Phase1 week210(?) questions and patient 1 discussion, i'm a broken record and old

Phase1 week210(?) questions and patient 1 discussion

I've never seen a company hype phase1 data like LCT did and i believe a lot of investors got burned by this. So that's why i keep bringing up why i think the phase1 data might be flaky and i think investors have a right to ask some tough questions of LCT. Plus since i have parkinson's, i think they deceived and created undo risk for the phase2b patients if the proper safeguards weren't taken to ensure the accuracy of the phase1 data and  created undo optimism.

Bottom line, in phase1, the most important thing was get the most accurate baseline UPRDS score from each patient. If for some reason a patient's score was not accurate and too high, from the patient faking it, from the patient just having a bad day, from the scorer scoring too high, WHATEVER, then if the subsequent scores were done more correctly and represented the more accurate lower baseline, then every subsequent score will be inflated and inaccurately show a benefit. If the baseline was too low, and all subsequent scores were more accurate and higher, then the treatment affect would be reduced. Just how did LCT guarantee to shareholders that the baseline UPDRS scores were accurate? Did they run more than 1 baseline UPRDS score? Every patient had been approved earlier for DBS and part of the screening process is taking these same UPRDS tests. So they had those scores for comparison.

https://www.otcmarkets.com/ajax/showNewsReleaseDocumentById.pdf?id=28834

1. What happened to the data from patient3 after week 110, it ain't there. Patients 3&4 were implanted in the same month and patient4's data is there.
2. I would like to know how they are sure that patients WERE unmedicated during the UPDRS tests after the initial baseline test. Do they have the patients come in at least 2hours early and observe them to make sure they aren't taking any medication? Are they sure the patient has not started taking a long lasting version of l-dopa, there is a newer version on the market that could give them 5 hour coverage, i don't know if it has been approved in NEW ZEALAND. There are drugs that make l-dopa last longer. There are one a day pillss available. If LCT can't prove the patient was unmedicated OR NOT PRETENDING TO BE WORSE THAN THEY REALLY AREi would not believe NTCELL has slowed or stopped progression. I would also like to see the ON UPDRS scores to see if they are the same, if progression has stopped then they should be the same or better. I would want to see the patient take their medication to become ON, if they were taking less then they claimed they needed to go ON I would be suspicious that they were medicated during the OFF testing. SINCE THE BASELINE EXAM is so critical, if a patient faked being worse or a scorer scored a little too aggressively, an inaccurated baseline score screws all the subsequent data for the patient. If he/she was still medicated at the baseline exam, their UPDRRS score would have been lower by at least -10 points and therefore if they are examined unmedicated in subsequent test any benefit would be reduced automatically by 10 points. Or the converse, if the patient for some reason, faking it or just having a bad day, had a much higher baseline UPDRS score than he/she should have gotten, then it would exaggerate the affect of the treatment because if all subsequent tests were taken on "good" days, the UPRDS scores would be possibly -10 better just because the baseline was too high.

WITH THE BASELINE SCORE BEING SO CRITICAL, WHAT SAFEGUARDS DID THEY USE TO GUARANTEE IT WAS ACCURATE? DID THE RUN IT MULTIPLE TIMES AND TAKE THE AVERAGE? DID THEY HAVE ANY IDEA WHAT THE NATURAL VARIATION WAS FOR EACH PATIENT FOR THEIR UPRDS SCORES BEFORE THE TRIAL STARTED? HAD ANYONE AT LCT RUN A PARKINSON'S CLINICAL TRIAL DEPENDING ON UPRDS SCORES.

WITHOUT BIOMARKERS, AND HAVING TO DEPEND ON A CLINICIANS POWER OF OBSERVATION TO MEASURE A PATIENTS PD, A UPRDS SCORE CAN BE MANIPULATED BY THE PATIENT OR CLINICIAN, EITHER PURPOSELY OR UNKOWINGLY. LCT NEEDS TO DESCRIBE HOW THEY PREVENTED THIS FROM HAPPENING IMH0, ESPECIALLY WITH PATIENT1.

1. It looks like patients 3 &4 got no benefit even from the placebo affect. The little bit of improvement they had could be attributed to just getting better scores because they have repeated the test so many times and i guess having an adrenalin rush being in the clinic, having doctors and nurses give you a lot of attention, etc.,etc, etc.
2. Has any patients besides patient 1 changed their parkinson's medication and if so, what have the changes been? If they added selegilene, azilect or amantadine, or similar drug then game over, that would explain the -5 point improvement.

5. Patient1 had about a 26% improvement over baseline at week 210. She improved almost 34% from week 184. With such a huge improvement, how many times did they test her? And again, how can they guarantee she isn't medicated?

1. 1. I find it interesting that patient 1 got such a huge improvement from her medication at the baseline measurement, going from OFF 87 to ON 27, a change of 60points!!! Could she have pretended to be just a little worse than she really was, it wouldn't be that hard to do. Or was she just having a bad day, it happens all the time with advanced pd'ers. Just how many times did they measure baseline? Once or multiple times and then took an average? Did they figure out what the normal UPRDS variance was for each patient before the trial or did they just take 1 BASELINE SCORE. What i find odd is that for patient1, she really didn't change much between weeks 22 and 184, all her improvement occured between weeks 0 and 26!!!!!! patients 3&4 look like they got no benefit, patient2 data seems to jump around and patient1, jeez, if she somehow got a really high baseline score at the initial measurement, say 20points higher, then for every other measurement she produced her true baseline, then if the treatment had no affect her scores would make sense.

Here's patient1's data

PATIENT1female, age 59, disease duration 23 years, UPDRS AT BASELINE (OFF)  87,  UPDRS AT BASELINE  (ON)  27 change: 60


PATIENT2  61,F,11,53,25 change 28
PATIENT3   60,M,6,74,32 change 42
PATIENT4  68,M,10,78,29 chang FF/ON SCORES were 51/19 change 35 I'm 63,male,diagnosed 2002.
"the increased dyskinesia in patient1 was resolved in by a reduction in their in their levodopa dosage.   the dosage remained the  same in the other 3 patients."


patient 1 change in levodopa dosage
baseline to week1   1800mg/day  (that's a high dosage)
week1 to week2   900-1600
week2-week3   1100-1800
week3 - current26weeks  600-1200


PET - AT WEEK26 POST IMPLANT THERE WAS NO CONSISTENT CHANGE COMPARED TO BASELINE
this procedure gives a picture of areas of the brain where l-dopa is or something like that.  the significance of this is there is a risk that all the affect is due to placebo and/or a patient is taking extra l-dopa or other pd drugs and not telling anyone.   in patient1, she did decrease her meds which is good  and she did experience increased dyskinesias  which is usually caused by too much dopamine which could be due to placebo or NTCELL.


I want to say i am not a pd clinician and am not an expert in statistics. What i have written are just the opinions of a layman who has watched many companies doing pd research involving drilling holes and having a great phase1 and a failed phase2, so i can at least ask what i hope are some intelligent questions and make some honest observations. But that said, i could be totally wrong in having any suspicions about the phase1 data and it is up to each investor to do their own dd. What i've written here is just a start and i hope it encourages investors to do more dd on biotechs.