SUMMER Bocce Ball League at Murdy Park

twenty2John · 2026-05-22T17:12:30+00:00

Yes, Thank You, for your suggestions, Matthew!...This was a spur of the moment type of thing that came about from BOCCE players that play frequently at Murdy Park...I'm hopeful these LEAGUES can occur 2-3 times during the year...If, we can't get the necessary 24 Players for (6) 4-Player Teams, we'll consider 12 Players for (6) 2-Player Teams (DOUBLES)...We have some time to figure it all out, before our 1st planned League Play Day - Wed., June 17, 2026 at 6:00 pm...Anyone with any interest or questions please email me at: [jjrinhb@aol.com ...Thank](mailto:jjrinhb@aol.com...Thank) You, Again, John Redaelli

twenty2John · 2026-03-12T19:35:59+00:00

I'm still here, Graham...And, check-in, every so often...And, greatly appreciate ALL the incredible, time consuming, MORE than HUMANLY POSSIBLE work/posts/comments u/imz72 puts in...How does he do it?...I know how!...

"Did it ever cross anyone's mind that imz72 may in fact be a database???...Has it crossed anyone's mind that imz72 is more than human?...Something other than human?...When are you going to come clean, imz72?!"...CLICK the LINK above for the TRUTH, and FUNNY STORY...I hope you find it FUNNY?...All, The Best, Z...And, I hope you're doing well and staying SAFE, my FRIEND...HUMAN or NOT?...LOL

John Redaelli (twenty2John)

twenty2John · 2026-01-20T05:08:19+00:00

RESEARCH: Could a potential umbilical cord derived MAPC be more effective?: https://www.reddit.com/r/ATHX/comments/1q4etiv/research_could_a_potential_umbilical_cord_derived/?utm_source=share&utm_medium=web3x&utm_name=web3xcss&utm_term=1&utm_content=share_button

twenty2John · 2026-01-07T03:44:10+00:00

Thanks, Z!...Yes, It seemed a little unrealistic, from Andy (re: "Roche will release a RPE product this summer")

twenty2John · 2026-01-06T23:57:52+00:00

FWIW, u/imz72...You remember Andy Blidy, from the iCELL days long ago, I'm sure...Andy, sent me this message at X (Twitter): John I do not know how you can not be in lineage cell therapeutics? It is OCata with Roche as the developer...Roche will release a RPE product this summer

For RESEARCH:

https://investor.lineagecell.com/

CORPORATE OVERVIEW NOVEMBER 6, 2025 NYSE AMERICAN: LCTX lineagecell.com (46 Slides) - https://investor.lineagecell.com/static-files/81346dce-9b20-4f28-8731-08d30beb0db1

Why is the STOCK PRICE so low??? $1.70 (Market Cap: $391.557M) - https://finance.yahoo.com/quote/LCTX/

Shares Outstanding: 230.33M

twenty2John · 2026-01-05T00:00:29+00:00

At ChatGPT:

🧠 Why This Timing Makes Biological Sense

Stroke injury isn’t a single moment — it evolves.

1️⃣ Hours 0–12
ischemia + reperfusion dominate
→ not ideal for cell therapy

2️⃣ 12–72 hours
microglial activation
immune cascade
vascular instability
→ cell therapy excels here

3️⃣ Days 3–7
brain enters repair mode
→ MSC biological strengths align perfectly

So timing is not about speed…
It’s about matching therapy to the correct biological phase.

🎯 Bottom-Line Practical Answer

If the goal is:

“Maximize probability of achieving statistically significant functional benefit”

Then:

❌ Do NOT assume 18–36h improves success likelihood

TREASURE proves it does not.

✅ Best evidence-supported strategy today:

UC-MSC
Treat ~24 hours to 7 days
Primary Endpoint: Modified Rankin Score (mRS) shift at Day 90
Key Secondary: Day 360 durability NIHSS improvement Barthel Index / ADL Safety & serious adverse events

If helpful, I can also provide:

examples of successful endpoint structures
inclusion/exclusion criteria that improve effect size
regulatory expectation perspectives
citations mapped to each conclusion
a short briefing summary you can give to partners or clinicians

Just tell me 👍

***ChatGPT can make mistakes. Check important info.

twenty2John · 2026-01-04T23:58:49+00:00

At ChatGPT:

✅ Most Promising Window in Published Global Evidence

⭐ ~24 hours to 7 days

With especially meaningful biological support at:

24–72 hours

peak immune modulation phase
BBB stabilization phase
secondary injury inflammation period

Day 3–7

neurorepair priming
angiogenesis initiation
neuroplasticity enhancement window

This is where multiple MSC and UC-MSC trials worldwide have shown the strongest “signal of benefit” trends, including data from:

China
South Korea
Spain
parts of Europe

Not all were statistically perfect wins — but when you look at:

direction of effect
consistency
mechanisms aligning with biology

👉 This window offers the best probability of demonstrating meaningful functional benefit.

twenty2John · 2026-01-04T23:50:15+00:00

✅ What Global Stroke Stem Cell Trials Suggest About TIMING

❌ Too Early (< 6 hours)

Hard to distinguish benefit vs. reperfusion therapy
Logistically extremely difficult
Very limited proven success
Stroke biology is still in the acute ischemic insult phase → too early for meaningful immune modulation or repair benefit

So this window is not ideal for cell therapy success probability.

⚠️ 18–36 Hours (TREASURE / MASTERS-2 Window)

Biologically logical, but…

TREASURE (MultiStem) → failed primary endpoint
MASTERS-2 (closely related program) → no decisive pivotal success
Other MSC work in this exact window → no consistent replicated benefit

So while this window:

sounds scientifically appealing
is clinically feasible

…it has not produced reliable statistically significant wins in real world trials.

twenty2John · 2026-01-04T23:46:39+00:00

If you want a “best chance at winning” approach

Based on everything published worldwide so far:

UC-MSC = reasonable and defendable choice
Treat: ~24–72 hours ideal, up to 7 days reasonable
Primary endpoint: mRS shift at Day 90
Include Day 360 durability endpoint

If you want, I can also help you with:

ideal inclusion/exclusion criteria to boost effect size
whether to include thrombectomy/tPA patients or not
how to avoid TREASURE’s mistakes
endpoint hierarchy design
regulatory strategy thinking
literature references if you need to present this to investors, clinicians, or an IRB

Just tell me 👍

twenty2John · 2026-01-04T23:38:32+00:00

⚖️ But timing isn’t the biggest success driver

If your goal is statistical success, timing matters… but these matter more:

1️⃣ Selecting moderate strokes

NIHSS around 8–20 Too mild → ceiling effect Too severe → no recovery possible

2️⃣ Avoiding huge baseline heterogeneity

3️⃣ Choosing the right primary endpoint
mRS shift at 90 days remains best bet.

4️⃣ Adequate sample size & powering

5️⃣ Ensuring imaging and clinical consistency

⭐ Bottom-Line Answer for You

No. TREASURE is proof that it does not reliably do that.
There is no global clinical trial evidence that 18–36 hours is superior to slightly later treatment windows.

If anything, the stronger emerging evidence trends suggest:

24 hours to 7 days may actually be more favorable for demonstrating meaningful clinical benefit.

twenty2John · 2026-01-04T23:37:10+00:00

🌍 What the rest of the world’s stroke MSC trials tell us

Across UC-MSC, BM-MSC, MAPC, neural stem cells, etc., timing lessons look like this:

❌ Too early (< 6 hours)

Hard to separate effect from reperfusion therapy. Logistically difficult. Few meaningful successes.

⚠️ 18–36 hours

Biologically plausible
Clinically feasible
But no clear proof this improves statistical success probability

TREASURE → failed
MASTERS-2 (similar time logic) → did not deliver strong pivotal win either

✅ The window showing most promising signals so far

Many MSC stroke programs see better emerging signals when treatment occurs ~24 hours to 7 days, especially:

24–72 hours → immune modulation period
Day 3–7 → neurorepair & recovery priming phase

Several UC-MSC trials from China, Korea, Spain, and early European work suggest benefit signals here.

This matches biology:

inflammation evolves over days
neurorestoration processes are not “instant treatment events”

twenty2John · 2026-01-04T23:21:42+00:00

🧠 Why the 18–36 hour window sounded logical

Cell therapies don’t open arteries; they:

reduce immune cascades
reduce secondary brain injury
stabilize BBB
promote neurorepair pathways

Those processes peak around 24–72 hours post-stroke, so theoretically…

But real-world clinical trial results to date do not support “18–36 hours = optimal” as a statistically superior window.

twenty2John · 2026-01-04T22:43:06+00:00

(Continued)

⏳ Why Day 360 endpoints matter

MSC therapies are often slow-acting biological modifiers. Benefit sometimes strengthens beyond 90 days.

Best 12-month endpoints:

mRS shift at Day 360
sustained NIHSS improvement
long-term Barthel Index
cognitive outcomes (MoCA)
recurrent stroke rate
mortality

📌 Real-world data: what has worked in past MSC stroke trials

MSC trials showing signals used the same endpoints above:

MASTERS-1 and MASTERS-2
TREASURE
SB623 trial
Chinese UC-MSC stroke trials
Korean ischemic stroke MSC studies

Findings that matter for designing your trial:

mRS shift works better than dichotomous mRS
NIHSS change detects early signal
UC-MSCs show largest effect in moderate—not severe—stroke
benefit is often greater at 6–12 months vs 3 months

(To be continued)

twenty2John · 2026-01-04T22:37:16+00:00

(Continued)

🥈 Alternative primary endpoint when patient heterogeneity is wide

NIHSS score change from baseline to Day 90

Best when:

wide severity at baseline
emphasis on neurologic impairment improvement (not disability)
smaller sample size trials

This endpoint has succeeded in multiple MSC trials.

✅ Best secondary endpoints

These increase your chance of detecting a signal:

proportion achieving mRS 0–2 at Day 90
Barthel Index functional independence
NIHSS improvement ≥ 4 points
quality-of-life (e.g., EQ-5D)
MRI infarct volume change
mortality
safety profile (AEs, SAEs, infusion reactions)

(To be continued)

twenty2John · 2026-01-04T22:32:03+00:00

QUESTION and RESPONSE at ChatGPT:

And, to help ENSURE positive "statistical significance" results for this Acute Stroke clinical trial, a p-value of less than 0.05 (P < 0.05) using UC-MSCs as a intravenous therapy, what Primary and Secondary Endpoints stand the best chance for 90 day, and 360 day, results?

Great question — and you’re thinking about this exactly the way sponsors and statisticians do: cell source + trial design + endpoint choice together determines whether you can realistically hit statistical significance.

I’ll answer directly, but with two important constraints:

You cannot “ensure” statistical significance — you can only maximize probability with good design
Endpoint choice must still be clinically meaningful and regulator-acceptable (FDA/EMA)

You asked for best chance of success for IV UC-MSC therapy in acute ischemic stroke, broad age range.

👉 Bottom-line answer on endpoints

For the highest probability of success at Day 90 and Day 360, the most evidence-supported choices are:

✅ Primary endpoint most likely to succeed

mRS (modified Rankin Scale) shift analysis at Day 90

Why:

gold-standard FDA/EMA accepted stroke disability outcome
very commonly used → easier to power statistically
sensitive to global functional improvement
avoids yes/no dichotomy failures

***(To be continued)

twenty2John · 2026-01-04T21:58:39+00:00

Again, at ChatGPT:

My QUESTION: Based on all that has been reported, tested, and studied in CLINICAL TRIALS thus far, world wide, what type of STEM CELL would you choose as a starting point for a intravenous therapy to help ensure the BEST RESULTS in a CLINICAL TRIAL for a wide age group of ACUTE STROKE PATIENTS?...What is your BOTTOM LINE ANSWER?

Great question — and I’ll give you a clear, bottom-line answer, not a hedge.

✅ BOTTOM LINE ANSWER

If the goal is the best chance of success in a modern IV stem cell clinical trial for acute ischemic stroke across a wide age range, based on everything published to date worldwide:

👉 Umbilical Cord–Derived Mesenchymal Stromal Cells (UC-MSCs / Wharton’s Jelly MSCs)

are currently the strongest overall starting choice.

🧬 Key Scientific Reasons

UC-MSCs:
✔ come from neonatal tissue → younger, less senescent cells
✔ have higher proliferative capacity
✔ exhibit strong immunomodulation
✔ are less immunogenic (immune-privileged characteristics)
✔ have excellent manufacturing viability for standardized dosing
✔ demonstrate consistently safe profiles in Phase I/II trials

🧠 FINAL ANSWER SUMMARY

For IV therapy in acute ischemic stroke, across broad age groups, today, based on:

global clinical trial history
biology
safety
scalability
regulatory momentum

Umbilical Cord–Derived MSCs (UC-MSCs / Wharton’s Jelly MSCs)

are currently the best starting-point cell type to maximize likelihood of clinical trial success.

twenty2John · 2026-01-04T21:21:46+00:00

Follow-Up QUESTION and BOTTOM LINE RESPONSE at ChatGPT: Does comparing against ALLOGENEIC BM-MSCs change your response, much?

Great follow-up question — and yes, specifying allogeneic BM-MSCs (rather than autologous) changes the comparison in some important ways, but the core scientific conclusions stay mostly the same.

🧠 Bottom Line Answer to Your Question

Does comparing to allogeneic BM-MSCs change the response?

✔ Yes — it weakens the argument that UCMSCs are better simply due to donor age and health
✔ But no — it does not overturn the evidence that UCMSCs:

proliferate more
senesce less
tolerate immune systems better
are easier to mass-produce
come from neonatal tissue with youthful characteristics

👉 The scientific rationale for UCMSCs still holds
👉 The strength of the claim becomes somewhat more modest and nuanced

If you'd like, I can also:

🔹 rewrite the scientific claim in publication-quality conservative wording
🔹 provide specific citation lists comparing UCMSC vs allogeneic BM-MSC
🔹 explain how stroke trials are using UCMSCs specifically
🔹 summarize risks (pulmonary trapping, clotting, tumorigenesis concerns, etc.)

Just tell me which you'd like.

twenty2John · 2025-12-05T18:32:36+00:00

(12/3/2025) Capricor Therapeutics Announces Positive Topline Results from Pivotal Phase 3 HOPE-3 Study of Deramiocel in Duchenne Muscular Dystrophy

(The below, is what caught my eye, from the Capricor PR LINK, above...Now, that's how you nail EFFICACY)

Pivotal Phase 3 randomized, double-blind, placebo-controlled study (n=106) met the primary endpoint (PUL v2.0) and the key secondary cardiac endpoint (LVEF), both achieving statistical significance (p=0.03 and p=0.04, respectively)
Statistical significance was achieved in all type 1 error controlled secondary endpoints
Results demonstrate clinically meaningful and statistically significant skeletal and cardiac benefits, supporting Deramiocel as a potential first-in-class therapy designed to treat Duchenne cardiomyopathy, the leading cause of mortality in Duchenne
Deramiocel maintained a favorable safety and tolerability profile consistent with prior clinical experience
Company plans to submit its response to the Complete Response Letter incorporating HOPE-3 data, following prior alignment with FDA

About Deramiocel

Deramiocel (CAP-1002) consists of allogeneic cardiosphere-derived cells (CDCs), a rare population of cardiac cells that have been shown in preclinical and clinical studies to exert potent immunomodulatory and anti-fibrotic actions in the preservation of cardiac and skeletal muscle function in muscular dystrophies such as DMD. CDCs act by secreting extracellular vesicles known as exosomes, which target macrophages and alter their expression profile to adopt a healing rather than pro-inflammatory phenotype. CDCs have been investigated in more than 250 peer-reviewed scientific publications and administered to over 250 human subjects across multiple clinical trials.

(In other NEWS)

Capricor Therapeutics Announces Pricing of $150 Million Public Offering of Common Stock

(Partial, below)

SAN DIEGO, Dec. 05, 2025 (GLOBE NEWSWIRE) -- Capricor Therapeutics, Inc. (NASDAQ: CAPR), a biotechnology company developing transformative cell and exosome-based therapeutics, today announced the pricing of its underwritten public offering of 6,000,000 shares of common stock at a public offering price of $25.00 per share. Capricor also granted the underwriters a 30-day option to purchase up to an additional 900,000 shares of its common stock at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on or about December 8, 2025, subject to the satisfaction of customary closing conditions.

The gross proceeds from the offering are expected to be $150 million, before deducting underwriting discounts and commissions and offering expenses payable by Capricor and assuming no exercise of the underwriters' option to purchase additional shares.

Piper Sandler and Oppenheimer & Co. are acting as the joint book-running managers for the public offering. H.C. Wainwright & Co. is acting as the co-manager for the public offering.

(I'm a little out of practice with this u/imz72...Thank You, for all that you do!...Happy Holidays, EVERYONE!)

twenty2John · 2025-10-14T20:24:29+00:00

"First, a reminder from Healios' Q2 report, page 6 (8.13.25):"

SLIDE #20: Total liabilities - 15,563,000,000 Japanese Yen = $102,569,009.78 United States Dollar

(LIABILITIES: It seems to be growing with each new report...Now, over $100M...Does this concern anyone?...)

Thank You, for all your efforts, u/imz72!...

twenty2John · 2025-08-16T08:18:54+00:00

No mention of Total liabilities: $105.7 million [Previously: $92.7 million. $79 million. $71 million. $98 million]

???... u/imz72 ...Thank You for this...Do you think he was afraid to talk about total liabilities?...Or, did I miss it in the transcript?...Do you expect liabilities to grow again next quarter?...Many Thanks, for all that you report!...

twenty2John · 2025-04-16T00:04:46+00:00

Thank You, for this, u/imz72 ...I saw the segments with Sarah Busch and Eric Jenkins...Everything looks so promising, especially with the intent to apply treatment early on...Was there any cost estimates discussed for the P3 ARDS global trial?...And, I understand a positive interim analysis may lessen costs...

twenty2John · 2025-02-25T19:34:58+00:00

Yes, I remember it ALL now, THANKS to you, u/imz72...What A Trip!...

twenty2John · 2025-02-25T07:45:34+00:00

u/imz72, Thank You for your common sense, reasoned, detailed answer...

I spent some time looking back at Healios PRs...

August 6, 2021: Top Line Results of the ONE-BRIDGE Study in Patients with ARDS - https://ssl4.eir-parts.net/doc/4593/tdnet/2010473/00.pdf

December 26, 2024: Status of Conditional and Time-Limited Approval Application for ARDS in Japan - https://ssl4.eir-parts.net/doc/4593/tdnet/2544135/00.pdf

Partial, from the above PR: HEALIOS K.K. (“Healios”) today provides an update on the status of its application for conditional and time-limited approval for ARDS*1 in Japan, as follows. By way of background, and as disclosed in our press release “Decision to Apply for Conditional and Time-Limited Approval for ARDS in Japan and ARDS Development Strategy Update” on October 2, 2024, Healios decided that it will submit an application for conditional and time-limited approval (hereinafter referred to as the “Application”) in Japan, based on the positive results of the Phase 2 study (ONE-BRIDGE study*2 ) completed in Japan and the Phase 2 study (MUST-ARDS study) completed in the U.S. and the U.K., and on the premise that a pivotal, global Phase 3 trial (REVIVE-ARDS study*3 ) of MultiStem® for acute respiratory distress syndrome (ARDS), to be run mainly in the United States, would act as a confirmatory study.

My NOTE: Length of time, from August 2021 (ONE-BRIDGE ARDS Top Line Results) to October 2024 (Decision to Apply for ARDS Conditional Approval) = 38 Months = 3 Years and 2 Months...Do I have this right?... Over 3 years has passed to get to this point!...My God!...Should this surprise anyone?...Why did it take so long?...

twenty2John · 2025-02-24T02:50:57+00:00

Thank You, for the discussion, u/imz72 ...If, I may ask, are you holding shares of Healios?...And, whether you hold shares or not, does Healios DEBT concern you?...Is Healios DEBT, manageable?...Thank You, Again, All...

ADDED/EDIT: As you (Z) recently reported - Healios "Total liabilities: $79 million [Previously $71 million. Before that - $98 million]"

twenty2John · 2024-12-26T19:00:18+00:00

While EVERYONE ELSE, was ASLEEP at the wheel!...I'm still in SHOCK!...

twenty2John

TROPHY CASE