Replies to post #144885 on Biotech Values

[biomaven0]

Too bad MNTA is now wasting their money in the overcrowded oncology space. :)

Seriously though, this is an interesting, albeit challenging, program. It's going to be challenging because my guess is you won't see much activity as a monotherapy, which makes development quite a bit harder. It might also not impact tumor size directly, which means the standard RECIST response metric might not be a good fit. So it's plausible to me that the efficacy might show up in OS rather than response rate, which again makes trials harder. (Most cancer patients die as a result of mets rather than from their primary tumor).

Here's a article from about a year ago talking about the landscape for this sort of program:

Cancer Microenviron. 2011 Aug 3. [Epub ahead of print]
Significance of Heparanase in Cancer and Inflammation.
Vlodavsky I, Beckhove P, Lerner I, Pisano C, Meirovitz A, Ilan N, Elkin M.
Source
Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine, Technion, P. O. Box 9649, Haifa, 31096, Israel, [e-mail].
Abstract
Heparan sulfate proteoglycans (HSPGs) are primary components at the interface between virtually every eukaryotic cell and its extracellular matrix. HSPGs not only provide a storage depot for heparin-binding molecules in the cell microenvironment, but also decisively regulate their accessibility, function and mode of action. As such, they are intimately involved in modulating cell invasion and signaling loops that are critical for tumor growth, inflammation and kidney function. In a series of studies performed since the cloning of the human heparanase gene, we and others have demonstrated that heparanase, the sole heparan sulfate degrading endoglycosidase, is causally involved in cancer progression, inflammation and diabetic nephropathy and hence is a valid target for drug development. Heparanase is causally involved in inflammation and accelerates colon tumorigenesis associated with inflammatory bowel disease. Notably, heparanase stimulates macrophage activation, while macrophages induce production and activation of latent heparanase contributed by the colon epithelium, together generating a vicious cycle that powers colitis and the associated tumorigenesis. Heparanase also plays a decisive role in the pathogenesis of diabetic nephropathy, degrading heparan sulfate in the glomerular basement membrane and ultimately leading to proteinuria and kidney dysfunction. Notably, clinically relevant doses of ionizing radiation (IR) upregulate heparanase expression and thereby augment the metastatic potential of pancreatic carcinoma. Thus, combining radiotherapy with heparanase inhibition is an effective strategy to prevent tumor resistance and dissemination in IR-treated pancreatic cancer patients. Also, accumulating evidence indicate that peptides derived from human heparanase elicit a potent anti-tumor immune response, suggesting that heparanase represents a promising target antigen for immunotherapeutic approaches against a broad variety of tumours. Oligosaccharide-based compounds that inhibit heparanase enzymatic activity were developed, aiming primarily at halting tumor growth, metastasis and angiogenesis. Some of these compounds are being evaluated in clinical trials, targeting both the tumor and tumor microenvironment.

[DewDiligence]

Clinicaltrials.gov entry for M402 trial:

http://www.clinicaltrials.gov/ct2/show/NCT01621243