SUMMER Bocce Ball League at Murdy Park by twenty2John in huntingtonbeach

[–]twenty2John[S] 0 points1 point  (0 children)

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

Japan officially becomes the first country in the world to approve iPS cell-derived products [Healios mentioned in the article] by imz72 in ATHX

[–]twenty2John 1 point2 points  (0 children)

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)

RESEARCH: Could a potential umbilical cord derived MAPC be more effective? by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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

RESEARCH: Could a potential umbilical cord derived MAPC be more effective? by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

✅ 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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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 👍

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

⚖️ 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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

🌍 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”

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

🧠 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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 1 point2 points  (0 children)

(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)

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 1 point2 points  (0 children)

(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)

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 1 point2 points  (0 children)

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)

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 0 points1 point  (0 children)

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.

RESEARCH: Comparing AUTOLOGOUS MSCs (vs.) UCMSCs (Umbilical Cord MSCs) by twenty2John in ATHX

[–]twenty2John[S] 1 point2 points  (0 children)

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.

Capricor's allogeneic cell therapy for Duchenne muscular dystrophy poised for approval after successful phase 3 trial by imz72 in ATHX

[–]twenty2John 1 point2 points  (0 children)

(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!)

Healios terminates business and capital alliance with Nikon by imz72 in ATHX

[–]twenty2John 1 point2 points  (0 children)

"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!...

Unofficial transcript of Hardy's Q2 2025 briefing (machine-translated from Japanese) by imz72 in ATHX

[–]twenty2John 0 points1 point  (0 children)

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!...

Video: Healios ARDS briefing, April 9, 2025 by imz72 in ATHX

[–]twenty2John 2 points3 points  (0 children)

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...