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.

Why pursue IPSC-derived MSCs, particularly in an allogeneic manner, if one could in theory simply use autologous unmodified MSCs? The answer to this may be the greater practicality of an off-the-shelf universal allogeneic product, but that could also be made without using IPSCs. I do wonder if there are data as to whether IPSC-derived MSCs somehow might be demonstrably better in terms of efficacy or safety, which had been suggested in the past by some work. For more information on the use of innovative stem cell products like MSCs for GVHD see item #1 in this post by Alexey (HT to him for his expertise in this area) on Mesoblast’s TemCell product, its approvals, and data so far.

Let’s see how this Cynata trial goes.

6 thoughts on “Cynata approval for 1st ever allo trial of IPSC-derived MSCs for GVHD”

  1. Hi msemporda:

    I appreciate you asking about innate differences among cell preparations. They do matter! While standing on this particular soapbox, I urge, beg, request, that clinical stem cell products be characterized by 21st century tools…like genomics.


  2. Dr. Ross Macdonald publically attributes the breakthrough potential of Allo iPSC “MSC” based products to their superior manufacturing process capabilities but the real elephant in the room is their likely superior efficacy possibilities over Gen1 adult “MSC” donor derived products. We discussed that in my interview with him and although he spoke to the issue he preferred to let the clinical data speak for that as things progress – needless to say Pluripotent sources are expected to be more potent in keeping with the literature. The interview is here for those that haven’t read it: (below the progress reports).

    One thing to note, the company isn’t the product producer/manufacturer, rather a development/marketing company set-up to manage the process of translation and commercialization (i.e. License out) of chosen iPSC derived “MSC” targets. They have a tech dev deal with the sci inventors at U of Wisconsin via WARF and manufacture in the US in Wisconsin also at Waisman Bio. This aspect of the partnership layer lends itself to a lean operation and with product data a sound biz model.

    In regard to existing adult “MSC” players not wanting to be seen to switch to Allo iPSC derived “MSC” products one of the first deals that Cynata has done is with an existing adult “MSC” company looking to optimize with a dev program using Cynata’s Allo iPSC derived product > apceth GmbH.

    My main question pertaining to the Pluripotent source products is the expression profiles in like to like culture/handling processes and testing situations or for that matter using proprietary methods – i.e. what are the innate differences and do they matter in side to side therapeutic application.

    Product by Process patentability remains a key issue here and bodes well for synthetically modified variants that perform.


  3. Wow! Some unexpected opinions!
    This therapy is based on Osiris getting approval in Canada for their bone marrow “MSCs” for reducing GvHD in children a number of years ago, when Randy Mills was Osiris’ CEO.
    I’m using quotation marks around the term “MSC” because they are not being functionally used as stem cells…they’re just fibroblastic cells that…hopefully…have anti-inflammatory effects.
    I like the idea of making these cells from iPSCs because they can choose the haplotypes of the cells so they better match patients, and the quality control is much better than the current methods for making these cells, whatever they actually are. Currently, a lot of quite different cells are called MSCs, so it’s not a well-defined descriptor.

  4. Paul,
    One reason for Cynanta using allogeneic iPSC as cellular source is that it would have been hard to raise investor money for an allogeneic product derived from a better pluripotent source ( hESC)

  5. “Why pursue IPSC-derived MSCs, particularly in an allogeneic manner, if one could in theory simply use autologous unmodified MSCs? The answer to this may be the greater practicality of an off-the-shelf universal allogeneic product, but that could also be made without using IPSCs.”

    I spoke to the top people at Cynata a few months ago. Their rationale is that allogeneic MSCs that are not made using their IPSc based protocol would need a significant number of donors due to the limited number passes before senescence kicks in and the limited number of MSCs that can be obtained from a single bone marrow donor aspirate.. They claim that they can make an UNLIMITED number of MSC like cells with their process and hope to get others to license their technology and run their own clinical trials. This small GvHD trial is a proof of concept that the cells are safe and viable. I look at this as a private label stem cell business model but don’t see how any company already in the stem cell business would switch over and, in effect, acknowledge they have a scaling problem with their own cells. Interesting.

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