Replies to post #75948 on Biotech Values

[DewDiligence]

Re: MNTA’s heparin-based cancer drug (M402)

The idea underlying M402 is simple: Heparins have strong anti-angiogenic properties, but unfractionated heparin and LMWH’s such as Lovenox don’t work as cancer drugs because the doses required to be effective for anti-angiogenesis would cause patients to bleed to death.

MNTA has thus designed M402 to retain heparin’s anti-angiogenic effect without its anticoagulation. This goal has been sought using the same techniques used to design M118: mixing and matching the various constituents of unfractionated heparin using MNTA’s proprietary restriction enzymes and informatics tools until the desired properties are achieved.

[DewDiligence]

Quiz: Other than MNTA, what company is developing carbohydrate-based drugs to treat cancer?

[DewDiligence]

MNTA M402 description from the 2009 10K report filed today (c/o rkrw on SI):

http://sec.gov/Archives/edgar/data/1235010/000104746910002115/a2197212z10-k.htm (page 9)

M402 is our next most advanced novel HSPG-based product candidate [i.e. M118 is first in line among MNTA’s proprietary compounds] and is engineered to have potent anti-cancer properties and low anticoagulant activity.

HSPGs are complex molecules present in the tumor microenvironment which play a role in the conversion of normal cells into cancerous cells and present growth factors, cytokines, and chemokines necessary for tumor cell growth, migration, and survival. M402 is designed to exploit this biology. Data from preclinical studies have shown that M402 has the potential to modulate angiogenesis and tumor metastasis through a variety of HSPG-binding proteins.

We currently have plans to advance M402 into human clinical trials in the first half of 2011 [#msg-46537561, bottom].

With a little added color, the above is essentially the same rationale for M402 that Craig Wheeler has given on CC’s (#msg-37030489) and MNTA presented at the 2009 AACR conference (#msg-37152092).

[DewDiligence]

This paper is tangentially relevant to MNTA’s M402…

http://www.ncbi.nlm.nih.gov/pubmed/20617422

›Assessment of Anti-Metastatic Effects of Anticoagulant and Antiplatelet Agents Using Animal Models of Experimental Lung Metastasis

Methods Mol Biol. 2010;663:241-59.

Amirkhosravi A, Mousa SA, Amaya M, Meyer T, Davila M, Robson T, Francis JL.

Florida Hospital Center for Thrombosis Research, Orlando, FL, USA.

It is well established that the blood coagulation system is activated in cancer. In addition, there is considerable evidence to suggest that clotting activation plays an important role in the biology of malignant tumors, including the process of blood-borne metastasis. For many years, our laboratory has used experimental models of lung metastasis to study the events that follow the introduction of procoagulant-bearing tumor cells into circulating blood. This chapter focuses on the basic methods involved in assessing the anti-metastatic effects of anticoagulants and anti-platelet agents using rodent models of experimental metastasis. In addition, it summarizes our experience with these models, which collectively suggests that intravascular coagulation and platelet activation are a necessary prelude to lung tumor formation and that interruption of coagulation pathways or platelet aggregation may be an effective anti-metastatic strategy.‹