biomarker development

Returning to Old Biotech Model, OncoMed Boasts of Seven Drugs in Clinical Trials by Mid 2015

For many years, the trend in biotech was for drug development companies to pursue one or maybe two drug candidates, or assets, as they’re called in industry parlance. Go lean and attract the attention of big pharma or investors in the late stage trials. But today’s guest says there is more innovation when the biotech organization invests in a technology platform that produces multiple drug candidates. Paul Hastings is the CEO of OncoMed, a company developing drugs that target cancer stem cells. He’s built OncoMed in what he says was the old model. By mid-2015, the company will have seven drug candidates in the clinic.

"There was a period of time when investors were only interested in late stage products that they could put their arms around and measure,” he says. "But I think investors woke up. . . .They realized that the innovation part of what we were doing before was suffering from this model.”

OncoMed was one of the first IPOs of the current bull market. Has Paul changed his management style since going public? Does he buy into the virtual drug development model? And what does he see for the industry in 2015?

In Autoimmune Disease, Finding Clarity Beyond the Genome: Stefan Muellner, Protagen

Today we bring you a story which fits nicely in the vein of personalized medicine. But this time with a twist.

We talk with the CEO of Protagen, a company that has developed a platform to find new biomarkers for disease, particularly autoimmune diseases such as SLE, or Systemic Lupus Erythematosus. But the platform is based on the hunt for genetic mutations. Rather the company is using antibodies, or proteins to better define disease and disease populations. The company is able to stratify auto-immune diseases better than we’ve done with genomics.

Protagen is in Dortmund, Germany and has recently announced a partnership with the German diagnostics powerhouse, Qiagen. Stefan Muellner is the CEO of Protagen. In today’s program he explains how his company’s unique protein library and platform will drastically improve treatment for autoimmune disease.

The Sad State of Biospecimen Science with David Rimm, Yale


David Rimm, Professor of Pathology, Yale University School of Medicine Bio and Contact Info

Listen (4:16) An unsexy science

Listen (5:36) A lack of certifications

Listen (6:20) Most pathologists not aware of the problem

Listen (2:48) Pathologists not reimbursed for providing research samples

Listen (7:44) Still no Tissue Quality Index

The next stop in our journey to better understand the impact of poor biospecimens on biomedical research takes us to Yale where we talk with pathology professor, David Rimm, about the new science of biospecimens.

In past interviews we’ve established the importance of better standards in the collection, handling and storage of biospecimens. David has developed some rare and unique training at Yale for the students of pathology, but still, he says that biospecimen science has not really taken off.

“Most scientists and pathologists are not aware of this problem,” says David, referring to the issue of sample degradation.

How is it the case that billions of dollars are spent studying samples that were not collected with any standards? Why are there no certifications for pathologists in this regard?

One thing that would help immensely and has been long hoped for is an assay that would tell whether a sample is still good, what David calls a Tissue Quality Index. Perhaps a researcher or pathologist does’t know where a sample came from or how long it’s been in storage. This Tissue Quality Index would be a scoring system for determining whether the sample could still be used for an application. David got a grant to develop the score, but didn’t quite get there with the one grant. He applied for another grant, but it was turned down. Regrettably, he says, it’s just not an important topic for traditional funders.

The holy grail of biospecimen science, a Tissue Quality Index, remains still to be grasped.

Podcast brought to you by: Quintiles - bringing people and knowledge together for a healthier world.

And by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

Cancer 2014: The Year in Review with Anna Barker


Anna Barker, Co-Director, Complex Adaptive Systems Center, ASU Bio and Contact Info

Listen (3:21) Andy's challenge

Listen (4:39) The year of immunotherapy

Listen (4:53) iSpy 2 and a new approach to clinical trials

Listen (6:42) The swan

Listen (6:35) A coalition of the willing

Listen (5:14) Six reasons biomarkers fail

In 2003, the then Director of the National Cancer Insitute, Andrew von Eschenbach, issued a challenge: “to eliminate the suffering and death from cancer, and to do so by 2015.”

Anna Barker is the former Deputy Director of the National Cancer Insitute, and she was at the meeting when Dr. von Eschenbach issued his challenge. Now at the end of 2014, we talk with Anna about the challenge and how far we have come. She offers her vote for the three most important developments in cancer this past year.

The Impact of Biospecimens on Clinical Study Design

We perform therapeutic and diagnostic clinical trials to learn the safety and efficacy of drugs and tests in a clinical setting.  Typically, we think about the biospecimens in a clinical study in terms of operational requirements such as sample collection, processing, storage and analysis.  Our ability to obtain and test high quality patient samples is an important consideration during the design of clinical research programs and may significantly limit the questions that we can ask in trials. 

For example, our ability to develop drugs for precision medicine in diseases such as cancer depends on access to high quality samples.  The fundamental elements of a trial are the objectives--what questions we intend to address--and the endpoints--what will be measured to answer those questions.   Trials are also defined by the patient population or the inclusion and exclusion criteria determining who is enrolled.   Successful clinical studies require careful planning and design of the study protocol to ensure that the study is feasible and that we capture the lessons learned.  Often, endpoints rely on patient samples for laboratory testing. 

Patient enrollment may require rapid laboratory testing for a molecular or genetic alteration to meet the inclusion criteria.  Researchers also collect patient samples for long term storage for future analysis in the hope that advances in technologies and disease knowledge will open new opportunities.  These study endpoints require robust biospecimen planning during the early development of research programs all the way through to the medical writing of the study protocol.   Study planning is typically based upon experience and expertise.  However, the industry is more frequently utilizing best practices and data-driven analytics and modeling. These tools will improve our planning and preparations for biomarker-driven trials that require biospecimens.

Targeted therapeutics and drug candidates that will rely on patient laboratory test results are becoming common in oncology and other diseases.  Diseases are also being reclassified by molecular biomarkers and complex laboratory tests.  As a result, the biospecimen considerations that have been discussed in the ongoing Biospecimen Series at Mendelspod are becoming critical success factors for drug development. 

In the planning stages we often would like to target a small patient population who may greatly benefit from a new drug compared to the general population.  We then have to ask if we can identify, test and enroll those patients if the samples for testing are difficult to obtain or unstable for shipment and testing.  Similarly, we may have a novel drug with a new mechanism of action that promises to address a critical clinical need.  In this situation we are often limited by the test to certain sample types that may cause a great deal of patient inconvenience or duress.   Difficulties in obtaining  repeated tumor biopsies is one example that has resulted in the development of tests that rely on surrogate samples that may be obtained from the blood.  These considerations often restrict many of our options for study designs include choice of diseases, patient populations and regions or clinical sites. These restrictions also impact the patient journey in the trial. 

Trial protocols summarize the collection and use of samples in a table or schedule of events or assessments.  What may appear to be a simple table, ultimately impacts the patient experience and determines trial feasibility and success.  Researchers must balance the potential knowledge gained, time, cost and risk to maximize the benefit of the study to current and future patients.  Biospecimen planning is increasingly an important part of this equation.  The Mendelspod series Back to Basics: Improving Biospecimens supports a greater understanding of the challenges and opportunities for improving how we utilize critical patient samples.  These improvements will also enable more powerful clinical studies, addressing challenging clinical questions and advancing novel drugs and diagnostics.

Historic Consensus Reached on Biospecimen Standards: Carolyn Compton, NBDA


Carolyn Compton, Professor of Pathology, ASU Bio and Contact Info

Listen (4:54) A historic new consensus

Listen (6:33) CAP committed to enforcement

Listen (2:50) Five core variables

Listen (5:16) Non-governmental leadership

Listen (4:20) Problem unique to biomedicine

Listen (3:25) Ramifications for our audience

Listen (4:48) Does this mean more work and higher prices?

A unique event happened at ASU last week that has the potential to positively impact all of biomedical research and therefore patients.

Carolyn Compton has been a tireless crusader for higher standards in biospecimen collection, handling, and storage. (See our interview earlier this year with Carolyn here where she argues that uneven sample quality is a major reason that biomedical research has such poor reproducibility rates.) Beginning as a pathologist herself, Carolyn has served at various organizations, including a stint at the National Cancer Insitute, which have prepared her for a special leadership role on the topic of biosamples. Last week she saw her long time dream come true.

“I’m delighted to report that we did in fact come to consensus after four days of discussion on what standards would be needed to raise the quality of ALL biospecimens from ALL patients to a standard that would be acceptable—perhaps not optimized—transparent and of known quality level for all patient samples. This is huge!” Carolyn exclaims in today’s show.

What does Carolyn mean by consensus? As we’ve been uncovering in our recent series on the topic, there have been no uniform standards in the collection, handling, and storage of biospecimens. It’s all been done with “poetic license” Caroly says. Until now. Last week Carolyn and a very special organization at ASU known as the National Biomarker Development Alliance put on two “convergence conferences” back-to-back that brought the major stakeholders—pathologists, physicians, patients, tool makers, and regulators—together AND found broad agreement on five basic standards to improve biospecimen handling.

This is indeed huge. Because the President and President Elect of the College of American Pathologists attended the conferences and committed to enforce these five basic standards in all of the labs which they accredit.

In her ebullience, Carolyn is careful to say that this is just the beginning, that the standards must now be written out and optimized. But it’s a very strong beginning which will have ramifications throughout the industry.

Who will be most affected? Patients, Carolyn says. Because tests, such as the popular HER2 assay for breast cancer, will be more accurate.

This story is not only unique in how it will change the course of the industry, but a powerful example of how non-governmental leadership can effect much needed change.

Podcast brought to you by: Quintiles - bringing people and knowledge together for a healthier world.

And by: Fluidigm - Make your biobank a quality research partner. Download the Evolution of Biobanking whitepaper today.

Janet Woodcock, FDA, on Biomarker Development and the Future of Clinical Trials


Janet, Woodcock, MD, Director, CDER, FDA
Bio and Contact Info

Listen (4:41) No agency charged with better translational outcomes

Listen (2:46) How will recent FDA move on LDTs impact biomarker development?

Listen (4:45) Lung Map and the future of clinical trials

Listen (3:07) What about trials of one?

Listen (4:12) Translation not just about getting to Phase I

Listen (1:49) How important are biosampling issues?

Listen (2:50) Diagnosis the foundation of medicine

Listen (2:25) Thoughts on drug pricing debate

Since becoming the Director of the Center for Drug Evaluation and Research at the FDA, Janet Woodcock has been a strong advocate for better science. But the FDA’s job as regulator is to protect and promote health, not particularly to focus on improving the process of drug development. In fact, Janet points out, there is no agency “charged” with better translational outcomes.

For this reason, Janet worked to set up the Critical Path Initiative some years back. This would be a program to bring together a consortia of different organizations to primarily focus on better biomarker development as well as to modernize clinical trials.

Today we ask Janet for an update on the program. Are we getting better biomarkers? And what do the clinical trials of the future look like?

“In the future, we’ll be setting up trials around patients and disease rather than setting up a trial around a drug,” she says in today’s interview. “We have too many questions to answer about treating disease than can be done by serial trials, each one one only addressing a question about a single investigational drug.”

She’s particularly excited about a new Lung Map trial being run by the NCI. This trial is about finding a second line treatment for patients with squamous cell lung cancer. Patients are enrolled into one of five different strata based on the biomarkers of their tumors. This is a trial that can go on and on, where if a patient doesn’t respond to one treatment, this patient can be moved to a different therapy. This type of trial is known as an adaptive trial and has strong support from the FDA.


What are Janet’s thoughts about "trials of one," where the health of the patient in the trial is more important than some future unknown patients as advocated by former guest on the program, Marty Tenenbaum?

And what does Janet think about the translational work of physician scientists who are enrolling their own patients in clinical trials based on those patients' biomarkers?

We explore with Janet the question of why diagnostics are valued so much lower than therapeutics in our culture. And at the end of the interview she offers some brave, if limited, comments about the current debate over drug pricing.

Podcast brought to you by: National Biomarker Development Alliance - Collaboratively creating standards for end-to-end systems-based biomarker development—to advance precision medicine

What Translational Gap? Michael Pishvaian on Advances in Tumor Profiling


Michael Pishvaian, Assistant Professor, Georgetown University; CMO, Perthera 

Bio and Contact Info

Listen (4:08) Untapped potential

Listen (6:24) What is the biggest challenge in the biomarker development process?

Listen (7:54) Taking personalized medicine to hospitals everywhere

Listen (5:30) Must do better in assessing value of personalized medicine

When we talk about personalized medicine, we often hear that doctors are out of touch with the latest research, particularly those not at major medical research universities. Not so, says Michael Pishvaian, researcher and doctor at Medstar Georgetown University Hospital.

Our first guest in a new series, "Democratizing Personalized Medicine: Advances in Tumor Profiling," Michael says that in the last two years the “retailization" of diagnostic tools has made personalized medicine for cancer available to all doctors.

Spending sixty percent of his time in research and forty percent seeing patients, Michael is involved in the entire flow of biomarker development, from discovery to patient care. His specialty is in GI cancers, where there is “an untapped potential for using biomarkers.” When Michael finds biomarkers that are useful to target a therapy, he’s immediately able to enroll his patients in a clinical trial.

But Michael works at a major research hospital. What about those doctors working in community hospitals?

Michael argues that all the new research on tumor biomarkers is being made available at the community hospital level.

“In just the last two to three years there has been a real explosion of retail diagnostic/molecular testing companies that have the capacity to give as much, if not more, genetic and molecular information about a patient’s tumor than can be found at any major institution,” he says.

Michael is the CMO for one such private company, Perthera, which is offering the latest in tumor profiling to doctors everywhere through their "virtual tumor board."

“I don’t think doctors are out of touch. . . . It’s not so much that they don’t have access or the knowledge base for personalized medicine. It really just has to do with time and effort and first hand experience to know how to put it all together,” he says.

The Lowdown on Adaptive Clinical Trials with Don Berry


Don Berry, Prof of Statistics, MD Anderson Cancer Center
Bio and Contact Info

Listen (5:39) What is the goal of I-SPY trials?

Listen (8:31) Why were adaptive trials not introduced sooner?

Listen (4:34) What is the latest from I-SPY 2?

Listen (3:06) What about other cancers and diseases?

Listen (3:51) We have barely scratched the surface with biomarkers

Listen (2:34) Thoughts on genetic testing space

Listen (2:35) Trials of one?

The development of therapeutic drugs is a lengthy and costly process and too often ends in failure during clinical trials. So, understandably, there is much interest in improving clinical trial design to take into account the individual biology of trial participants. This more precise approach not only has great potential to improve the chance for the therapy to succeed, it provides better outcomes for patients in the trial.

The I-SPY trials are just such an approach. These national studies are designed to identify biomarkers predictive of response to various therapies throughout the treatment cycle for women with breast cancer. These trials are being called adaptive because there are changes in design throughout the trial based on an examination of accumulated data at various interim points in the trial. A patient may start with one therapy, but end up in the same trial with another therapy.

Don Berry is the founding head of the division for Quantitative Biosciences at MD Anderson Cancer Center. He is one of the principal designers of the I-SPY trials.

Are there trials in progress for cancers other than breast cancer? Will adaptive trials be broadly adopted? How can we develop better biomarkers?

Join us today in learning about this promising new approach to clinical trials directly from one of the principal architects.

Podcast brought to you by: National Biomarker Development Alliance - Collaboratively creating standards for end-to-end systems-based biomarker development—to advance precision medicine