How This 1 Company Is Attempting to Overcome One of Cancer's Greatest Risk Factors

Cancer is one of the scariest disease diagnoses imaginable, at least according to one U.K. study, and that's primarily because researchers, despite decades of work and collaboration, are still scratching the surface on what triggers cancer in the first place. If we don't fully understand the triggers and risk factors well enough, it can make it difficult for researchers to ultimately fight the disease and not just the symptoms of cancer.

What's potentially scarier is that the World Health Organization in February projected that global cancer rates could rise by as much as 57% over the next 20 years from an estimated 14 million cases annually to 22 million.

As we saw last year by taking a deeper dive into the 12 most-commonly diagnosed cancer types, there is a laundry list of risk factors that can lead to an increased risk of getting certain types of cancers. Obesity, diabetes, alcohol consumption, and smoking are just some of the factors that appeared with some regularity. Yet no factor seemed to stand out more, at least to me, than age.



Source: Thomas Leuthard, Flickr.

One of cancer's greatest risk factors
While all cancers are different, and a person at any age can get cancer, the general consensus among the scientific community is one reason cancer rates have gone up is because life expectancy rates have also risen. Data from the World Bank sows that life expectancy in the U.S. has jumped from the rough equivalent of 70 years in 1968 to just shy of 79 years as of 2011. This progress, though, appears to have come at the cost of a higher incident rate of cancer.

A study released in February from the National Institutes of Health postulated that DNA methylation over the course of our lives can alter "interactions between DNA and the cell's protein-making machinery." As the study described, these DNA changes amount to it being tougher and tougher for genes to continue to carry out their normal function and, instead, mutating into a cancer cell because it's "easier."

Of course this is just one theory, and I'm sure if you scour medical books or the Internet you'll find a handful more where this came from. The point being that the older we get, the chance that we get cancer seems to increase, even if we don't fully understand the "why" component.

The typical response to fighting cancer by most pharmaceutical companies is to target the replication process itself or specific cancer-cell protein signatures. While varying in effectiveness based on the type of cancer involved, this equates to treating the symptoms and not necessarily the underlying cause of cancer. One biopharmaceutical company, however, has a unique and revolutionary approach that just might even the score with father time's increased risk of cancer.

Battling the disease, not just the symptoms
The biopharmaceutical company in question is OncoMed Pharmaceuticals and what makes it so unique is that it's clinical-stage therapies are designed to attack cancer stem cells, or CSCs.

CSCs are believed to be self-replicating according to the National Cancer Institute, and produce progenitor cells similar to what normal stem cells do in our body. These progenitor cells help repopulate tumor cells which have been destroyed by chemotherapy treatment of the body's immune response. CSCs are believed to be incredibly resistant to most types of chemotherapy and radiotherapy, making it difficult to eradicate them. Finally, CSCs are also suspected to be one of the primary causes of secondary tumors, relapses, and global metastases. Again, these are theories as a lot about CSCs is still being studied, but this marks a possible pathway to fight the root cause of a disease and not necessarily just its outer layers. 

OncoMed's solution is to develop a number of therapies which target CSC proteins to block their ability to replicate and proliferate progenitor cells.


Source: OncoMed Pharmaceuticals.

The company's lead product is demcizumab, a mid-stage product designed to block notch-signaling (specifically DLL4) in CSCs. In a phase 1 pancreatic cancer study in combination with Gemzar, demcizumab delivered four RECIST partial responses and an additional seven cases of stable disease out of 16 evaluable patients (a clinical benefit of 69%) while also being well-tolerated. In the 5 mg dose the median progression-free survival observed was 176 days.

Another exciting experimental therapy currently in two phase 1b/2 studies is OMP-59R5, an anti-CSC antibody that binds with the notch 3 receptor and prevents signaling through notch 2 and notch 3. Last year OncoMed noted in in its phase 1 study that OMP-59R5 was well-tolerated in patients with solid tumors and that it prolonged stable disease in some patients when dose at 2.5 mg/kg or higher.

In addition to demcizumab and OMP-59R5, OncoMed has three additional phase 1 studies ongoing and at least seven other preclinical programs listed on its website.

Source: Geralt, Pixabay.

A collaborative list of heavy-hitters
Another thing you'll note is that OncoMed has plenty of funding and a lot of heavy-hitter partnerships. None might be bigger than the mammoth deal it struck with Celgene in December. Celgene put up $155 million in upfront payments to OncoMed, purchased $22.5 million in OncoMed's common stock, and pledged up to $3.3 billion (with a "b") in milestone payments for the co-marketing rights for up to six of OncoMed's therapies, including demcizumab, and five preclinical therapies including OMP-305B83, an anti-DLL4/VEFG notch receptor, and anti-RSPO-LGR. Of course it'll be up to OncoMed's therapies to outperform in studies as to whether it sees a dime of that $3.3 billion or not, but the sheer magnitude of the milestone potential is huge!

But, Celgene isn't the end of it. OncoMed also has a strategic partnerships with GlaxoSmithKline and Bayer .

Its collaboration with GlaxoSmithKline extends back to 2007 and could equal nearly $700 million in milestone payments over the length of its co-marketing program, which currently covers OMP-59R5 and phase 1 experimental anti-notch 1 therapy OMP-52M51.

OncoMed's partnership with Bayer is a bit more recent, beginning in 2010, and will comprise up to five agents targeting the Wnt-signaling pathway. All told, OncoMed received $40 million upfront and could see an additional $387.5 million per program in addition to mid-single to low-double-digit royalties if approved.

Added together this represents around $6 billion in aggregate milestone potential is OncoMed's pipeline is successful -- although that thought is probably a bit utopian.

The usual risks implied
But, as with all wholly clinical stage cancer-focused biopharmaceutical companies two major risks are implied. The first is that OncoMed is likely to continue burning through cash in the near-term as it furthers its clinical-stage compounds and continues to uncover new anti-CSC compounds in the preclinical setting. It has more than ample cash to continue its work at the moment, but there's no guarantee that it will have ample cash a few years from now.

Secondly, the failure rate for cancer therapeutics is fairly high. It's sometimes possible to gauge the effectiveness of a therapy based on a previous clinical comparison to an already approved drug that works along the same pathway. Anti-CSC drugs like that being developed by OncoMed have no prior comparison, which makes its technology highly intriguing, but its effectiveness still somewhat unknown.

Overall, though, I believe OncoMed could have the necessary tools to tackle cancer from the source of cell differentiation rather than merely attempting to alter cell proliferation. While we're not talking about a cure necessarily, we are beginning to see a possible shift in how cancer-focused companies approach cancer treatment, and as such, I would strongly suggest you add this biopharmaceutical company to your watchlist moving forward.

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The article How This 1 Company Is Attempting to Overcome One of Cancer's Greatest Risk Factors originally appeared on Fool.com.

Sean Williams has no material interest in any companies mentioned in this article. You can follow him on CAPS under the screen name TMFUltraLong, track every pick he makes under the screen name TrackUltraLong, and check him out on Twitter, where he goes by the handle @TMFUltraLong. The Motley Fool recommends Celgene. Try any of our Foolish newsletter services free for 30 days. We Fools don't all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

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