The Pierian Spring Blog
Written by: Steve Piccoli, Chief Science Officer
Recent published results (AACR 2018 and NEJM) from the Merck KEYNOTE-189 trial in non-squamous non-small cell lung cancer (NSCLC) proved to be very exciting in the world of oncology. The study showed that patients treated with pembrolizumab (Keytruda™) plus chemotherapy had significantly longer overall survival (OS) and progression-free survival (PFS) compared with those who received chemotherapy alone, meeting both its primary endpoints.
Great news for patients! But, could this be even better news?
Pierian Bioscience’s ChemoINTEL platform is designed to determine the sensitivity of tumor cells to an array of chemotherapeutic drugs, including the two (carboplatin and cisplatin) chosen at the discretion of the treating physician in the trial. Neither drug is 100% effective in treating NSCLC, but one may be more or less effective than the other in an individual patient. Rather than assigning the drug by chance as was done in this study, if quality information regarding the activity of both is available before treatment is even begun, such as that generated by ChemoINTEL, then the more appropriate and effective therapy can be directed to the patient. This would have the effect of improving patient outcomes and the overall success rate of the therapy—let alone improving the results of the clinical trial.
Analogously, ImmunoINTEL was devised to inform on the detailed immune response state of the tumor undergoing treatment. This is important as the immune response to tumors is quite complex. Normally, cells of the immune system can inhibit tumor growth and progression through the recognition and rejection of malignant cells, a process referred to as immunoediting. Frequently, tumors have altered the normal immunological responses in order to escape detection and elimination. This can also promote tumor cell growth and survival through the induction of oncogenic inflammation. Thus, a more detailed analysis of the relationship between tumors and the immune system can help to determine which immune-oncology drug might be most effective, and whether or not a particular patient will respond to the biotherapeutic of choice.
Together, ChemoINTEL and ImmunoINTEL may help to positively impact the approach to cancer treatment for both patients and providers in an effort to deliver on the promise of personalized medicine: the right treatment for the right patient at the right time.
In June 2017, clinical staff from Pierian Biosciences attended the annual meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, IL. The ASCO annual meeting brings together approximately 35,000 oncology professionals from around the world to present and discuss the results of the latest cancer research trials, potential new therapies and diagnostics, and state-of-the-art treatment options. In short, ASCO offers attendees informative educational and scientific sessions that highlight the latest in cancer research and treatment.
Three overarching themes of the ASCO meeting revolved around the increased push for personalized medicine; most notably, using advanced diagnostics to find the right drug for the patient at the right time, as well as significant progress being made in the areas of “targeted” therapeutics and immuno-oncology. For the second consecutive year, ASCO President Dan Hayes, MD remarked that a bad test or a bad biomarker is as bad or worse than receiving an ineffective drug. Hayes went on to explain that any diagnostic test that “inappropriately” directs an oncologist to give a patient a certain therapy can result in denying that patient an effective treatment.
There were active discussions regarding the need to improve clinical trial designs to ensure that the appropriate population is being studied. On the topic of clinical trials and personalized medicine, researcher Andreas Du Bois presented his team’s recent findings from their randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in patients with recurrent ovarian cancer—a study with conclusions that align with Pierian Biosciences’ mission, vision, and product development.
In the study, patients with recurrent Epithelial Ovarian cancer were randomly selected to receive surgery to remove the tumor followed by standard of care chemotherapy or only chemotherapy. The conclusions indicate that patients receiving the secondary debulking surgery seemed to fare better and have lower morbidity rates than those without surgery.
The goal of personalized medicine is not just to guide the initial treatment of each patient’s cancer, but instead personalization is needed for each cancer recurrence in the same patient. For many patients, cancer may be a chronic condition that they will fight their entire lives.
At Pierian Biosciences, we are developing a chemosensativity assay, ChemoINTEL, to test tumor tissue and accurately predict its response to a variety of chemotherapy drugs. Using multiple markers, the ChemoINTEL assay is designed to measures the in vitro apoptotic response of a patient’s tumor to a variety of chemotherapy drugs in an effort to determine the tumor’s sensitivity within 72 hours of the tissue’s arrival in the lab. With a cancer recurrence, oncologists must be able to quickly and accurately personalize the treatment again, while pushing aside the knowledge of any prior treatment success, because the new tumor may well have different biology than the previous tumor. The ChemoINTEL assay can test tumor tissue at each recurrence to reveal its sensitivity and to significantly influence the resulting treatment regimen(s).
Any follow-up data and subsequent studies on the recurrent ovarian cancer study will help to determine how the second-line treatments fare in the long term. This study may spur similar trials in other recurrent solid tumors and further emphasize the need for personalized diagnostics and treatment with each recurrence.
Complementing the ASCO meeting’s push for personalized medicine and the recurrent ovarian cancer study results, Pierian Biosciences’ platforms (ChemoINTEL, PathwayINTEL and ImmunoINTEL) are being designed and tested to deliver specific, actionable, personalized information regarding the most appropriate cancer treatment for each patient and each tumor. Pierian Biosciences is focused on enhancing the quality of life for cancer patients by providing actionable information to allow personalized treatment every time cancer occurs.
What we learned from ASCO 2017
Former Vice President Joe Biden’s cancer moonshot may have to wait, due to proposed cuts in the National Institutes of Health (NIH) budget. But for the more than 30,000 cancer researchers, biopharma executives, investors, and public health officials who gathered at the annual meeting of The American Society of Clinical Oncologists (ASCO) recently, there’s still plenty of reason for optimism in cancer treatment. Here’s what caught our attention at ASCO 2017:
Drug combinations may seem random now, but more are embracing it as a treatment model
If one is good, two or three seem to be better. While immunotherapy holds great promise, what looks even more promising is combining therapies, whether it’s two immunotherapy medications together or putting them together with more conventional treatments like chemotherapy and radiation. However, there’s a level of randomness to the combinations put forward that bears further scrutiny. The combinations haven’t been shown to be effective in a majority of patients, and the approaches, according to some, “are a bit like throwing spaghetti at the wall to see what sticks.” Most researchers agree the combination approach, while still in need of greater refinement, is a worthwhile pursuit for cancer treatment.
Medicaid expansion states saw earlier diagnosis of colorectal cancer (CRC)
CRC is often asymptomatic in its earliest and most treatable stages. Screening is critical for bringing down the mortality rate of one of the country’s deadliest cancers. In states where Medicaid expanded, thus expanding the number of people eligible for having their CRC screening covered by the Affordable Care Act, there were earlier diagnosis rates for CRC. While the ACA is headed for an overhaul, cancer researchers were encouraged by the trend.
“Financial toxicity” plagues patients and their families
Cost is a bigger issue than ever – it even has a new term: financial toxicity. Duke University’s Yousuf Zofar, MD, MHS, an associate professor of medicine, has studied the financial effects of cancer care on patients and their families, and finds that they can be just as damaging as the cancer itself. According to the American Journal of Managed Care, results of a panel discussion moderated by Dr. Zofar emphasize the need for the cancer treatment community to come up with a single solution for financial toxicity.
Precision medicine is a promise not yet delivered
Pierian Biosciences is uniquely focused on developing treatment-directing assays that help clinicians target exactly which chemotherapeutic, targeted agent, biologic, or immunotherapeutic agents kill a specific patient’s cancer cells. These assays offer the hope of truly individual, personalized cancer treatment plans. But at ASCO, there was a lot of discussion about how “precise” precision medicine actually is at this time. Larotrectinib, as pointed out by Health News Review, received a lot of attention at ASCO. The new drug showed that “76 percent of patients had tumor shrinkage across 17 different types of tumors. Of those with tumor shrinkage, nearly 80 percent did not have the original tumors rebound — or any new tumors grow — after a year of therapy.” The drug has received Breakthrough Therapy Designation from the Food and Drug Administration (FDA). But tumor shrinkage is only one of many data points to capture in determining the drug’s overall effectiveness. Benchmarks such as median progression-free survival, median overall survival, or duration of response still need to be determined.
There’s reason for optimism
Siddhartha Mukherjee, author of “The Emperor of All Maladies” and “The Gene,” encouraged the ASCO audience to see the silver lining in some of the uncertainty surrounding the future of cancer treatment. From an article in the Washington Post, Mukherjee spoke with hope for the future: “Cancer treatment is entering a promising, if challenging, adolescence…and his fellow oncologists, after years of being hamstrung by a lack of technological tools and treatments, now have therapies to deploy in a thoughtful, reasoned and compassionate way. ‘Always keep in mind, Mukherjee urged the physicians, what it feels like to be a patient in this world.’” We at Pierian Bioscience are dedicated to developing very accurate and reproducible treatment-directing assays that will fulfill the promise of personalized medicine: the right drug for the right patient at the right time. We are focused on helping clinicians target exactly which chemotherapeutic, targeted agent, biologic or immunotherapeutic agent(s) will be most effective against a specific patient’s tumor to allow the physician to truly individualize or personalize each patient’s cancer treatment plan.
In late February, the American Society of Clinical Oncology (ASCO) partnered with the Society for Immunotherapy of Cancer (SITC) to host the first ASCO-SITC Clinical Immuno-Oncology Symposium, held in Orlando. We learned, along with 1000 other attendees, about the leading clinical research regarding immunotherapy (IO) treatment and the exciting, yet, gradual move from IO research to actual patient application.
The concept of immunotherapy, using the body’s immune system to help fight cancer, is making tremendous strides in today’s cancer research. In just the last five years, research has proven that manipulation of the immune system can control, or in some cases, completely eradicate tumors. As chemotherapy, targeted therapy, radiation therapy, and surgery are used to aggressively destroy cancer cells, with IO, researchers are working to develop strategies to harness the body’s own immune system to combat cancer. When the immune system is strengthened, risk on the patient’s long-term health is reduced in comparison to more aggressive cancer treatment approaches.
What happens when IO therapy is combined with traditional treatment approaches? The potential for positive outcomes in the oncology field grows even more substantially. Researchers have been testing immunotherapy as one component in combination cancer treatment, and the idea is gaining traction. At ASCO’s symposium, many presenters mentioned the theory of the “abscopal effect” (ab meaning “away from,” and scopus meaning “target”), a term coined in the 1950s to describe the phenomenon when treating metastatic cancer with radiation. The abscopal effect occurs when the localized treatment of a tumor causes not only a shrinking of the treated tumor, but also a shrinking of other tumors outside the scope of irradiated area. In 2015, EB Golden and colleagues ran a clinical trial which demonstrated that abscopal responses were consistently detected in patients treated with the combination of radiation therapy and immunotherapy. In practice, a breast cancer patient receiving IO combined with radiation has been shown to demonstrate a positive response on a spinal lesion or other location in addition to the irradiated tumor. The thinking is that radiation primes the immune system to recognize tumor-specific targets as those cells die, which is then translated into a systemic effect.
Research combining chemotherapy and immunotherapy was also presented and discussed. To change the tumor’s microenvironment, researchers are using doses of chemo to destroy cells that are blocking the immune system from functioning, instead of using the dosage required to kill cancer cells. This process converts the “unresponsive” cancers to responsive, allowing immunotherapy to work effectively.
But what dose and schedule of chemotherapy is enough to kill the cells blocking the immune system, yet not so strong that it wipes out the body’s defense mechanism? Which cytotoxic is best, what is the best dose and schedule, is this approach beneficial for all tumor types and all patients? Which patients would respond better to a combination of immunotherapy plus chemotherapy as opposed to those who would fare better with one treatment or the other? There are clearly more questions than answers at this time.
At the symposium, a recognized leader in the field, Lisa Butterfield, led a session on “Immune Biomarkers in the Blood” featuring research findings on immune biomarkers and their ability to offer insight into the interactions between the immune system and cancer. These interactions can help to define which immunotherapy should be selected to best defend the body using its immune system.The current research focus is on finding markers that suggest a patient will respond to any immunotherapy (IO), rather than using the biomarker to determine which IO would work best for their specific tumor and cancer.
The more we know, the better the outcome. At Pierian Biosciences, we’ve invested years of research in developing a series of functional assays including our latest platform, ImmunoINTEL. The ImmunoINTEL platform is being developed as a functional I-O platform incorporating information from intra-tumoral as well as peripheral immune mediators that will predict which immunotherapeutic will be of greatest benefit for each individual patient. Our goal is for the information provided by the assay to deliver the intelligence needed to determine which treatment or combinations of treatment will be most effective based on a patient’s actual tumor response in the lab, before introducing the treatment to the patient. A functional assay should more precisely predict a cancer treatment outcome and thereby increase efficacy cut costs by eliminating ineffective treatments, avoid the toxicity associated with ineffective therapies and improves the patients overall quality of life, resulting in a more effective and successful treatment experience from day one. We call that a win/win.
Immunotherapy is making great strides in the treatment of cancer, evidenced by the fact that the ASCO-SITC Immuno-Oncology Symposium drew 1,000 of us who came to listen. At Pierian, we too, are embracing immunotherapy by providing the tools that oncologists need to develop customized treatments that result in significantly improved treatment outcomes.:
 Winslow, R. Cancer’s Super-Survivors/How the Promise of Immunotherapy Is Transforming Oncology. Wall Street Journal. Dec 4 2016.
 Disis, M.L. & Kaufman, H.L. Cancer Immunotherapy: The End of the Beginning or the Beginning of the End. Ummunsym.org Daily News, published February 17, 2017.
 Mole, R.H. Whole body irradiation; radiobiology or medicine? Br J Radiol 1953; 26:234-41. 10.1259/0007-1285-26-305-234
 Golden EB, Chhabra A, Chachoua A, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 2015;16:795-803. 10.1016/S1470-2045(15)00054-6
 Thaker, P. H. (2017, February). Phase I study of the safety and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer. Poster session presented at the ASCO-SITC Clinical Immuno-Oncology Symposium, Orlando, FL. Retrieved from: http://meetinglibrary.asco.org/content/178595-194
 Nyberg, K. (2017, February 24). Leveraging Immune Biomarkers in the Blood to Guide Immunotherapy—Current Application and Future Prospects [Daily News]. Retrieved from http://immunosym.org/daily-news/leveraging-immune-biomarkers-blood-guide-immunotherapy-current-application-and-future
CLIENT: Pierian Biosciences
DATE: February 17, 2017
PROJECT: PR – Blog post – Response to FiercePharma article
Author: Robert Henry
A recent FiercePharma article on the top 15 cancer drugs for 2022 predicts they will total nearly $90 billion in sales. That’s a big jump, considering global spending on all cancer drugs was $107 billion last year. Immunotherapy-based drugs, largely described as checkpoint inhibitors, are a big driver in these price increases. According to FiercePharma, “This brand-new category of cancer drugs works by activating the immune system, enabling it to recognize cancer cells and destroy them. The class of drugs has achieved unprecedented efficacy in a broad range of cancers and provides a much-needed new treatment approach alongside chemotherapy and targeted cancer drugs, which tend to lose efficacy over time.”
The emerging field of immuno-oncology shows great promise, despite the high price of immunotherapy drugs. That’s not the case for some chemotherapy agents. According to a study in JAMA Internal Medicine, several chemotherapy drugs did not to offer the long-term survival rates to justify their high price.
For cancer warriors – clinicians, patients and researchers – it’s time to deploy new weapons in the fight against cancer. We’re entering this fight with technology platforms based on the MiCK and CEER assays, now renamed ChemoINTEL and PathwayINTEL respectively, to help clinicians identify the most effective targeted therapy for cancer patients. They provide patient-centric, personalized intelligence on the effectiveness of chemotherapy and targeted therapy treatments, to help support clinical decision-making and drug development. Our strategy is to conduct clinical studies to support regulatory approval of these platforms by the Food and Drug Administration.
Cancer isn’t going away. Chemotherapy drug prices aren’t going down. Providers and researchers need more tools in their toolkit. At Pierian, we’re working hard to bring our treatment directing diagnostics to transform the cancer treatment experience for cancer patients across the globe.
Client: DiaTech Holdings/Pierian Biosciences, Inc.
Date: September 21, 2016
Project: PR – Op-Ed: Response to New Clinical Trials Requirements from HHS
Cancer deaths have declined substantially in the past decade. According to the National Cancer Institute, from 2003 to 2012, cancer deaths rates decreased by 1.8 percent per year among men, 1.4 percent per year among women, and 2.0 percent per year among children. While these are certainly promising developments, cancer isn’t going away any time soon.
For many cancer patients, hope for a cure lies in the results of clinical trials, which might point to newer, more effective treatments. The 2016 announcement from the Department of Health and Human Services, which calls for making information about clinical trials more widely available, offers these patients a ray of hope. It improves people’s ability to find clinical trials in which they may be able to participate and access investigational therapies.
As a member of the biotech community, I’m delighted about the new requirements. No matter what the results might be, the more clinical trial information is shared, the faster we develop transformational diagnostic tools and therapies.
These requirements coincide with our own clinical trials journey. Our technology platforms based on the MiCK and CEER assays and now renamed ChemoINTEL and PathwayINTEL respectively, help clinicians identify the most effective targeted therapy for cancer patients. They provide patient-centric, personalized intelligence on the effectiveness of chemotherapy and targeted therapy treatments, to help support clinical decision-making and drug development. Our strategy is to conduct clinical studies to support regulatory approval of these platforms by the Food and Drug Administration.
Prior to the new rules going into effect, the sharing of summary results for clinical trials was inconsistent. Effective January 18, 2017, summary results must be posted within a year of a trial’s completion, even if the product being tested is not yet FDA-approved.
This is a step forward for patients and their families looking for promising new treatments. According to FDA Commissioner Robert M. Califf, M.D., “When people participate in clinical trials, they are volunteering to create generalizable knowledge to help others in the future and we want their participation honored by ensuring that the existence of trials and their results are available to all patients and their healthcare providers, as well as researchers.”
Some in the biotech community may be wary that all this transparency might interfere with their proprietary solutions. But clinical trials are everyone’s risk, responsibility and ultimately, reward.
The more information we share, whether positive or negative, the more we can drive down the cancer death rate even further. That’s good news for everyone.
.Robert Henry is the president and chief executive officer of Pierian Biosciences
Cancer. The numbers tell the story. 1.6 + million people diagnosed this year. National expenditures for cancer care totaling nearly $125 billion. Significant advances in the last thirty years of creating standards of care for many diseases. Effectively treating cancer goes beyond a standard approach. Welcome to the era of personalized medicine; treating patients as individuals, a therapeutic, biomarker-based approach emphasizing the use of personal genetics. Now imagine taking this method one step further. Curating actionable information related to the targeted treatment, delivered directly to physicians.
A powerful combination of data, bioscience, art and intelligence.
We are Pierian Biosciences. Our mission is profoundly changing the cancer treatment experience for patients and providers.
Our name, a Greek mythology reference to a metaphorical knowledge source of art and science. Our company is Inspired by Dr. Paul Kalanithi’s indelible book “When Breath Becomes Air”, detailing his relationship with medicine, through the moment of diagnosis and then treatment. The precision used as he writes about the first time he looked at his scans and the terrible time when his oncologist is away, treating him as a problem, not a patient. Denied the medicine he needs by a resident who provided the “standard of care.”
Pierian Biosciences model and innovative approach are rooted in individuality. Integrating an individual’s response and the variability in their individual instance of cancer to determine the right course of treatment. Taking the data one step further, Pierian gathers information throughout the entire treatment process, from diagnosis to recurrence. Providers now have a wealth of information, beyond the average and genetic profile.
Harvesting that information and measuring cancer cells in real-time is what matters. Breakthrough medicine. The right information, served at the right time, leading to predictive and personalized cancer treatments.
Customizing cures based on the person, not the disease. Measuring molecular changes in cell structures over a 48-hour period, providing physicians and clinicians feedback as to what chemotherapies may predict positive outcomes. Real-time, actionable information.
We are Pierian Biosciences. Personalized Cancer Intelligence.