√ Stem Cell Good News For The Holidays: Biotechs, Fda, Organoids

I can see many reasons to be jolly on the regenerative medicine front as we get deeper into the holiday season as there is quite a lot of stem cell good news even if there is also some not so good news.

In today’s post the focus is on the good news of late.

Atsuhiro Taguchi and Ryuichi Nishinakamura, part of Figure 4, Cell Stem Cell 2017, kidney organoids in development.

Semma Therapeutics, a stem cell diabetes biotech, raised more than $110 million. I’m eager to see how the next few years play out with the healthy competition between them, ViaCyte, & others in this area. The end result of this good news now will hopefully be at least one safe, effective new diabetes treatment in the future within less than a decade. You can read my recent interview with ViaCyte leadership here.

More on the biotech front, as Amgen invests big bucks into direct reprogramming firm Fortuna, which focuses in part on the development of autologous neural stem cells for a variety of conditions.

The promise of cell-gene therapy combos is exemplified by the recent effort that restored basically the entire epidermis of a young boy with epidermolysis bullosa, who would have otherwise died. You can read about my take on the Nature paper reporting this finding here. It’s one study, but I see it as good news. You have to start somewhere with a new, transformative approach.

Recent FDA actions and words on stem cells are good news on a number of levels in terms of clarity and strength, which I will optimistically say are likely only the beginning of a different phase in our field. See more of my thoughts and information on this here. I believe that new Commissioner Scott Gottlieb is serious about differentiating between good citizens in this arena, whose path we should facilitate, and those on the other end of the spectrum who are after patient’s money and willing to risk their customers’ health and even lives. You can see text of Gottlieb’s broader testimony last week before Congress on 21st Century Cures here.

There are unfortunately usually too many steps from discoveries to the bedside to help patients, but each step is something to be happy about as long as we have a balanced view and don’t succumb to hype. New work on the organoid front suggests the idea of “kidneys in a dish” is a step closer to a future reality. The scope of kidney disease is so profound that more effort is needed in this area. You can see the beautiful data above (part of Figure 4 from their Cell Stem Cell paper) from the work by Atsuhiro Taguchi and Ryuichi Nishinakamura mentioned in the overview article.

What’s your stem cell good news for the holidays?

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√ Mesoblast Gets Fda Rmat; List Of 10 Total Designations So Far

Australian stem cell biotech Mesoblast announced that it has received regenerative medicine advanced therapy (RMAT) designation from the U.S. FDA. This is very good news for the company and an encouraging development for the field.

Interestingly, last month the FDA clarified that there is expanded RMAT designation that can include gene therapies too. At the Meeting on the Mesa in October, an FDA official reportedly presented data indicating that about 1/3 applications for RMATs were granted (see image below from Twitter).

This recently announced RMAT designation is for Mesoblast’s stem cell therapy for heart failure. I’ve posted regularly about Mesoblast over the years and it has been in the stem cell arena for the long haul.

Mesoblast’s RMAT designation is part of a continuing musim whereby the FDA, via the 21st Century Cures Act regenerative medicine provisions, has been rapidly issuing RMAT designations to stem cell biotechs.

Here is a list of the approved RMATs I could find so far:

• Humacyte (Vascular Access for Hemodialysis)


• Enzyvant (DiGeorge syndrome)


• jCyte (Retinitis Pigmentosa)


• Asterias (AST-OPC1, spinal cord injury)


• Athersys (MultiStem)


• Juno (JCAR017; CAR-T)


• BlueBird Bio (Lentiglobin in SCID, scroll down to page 3)


• Fortress Biotech (Cellvation’s CEVA101, traumatic brain injury)


• Kiadis Pharma (ATIR101, blood disorders)


• Mesoblast (Heart Failure, mesenchymal precursor cell therapy)

But I think there are probably more out there. If you know of others not in my list, please let me know. Again, going back to the Meeting on the Mesa, from the FDA slide it seemed like even back then a few months ago there were already 9 approved and possibly 1 pending. Unless a company or other entity announces they got an RMAT, then it seems the FDA isn’t going to be announcing it or providing that informasi on a database as of yet so it can be hard to find such news.

Meeting at the Mesa image on Twitter

Seeking Alpha has more specifics of Mesoblast’s RMAT:

“Mesoblast Limited (NASDAQ:MESO) announces that the FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation for its mesenchymal precursor cell (MPC) therapy for the treatment of heart failure patients with left ventricular systolic dysfunction and left ventricular assist devices (LVADs).

RMAT status provides for more frequent interactions with the FDA, including discussions of whether Priority Review and/or accelerated approval is appropriate.

A 30-patient pilot trial of Mesoblast’s MPCs at a dose of 25M cells in heart failure patients with LVADs, provided the basis for RMAT designation.

FDA has invited Mesoblast to discuss the development strategy and the evidence needed for approval in an efficient manner.”

For more information from the FDA on RMATs see here and here. In the latter, CBER Director Dr. Peter Marks blogged about RMATs going live.

I see RMATs as a regulatory experiment in the stem cell and regenerative medicine field. So far the RMAT experiment is moving fast, but I haven’t seen reason for clear worry as it is implemented. For instance, I’m not aware of any for-profit stem cell clinic related business having received an RMAT, although at least one self-reported having submitted an application earlier in 2017 that may have been unsuccessful or put on the back burner by the company. Overall, can direct-to-consumer stem cell clinic businesses that have traditionally worked around FDA pre-market approval meet the RMAT hurdle such as for robust data? We’ll see.

Note that one of the quirks of the RMAT system is that they were originally to be called RATs, but I think most would agree that RMAT is a better acronym. The other interesting thing about RMATs is that their availability negates the common excuse by some American stem cell clinics that they give non-FDA approved stem cells to patients because the FDA supposedly doesn’t offer faster options for oversight.

Let’s see how the RMAT experiment goes in 2018. I’d say I’m cautiously optimistic at this early stage.

Note that I’m relying primarily on company’s own announcements of RMAT designation approval from the FDA so in some cases I can’t independently confirm the designation, but have no reason to doubt them.

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√ Stem Cell Good News On Biotechs Cool New Organoid Paper

There’s some recent stem cell good news out there including new papers and biotech developments.

The stem cell and regenerative medicine field is really diverse and runs the gamut from really worrying stuff to very exciting, legit developments. In this post, I’m going to focus on the encouraging recent developments. What do I see as the good news out there so far in 2018? I’m going to go through some of the highlights below and include quotes from announcements in some cases.

• Stem cell treatment for Crohn’s Disease approved in Europe. 

“The European Commission has approved Alofisel (darvadstrocel), a stem cell therapy to treat complex perianal fistulas — one of the most disabling complications of Crohn’s disease. The cell therapy represents an alternative to multiple surgeries for patients with Crohn’s that have shown an inadequate response to at least one conventional biologic therapy.

Previously known as Cx601, Alofisel was developed by the Belgian biotech TiGenix and is licensed to the Japanese pharma Takeda. The marketing authorization comes with a €15M milestone for TiGenix, which will now proceed to transfer the authorization to Takeda.”

Pham, et al., Figure 2, NeuroReport

This provides concrete hope for Crohn’s patients suffering from this condition. If approved in coming years in the U.S. this would also be a milestone as a new type of approved stem cell therapy beyond HSCT and specific cord blood-related uses that are OK now.

• Generation of vascularized human brain organoids.

One of the limitations of organoid technology generally and for brain organoids is simple diffusion. As much as we grow organoids in ways that maximize nutrient and oxygen availability, organoids can only grow healthy up to a certain point. Also, without vasculature, organoids are missing a key normal physiological component.

Now a new paper from right here at UC Davis by a team at our Stem Cell Program reports a groundbreaking methodology for generating human brain organoids that are vascularized.

This kind of technology could address the earlier mentioned roadblocks and catalyze exciting new developments. Kudos to the team of my great colleagues (listed in authorship order on the paper): Missy T. Pham, Kari M. Pollock, Melanie D. Rose, Whitney A. Cary, Heather R. Stewart, Ping Zhou, Jan A. Nolta, and Ben Waldau.

You can see Figure 2 above from this paper.

• FDA Grants Orphan Drug Designation to Cynata’s Lead Cymerus™ MSC Product, CYP-001

For a stem cell biotech to get orphan drug status for a product is a major positive development. Cynata recently got this good news on their CYP-001 product for treatment of acute graft versus host disease. From the company:

“CYP-001 is based on Cynata’s Cymerus technology platform, which uses induced pluripotent stem cells (iPSCs) to generate an unlimited number of uniform, therapeutic mesenchymal stem cell (MSC) products based on a one-time blood donation from one 4dukt donor.”

You can see my interview with Cynata CEO Ross MacDonald here.

• RMATs grow.

The list of regenerative medicine advanced therapy (RMAT) designations grew to 15 recent. You can see my full list here. I see this as good news and haven’t seen any approvals that stand out as particularly concerning, but the RMAT kegiatan is a regulatory experiment and we don’t know how it will turn out. I’m hopeful it’ll be a net positive for the field and patients with some RMATs ultimately turning into approved therapies in the future, proven safe and effective.

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√ Magenta Therapeutics Good News-Bad News Trial Data

Magenta Therapeutics is a biotech company with a portfolio including stem cell products. Their most well known investigational drug product is an expanded umbilical cord stem cell product called MGTA-456, an “ex-Novartis” product. Magenta just released new trial data on MGTA-456, which I see as a case of good news-bad news, and investors seem to have had a similar reaction.

Image from Magenta on MGTA-456.

The company describes MGTA-456 as, “a first-in-class allogeneic stem cell therapy consisting of a single umbilical cord blood unit expanded with an aryl hydrocarbon receptor (AHR) antagonist then administered to a patient through a bone marrow transplant.” A key feature of the product is its higher cell dose. You can see an image from the company explaining the idea behind the production and use of MGTA-456.

As FierceBiotech points out, the good news from data from abstracts for the upcoming ASH meeting is that there are some signs of strong efficacy:

“MGTA-456 is an ex-Novartis therapy, based on cord blood-derived stem cells, that aims to improve the dose that can be delivered in allogeneic hematopoietic stem cell transplants (HSCT)—an important therapy for patients with inherited metabolic disorders such as Hurler syndrome who don’t have a matched donor.

By allowing a larger cell dose, MGTA-456 is intended to reduce the time it takes for white blood cell populations to recover after HSCT, which involves destruction of the bone marrow as a first step. The new data shows that using MGTA-456 cut that to one day from a historical average of around eight days.

Moreover, all five patients treated—two with Hurler syndrome and three with adrenoleukodystrophy—met the main objective of successful stem cell engraftment 42 days after the transplant, which tops historical success rates of around 32% with regular, unexpanded cord blood transplants.”

This is encouraging, but one “asterisk” here is that this is such a small group of patients (N=5) that we should be cautionary at this point. Note that Hurler Syndrome is also known as mucopolysaccharidosis type IH.

Unfortunately, the bad news here is that the two pediatric patients with Hurler syndrome both had adverse events in the form of autoimmune cytopenia in each case. One died. Magenta suggests based on feedback from “scientific leaders in the field” that the death was not necessarily related to MGTA-456, but I don’t see how they can be sure at this point. It’s reasonably possible that the allogeneic product caused the autoimmune reaction, but admittedly I’m definitely not an expert in that specific area. Further study with more patients will help clarify the risks here.

What does the future hold? Magenta is continuing with the work, will limit participation in this area to those older than the pediatric patients who had the adverse events, and also plans soon to study MGTA-456 in sickle-cell disease and possibly blood cancers.

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