Platform of Photodynamic Drug R & D

Photodynamic therapy (PDT), developed in the end of seventies last century, is a new technique for the selective treatment of vessel hyper-plastic diseases, e.g. cancers. Following with operation, chemotherapy and immunologic treatment, the technique is a new way to treat cancer under the development of R & D, and has become one of the most active topics studied by the scientists relating to the cancer treatment.

The launch of the first photosensitive drug, Porfimer Sodium, in United States, Canada, Europe Union, Japan and Korea, during the period of 1993 to 1997, provokes the fast development of the R & D of photodynamic drugs. As the successful R & D results to develop new photodynamic drugs and laser producing facilities, the development of PDT has reached the highest level and been developed used more popularly in recent years. There are more than a dozen of new photodynamic drugs emerged in market or in the stage of clinical studies globally. In addition of cancer treatment, PDT has more therapeutic usages and is also used to treat Condyloma acuminatum, naevus flammeus (port wind stain), Age-related Macular Degeneration (AMD), Rheumatoid arthritis, angiostenosis and so on. It is believed that PDT will be ranked in the regular clinical treatment region.

Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. (FDZJ) closely pays attention and keeps pace with the international development of PDT, collaborated with The Second Military Medical University, that is regarded as the pioneer of PDT R &Ｄ inside China，early in 1999, FDZJ organized FDZJ PDT R & D Centre to concentrate the study of PDT drugs. Most well-known researchers gathered and joined the centre. It is a professional institute to deal with photodynamic drug R & D, and then the PDT R & D platform of FDZJ was then successfully established.

During the past years, PDT R & D was one of major research fields in FDZJ and important results were produced there. The new chemical entity and the class one new drug, Hemoporfin, developed by FDZJ, for the treatment of naevus flammeus (port wind stain) has been moved to clinical trial phase III stage. ALA, to treat condyloma acuminatum, has been listed in market since 2007. New chemical entity and class one new drug, Duteroporphyrin, to treat cancer, has got the approval for clinical trial issued by SFDA in January, 2009. 3 Photodynamic new drugs covering five indications have been produced in this platform. More projects relating to the R & D of photodynamic drugs are also carried out. Six patents including one PCT have been produced. FDZJ has become one of the most potential R & D companies for PDT drugs.

Aminolevulinic acid Hydrochloride（ALA^®）

ALA is regarded as the second generation of photodynamic drugs in recent years and is a precursor found in hemoglobin synthesis. The quantity of endogenous ALA is very small and no photosensitive activities were found. When exogenous ALA administrated, ALA is absorbed, accumulated by the cells, particularly by the hyper-plastic cells, and then converted to PpIX which is a powerful photosensitive material. When exposed to light with an appropriate wavelength, PpIX induces a photodynamic reaction. Active oxygen ions and radicals are generated and then kill the abnormally growing cells. Meanwhile, the normal cells are remained un-affected.

ALA is used for the treatment of condyloma acuminatum（CA）. CA cells are similar as the tumor cells characteristic of hyper-plastics. ALA selectively distributes and accumulates in the CA cells and kills the cells without affecting for normal cells around when exposed to light with special wave length and energy. It is especially useful to clear the sub-clinical infection and reduces the recurrence rate of CA.

The advantage of ALA-PDT:The indication was innovatively developed by FDZJ. The clinical trial showed the efficacy of the treatment. The clearance rate reached 95%, the recurrence rate was lowed than 10%. The patients were well tolerated. The experts evolved in the trial all regarded ALA-PDT was the first-line treatment for CA infected inside of urethra. It is also the main treatment for CA outside of urethra since the recurrence rate is much lower (15%) than that of other treatments.

Status of the Project: Listed in market

Hemoporfin

Hemoporfin, innovatively developed by this company as a new chemical entity, is a porphyrin monomer and used to treat naevus flammeus (port wind stain), Age-related Macular Degeneration (AMD) cornea vessel hyper-plastics and so on. Hemoporfin-PDT is now regarded as one of the simplest and effective methods to treat these kinds of blood vessel diseases.

Hemoporfin-PDT, mechanism and characteristics:
The pharmacologic base for the treatment of naevus flammeus: Photosensitive drug administrated by iv highly concentrates in the blood, and then quickly absorbed by the vessel endothelia cells. However, the cells on cuticular layer absorb less. The difference of the concentration of the drug is then produced. When an irradiation of laser with special wave length is used to vessel endothelia cells, the photodynamic reaction will take place in the special region. The cells absorbing drug will be injured selectively to cause the damage of the deformed capillary network and the epidermic cells remains un-affected. The dermis layer under the capillary network is also un-affected due to the controlled exposing of laser.

Hemoporfin is a pure compound with clear elucidated structure. Hemoporfin-PDT produces effective results in the therapy. The mechanism is clearly studied. The drug has a high metabolism rate and the short time of light-prevention is required. The treatment is safe, effective and possesses less reverse reaction. The quality of drug is easily controlled. Therefore, the drug is regarded as an ideal one for the treatment of naevus flammeus.

The statues of the project: Obtained the New Drug Certificate

Duteroporphyrin
Duteroporphyrin is a photodynamic drug with a stable composition and clear structure has been elucidated for the each composition. The photodynamic properties of anti-tumor of each component have been well-studied on the model of animals. With the structure of porphyrin, it is used to treat cancer in PDT and FDZJ owns the whole IP.

The study showed that Duteroporphyrin had strong photodynamic injury activities to kill tumor cells and relatively low photo-toxicity. The chemical structures of the bio-photo-active material with anti-tumor activities were clear, so the quality and the efficacy were able to control. The study also showed that clearance of the drug in body was fast and then the accumulation would not take place easily. These properties make the Duteroporphyrin a photo-safe drug to avoid the toxicities found in most photodynamic therapies as a main reverse reaction, whose patients engaged in PDT must be kept in darkness for a quite long time, e.g. patients administrated PHOTOFRIN^®and HpD must stay in darkness for one to two months. Duteroporphyrin -PDT is then a perfect way in this field.

Duteroporphyrin has stable compositions with clear structure. It does not contain photosensitive porphyrin which has no anti-tumor activities. Therefore the quality and efficacy are easy to control. The efficacy to inhibit the cancer cells in vitro and planted cancer cells has been conformed. The metabolism is fast. The reverse reaction is less and the light-prevention time is short. It will be a hopeful new drug to treat cancer as a photodynamic drug. The preclinical study has been totally completed and clinical trial permission was issued by SFDA in January, 2009.

The status of the project: the permission of the clinical trial issued.