SAN DIEGO, CA–(Marketwire -02/18/12)- Medistem Inc. (Pinksheets: MEDS.PK – News) announced today initiation of joint efforts with the Chinese conglomerate, Shanghai Jia Fu Medical Apparatus Inc, in developing the Endometrial Regenerative Cell (ERC) “universal donor” stem cell product for the Chinese market. The initial focus of the collaboration will be treatment of critical limb ischemia, an advanced form of peripheral artery disease. Medistem has previously received FDA clearance to begin a Phase I clinical trial using the ERC stem cells in this patient population. A scientific publication providing the rationale and supporting data for utilization of ERC in treatment of critical limb ischemia may be found at http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf.

“Medistem has over 10 peer-reviewed scientific papers published with academic groups from China over the past 5 years. The Team is very eager to expand our collaborations with China not only in science, but now in product development,” said Thomas Ichim, CEO of Medistem. “Given that Shanghai Jia Fu Medical Apparatus Inc is actively working in the area of clinical translation of cellular therapy, we believe this group is an ideal partner for our entry into development of therapeutics for the Chinese population.

Shanghai Jia Fu Medical Apparatus Inc currently has commercialized autologous cytokine activated killer cell therapy for cancer, as well as autologous bone marrow for treatment of critical limb ischemia; the company is interested in exploring expansion into allogeneic “off the shelf” products. As part of the initial collaboration, Medistem will provide ERC stem cells for research use and Shanghai Jia Fu Medical Apparatus Inc will support ongoing experiments. All data generated will be provided to Medistem.

“This is an example of a 2 +2 = 8 synergy,” said Mr. Wei Zhang, CEO of Shanghai Jia Fu Medical Apparatus Inc. “By leveraging cutting edge technology developed by Medistem in the context of our existing cell research and therapy infrastructure, we hope to accelerate Medistem’s development program, while at the same time bring new research to China.”

“In 2003, Dr Wei-Ping Min’s group, together with Medistem’s CEO Dr Thomas Ichim, were the first to apply the technology of RNA Interference to the immune system, by silencing the autoimmune disease-associated gene IL-12p35(2),” said Dr. Peter French. “In the current paper, Dr. Min expanded these studies to a disease-relevant model, and using stem cell-derived dendritic cells was capable of developing promising preclinical data relevant to rheumatoid arthritis.”

By specifically “silencing” various genes, Benitec Biopharma’s ddRNAi technology is capable of modulating stem cells outside of the body, in order to endow them with new desired therapeutic activities. The first clinical study which combined stem cell therapy with Benitec Biopharma’s ddRNAi technology was in a trial of AIDS-related lymphoma patients, the results of which were published in 2010 and showed the safety and feasibility of the approach(3).

In the current paper, ddRNAi was used to generate dendritic cells that acted as a “tolerogenic vaccine,” which specifically blocked the pathological immune response in rheumatoid arthritis, without blocking healthy immune responses. It is contemplated that by blocking pathological immunity, ddRNAi-modified stem cell-based therapies, such as those being developed by Medistem, could provide novel treatment and curative approaches to tissue that has been damaged. In the case of rheumatoid arthritis the tissue would be cartilage and synovium.

“Medistem is the first company to take a stem cell from discovery to clinical trials in the short span of four years,” said Dr. Weiping Min. “This is a unique example of merging basic research, as performed in my laboratory with the translational expertise of Dr. Ichim’s company.”

Medistem has previously published work in the area of rheumatoid arthritis, however the company’s main efforts are currently focused on heart failure, for which it has started the RECOVER-ERC 60 patient double blind, dose escalating, placebo controlled trial using its Endometrial Regenerative Cell (ERC) universal donor stem cell. The company also has a critical limb ischemia trial recently approved by the FDA.

“In our opinion the Benitec Biopharma technology platform is the only means of inducing the stable expression of gene silencing in a stem cell,” said Dr. Ichim, CEO of Medistem. “Given that Benitec Biopharma has pioneered ddRNAi for human therapy, and has been involved in applying it to stem cell manipulation, we are eager to continue our collaborations and finding means of leveraging the unique properties of the ERCs with the transformational technology of ddRNAi to develop novel cell therapies for a range of chronic life-threatening human diseases.”

“Benitec Biopharma and Medistem are in discussions as to how to advance this work both in rheumatoid arthritis and in a range of other disease states that would lend themselves to such a novel combination therapy,” Dr. French added.

SAN DIEGO, CA–(Marketwire -01/30/12)- Medistem Inc. (Pinksheets: MEDS.PK – News) together with its Russian Licensee, ERCell LLC, announced successful dosing of 3 heart failure patients in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The announcement was made at the Cardiovascular Stem Cell Research Symposium http://celltherapy.crf.org/.

The trial is aimed at assessing safety and efficacy of the company’s Endometrial Regenerative Cell (ERC) stem cell product in 60 heart failure patients who have no available treatment options. The “Universal Donor” adult stem cells will be administered using a novel catheter-based retrograde administration methodology that directly implants cells in a simple, 30 minute, procedure. A recent publication describing 2-year follow-up of angina patients administered bone marrow cells treated with the “retrograde procedure” authored by Dr. Amit Patel of the University of Utah, the International Principle Investigator of the trial, may be obtained at http://www.translational-medicine.com/content/pdf/1479-5876-9-183.pdf.

“We are honored to have had the opportunity to present at the prestigious Cardiovascular Stem Cell Research Symposium, alongside companies such as Athersys, Aastrom, Pluristem, Cardio3, Cytori, and Mesoblast,” stated Thomas Ichim, CEO of Medistem. “The RECOVER-ERC trial is the first trial combining a novel stem cell, with a novel administration procedure. Today cardiac administration of stem cells is relatively invasive and can only be performed at specialized institutions, we feel the retrograde procedure will circumvent this hurdle.”

Medistem’s ERC stem cell product is different from other adult stem cells in that it is derived from the endometrium (lining of the uterus). The endometrium grows every month before menstruation, in anticipation of implantation. The growth of the endometrium is associated with a very high degree of new blood vessel production, a process called angiogenesis. Conditions such as heart failure, and peripheral artery disease occur because of reduced circulation to the heart or legs. Medistem believes that by implanting ERC, the body will generate new blood vessels that will increase circulation. Proof of concept animal studies supporting the use of these cells in critical limb ischemia http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf, and cardiac damage http://onlinelibrary.wiley.com/doi/10.1634/stemcells.2007-0826/pdf have been published in the peer reviewed literature.

Medistem recently obtained FDA clearance to begin Phase I trials in the US for treatment of critical limb ischemia, an advanced form of peripheral artery disease, which causes approximately 150-200,000 amputations per year in the USA. The trial will be conducted by Dr. Michael Murphy at Indiana University.

“Heart failure is one of the major scourges on the Russian population. We are extremely pleased that that the pioneering work Medistem has been performing in the USA, is now being conducted in Russia through Medistem’s licensee ERCell LLC,” said Dr. Olga Bockeria, Professor of Cardiology at the Bakulev Center for Cardiovascular Surgery, the site conducting the trial.

Tereza Ustimova, CEO of ERCell LLC, who has signed an exclusive license/technology transfer agreement for use of Medistem’s ERC product in Russia, stated, “It has been a pleasure to work with the teams of Dr. Leo Bockeria, Principle Investigator and Dr. Amit Patel the International Principle Investigator begin the first clinical trial of a ‘Universal Donor’ stem cell in Russian history.”

“It is critical to emphasize that the stem cells used here are from healthy adult volunteers that have been screening according to strict criteria and do not involve embryonic or fetal tissue,” said Sergey Volzhenkin, Board Member of ERCell. “Given that under current manufacturing processes one donor generates 20,000 patient doses, we believe that we are not only developing a stem cell therapy, but an actual drug that can be manufactured inexpensively, distributed extensively, and administered at the patient’s bedside without need for complicated procedures.”

Although this is the first formal clinical trial assessment of the ERC stem cell in cardiac conditions, Medistem and international collaborators published a peer reviewed paper in 2010 describing the first use of ERC in a heart failure patient. The manuscript is freely available at the following link: http://www.intarchmed.com/content/pdf/1755-7682-3-5.pdf.

“I am pleased with the smooth technology transfer process and agility that ERCell exhibited in working with Bakulev on making our clinical trial a reality,” stated Vladimir Zaharchook, Vice Chairman and Vice President of Medistem.

The RECOVER-ERC TRIAL

The clinical trial will recruit 60 patients with congestive heart failure, which will be randomized into 3 groups of 20 patients each. Group 1 will receive 50 million ERC, Group 2 will receive 100 million and Group 3 will receive 200 million. Cells will be administered via catheter-based retrograde administration into the coronary sinus, a 30 minute procedure developed by Dr. Amit Patel’s Team. Each group will comprise of 15 patients receiving cells and 5 patients receiving placebo. Efficacy endpoints include ECHO and MRI analysis, which will be conducted at 6 months after treatment. The trial design is similar to the recent Mesoblast Phase II cardiac study, in order to enable comparison of efficacy.

SAN DIEGO, CA–(Marketwire -01/24/12)- Medistem Inc. (Pinksheets: MEDS.PK – News) announced today appointment of Dr. Alan Lewis to the company’s advisory board. Dr. Lewis spent 15 years at the pharmaceutical company Wyeth-Ayerst, where he was Vice President of Research, leading translational research efforts in diabetes, CNS, cardiovascular, inflammatory, allergy and bone metabolism diseases. He subsequently became CEO of Signal Pharmaceuticals, a drug development company that he successfully merged with Celgene. After this success, Dr. Lewis joined Novocell, Inc. (Viacyte), a preclinical diabetes stem cell company. As CEO he helped the company raise $27 million. He subsequently became CEO of the Juvenile Diabetes Research Foundation, the largest funding body in the world for diabetes research, which in 2010 reported a revenue of > $200 million.

Critical limb ischemia, the condition that Medistem has a FDA IND for, is a complication of diabetes that causes approximately 150,000-200,000 amputations per year in the USA.

“Dr. Lewis is a true example of a ‘translational scientist.’ Not only is he an accomplished academic, with over 120 peer reviewed publications, he is one of the few people who has the gift to successfully fund and manage the process of turning science into ROI,” said Dr. Vladimir Bogin, Chairman of Medistem. “It is a great honor for us to have someone of the caliber of Dr. Lewis join the Medistem Family.”

Medistem has recently accomplished the important milestone of obtaining FDA approval to begin clinical trials. This makes Medistem’s intellectual property the youngest in the field of clinical cell therapy, given that the company’s Endometrial Regenerative Cell product was only discovered in 2007.

“I have been observing Medistem’s progression since Dr. Thomas Ichim, the current CEO, joined the company in 2007. It is quite fascinating to have watched the story evolve from discovery to clinical trials in such a short period of time,” said Dr. Lewis. “Given my previous work in the area of diabetes, I am well aware of critical limb ischemia as a devastating consequence of this disease. By working with key opinion leaders such as Indiana University’s Dr. Michael Murphy, Principle Investigator of the FDA approved study, and Dr. Hugh Taylor, Chief of Reproductive Endocrinology and Infertility at Yale University, I pledge to do my best in improving the lives of these patients.”

SAN DIEGO, CA–(Marketwire -01/23/12)- Medistem Inc. (Pinksheets: MEDS.PK – News) together with its Russian Licensee, ERCell LLC, have received approval to initiate the first double-blind, placebo controlled universal donor stem cell trial in Russian history.

The clinical trial, Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC), is being led by Principle Investigator Dr. Leo Bockeria, Chairman of the Backulev Center http://www.bakulev.ru/en/about/director/ .

The Backulev Center is Russia’s premier institute for cardiovascular surgery and cardiology. Every year the Backulev Center performs approximately 30,000 diagnostic and treatment procedures, which includes 7,000 open heart surgeries and more than 12,000 angioplasties.

The RECOVER-ERC trial will recruit 60 patients with congestive heart failure, and randomize the patients into 3 groups of 20 patients each. Group 1 will receive 50 million ERC, Group 2 will receive 100 million and Group 3 will receive 200 million. Each group will have 15 patients receiving cells and 5 patients receiving placebo. Efficacy endpoints include ECHO and MRI analysis, which will be conducted at 6 months after treatment.

“I joined Medistem and personally invested into the company because of its strong science and intellectual property position. It is this strong science that has allowed for such a rapid progression of the ERC product from discovery, to animal studies, and now to approval for initiation of efficacy finding studies,” said Dr. Vladimir Bogin, President and Chairman of Medistem, and a Yale-trained physician practicing in the USA. “As a medical doctor I see the suffering and lack of options for patients with CHF. I am proud that our team is able to offer hope.”

This is the second clinical trial that Medistem has been granted approvals for. In September 2011, the company received FDA clearance for beginning a 15 patient trial treating critical limb ischemia patients together with Dr. Michael Murphy at Indiana University.

“We are especially grateful to our Russian licensee ERCell LLC which has worked intensely with our CRO and the Backulev Center in laying down the groundwork for this approval,” said Vladimir Zaharchook, Vice President and Vice Chairman of Medistem. “To our knowledge, ERCell is the only company in Russia working on a stem cell product that can be reproducibly manufactured, frozen, and sold as a drug, not a procedure.”

“This approval is a key milestone for ERCell. Given that Russia has one of the highest incidences of heart failure per capita in the world, we are confident that we can make a difference in patients’ lives and position Russia as an international leader in cell therapy,” said Tereza Ustimova, CEO of ERCell.

Dear Fellow Shareholders,

The last year has been remarkable for Medistem: new investors, new collaborators, and an FDA approval. The FDA approval is for a 15 patient study investigating the safety and therapeutic effects of company’s universal donor stem cell product, the Endometrial Regenerative Cell (ERC) in patients with critical limb ischemia. The trial is led by Harvard-trained Dr. Michael Murphy from Indiana University, who was the first physician in the US to use stem cells for treatment of this condition. Dr. Murphy is considered the premier clinical investigator in treatment of critical limb ischemia with stem cell-based approaches. To date, he is the only clinical research to be running a pivotal Phase III registration trial in the US for marketing approval.

Medistem believes the ERC is superior to other treatments for critical limb ischemia because of the cell’s natural ability to create new blood vessels in tissues with poor circulation. The market for critical limb ischemia treatments is approximately 2.9 billion per year in the US.

The FDA approval positions Medistem as the only company to have taken a cellular product from discovery to clinical trial in 4 years, a process that usually takes 10-15 years. The rapid entry into the clinic makes the company’s composition of matter intellectual property on the ERC stem cell the youngest out of all the clinical stage stem cell companies. Additionally, this is the first time any regulator has cleared clinical trials from a stem cell source that is not bone marrow or cord blood/placenta derived.

Upon trial completion, which is anticipated to take 18 months, Medistem anticipates initiation of a Phase III pivotal trial, which if successful, will ultimately clear the way for FDA marketing approval.

Concurrent with our successes in the US, Medistem has taken an active role in accelerating commercialization in Russia. Through its Russian licensee ERCell OOO, Medistem has initiated a collaboration with Dr. Leo Bockeria, Chairman of the Backulev Center for Cardiovascular Surgery. This is the largest cardiac care facility in Russia. Through this collaboration 2 end stage congestive heart failure patients have been treated with the company’s product and a 60 patient double blind placebo controlled trial is being planned. Congestive heart failure is approximately a 30 billion dollar a year market in the US.

Other notable events of this year include: a) selling non-core intellectual property for cash; b) outlicensing veterinary use of ERC to the company RenovoCyte LLC; c) publication of 10 peer-reviewed research papers; and d) filing a patent application on a method of non-invasive stem cell administration in patients with heart failure.

We are happy to state that the Medistem Team has grown this year. We welcome Don Dickerson as CFO. Don is a senior finance executive with over 25 years of domestic and international experience in the technology and healthcare fields managing both start-up and large-scale projects and operations. Don has managed multiple global-scale projects exceeding 200 million dollars. We also welcome Dr. Hugh Taylor, Professor at Yale University, and the world expert on the biology of the endometrium to our Scientific Advisory Board.

2011 has been a seminal year for Medistem. We have re-energized the company, achieved multiple strategic milestones and enter 2012 with a clear plan and resources to achieve the full value of the ERC stem cell.

Sincerely,
Thomas E Ichim,
Chief Executive Officer
Medistem, Inc.

The CERC is a “universal donor” stem cell product that does not require matching with the recipient allowing for the generation of standardized products that can be delivered to the office of the veterinarian ready for injection. This is in stark contrast to current stem cell therapies utilized in veterinary applications which require the extraction, manipulation, and subsequent replantation of tissue from the animal being treated. CERC is the canine equivalent of Medistem’s Endometrial Regenerative Cell (ERC). Medistem was recently granted approval from the FDA to initiate a clinical trial in human patients using its ERCs.

“Endometrial Regenerative Cells produce substantially higher amounts of growth factors as compared to other adult stem cells, are potent at inhibiting inflammation, and can home to the site of tissue injury and exert a healing effect,” said Dr. Greg McDonald, Chief Veterinarian of the McDonald Animal Hospital.

David Koos, Chairman and CEO of Entest, commented, “This marks the beginning of a new era in veterinary regenerative medicine. For the first time a stem cell product exists which can be generated inexpensively in the laboratory, shipped and stored frozen at the office of the veterinarian, and injected intravenously without need for specialized equipment. We believe that positioning ourselves in the veterinary market will allow rapid proof of concept, both clinically and financially.”

“As a practicing veterinarian I witness first-hand the devastating effects of osteoarthritis in pet dogs, for which no curative treatment exists to date,” said Dr. Shelley Zacharias, of RenovoCyte (www.renovocyte.com). “Promising data from this pilot study will be a fundamental step in creating a clinically-applicable stem cell therapy that is inexpensive, easy to use, and can be implemented on a wide-scale.”

A spokesperson for Entest noted the Company is also currently conducting a 10 dog safety study on its immune-therapeutic cancer vaccine for dogs, having treated 3 dogs so far.

Dr. Taylor is Professor of Obstetrics, Gynecology, and Reproductive Sciences; Section Chief, Reproductive Endocrinology and Infertility; Director, Yale Center for Endometrium and Endometriosis and Director of the Yale Center for Reproductive Biology.

“Dr. Taylor has literally defined the field of endometrial stem cells. His fundamental discovery of the bone marrow origin of endometrial cells in humans was one of the major forces behind the now growing field of endometrial stem cell research,” said Thomas Ichim, CEO of Medistem. “We strongly believe that Dr. Taylor’s deep scientific understanding of biological mechanisms occurring in the endometrium will serve as a foundation for our clinical development programs.”

Medistem is the first company to obtain regulatory approvals by the FDA and international regulators for using endometrial derived stem cells, the Endometrial Regenerative Cell (ERC), for the experimental treatment of patients. It appears that one of the major functions of the Endometrial Regenerative Cell in the body is to produce new blood vessels, a process that occurs every month before menstruation. Medistem is focused on harnessing this natural function of the Endometrial Regenerative Cell to produce new blood vessels in the limbs and hearts of patients with poor circulation.

“I am honored to join the Medistem Team, which has a consistent track record of rapid clinical development while concurrently performing in-depth mechanistic analysis behind their products,” said Dr. Taylor. “We are eager to take the lessons learned from our animal models and work with the Medistem team to translate them into new medicines.”

The study will involve intravenous administration of a canine equivalent of Medistem’s Endometrial Regenerative Cells (ERC). Medistem was recently granted approval from the FDA to initiate a clinical trial in human patients using its ERCs and RenovoCyte is the exclusive licensee of ERC technologies for veterinary applications.

“The Endometrial Regenerative Cells are a type of stem cell that produce substantially higher amounts of growth factors as compared to other adult stem cells, are potent at inhibiting inflammation, and can home to the site of tissue injury and exert a healing effect,” said Dr. Greg McDonald, Chief Veterinarian of the McDonald Animal Hospital. “To our knowledge this is the first clinical trial of a universal donor stem cell that already is being used in human medicine, and now we have the opportunity to offer it to our clients.”

Osteoarthritis is considered one of the most common causes of lameness in dogs and decreased quality of life. It is caused by a deterioration of joint cartilage, followed by pain and loss of range of motion of the joint.

“It is our commitment to provide access to the most cutting-edge veterinary medicines for hospitals under the Entest umbrella,” said David Koos, Chairman and CEO of Entest. “The collaboration with RenovoCyte and Medistem allows not only access to various stem cell treatment technologies, but also veterinary stem cell banking.”

“In contrast to other stem cell approaches in the area of veterinary medicine, the use of ‘universal donor’ cells allows for delivery of a standardized therapeutic dose to each animal. If these studies are successful, we look forward to substantially expanding the use of these cells as an ‘off the shelf’ stem cell product,” said Dr. Shelly Zacharias, Director of Veterinary Operations at RenovoCyte.

Current stem cell therapies utilized in veterinary applications require the extraction, manipulation, and subsequent replantation of tissue from the animal being treated. The Canine Endometrial Regenerative Cell (CERC) therapy is unique in that a product is delivered to the office of the veterinarian ready for injection.

SAN DIEGO CA–(Marketwire – Oct 20, 2011) – Medistem Inc. (PINKSHEETS: MEDS), a clinical stage adult stem cell company, reported today on a publication of a novel method of preventing transplant-associated ischemic liver injury using a nanotechnology delivery system that selectively targets hepatocytes.

In collaboration with Dr. Wei-Ping Min from the University of Western Ontario, the group demonstrated that nanoparticle administration of targeted short interfering RNA (siRNA) was effective at protecting livers from damage caused by oxygen and nutrient deprivation.

“During transplantation, since organs are transported across great distances, the cells undergo what is called ‘ischemic injury’ as a result of being outside of the body,” said Thomas Ichim, CEO of Medistem. “The company is currently using its Endometrial Regenerative Cell (ERC) universal donor stem cell product to treat ischemia in legs and hearts. Through the collaboration with Dr. Wei-Ping Min’s lab, Medistem is trying to elucidate molecular mechanisms of ischemic injury as well as develop additional pipeline candidates.”

The peer-reviewed paper describing the discovery, titled, “Targeted gene silencing of TLR4 using liposomal nanoparticles for preventing liver ischemia reperfusion injury,” was published in the American Journal of Transplantation (link http://www.ncbi.nlm.nih.gov/pubmed/21794086). The technology described in the publication can theoretically be applied to ischemic conditions including stroke, heart attack, and bypass-associated kidney failure.

“Medistem is one of the few companies that not only has clinically developed stem cell products, but also has a strong academic interest in understanding the biological mechanisms by which conditions like ischemic injury are manifested,” said Dr. Wei-Ping Min, Senior Author of the publication. “The fact that Medistem received FDA approval to begin clinical trials using their stem cells attests to the fact that the company possesses substantial scientific depth while still pursuing an aggressive commercialization program.”