clinical trials

The Current State of Coronavirus Vaccines with Jeff Stein, Cidara Therapeutics

What is the key to getting a coronavirus vaccine? “Manufacturing,” says today’s guest, Jeff Stein of Cidara Therapeutics.

Jeff joined us just last fall to talk about his company’s exciting new technology, an immunotherapy, that is a universal flu preventative and therapy. Yes, you read that right. A universal flu preventative.

So we were eager to have Jeff on the podcast again and ask the burning $64 million question: Will Cidara’s technology work on the coronavirus? Indeed, it will. Jeff says the company has a clinical development candidate, CD377, which will work on all members of the coronavirus family.

While Jeff is here, he gives an update on the various vaccine programs going on around the world, including the mRNA product we all heard about this week from Moderna Therapeutics.

Is Jeff as optimistic as President Trump about having a vaccine by end of year?

“It’s possible, but not probable.”

Cancer: Year in Review 2015 with Anna Barker

As we begin the countdown to the new year, we take a look back at 2015 in cancer research, treatment and prevention. Mendelspod is increasingly becoming known for the coverage of genomics and precision medicine, and cancer as a disease area offers a specific window whereby we can look at practical outcomes.

Anna Barker is the director of the National Biomarker Development Alliance (NBDA). Formerly the deputy director of the National Cancer Institute (NCI), she has worked on cancer her entire career and seen first hand the triumphs and setbacks. Last month at the National Press Club in Washington, D.C., Anna announced the creation of GBM-AGILE, a new kind of clinical trial for a very tough, rare cancer, glioblastoma multiforme. The project is the culmination of the work of Anna and many others to come up with a better system for validating biomarkers. This single trial is a global endeavor and already becoming a "movement" in cancer research with over a hundred and forty experts getting involved. Folks at the FDA are saying that GBM AGILE “raises the bar for clinical trials.”

Along with new ways of doing clinical trials, 2015 has also seen the explosion of new blood-based cancer tests known as liquid biopsies. Still mostly research projects, these tests will potentially offer patients a non-invasive alternative to expensive and painful solid tumor biopsies and offer the promise of someday improving cancer screening and prevention.

Immunotherapy drugs continued to dominate the list of FDA cancer drug approvals in 2015 with the first approval of an oncolytic virus therapy and the first approval of combination immunotherapy. In today’s interview, Anna reminds us that the recent breakthroughs in immunotherapy are the result of a 40 year journey. She goes on to question the herd mentality reflected in the over pursuit of certain targets.

Anna wraps up her review by pointing out the opportunity to go after rare cancers, such as GBM and some childhood cancers. She says the more common cancers such as the big epithelial cancers—breast and lung— are dauntingly complex with "gazillions of mutations.” But with rare cancers, “we can follow the genomic changes through to the cells, to the organs, and to the organism. I’m thinking that we should all begin to take a careful look at some of the rare cancers,” she concludes.

Is This the Future of Clinical Trials for Cancer? Stanley Hamilton on the NCI’s New MATCH Trial

It’s taken some time, but the NCI is finally sponsoring a big time clinical trial for cancer where the patients are organized by the genomic pathway that defines their cancer rather than the organ type.

"Instead of being a breast cancer trial, or a colorectal cancer trial, or the usual construct that’s been used, this one is obtaining biopsy specimens from patients with a whole variety of differing tumor types, evaluating them with a standardized platform to identify abnormalities, and then linking those abnormalities to arms in the trial with drugs targeted to those abnormalities. This is a completely new way of doing a clinical trial and becomes an important step in moving forward a precision medicine cancer therapy approach,” says today's guest, Stanley Hamilton, head of Pathology and Laboratory Medicine at MD Anderson Cancer Center.

How are the four centers participating in the trial going about selecting patients for this new trial? And what pathways does Stanley foresee dominating the trial?

Stanley’s lab has chosen to use Thermo Fisher’s Ion sequencers to characterize the patients’ genomic pathways. Why? Find out the answer to these questions in today’s interview with one of the leading PI’s for this unique clinical trial.

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.

The Daunting Task of Managing Biospecimens at the World's Largest CRO: Diane Farhi, Quintiles


Diane C. Farhi,, MD, Senior Medical Director, Quintiles Laboratories Bio and Contact Info

Listen (6:37) Tracking clinical samples around the world

Listen (5:34) How to measure sample stability

Listen (3:37) New software needed

Listen (5:07) Challenges from the increase in DNA sequencing

As we’ve been uncovering in our special series, Back to Basics: Improving Biospecimens, the issues around biosample collection, storage, and delivery here in the U.S. can be overwhelming. But Diane Farhi and her team have to manage on a global scale at Quintiles, the world's largest CRO. Who better to take us into the practical issues around sampling?

'Harmonization' is the name of the game in dealing with a global laboratory, says Diane, the Senior Medical Director at Quintiles. Diane and her team are dependent on a world wide delivery system, and that can bring with it many variables which impact samples.

“The whole issue of transport--how long it takes, what the temperature variability is within the package, impacts of alterations in flight schedules due to natural disasters and strikes and other event--all impacts the quality of our specimens when they finally arrive at one of our global laboratories,” she says.

In today’s interview, Diane shares some of the ways that the team at Quintiles mitigates the sampling issues that lie beyond their control. She also details some of the new challenges that have come with the dramatic increase in RNA and DNA sequencing.

Podcast brought to you 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

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

Biotech Superstar Seeks to Foster Collaboration in the SF Bay Area

Guest: Una Ryan, PhD, Chair, Bay Area BioEconomy Initiative

Bio and Contact Info

Chapters: (Advance the marker)

1:43 Returning to childhood mission

9:14 Improving the image of big pharma

10:54 Goals of Bay Area BioEconomy Initiative

21:50 Investing in women led companies

24:59 You need at least two women on the board

27:14 Honored by the Queen of England

When we first saw Una Ryan on an investor panel at last year's SynBioBeta, she immediately won us over with her unpretentious, even childlike simplicity combined with a powerful ease developed from years of experience. This life science superstar has done it all, from being researcher chipping away at tenure, to founding companies, to sitting on many organizational boards, including chair of MassBio for a decade.

In today's interview Una (pronounced Yu-na) talks about returning to the dream of her five year old self. As a girl in London she was inspired to a kind of "missionary zeal" by a television program about a man with leprosy. At that moment she decided that she wanted to cure the world of "these dread diseases."

After moving to San Francisco a year ago, Una has led the formation of the Bay Area BioEconomy Initiative (BAB), a non-profit with the aim of bringing together the life science crowd. The goal of BAB is now threefold: first, to create a single IRB that various institutions can adopt to speed up the process of clinical trials; second, to bring researchers and entrepreneurs together with experienced industry leaders; and third to focus on what happens to the startup after graduation from the incubator.

"I'm not a big believer in the fish model where you throw a lot of eggs in the sea and one or two survive," she says, likening the care of startups to natural reproduction. "I like the mammal model where you nurture people to adulthood."

As an investor, Una is keen on synthetic biology. The challenge with this sector is to come up with products that are useful to people, she says.

"I think the public doesn't want to hear about all the clever technology. They want to know what's useful, friendly, and cheap that they can use."

The conversation can go anywhere with Una, as she draws on such breadth of experience. We keep this interview under thirty minutes, but look forward to having her back to the program for more.

Podcast brought to you by: Your company name here. - Promote your organization by aligning it with the great content.

4 Reasons Clinical Trials Don't Work: Marty Tenenbaum, Cancer Commons


Marty Tenenbaum, Founder, Cancer Commons

Bio and Contact Info

Listen (4:28) Why Cancer Commons?

Listen (6:07) Four reasons why clinical trials don't work

Listen (6:57) How do we go about changing the system?

Listen (4:35) What do you mean by Rapid Learning Community?

Listen (4:48) What obstacles do Cancer Commons partners face in sharing more data?

Listen (1:24) The difference between a cancer researcher and a patient is a diagnosis

"At the end of the day, we're all patients," says Marty Tenenbaum, Founder of Cancer Commons, in today's interview.

Marty is a tough cookie. He's a survivor of metastatic melanoma--not a fun one--and he's been getting traction around the biomedical research industry.

Here's the thing. Marty's survival was really by chance.

Cancer has been called the "great equalizer," and Marty is fond of saying that "the only difference between a cancer researcher and a cancer patient is a diagnosis." He is on a mission to work with researchers, doctors, policy experts, and patients to improve the system so that success is not just an accident.

But how does one who is not a researcher or leader in the industry go about that? Marty sees the best opportunity in changing the way clinical trials work. In today's interview, he lays out four reasons why the current system fails patients. And he offers his ideas to fix it.

This is where Cancer Commons comes in. Already a successful web entrepreneur, Marty is attempting to break down the walls between trials and patient care with a new "clearing house" for cancer patients. Ideally, he sees a system that would allow for a "trial of one"--where a patient in treatment has access to an experimental therapy. The goal would be to focus on the patient's own recovery and not only some future patient. Important also would be that much more of the patient's data would be available to expedite research and medical therapy.

A good deal of the funding for Cancer Commons has come from Marty's own pockets. He did well as an entrepreneur. And then he survived a tough cancer. He's now devoting all his resources to creating a new paradigm that puts the patient not at the end, but at the beginning of the process,so that many more patients will have the chance he did.

Podcast brought to you by: BioConference Live's "Cancer: Research, Discovery and Therapeutics" - taking place online Oct 16-17, 2013. Register for free now.