Posted on October 4th, 2016
by Jeffrey Bacha
In an era where biotech news has been dominated by elegant immunotherapy approaches in the fight against cancer, an “old-school” approach has begun to re-emerge.
SV Life Sciences, AbbVIE (ABBV) and Merck KGaA recently invested more than $33 million in a start-up company called Artios Pharma. Artios is going after the enzymes involved in DNA repair as a way to treat cancer.
Our DNA is constantly under attack from environmental agents like skin cancer-causing UV rays and environmental toxins that induce mutations. Our body employs a rigorous system of checks and balances to address this damage through numerous DNA repair mechanisms. Errors that slip through the cracks are associated with cancer and other diseases.
The basic premise behind Artios is that cancer cells replicate faster than normal cells and rely on DNA damage repair systems more than healthy cells; therefore, inhibiting DNA mechanisms might hit tumors more selectively than healthy cells.
An example of success in targeting DNA damage repair mechanisms are PARP inhibitors. PARP inhibitors work by stopping the poly ADP ribose polymerase (PARP) enzyme from repairing breaks in DNA.
The first PARP inhibitor, Lynparza™ (olaparib) was launched by AstraZeneca after being granted accelerated approval by FDA for a subset of advanced ovarian cancer for patients who have failed three or more prior lines of chemotherapy. The drug is expected to reach $2 billion in sales at its peak.
When one company achieves success, others follow as quickly as possible. As such, Tesaro’s PARP inhibitor, niraparib, is expected to win FDA approval later this year and Abbvie’s velaparib is undergoing Phase III clinical trials.
DNA insults from chemotherapy may also trigger DNA repair mechanisms. In fact, it is often these mechanisms that are responsible for a tumor’s resistance to chemotherapy. Understanding how they relate to a particular chemotherapy represents another approach to using DNA repair mechanisms in the fight against cancer. The differences between two drugs can be exploited to overcome drug resistance as well as for synergistic combination chemotherapy.
This concept can also provide opportunities to exploit established or previously abandoned drugs in new ways. Indeed, Celgene took this approach in understanding mechanism to support the development of Thalomid® (thalidomide) for leprosy and a rare form of leukemia. This product became the foundation upon which an $80 billion company was built.
VAL-083 is a “first-in-class” small-molecule alkylating agent. Alkylating agents represent some of the earliest chemotherapies employed in the treatment of cancer and are still among the most widely used agents today.
Prior human clinical trials sponsored by the US National Cancer Institutes demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 was ultimately neglected in favor of other drug candidates that had longer remaining patent life at that time.
By investing in state-of-the-art research using modern science to better understand how VAL-083 attacks a tumor’s DNA, we can identify subtle differences in how VAL-083 interacts with the body’s DNA repair mechanisms compared to other widely used chemotherapies. This research has resulted in more than 100 global patent filings by DelMar for VAL-083 since we founded our company in 2010.
This knowledge may also, in turn, allow us to address unmet medical needs defined by valuable cancer niches where patients’ tumors have become resistant to or exhibit biological features that make them unlikely to respond to currently available chemotherapy.
The table below outlines what we’ve learned so far. The differences may be subtle, but they provide direction to our clinical development strategy.
Over the past year, we have presented data at scientific meetings demonstrating that VAL-083 is active against adult brain tumors, lung cancers, ovarian cancer and childhood medulloblastoma that are resistant to other chemotherapies.
Importantly, each of these indications is a tumor-type where data from prior human clinical trials have already demonstrated promising activity. It is our hope that this deeper understanding of DNA repair mechanisms will position us to leverage VAL-083’s prior clinical validation to illuminate the dark corners of unmet medical needs in the modern treatment of major cancers.
Forward Looking Statements
Any statements contained in this blog that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations, but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in our filings with the SEC, including, our current reports on Form 8-K.
This Blog is official and sanctioned by DelMar Pharmaceuticals, Inc.