We are now here... and all bets are on the table!

[Ceasar de Cuenca]

I am sure that Lanza, Mickunas, Rabin, and Bill Caldwell are all as excited as I am considering
the events that will be unfolding in the coming months.

Last night, I spent many hours going back over our patents, published materials, conference presentations,
videos, and comments on a very specific topic. And, this is the engraftment of the RPE Cells on the BM.
I was looking at the characteristics of the RPE Cell surfaces, the influence of integrin, and the age and the health of the BM... all, and everything and as much studies/trial information in animals and humans, as these influence the engraftment process of the RPE Cells into the BM.

This is the heart of ACTC's trials.

This morning and most of today, I am still looking for any negative data that will make me doubt or change my mind in regards to my confidence that ACTC will be successful.

Off course, I know that anything can go wrong!

On the other hand, if there is any team, anywhere, who knows this issue... It is Lanza's team.

But, I want to make sure... for my own peace of mind.

So, I reviewed our RPE patents, and Wow! Many times, and this patent is worth much much more than
one can imagine. Reviewed, again, the pre-clinical studies and animal models, reviewed other studies involving cadaver RPEs, fetal RPEs, and adult RPEs... and its engraftment results and issues...

And hell! after many hours... I still could not find any data that will dampen my judgement call that ACTC is very close to a home run.

And yes, if there are any PHDs around who will tell me that something can still go wrong... I agree.
But heck, anything can go wrong on anything, any day... but I am not talking about this kind
of statistical probability.

I just had a very nice Reserva Chianti from Tuscany and a double cappuccino...
and I am mellow.

I suppose I have done looking at all the possible things that can go wrong... and I am ok.

I am happy.

Best and just making sure,
Cuenca

[bo-bo241]

Today is my 4th year anniversary owning ACT stock and quite happy about all progress and sugested outcomes. Really looking forward to this years events. I am hoping that indeed OHSU is one of the sites. It is a great teaching hospital and right next door to Casey Eye Institute, where the rat tests were done. I'm Oregonian and proud to be on this threshold, best to all of us and ACT.

[BioDigger]

Well, Cuenca, I had a personal experience today. Had my eye exam and was informed that my AMD had advanced in the past three years. I can't see anything different yet but my MD says it is advancing and that I will go blind eventually. He knows about ACT and said that their stem cell treatment would NOT help my type of AMD. He did say other companies were working on AMD treatments that would apply. That was the first time I had heard there might be different forms of AMD and that not all were stem-cell treatable. I posted a rather long post earlier today but it seems to have disappeared. At least I can't find it. But it is that kind of 'surprise' that bothers me, it is the shot from left field because it can cause treatment "failures" and we all know what that will do to the PPS. Guess we'll see if this post makes it past the monitors.

BD

[stemedga]

Ceasar,
I support all what you say here. We are not perfect in what we do in the lab. That is why it is research. These trials are perhaps the greatest event since the invention of the wheel. People scream why don't the trials start already..... This is the most scrutinized event and rightly so, for they are crossing every T and checking and rechecking. Patience and you have just stated why. The ACT Lanza Team will not accept failure.

[bobo]

Ceasar,
Reserva Chianti from Tuscany, a double cappuccino, and your sure Bill Caldwell is as excited as you are. I'll have some of that Chianti, and cappuccino please. lol. Thanks again Ceasar for your insightful analysis of the facts.
bobo

[allmar]

I agree with the analysis.

[Bullard]

Thanks for sharing your perspective Ceasar. Uncertainty is embedding is in the fabric of everything but the failure of the RPE cells to graft appears remote. My analysis is more focused on degree of success (i.e. - at what point in the progression of the disease will the RPE cells show improvement and to what degree?). The answer to that question will probably determine if we're a $2 billion cap company or a $100 billion cap company in the next five years.

[Harlem]

Glad to see your post!!! thank you

[eigenman]

Thanks for sharing your perspective Ceasar. Uncertainty is embedding is in the fabric of everything but the failure of the RPE cells to graft appears remote. My analysis is more focused on degree of success (i.e. - at what point in the progression of the disease will the RPE cells show improvement and to what degree?). The answer to that question will probably determine if we're a $2 billion cap company or a $100 billion cap company in the next five years.

Keep in mind that the researchers of the BM paper 2 months ago said in an email they have a method that they believe will help attachment in the severely damaged BM cases.
Attachment is the key here and it sounds like it will only get better.

[great-grandma]

Thanks, Caesar, for all the work you do. I always look forward to your posts.

[jckrdu]

I believe the Phase I safety trials will be a homerun, and I believe we'll see some level of engraftment of the RPE cells in the early Phase 1 results. I do like that Rabin is working to set expectations via his statement in his recent email where he wrote: "Certainly, the patient selection of the first cohorts in the trials, particularly of the AMD patients (who will tend to be elderly with severely deteriorated sight) may impact our engraftment viability."

I'm still not 100% certain when younger Dry AMD patients with better sight and a higher probability of viable engraftment will start to be enrolled. Do we have to wait until the first 12 patients (over 55 with severely deteriorated sight) get all the way thru Phase I before younger patients are enrolled? That's my understanding.

[jckrdu]

I believe the Phase I safety trials will be a homerun, and I believe we'll see some level of engraftment of the RPE cells in the early Phase 1 results. I do like that Rabin is working to set expectations via his statement in his recent email where he wrote: "Certainly, the patient selection of the first cohorts in the trials, particularly of the AMD patients (who will tend to be elderly with severely deteriorated sight) may impact our engraftment viability."

I'm still not 100% certain when younger Dry AMD patients with better sight and a higher probability of viable engraftment will start to be enrolled. Do we have to wait until the first 12 patients (over 55 with severely deteriorated sight) get all the way thru Phase I before younger patients are enrolled? That's my understanding.

I'll talk to myself a little here: On the other hand, Rabin's statement specifically states that patients in the "first cohorts" will be elderly with deteriorated sight. To me, that implies that patients in the later cohorts will have better sight. So maybe after results are in for the first 2 cohorts (patients 1-6) we'll start enrolling younger patients with better sight?

[Actc_fan]

I'll talk to myself a little here: On the other hand, Rabin's statement specifically states that patients in the "first cohorts" will be elderly with deteriorated sight. To me, that implies that patients in the later cohorts will have better sight. So maybe after results are in for the first 2 cohorts (patients 1-6) we'll start enrolling younger patients with better sight?

Your guess is as good as mine, but that would make sense to me. Once they are seeing good safety results in the first few patients, I would think they would want to test the limits of both halting progression of the disease and trying to demonstrate improvement. I imagine improvement might come easier in patients with less damage. JMHO

[jckrdu]

Your guess is as good as mine, but that would make sense to me. Once they are seeing good safety results in the first few patients, I would think they would want to test the limits of both halting progression of the disease and trying to demonstrate improvement. I imagine improvement might come easier in patients with less damage. JMHO

I think that's the way it will go. I was getting hung-up on the entry criteria posted on clintrials.gov, and was working under the assumption that it was static. I now believe that after safety results are validated for the first 2 cohorts, we'll see an update to the entry criteria on clintrials.gov where we'll be able to enroll younger patients with better sight. This all makes sense as this is a combined Phase I/Phase II study.... and Phase II is testing for efficacy..... and in order to test for efficacy you need to enroll younger patients at earlier stages of the disease.

[ACT4me]

Salut !! C.C

[adventurous]

Please everyone keep in mind that when there is news on safety results of Phase I trials that if there is no mention of improved vision do not be disappointed. I think some people are under the assumption that these older cohorts will regain some vision. While apparently possible, the YES/NO of the clinical trial is SAFETY and not effectiveness.

So when results come out simply stating that there's no adverse reaction, but no mention of improved vision, do not be disappointed. You may even see a drop in pps due to many people expecting a miracle. Case in point: Geron. They released patient 1 had no adverse side effects. The stock didn't skyrocket. In my opinion it was phenomenal news, but the market only wants to hear about efficacy and not safety.

Just my .02c

[Mtn Man]

I'll talk to myself a little here: On the other hand, Rabin's statement specifically states that patients in the "first cohorts" will be elderly with deteriorated sight. To me, that implies that patients in the later cohorts will have better sight. So maybe after results are in for the first 2 cohorts (patients 1-6) we'll start enrolling younger patients with better sight?

The enrollment criteria is here Search of: MA09-hRPE - List Results - ClinicalTrials.gov for both trials AMD and SMD.

AMD 55 years or older
SMD 18 years or older

The question I have is, are we looking for the same attachment to the BM for both AMD and SMD? If so, then we may get to see an attachment difference between older and younger BMs. Maybe, SMD and AMD are too disparate to compare across the two studies.......

If any of our in-house Dr. can review some of the eligibility criteria it would be interesting to hear their thoughts.

Mtn Man

[eigenman]

The enrollment criteria is here Search of: MA09-hRPE - List Results - ClinicalTrials.gov for both trials AMD and SMD.

AMD 55 years or older
SMD 18 years or older

The question I have is, are we looking for the same attachment to the BM for both AMD and SMD? If so, then we may get to see an attachment difference between older and younger BMs. Maybe, SMD and AMD are too disparate to compare across the two studies.......

If any of our in-house Dr. can review some of the eligibility criteria it would be interesting to hear their thoughts.

Mtn Man

I'd like to know how damaged young Stargardt's patients' BM's are compared with people with AMD. I know as you get older AMD can damage the BM more and more, but I don't have any data on the BM's of Stargardt's patients. Are the BM's in good or bad shape at a young age?

[jckrdu]

The enrollment criteria is here Search of: MA09-hRPE - List Results - ClinicalTrials.gov for both trials AMD and SMD.

AMD 55 years or older
SMD 18 years or older

The question I have is, are we looking for the same attachment to the BM for both AMD and SMD? If so, then we may get to see an attachment difference between older and younger BMs. Maybe, SMD and AMD are too disparate to compare across the two studies.......

If any of our in-house Dr. can review some of the eligibility criteria it would be interesting to hear their thoughts.

Mtn Man

Mtn Man - Yes, I saw the enrollment criteria. See my subsequent post where I state my belief that clintrials.gov and the enrollment criteria will be updated after the first 2 cohorts report satisfactory safety data. My thought is that we'll see the enrollment ages reduced after cohorts 1-2 so younger patients are enrolled to test for efficacy in this combined Phase I/II study. On your second question, I suspect we'll see better RPE engraftment in the SMD patients for cohorts 1-2, but an eye doc is better to respond to that question.

[Superfeeed]

Well, Cuenca, I had a personal experience today. Had my eye exam and was informed that my AMD had advanced in the past three years. I can't see anything different yet but my MD says it is advancing and that I will go blind eventually. He knows about ACT and said that their stem cell treatment would NOT help my type of AMD. He did say other companies were working on AMD treatments that would apply. That was the first time I had heard there might be different forms of AMD and that not all were stem-cell treatable. I posted a rather long post earlier today but it seems to have disappeared. At least I can't find it. But it is that kind of 'surprise' that bothers me, it is the shot from left field because it can cause treatment "failures" and we all know what that will do to the PPS. Guess we'll see if this post makes it past the monitors.

BD

Biodigger, can you PM me your eye docs name so I can send him an email. He is obviously not understanding you or you did not provide him the correct information. I am thinking Dr. Lund knows a bit more about the RPE cells ACT is using and so is not the some odd 25 Opthamologist members iCELL has. BTW what kind of AMD do you have wet or dry?

thanks

SF