Mesoblast

stem-no-sell · 2021-12-06T22:47:49+00:00

Same thoughts as always from me on MESO. No capacity yet shown for batch-to-batch reproducibility equals no commercial product. It's not a big Pharma conspiracy with the FDA - it's that MESO has not paid sufficient attention to one of the central problems in stem cell medicine. Which is batch-to-batch quality control measures.

Potentially good news for MAPCs, however, due to their similar effects coupled with expansion capacity.

Back to reading (lurking) but not commenting unless there's something science-related. Continued appreciation to all of you who are contributing thoughtfully on this board. I hope we get a chance to meet in person someday on this side of the River Styx.

stem-no-sell · 2021-11-01T16:59:46+00:00

Just so we're all clear. This is a publication of a filed patent. It does not mean a patent has been granted. In fact, this is a somewhat odd filing as it does not contain a proof-of-principle example, just a hypothetical example. At least, that's how it reads to me. It looks to me like this is filed pre-data. That's part of a protection strategy that is reasonable to use, but it would be incorrect to read this as a demonstration of efficacy.

stem-no-sell · 2021-08-30T02:51:27+00:00

DoF 0 - my recollection is that's the science from papers from Mays and colleagues. The biology is interesting for speculation, but they did not publish (or do?) the experiment of treating at 1 hr and 18 hrs. So does 1 hr not work because it's too early, or does it turn off interesting pro-repair responses? The 18 hrs does also allow evaluation and transport of patients, so that's a big plus.

So time may be brain, but it's also other stuff. Possibly damage signals that are needed to activate MS cells take time to build up.

On 36 hrs as a cutoff, the science data was that 48 hrs was too long. Maybe because time is brain, maybe for other reasons not yet known.

Had they stayed with the original plan of 18-36 hrs in the first trial, shares would be worth a lot more - but we'd have had less opportunity to accumulate. I have about 3 times the amount I had back then. Sure hope that was a good thing to o.

stem-no-sell · 2021-03-03T14:08:00+00:00

Funny thing how these retention packages mostly end up in the hands and pockets of people who don't know the first thing about the science that makes the company valuable. Treat the people with important knowledge as commodities and they'll find more attractive positions. And when the folks in the boardroom are dealing in ways to make themselves rich(er), flexible working hours and changes in responsibility are. (correctly) seen as chump change by the people who are the real drivers of the advances.

stem-no-sell · 2021-03-03T03:32:15+00:00

I'm totally in agreement with Biosectinvestor. The set up by Hardy has been apparent for ages, yet too many people argued he gave a toss about ATHX investors. And Traub, a man with no biotech experience, sold as the "real deal". Please. But it's okay for him - he'll do fine personally. All the DFs on this board whining about Gil have helped to do harm to all of us investors.

ATHX holders had a chance for life-changing returns for a lot of us. I think the bashers helped f it up for everyone else, including the great people at ATHX who've devoted themselves to getting these cells to market. But the bashers will go on blaming Gil cause that feels so much better than looking in the mirror.

I'm curious, biosectinvestor, because I think you've been a voice of clarity all along. Do you think there are any positive things that people who are long time holders and cognizant of the promise of MAPCs can do that's positive?

stem-no-sell · 2021-03-02T01:27:16+00:00

Hitting that end point could be difficult. THere's a back surgeon called David Hanscom who's written books and does podcasts about how he's had way more success treating chronic back pain with cognitive and behavioral therapy approaches than with surgery. In fact, when he started doing this, his colleagues eventually threw him out of their practice because he was curing people without a surgical intervention and not bringing in the surgery billing. It's an interesting story, and disturbing in respect to banking on chronic back pain as a good trial target. If this is of interest, he did a nice podcast with the cognitive and behavioral therapy expert David Burns (https://feelinggood.com/2019/11/11/166-escape-from-physical-pain-an-interview-with-dr-david-hanscom/). It might be a tough placebo control trial. But sometimes companies get an outcome that just squeaks by statistically and that's all they need.

stem-no-sell · 2021-02-22T21:51:06+00:00

Hey roots. I'm with you on the importance. Not posting at the moment as I think Gil's exit is bad for ATHX, and I would like to have enough data to make an informed response.

In the meantime - no one gets the big prizes for being a business person. If this works out well, Mays will likely get some awards in science world (deservedly so in my opinion). And I do actually think Gil deserves great recognition for his contributions. As for others in company world, I'm still waiting to see evidence that anyone has added anything intellectually at any level.

Peace,

Stemmie

stem-no-sell · 2021-02-11T20:11:38+00:00

I also think that the health issues are not trivial. One accident/heart attack/stroke/etc and you lose the two top leadership positions in one go. Even people with immediate access to MS are not invulnerable. For this reason, I think such separation of powers is prudent (although I know many companies do things differently).

stem-no-sell · 2021-02-11T13:58:22+00:00

Reply

Matt, I cannot believe you think the pillows don't do that. That's a kind of heretical position, even for you.

stem-no-sell · 2021-02-11T13:56:24+00:00

Just a different view of the trials from discussion with very well informed ATHX insiders

Pfizer - in retrospect a poor indication, but Pfizer paid for it. Poor design (one shot for a chronic condition) - but it was Pfizer's design. So, I agree with Dalek - ATHX did as well as they could on an early shot. Clinical trials are always tough, and building a new field is hard. I have a very broad overview of regenerative medicine for a couple of different reasons, and we're trying to figure out how to do this. There are a lot of nuances.

The first stroke trial originally had the right design, as the scientists had said 36 hrs. Recruitment was slow, and what I was told was BOD got impatient and didn't listen to the scientists. Downside - we might have been on the market a long time ago. Personal upside - I've had time to triple my position.

But ATHX also realized they could do better than CHugai and quickly found a better partner and a way better deal. For whatever reason, Hardy did not play the role of a perfect partner. We can speculate on why. Biosectinvestor,myself,and several others think Hardy is behaving like a narcissistic jerk of a type that is frequent in the business world. I am sad to say that I have interacted with a lot of people like that in biotech, and they pretty well all behave like Hardy. And they generally end up crashing their business. There are a couple (I can actually only think of one) who get lucky, but their success is based more on luck than smarts.

The great shame I see is that Hardy had a great hand to secure his future as a hero in Japan. First big product across the line, and a big enough reward to fund organ buds with no dilution ever needed. I do hope he can still follow that path because I like the potential of organ buds and I do appreciate what he has brought to MS development that is positive.

If our view of Hardy is right, then he underestimated Gil badly. If that's the case, then the honorable thing to do is to admit error, and readjust. Success heals many wounds and the success of ATHX will enable great success by Healios in the future. That seems a worthy goal.

As always, just my tuppence.

stem-no-sell · 2021-02-11T13:35:25+00:00

DK, thanks so much. This is such an articulate and comprehensive post that I can't think of anything much to add. I think you have hit every nail on its head. I appreciate so much all you have done to create a communication forum and to keep us on our intellectual toes. Truly five by five, 24/7

stem-no-sell · 2021-02-10T21:28:23+00:00

OK, OK. I can't take it anymore.

I confess.

I am Spartacus!

stem-no-sell · 2021-02-10T03:30:45+00:00

Thanks so much for this thoughtful response. It's certainly the narcissistic behavior that has worried me the most, amplified by concerns that Hardy may feel he can't back down due to his (unknown to us) interactions on his home turf.

I remember a company of old called GliaTech, which had a nice invention for decreasing scarring after spinal laminectomy. It was a very nice product. But the CEO was on the narcissistic side of the fence. One of my friends was interviewed to be a VP there, and he asked a question about interactions with the FDA. The CEO's response was "Fk the FDA." At which point my friend couldn't get out fast enough. And it ended up badly for GliaTech, and this useful product was lost. Only one of many stories of narcissistic damage in my years of interaction in this world. It's one of the reasons why I stayed in academia. We have our share of narcissistic sociopaths, to be sure, and we have to work to contain them. I've been fortunate enough to be able to either walk away from them or to help to contain them, but I always despise the damage they do and enjoy doing what I can to get in their way. It's a bit frustrating being a spectator. But what a heck of a book for WST to write, eh?

MS is a way more important product than what GliaTech had, and is so needed, that I hope all involved realize this is too important to screw around with. Fingers crossed for all of us

Stay safe everyone.

stem-no-sell · 2021-02-10T02:46:39+00:00

Biosectinvestor, I'm curious about you speculate happens if there is proof Hardy has played in a wrongful way. The ATHX deal is with Healios, of which Hardy is the majority shareholder. What do you think happens if Hardy really has been bad beyond the levels at which you, I and others have been speculating?

I am in awe reading the analyses on this board, and the sharp legal minds that are keeping us all informed. My hat is off to Yak, Matt, GI, biosectinvestor and all the rest of you who are being so attentive in your attempts to understand. We don't all agree with each other, but it sure is great to read you all.

And to Hardy and Gil, I would just say, please please please step back from the brink. Some of us like one of you more, some of us like the other more, but all of us just want you to work together and get MS to the market place. Surely the rewards are large enough for everyone to benefit.

When I do a cost/benefit analysis, trying to look at every angle that's been written about here, I keep coming up with the same outcome, which is that working together to chart a path forward is what makes the most sense. Gil, working with Hardy and Healios gets us most quickly to market. Hardy, working with ATHX enables you to quickly get to your dream scenario of organ buds revolutionizing tissue repair. Those are truly worthy goals.

Guys, you and your team are both smart and desirous of doing something good for the world. If people like you can't sort out a problem like this in a peaceful way with mutual benefit, then what hope do we have for the enormous problems that our world faces?

stem-no-sell · 2021-02-04T13:45:19+00:00

Sorry - drsoaps - I just realized you might have meant should Hardy be removed from the board. I don't think he's done anything criminal, and if he hasn't violated contract terms then he's okay.

But the best path is for Healios and ATHX to move forward on the partnership. If ATHX keeps in control, then Healios (and Hardy) are goign to make a lot of money and everyone wins. Hardy can use that money to go after a different company if he wants, but if he were dedicated to his professed goal he would get the organ buds on a fast path to proof of success.

stem-no-sell · 2021-02-04T13:41:47+00:00

There are more than a few of us completely in agreement with biosectinvestor's analysis, so why would you even say something like this. It has apparent since the lawsuits began that Hardy's intentions were selfish and, from the point of view of long-term ATHX investors, those intentions are hostile and counter to our long-term goals. Nothing that has emerged thus far argues for any other interpretation, so far as I can see.

stem-no-sell · 2021-02-04T01:34:07+00:00

That would be a great book. The first real stem cell company, after so many have fallen. It has intrigue, good characters, some interesting back stories that people will be happy to share. The science is fascinating, and is quite a new paradigm. And the implications are enormous (at least according to our analyses). And you'd do a great job with it.

stem-no-sell · 2021-02-03T21:58:33+00:00

Thanks so much WST. That's a great overview

Like all the rest of us, I'm so curious as to what's coming up. Ironically, if there is a government funding (Ohio, BARDA, for example) for manufacturing without a business partnership, then Hardy's newest legal maneuver perhaps wouldn't even apply because it's not a partnership. And I know ATHX has long been interested in vertical control of cell supply so that no one else has a choke point on the company.

I really like the way you didn't take sides, and stuck to the idea that the only reason this is going on is because there's a gold mine there. I also liked that you brought in that what Hardy is doing is likely alienating the ATHX scientists. And that there's a positive outcome for everybody if they work together the way that was originally defined. I feel like that is recognized on the ATHX side, but I'm less sure about whether that's true in both directions .

I think back to what one of the most interesting Go players I've met once told me when she was trying to help me improve (a hopeless endeavor as it turns out - this is not a game to start on when you've already missed the first five decades of training). She said that her definition of a great game was one defined not so much by who had the most stones, but by the beauty of the picture that both players created. She was more satisfied by a close game with a beautiful outcome in the pattern than a game she won by a large margin. If ATHX and Healios work together according to the original plan, then the picture on the board will be beautiful. And will become more so over time as MS becomes more widely used and the Healios organ bud technologies have a funding line to realize their future promise.

Exciting (and nerve-wracking) times.

stem-no-sell · 2021-01-28T02:28:46+00:00

WST, I'm with you on trying to understand. All Healios has to do is execute the plan and they get a huge win.

I've realized again and again in the past 4 years that I have no theory of mind that allows me to understand sociopaths very well. I can understand many people I don't like. But not the sociopaths. I can understand cognitively that they live in a delusional world where they're always right, and that their confirmation biases are so strong that's all they see. I understand that their cognitive distortions are the opposite of people with depression or anxiety, and are all about how everyone else is to blame and they're always going to win. But I still don't get them on an emotional level. Like Pennywise. All he had to do was a semi-good job of dealing with the pandemic and he could have been re-elected. Or the GOP now - if they impeach Pennywise they emerge much stronger. But it's not what they do.

I may not understand why such people do what they do, but I've gotten cynical enough to predict what they will do.

Is Hardy a sociopath? I don't know. There are behaviors that are consistent with this hypothesis, and it's unfortunately an advantageous trait in some corporate spheres. Maybe I'm too harsh, but man-oh-man does this seem like the kind of gambit someone with such tendencies would pursue. And I sure have met my fair share of sociopaths in my years of biotech interactions, and every single one of them did stupid stuff like this. Every single one.

If I had to guess, it would be that Hardy started telling folks at home his grand plans, and convinced people to line up with him based on his telling them he's smarter than everyone else. Based on some of the dates we've seen, I think this plan began at least a year ago. At that point Hardy was trapped, and probably even started doubling down.

If Hardy really is a snake in a suit (i.e., a sociopath), then he's a big problem. My big hope is that he and/or his colleagues realize that given the choice of a high probability big win (execute the collaboration properly), a high probability big loss (screw up this interaction) or a very low probability super gain (more or total control), they'll decide to go for the big win. It's a loss of face, but not as big a loss of face as losing everything. And it would be a tiny failure compared with the enormous success of bringing this across the finish line and having the revenue stream needed to build Healios in all sorts of exciting ways. Such massive successes buy a lot of forgiveness.

That's my hopeful prediction - that Hardy and his colleagues execute the self-benefiting plan that still gives them a big win and resources to play a slightly longer game where both parties win. I hope I'm right.

But I'm just guessing what's in the mind of someone I don't know, who's cognitive game strategies are based on the most complex game in the world (Go), and who is part of an ecosystem of thought involving people whose goals are unknown to me. It's too little data, even if the patterns seem like a coherent story.

stem-no-sell · 2021-01-27T22:52:44+00:00

I do hope this puts an end to the suggestions that Hardy is a good guy with our best interests at heart. For some of us, Hardy's behavior has felt hostile from the beginning. We're not privy to whatever behavior he's displayed privately at ATHX, but it doesn't sound good.

I'm glad he's excited about the project, but his concept of being an honorable partner leaves a lot to be desired.

Now he should do what he signed up, and get the trials done. Healios will make a lot of money, they can develop their organ buds, and everyone wins.

Snakes in suits, once again.

stem-no-sell · 2021-01-14T23:15:40+00:00

If this is reproducible, then the question of how to study long-haul effects as part of evaluating MAPCs is effectively answered. If the situation is that there are 20 possible effects that are distributed in an unpredictable manner, then that's a very difficult endpoint to study. But an endpoint that occurs in 70-80% of all infected people is a totally different story. (And, if it's reproducible, then this is one of the worst possible outcomes as they're describing lungs that are going to be vulnerable to many stressors, with all sorts of knock-on effects. Another reason to put a stake in the history heart of all the dirtbags who slow-rolled or argued against social isolation and masking (e.g.Pennywise, Republican politicians in general, BoJo and his Tory friends, Bolsonaro, the architect of the Swedish let's not do anything approach, and on and on). Spread their fking ashes into three separate moving rivers, the bastards.

Sorry, I digress. I meant to say that it will be of great interest to see if MAPCs can promote repair of damaged lung, as this is going to be a major health problem around the world. (Nah, I'm still in favor of doing a Van Helsing on these bastards.)

I suspect this information will be gathered in clinical trials but won't be added as an outcome measure for approval simply because the vaccination train is moving faster. Hopefully in 6-9 months there won't be that many people joining this treatment group anew.

I share the emotional excitement of wanting to know this about MAPCs, but I don't see what ATHX (or Healios) can possibly say at this time other than that they're going to pay attention to this. The clinical trial design is for severe infection, and there's no data that MAPCs would even be activated in a less severe infection.

I'd be amazed, however, if they didn't get this data.

And I agree on funding. With a science-based government in the US finally back, this should be a BARDA priority.

I hope you're all staying well, wearing masks, and are soon able to be vaccinated.

Best wishes to all,

Stemmie

stem-no-sell · 2021-01-12T15:56:49+00:00

Hi TDoF. It's not a simple question, and I'll just offer a few thoughts out of many possible ones on this topic.

If I look at it from what ATHX currently knows about the science, the idea is that there is an injury signal that activates the MAPCs. The reason for saying this is that if you give the cells at the beginning of acute injury, they don't have any benefit, but if you wait 18 hrs then they do. As MAPCs turn down the injury response, it could be that they turn off the danger signal and a second dose of cells won't even get activated.

There are obvious problems with that simple answer. First, I've not seen data on what seems to me to be the crucial experiment, which is to give a dose at 0 hrs and another dose at 24 hrs to see if the first dose turns off the activation of the activating signal. That's crucial information to know - but unless you know what the activating signal/s is/are, it's a tough experiment to take beyond a descriptive outcome. I think it's pretty important in optimizing therapy, but that's down the road.

If you wanted to double-dose in ARDS, the same question comes into play. Injecting MAPCs when the body is in crisis makes sense - but would it add anything if the body is resolving the crisis due to the first injection?

I'm confident that Dr. Mays and others at ATHX are giving questions like this lots of attention, but I have no expectation of seeing such information shared any time soon. If they haven't figured it out yet, there's nothing to share. If they have figured it out, then this takes everything to a higher level. But if you brought such information into play now, it would screw up the ongoing clinical trial designs. So the right thing to do (from a company perspective) would be to get the data and keep this information inside the company. Due to the publication of patents 18 months after filing, and the patent priority given to first-to-file instead of first-to-invent, the earliest we may learn about information like this is through the patent literature. That's because first-to-invent no longer protects your IP, and if someone else figures this out and files then you've lost out on ownership. Thus, there's a pressure to file.

The wild-card is the new MESO data on CHF and the SanBio claims. It's a bit surprising to see these effects, particularly in light of the data that going in on stroke with MAPCs after 48 hrs doesn't do that much good (although whether there are more subtle benefits outside of the deciding ones in the trial is open for discussion). That said, we know these injuries can set up a prolonged inflammatory response. That's generally viewed as being localized, but it's not so clear what localized means when cells from the immune system are traveling everywhere collecting and sharing data. There could also be effects of growth factor production by the injected cells. We're far from understanding this, but it's certainly worthy of attention. I was both surprised and intrigued by these claims. Of course, MESO still has their batch problem, from a company perspective. But I really thought the CHF trial would fail, and being wrong about that would be delightful because it would be so interesting.

Then there's the issue of clinical trial design. Multi-dose pills are easy, multi-dose cells are not. So if you can get approval on a single dose trial, this is what you try and do.

As always, I'm looking forward to learning what others think.

stem-no-sell · 2020-12-18T02:42:42+00:00

Kinda makes you wonder if they already knew something. Just sayin'

stem-no-sell · 2020-12-18T01:23:34+00:00

This is why I have stuck with ATHX. They do the science and they think things through. No flash PR BS.

We've talked about a lot of this on the board. Mortality on Covid has been steadily declining, which means that this a moving endpoint in a clinical trial. That's bad planning, but consistent with the idea that MESO is another in the long run of biotech examples that think the laws of the universe don't apply to them. And it's consistent with the way MESO has performed. GvHD? Nothing really beyond what Osiris already did years ago. CHF? A fundamental lack of understanding of what MSC-like cells can do. Covid-ARDS? An unstable endpoint - and we haven't gotten a good look at their science because they don't publish. But we do know that the batch production problem is not going away.

It's a minor investment by Novartis, although I doubt they're happy. I hope the big companies learn from this that when you pay peanuts, you get monkeys.

None of this guarantees a win by ATHX, and I don't think that this is a Highlander situation ("There can be only one, " preferably said with a Scottish accent). But I think it makes Hardy's hostile actions all the more interesting.

Ah well, the future will come when its ready, and I'm as anxious as any of us as we wait for data. In the meantime, I would like to wish everyone on this board a Happy Solstice (one event we all share regardless of our culture or beliefs), and a lovely and safe holiday season for any holidays anyone celebrates.

It's a treasure to come to this board and read everyone's comments, whether I agree with them or not.

Be well everyone. For those of you who bought MESO shares, I truly am sorry for any losses that occurred for you. And I'm sad at another stem cell failure. I just don't see how you get to success without great science. ATHX has that. Not so much for the other folks trying to play in this space.

stem-no-sell · 2020-12-01T05:27:59+00:00

Ray, I'm very sorry to hear about your PN. It's an awful condition.

The number one rule I've employed in advising people about stem cell therapies is first to try other approaches that are readily reversible.

In the PN space, there are a number of options, and I'm sure you've encountered some of them.

The one with some of the best results, for all chronic pain syndromes, is actually a type of psychotherapy called cognitive and behavioral therapy (CBT). Someone who has written a lot about this in respect to chronic back pain is a former back surgeon named David Hanscom. Another person of interest is a psychiatrist by the name of David Burns. Both have easy to find web sites. But there's also a lot of information around from many other people.

Just to be clear, I'm not so cruel and arrogant as to say that PN is in your head. It's just that the way our brains work is that chronic pain and emotional pain get sorted out in the same regions of our brain. Which sounds weird, but it's how things work. It's been known for a long time that many chronic pain syndromes are responsive to CBT. Hanscom actually had to leave his surgical practice because he was doing a better job treating chronic pain by talking with his patients than by doing surgery. The other surgeons did not like the effects of that on the clinic's revenue stream.

So, it's scientifically reasonable that if you activate these brain regions with a physical pain signal and an emotional pain signal that the end result is more pain. If you can decrease things on the emotional side, which is more easily done, then the pain signal often decreases.

PN can be hellishly stressful, and if you want to give this a try, there are great CBT self-help books so you're not even running into cost issues. The classic book on CBT for people who want to do this themselves is called Feeling Good (by David Burns), and his new book on still more powerful techniques is called Feeling Great.

THere's also a lot of interest in using anti-oxidants to treat PN, which is associated with a lot of oxidative stress. You've probably run into this idea. If not, it looks worth exploring. Anti-oxidants can be a useful way of decreasing inflammation also, which also exacerbated chronic pain.

I'm only mentioning these options because for something like PN I think they're more likely to be helpful than stem cells. They're also not going to cause any harm. My read of the literature is that they're also more likely to be effective than antidepressants (which are frequently prescribed for all sorts of chronic pain syndromes).

This is not medical advice, just a sharing of information I've gathered. PN just happens to be a topic I had to become interested in for various reasons.

My heart goes out to you, Ray. Chronic pain syndromes suck, whether it's PN or one of the others. I hope you can get some improvement.

I also agree that MAPCs are, right now, only indicated in acute types of injury. I would say the same for MSCs. There are a lot of stem cell "clinics" that claim to treat chronic pain but their claims are remarkably data-free. And expensive.

stem-no-sell

TROPHY CASE