SOURCE: Laurantis Pharma OY

Laurantis Pharma OY

March 06, 2012 14:30 ET

Research Team Discovers Four-Fold Improvement in Ability to Restore Lymphatic Function With Adenovirally-Delivered VEGF-C Gene Therapy After Lymph Node Transplant Surgery Compared to the Surgery Alone

On Lymphedema Awareness Day, Researchers Present Pre-Clinical Data Offering Cautious Hope for Breast Cancer Patients Suffering From Secondary Lymphedema

VENTURA, CA--(Marketwire - Mar 6, 2012) - Lymphedema Awareness Day was established to support the needs of patients with lymphedema and to raise awareness for the need to develop new treatment options. Today, researchers have presented investigational pre-clinical data on the first potential pharmacologic agent used in combination with surgery for the treatment of breast cancer associated lymphedema at the Gordon Research Conference for Molecular Mechanisms in Lymphatic Function & Disease.

"Currently there is no advanced pharmacologically-based therapeutic for lymphedema," said Stanley G. Rockson, MD, Director, Center for Lymphatic and Venous Disorders, Stanford University School of Medicine, and Principal Investigator of the upcoming "first in human" trial for Lymfactin. "Although the research is still early, the preliminary data show a remarkable improvement in the ability to successfully conduct lymph node transplant surgery with the benefit of Lymfactin."

Lymphedema occurs in about 20 percent of the three million patients with breast cancer. The condition occurs from trauma to the lymph nodes, and blockages in the lymphatic system as a result of breast cancer treatment. The symptoms include painful swelling and inflammation of the limbs.

Turku, Finland-based Laurantis Pharma Oy is developing Lymfactin™, a vascular endothelial growth factor C (VEGF-C) in an adenoviral vector, for the treatment of secondary lymphedema associated with breast cancer. The therapy with Lymfactin involves a surgical operation where a lymph node flap is harvested from the patient's lower abdominal wall and injected with Lymfactin, which leads to the transient presence of the adenovirus containing the VEGF-C gene. The lymph node is then transferred to the axillary region.

"This new treatment is very promising," said Wendy Chaite, Founder, Lymphatic Research Foundation, a national organization devoted to advancing lymphatic research and to finding improved treatments and cures for lymphedema and lymphatic diseases. "Lymphedema is one of those seldom discussed but far too common conditions that biotech and pharmaceutical companies have yet to explore. Although this research is at an early stage, the lack of any advanced treatments makes this research all the more important for those who suffer from this condition."

Professor Kari Alitalo of the University of Helsinki, who made the discovery that the growth factor VEGF-C regulates the growth and development of the lymphatic system in humans and other mammals, presented the findings. From this discovery and in association with his co-workers Dr. Tuomas Tammela and Dr. Anne Saaristo, they identified that if VEGF-C is injected into tissues in mice and subsequently in pigs, growth of new lymphatic vessels and the restoration of the lymphatic architecture is catalyzed. Previous studies have shown that transferring lymph nodes from the inguinal region to the axillary region in patients with secondary lymphedema following their treatment for breast cancer was found to offer a slight improvement in their condition. Removal of old scar tissue from the axilla is considered an important step of this procedure.

The team in Finland then went a step further and showed that by combining VEGF-C injections with lymph node transfer in animal models using mice and then pigs, the response seen was even better than lymph node transfer alone. The results in mice indicated that lymphedema treated with lymph node transfer alone resulted in about 20% improvement. However, when combined with the administration of VEGF-C, the overall response was increased to around 80%.

In collaboration with Dr. Rockson, Dr. Anne Saaristo, MD and Prof. Kari Alitalo, Laurantis researchers, are developing a treatment to potentially enable much higher transfer success. The Company plans to start a phase I/II study in patients with breast cancer associated lymphedema in early 2013. Lymfactin is an investigational therapy and has not been approved by the U.S. Food and Drug Administration.

Target Indication: Breast Cancer Associated Lymphedema
The impairment of lymphatic drainage caused by dysfunction of the lymphatic vasculature leads to an accumulation of proteins and associated fluid, and finally to lymphedema -- a chronic progressive swelling of the affected tissues. Lymphedema can either be hereditary -- in which case it is diagnosed as "primary lymphedema" -- or it can occur as a consequence of a disease, trauma, surgery, or radiotherapy and thereby diagnosed as secondary lymphedema.

Current treatment of lymphedema focuses on minimizing swelling, controlling pain, preventing infection, and improving the patient's overall quality of life. Treatments include exercise, wrappings, massage, pneumatic compression and compression garments. In severe cases of lymphedema, a surgery may be considered to remove excess tissue in the limb. While this reduces severe swelling, surgery cannot cure lymphedema.

Scientific Rationale
Vascular endothelial growth factors (VEGFs) are involved naturally in all types of vascular growth and are capable of directly inducing the growth of blood or lymphatic vessels in vivo. Vascular endothelial growth factor receptor 3 (VEGFR-3) is a major signaling pathway for lymphangiogenesis (growth of new lymphatic vessels) and is a high-affinity receptor for VEGF-C and VEGF-D.

VEGF-C and VEGF-D induce the growth of lymphatic vessels through VEGFR-3 and are the primary growth factors associated with lymphatic vessel growth. VEGFR-3 signaling is required for the survival and maintenance of lymphatic vessels during embryonic development and inactivating mutations in VEGFR-3 lead to lymphedema and incomplete development of lymphatic vasculature in both mice and humans. VEGF-C is currently the only known growth factor that is both potent and specific enough to potentially be used in a lymphedema therapy.

Preclinical Data
Laurantis has shown in the preclinical studies that adenovirally-delivered VEGF-C is the optimal growth factor for a lymphedema therapy. In a series of experiments, the effects of adenovirally-delivered VEGF-C were compared to controls in which seroma formation, lymphatic vessel function, lymph node morphology and histology were studied. Two months after transfer, VEGF-C-treated lymph nodes were larger than the treated controls and more lymph vessels had been formed. Adenovirally-delivered VEGF-C in support of lymph node transfer is a viable option for the treatment of lymphedema.

About Laurantis Pharma
Laurantis Pharma is a clinical-stage specialty pharmaceutical development company with a broad portfolio of first-in-class products based on two proprietary technologies. The Company's lead products target the treatment of a variety of inflammatory diseases and conditions including lymphatic disorders, atopic dermatitis, dry eye syndrome, and interstitial cystitis, as well as the treatment of bladder cancer.

The Company's pipeline includes proprietary and patent-protected formulations and applications of cis-urocanic acid (cis-UCA), a locally acting anti-inflammatory and anti-proliferative agent. Laurantis Pharma is also developing Lymfactin™, a vascular endothelial growth factor C (VEGF-C) in an adenoviral vector, for the treatment of secondary lymphedema. Laurantis Pharma is located in Turku, Finland.

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