Cynata approval for 1st ever allo trial of IPSC-derived MSCs for GVHD

cynataCynata Therapeutics Limited has received approval from UK regulators to start a first-of-its-kind allogeneic IPSC-based trial of MSCs for graft versus host disease (GVHD). Cynata also had some big news a couple weeks back with a deal with Fujifilm.

The company is aiming to recruit 16 patients to test whether the MSCs (a type of adult stem cell) made from pluripotent stem cells created in the lab is safe and eventually whether it can aid patients facing GVHD, a potentially life threatening consequence of bone marrow/hematopoietic stem cell transplantation. There are 4 key bullet points the company released on the study:

  • “UK regulatory authority MHRA approves Phase 1 trial with Cymerus(TM) MSCs
  • World first clinical trial with allogeneic iPSC-derived product
  • Major milestone for stem cell therapeutics and regenerative medicine
  • Cements Cynata’s global leadership in second generation MSC therapeutics”

Another allogeneic IPSC study, this one in Japan and led by Masayo Takahashi, appears to be on the cusp of beginning using IPSC-derived retinal pigmented epithelial cells (RPEs) to treat macular degeneration. An earlier related autologous clinical study began with one patient receiving autologous IPSC-derived RPEs, but was halted due to regulatory changes in Japan. Also, IPSC-derived RPEs from a different patient were found to have a few mutations, which I’m still unclear as to whether had any significance.

Takahashi’s team just published a couple important papers on the allogeneic therapy reporting encouraging pre-clinical data in non-human primates where there wasn’t rejection. My sense is that their human clinical study is likely to start early in 2017.

I expect between these trials and other coming new ones we could see a half-dozen or so IPSC-based trials in the works by the end of 2017. Exciting times in the pluripotent stem cell-based clinical translation arena.

One question here with Cynata’s approach that first comes to mind relates to the question or autologous versus allogeneic therapies.

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TGIF: Stem Cell Stream of Consciousness for the Week

It seems like Fridays are always a good time for reflection.

It’s not like the scientist’s week ends on Friday sad to say, but still at least we can pause momentarily and reflect on the maelstrom that is our lives, while cracking open another diet Coke or pouring another cup of coffee.

This week was a great one for getting into some intense discussions with other scientists both in person and electronically.

CRISPR the talk of the biology town. Everyone is talking about CRISPR-Cas9. There are many subtopics. I’m just going to throw them on the table in a stream of consciousness here. Gee, CRISPR is not as specific as I thought. Uh oh, CRISPR is harder to get to work than I thought (as portrayed in early papers). CRISPR is fricking awesome. Oh, **** , people are going to CRISPR human embryos? The people who innovated CRISPR-Cas9 like Jennifer Doudna are amazing and deserve a Nobel Prize.

CIRM change leaves some feeling unsettled. There is starting to be a feeling of disconnect, especially amongst more basic stem cell researchers, with CIRM.

CIRM just isn’t–at least so far in the existence of CIRM 2.0–funding basic or early translational stem cell research much or at all any more. Maybe it will in the future as there have been hints about that, but support from CIRM in a major way for important, basic stem cell research is probably basically over. The wildly successful and positive CIRM Bridges Program is nearing an end. The CIRM T32 training program are winding down. Many of the early-mid-stage CIRM grants are ending.Lujan paper

There’s definitely a feeling in the California stem cell community of CIRM kind of having moved on from a whole class of stem cell researchers barring those fortunate few who still have grants. Maybe there can be a future reunion.

CDI Buyout Big Bucks. Fujifilm shelled out almost a 1/3 of a billion dollars for Jamie Thomson’s Cellular Dynamics International (CDI). I guess IPSC are really worth big bucks, although CDI isn’t so IPSC-specific anymore. Regenerative Medicine is now proving its worth big bucks. Billions and billions?

Cool New Wernig Lab paper in Nature, but what does it mean? I saw that new Wernig lab Nature paper with Garry Nolan’s uber-fancy FACS-mass spec data. Those SPADE analysis images that look like trees branches into rainbowy fractals sure are pretty. Is it like some kind of heatmap-esque, principle component, multidimensional analysis coolness? Yeah, I’m going to have to read this Wernig lab paper more carefully.

Over at the Stanford media the wonderful Krista Conger boiled the paper down to say that there is a defined “transition state” during reprogramming.

Was Fujifilm CDI acquisition a good move by the companies?

The big stem cell news already this week is the acquisition by Fujifilm of Cellular Dynamics International (CDI) for a whopping $307 million dollars or about $16.50 per CDI share. You can read the press release here.

It was less than two years ago that CDI did its IPO with an initial offering of about $46 million.Cellular Dynamics

Fujifilm reportedly has a multibillion-dollar war chest for buying into the life sciences sector and a growing interest in regenerative medicine. Note that there’s some fun, but perhaps over the top speculation going on in terms of whom they might snap up next.

CDI is an unusual company in the sense that it began about a decade ago with a very sexy idea of using human pluripotent stem cells to cure disease, but now as xconomy.com refers to it is focused more in the “unsexy” business of manufacturing cellular products from stem cells.Fujifilm Logo

Although the production side of regenerative medicine may not sound very innovative, it turns out that the reality is that making high-quality, functional, and pure differentiated cell products from pluripotent stem cells is no easy task. Throw in making such products from human induced pluripotent stem cells (IPSC) and it starts to become very exciting and important.

So was this a good move by Fujifilm and CDI?

Good news for the stem cell/regenerative medicine field overall?

My sense is an initial “yes” all around overall, but with some remaining questions.

If Fujifilm wants to grow a presence in IPSC and more generally the regen med arena, it now has made a big step forward. CDI has worked with CIRM, NIH, and a number of biotech companies. Again, the process of making the “real deal” pure, functional cellular products from IPSC is very important and valuable. The evolving CDI “superdonor” IPSC bank is very cool and could have huge value.

Perhaps something we could learn more about is how Fujifilm will make use of the unique IP of CDI specifically. Also how does the fact that CDI has to license IPSC technology via the Yamanaka Patents come into play? What about the overall price tag just over $300 million?

From the press release comes the Fujifilm perspective:

Commenting on the transaction, Shigetaka Komori, Chairman and CEO of Fujifilm, said, “We are delighted to be able to pursue the business from drug discovery to regenerative medicine with CDI, which develops and manufactures iPS cells. We have optimal scaffolding material, ‘recombinant peptides’, for cell generation and technologies useful for regenerative medicines such as material science and engineering. Our group company, Japan Tissue Engineering, markets regenerative medicine products in Japan. By welcoming CDI to the Fujifilm Group and by combining the technologies and knowhow of both companies, we will seek synergies and efficiencies to be more competitive in the field of drug discovery and regenerative medicine.”

From a CDI perspective, this seems like a major win for their team, who will benefit greatly financially from this deal. Although Fujifilm intends to maintain CDI as a Wisconsin-based subsidiary, as xconomy.com points out it’s not clear what this deal means for the employment of the 150+ CDI workers there longer term. “Synergies” and “efficiencies” after an acquisition can mean reductions in employees. It seems likely that Fujifilm will continue the momentum of CDI and help to give clinical meaning to the efforts of the CDI scientists:

Robert J. Palay, Chairman and CEO of CDI, added, “CDI has become a leader in the development and manufacture of fully functioning human cells in industrial quantities to precise specifications. CDI and Fujifilm share a common strategic vision for achieving leadership in the field of regenerative medicine. The combination of CDI’s technology with Fujifilm’s technologies, know-how, and resources brings us ever closer to realizing the promise of discovering better, safer medicines and developing new cell therapies based on iPSCs.”

For the field overall, this deal is good news. It would seem a clear, strong indicator of the great, concrete value of regenerative medicine and cellular therapies. Nearly a third of a billion dollars is nothing to sneeze at. Notably, this is not about clinical trials or that kind of specific pipeline, but more about concrete cellular products and technology. That’s an important distinction because in this sector oftentimes most of the value and growth emphasis is placed on rapid bedside potential.

Disclaimer: this post is not financial advice and the author has no financial interest in either company.