Urologic Pipeline

Tengion's primary focus is the development of product candidates to targeted urologic applications where the current standard of care involves surgical procedures to replace or augment diseased bladder tissue through the use of bowel tissue harvested from the patient. The Company has developed a portfolio of product candidates in this area and has clinical experience in two Phase II clinical trials.

Neo-Urinary Conduit™ and Neo-Bladder Replacement™

Tengion has two product candidates for the treatment of patients who require removal of their bladder in connection with the treatment of bladder, abdominal or pelvic cancer, or other severe bladder disease. The Neo-Urinary Conduit, for which the Company has initiated a Phase 1 clinical trial, is a physiologically functional tissue with a three-dimensional structure that diverts urine from the ureters to a removable, disposable bag, or ostomy bag, outside the body after removal of the bladder.

The Neo-Bladder Replacement™, which is in pre-clinical development, is a physiologically functional tissue with a three-dimensional structure that diverts urine to a native bladder-like structure (also called an orthotopic neo-bladder). The Neo-Bladder Replacement™ is connected to the ureters at the distal end and the urethra at the proximal end, and will enable patients to store urine without the use of an external bag.

Current treatment for patients undergoing cystectomy is creation of a conduit or bladder replacement with the use of bowel tissue. The purpose of the Neo-Urinary Conduit™ and the Neo-Bladder Replacement™ is to avoid the complications associated with removal of bowel tissue within a urinary excretion context. Complications are listed below:

• Bowel complications. Early complications are usually related to the bowel surgery required to harvest tissue for reconstructive use and typically consist of leaks, fistulas and obstructions. Because vitamin B12 is absorbed in the bowel tissue, the loss of tissue can result in anemia and neurologic abnormalities. Additionally, malabsorption of salts and lipids can lead to diarrhea. Patients with neurogenic bladder are prone to bowel movement problems even before surgery and the removal of bowel tissue may either exacerbate existing conditions or create new motility problems. These conditions further contribute to the substantial physical and psychological morbidity in these patients.
• Absorption issues. Use of bowel tissue often leads to electrolyte and metabolic imbalances, which can cause bone loss. Certain drugs taken by the patient may be reabsorbed by the implanted bowel tissue, potentially leading to unintended toxic levels. The exposure of intestinal surface to urine also results in the inappropriate absorption of ammonium, chloride and hydrogen ions as well as potassium loss, leading to chronic metabolic imbalances or abnormalities.
• Infection. Persistent and recurrent infections are typical in patients with bowel tissue reconstruction. Infections may reach the kidney and become life-threatening. Bacteria normally found in bowel tissue can serve as a source of infection and septic complications when repositioned into the urinary tract.
• Stone formation. One of the consequences of persistent infection is the development of stones.
  Stones are hard masses which can cause pain, bleeding, obstruction of urine or infections.
• Mucus. Bowel tissue, when repositioned in the urinary tract, continues to secrete mucus.
  Mucus increases the risk of stone formation and the viscosity of urine, and in the case of bladder augments, may require bladder irrigation and more frequent catheterization.
• Cancer. Malignancy, although rare, is a well-recognized complication following bladder augmentation using bowel tissue, or enterocystoplasty, and other reconstructive surgeries that incorporate bowel segments into the genitourinary tract.

Neo-Bladder Augment™

The Tengion Neo-Bladder Augment™ is being developed for patients with neurogenic bladder, or dysfunctional bladder due to some form of neurologic disease or condition, for which treatment often requires an augmentation of the bladder in order to relieve high pressure and incontinence.

Current treatments for neurogenic bladder include medical management through a combination of medication and clean intermittent catheterization and, in advanced cases, surgery. Surgical procedures, such as bladder augmentation, are often considered when other medical and less-invasive treatments fail to adequately lower bladder pressure or reduce the frequency of incontinent episodes. Enterocystoplasty involves a surgical procedure during which a section of the patient’s bowel is removed and then used to augment the existing bladder seeking to increase compliance and capacity.

The purpose of Neo-Bladder Augment™ is to eliminate gastrointestinal surgery when conducting urologic augmentation surgery and to avoid or reduce chronic, serious and frequent complications and side effects associated with the use of gastrointestinal tissue (see list of complications above).

Tengion has completed two Neo-Bladder Augment™ Phase II clinical trials: one in pediatric patients with neurogenic bladder caused by spina bifida, and the other in adult patients with neurogenic bladder caused by spinal cord injury.