EXACT SCIENCES is developing technologies that help to eradicate mortality from common cancers — starting with colorectal cancer — by applying advances in the field of genomics to facilitate the early detection of disease.
EXACT Sciences’ first target is colorectal cancer, the second leading cause of cancer deaths and the most deadly cancer among non-smoking men and women in the United States. Annually, there are nearly 154,000 colorectal cancer cases diagnosed and 52,000 deaths due to this disease. It is estimated that roughly one-third of colorectal cancer-related deaths could be saved if more people underwent regular screening.
Of those diagnosed, nearly half are expected to die within five years, since most cancers are detected when the cancer is less treatable. For those whose cancer is detected at an earlier stage, the five-year survival rate can be greater than 90%. The American Cancer Society recommends that all Americans age 50 and older be screened regularly for colorectal cancer. Unfortunately, only a fraction of this population is screened for the disease, as currently available screening technologies are considered by many as either too invasive or inaccurate.
EXACT Sciences is developing a next-generation (V3), stool DNA (sDNA) based screening test for colorectal cancer (CRC) which has demonstrated the ability to detect both early-stage cancer and pre-cancerous growths. The Company's sDNA-based screening technology platform has also demonstrated the ability to detect related GI cancers and pre-cancers.
In June 2009, EXACT Sciences announced a collaboration and licensing agreement with the Mayo Clinic that is focused on developing patient-friendly diagnostics that reduce deaths from CRC. According to projections by the American Cancer Society (ACS) there will be 146,970 new cases of CRC and nearly 50,000 deaths attributable to the disease in 2009 in the U.S. alone, representing the second most common cause of cancer-related death following lung cancer (60,000 deaths) and ahead of breast cancer (about 41,000 deaths).
Under the license agreement, the Company has secured exclusive rights to intellectual property (IP) developed by David Ahlquist, M.D., Mayo Clinic, including patents that cover advances in sample processing, analytical testing and data analysis associated with non-invasive, sDNA screening for CRC. EXAS will make up-front, milestone, and royalty payments to the Mayo Clinic and will provide funding for future work in Dr. Ahlquist's lab in exchange for the exclusive rights to commercialize any promising results from this collaboration.
EXACT Sciences owns a strong patent estate for CRC screening, including the following: (1) platform technology: exclusive licenses to digital PCR and BEAMing technology (both stool + peripheral blood detection) from Johns Hopkins University (JHU) for the detection of CRC; (2) content: APC (adenomatous polyposis coli)and p53 (these are two common genetic mutations associated with CRC) licensed from GENZ with diagnostic testing kit rights + exclusive licenses to key tumor biomarkers such as Vimentin; (3) methods: broad IP for stool sample processing.
Last summer, EXAS announced the published results of a study in which stool and blood plasma were compared head-to-head for the detection of CRC using an improved BEAMing DNA detection technology (V3) from JHU. Study results demonstrated 92% sensitivity for detecting CRC in stool samples, which outperformed blood plasma testing - especially in the detection of early stage disease, which is crucial to have a positive impact and decrease mortality as CRC has a much better treatment outcome when diagnosed at early stages.
BEAMing describes an assay technology which incorporates the use of "Beads, Emulsion, Amplification, and Magnetism". The technology is a useful method for performing single-molecule analysis of DNA or "Digital PCR" that has been demonstrated to provide a high level of sensitivity for the detection of mutations or deletions in gene sequences of interest.
In the study, a total of 25 sDNA samples from CRC patients were analyzed and a next generation sDNA technology (V3) correctly identified 23 (92%) of the cancers. In the 16 of 25 cases where there were paired stool and plasma DNA samples, the sDNA technology detected mutated DNA in stool in 14 cases (88%) while only 8 (50%) corresponding plasma DNA samples had detectable levels of mutated DNA. In addition, when late-stage disease (Stage IV) is removed from the total, non-invasive sDNA performance remained at 86% (12/14) while plasma DNA performance fell to 43% (6/14). The results of the study, Analysis of Mutations in DNA Isolated from Plasma and Stool of Colorectal Cancer Patients, were published in the August journal of Gastroenterology.
A week after the Mayo Clinic deal, EXAS announced that it received a $1M loan from the Wisconsin Department of Commerce to relocate its headquarters and operations from Marlborough, MA, to Madison, WI. The Company’s expansion plans include the creation of up to 150 jobs over five years as EXAS achieves commercial milestones for its non-invasive sDNA screening test for the early detection of CRC. The relocation to Madison follows a management overhaul in March that brought a new leadership team from Third Wave Technologies, including the new President & CEO, Kevin Conroy.
Third Wave was acquired by Hologic (NASDAQ:HOLX) in 2008 for $582M, and the management team now at EXAS led the development through FDA approval for two human papillomavirus (HPV) molecular diagnostic tests in addition to a test for cystic fibrosis. The new executive leadership team is expected to restore investor confidence in EXAS once their strategic plan is communicated to correct the backwards development of the Company's promising sDNA technology for the average risk population in the detection of CRC.
EXAS secured inclusion for its sDNA technology in the World Gastroenterology Organization, U.S. Multi-Society Task Force, and ACS guidelines for CRC screening before successfully developing a FDA-approved, fully automated test to fully capitalize on this major commercial and preventative medicine (i.e. saving lives) opportunity. Thus, LabCorp (NYSE:LH) currently markets ColoSure on a homebrew basis with little in the way of sales or third-party reimbursement (i.e. insurance or government) – which is unlikely to change until FDA approval is secured for the Company's V3 technology.
The exclusive agreement with LabCorp runs through the end of 2010 for the use of EXACT’s IP as part of a commercial testing service for CRC screening, which was launched as ColoSure last summer by LH on a homebrew, non-FDA approved basis. ColoSure is a single-marker sDNA test for the detection of CRC at all stages for asymptomatic, average-risk patients who are unwilling or unable to undergo a more invasive structural exam such as colonoscopy (the current gold standard). Published studies involving patients known to have invasive CRC show that ColoSure has a sensitivity range of 72-77% and a specificity range of 83-94% while the detection rates for general population screening have yet to be determined.
During Mr. Conroy’s tenure as chief executive of Third Wave, he oversaw the development of two human papillomavirus (HPV) molecular diagnostic tests, including their successful clinical development. Importantly, both of Third Wave’s HPV tests secured FDA marketing clearance, in addition to the Company’s InPlex cystic fibrosis test. .
Adding further value to the Company’s non-invasive sDNA CRC screening IP, the results of a population-based, case–control study published in the medical journal, Annals of Internal Medicine, concluded that colonoscopies may actually prevent 60%-70% of CRC, rather than the previously quoted rate of 90% for the test. While colonoscopies are still effective at preventing CRC and will continue to be widely recommended and used; the study highlights limitations of the procedure - especially in the detection of flat and right-sided lesions, with the latter accounting for about 40% of all CRC cases.
The potential for an effective, non-invasive CRC screening test for the average risk population is also a global opportunity as a report concluded that the E.U. needs to double the current rate for cancer screenings in order to reduce preventable deaths. The report calls on the 27 member countries to improve large-scale screening programs for target groups regardless of their symptoms, and only 12 member countries currently have programs for CRC screening.
Pap Screening has reduced cervical cancer mortality by 74% from 1955-1992 (with less than 4,000 deaths per year now from the disease. Characteristics for a successful screening test in the setting of oncology include the following: (1) the test must detect both cancers and pre-cancers; (2) regular testing intervals to allow for the removal of tumors without the need for chemotherapy; and (3) the removal of pre-cancerous lesions to reduce the occurrence of disease and overall mortality. Only sDNA-based screening tests allow for the non-invasive, patient-friendly detection of both cancers and pre-cancers, which can be combined with colonoscopy + pre-cancer removal for a drastic reduction in CRC mortality.