe the company missed an opportunity at the Analyst Day to provide additional details which could have helped further the understanding of PBI-4050.
We explained why. We will disclose the exact receptors in peer reviewed publications in partnership with some of the most reputable organization, Montreal Heart Institute, Vanderbilt University etc at a later time
In our opinion, a convincing, novel, differentiated and well-described mechanism has not yet been elucidated for PBI-4050, and we find this atypical for a biotech drug at this stage of development.
We have identified and know exactly what the exact mechanism of action is. WE HAVE CONFIRMED THE RECEPTORS AND MECANISM OF ACTION MANY, MANY TIMES OVER
As we have previously noted, data for ~30 PBI-4050-treated IPF patients was super-imposed on results for 500+ patient phase 3 registration trials for pirfenidone and nintedanib, which is scientifically misleading in our opinion.
We have explained our rationale for this, it gives an idea and a basis for a visual comparison. Both placebo and standard of care drugs show a decrease in FVC. WE DO NOT, we explicitly noted that our results were on a limited number of patients and we have labelled our data EARLY SIGNS of efficacy. Can we be any clearer?
Additionally we note that results for approximately 1/3 of PBI-4050-treated IPF patients were left out of the graphic.
Yes and we will report on the full set of patients once the last 10 have completed the 10 weeks and with the data compiled and analyzed.
For the metabolic syndrome and type 2 diabetes study, HbA1c changes for 17 patients were presented at the Analyst Day, even though the trial ended in October with 24 patients. Alstrm Syndrome results also appear to have excluded at least one patient (data was presented for patients 1-5 and 7).
The 17 patients we reported on in our slides had an HbA1c of 7.5% or greater. A recognized inclusion criteria for other diabetic approved drugs used for their clinical trials. We have presented that data to allow for apples to apples comparison purposes. We even have presented data on HbA1c levels of 8% and greater where we show a meaningful reduction of 1%. We are not excluding patients, we are reporting on the inclusion criteria used by the industry. The data generated on the 24 patients is already meaningful.