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Friday, May 15, 2009

Cell Therapy Industry HiLites 2009-05-15


I'm back.

That on the left my friends is the new squawking reason I've been quite on the blogosphere and Twitter scene for the past few weeks!

I know this issue of my Industry HiLites has some rather stale news but it also has some recent news. What I can't promise is that I've captured all the cell therapy related news from the past few weeks. I'll attempt to back fill as time permits.




"Cell Therapy is expected to be one of the most important innovation drivers of modern medicine". See below who is the source of such zeal!

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If you missed the Invitrogen-sponsored breakfast session at the 2009 Phacilitate Cell & Gene Therapy Forum in Washington, DC, the session videos are now posted for your convenience.

Realizing the potential of cell therapy: new enabling platforms
Brian Newsom, Cell Therapy Business Development Leader, Invitrogen/Life Technologies

Exciting lentiviral platform technology applicable to clinical indications from leukemia to HIV
Dr. Boro Dropulic, President and Chief Scientific Officer, Lentigen, Inc.

20-year history of Organogenesis

Katie Faria, Director, Process Development, Organogenesis, Inc.

Contact them at celltherapysystems@invitrogen.com if you want to engage in a discussion about how Invitrogen™ Cell Therapy Systems can deliver proven products and expertise to help with your translational research and clinical development plans. Find more videos and information about their products and services (including immunotherapy, stem cells, and tissue engineering) go to www.invitrogen.com/celltherapy.
______________________________________________________


The race is on between Dendreon and Osiris to be the first cell-based therapeutic approved in over 10 years. Osiris Therapeutics, Inc. (NASDAQ:OSIR) has confirmed with the U.S. Food and Drug Administration, receipt of the first portions of its BLA (Biological License Application) for Prochymal as part of a rolling submission. Dendreon expects to file revisions to its already-filed BLA by Q4 of this year. If things go as Mitch Gold (Dendreon CEO) predicts, it looks like Dendreon will win the race to market but they are not competitive products and everyone wins if they are both approved regardless of the order!

Meanwhile, troubled cell therapy company Isolagen, Inc. (AMEX: ILE) received good news from FDA recently that its BLA has been accepted for full review - decision due by Jan 4.

FINANCIAL

Dendreon, Corp (NASDAQ: DNDN) raised $221 million in a public offering of nearly 12 million shares of its stock at $19.20 per share. After announcing the offering only last week, the company said the money will be used to “develop manufacturing facilities, a distribution network, an information technology platform and other infrastructure, to hire sales and marketing, manufacturing, quality and other personnel in preparation for the licensure by the FDA and commercialization of Provenge, and for general corporate purposes, including working capital.”

**

Back in April, Opexa Therapeutics, Inc. (NASDAQ:OPXA) announced the closing of an initial tranche of a private offering for gross proceeds of approximately $1.1 million. Opexa will use the proceeds from the financing to support the ongoing partnering discussions for both its Tovaxin® T-cell program for multiple sclerosis (MS) and stem cell therapy for diabetes. Participating in the financing were existing shareholders, consisting of institutional investors, private individuals and members of Opexa’s Board of Directors.

**

Cell therapy company Isolagen, Inc. (AMEX: ILE) received bridge financing to allow it to seek debtor-in-possession financing in conjunction with a possible chapter 11 filing. Meanwhile, they've filed their latest 10Q with the SEC for those interested in the gory details.

**

The California Institute for Regenerative Medicine (CIRM) has handed out 15 grants worth $67.7 million to 13 not-for-profit and two for-profit organizations, BioTime and Novocell. An additional 12 grants which were recommended are on hold and money will made available only if funds allow. They will consider those grants in June. Novocell has been awarded $5,405,397 for its embryonic stem cell-derived diabetes therapeutic program and BioTime has been granted $4,721,706 to facilitate the use of its ACTCellerate™ technology for manufacturing patient-specific therapeutic products through the expansion of over 140 highly purified primitive human embryonic progenitor cells (hEPCs) from hES or iPS cells.

Novocell will receive two funding awards totaling $6.2 million from CIRM. The grants cover development of methods for delivery and monitoring safety of human embryonic stem cell (hESC)-derived pancreatic cells for diabetes cell therapy.

**

Virxsys Corp. of Germantown, Md., and Rockville’s GlobalStem Inc. are the only two private companies among the recipients of nearly $19 million of funding for stem cell projects granted recently by the Maryland Stem Cell Research Commission to 59 projects out of 147 applications that it received. GlobalStem's project is entitled "Scale-Up Manufacturing, Authentication, and Banking of Human Pluripotent Stem Cells" and curiously Virxsys' is "Developing safer methods for induced Pluripotent Stem (iPS) cell generation using Spliceosome-mediated RNA trans-splicing (SMaRTTM) technology".

**

While functionally the company is in a deep coma for the moment, according to a recent SEC filing, Cell Genesys, Inc. (NASDAQ:CEGE) is continuing to explore financing alternatives and consider strategic alternatives, including merger with or acquisition by another company, further restructuring, other sales of non-core assets, and other potential technology outlicensing or liquidation of the company.

**

Embryome Sciences, Inc. parent co BioTime, Inc. (OTCBB:BTIM) has raised $4M with a possible $16M in total with the potential sale of additional shares and warrants.


CLINICAL

Pervasis Therapeutics received Orphan Drug Designation for Vascugel cell therapy as they
prepare for a phase III trial of the product.


**

Osiris Therapeutics, Inc. (NASDAQ:OSIR) completed patient enrollment in the second of its Prochymal Phase III trials for Graft vs. Host Disease (GvHD).

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I have to confess that until I read this recent press release from ReNeuron I was suffering under the misconception that the regulatory framework for cell therapies in Europe was becoming clearer but listen to this nightmarish-sounding bureaucratic cluster-schmuck. ReNeuron Group plc (LSE: RENE.L) provided a regulatory update regarding its ReN001 stem cell therapy for stroke. In January of this year, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) granted regulatory approval for a Phase I clinical trial with ReN001 in disabled stroke patients, to be undertaken in Scotland at Glasgow Southern General Hospital. The decision was ratified by the Commission on Human Medicines, with the support of its Clinical Trials Expert Advisory Group which was also involved in reviewing the application.The Company has since submitted the clinical trial application to the Gene Therapy Advisory Committee (GTAC) who, in addition to their existing gene therapy remit, were recently given responsibility to act as the national research ethics committee for stem cell therapy clinical trials in the UK. The Company has been notified by GTAC that a Provisional Opinion has been granted in respect of the applicatio , subject to the resolution of a small number of points raised pertaining to non-safety-related pre-clinical data and the clinical trial protocol. The Company is reportedly currently working to respond to the points raised, the majority of which involve straightforward amendments to the clinical trial protocol. Further clarification is being sought by the Company, particularly within the context of the above-mentioned regulatory approvals already received, regarding one request for further non-safety-related data by GTAC, the provision of which would potentially delay the start of the clinical trial by a few months. Meanwhile their IND in the U.S. remains on hold after well more than a year has passed since its submission.

**

Cellerant Therapeutics, Inc. announced the dosing of the first patient in a phase 1 trial of CLT-008 for hematological malignancies. CLT-008 is an allogeneic cell therapy designed to rapidly produce mature neutrophils and platelets in vivo and facilitate long-term engraftment in patients undergoing bone marrow or cord blood transplantation, or being treated for chemotherapy- or radiation-induced neutropenia among other applications. CLT-008 is said to have the potential to make cord blood transplants safer and more available for everyone regardless of age, size, or ethnic and racial background. In preclinical testing CLT-008 has reportedly shown to provide hematopoetic support to enable long-term engraftment of blood-forming stem cells, which could lead to broader use of cord blood transplants as an effective therapy for multiple life-threatening blood diseases. The company intends to study CLT-008 to addresses several significant markets and including neutropenia in the near future.

Led by Dr. John Wagner, Professor of Pediatrics and Director of the Division of Hematology-Oncology and Blood and Marrow Transplantation at the University of Minnesota, the Phase 1 study is an open-label, dose-escalation trial and will investigate the safety and tolerability of CLT-008 in 20 to 25 patients undergoing cord blood transplants.

**

ERYtech Pharma has started its phase II clinical trial of GRASPA as first-line treatment among patients with acute lymphoblastic leukaemia (ALL) aged 55 and older. A first cohort of 3 patients has already been recruited for the 30 patient study in France. GRASPA® is an enzyme formulation of L-asparaginase which is clinically delivered entrapped in homologous red blood cells.
**

Ever-innovative Medistem Inc. (PINKSHEETS: MEDS) is bringing pre-clinical research, commercial cell therapy clinical practice outside the U.S., and veterinary stem cell protocols together to report positive multiple sclerosis data using fat stem cells. A recent paper describes the scientific rationale and preliminary results of three patients with multiple sclerosis treated with their own fat derived stem cells. The paper provides some evidence that a stem cell-rich component of adipose tissue, called the Stromal Vascular Fraction, can concurrently immune modulate, while inducing regenerative activities in multiple sclerosis patients.


Publication collaborator, Dr. Robert Harman, CEO of Vet-Stem, has treated over 3,500 horses and 1,500 dogs with fat derived stem cells for inflammatory conditions such as osteoarthritis immune-mediated polyarthritis. The article, titled "Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis," appeared today in the Journal of Translational Medicine (http://www.translational-medicine.com), and was a collaboration between scientists and clinicians from Medistem; the University of Western Ontario; Hospital CIMA, San Jose, Costa Rica; Indiana University; Cell Medicine Institutes; University of California, San Diego; and University of Utah


COMMERCIAL

Finally, we hearing some more about David Mooney's company InCytu, Inc. which makes "smart biopolymer devices that enable in vivo cell programming".
I hear a lot of great talks but I have to confess hearing Mooney speak last year topped the list for 2008. This stuff might be too intelligent (read "complicated") to be commercializable but it certainly doesn't lack for brilliance.

The first of their in situ bioreactive devices (iBDs), coined Cellarium(TM) by the company, will be an intelligent biopolymer scaffold that once implated releases a factor that selectively attracts dendritic cells (DCs) into the scaffold, presents antigenic (melanoma specific) proteins to them, and then, upon maturation, releases the activated DCs to home to the lymph nodes where they stimulate T cells to specifically attack the melanoma.

This takes the whole notion of cell therapy (traditionally involving the ex vivo manipulation of harvested cells for implantation) and turns it on its head by doing in vivo what we have believed can/must be done in cGMP facilities.

Now this is all a long way off and the Lord Almighty knows we have had more than our share of cell-based cancer vaccine failures but other applications in the pipeline include chronic ischemia, peripheral vascularization, muscle regeneration and even potentially stroke and CNS disease.

InCytu plans to develop partnerships for product sales and marketing but retain control of the cGMP production of its iBD devices. The company's product development facility is in Lincoln, RI likely for reasons associated with its CEO - serial CEO and cell therapy entrepenuer, Alfred Vasconcellos, who has been involved with CytoTherapeutics, ETEX, LCT, Sertoli Technologies. LCT Biopharma, Multicell, and cut his early teeth in Pfizer's Strategic Market Development group. Vasconcellos was most recently the CEO of LCT Biopharma Inc. which is the wholly owned subsidiary of diabetes cell therapy company Living Cell Technologies Ltd (listed on the Australian Securities Exchange (ASX:LCT) and the US-based OTCQX (OTCQX:LVCLY)
from New Zealand and now conducting a trial in Russia.

**

Dendreon (NASDAQ:DNDN) CEO Mitchell Gold's ship came in when he recently sold 600,000 shares of the company at $24.92 apiece on April 29, generating gross proceeds of $15 million.

Meanwhile Dendreon is going on a hiring binge in prep for FDA approval of Provenge.

**

It is interesting to see the different approaches companies take to competitive IP. Whereas Osiris appears content for the moment to let companies develop all kinds of MSC products without interference, Stem Cells, Inc couldn't be more aggressive in litigating any IP they believe infringes on their patents, like that of Neuralstem. Cytori and Vesta had a similar battle.

StemCells, Inc. (NASDAQ:STEM) recently announced that the U.S. Patent and Trademark Office (PTO) has upheld the validity of the remaining two neural stem cell patents which were subjected to reexamination proceedings commenced by Neuralstem, Inc. The upheld patents are the subject of two related lawsuits initiated by StemCells against Neuralstem, which allege infringement of a total of six patents. These six patents collectively claim the manufacture and use of human neural stem and progenitor cells as tools for drug discovery and as therapeutic agents. The PTO’s decision to uphold the two patents is final and cannot be appealed. Consequently, StemCells is asking the federal district court in Maryland to resume the infringement lawsuits against Neuralstem.


“The PTO’s latest action is a reaffirmation of the validity of the patents asserted against Neuralstem. Each of our reexamined patents has now been twice tested and twice granted by the Patent Office,” said Martin McGlynn, President and CEO of StemCells, Inc. “We now look forward to our day in court. Litigation can be a slow and meticulous process, but we plan to ensure that those who wish to commercialize neural stem cells for drug discovery or therapeutic uses, recognize the validity and value of our patents.”

**

Lonza Group Ltd is expanding its cell therapy business with the construction of a new facility in Singapore representing a $27 million investment for the first phase which will include two manufacturing suites that are expected to come on-stream by mid-2011. The company which reportedly already operates 12 cGMP-certified cell therapy manufacturing suites in the U.S. and Europe, said the Singaporean cell therapy suites will be next to the company’s existing large-scale mammalian production plant and additional suites could be added in the future to meet increased demand.

This comes after Lonza's announcement in January that it was spending $26m to expand cell therapy manufacturing capacity at its facility in Walkersville, Maryland, US installing three class 10,000 cell production suites as well as the requisite clean room and processing space at the plant, all of which will be housed in a 44,000 sq ft, purposed designed building.

Here's my favorite part of this story. Lonza is a $2.65 billion/yr multinational company and quoted in the release is Lonza CEO, Stefan Borgas, saying:
"Cell Therapy is expected to be one of the most important innovation drivers of modern medicine".
**

Pfizer is clearly seeing ocular therapies as an important franchise for its regenerative medicine enterprise. After making a seed-like investment of $3M last year in the startup EyeCyte Inc, Pfizer has now announced a collaboration with University College London to advance development of stem cell-based therapies for age-related macular degeneration (AMD). The London Project to Cure Blindness, led by Professor Pete Coffey (UCL Institute of Ophthalmology), is involved in producing a cell replacement therapy from human embryonic cells; a therapy which it aims to introduce into clinics by 2011. The goal is to replace cells essential for “seeing” lost through disease at the back of the eye. The UCL–Pfizer collaboration will accelerate the research process by bringing together the pioneering work of UCL’s researchers in the field of cell-based therapies and Pfizer’s expertise in design and delivery of therapeutics.

Under the terms of the agreement, Pfizer will provide funding to UCL to enable research into the development of stem cell-based therapies for AMD as well as other retinal diseases. Pfizer will also contribute expertise in the design and execution of clinical studies, interaction with global regulators, and in product manufacturing techniques. After the completion of preclinical safety studies, Pfizer will have the option to conduct clinical trials to determine efficacy of treatment and commercialize any resulting product.


Pfizer also recently signed deal with WARF for rights to human embryonic stem (hES) cells for dev of new drug therapies

**

One of the topics of discussion among those of us trying to lead the charge in commercializing cell therapies is the lack of experienced executive leadership at the helm of many cell therapy companies. Novocell, Inc, as it has done before on several fronts, is leading by example by hiring a seasoned biotech executive as its new President & CEO to replace Alan Lewis who went to lead the JDRF.

Novocell, Inc. recently announced the appointment of John West as President, Chief Executive Officer

"Novocell addresses one of the largest commercial and medical opportunities in stem-cell-derived therapeutics, and its team is increasingly recognized for its scientific and IP leadership,” said Mr. West. "I look forward to working with Novocell through clinical development and market launch and to growing a major new business.”

West, former CEO of Solexa, Inc. (NASDAQ:SLXA - News), brings more than 27 years of experience building profitable businesses from transformational technologies in the life sciences industry. Mr. West served as Chief Executive Officer of Solexa from 2004 until the company’s acquisition in 2007. When Mr. West joined Solexa, it was a private venture backed company with a radically different biochemistry and molecular biology for DNA sequencing. During Mr. West’s tenure, the company became public through a reverse merger, raised almost $100M and launched its first commercial product. This product lowered DNA sequencing costs over 100-fold, achieved almost $100M revenue in its first full year and became the dominant system for genome-scale genetic research. Mr. West led sale of the company in 2007 to Illumina, Inc (ILMN) for over $600M, and the business market cap subsequently exceeded $1B. Prior to Solexa, Mr. West served as VP of DNA Platforms, approximately a $1B business, at Applied Biosystems (ABI) (now Life Technologies). Mr. West’s responsibilities included the company’s businesses in DNA sequencing, preparative and real-time PCR, DNA synthesis and arrays. Prior to joining ABI, Mr. West was President of Princeton Instruments, a private company with transformational technology for low light imaging and spectroscopy. During Mr. West’s tenure, the company grew over 10 times in revenue, with much of the growth leveraging advances in cell biology. The company was sold to Roper Industries (NYSE:ROP - News), where Mr. West continued as subsidiary President. Mr. West holds B.S. and M.S. degrees in engineering from MIT, and an M.B.A. in finance from the University of Pennsylvania’s Wharton School.


**

Advanced Cell Technology, Inc. (Advanced Cell, ACT) (OTC: ACTC) and Korea-based CHA Bio & Diostech Co., Ltd. (CHA Bio), formerly known as CHA Biotech, Co., Ltd. and whose shares are publicly traded on KOSDAQ, announced that the parties have entered into a licensing agreement under which Advanced Cell will license its proprietary “single blastomere technology,” which has the potential to generate stable cell lines, including retinal pigment epithelium (RPE) cells for the treatment of diseases of the eye, to CHA Bio for development and commercialization exclusively in Korea. ACT received an undisclosed up-front license fee.

**

At this year's ISCT conference, Invitrogen, a division of Life Technologies (NASDAQ:LIFE), announced a new technology to separate undifferentiated stem cells from those that are differentiated by utilizing magnetic beads that latch onto a common marker on embryonic and induced pluripotent stem cells, which are not considered as suitable for transplantation as those which are differentiated because of the potential of unregulated cell growth, removing them from a culture in less than 45 minutes. This leaves behind highly pure and differentiated cells that are unaffected by the process.

**

Histogen Aesthetics, a division of Histogen focused on providing unique, clinically proven, human skin cell-derived products for aesthetics medicine, has announced the launch of the ReGenica™ Rejuvenation System for anti-aging and post-resurfacing.

Histogen Aesthetics utilizes a proprietary manufacturing process in which newborn dermal fibroblast cells are grown on beads in controlled bioreactors that maintain an embryonic-like environment, including low oxygen and low gravity conditions. During this process, the cells secrete growth factors such as Keratinocyte Growth Factor and Vascular Endothelial Growth Factor, and soluble extracellular matrix proteins such as collagens, laminin and decorin, which are associated with skin renewal and scarless healing. The resulting product is ReGenica, a complex made up of the naturally produced cell signaling materials and embryonic-like proteins which support the epidermal stem cells that renew skin.

**

Stem cell therapy faces more scrutiny in China but regulations remain unclear for companies that supply treatments.

**

Hemogenix, Inc. is stepping up the heat a little in its competitive battle with Stem Cell Technologies, Inc. over the preferred assay method for stem cell quality control and potency. Hemogenix recently sent out an email and posted a statement on the homepage of its website
saying "It has taken Stem Cell Technologies 6 years to acknowledge one of the basic concepts of the HALO Platform: By counting undifferentiated colonies at 7 days, they are actually counting clusters of "proliferation units" which can, in turn, be measured using ATP without any manual enumeration of colonies at 7 days. "


MISCELLANEA

FDA CBER's Cellular, Tissue and Gene Therapies Advisory Committee held a meeting over the last couple day. On May 14 in the morning, in open session, the Committee was scheduled to discuss the potential for Chlamydia trachomatis and Neisseria gonorrhea transmission by human cells, tissues, and cellular and tissue-based products (HCT/Ps) that are recovered from the reproductive system or gestational tissues (e.g., amnionic membrane and placenta, cells recovered from menstrual blood, foreskin, placental/umbilical cord blood derived cell products), or other sources. In the afternoon, in open session, the Committee will discuss animal models for porcine xenotransplantation products intended to treat Type 1 diabetes or acute liver failure. On May 15, in open session, the Committee intended to: (1) Receive an update on Guidance documents from the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research and the Center for Veterinary Medicine and (2) discuss clinical issues related to the FDA draft guidance ``Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage.''

FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the
meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA's Web site after the meeting. Meeting material is available online here.

**

BrightTalk recently hosted a stem cell webcast summit including presentation by ISCO - check it out here.


Sign-off

So with that I'm easing back in. As mentioned, I'll try to back fill any news I missed and get back on schedule. Until then... ciao.


3 comments:

Clinical Trial Regulations said...

Good post... Thanks......

Otr 214423 said...
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Otr 214423 said...
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