Baxter ($BAX) Signs with NeoStem ($NBS) for Manufacturing in their Phase III Trial - Also a CD 34+ Cell

Daily Dose Conclusion: Baxter (BAX) press release below, names NeoStem’ s (AMEX: NBS) Progenitor Cell Therapy (PCT) division as the selected manufacturer for their Phase III trial with the Baxter CD 34+ cell. We see this as validation for NeoStem on three fronts:

1. Great revenue source for PCT
2. Validation of NeoStem’ s own CD 34+ based Amorcyte trial, in market niche STEMI (heart attacks), and
3. Close relationship between these two companies ! NeoStem looks like a compelling value play with the expected divestiture of the China Generics business as the next major catalyst. 

Flash Player 9 or higher is required to view the chart
Click here to download Flash Player now

View the full NBS chart at Wikinvest

Baxter Initiates Phase III Adult Stem Cell Clinical Trial for Chronic Cardiac Condition

Study Aims to Deliver Adult's Own Cells As Treatment for Chronic Myocardial Ischemia

DEERFIELD, Ill., February 28, 2012 - Baxter International Inc. (NYSE:BAX) announced today that it has initiated a phase III pivotal clinical trial to evaluate the efficacy and safety of adult autologous (an individual's own) CD34+ stem cells to increase exercise capacity in patients with chronic myocardial ischemia (CMI).

Chronic myocardial ischemia (CMI) is one of the most severe forms of coronary artery disease, causing significant long-term damage to the heart muscle and disability to the patient. It is often diagnosed based on symptoms of severe, refractory angina, which is severe chest discomfort that does not respond to conventional medical management or surgical interventions.

"The prospect of using a person's own adult stem cells to restore and repair blood flow in CMI is a very exciting concept based on a biological regenerative approach," said Norbert Riedel, Ph.D., Baxter's chief science and innovation officer. "The goals of this phase III trial are aligned with Baxter's overall mission to develop life-saving and life-sustaining therapies and it will help us determine if the therapy can make a meaningful difference for CMI patients."

The trial will enroll approximately 450 patients across 50 clinical sites in the United States, who will be randomized to one of three arms: treatment with their own autologous CD34+ stem cells, treatment with placebo (control), or unblinded standard of care. The primary objective is to evaluate the efficacy of treatment with CD34+ stem cells to improve the functional capacity of patients with CMI, as measured by a change in total exercise capacity at 12 months following treatment. Secondary objectives include reduced frequency of angina episodes at 12 months after treatment and the safety of targeted delivery of the cells.

After stem cell mobilization, apheresis (collecting the cells from the body) and cell processing, participants will receive CD34+ stem cells or placebo in a single treatment via 10 intramyocardial injections into targeted areas of the heart tissue. Efficacy will be measured by a change in total exercise capacity during the first year following treatment and safety data will be collected for two years. Stem cell processing will be conducted in GMP facilities in the United States by Progenitor Cell Therapy (PCT), a subsidiary of NeoStem, Inc. To learn more or enroll, visit www.renewstudy.com or www.clinicaltrials.gov .

This trial is being initiated based on the phase II data, which indicated that injections of patients' own CD34+ stem cells may improve exercise capacity and reduce reports of angina episodes in patients with chronic, severe refractory angina.

"The phase II trial provided evidence that this strategy, leveraging the body's own natural repair mechanisms, can improve exercise capacity and reduce chest pain, the first time these endpoints have been achieved in a population of patients who have exhausted conventional treatment options," said Douglas Losordo, MD, vice president of new therapeutic development at Baxter.

CD34+ cells, which are blood-forming stem cells derived from bone marrow, are comprised of endothelial progenitor cells (EPCs), which develop into new blood vessels. Previous preclinical studies investigating these cells have shown an increase in capillary density and improved cardiac function in models of myocardial ischemia.

About Baxter
Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

Baxter ($BAX) Completes Acquisition of Synovis

Baxter International Inc. (NYSE:BAX) announced that the company has completed its planned acquisition of Synovis Life Technologies, Inc. (NASDAQ: SYNO), following approval of the transaction by Synovis shareholders.  The acquisition expands Baxter's regenerative medicine and BioSurgery franchise by adding biological and mechanical products from Synovis used for soft tissue repair and microsurgery in a variety of surgical procedures.

"The acquisition enhances Baxter's ability to offer a broad range of tools used to repair and reconstruct soft tissue damaged by disease or injury, as well as specific tools used in a variety of microsurgical procedures," said Ludwig Hantson, president of Baxter's BioScience business. "We look forward to welcoming the Synovis employees and organization into Baxter as we begin the business integration process."

Baxter's technological leadership in the development of biosurgical and regenerative medicine products is grounded in advancing innovation, enhancing surgical techniques and improving patient outcomes. Baxter advanced the field of tissue sealing and hemostasis more than 30 years ago with the development of TISSEEL Fibrin Sealant (sold under the name TISSUCOL in several countries around the world). Today, Baxter is adding the Synovis soft tissue repair and microsurgery products to the company's existing line of biological products and delivery devices used for hemostasis, tissue sealing, adhesion reduction, and hard tissue regeneration.

Synovis shareholders approved the offer of $28 per share, which equates to $325 million of equity value or approximately $260 million after adjusting for the net cash. Synovis reported annual sales of $82.4 million for the fiscal year ending October 31, 2011.

Synovis develops, manufactures and markets medical devices used primarily in surgical procedures for soft tissue repair, including PERI-STRIPS DRY, TISSUE-GUARD and VERITAS Collagen Matrix. These products are used in a variety of surgical procedures, including obesity surgery; patching the lining of the brain, vessels, and cardiac defects; hernia repair; and vascular surgery. The Synovis portfolio also includes products used in microsurgery, such as the COUPLER, FLOW COUPLER and GEM MICROCLIP. These products are used for joining small diameter vessels during autologous tissue breast reconstruction; sealing small blood vessels; and head, neck and hand procedures. Its newest business area is orthopedic and wound management products, with applications ranging from the repair of rotator cuff and other tendon injuries to advanced wound management. These products are primarily used by reconstructive, orthopedic, sports medicine, podiatric, and vascular surgeons.

Daily Dose Conclusion: Baxter is quietly building a stronger position in the regenerative medicine space. We know that the company is also developing a CD34+ cell Therapeutic for cardiac ischemia and has brought Douglas Losordo MD, one of the best known cardiologists and cell biologist, stem cell pioneers. This tells us that the company is serious.  NeoStem (NBS) is a great value pure play using a similar technology.

BBC: Stem cells used to 'heal' heart attack scars

An exciting article appeared in the BBC many weeks ago, and continues to cycle through the media. It has to do with some exciting but early work done in the area of expanding heart cells (myocytes).

_________________________________

Damage caused by a heart attack has been healed using stem cells gathered from the patient's own heart, according to doctors in the US.

The amount of scar tissue was halved in the small safety trial reported in the Lancet medical journal.

The authors said there was also an "unprecedented" increase in new heart muscle.

The British Heart Foundation said it was "early days", but could "be great news for heart attack patients". A heart attack happens when the organ is starved of oxygen, such as a clot blocking the flow of blood to the heart.

As the heart heals, the dead muscle is replaced with scar tissue, but because this does not beat like heart muscle the ability to pump blood around the body is reduced.

Doctors around the world are looking at ways of "regenerating" the heart to replace the scar tissue with beating muscle. Stem cells, which can transform into any other type of specialised cell, figure prominently in their plans.

Heart to heart

This trial, at the Cedars-Sinai Heart Institute, was designed to test the safety of using stem cells taken from a heart attack patient's own heart.

Healing the Heart

This is the second group of doctors to report using cells taken from a heart to heal a heart. In November 2011, another safety trial showed the cells could be used to heal the hearts of heart failure patients who were having heart bypass surgery. The heart is not the only source for these stem cells and other fields are much further ahead.

The largest ever trial of stem cell therapy in heart attack patients is about to get under way in Europe. The BAMI trial will inject 3,000 heart attack patients with stem cells taken from their bone marrow within five days of the heart attack.  {(We know a little bit about this trial, it is based on bone marrow derrived cells that home to the peri-infarc zone via an ischemic gradient.  This is very similar to the mechanism of action that NeoStem's (NBS) Amorcyte claims on their bone marrow derrived cells (CD 34+ /CXCR4+) enriched marrow cells, injected into the IRA (infarc related artery). The BAMI trial is similar in design to NBS trial but with a few major differences. The product is not enriiched for CD 34+ cells and the dose is not as concentrated).}

• Cardiac cells 'heal heart damage'

Within a month of a heart attack, a tube was inserted into a vein in the patient's neck and was pushed down towards the heart. A sample of heart tissue, about "half the size of a raisin", was taken. This was taken to the laboratory where the stem cells were isolated and grown. Up to 25 million of these stem cells were then put into the arteries surrounding the heart. Twenty five patients took part in the trial. Before the treatment, scar tissue accounted for an average of 24% of their left ventricle, a major chamber of the heart. It went down to 16% after six months and 12% after a year. Healthy heart muscle appeared to take its place. The study said the cells, "have an unprecedented ability to reduce scar and simultaneously stimulate the regrowth of healthy [heart] tissue".

One of the researchers Dr Eduardo Marban said: "While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle. "This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. "The effects are substantial, and surprisingly larger in humans than they were in animal tests."

 Dr. Iqbal Malik: ''This is one small step''

However, there was no increase in a significant measure of the heart's ability to pump - the left ventricle ejection fraction: the percentage of blood pumped out of the left ventricle.

Prof Anthony Mathur, who is co-ordinating a stem cell trial involving 3,000 heart attack patients, said that even if the study found an increase in ejection fraction then it would be the source of much debate.

He argued that as it was a proof-of-concept study, with a small group of patients, "proving it is safe and feasible is all you can ask".

"The findings would be very interesting, but obviously they need further clarification and evidence," he added. Prof Jeremy Pearson, associate medical director at the British Heart Foundation, said: "It's the first time these scientists' potentially exciting work has been carried out in humans, and the results are very encouraging. "These cells have been proven to form heart muscle in a petri dish but now they seem to be doing the same thing when injected back into the heart as part of an apparently safe procedure.

"It's early days, and this research will certainly need following up, but it could be great news for heart attack patients who face the debilitating symptoms of heart failure."

Prima BioMed files for NASDAQ listing (ASX: PRR)

Just a quick heads up that Australian biotech company Prima BioMed (ASX: PRR) has filed for a NASDAQ listing of American Depositary Receipts (ADR). Once the listing is complete the company will have a dual listings of its securities on both the Australian Securities Exchange (ASX) and NASDAQ. Every one ADR will represent 30 common shares, so Prima at $0.17 cents would trade at $5.10 and a market cap of >$160 mln.

Prima’s proposed NASDAQ listing will be a Level II ADR compliance listing, and is being managed by Bank of New York Mellon and US broking houses Deutsche Bank AG, Noble Financial and Aegis. Prima did say that they are currently unable to say precisely when the shares will actually list and trade but we expect it will be soon.

Here the big question: Is this a blessing or a Curse ?

Prima is listing on the NASDAQ for better exposure and most importantly access to U.S. capital markets. The company is now beginning a Phase III trial in ovarian cancer using a dendritic cell based vaccine (in the U.S., Progenitor Cell Therapy (NeoStem-NBS) is doing the manufacturing, recall that PCT did the clinical work for Dendreon's Provenge and is also working for Coronado (CNDO) and Immunocellular (IMUC). If anyone can make sure that the "manufacturing goes off with-out a hitch” its PCT-NBS. 

So the next big question, is does it work ? Ovarian is a very tough indication and the life expectancy of Ovarian cancer varies a great deal. Prima's Phase II data was not double blinded cross-over so the results are not definitive. No way to say what the results of the current global PIII trial will be yet. We do know Prima will likely need to raise capital at some point ahead (thus the U.S. listing).

Perhaps the most important event that investors will watch will be not Prima at all, but Merck KG who is running the StimuVax trial which like Prima's product (C-Vac) targets the MUC-1 antigen (over-expressed in ovarian cancer).

If StimuVax works, Prima could rock, if not, it could flop as it validates one way or another the MUC-1 antigen as a target.

Let’s watch Prima and see how the company does as they work to build a U.S. institutional presence and present their data to the scrutiny of US investors.

Osiris (OSIR): Look's Like Sanofi (acquired Genzyme) is saying No to Prochymal

News is swirling on Osiris Therapeutics (NASDAQ: OSIR) that Sanofi (SNA) in the post Genzyme (GENZ) acquisition will discontinue Prochymal for GvHD. Prochymal is a mesenchymal cell (MSC) that is allogeneic. Similar to what Athersys (ATHX) is developing with multi-stem. Osiris has struggled with GvHD and even Biodefense company Soligenix (SNGX), just reverse split 20:1, saw Orbec, a locally acting steroid that had every indication of success fail when the pivotal trial was halted for futility. In Biotech land we often say that the "graveyard is full of companies who tried to develop xxx for yyy indication", in this case its GvHD.

We would advise investors to try to understand the following when evaluating a new cell therapy:

What is it? What we mean is "what is the active ingredient". An allogeneic MSC means a lot of things, it’s a heterogeneous cell population, and as such, just not that well defined, so from a starting point, other than saying there is a paracrine effect where the cells act like cellular Advil, it’s a tough climb to say, what is it ?

Next - What does it do exactly ? or What is the Biological Mechanism of Action (MOA) and as such, what is the clinical effect that will be measured in the trial ? How closely related are they ? Again, these are critical elements that the FDA will look for beyond, I squirt it in, and it works. Don't forget dose, homing, and integration.

Thus far developers of cell therapy seem to be struggling with these questions with a few exceptions. Baxter (BAX) and NeoStem (NBS) stand out, with a highly defined cell product (CD34+/CXCR4) cells for Preservation of Heart function. Islet BioSciences stands out with their porcine islet cells (pig) for diabetes.

Daily Dose Conclusion: OSIR has approx. $50 mln in cash as of Sept. 2011 against a $160 mln market cap. Prochymal is still being developed for a number of other indications from Crohn's disease, Type 1 diabetes and Cardiovascular indications. With that said, we need to do more analysis to understand the probabilities of success in these areas given the questions (what is it, MOA, clinical effect) that we raise above.

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.

Flash Player 9 or higher is required to view the chart
Click here to download Flash Player now

View the full NBS chart at Wikinvest

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).