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• Cell Therapy
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Cell Therapy

Overview

Stem-cell therapeutics and red blood cell production for the treatment of hematological malignancies via hematopoietic stem cell transplant or any medical procedure requiring red blood cell transfusion. A stem cell is an extraordinary type of cell that has the ability to self-renew over time and can also give rise to all of the different cell types present in blood. Development and testing of our long-term hematopoietic stem cells has demonstrated the effectiveness of these cells in treatment of a variety of cancers in animal models. Transitioning into the clinical setting, the lead indications for this program include acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Taiga is also leveraging its patented stem cell technology to develop a safer and more efficient method to produce large amounts of red blood cells for medical use.

THE HEMATOPOIETIC STEM CELL (HSC) TRANSPLANTATION OPPORTUNITY

Table 1: Estimated U.S. HSC transplants by cancer type, 2006 (Source: DaVinci Oncology Specialists)
	2006 Transplants
Acute lymphocytic leukemia (ALL)	2,837
Acute myeloid leukemia (AML)	4,621
Chronic myeloid leukemia (CML)	2,475
Hodgkin’s disease	5,030
Non-Hodgkin’s lymphoma	13,124
Multiple myeloma	2,978
Total	31,065

HSC transplants have been performed by physicians for decades to treat a variety of deadly diseases, in particular cancer. Patients are initially treated with high dose chemotherapy drugs that ablate existing bone marrow cells, including HSCs. The subsequent treatment of these patients with healthy HSCs restores the patient’s hematopoietic system.

The success of HSC transplant in specific cancers has led to significant use. As described in Table 1, >30,000 HSC transplants were performed in the U.S. in 2006 among leukemia and lymphoma patients alone.

Though HSC transplantation has become a successful approach and is standard of care for many cancers, the technology currently employed in HSC transplantation has not been adapted to address the significant problems associated with the procedure that limit both its effectiveness and the breadth of its use.

The specific technical hurdles limiting the use and the effectiveness of HSC transplant are:

1. Cell numbers. Obtaining a sufficient number of HSCs to ensure successful engraftment of the HSC transplant.
   • Often the optimal number of cells needed for an adult HSC transplant is not available and results in a failure to engraft.
   • Ensuring sufficient cell numbers in HSC transplant for cancer indications has significant clinical benefits, including increased survival, improved bone marrow function, and a lower incidence of subsequent Myelodysplastic Syndrome.
   • Cases that require multiple rounds of bone marrow (HSC) transplantation pose a particularly difficult challenge, in terms of procuring a sufficient number of stem cells.
2. Cell purity. Achieving sufficient cell purity to allow HSC transplant into non-matched transplant recipients.
   • Because HSCs harvested from either bone marrow or peripheral blood are contaminated with donor immune cells, HSC transplants are only successful when the donor and recipient are matched (histocompatible).
   • Obtaining pure HSCs allows the transfer of donor cells into ANY recipient.

Taiga has proprietary solutions to the two key technical hurdles associated with HSC transplantation that provide the opportunity to fundamentally transform the therapy of many life-threatening cancers.

TAIGA’S SOLUTION FOR HSC TRANSPLANTATION

Taiga has addressed the technical hurdles associated with HSC transplant by developing patented technologies that allow for the unlimited expansion and purification of undifferentiated HSCs ex vivo. The expanded HSCs are fully functional stem cells, as demonstrated by their ability to repopulate bone-marrow depleted mice with functional cells of all hematopoietic lineages. This is the first time that long-term repopulating, self-renewing HSCs have been expanded to such an extent.

Using these technologies, Taiga’s goal is to develop a single Universal HSC product for broad use in HSC transplant. A universal product would have several critical benefits over current approaches that would make it an attractive therapy for use in the clinic:

• Removes the need for donor / recipient histocompatibility, greatly expanding the population of patients eligible for HSC transplant.
• Creates a single standard for the preparation and transfer of donor HSC cells (current protocols for HSC harvest and preparation vary widely and perform inconsistently in practice).

RED BLOOD CELL DEMAND AND OPPORTUNITY

Transfusion of red blood cells (RBC) is commonly needed in many clinical and surgical practices. On average, 39,000 units of blood are needed every day and data from 2004 indicate that 29 million units of blood were transfused in one year (source http://www.aabb.com). This procedure has singe-handedly saved many lives over the past 60+ years, and demand continues to increase with advances in medical treatments and an aging population, but is increasingly difficult to provide for the following reasons:

• The supply of blood components available from transfusion has steadily decreased over the past number of years, and will continue to do so, with more complex and thorough diagnostic testing for blood borne infectious diseases.
• The performance of stabilized and recombinant hemoglobins and oxygen transporters (perflourocarbons) has been disappointing and these approaches will have to overcome important development hurdles before replacing RBC transfusion in the clinic.
• Increasing reports of potential unwanted side-effects of long-term exposure to recombinant erythropoietin (EPO) suggest that additional studies of this widely used product may be warranted.
• While some initial attempts have been made to derive RBCs from hematopoietic stem cells in vitro (bone marrow, cord blood and peripheral blood), they are expensive and labor intensive, and suffer from the absence of a defined and continuous supply of RBC progenitor cells.

Ready access to a continuous supply of RBC progenitors that could generate a defined RBC product for transfusion would alter the practice in the clinics and render blood transfusion a safer and more extensively used procedure.

TAIGA'S SOLUTION FOR RBC PRODUCTION

Taiga is currently developing a novel method that uses our conditionally-transformed long-term repopulating hematopoietic stem cells as the source of a continuous and defined supply for the production of RBCs. This technology can either provide mature RBCs for immediate transfusion, or RBC progenitors for transfer and short-term reconstitution of the RBC compartment in patients. Furthermore, the enucleation of mature RBCs should alleviate concerns of any genetic modification. One of our ultimate goals for this project is to engineer a RBC product that has a longer shelf life that would enable far enough transport to reach patients who don’t have access to red blood cell therapy currently.