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Appendix To The “Stem Cell Biotech” Article

This post contains supplementary tables, details and bibliography relating to the article "Is It Time To Invest In Stem Cell Biotechs?" published on Seeking Alpha on June 3.

Historical perspective - List of main publicly traded stem cell biotechs (supplementary tables)

The following tables provide an overview of publicly traded biotechs and gives a good idea of the state of the industry as of June 1, 2016.

The first wave (1980 to 2000) - The enduring stem cell pioneers

The "first wave" of stem cell biotechs comprises mostly U.S. companies that were founded as early as 1980, although some of them actually went public as late as 2007. All of those companies have been going through rough times, and all of them are still small-cap biotechs today. The following table presents the main historical biotechs active in stem cell research and that were still listed until recently (on major stock exchanges), although some of them divested their stem cell pipeline some time ago.

- Table 1: List of publicly traded stem cell biotechs from the "first wave"




Overview / Most advanced compounds

Market Cap

StemCells, Inc (STEM)



The very first stem cell biotech to be publicly traded, StemCells' history is as long as it is turbulent (and dilutive for historical shareholders).After years of struggle to develop its embryonic stem cell pipeline, the biotech just announced the winding-down of its operations, ending over three decades of research in the field.


(operations to end soon)




BioTime entered the field of regenerative medicine only in 2007 when Geron's founder joined as CEO. The biotech is now developing several product-candidates including embryonic stem cell therapies (which it acquired from Geron and Ocata) through its subsidiary companies Asterias (NYSEMKT:AST) and Cell Cure Neurosciences.


Geron Corp. (NASDAQ:GERN)



Geron was one of the earliest pioneers of regenerative medicine and it was responsible for the very first commercial stem cell trial in the U.S. However, the biotech abandoned its stem cell pipeline in 2011 to focus on other assets.



formerly known as Aastrom Bio



Vericel began transforming into a mostly commercial cell therapy company in 2013 with the acquisition of Genzyme's regenerative medicine business. In parallel it is still developing its own stem cell-based product, Ixmyelocel-T, which delivered Phase 2 results in chronic heart failure some weeks ago.


Caladrius (NASDAQ:CLBS)

formerly known as NeoStem



Caladrius delivered some interesting Phase 2 data but the last few years were very harsh on the company which had to abandon ongoing developments in acute myocardial infarction and melanoma to focus its increasingly limited resources on a treatment for type 1 diabetes.


Ocata Therapeutics

formerly known as Advanced Cell Technology



Ocata is developing a pipeline of human embryonic stem cells (hESC) which entered Phase 2 a few months ago - the company then sold itself to Astellas (OTCPK:ALPMF) for $379 million in February 2016.


(acquisition price)



2005 (AIM, London)

ReNeuron is developing therapies based on its neural stem cell (Phase 2 in stroke recovery and Phase 1 in critical limb ischaemia) and retinal progenitor cell (Phase 1 to start in retinitis pigmentosa) programs.


Osiris Therapeutics (NASDAQ:OSIR)



Osiris, once a pioneer of stem cell clinical development, turned into a fully commercial stem cell company after selling Prochymal, its in-house allogeneic MSC product, to Mesoblast in 2013 - from then, the company has known a couple of good years before disclosing accounting problems which crushed the stock.


Neuralstem (NASDAQ:CUR)



Neuralstem develops neural stem cells for the treatment of ALS and other neurodegenerative diseases. The biotech just announced it was cutting staff and looking for partners to help it cope with a critical lack of cash.


Athersys (NASDAQ:ATHX)



Athersys is developing MultiStem (allogeneic MSCs) which had some disappointing clinical results over the years but finally delivered positive one-year follow up results from a Phase 2 trial in acute stroke - the biotech is now betting a lot on this asset and the potential of the cell therapy market in Japan.


(Sources: author's own research and publicly available information)

Note: Stem cell companies with market cap below $10m (other than StemCells Inc.) are not listed in this table. This includes Cesca Therapeutics (NASDAQ:KOOL), created in 2014 from the merger of ThermoGenesis Corp. and TotipotentRx and expected to launch a Phase 3 trial of autologous MSCs in critical limb ischemia (based on a very small open-label Phase 1/2 trial conducted in India - see this article for caution).

The second wave (2000 to 2015) - The stem cell biotechs of the 21st century

The "second wave" of stem cell biotechs comprises a majority of companies based outside of the U.S. This is a result of the increased transition from non-commercial academic research conducted in hospitals and universities to commercial companies (spin-offs) that occurred mostly in Europe, Australia and Israel during the last decade.

- Table 2: List of publicly traded stem cell biotechs from the "second wave"




Most advanced compound

Market Cap

Pluristem Therapeutics (NASDAQ:PSTI)



Pluristem is based in Israel and is developing therapies based on placenta-derived stem cells. The biotech's pipeline is currently in Phase 1/2 trials but Pluristem is betting a lot on Japan's market to take some shortcuts.


Mesoblast (NASDAQ:MESO)


2004 (ASX)

2015 (NASDAQ)

Mesoblast is an Australian company currently holding the title for "biggest stem cell biotech" - it is the only one which valuation reached $1 billion recently. It has several Phase 3 trials going on and one product fully approved in Japan (TemCell).


Brainstorm Cell Therapeutics (NASDAQ:BCLI)



Brainstorm is an Israeli company developing MSC-based autologous therapies for neurodegenerative diseases. It has a Phase 2 trial ongoing in ALS.


Cytori Therapeutics (NASDAQ:CYTX)



Cytori is developing therapies based on its Celution device extracting fresh autologous cell product, which is currently in a Phase 3 trial for the treatment of Scleroderma and two other Phase 2 trials.




2007 (Euronext)

TiGenix was the first company to bring a cell therapy product to the market in Europe, ChondroCelect, in 2009. It was first to reach positive ITT results in a large Phase 3 stem cell trial in 2015, and the biotech is now planning to put its product (Cx601) on the market in 2017 in Europe and 2020 in the U.S. It also has Phase 2 trials in acute myocardial infarction and severe sepsis - see details in this article.


Regeneus (RGS)



Regeneus is selling autologous therapies in Australia and developing Progenza, an allogeneic adipose-derived stem cell product for the treatment of osteoarthritis.




2013 (Euronext)

2015 (NASDAQ)

Celyad has a Phase 3 stem cell trial in the treatment of chronic heart failure (CHF) poised to deliver results in a few weeks (end of June).


Capricor Therapeutics (NASDAQ:CAPR)



Capricor is developing allogeneic cardiac stem cell therapies for the treatment of chronic heart failure. Its lead product, CAP 1002 (cardiosphere-derived cells), is in a Phase 2 trial.


Bone Therapeutics (OTC:BNZPF)


2015 (Euronext)

Bone Therapeutics is developing MSC-based treatments for bone fracture repair and prevention. It has one autologous product in Phase 3 trials and one allogeneic therapy in Phase 2.


(Sources: author's own research and publicly available information)

Lessons learned (additional details)

There seems to be a pattern emerging from this quick historical overview of public stem cell biotechs.

On the one hand, some of the oldest "first wave" stem cell companies either abandoned or drastically reduced R&D efforts in favor of commercial operations, after decades of clinical development, in the hope of cutting losses and generating recurring revenues (Osiris, Vericel). Meanwhile, some other companies are still struggling to finance the development of early to mid-stage products (Phase 1/2), even though some of these products actually start to deliver interesting data, such as Athersys' MultiStem in its stroke program - see this article for details.

On the other hand, the more recent "second wave" stem cell companies seem to have achieved a much more efficient path to product development, with most of them reaching Phase 3 or beyond and gaining tangible commercial perspectives in the very next years. Indeed, despite their shorter existence, some of those companies currently have a much more mature pipeline than some older stem cell biotechs and they can claim the very first large stem cell clinical successes - although, strangely, it does not automatically translate into a higher market cap.

This difference could perhaps be explained by the fact that, compared to the early pioneers of the 1980's, most of those younger biotechs began developing technology platforms based on a further 10 to 20 years of continued academic research. This probably helped them initiate their trials with a more targeted approach - i.e. choosing the right type of cells to treat the conditions which would benefit the most from those therapies. As a financial illustration of this, Celyad burned ~$110 million since inception and it has a pivotal Phase 3 trial about to deliver results; TiGenix has used ~$200 million and it has managed to get 2 different cell products through the clinic; Mesoblast burned ~$316 million and it has one commercialized product and several ongoing Phase 3 trials. Meanwhile, StemCells Inc. and Ocata have burned over $456 and $367 million over the years, respectively, and those companies are still in mid-stage development with Phase 2 drug candidates.

Selected bibliography and ressources for the article

Stem cell industry trends and data:
Van Servellen, A. & Oba, I. "Stem cell research: Trends in and perspectives on the evolving international landscape", Research Trends, 2014
Das, R. "Regenerative Medicine: Could This Be Healthcare's Saving Grace?", Forbes, 2015

Historical perspective articles:
Hollmer, M. "Stem cell research advances in fits and starts", FierceBiotech, 2012
Boston's Children's Hospital "History of stem cell research - a timeline"
O'Brien, J. "The great stem cell dilemma", Fortune, 2012

Cell therapy manufacturing and industrial challenges:
Grant, R. "Planning for Commercial Scale of Cell Therapy and Regenerative Medicine Products, Part 1 & Part 2", BioProcess Intl, 2015
Brandenberger, R. et al. "Cell Therapy Bioprocessing", BioProcess Intl, 2011
Dodson, B. & Levine, A. "Challenges in the translation and commercialization of cell therapies", BioMed Central, 2015
Lechanteur, C. et al. "Clinical-scale expansion of mesenchymal stromal cells: a large banking experience", BioMed Central, 2016
Bersenev, A. "Success of cell therapy products after approval", StemCell Assays, 2012

Cell therapy regulations & reimbursement strategy:
CJ Partners, "Regenerative Medicine in Japan", 2016
Holland & Knight, "Webinar: Reimbursement Strategies for Stem Cell Products", 2013
Stanton, D. "US Gov: Critical need for reproducible regenerative med manufacturing processes", BioPharma Reporter, 2016
Bersenev, A. "On conditional approval of cell therapy products", Cell Trials Blog, 2015

Disclosure: I am/we are long TGXSF, CYAD.