Regenerative Medicine / Cell Therapy at Biotech Showcase 2014

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As many of you know, during the week of January 13, healthcare and life science executives meet investors in San Francisco for a flurry of conferences, meetings, parties, and general mayhem.  

The EBD Biotech Showcase is one of several events taking place that week and it the one of particular interest to us because it has the most concentrated focus on regenerative medicine and cell therapy companies.  The full list of presenting companies is here. For those of you on Twitter, follow #BTS14.

We've gone through and picked out the regenerative medicine and cell therapy content.

Sponsored by the Alliance for Regenerative Medicine, the 4th annual Regenerative Medicine Industry Briefing kicks off the meeting at 8 am on Monday morning (Jan 13th) .  This year it is in the big plenary room and it promises to be the best yet.  Invite your friends, investors, partners, and media contacts.

We spotted the following 29 companies scheduled to present at various times as shown on the schedule spanning Monday through Wednesday:

Adaptimmune
Advanced Cell Technology
AlloCure
Bone Therapeutics
Cell Medica
Cell2B
CTI Clinical Trial and Consulting Services
Cytori Therapeutics
DiscGenics
Fibralign
Harvard Apparatus Regenerative Technology
International Stem Cell
Kiadis Pharma
MaxCyte
MolMed
NeoStem
Neuralstem
Northwest Biotherapeutics
NovaRx
PharmaCell
Pocastem
Q Therapeutics
RepliCel Life Sciences
RhinoCyte
Sernova
TiGenix
TVAX Biomedical
TxCell
ViaCyte

Because it is a full schedule with 4 concurrent tracks, we made our own schedule of regenerative medicine and cell therapy presentations. In case it is useful, we provide it here for you to download and use.  

2014 EBD Biotech Showcase Regenerative Medicine and Cell Therapy Presentation Schedule (PDF)*

    This schedule is sponsored by

* We can't promise we didn't miss a company, screw up the schedule somehow, or that EBD might not change things between now and the event.  You should really check this against the EBD program and please... rely on this resource in your discretion. 

Washing cryopreserved cells. An emerging need or disappearing process?

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I’m not a fan of the allogeneic vs autologous business model debate because I don’t believe it’s a debate that rages other than at conference panel sessions.  Most investors, researchers, and executives recognize that there will almost certainly be room for both to succeed and that the winner in any particular indication will be largely determined by proven clinical efficacy over the standard of care and other available treatment alternatives.

Cryopreserved vs Fresh

The oft-touted primary commercial advantage of allogeneic cell therapy products over their autologous counterparts is the ability to inventory standardized products for later on-demand distribution and use.  This contributes to the ‘economies of scale’ advantage allogeneic products enjoy.  Certainly this is true.

Critics of the autologous business model cite the high cost of single-batch lot sizes and short shelf-life of autologous products- often shipped fresh - as the primary drivers of the high cost of these types of products and the variation in cell composition of therapeutic products derived from patient to patient.  Certainly also true.

Nonetheless, the two issues most involved in a debate comparing the business models are cost and price implications of the relative bioprocessing scalability and distribution costs of each model.  For sake of convenience it is most often assumed that allogeneic cell therapies are cryopreserved and autologous products are delivered fresh from the manufacturing site to the clinic for delivery to the donor-patient.  This is, of course, an over-simplification because it is not always true.    

Take, for instance, Opexa Therapeutics’ Toxavin which involves the cryopreservation of multiple doses (potentially representing several years) of treatment from a single patient apheresis.  This is in stark contrast with Dendreon’s Provenge which requires a new apheresis for each of three monthly treatments and a limited shelf-life of a fresh product of approximately 72 hours. One cannot avoid concluding that the likely cost implications of such a difference are bound to be significant considering the differences in upstream collection, processing, and distribution costs.

I want, however, in the last few paragraphs of this post to focus attention on a couple of aspects related to cryopreservation of cell therapeutics.  Firstly, as a digression, I am often left with the impression that executives and analysts alike often over-estimate the cost of shipping fresh products (with their temperature and time sensitivities) compared to the costs associated with shipping cryopreserved products which most often require heavy and bulky LN2 shippers as well as facilities and personnel experienced with receiving and handling cryopreserved products at regional repositories and local pharmacies.

 

Does the existence of cryoprotectant excipients dictate point-of-care cell washing?

Currently the short answer is “not necessarily”.  The primary point I want to address here, however, is related to the costs currently associated with balancing the excipient and processing requirements involved in cryopreserving, storing, and thawing cells on the one side with the need to have a product that is clinically safe, effective and well tolerated by the patient on the other side.  Companies developing cryopreserved cell therapies have three choices in this regard:

1. Infuse the patient with a product that includes cryopreservant excipients (almost always including some levels of DMSO being the overwhelmingly dominant reagent) recognizing the impact on patient experience and infusion volumes (a more significant concern in bodily regions where capacity is small (e.g., heart) or potentially sensitive (e.g., brain). 
2. Invest in developing an infusion-ready formulation that significantly minimizes the amount of excipients.  This may or may not involve a thaw or post-thaw dilution.  
3. Commit to a process that involves point-of-care, post-thaw washing and re-concentration of the product to remove excipients and minimize the volume size of the product to be infused.

In terms of examples, we believe Mesoblast is currently in the first camp, Celgene has pursued the second strategy, and Athersys is an example of a company using the 3rd approach.  Each have a similar cell type and all three are pursuing some of the same indications. 


Some companies have worked hard to bring to market cryoprservant formulations that reduce the amount of DMSO (e.g., BioLife Solutions).  Some predict that in the near future DMSO-free cryoprservants will be a real fourth option (e.g, Essential Pharma's Cryo-Ess currently for Research Use Only). 


These products will have to be pioneered by some early-adopters before they are readily considered by the majority of players in a field which is oft-defined both by its dogged pursuit of precedent and reticence to be mold-breaking and innovative.

Stem cell transplanters are also faced with deciding between first and third course.  While different considerations and drivers apply to them vs companies developing s.351/ATMP products, they are still faced with the decision to wash or not.

What factors to consider in the “to wash or not wash” debate?

Of the many and somewhat differing factors to take into account, cell therapy developers and stem cell transplanters share a number of common considerations when deciding how to treat cryopreservants in the clinical setting:

• Regulator’s general tolerance of DMSO in the final product formulation to-date.  Despite this record of tolerance, it is expected that for certain indications and/or for certain types of routes of administration, there may be significantly more regulatory scrutiny concerning injecting DMSO.  Indeed, DMSO is classified as a Class 3 (relatively low risk) solvent in ICH Q3C with a recommendation of 50 mg/day as upper threshold below which one does not need to ‘justify’ its presence.  The typical DMSO solutions used in cell therapy labs contain about 1 gram (not mg) per mL before dilution-- so if used at 10% in final product, this translates to 100 mg per mL. Therefore a 10 mL cell therapy product (at 10% DMSO) would contain 1000 mg (1 gram) of DMSO (20 times the ICH threshold).

It may be worth noting that apparent regulatory tolerance of the infusion of DMSO may be somewhat tied to the fact that most previous applications have involved the IV injection - allowing for excipients to e rapidly diluted in systemic circulation.  For cell therapies delivered some other way, potential toxicity may be a more significant concern.

• Concentrations of 10-20% DMSO has been traditionally used since the dawn of stem cell transplantation with minor reports of allergic reactions (e.g., hives, itching or facial or glottal edema) and only rare reports of more serious anaphylactic/oid reactions. Side effects of DMSO include hypernatremia, fluid overload, dysgeusia (distorted taste), nausea, vomiting, elevated liver enzymes, hemolysis, renal failure, and allergic reaction.  DMSO toxicity is the most common complication of stem cell transplantation with symptoms including flushing, rash, chest tightness, nausea and vomiting, an cardiovascular instability (as outlined in the Circular of Information for the Use of Cellular Therapy Products).  Ruiz-DelGado recently reported dimethyl sulfoxide-induced toxicity in cord blood stem cell transplantation and reviewed the literature (Acta Haematol. 2009;122(1):1-5).  The authors reported the incidence of any cord blood infusion reaction ranging from 4% to 65%, with life-threatening infusion reactions occurring in up to 4.6% of patients. 

It is worth noting that  the FDA’s Pharmacovigilance Review Memo, related to the FDA’s recently approval of the New York Blood Centers BLA for its cord blood progenitor product named “Hemacord”, includes the following statement:  

“Exposure to DMSO and Dextran-40, though not completely avoidable, can be limited by proper preparation before infusion of cord blood. Warnings and instructions for preparation (e.g. thawing, washing, dilution) should be included in the label.”

• Even for those patients who do not experience any toxicity, allergic, or anaphylactic/oid reaction, there is an undisputed and significant ‘garlic’ odor and taste experience by the patient as well as the issues related to having to consent around the infusion of such excipients.

• One of the outstanding regulatory questions is to what extent regulators will consider point-of-care washing steps to be a final manufacturing step.  Closely related, but not necessarily intrinsically tied to this issue, is the question of whether a final release assay will be required to test a final product which was washed and re-concentrated post-thaw.

• Finally, one is tempted to wonder whether to what extent regulatory opinion, commercial strategies, development pathways are influenced by what has been to-date a lack of commercially acceptable and viable technical solutions to post-thaw washing and re-concentration.

On this last note, Cell Therapy Group is working with Stem Cell Partners on bringing to market what we believe is potentially a simple, quick, cost-effective, easy-to-use density phase washing centrifugation device utilizing commercially available reagents and centrifuges – the EnsuraSep Cell Washer.  

Have a quick spin through the brief technology outline at www.cellwasher.com and I would be happy to discuss it further with anyone interested.  

We are working on different configurations and sizes of that device for different applications. Stem Cell Partners is working with our clients to design custom canisters and reagent-formulations to meet their specific requirements.  Stem Cell Partners is also working on alternative centrifugation-based device that has a wider-capacity range. 

While we believe the Ensura-Sep Cell Washer may enable a simple and rapid washing and concentration of a cell suspension in a single centrifugation step, CTG is also working with other companies who are pursuing other solutions using different technologies such as filtration.

There is currently much expert divergence on the question of what role point-of-care cell washing/concentration may play in the future of cell therapies.  I invite any and all comments or feedback on this post either using the comment function here or in the discussion thread mentioned below in the LinkedIn Cell Therapy Industry Group.

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Much thanks to a great discussion thread in the LinkedIn Cell Therapy Industry Group called “Clinical preparation of frozen cell therapy products” which inspired must of this content with a special nod to Jon Rowley, Reinout Hesselink, EJ Read, Christopher Bravery, and Ali Mohamed.

Commercializing Cell-based Regenerative Medicines

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When introducing a regenerative medicine cell based product to a commercial setting, there are a number of things to take into consideration to ensure a commercially viable and safe product for patient use.

In this QandA interview by Pharma IQ, William Fodor, Director of Translational Sciences, Cell Therapy Group, gives a few insights into the commercial manufacturing scale‐up process of cell therapies.

Listen to the podcast here (registration required) or read the transcript below:

Pharma IQ: Can you give some advice on the best way for a company to develop standards for commercialization to improve safety?

W Fodor: As with any biological product, you have to do all the appropriate testing and there’s really no standards necessarily to be developed by the company because the regulatory process is pretty well outlined by the FDA and CBER. Cell therapy products are regulated by the office of Cell Tissue and Gene Therapy Division. So, it’s not that you need to develop standards for commercialization you just need to follow the regulations by demonstrating to the FDA that your product is safe, and maintains the identity, in other words, your product doesn’t change during your regular manufacturing process. Purity and potency are all assays that need to be developed within the manufacturing process for your particular cellular product.

Pharma IQ: And what are some approval processes and pitfalls to be aware of within the scale-up process?

W Fodor: As you are scaling up your process to meet clinical trial requirements and eventually commercialization, you absolutely need to maintain current good manufacturing practices, cGMP.  Typically, during a phase one, you can get away with certain reagents that may not be fully GMPs. Or in other words, if you use a growth factor or a certain media that doesn’t have or isn’t manufactured under full GMPs, as long as you test that particular reagent or media that you are using to ensure safety and sterility, you can typically get away with that in the phase one clinical trial process. But when you move to a phase two, you need to make sure that all your reagents and medias and any compounds that come in contact with your product are all manufactured under cGMP.

Pharma IQ: What are some technology transfer and patent protection concerns to be cognizant of?

W Fodor: With any cellular-based product, if there’s a technology that is out there that a company wishes to pursue, to improve yield, or the manufacturing process, you need to demonstrate that that technology fits within your manufacturing process. So typically, what is done is you’ll do validation runs to ensure that that new technology satisfies the regulatory process for your manufactured product.

With respect to patent protection, again, that company needs to maintain their IP portfolio and needs to make sure that they’re not infringing other intellectual property and that’s just standard for the industry.

Pharma IQ: And do you have any tips for ensuring quality and consistency no matter how little or how much one is producing?

W Fodor: Yes, when you manufacture a cell-based product, it’s not that much different than any other biologic product. And so, during your  manufacturing runs, whatever scale it is, you have to ensure safety, such as sterility tests for microplasma, or other adventitious agents; as well as bioburden and endotoxin.  These are all tests that  need to be performed.

You need to have an identity test to make sure that your cell product, at whatever scale you are manufacturing, that at the end of that manufacturing run, the product hasn’t changed. Again, no matter what scale you’re at, you need to make sure the identity of the product is consistent from batch to batch.

For identity, you can do a number of things for a cell-based product, if you want to look at cell surface antigens to ensure that the cell surface proteins on your cellular product don’t change over time or through your manufacturing process. And typically, what you like to do is keep it relatively simple. You don’t want to test for a hundred things because you’re just asking for the potential for something within those hundred tings to change. So typically, what you do is maybe three to four cell surface antigens to ensure your product identity is consistent. You can also run PCR tests to determine that an intracellular protein of interest doesn’t change during your manufacturing process.

You also need to ensure for purity, so you want to quantify the purity of your active cell type or your tissue type. And then potency; you need to demonstrate the product has a consistent potency and the biological activity of that final product doesn’t change during the manufacturing process.

And then typically, what you do is you archive. You archive samples from your manufacturing process. You cryopreserve those so you can always go back to ensure that that a particular batch was consistent with other batches that were manufactured.

To contact Bill for any follow-up or other questions related to cell therapies, see his contact information on the Cell Therapy Group website.

For a PDF copy of this interview, click here to download.

Cell Therapy Industry Video Channel

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Cell Therapy Group and BioBusiness.TV are pleased to announce they are collaborating to build a "cell therapy" video channel focused on the cell therapy industry.  The initiative is part of BioBusiness.TVs "Best of the Web" initiative intended to bring together publicly available video content that complements their original content.

The Cell Therapy channel will focus on cell-based therapeutic products which are in clinical development by or are commercially available from companies around the world.   We will update this channel frequently.

To view other video content, see Cell Therapy Group’s YouTube channel.

To recommend video content, submit your comments below.

Cell Therapy's Got Talent Technology Showcase - A Call for Cell Therapy Manufacturing Technology Presentations

in collaboration with:

In an effort to showcase the latest technologies driving the production of cell therapies, the Cell Therapy Group and Informa Life Sciences are proud to announce the introduction of the "Technology Showcase" session and award to be held in conjunction with Informa's Cell Therapy Manufacturing conference to be held 30 November to 1 December 2011 in Brussels Belgium.

Having held the same conference last year in London, Informa is committed to building on the success of last year's event by continuing to create a meaningful European forum for the issues related to the clinical and particularly commercial-scale production of cell-based therapies.

The Technology Showcase session, taking place on the main agenda, will feature 6 x 10 minute presentations from innovative companies developing cutting-edge technologies in the field of cell therapy manufacturing, and is particularly relevant to SME and academic groups with limited marketing resources.

All presentations will be reviewed by the Scientific Advisory Board with the winner announced at the end of the session. Exposure on BioProcess International's website is also included.

Technologies we'd like to promote include:

• Manufacturing systems including bioreactor technologies
• Cell harvest/collection technologies
• Cell storage/logistics technologies
• Clinical cell delivery and/or other point-of-care technologies
• Automation technologies
• Cell separation system
• Cell process devices
• Innovative reagents, scaffolds, matrices, and other “ancillary” tools
• Technologies to close currently open systems
• Suspension-based production systems
• Disposable technologies

How to apply:

To apply to present companies must submit an abstract (<300 words) to daniel.barry@informa.com and lbuckler@celltherapygroup.com outlining the product or service to be presented and why it is a critical technology related to cell therapy manufacturing.

The deadline for applications is SEPTEMBER 15 2011 - Priority given to early submissions

The cost of taking part in the Technology Showcase is £2,700 which includes the following benefits:

• 1 x 2-day conference pass (normal price £1,599)
• 10-minute podium presentation within main conference room
• 1 poster display in the Exhibition Hall
• Marketing - company logo displayed on website and event guide
• Exposure in BPI Magazine

Terms and conditions:

To be eligible the product or service to be presented must be:

• On the market for no less than 2 years or expected to be on the market no later than Q4 2012
• Appropriate for, applicable to, and compliant with clinical-grade manufacturing requirements (technologies only available for research use will not be considered)

Plus...

• The company must have no more than 15 employees
• The company has been running for no more than 5 years, and
• The company generates annual revenue of no more than $5m

For further information please contact: daniel.barry@informa.com or lbuckler@celltherapygroup.com

Biotech tax credit appears perfectly designed for cell therapy companies to recoup research dollars spent in 2009-10

Stewart Lyman of Lyman BioPharma Consulting posted a great article in today's Xconomy summarizing some key points and links to more information about the rules governing the Therapeutic Discovery Project Credit which have now been released by the US Treasury Department. Today, a detailed fact sheet was released about the tax credit program and it seems almost perfectly designed for most cell therapy companies.

Lyman points out a few important details about the application schedule including:

1. The Formal IRS applications (Form 8942) will not be available until June 21st or thereabouts.

2. The application period opens on June 21 and ends on July 21. The postmark on the application is deemed to be the date of delivery. Preliminary review of the applications is to be completed by Sept. 30; this is to ensure that applicants are eligible taxpayers and that their applications are complete. Applicants will receive determinations as to whether or not they qualify for credits and/or grants, and how much they will receive, by Oct. 29.

By way of a little more background, the following is excerpted from a March Forbes.com article by Dean Zerbe:

What does the credit cover?

The credit/grant covers research in tax years beginning in 2009 and 2010. The taxpayer is provided a 50% credit/grant for qualified investments in "qualifying therapeutic discovery projects." What expenses count as qualified investments? The aggregate amount of costs paid or incurred in the taxable year for expenses necessary for and directly related to the conduct of a qualifying discovery project. What doesn't count? The pay of employees covered by 162(m)(3) of the tax code--think CEOs--doesn't count. Other excluded items: interest expenses; facility maintenance expenses (e.g. mortgage or rent payments, insurance, utility and maintenance and costs of employment of maintenance personnel); and certain indirect costs (basically general and administrative costs) as defined in the Treasury Regulations at 1.263A-1(e)(4).

What is a qualifying therapeutic discovery project?

According to the legislation, it's a project designed to do one of three things:

--Treat or prevent diseases or conditions by conducting pre-clinical activities, clinical trials and clinical studies, or carrying out research protocols for the purpose of securing federal government approval by the FDA.

--Diagnose diseases or conditions or to determine molecular factors related to diseases or conditions by developing molecular diagnostics to guide therapeutic decisions.

--Develop a product, process or technology to further the delivery or administration of therapeutics.

Finally, to qualify, a venture may not have more than 250 employees in all businesses of the taxpayer--meaning a small biotech project at a big company wouldn't qualify.

Which biotech companies might benefit?

Those that are investing significant resources in pre-clinical or clinical studies, which may take years to come to fruition to ultimately satisfy FDA requirements, could now recoup a significant portion of their expenses. Additionally, biotech start-ups focusing on the development of diagnostic assays or applications to advance therapeutics and treatments can also benefit. Finally, companies currently engaged in basic or applied research which may ultimately contribute to curing caner within the next 30 years may also be excellent candidates. Along these lines, companies studying signal transduction pathways, gene therapy and stem cell research seem like prime candidates.

The Cell Therapy Group will be collecting more information about the tax credit and service providers who might be recommended to assist in the application if needed. Contact CTG for more details or watch here for more information.

Google to Invest in Regenerative Medicine

While the US government prints money to shore up failing and broken business models which no one likes but are considered simply too big (not too important or significant or even useful) to fail, Google is making money and investing it in start ups who expect nothing less than to create "disruptive, even world-changing technologies".

No suggestion here that GOOG is being altruistic, just that this is the way the new entrepreneur and investor class thinks. Opportunity and money are to be found in technologies that improve the way we live, work, play, eat, and think... and perhaps even improve the world.

To Google Ventures this has already meant wind farms, carbon emission reduction systems, green vehicles, and medical cures. To former Microsoft chief scientist Nathan Myhrvold and his high-level think tank, Intellectual Ventures, this means creating TerraPower - a company intending to revolutionize the nuclear power by developing reactors run on waste uranium - and also actively looking at regenerative medicine technologies.

Having formed the fund a little over a year ago, Google is only now starting to make a splash with the fund. Officially the fund has no specific industry focus saying on the Google Ventures website FAQ:

We are interested in a wide range of industries, including (but not limited to) consumer Internet, software, hardware, clean-tech, biotech, health care and others. First and foremost, we're looking for entrepreneurs who are tackling problems in creative and innovative ways, with the potential for significant financial return.

Unofficially and yet not so quietly, Google has named a few broad areas of interest. An article in Monday's New York Times quoted Google Ventures' managing partner, Bill Maris as saying that while they were not going to name particular investment themes, a few broad ares of interest include:

regenerative medicine, bioinformatics, cloud storage, companies that use large data sets, online monetization and mobile.

There it is. Regenerative medicine right there front and center.

In typical Google tradition, Maris, who looks all of 30 years old on the website, has a successfull and multidisciplinary track record. He was involved in founding Web hosting pioneer Burlee.com (now part of Web.com), where he built much of the key computing, network and technological infrastructure.Prior to that, Bill was a biotechnology and healthcare portfolio manager for Stockholm, Sweden-based Investor AB. Bill’s background also includes research at the Duke University Medical Center, Department of Neurobiology.

Google Ventures is said to be aiming at investing about $100 million a year. Any portion of that for regenerative medicine is more than welcome.

While traditional VC money remains reticent to back RM in any signifant way, Google's move confirms a trend we've been seeing and talking about at the Cell Therapy Group for the past 12 months or so. The multinational lifescience, biopharmaceutical, and healthcare companies along with strategic investors all now have regenerative medicine on their radar. They are all quietly and not-so quietly developing internal and external regenerative medicine strategies.

Please join us in welcoming regenerative medicine to the radar screen. It's bound to be an exciting ride ahead.

Cell Therapy Industry HiLites 2009-06-12

“Autologous manufacturing is not the deal breaker it used to be. If these [cell-based] vaccines work for really difficult-to-treat diseases, the manufacturing issues will be worked out.” Howard Liang, MBA, Ph.D., Analyst and Biotechnology Managing Direct at Leerink Swan. "Special Report: Customized Cancer Vaccines Finally (Maybe) Arrive". GEN News Highlights. 12 June 2009.

Amen. Glad to hear someone else saying it.

_______________________________________________________________

Ok, well, if no one else wants to advertise here...

This issue of Cell Therapy Industry HiLites is brought to you by the charming, witty and occasionally useful folks at the cell therapy group.

Looking to access intel from one of the most comprehensive databases in the cell therapy and regenerative medicine industry?

Want to raise the profile of your company?

Need to find the next big opportunity?

Let us help.
We love to feel used.

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FINANCIAL

Neuralstem, Inc (NYSE AMEX: CUR) received notice from the NYSE Amex Exchange that its shareholder’s equity has dropped below the $2,000,000 threshold required by the NYSE Amex for continued listing. The Company intends to submit a plan to the Exchange. CEO and President Richard Garr said, “We are confident that the company will be in compliance.”

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National Institutes of Health has awarded a $5 million grant to Q Therapeutics (co-founded by former NIH researcher Mahendra Rao), the University of Utah's Cell Therapy Facility and Johns Hopkins University School of Medicine to start human clinical trials of Q-Cells for myotrophic lateral sclerosis, or ALS -- better known as Lou Gehrig's disease.

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Opexa Therapeutics, Inc. (NASDAQ: OPXA) received a favorable ruling from NASDAQ allowing an extension to regain compliance and continue the listing of the Company’s securities on The NASDAQ Capital Market.


CLINICAL

StemCells, Inc. (NASDAQ: STEM) announced positive data from its Phase I clinical trial of its proprietary HuCNS-SC® product candidate (fetal-derived purified human neural stem cells). The six-patient Phase I trial was designed primarily to assess the safety associated with transplanting HuCNS-SC cells as a treatment for infantile and late infantile NCL, often referred to as Batten disease

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Celsense, Inc. is one of the recipients in a 4-year $1.95M grant from the National Institutes of Health to test its in vivo cell trafficking MRI reagent in human clinical studies. The funded studies will be the first effort to evaluate Cell Sense, the Company’s fluorocarbon-based magnetic resonance imaging (MRI) cell tracking reagent, for clinical use. Additionally, the studies will garner preliminary data critically important for improving immunotherapeutic delivery strategies in metastatic colorectal (CRC) and other forms of cancer.

The Cell Sense technology makes transplanted cells visible by MRI. Therapeutic cells are labeled ex vivo with the Cell Sense reagent prior to administration to the patient. Cell migration and biodistribution are subsequently monitored using fluorine-19 (19F) MRI or magnetic resonance spectroscopy (MRS).

The key advantage of Cell Sense is purported to be that the 19F images are extremely selective for the labeled cells, with no background signal from the host’s tissues. Furthermore, accurate cell quantification in regions of interest is possible. Existing data from pre-clinical studies using human cells is said to show that the Cell Sense reagent is highly biocompatible inside cells and does not affect their innate function.

A clinical-grade version of the Cell Sense reagent has been formulated by Celsense, Inc. and is currently being subjected to mandatory in vitro and animal safety studies in preparation for human trials.

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Never a company to shy away from making bold and early claims, Advanced Cell Technology, Inc. (OTC:ACTC.PK) Chairman and CEO William M. Caldwell IV said earlier this week that they are completing the "finishing touches" on a submission to seek FDA approval to conduct human clinical trials with a cell therapy that may be able to address many of the 200 plus known retinal diseases.

COMMERCIAL

It's hard to put this story under any one category but since the financial terms weren't released and it's not yet clinical, I'll call it "commercial". J&J's Ortho Biotech Oncology Research & Development, a unit of Centocor Research & Development, Inc., has announced that it has entered into a five-year Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), with Steven A. Rosenberg, M.D., Ph.D., chief, Surgery Branch, serving as the NCI principal investigator, to research and develop novel cell therapy technologies as potential treatments for a variety of cancers.

The deal bring together Ortho's and Rosenberg's adoptive immunotherapy technologies designed to work by helping the immune system fight cancer.

Rosenberg has been a pioneer in the field of adoptive immunotherapy of cancer developing Tumor Infiltrating Lymphocytes (TILs) - T cells obtained from a patient's tumor, expanded and then re-administered to actively seek and destroy cancer cells. In recent years, Dr. Rosenberg's team developed a new technology in which T cells obtained from a patient's blood are genetically engineered to express receptors that give them specific immunity against cancer cells and then re-administered.

Meanwhile, researchers at Ortho Biotech Oncology Research & Development independently developed a different and proprietary adoptive immunotherapeutic approach that uses tumor antigens and other materials to stimulate T cells from a patient's blood to become Cytotoxic T Lymphocytes (CTLs), which recognize and attack tumor cells.

Both technologies show postive early clinical results in melanoma, a type of skin cancer that ranks sixth among U.S. men and seventh in U.S. women for the most commonly diagnosed cancer, according to the NCI.

Under the CRADA, Dr. Rosenberg's lab will conduct a clinical trial in melanoma patients using Ortho Biotech Oncology Research & Development's proprietary technology. It is hoped that the technology will be effective in other types of cancer, as well.

They expect to begin clinical testing of the immunotherapy technology in melanoma patients by the end of 2009, with the possibility of additional studies for other types of cancer and other technologies in years to come.

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Cellular Dynamics International, Inc. has secured an exclusive license on a patent portfolio surrounding cardiovascular progenitor cells. The license covers differentiation of stem cells into all cell types of the human heart. The patent portfolio was generated by and obtained from Gordon Keller, Ph.D. and Mount Sinai School of Medicine.

Cardiovascular progenitor cells are capable of further differentiation into the multiple cell types of the heart, including cardiomyocytes, endothelial cells, and vascular smooth muscle cells, both in vitro and in vivo. CDI intends to commercialize the technology to the pharma and biotech industry for predictive toxicology and screening purposes. Iit's not clear whether the license also includes clinical applications but if so they may be looking for licensing partners given their current lack of interest in developing these cells into therapeutics.

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In a not-so-surprising move, StemCells Inc (NASDAQ: STEM) has decided to close StemCell Sciences in Melbourne, Australia after its acquisition of the company in March. British staff will now be holding their breath to see if the same will happen to them. STEM says it has offered relocation packages to employees should they wish to move to sunny California. This leaves one "stem cell" firm in Australia where previously there were four (SCS, Bresagen, Embryonic Stemcells Inc and Mesoblast). If there is good news it is that, if I recall correctly, the three others were acquired and not just shuttered.

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After many months of actively looking to offload its contract manufacturing subsidiary, Fresenius Biotech, has finally sold EUFETS AG to BioNTech AG. BioNTech is looking ot leverage the acquisition to further its quest to develop innovative molecular immunotherapies and biomarker based diagnostic approaches for individualized treatment of cancer and other severe human diseases.

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Having used a contract manufacturer for what and when they needed, BioLife Solutions has now reverted back to internal manfucturing with the completion of construction and validation of their internal GMP manufacturing facility. Recently they gleefully released the first production lot for sale of their biopreservation media products made in the new Bothell, WA plant.

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StemCyte Therapeutics is collaborating with Chennai-based Apollo Hospitals in joint venture with Ahmedabad-based Cadila Pharmaceuticals to set up what reports to be a first-of-its-kind umbilical cord blood (UCB) public bank for India.

**

Ok this news is a little soft but its a product that continues to be reinvented and a company we don't hear from much so I'll give them the space. HepaLife Technologies, Inc. (OTCBB: HPLF) (FWB: HL1) (WKN: 500625) has expanded their Advisory Board to support planning (e.g., refine the clinical strategy and patient treatment protocols) for their expected bioartificial liver clinical trial. HepaLife is developing a cell-based bioartificial liver system, HepaMate, as a potentially lifesaving treatment for liver failure patients. HepaMate is comprised of a blood plasma separation cartridge, a hollow-fiber bioreactor filled with proprietary porcine liver cells, a charcoal column, an oxygenator, circuit tubing and a plasma reservoir. These components are assembled into a patented blood/plasma circulation system, which is placed on the HepaDrive perfusion platform. The HepaMate technology has previously been tested in clinical studies involving more than 200 patients and has been the subject of over 50 scientific papers. It is anticipated that the upcoming trial would be a pivotal trial of the technology.

**

ThermoGenesis Corp. (Nasdaq: KOOL) mentioned in a recent press release that their Res-Q system - a point-of-care system designed to collect, process, and reinfuse bone marrow stem cells for therapeutic use, is anticipated to be launched on the market this month. Presumably in markets outside the US? They also discussed that they had received $500,000 in an SBIR grant from the NIH to study and develop biomaterials that can be used to deploy placental stem cells in bone repair and regenerative medicine applications. Now free money is free money but this seems a bit of a stretch to me for a company not without its struggles in its penetrating the market with its current cord blood storage and cord blood/bone marrow process systems. Apparently the the Res-Q platform is also being studied for potential use in the preparation of platelet rich plasma (PRP) from peripheral blood. Give them credit for continuing to think long-term and cross-platform despite struggles with their existing products.

**

"No more pads or tampons, period." Lifecell International is set to introduce in India next month menstrual cups as a cost-effective option to control menstrual flow in women and as a preparatory move for the company's menstrual-blood banking project called Femme, which is scheduled to begin in July


MISCELLANIA

Xconomy's Luke Timmerman does a nicewriting up an informative piece on Denderon's recent AGM and the thinking around the company of what will be involved in taking the company "all the way".

**

Ok its another pre-clinical item (which I rarely cover) but again this one's just too cool to ignore. The New Scientists did a nice job of looking at Doris Taylor's work at University of Minnesota. Her team is looking to expand on their success creating rat hearts using stem cells. The ultimate goal is to some day create a limitless supply of transplant organs for humans. The team took stripped-down scaffolding of one rat heart and coated it with tissue produced from another rat's stem cells. They now want to repeat the procedure using hearts and other organs from human cadavers or larger animals.

**

The NIH received 49,015 comments in response to its draft guidelines for human stem cell research. One of those was submitted by CIRM.

**

President Barack Obama should appoint a commission on stem cell research to help the therapy fulfill its promise to save lives and reduce medical costs, says Geron Corp. Chief Executive Officer Tom Okarma.

**

The California Institute for Regenerative Medicine (CIRM) received 73 preapplications for the CIRM Disease Team Awards RFA 09-01. The principal investigator for 15 of those applications is based with a for-profit entity. All of the teams proposed a wide variety of collaborators with several of the not-for-profit principal investigators citing collaborators in the for-profit sector. After review by a panel of outside experts and the CIRM in-house science team, a subset of these teams have been asked to prepare a full application, which will be due to CIRM July 16. Word on the street is that to-date just over 20 of the 73 have been given the green light to the next step.

**

StemCellDigest.net has posted a handy chart covering the public companies they follow in the stem cell sector showing the types of stem cells and business from which theyy hope to derive income as evidenced by the company's own statements, owned intellectual property, and/or areas of research. The one critically useful but missing column is the phase in which each of these products in.

**

One of my contacts, Scott Shields, Reimbursement and Health Policy Consultant at Argenta Reimbursement Advisors and owner of Blue Train Consulting Group, LLC has launched "The Reimbursement Wiki".

It promises to be a valuable online resource for reimbursement information particularly for those of us who do not work in that field full time. Below is his announcement of the site's launch:

I am announcing the public availability of my Reimbursement Wiki. I have compiled links to coding, coverage, and payment information, as well as information such as the following: - Medicare (URLs for rules, topics such as surgeries, compounding, CED, MS-DRGs, DME, inpatient list, laboratory and diagnostic testing, etc.) - Managed Care (URLs for medical/coverage policy sites at various payers, technology assessment organizations, literature on coverage decision making, etc.) - Medicaid (URLs for CPT/HCPCS code lookup by state for payment info, state fee schedules, drug product data, etc.) - Payment (URLs for Medicare payment basics, top 200 CPT/HCPCS codes, top 100 lab procedures, literature on drug pricing, etc.) There is plenty more -- basically, reimbursement and health resources I have collected in one place for reference purposes. The URL is http://reimbursement.atwiki.com. The Reimbursement Wiki is ongoing project of mine, and I add material based on topics of current work, so not all topics are represented equally. Nevertheless, I find it an invaluable resource, and I hope you do, too. Access to the Reimbursement Wiki is free. Please register at http://reimbursement.atwiki.com/signup, and email me your @ID. I will then invite you through the wiki. My email address is scott@argentaadvisors.com, or you can contact me via LinkedIn.

Sign-off

Organogenesis, Inc has established an annual scholarship program with Canton High School to honor a graduating senior pursuing a career in life sciences research or biomedical engineering. Kudos for them. We need more of that! Me? I sponsored a child this week. No big deal but it reminds me to remind you...

...find a way to make a difference in your world today.

One more thing. You want to make sure you hear cell therapy-related news faster? Get on Twitter and follow me. I'm @celltherapy.

Ok. Hope you found that useful. I'm trying to get back to my every Friday schedule here. I'll do my best. Happy weekend.

Lee Buckler, BEd, LLB
Cell Therapy Group
Principal

toll-free: 1-877-760-1966
direct phone: 778.278.6311
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Email: lbuckler@celltherapygroup.com
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Skype: lee.buckler | Twitter: @celltherapy

Cell Therapy Group. Your Cell Therapy Business Consultancy.
www.celltherapygroup.com | www.celltherapyblog.com

Cell Therapy Group & BioBusiness.TV collaborate to bring online coverage of cell therapy content from the 2009 Phacilitate Cell & Gene Therapy Forum

We are back from the Phacilitate Cell & Gene Therapy Forum 2009 and we've captured some highlights, which include Lee Buckler's review, some great interviews, brand new Mash Ups, and 60sec Pitches. Take a look!

The BioBusiness.TV Team.

Lee Buckler's Cell Therapy '08 Review and '09 Outlook.

Some of the exciting things we've seen in 2008 are:

• the involvement of pharma in cell therapy, investing like they haven't before, developing cell therapy products as drugs, and not just tools (including companies such as Pfizer, GSK, Roche, and Novartis)
• the number of late stage companies in the sector such as Osiris (see: Osteocel / NuVasis, and Prochymal + Chondrogen / Genzyme deals), Dendreon, and others
  
• the financing, partnerships and M&A activity with $400M private equity investment, $100M M&A, and $1.8bn in non-M&A deals.
  

Some things to watch for in 2009 are:

• some of the late stage companies (Osiris and Dendrion - i.e. Provenge results in April)
• the struggling cell therapy companies and how they will find cash (M&A, Government, VC?)
• the role of the new Obama administration and the public pressure, interest, and enthusiasm for cell therapy.

Watch Program »

_____________

Harvard Steps Into the Cell Therapy Funding Gap with a Mission for Academic Research to Get to Patients.
Brock Reeve explains the functioning of the Harvard Stem Cell Institute (HSCI). The HSCI is looking to make the bedside-to-bench and bench-to-bench loop in a way that is unequaled anywhere, with the university and its 11 affiliated hospitals, drawing resources from the various schools (law, business, government, divinity). Brock tell us about about the HSCI partnership with GSK, as well as the other relationships they are seeking and building at the moment.

Watch Program »

_____________

Roche's Vertes on Big Pharma's Interest in Cell Therapy.Alain Vertes of Roche presents the interest of his company in the cell therapy. He highlights the main points of his panel presentation:

1. Cell therapy is not a passing fad
2. Cell are not just transplants, they can also be drugs
3. Paradigm shifting applications for cell therapy
4. Protecting intellectual property
5. Potential for stunning efficacy and low risk of side effects.

Watch Program »

_____________

US and EU Regulatory Synergies, and EMEA Committee for Advanced Therapies.
Christopher Bravery comments on the new committee for advanced therapies of the EMEA, and its impact on the development of cell therapy in Europe. Christopher also reflects on the similarity between US and European regulatory environments, and the importance of considering that in planning pivotal studies. He also gives us his definition of Cell Therapy and explains the business of ERA Consulting.

Watch Program »

_____________

'Mash UP'. Delegate responses to the following questions:

• How Would You Define Cell Therapy?
• Are We Going to See New Cell Therapy Products in the Next 2-3 Years?
• How Many Cell Therapy Products Are On the Market Today?
• What Are Some of the Exciting Things Happening in Cell Therapy?

_____________

60sec Pitches

• Athersys, Inc. - 60sec Pitch
• Florida Biologix - 60sec Pitch
• Maxcyte, Inc. - 60sec Pitch

_____________

Interested in your company sponsoring future content like this focusing on the cell therapy market for BioBusiness.TV? Interested in sponsoring a cell therapy "channel" on the site? Contact Lee Buckler @ [the] Cell Therapy Group.

Cell Therapy Industry HiLites 2009-01-02

Happy new year everyone.

2009 feels like it has the potential to be the somewhat overlooked precursor to the 2010 milestone - not that that's bad just perhaps a "building" year rather than a champagne-popper. Whatever it turns out to be I wish you all a happy and prosperous year.

Based on how slow this week was, I fear next week. I predict a killer backlog of pent-up news on its way. In any event, here's what trickled out this week...

Last week Medistem announced it had filed an IND for use of their new endometrial regenerative cells (ERC) for treatment of critical limb ischemia.

ACT & CHA Biotech have rethought the name for their new joint venture (formerly announced as "Allied Cell Technology" the acronym for which is also 'ACT') - opting instead for the more distinct but lengthy, "Stem Cell & Regenerative Medicine International".

Stem Cell Sciences plc, which is listed in Australia and the United Kingdom announced that it had received a GPB200,000 ($A426,348) loan to use for working capital. In return, the third-party lender has been granted an exclusive period to conduct further due diligence in relation to Stem Cell Science's business and assets. Stem Cell Sciences said it was not in talks with any third parties that might lead to an offer for the issued share capital of the company. Stem Cell Sciences, whose shares have been suspended from quotation since November 26 pending a review of the company's financial position and strategic options, last traded at 15 cents.

Wading now into deep speculation, this tickles the senses like a move Stem Cells Inc might make (I have no information upon which to base this except their past actions) though the SCS assets would not seem to fit with STEM's portfolio. In that respect, this would seem like more of a natural acquisition by Pfizer which did a 5-year deal with SCS in November. I suspect we shall soon see...

Just to make things a little more curious, SCS later announced publication in Cell of a pioneering technique for creating authentic ES cells from rats. They believe the publication to be the first in which germ-line transmission from rat ES cells has been definitively demonstrated. It uses technology licensed exclusively to SCS from the University of Edinburgh and developed by Professor Austin Smith and his team, now at Cambridge University.

Alright this isn't a business item but it has business ramifications and I've discussed this issue in my blog a number of times. "Definite and measurable neurological and ophthalmological improvement." That was the clinical observation of ophthalmologist, Dr. Jack Guggino, in comparing 5-year old Xavier's post stem cell treatment exam results with those of a pre-treatment baseline exam. Xavier, diagnosed at age 2 with optic nerve hypoplasia, was flown to China for a controversial stem cell treatment from the sort of clinic that is drawing much criticism from the global scientific community. These clinics are criticized for, among other things, lack of transparency, formal clinical trials, peer-reviewed publications, and patient follow-up to track long-term clinical results. Recent criticism has suggested results are exaggerated and risks downplayed. Nevertheless, if Xavier were my child what would I do? Ok perhaps it would take something terminal and I'm not saying I would, I'm just sayin'...

Just to polish off the year with a little more successful fundraising news, International Stem Cell Corporation (OTCBB:ISCO) announced it has received the first $1 million tranche of an anticipated private equity financing of up to $5 million to be funded over the next several months. The total amount of the financing is intended to allow the Company to retire its existing secured debt and fund operations of the Company as it moves forward with planned pre-clinical trials in the first quarter of 2009.

Watch for a blog coming soon adding up my totals for how much was raised this year by companies in the space.

In a curious case of the company vs the newspaper, the Seattle Times reported on Dec. 24 that CellCyte Genetics had shut down and was unable to pay rent on its Bothell headquarters citing the company's delayed SEC filing. The company, whose shares trade over-the-counter and in the Frankfurt Stock Exchange, saw its value soar past $400 million last year but since plummeted in the midst of questionable activity currently under investigation and the subject of litigation. CellCyte's shares plummeted in January after The Seattle Times published stories describing the stock-promotion efforts and inconsistencies in the résumé of CellCyte Chief Executive Gary Reys. Clearly the Times and CellCyte are not on talking terms because on Dec. 29 Cell Cyte issued a press release saying the Times had it all wrong citing an Aug. 14 press release in which the Company reported progress in its bioreactor business segment and generally described its development plan to commercialize its bioreactor product line. CellCyte reiterated its intent to execute this development plan in 2009.

The company's Form 10-Q, filed Dec. 22, states:
"As of September 30, 2008, the Company had a working capital deficit of $897,402, and an accumulated deficit of $9,890,982 incurred through September 30, 2008. The Company has no revenues. Management forecasts operations during the coming year will need approximately $2,500,000 in additional working capital, which is expected to come from issuance of convertible notes and private placements of stock."

The filing laid out detailed plans for the company over the next 12 months but also stated the following: "As of September 30, 2008, we had cash in the amount of $5,734 and a working capital deficit of $897,402. Our planned expenditures over the next 12 months are expected to amount to approximately $2,500,000 and will exceed our cash reserves and working capital. We presently do not have sufficient cash to fund our operations and have curtailed significantly all activities. We anticipate that we will require additional financing in order to pursue our plan of operations for the next 12 months. There can be no assurance that we will obtain any additional financing in the amounts required or on terms favorable to us. If we are unable to obtain additional financing, we may have to abandon our business activities and plan of operations."

The Seattle Times may be guilty of a little prognostic reporting here but it certainly does seem like CellCyte will have to pull a wee little rabbit out of the hat to keep things going. Having said that, I've certainly heard the premature predictions of the imminent demise of many a cell therapy company before only to watch them 'pull a phoenix'. I like it when that happens.

I don't pretend to fully understand the Cytori patent portfolio and after the legal wrangling settled who ended up with what for what but Cytori announed the issuance of U.S. patent # 7,470,537 (the ‘537 patent) covering adipose-derived stem and progenitor cells to the University of California. The patent application containing these claims is jointly owned by the University of California and the University of Pittsburgh. The composition of matter patent is licensed to Cytori through its agreement with the University of California. The cells covered by the issued claims are believed to encompass a clinically important subpopulation of cells within adipose tissue.

BIO says one in four of the 370 publicly traded U.S. biotech companies have less than six months of cash on hand. But it's not just industry that's impacted by the economic crunch. The global financial crisis may do what opponents of California’s $3 billion state-sponsored stem cell research experiment could not: dry up funding. To keep the money flowing, later this month CIRM will weigh a contingency financing plan that could include bond anticipation notes and a private placement with major philanthropic backers.

And that brings me to my challenge to you all. I know money is tight but it is even more important in times like this that we remember to support the non-profits that support life as we know it for so many. This is true in your local community, on a global scale and it is also true in the industry in which you work. The non-profit organizations that provide critical support to the cell therapy industry need your financial support and your volunteer contributions. This week I announced that I've committed the Cell Therapy Group to supporting ISCT by way of a 2009 corporate membership. Please consider doing the same.

And that, my dear readers, polishes off 2008 and the first couple days of 2009. That's the cell therapy industry the way I saw it over the holiday season.

As Robert A. Preti is fond of saying... "Be careful out there".