Technology Basis of CM101 and Mechanism of Action (Lay Description)

TumorEnd® Unique Technology for Tumor Vasculature Disruption:

Targeting tumor blood vessels for immune system disruption:

CM101 is a bacterial-derived polysaccharide biologic which targets a specific lectin receptor protein, HP59, that  is exposed inside the newly formed blood vessels of a tumor(1).  

The interaction of CM101 and HP59 activates complement, resulting in an inflammatory cytokine cascade (inflammation signal) which attracts CD69+ activated granulocytes (specialized white cells) that disrupt the tumor neovasculature (new blood vessels) and attack the surrounding tumor.  

A published, successful, Phase I Clinical Safety Trial of CM101, performed under FDA IND #4385, showed a 33% effectivity rate in a group of 15 refractory patients with 4-5 months life expectancy (2).

In this published Clinical Trial, 3 of the 15 patients had significantly extended life expectancy, while the goal of the trial was only to establish safety.

Patient 1:  Cancer:  Classic Kaposi’s Sarcoma:   All tumors on the patients lower left leg and foot disappeared over the 12 week course of the trial.   He was followed for 10 years without recurrance.

Patient 2:  Cancer:  metastatic duodenal carcinoma, age 43:   Metastases became inflamed, and shrank or disappeared.   One shrunken tumor was excised and found to be infiltrated with granulocyte white cells.   New metastases appeared at 7 and 18 months and were successfully treated with CM101.    Tumor in left arm not accessible by immune system due to extensive removal of lymph nodes, radiation damage.  This tumor was releasing metastatic cells and the patient refused  amputation.   She survived 4 years beyond the Clinical Safety Trial.

Patient 3:  Cancer:  liver metastatic colon cancer:   3 large liver tumors, 6, 9 and 12 centimeters, all were reduced in size, progression halted for several months, life extension 18 months.

Toxicity:  There were no clinically unmanageable toxicities produced by CM101.  Observations were as follows(2):

            1. Febrile:  (Body Temperature)  All patients with tumors had an increased temperature and chills due to the inflammatory response to the tumor.  This is planned to be manageable with Tylenol, which is not an anti-inflammatory. Therefore CM101 is also a diagnostic for the presence of solid tumors.

            2. Tumor-specific Pain:   Patients who responded felt pain in the tumor area due to the inflammatory attack.  This is manageable with pain medication.  It can also function as a diagnostic, locating tumors by pain foci.

            3. Dyspnea:  (Breathing) affected in some patients, possibly with lung disease or involvement, but clinically manageable. 

1) Fu C, Bardhan S, Cetateanu ND, Wamil BD, WangY, Yan H-P, Carter CE, Shi E, Venkov C, Yakes FM, Page DL, Lloyd RS, Hellerqvist CG. Identification of a novel membrane protein HP59 with therapeutic potential as a target of tumor angiogenesis. Clin. Cancer Research 7: 4182-4194 (2001).

2) DeVore RF, Hellerqvist CG, Wakefield GB, Wamil BD, Thurman GB, Minton PA, Sundell HW, Yan H-P, Carter CE, Wang Y-F, York GE, Zhang M-H, Johnson DH.: A phase I study of the antineovascularization drug CM101. J Clin Canc Res. 3: 365-372 (1997).