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Thursday, July 24, 2014

Lessons from Toronto on the Future of Regenerative Medicine in Japan

One of the early pioneers of cell therapy as we know it today is Professor Arnold Caplan commonly thought of as responsible for the identification and isolation of the mesenchymal stem cell.  Several years ago Dr. Caplan launched a summer course at Case Western Reserve University he called Business of Regenerative Medicine. This year it was hosted by the Centre for Commercialization of Regenerative Medicine (CCRM) in Toronto - the first time it's been hosted outside of Cleveland.  

I was fortunate to be invited to participate in this year's 7th Annual “Business of Regenerative Medicine: New Therapies, New Models”.  Signals blogger, Mark Curtis, has done a nice job of summarizing the highlights of this year's course.  

One of the most valuable take-aways for me was from a talk given by the inimitable Professor Chris Mason of University College London who has reportedly been advising Japanese lawmakers and regulators on their new proposed regulatory framework for regenerative medicine.  

Let me back up.  In June 2012, regenerative medicine was given priority status in the national Cabinet Secretariat’s Five-year Healthcare Innovation Strategy. In October 2012 Prof. Shinya Yamanaka of Kyoto University won a share in the Nobel Prize in Physiology or Medicine for his work in the development of iPS cell technology. This solidified regenerative medicine as an area of national pride and one of the areas in which Japan wanted to demonstrate innovative global leadership not just for scientific discovery but for the development of an industry around those discoveries. However, the Japanese regulatory framework which applied to cell therapies was widely recognized as being in desperate need of revision in order to support true commercialization of these products.  It made sense, then, that the Japanese started their innovation with the regulation. 

In November 2013, the Japanese legislature (the National Diet) passed legislation that revised Japan's Pharmaceutical Affairs Law and created the new Regenerative Medicine Law intended to be the groundwork for establishing Japan as a global leader in regenerative medicine in the years ahead. The import of this legislation was that it created a legislative mandate to create regulation that established an expedited development and commercialization pathway for regenerative medicine therapies while continuing to ensure and protect patient safety. The legislation passed with overwhelming support in both the lower and upper houses of the Diet.  Since then the policy makers and regulators at the MHLW and PMDA have been busily attempting to build a regulatory framework around this mandate.

There has been a lot written about this potentially ground-breaking approach to regulating cell therapies (see also here and here) but until now I have seen very little detail around how the mandate of the new law might be translated into operational regulation.  On that front, here is my brief second-hand synopsis of what I think I learned from Chris:

  • conditional approval will be available to any cell therapies that provide evidence of safety and early signals of efficacy - this is reportedly not limited in any way by the indication or by product type 
    • in other words there is no need to be addressing an orphan indication or for the product to be autologous in order to qualify
    • at least in the early days of this implementation it is expected that this data will be 'imported' from trials conducted outside of Japan 
  • once conditional approval is granted, a sponsor company will have 7 years to obtain final approval
    • there is likely to be a requirement that a product be manufactured in Japan to obtain final approval 
  • conditional approval will also come with reimbursement though there is no indication yet as to how pricing will be determined
  • there is an expectation that the pivotal studies needed to obtain final approval will be done outside of Japan - since the product is already being sold in Japan, conducting a placebo-controlled trial would be next-to-impossible
There are a number of Japanese companies already in the regenerative medicine and cell therapy space that may be the initial and primary beneficiaries of this new regulatory paradigm.  Most of these are involved in the Forum for Innovative Regenerative Medicine (FIRM) established in 2011 to promote and support the commercialization of regenerative medicine in Japan. 

As largely an industry organization, FIRM really started emerging as a key national player with its involvement in the development of this newly emerging regulatory framework.  To quote FIRM, "Commercializing this state-of-the-art technology is not just a question of scientific and biotechnological prowess; the broad-ranging manufacturing capabilities nurtured by Japan’s industrial community will also be an indispensable element. Indeed, this is an opportunity for Japan to leverage its unique technologies to grow an internationally competitive industry."

Over the past months it has been interesting to observe how companies in Japan (even large multinational conglomerates) have responded to this new national mandate.  Many of them appear quite anxious to demonstrate to their shareholders, government, and peers that they have active programs in regenerative medicine and thus are supporting this national initiative.  This appears to be creating considerable appetite among Japanese companies, many of whom have not been in the sector to-date, for regenerative medicine technologies with which they can associate. 

As a result of this phenomenon, we expect there will be many regenerative medicine companies outside of Japan which will find wins for themselves as a result of this national initiative.  Naturally, companies in the regenerative medicine and cell therapy space outside of Japan are tripping over themselves to prioritize Japan as part of their corporate planning and to elucidate their Japanese strategy to investors and partners as a competitive advantage and potential earlier route to market if not return on investment.  Some of the companies distinguishing themselves early in this race are Cytori (NASDAQ:CYTX), Mesoblast (ASX:MSB), and Athersys (NASDAQ:ATHX). 

Cytori has long been in Japan and is making sure no one forgets that by press releasing the importance of their Japanese focus.  

Mesoblast inherited a Japanese licensee when they took over the Prochymal portfolio from Osiris.  JCR Pharmaceuticals has the license for the allogeneic mesenchymal stem cell (MSC) product in Japan to treat steroid refractory graft-versus-host disease (GvHD). Mesoblast has announced its intention to leverage this door to the Japanese market. Given that the product has already received approval in Canada and New Zealand for pediatric GvHD, it has been speculated that JCR may be the first company to secure conditional approval for a cell therapy in Japan.

Not to be outdone, Athersys announced in January, "We are actively evaluating the potential for accelerated development of MultiStem cells in a number of therapeutic areas in Japan, and will seek to establish strategic collaborations to assist in the rapid development of products that will help Japanese patients.

One of the sleepers in this race may be an emerging regenerative medicine company named RepliCel Life Sciences (TSXV:RP).  In May 2013 RepliCel announced a Collaboration and Technology Development Transfer Framework Agreement with Shiseido Company, Limited (Tokyo Stock Exchange Code: 4911) for an exclusive geographic license for RepliCel’s RCH-01 hair regeneration technology.  Shiseido has an exclusive geographic license to use RCH-01 in Japan, China, South Korea, Taiwan and the ASEAN countries.

This deal garnered RepliCel ~$4M in upfront cash and was valued at over $30M in milestone payments and sales royalties.  Perhaps more importantly, since that time the companies have executed a tech transfer agreement, RepliCel was granted a key patent in Japan, and Shiseido recently celebrated the opening of its new cell-processing facility at the Kobe Biomedical Innovation Cluster (KBIC).  This facility will focus on the commercialization of RepliCel’s RCH-01 hair regeneration technology for Shiseido's markets.

In speaking with management, I understand Shiseido has plans to conduct its own clinical trial of the product in Japan and that the companies are collaborating closely (through a joint development committee) on the continued improvement of the technology to ensure a single product emerges.  This means there will be data from two concurrent trials (RepliCel's proposed phase 2 trial in Germany and Shiseido's proposed trial in Japan).

My own take on this is that it seems RepliCel/Shiseido may be well positioned to take advantage of early conditional approval of this technology in Japan in a way that generates near-term revenue while they continue to generate clinical data and optimize the treatment (dose, frequency) and manufacturing.  In due course this data will be available to RepliCel to use in licensing discussions for non-Shiseido markets.  Furthermore, RepliCel/Shiseido have already solved the anticipated hurdle of having manufacturing in the country as a predicate to eventual final approval.

The fact that their Shiseido collaboration may position RepliCel as a leader among foreign companies taking early advantage of this new regenerative medicine framework in Japan has not been lost on management (see here) but given RepliCel's expanded technology platform and product/clinical pipeline combined with the 3rd party validation and unique attributes of the Shiseido deal, I'm not sure the message has sunk in with investors yet given the ~$30M market cap.

I'll be watching the Japanese regenerative medicine race with great interest over the next few months.  It has been reported that there will be a MHLW-sponsored public comment period for the new regenerative medicine law announced soon. All stakeholders are encouraged to provide feedback on the new legislation aimed at regenerative medicine therapies. 

Also of note will be to monitor how other regulatory agencies respond.  Already we have seen moves toward expedited or conditional approvals (in limited circumstances) in Europe and potentially expedited pathways (e.g., breakthrough designation) in the U.S.  Other jurisdictions such as South Korea, Canada, and Australia have apparently taken a more functional approach to expediting certain cell therapy product approvals but on a case-by-case basis.

Monday, May 26, 2014

RepliCel -- Treating Functional Cellular Deficits. An Interview with CEO, David Hall

Despite us both living in the Vancouver area and both being involved in cell therapy, I didn't meet David Hall until we were both in La Jolla late last year for the Alliance for Regenerative Medicine's Stem Cell on the Mesa meeting.  Since then we've been keeping in close contact and I have had opportunity to learn a lot more about him, his team, RepliCel, and the company's technology.  

The company is by all appearances a company on the tail end of a number of significant transitions in terms of its structure, finance, clinical pipeline, and even the breadth of its underlying technology.  The company is now unveiling RepliCel 2.0 (my term, not theirs) which builds on the company's core expertise and platform technology but combines newly added assets and clinical strategies that create end-to-end solutions and multiple pillars around which shareholder value is being created.

David presents a sound logic for the transitions through which he has taken the company in the past 18 months and the pace of that change.  He does, perhaps more than many CEO's I have had the opportunity to interview, present a strong and focused vision for the company with a clear goal and a well-defined pathway for how he intends to get the company there.  From my vantage point, this vision permeates into most aspects of the company from clinical trial design, to patent strategy, to defining collaborations, and even recruiting.

Suffice it to say I have been increasingly impressed by what I see and welcome the opportunity to share the interview below with you.  I hope you enjoy learning a little more about RepliCel as much as I have.

CTB:  Tell us a little about your background, David, and how you got involved in a cell therapy company?

DH: My initial career was in finance working on both sides of the street as a money manager and as a banker and analyst.  It was as a banker that I came to join ID Biomedical which then led to my joining Angiotech Pharmaceuticals not long after it was started.  During my time there I served as Chief Financial Officer, Chief Compliance Officer and Treasurer and Corporate Secretary.  After 20 years in life sciences, I spent time focused on public policy in BC and Canada as it related to developing our BC life sciences industry.   During that time I was approached to look at a cell therapy company developing a treatment for pattern baldness.  Despite my lack of empathy at that time for pattern baldness as a disease, I was struck by the elegance of this group’s scientific approach and how that might be expanded into other treatments where there was a deficit of healthy active cells.

CTB: Can you give us a snapshot of RepliCel as a company?

DH: RepliCel is treating cellular deficits in two main areas. The first is addressing conditions where there is a deficit of healthy functioning fibroblasts such as chronic tendinosis and damaged skin. 

The second is in treating pattern baldness where there is a deficit of dermal sheath cup cells that are responsible for maintaining a hair follicle cycle of fiber production.  

In addition, we have developed cell manufacturing technology and procedures to support the potential commercialization of these indications as well as specialised delivery devices which in themselves are unique and have the potential for licensing for other medical and cosmetic uses.  We believe the manufacturing and delivery assets are very important to the company as you need to be able to demonstrate scalability and commercial delivery.

CTB: What is the company’s technology?

DH: RCH-01 is our treatment for pattern baldness.  This technology specifically focuses on replacing a deficit of healthy active dermal sheath cup cells (DSCs).  Our product thesis is that these DSC cells control and maintain the population of dermal papillae (DP) cells in a hair follicle and the number of DPs determine the length and thickness of the hair fibre.  In patients with pattern baldness (men and women), DSCs are compromised by the androgen hormone for no known reason.  It is kind of like the reverse of unwanted or aggressive hair growth.  Some people have five-o-clock shadows when they are 15 and others don’t shave until they are 20+.  In pattern baldness, the androgen hormone compromises hair growth.  RCH-01 addresses the deficit of the active DSC cells in the areas of pattern baldness in the scalp.

The RCT family of products* are for the treatment of chronic tendinosis including Achilles, patellar  and both golfer’s and tennis elbow.  In each case we are addressing a deficit of healthy active fibroblasts.  The scientific thesis is that this chronic disease is the result of incomplete healing cycles due to a deficit of healthy functioning fibroblasts.  Our early human clinical work on chronic tendinosis was done by our collaborator, Dr. David Connell, using fibroblasts isolated from the dermis.  Our program is based on using fibroblasts isolated from the hair follicle due to their ability to express higher levels of type I collagen than dermal fibroblasts.  Type I collagen is the main cell constituent of a tendon.  (*RCT-A-01, RCT-P-01, RCT-G-01 and RCT-T-01)

RCS-01 is focused on replacing damaged or non-functioning fibroblasts in the dermis.  Fibroblasts damaged by UV irradiation, smoking and other factors stop producing healthy amounts of collagen and the constituents of the skin’s extracellular matrix.  As a result, the skin loses its texture.  Similarly, acne and burn scars are targets for us to deliver highly expressive fibroblasts to initiate remodelling of the damaged skin. 

The supporting manufacturing technology is also a critical asset to the company as we believe our process is scalable.  

In addition, we have developed a very unique injection cell injection device for dermal injections for both our derm and pattern baldness program.  This device minimizes shear force, optimizes staged cell delivery, and has a built in freezing element that obviates the need for any kind of anesthetic and can control both volume and depth of injection.

CTB: Where are you doing your trials?  Why Europe and Canada?

DH: All of our trials are being conducted under the terms of reference from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).   Each trial is designed to meet these international standards of which all of the western nations are members.  As such, all of our data up to Phase 2 are admissible towards Phase 3 pivotal programs in each jurisdiction.  

Our RCS-01 trial is being done in Germany.  The co-founder of the Company Dr. Rolf Hoffmann, is located in Germany and he is leading this initiative.  Similarly, our RCH-1 treatment is being conducted in Germany at the Charité Hospital in Berlin.  The Charité is one of the largest teaching and research hospitals in Europe.  In addition, the technology itself was first developed in Dr. Hoffmann and Dr. McElwee’ s lab at the University of Marburg in Germany.  There is history with these technologies in Germany and in addition, the cells are being processed by our contract manufacturer in Austria.

The clinical trial for RCT-A-01 will  be conducted at the University of British Columbia because it is a world centre of excellence for sports medicine research including tendinosis.  We have three very special advisers leading the development of the clinical trial protocol including Dr. Ross Davidson, Dr. Jack Taunton and Dr. David Connell.  Each of them are key opinion leaders in sports medicine.  It is also convenient to have this trial in our own city, but it was not the deciding factor.  Reputation, skills and the ability to recruit patients were the deciding factors.  The cells will be processed in Austria; however, we are moving to bring online a second contract facility validated in North America at the Centre for Commercialization for Regenerative Medicine in Toronto. 

CTB: What is the strategy for the U.S. market?

DH: The US market will be addressed from two angles.  First, we are presenting our fibroblast program to the US military under their peer reviewed medical research program.  The DoD has a great interest in musculoskeletal research to deal with damaged tendons and skin.   We believe our programs are ideally suited for their needs and are preparing filings for funding for clinical programs both in Canada and the US.  The second approach is to undertake phase 2 clinical work on other target tendons in the US after we have gotten our RCT-A-01 program launched.  Importantly, all of our trials are being conducted under ICH standards with the US regulatory pathways in mind. 

CTB: Tell us about the deal you did recently with Shiseido and what your drivers were for that kind of deal?

DH: In 2013 we completed a geographic license with the Shiseido Company.  Shiseido has its own hair research lab and they had come to the conclusion that our approach was the leading cell therapy technology for treating pattern baldness.  

We were interested in doing a geographic license for Japan and parts of Asia for three main reasons.  The first was to have a third party validation of our science and technology which is always important to a start-up company.  The second was to be partnered with a large company whom had the resources (both human and financial) to conduct their own clinical program which along with our program would more than double the data being collected as we work towards establishing our dosing and other protocols for the technology in humans.  Thirdly, Shiseido has committed to cell therapy in a significant manner including having commissioned and now opened a purpose-built cell processing centre in Kobe Japan, in the heart of the country’s regenerative medicine initiative.   

Our ongoing collaboration will see technology improvements shared between parties.   Financially, we received $4 million up front, future milestones totaling approximately $30 million as well as middle single digit royalties on sales.  We are very pleased with our collaboration with Shiseido.  They are a focused and dependable collaborator.

CTB: From our perspective, the company is significantly under-exposed both in the regenerative medicine industry and investment communities.  Can you give us a sense of why you think that might be and your plans in that regard?

DH: Every company has its own chronological pathway to develop a profile in its industry and in the public domain.  During the later stages of 2012 and through 2013 RepliCel was very concentrated on completing the Shiseido transaction as well as completing the filing of PCT patent applications on its fibroblast platform.  Until we had completed the task of protecting our expanded technology, it did not serve the company to disclose these activities.  

Now in 2014, we are completing the next round of financing, pushing hard on our clinical filings to launch 3 clinical trials and now have the freedom to discuss our programs.  As such, we are going to be out in the public domain at conferences and doing roadshows in order to get the RepliCel story known and followed both in industry and in the capital markets.

CTB: While many of the companies in the cell therapy sector are focused on indications like cardiovascular disease, oncology, autoimmune disorders, or diseases of the central nervous system, RepliCel is going after sports injuries, baldness, and wrinkles.  Do you see these indications as low-hanging fruit?  Do these indications battle problems of lower-margin and/or reimbursement challenges?

DH: I would agree that our programs are low hanging fruit in the regenerative medicine business and that is an attractive distinction.  Furthermore, as an autologous therapy, there is less risk of rejection than an allogeneic therapy. 

Our therapies are designed to simply multiply a patient’s particular cells that are in deficit and then deliver it to the area of deficit.  We are not differentiating or inducing cell change, we are simply letting the cells do what they normally do when placed in the area of the wound or damage.  

A lot of regenerative medicine is focused on very complex processes that take a source cell and then engage in extensive cell manipulation and/or differentiation.  While these treatments are going to arrive in the future, today they are very difficult therapies to perfect both in assuring that the cell differentiations are exact and controlled and that the cells are delivered in volume and stay and function where they are needed.  Our process is just simpler.  So, yes, this is low hanging fruit in terms of safety risk and the commercial development timeline.

In terms of margins, we are quite confident in our ability to demonstrate manufacturing scalability.  In terms of reimbursement, initially we have only one product that would need pharmacoeconomic validation and that is the tendon program.  However, we know that we can replicate and deliver a tendon program at a reasonable cost and that there is no current clinically established solution for chronic tendinosis.  Therefore, we do not anticipate any problem pricing at a good margin.  In terms of the derm program, the initial focus is a cosmetic therapy and I think pricing a solution for sun damaged skin, wrinkles, etc. should not be an issue.  A treatment with good efficacy will have no problem getting a premium price. In terms of margins on a treatment for pattern baldness, it would be priced against the current standard of care which is hair transplant surgery.  And at that price, we can make good margins.

CTB: Many of the cell therapy products already approved are in the musculoskeletal, dermatology, and wound repair space and none are a run-away success.  Does it worry you to be also focused on these areas for your near-term opportunities?

DH: That is a statement on the relative efficacy and difficulty of delivery.  Approval does not necessarily equate to commercial success.  We believe that our programs will have significant efficacy for their targeted indications, be easily delivered and they will become the gold standards.  But that is the nature of product development; you have go out and demonstrate efficacy!  One comment on wound repair is that we are not at this time interested in pursuing open wound repair as that space has many solutions ranging from complex cell therapies to medical devices.  It is a crowded space and we prefer at this time to prove our platforms where we are confident in our success and are not populated by other treatments.  

CTB: Your initial focus is on autologous applications of the hair follicle-derived cells, what are plans to address some of the commercial (cost) challenges presented by autologous cell therapies already on the market?

DH: As mentioned above, we are focused in parallel to our clinical development programs, on developing a scalable process for our cell manufacturing.  We see this as a process engineering program and not a development process requiring scientific breakthroughs.  This development program is underway.  It is also true that we believe that our hair follicle derived cells are immune privileged and that in the future, our technologies could well become an allogeneic offering.  But that is down the road. 

CTB: Few companies of ReplCel’s size and market cap are simultaneously tackling multiple products in clinical trials let alone also the concurrent development of a proprietary delivery device.  Some might argue it would be more prudent to preserve capital to ensure you have what it takes to move one product further down the line.   Can you give us a sense of your why you prefer this multi-pronged strategy?

DH: Our programs are inherently cheaper to develop and test than more complex cell therapies and for that matter, new chemical entities or biologics.  We are simply expanding a patient's cells and giving them back to them.  It is just cheaper to do than other therapies.  As such, we can undertake more programs and I would argue that for shareholders, more shots on goal helps to mitigate risks associated with clinical programs.  We believe we have a single focus on leveraging our core expertise around cells derived from the hair follicle organ and finding meaningful clinical applications for those cells.  Optimizing the manufacturing and delivery of those cells just makes sense as part of the risk mitigation and value optimization of those assets.

CTB: To those investors interested in the regenerative medicine and cell therapy sector, where does RepliCel fit in the industry and how do you think it stacks up against sector comparables as an investment opportunity?

DH: I would characterize RepliCel as a mid-stage development company that exists between earlier approved products like Apligraf and Dermagraft for wound healing, and much more complex cell therapy clinical development programs.  There are other mid-stage programs like Athersys' MultiStem and Mesoblast’s Mesenchymal Precursor Cells.   However, I would argue that our simple cell replication process of a target cell deficit is simpler to manufacture and deliver than many cell therapies.  So, I would characterize our development programs as lower risk.  Nevertheless, I would also say to investors that regenerative medicine is going to be a huge field in the future as science and technologies evolve.  This industry will be delivering incredible medical solutions for patients in the future.  

 CTB: Talk to us a little about the stock.  It’s very lightly traded on both the Toronto venture exchange and over-the-counter bulletin board.  What’s the plan going forward in terms of its listing and liquidity?

DH: Yes, it is true our trading has been low.  That is a direct function of our tightly held stock, (management, founders, etc., own approximately 45% of the stock) and the fact that we were very focused in 2103 on our partnership and the patent filings.  As discussed above, we are now launching our story on a focused basis that will see the company out on road shows delivering its message to potential investors.  We think that RepliCel is an attractive and unknown story which will have a good reception.  That effort is focused on addressing the valuation and liquidity.  In terms of listing, the natural progression as we develop assets and valuation is to up list which we will be pursuing.

CTB: Where do you see RepliCel in 18-24 months?

DH: On a clinical basis, we will have data in both our tendon and derm programs and will be closing in on the clinical trial data for our treatment for pattern baldness.  We should at that time be initiating at least one other tendon program and a phase 2 derm program.  We will have developed clinical protocols for two new indications for our fibroblast platform (not yet being disclosed due to patent work) and we will have demonstrated scalability of our manufacturing platform.   If we accomplish this as planned, we will have established an extremely valuable group of assets.   

CTB:  Thank you, David, for the opportunity to spend some time learning more about RepliCel and your plans for the company.

Tuesday, May 20, 2014

BioKorea 2014 - A focus on cell therapy and regenerative medicine

I am pleased to be working this year with BioKorea and the Korean Global Stem Cell and Regenerative Medicine Acceleration Center (GSRAC) to host a full-day regenerative medicine track during the BioKorea conference at the end of May.   

The Korean Ministry of Health and Welfare and regenerative medicine industry are blazing an innovative trail in terms of the commercialization of cell-based therapies which the world is watching with increasing interest. The Korean approach to and pace of product approvals has attracted the attention of investors, entrepreneurs, and regulators alike. On the Korean side, companies with commercial products are eager to expand into other markets. This involves technology transfer, securing partnerships, and subjecting their products to different types of regulatory requirements and clinical testing. 

Companies outside of Korea are increasingly interested in identifying and how to involve Korea in their product development plans if it means an expedited pathway to commercial approval. This would likely involve identifying a Korean partner (or investors) and establishing a deep understanding of and relationships with the Korean regulators and industry.

In order to satisfy the needs of the industry both within and outside Korea it is critical to establish a closer working relationship between industry organizations, facilitate a better mutual understanding of the different markets, and create mechanisms for companies to further their goals by helping them identify partners, understand regulatory differences, establish critical relationships, find investors, etc.

This event is intended to create the initial framework for enhanced international collaboration between Korean and the global regenerative medicine industries.

Attendees will:
  • gain a more in-depth understanding of the opportunity and challenges in transferring a commercial product from Korea to other markets
  • hear case studies of collaborations between pharma and regenerative medicine companies
  • learn about the unique advantages and challenges of commercializing regenerative medicine products in Korea
  • learn about the perspectives of the pharma industry on regenerative medicine including cell-based therapies
  • have opportunity to establish contacts with international pharma executives, regenerative medicine companies, and potential partners and investors
  • have opportunity to identify companies from other markets potentially interested in (a) finding a partner, and/or (b) seeking to license and/or partner with Korean companies to take their product(s) into other markets
  • participate in networking activities with representatives of the global and Korean regenerative medicine industry
  • have opportunity to showcase the Korean biotechnology industry and capabilities to members of the global industry

The focus of the session is to facilitate increased collaboration between Korean and international regenerative medicine companies by creating a forum for exploring a better understanding of the Korean regenerative medicine industry and the potential for creating partnership, licensing, and investment opportunities emerging out of and interested in going into Korea.  

We are pleased to have a full day of exciting content from both Korean and international speakers from multinational pharmaceutical companies, Korean representatives, and regenerative medicine companies from around the world.  

In addition to the full-day program, we are also facilitating partnership discussions, networking events, and meetings (if requested with the Korean Ministry of Health & Welfare (formerly the KFDA).

BioKorea will be held May 28-30 at the KINTEX Exhibition Center in Goyang city near both Seoul and the Incheon International Airport. BioKorea, is organized by the Korea Health Industry Development Institute, KHIDI, as a government (Ministry of Health and Welfare)-affiliated organization and Chungcheongbuk-do Province, which is the center of Korean biotechnology, life sciences, and healthcare.  The annual event first started in 2006 and is expected this year to attract 13,000 participants and over 260 exhibiting companies.

Track 3. Stem Cell and Regenerative Medicine: Thursday, May 29
This track aims at facilitating international cooperation and global commercialization
among companies in the stem cell and regenerative medicine, and will serve as a forum of discussion and deliberation for domestic and foreign business enterprises.

The applicants will have opportunities to take part in the following:
   Session I: Introduction to the current status of domestic and foreign markets
and industries of stem cell and regenerative medicine
   Session II: Case studies on technology licensing out between regenerative
medicine companies and large-scale companies
   Session III: Publicity for domestic and foreign regenerative medicine companies
and their products
   Partnering: For those companies which seek opportunities, a meeting place will be provided for their matching commercialization needs.

To help give a little more flavor to this event and the state of the industry in Korea, I had the opportunity to interview Professor Bryan Choi, who is Vice-Director of the GSRAC and has been much of the energy behind making the event a reality.

Welcome, Bryan. Can you start by telling us a little bit about the Global Stem Cell and Regenerative Medicine Acceleration Center (GSRAC) and how you yourself got involved in regenerative medicine?

GSRAC is a government commissioned strategic center that helps the Korean government (a) establish appropriate policy and regulations, (b) facilitate the translation of research to the clinic, and (c) assist RM companies accelerate market entry of their products.  I, myself, am a researcher in regenerative and happen also to be involved in the management of the GSRAC. 

Give us a sense of the state of the regenerative medicine sector in Korea. 

RM is one of hottest areas of interest in the biomedical and pharmaceutical field and is being supported a lot by the Korean government. At the same time, we are also struggling to move forward with some of the technical and commercial aspects of these products. 

How many cell therapy products are commercially approved in Korea to-date and how many are in pivotal trials? 

I know approximately 18 cell therapy products have been launched in the Korean market and 3 of them are stem cell products.

In the past couple years, the world has been watching the development and commercialization of regenerative medicines, especially cell-based therapies, in the Republic of Korea with considerable and growing interest. This is largely driven by a number of cell therapies (including stem cell products) approved for commercial distribution by the Korean Ministry of Food and Drug Safety (MFDS) (formerly the KFDA) and the perception that the regulatory pathway to commercial approval appears to be more proactive and expedited than what exists in the United States and Europe. Can you comment on this?

I cannot say it is exactly proactive but it could be fairly perceived as relatively ‘expedited’ (compared to many other jurisdictions) due to the fast but not abbreviated process of MFDS. MFDS has similar principles to those of the US and Europe for the approval of cell therapy products. A final decision for a submitted product is case dependent. 

We hear rumor that there are changes being considered to the regulation of cell therapies in Korea, can you comment? 

We are currently talking about the need for a new, revised regulation that fits better for RM products but it is not yet formalized. 

What is the level of interest or activity among Korean investors or large life science companies in investing in Korean regenerative medicine?  Are you seeing any growth of interest in entering the Korean market from regenerative medicine companies outside Korea?

Recently they are getting more interested in RM. Some investment deals have been done recently between RM companies and Korean pharmaceutical companies. Where we have yet to see any notable activity is that of foreign investment or interest in the Korean RM market – even by the large multinational firms. 

Tell us about BioKorea and your plans for a regenerative medicine track at this year’s conference. What do you hope to accomplish with this event?  

In BioKorea 2014, we have a RM track (Track 3) which deals with business development and partnering in the RM industry. We invited more than 10 speakers of RM experts or from RM companies to talk about business models in regenerative medicine and partnering opportunities particularly between Korean and foreign RM companies.
How can people find out more about the event and what are the ways they can participate?

Please refer to the following websites: and  

Will representatives of the Korean Ministry of Food and Drug Safety (MFDS) be at the conference and available for participants to interact with if they wish?

MFDS representatives may be at the conference but we are also planning a separate meeting with MFDS for those interested. 

Will there be opportunity for companies from outside Korea to identify and speak with potential Korean partners that might be potentially interested in in-licensing or out-licensing products?

It is always welcomed. You can participate in the business partnering any time before the end of BioKorea 2014, and may also give an introduction of your company in the session III of the RM track, if a slot is available. Please contact us (bryan [at]gsrac [dot] org) for the availability. 

Thanks Bryan.  I am very much looking forward to the event.

Tuesday, April 15, 2014

An Interview with BioCision. Why Innovating for Reproducibility is Good Business.

BioCision is one of those companies that easily catches your attention (they use lots of bright colors) but might take awhile to be a regular part of your consciousness.  After all, laboratory and bioprocessing tools are not the sexiest product category.  Because of that, I tried to ignore BioCision for some time as a company that looked interesting but was too 'laboratory-focused' for my tastes.

What eventually forced me to take a closer look at this company was their clear commitment to two things:  (1) making standardization and simplicity major driving forces for their innovation, and (2) online audience engagement not just for marketing but as an incredibly useful tool in driving the innovation feedback loop.

Also, I'll admit I was completely wrong about them only offering research laboratory tools. It turns out their applications may indeed offer even more value to those involved in clinical production.

They are a private company quietly but busily innovating around some of the most basic biologic handling issues in the lab or manufacturing suite -- often solving problems you didn't know you had until you are presented with the solution.  They are an interesting mix of conservative yet innovative - bold but basic.

Long-story short:  this company has really grown on me as the 'read deal' such that theirs is the first corporate advisory board I recently agreed to join (there's my disclosure).  

A company is, of course, about a lot of people doing a lot of important things (big and small) that collectively make it a success but there's no doubt that Rolf Ehrhardt, the company's President and CEO, has stamped the company with his imprint.  Because it is so clear to me that the BioCision culture and modus operandi is very much an imprint of Rolf's personality (as is often the case with companies a la Apple, Miltenyi, etc), I had to sit him down for an interview.  That is what follows and I hope you find it interesting if not informative.

CTB: Tell us about BioCision and the sector(s) you serve? 

The reproducibility of scientific studies has become a major issue in life science research from drug discovery and development through to clinical trials as researchers around the world continue to use different protocols for processes associated with sample preparation, cryopreservation and cold chain management. The scientific community is now becoming more aware of factors that affect sample integrity and experimental variability. By standardizing handling, storage, and transportation protocols we can vastly improve the quality and reproducibility of preclinical and clinical data, helping to accelerate the transition from lab research to drug development and market launch.  

That’s where BioCision comes into play. In 2007 a group of scientists, biomedical engineers, and drug discovery experts founded BioCision to develop laboratory tools with standardization in mind in order to set a new bar in temperature control for biomedical samples. Today our products are used by researchers around the world in pharmaceuticals, biotechnology, academics and healthcare. We are positioned for continued growth in multiple sectors including cell therapy, regenerative medicine, biobanking, bioprocessing and cold chain management. 

CTB: What would you say is BioCision’s underlying philosophy or business approach?

Our goal is to enable researchers to achieve the highest attainable levels of pre-analytical sample reproducibility and consistency – experiment to experiment, lab to lab and site to site. In order to accomplish this, we are very focused on our role as a leading advocate for the standardization of biomedical samples for basic, pre-clinical and clinical research.

In addition to our novel products, our business strategy is based on our ability to engage and mobilize the scientific community around this effort to improve reproducibility and develop new sample handling standards. We just announced the creation of a new scientific advisory board that includes internationally recognized researchers who are uniquely qualified to help BioCision develop additional products and support solutions that are able to address standardization challenges for our customers. 

We look forward to working closely with the members of our advisory board, especially as we continue to expand our position as a global partner to support research and product development, in cell therapy in the years ahead. 

We have also been able to leverage social media platforms not only to share and support our message of preserving sample integrity but engaging our audience on their innovation needs. For example, we have worked hard to develop and maintain a blog called “Sampling Science®” to keep our readers informed about standardization efforts in cell therapy research and other fields of interest.  Most recently, we created a discussion group called “Scientists Against Sample Abuse™” - or “SASA™” - to continue this important conversation about improved sample handling with customers and fellow advocates.

In the end, these efforts have resulted in a growing community of laboratory researchers and clinicians who understand the significant impact that sample/drug handling and storage techniques can have on study results and even the efficacy of new biological therapies.

CTB: Your products seem to have a very strong visual design concept that’s reminiscent of Apple or Miltenyi.  How important is that to the company?

The design of our products is positioned as a significant value-added benefit for our customers. On the surface, the fluorescent colors we use for our products bring a spot of fun to the laboratory and help us stand out at exhibitions and medical conferences. But there’s much more behind our design strategy. 

The use of color-coding also helps laboratories work smarter and reduce the risk of errors. Most labs still use buckets of ice, refrigerators, water baths and mostly white, grey or glass containers for biomedical sample handling and storage. This makes it difficult to organize samples in an intuitive way, leading to delays or errors in processing that can affect sample quality and results. 

We try to design products based on how scientists actually interact with samples. We make it possible for researchers to use color to streamline operations and improve the quality and efficiency of lab procedures. The use of color makes it easier to store and organize similar samples. Labs can develop storage protocols based on color so any researcher is able to easily find a sample. We envision a future where products can be custom-designed and color-coded to meet the needs of major laboratory systems around the world. 

CTB: Has the company done much in the way of partnerships with larger companies?

Last year, we announced an agreement with the American Type Culture Collection (ATCC), the world's leading provider of authenticated biological material, that enables the development a custom line of products including the CoolCell LX cell cryopreservation device.  As a result, ATCC cell-freezing protocols recommend the use of CoolCell LX containers to maintain an optimal controlled and standardized freezing rate. Their protocols are widely used as the industry standard in global biomaterials research. 

This year we are working on a couple of exciting projects. The first is with TxCell, a French company that is developing cell-based immunotherapies for the treatment of severe chronic inflammatory diseases. Several of our products are being used to support temperature control and the processing and handling of cell therapies in their Phase IIb clinical trial investigating the use of an antigen-specific regulatory T (Ag-Treg) autologous cell-based immunotherapy for the treatment of patients with moderate to severe refractory Crohn’s disease. In this effort our CoolCell alcohol-free cell freezing container is being used to freeze Type 1 regulatory T (Tr1) cells in Aseptic Technology ampules. 

It’s an interesting case study, because in previous trials, TxCell used electronic programmable freezers to manage the cell freezing temperature. However, the Phase IIb trial will involve collection of cells from multiple sites, prompting  TxCell to choose the CoolCell containers for cell freezing, because they provide the same freezing outcomes as programmable freezers, while being much easier and much less expensive to deploy to multiple clinical sites due to their portability, lack of necessary maintenance and ease of use. TxCell is also using our CoolRack and CoolBox ice-free cooling systems in the cell handling stage to standardize the temperature of the cell preparation, media, and cryopreservatives to 4°C without the use of ice and reduce the risk of drug-product contamination. Because the efficacy of regulatory T cells can change without proper and reproducible handling methods, the standardization of pre-analytical drug sample handling, cryopreservation and storage are key to ensuring consistent trial results. 

TxCell will present additional details on the use of CoolCell containers for cell freezing during a poster session at the 20th Annual Meeting of the International Society of Cellular Therapy in Paris this April. 

A related paper has also been published in the March issue of BioProcess International titled “Effective Cryopreservation and Recovery of Human Regulatory T Cells.”

Earlier this year, we received a $4 million equity investment from Brooks Automation, a global provider of automated sample storage systems for compound management and biorepositories. The investment initiates a strategic partnership that will support the development of innovative sample handling solutions for cold chain management and the handling of drug products. 

In just the past few years, numerous independent publications have endorsed and recommended the use of BioCision products in their methods and protocols sections. We look forward to partnering with more companies in the years ahead by offering innovative solutions to temperature control and sample handling and storage needs. 

CTB: What product offerings do you have in the cell therapy space?

We are perhaps best known for our CoolCell cell freezing containers, which provide a reproducible  freezing rate of 1°C/minute when placed in a -80°C freezer and have become the new industry standard for cell cryopreservation in research and clinical applications, including cell therapy. The rate at which stem cells are frozen is crucial to the overall success of cryopreservation process and the freezing rate should be measurable in a way that does not rely on the freezer size or model and should also be equal across all samples in a freezer.  Our CoolCell SV series is specially designed to fit closed-system, injectable glass ampoules that are popular in the cell therapy space where aseptic vials are critical for minimizing contamination. 

A recent independent example of our product in use in the cell therapy space was published in the Journal of Autoimmunity. Researchers cited the use of a CoolCell freezing container for studying the role of T cells in myasthenia gravis. The CoolCell freezing container was used to gradually freeze cells isolated from the blood of both patients and healthy donors for long-term storage while sample collection was underway.

Our CoolRack® and CoolBox™ ice-free cooling systems are also commonly used to standardize the temperature of cells, cell media, and cryopreservatives prior to the cryopreservation stage. 

More recently, we have developed a product called CoolStation™ which is a mobile ultra-low temperature workstation.  The CoolStation systems provide an ultra-low temperature open-top work space through the use of dry ice or LN2 where a variety of operations such as cryogenic packaging, sample sorting or transport, or sample freezing can be performed.  For example, by placing a CoolStation next to a biosafety cabinet during cell preparations, cells could be placed into a CoolCell freezing container and the CoolCell could be directly placed in the CoolStation for immediate freezing, limiting the non-frozen exposure to DMSO or other potentially harmful cryoprotectants. 

CTB: Why have you decided to expand into the field of cell therapy?

Cell therapy is a rapidly expanding field that holds great promise for future clinical applications and early trials continue to yield positive results. But in the grand scheme of things this is still a very new field of research. Just a few years ago it was often assumed that small variations in cell temperature or cryopreservation would not dramatically affect the outcome of an experiment.  As cell therapy research has advanced we now have a much better understanding of how stem cells behave in different environments, and it’s clear that even slight changes in temperature management can have major implications for the efficacy of the final therapeutic product. Today, we regularly find and share reports on the importance of proper sample handling, particularly related to temperature control, to ensure the reproducibility of cell therapy research.

For example, following workshops organized by the U.S. National Institutes of Health (NIH), the journal Nature recently launched an initiative to more systematically ensure key methodologies are reported by researchers, including the creation of a checklist prompting authors to disclose certain technical and statistical information.

The movement to minimize irreproducibility in cell therapy research has led to growing interest in BioCision’s innovative solutions as researchers discuss different tools and protocols for handling and storing samples. 

CTB: How do you decide on new products to develop?

We remain focused on sample standardization in all areas of life science and clinical research and are continuously developing and improving tools that address common problems related to biomedical sample handling and storage. 

Currently we are working on three main areas of product development. First, we continue to advance our cell freezing and related workflow solutions, with a special focus on stem cells and primary cells for research. Second, we are developing new solutions for sample handling before and after long-term storage (i.e. Biobanking). And third, we are studying clinical and diagnostic applications where maintaining consistent temperatures - either cold or warm - is critical, for example in home-based assays and cold chain management for short transport. 

In these efforts we are always actively seeking partners and collaborators who have an application for our innovative technology. 

CTB: Are you working on any new technologies that the cell therapy sector should be excited about?

Yes.  We have a number of products related to the cell cryopreservation workflow in various stages of development, some of which will be released at the ISSCR annual meeting in Vancouver in June, and these products will directly relate to cell therapy and aid in further standardizing cell handling.  And, as mentioned above, we are working with Brooks Automation to develop new products that will also apply to the cell therapy workflows.  

CTB: Will you be at the upcoming ISCT conference?

Yes, we’ve been looking forward to this year’s conference for quite some time. Working closely with TXCell, we are excited to present an abstract during the poster session that will analyze the benefits of using our CoolCell freezing containers in the manufacturing of an autologous antigen-specific Treg (Ag-Treg) cell-based immunotherapy for the treatment of patients with severe refractory Crohn’s disease. Researchers investigated CoolCell freezing containers as an alternative to the classical programmable freezer and developed a new standardized method of cell therapy product cryopreservation. It’s a major first step towards the use of cell therapy in the clinic. 

We also plan to present an abstract in collaboration with researchers from Dr. Jeff Bluestone’s lab at the University of California, San Francisco who are investigating the cryopreservation of peripheral blood mononuclear cells (PBMCs) with the intention of isolating regulatory T lymphocytes (Tregs) for autologous cell-based immunotherapy treatment in patients with autoimmune diseases or transplantation recipients. Similar to the TxCell study, the UCSF team investigated CoolCell freezing containers as an alternative to programmable freezers to cryopreserve PBMCs. They concluded CoolCell containers can help overcome challenges associated with multiple clinical site collections in cell therapy research because our device is less expensive, portable, lacks necessary maintenance, and is easy to use. 

CTB:  Thanks for the taking this time with us.  We look forward to hearing more about what the company has in store for the cell therapy sector soon!

Oh ya.  And remember that bit about social media?  Check them out: