SANUWAVE Health (SNWV): Pulsed Energy and Stem Cells ? Stay Tuned !

Last week at the Cell Therapy Cardiology Conference held at Columbia Presbyterian Hospital we heard KOL's (Key Opinion Leaders) from just about every stem cell company at the meeting. Several presentations held great interest for all, one in particular from Dr Zeiher of t2cure was quite interesting. t2cure (German - private) has been working on bone marrow derived cell therapy product for AMI. According to Dr Zeiher (founder) pre-conditioning cardiac ischemic patients with sound wave energy (much like the probes that are used to break up kidney stones). The company believes that they can pre-condition ischemic hearts, active a homing signal (stromal derived factor-1 SDF-1) that will allow the active cells in marrow (CD34+ / CXCR4+) cells to lock in on the ischemic area and create new blood vessel formation.

Daily Dose Conclusion: Sanuwave (OTCBB: SNWV) has demonstrated that their device does enhance healing and probably through the mechanism that Dr Zeiher was presenting last week. Sanuwave missed their primary endpoint (100% wound closure in diabetic foot ulcers - DFU) but they really only just missed it. Wounds that had not healed without their therapy healed 99%. The last 1% is almost impossible to get perfect closure, and as a result, the FDA has requested they do another trial. While we are not sure what the action plan at Sanuwave will be, we do see this technology as important to the stem cell space.

NeoStem's ($NBS) First Patient is Enrolled in Amorcyte Trial

Wow, what a long way NeoStem (NYSE AMEX: NBS) has come. In the past year this company has been transformed from one focused on pre-clinical VSEL's which hold promise of being a naturally pluripotent adult stem cell to a Phase II clinical company with a well-designed, well vetted therapy (CD34+/CXCR4+ Cell derived from a patient’s own bone marrow) for the preservation of Heart function. The name of the trial is PreServe!

From the press release:

"The study is a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of infarct-related artery infusion of AMR-001, an autologous bone marrow derived cell therapy enriched for CD34+ cells. AMR-001 is administered 5 to 11 days post-stent placement in patients diagnosed with an ST segment elevation myocardial infarction with ejection fraction less than or equal to 48%, as determined by cardiac magnetic resonance imaging."

This is a critical element of the NeoStem story. Unlike most of the other companies who are also working in the heart attack space, NeoStem is based on their understanding of the underlying biology of heart attacks. It typically takes 5-6 days for the ischemic signal from the healthy but overworked myocytes (heart cells) that surround the infarct tissue to build up to a point where the CD34 cells can migrate locally via their cell receptor (CXCR4). They then modulate the process of angiogenesis where it’s needed.

In other words, if you give cells too soon, it becomes cellular Advil (calming down inflammation) but not really modulating the localized needs around the peri-infarct zone, and if you give cells too late, the myocytes are not rescued. This is the only cell therapy company we are aware of that has been so explicit with their understanding of the active cell type (it’s not a gamish of stem cells, its CD 34+ cells), delivered at a specific dose, at a specific time.

Conclusion: Look for news from NeoStem on this trial which has the potential to transform the way heart attacks are treated. This will take 12 months to complete enrollment with data 6 months after last patient is treated. Also keep an eye out for the company to divest their 51% ownership in the China Generics company. This should be a welcome event by The Street that could unlock significant shareholder value.

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Today, January 25, 2011, NeoStem Senior Management, Subsidiaries Invited to Speak at Seventh International Conference on Cell Therapy for Cardiovascular Disease; $NBS

NeoStem, Inc. (AMEX: NBS; Stock Twits: $NBS) is an emerging biotechnology company engaged in the development and manufacturing of cell-based therapies in the U.S. Its January 2011 acquisition of Progenitor Cell Therapy, LLC ("PCT") is central to the Company's strategic mission of capturing the paradigm shift to cell therapy. The acquisition of PCT gives NeoStem not only access to a world class contract manufacturing cell therapy company but provides a platform and expertise around the evaluation, development and regulatory requirements to develop autologous, allogeneic, immunomodulatory and vaccine-based therapeutics. 

NeoStem announced that several of its representatives have been invited to present at the Seventh International Conference on Cell Therapy for Cardiovascular Disease held from January 25-27, 2012 in New York City. The invited include NeoStem’s Chief Medical Officer, the lead investigator for its PreSERVE Phase 2 clinical trial for AMR-001 for preservation of heart function in post acute myocardial infarction patients, and the President of Progenitor Cell Therapy, LLC, a NeoStem subsidiary. 

The Cardiovascular Research Foundation is organizing the conference, which will be held at the Myrna L. Daniels Auditorium in the Vivien and Seymour Milstein Family Heart Center at NYPH/Columbia University Medical Center.

The program “will be dedicated to the evolving field of cell-based therapies being developed for the repair and regeneration of cardiac and vascular disease, as well as related diseases such as diabetes and stroke.” The conference this year “will focus on preclinical and clinical studies on the path to commercialization, highlighting the status of molecular, cell, and tissue products in addition to delivery systems. Leaders from the international community will convene to present their work, experiences, observations, and opinions on the benefits and unmet challenges of cell-based therapies.”

NeoStem will present as follows:

• At 4:30 PM on Wednesday, January 25, Andrew L. Pecora, MD, FACP, Chief Medical Officer of NeoStem, will speak on an industry session entitled "Focus on Acute Injury Technologies."
• At 9:20 AM on Thursday, January 26, Arshed A. Quyyumi, MD, FRCP, FACC, principal investigator of the PreSERVE AMI Phase 2 trial and Professor of Medicine and Cardiology at Emory University, will speak on a panel entitled "Early and Next Phase Studies" within a session entitled "Acute Injury: STEMI and NSTEMI".
• From 7:30 to 8:30 AM on Friday, January 27, Robert A. Preti, PhD, President of Progenitor Cell Therapy will speak as part of Industry Session III entitled "Focus on Procedure, Systems Management, and Advanced Technologies."

Dr. Pecora, CMO of NeoStem, commented,

"As a presenter at the first industry session, I look forward to informing industry leaders about the PreSERVE Phase 2 clinical trial for AMI which is now open for enrollment and may provide data readout 18 months from the first patient enrollment, as well as discussing the recent patent issued to use the Amorcyte technology beyond cardiovascular disease." 

Chairman and CEO of NeoStem Dr. Robin L. Smith added,

"This conference represents validation that the development of cell therapies for diseases outside of bone marrow transplantation is progressing as represented by their current clinical data. Our acquisition of Amorcyte last year has positioned NeoStem to be a leader in the cell therapy cardiovascular space. We are excited to be a part of the developing science represented by this important conference and share our expertise represented by the progress with Amorcyte and our capabilities to assist the field with the manufacturing services of PCT."

Read the full news release at PR Newswire. 

Which Cell Therapy companies present the best value?

Which Cell Therapy companies present the best value?

We developed an analysis using public filings and annualizing the most recent quarters as of 12/31/11. As such, the accuracy is subjective to our proprietary algorithm, and this list is not mean to be all comprehensive.

We conclude that ex leaders Dendreon and MesoBlast make the space very inexpensive. The sample below represents just over $500 million in market cap for eight of the selected public companies (ex DNDN and MSB). These companies have 3 - PIII trials, 5 PII trials and several P1 trials (based on these crude metrics).

We conclude that is worth investors time to understand among these companies in terms of what they are doing and the associated probabilities of success of their trials. Recent data peaks from the Cardiology space suggests that Baxter (BAX) and their CD34 cell type may be very viable. NeoStem has a very similar approach. The retrenchment in MesoBlast shares since that company presented data at AHA in November is of concern. Cytori, Aastrom, Athersys all have active programs in cardiology while Athersys lead program is partnered with Pfizer for Ulcerative Colitis and Aastrom is entering a Phase 3 trial in CLI.

By price ($), Osiris, MesoBlast, and Dendreon are the highest $ priced stocks:

But that starts to change as we migrate to market cap:

And if we eliminate Mesoblast and Dendreon we get a better picture of the rest of the field:

And that picture changes as we adjust for debt and cash: (enterprise value). In all fairness here, we know that NeoStem with $20-$30 million in value from their China generic company, could be the cheapest name and others are / will raise capital but ex China, Athersys is the “cheapest name”.

Looking at R&D spending: IMUC, Prima and NeoStem are among the most efficient but in fairness one must adjust for the fact that Aastrom is embarking on a pivotal trial versus Prima just starting their P3 and NeoStem their P2.

Revenues: Here we have excluded NeoStem’s $65 million from China which means PCT (Cell Therapy CMO) is running at close to $10 million in annual revenues (currently).

Cytori (CYTX) Publishes Apollo (P1/2a Heart Attack) Data

Cytori – (CYTX):  Publishes Appolo Results

Cytori Therapeutics (NASDAQ: CYTX) published previously reported six-month outcomes from their Apollo trial. This was an EU trial evaluating adipose (fat) derived stem cells (ADCs) in patients with acute myocardial infarction (heart attack or AMI).

Apollo was small at N=14-patients but it was a prospective, randomized, double-blind, placebo-controlled, feasibility trial (Phase I/IIA).

In the Apollo trial all patients were treated with standard-of-care and subsequently underwent an abdominal liposuction. Each patient's adipose tissue was processed by the Celution® System where ADRCs were extracted, washed and concentrated into a syringe of clinical grade cells. Within 36 hours of the myocardial infarction and no longer than 24 hours after undergoing percutaneous coronary intervention, patients received an injection of either 20 million ADRCs (n=10) or a placebo (n=4). Improvement in cardiac function by SPECT  and an improvement in blood flow  as well as a reduction in scar formation (infarct size).

Cytori claims that the “advantage of adipose tissue as a cell source is that it allows physicians to get a meaningful dose of a patient's own cells at the point-of-care when using the Celution® System without cell culture or use of donor cells". The paper’s author also states, "We believe delivering cells within the first 24 to 36 hours takes advantage of the body's signaling and initiates the repair process before irreparable damage occurs".

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Cell Therapy in Cardiology: Conference Begins in NYC Tomorrow

Just a reminder that tomorrow through Friday a very important conference in NYC takes place: The Conference on Cell Therapy for Cardiovascular Disease.

Web site: http://celltherapy.crf.org/conference/overview.html

This is an off-wall street conference that is focused on reaching the medical community: Clinicians and clinical investigators, interventional cardiologists, noninvasive cardiologists, cardiac surgeons, research associates, basic science investigators (cell and molecular biologists), hospital administrators, program directors, legislators, and regulatory agency personnel to name a few. We will be attending.

A few key panels to be aware of:

• Wednesday: Industry Session I. Focus on Acute Injury Technologies: 4:30 pm - 5:30 pm. The participants include Linda Marban, Alexander M Milstein, Andrew Pecora (NeoStem CMO), Kai Pinkernell, Anthony Ting, Christine Wallrapp
• Thursday: Acute Injury: STEMI and NSTEMI, 8:45 am - 10:15 am. Moderators: Timothy D. Henry, Andreas M. Zeiher. Participants: Henricus J. Duckers, Raj Makkar, Marc S. Penn, Arshed A. Quyyumi (PI in NeoStem’ s Amorcyte trial) , Warren Sherman, Wojciech Wojakowski. We note that Dr. Zeiher is a moderator. Dr Zeiher is concerned one of the most prominent thought leaders in cell therapy and cardiology.
• Thursday 10:45-12:15: CLI/CMI. Moderators: Douglas W. Losordo, Amit Patel. Discussants: Todd J. Brinton, Timothy D. Henry, Thomas F. O'Donnell, Emerson C. Perin, Christof Stamm, Gustav Steinhoff

On this panel we note the presence of Doug Losordo who is also one of the most respected key opinion leaders in cell therapy and is also a pioneer on CD34+ cells and cardiology. Dr. Losordo is the PI in Baxter's CD34+ trial. NeoStem also is running a CD 34+ trial.

• Trial 1: CD34+ Cells for Refractory Angina: ACT 34 CMI Update and Phase 3 Study Design. Timothy D. Henry
• Trial 2: Adipose-Derived Cells for Chronic Ischemia: The PRECISE Trial, Emerson C. Perin
• Trial 3: Update on Standardization of CD133 Intramyocardial BMSC for Intramyocardial Delivery, Gustav Steinhoff
• Trial 4: BMAC for CLI: A Phase III Trial, Thomas F. O'Donnell
• Trial 5: Placenta-Derived Cells for CLI, Christof Stamm

WBB Upgrades NeoStem ($NBS), Target = $2.00

WBB Securities upgraded NeoStem (NASDAQ: NBS) to a Buy with a 12 months price target of $2.00 per share. The report cited a few reasons which include:

1. Expansion of the intellectual property associated with Amorcyte beyond STEMI (Heart attacks) to all Vascular Insufficiency.
2. New PCT clients on-board such as Immunocellular (IMUC) - (working on a dendritic cell based approach to brain cancer), and Islet BioSciences (microencapsulated insulin-producing, pathogen free swine (pigs) for type 1 diabetes’s. NeoStem actually gets a royalty on commercial sales (utilizing PCT's manufacturing currency to participate in clients downstream revenues).
   
3. Divestiture of China Generic company (WBB estimates $25 million).
4. The start of the Amorcyte Phase II trial.

Tigenix: Allogenic Cell Therapy for Complex Anal Fistulas, $TIG

Last week at the BioTech showcase Tigenix (NYSE Euronext: TIG) presented as part of a panel of companies talking about auto-immune disease and many possible indications. One that caught our attention was Cx601.

Cx601 is an "EU-medicinal product" based on expanded mesenchymal stem cells obtained from adipose tissue (eASCs). This product is a member of the new generation of cell therapies.

• According to Tigenix: Cx601 is the first medicinal product based on allogeneic (collected from donors) eASCs to be approved for clinical trials worldwide.
• Cx601 is able to activate the physiological repair mechanisms of the body thanks to its capacity to interact with the body.
• Prior clinical trials with eASCs suggest that Cx601 has a great therapeutic potential based on its anti-inflammatory, healing, and immunoregulatory properties.

Cx601 is a suspension for injection that contains donor-derived stem cells isolated and expanded from adipose tissue obtained by liposuction.

Cx601 is being evaluated in a Phase II clinical trial for the treatment of complex perianal fistula in patients with Crohn’s disease. Cellerix estimates that it will be able to start in 2011 the last phase of clinical development before starting the approval process.

A perianal fistula is an abnormal connection between the perianal space and outside skin surface. A fistula is considered to be complex when its treatment involves a high risk of causing loss of anal continence, the fistulous tract crosses more than 30% of external sphincter (high trans-sphincteric, suprasphinctetic, and extrasphincteric), several tracts are found, is recurrent, or patient has incontinence, local irritation, or Crohn’s disease.

Current treatment for complex fistula in patients with Crohn’s disease is poorly effective and costly. Patients with complex fistula but no inflammatory disease require surgery, with its attendant risk of fecal incontinence. We would note that Ventrus (NASDAQ: VTUS) is another company outside of Cell Therapy that is working in this area.

Cx601 acts by controlled reduction of inflammation in the fistula, promoting adequate homeostasis through the release of anti-inflammatory factors which in turn promote natural fistula closure.
Cx601 has been designated as an orphan drug by the European Medicines Evaluation Agency.

Clinical Development: An allogeneic therapy based on eASCs in clinical phase
The program is based on the local administration of allogeneic eASCs for the treatment of complex perianal fistula in patients with Crohn’s disease. Safety of this treatment has been documented by its use for treating patients in a compassionate use program. Designation as an orphan drug for Europe was achieved in a record time.

A Phase I/II, open label study of this product for the indication of complex perianal fistula derived from Crohn’s disease has been done (24 patients across 6 centers). The primary objectives of this study were to :

• To show that administration of allogeneic cells from healthy donors is safe.
• To assess the efficacy of Cx601 in terms of complete closure of complex perianal fistula 12 and 24 weeks after initial drug administration.

Tigenix is now hoping to move this program forward to a pivotal trial. Given the fact that Tigenix has developed ChondroCelect^®, the company’s lead product for cartilage regeneration in the knee we believe this company is worth watching.