precision medicine


Seattle Startup Takes Precision Oncology to the Next Step: Carla Grandori, CEO, SEngine

Carla Grandori was for thirty years a cancer researcher most recently at the Fred Hutch in Seattle. She had her personal reasons for working on cancer, she tells us in today’s show. Now, she’s the CEO and founder of SEngine, a startup offering something completely new for oncologists around the country.

Carla says she was motivated to step out of the research lab when two patients came to her personally and asked her, “can you study my cancer?”

“When I heard that second request, a light went off. I had thought maybe in 10 years the research would be useful. But then this patient made me think, ‘no, I think we can help now.' When I realized the potential of our technology to help patients immediately, I saw no more boundaries. I said, 'we have to get there.’"

What is this technology? And if it’s so powerful, why hasn’t it been offered before?

SEngine's (think Search Engine) new test, called PARIS, screens individual patient tumor cells onsite against a complete library of over a hundred and fifty cancer drugs. Before now with say, Foundation Medicine, there has been much progress in sequencing tumors and offering lots of omics data virtually. But the PARIS test goes a step further, screening a patient’s actual cells in real time while also combing through accompanying omics data. Until now we didn’t have the technology to deal with the samples with enough precision and in small enough quantities, nor the necessary robotics and software.

The company received CLIA certification back in June and the test is for sale to oncologists now. The next step for SEngine is to build up a major clinical utility validation.

Immuno Oncology 2017: Looking Back, Looking Forward with Rachel Laing and Olivier Lesueur

Immuno oncology is now the dominant topic at Mendelspod. From shows with CEOs presenting new panels of predictive biomarker tests, to the firsts at the FDA with the CAR-T approvals as well as the first approval of a drug (Merck’s Keytruda) based on a common biomarker (MSI) rather than on a tumor type, to scientists discussing rare cells of the immune system, we had more podcasts on this topic than any other in 2017.

Rachel Laing and Olivier Lesueur are partners at Bionest, a global life science consulting firm. They work with companies on both the drug and the diagnostic sides of immuno oncology and are at ease switching back and forth between the two in today's discussion.

Complexity is the key word, says Rachel. Immuno oncology has turned the development of biomarkers on its head. Whereas formerly with a simple companion diagnostic, one starts with a very specific biomarker develops from there.

“With immuno oncology, it’s very different from that,” she says. "You’re not just dealing with a tumor cell and the signaling that goes on there, you’re dealing with the immune system. And there’s a lot of interplay between the tumor, the microenvironment, and the immune system. It’s unrealistic to think you could get away with just measuring one biomarker.”

What are the challenges for diagnostics companies in commercializing various biomarkers into ongoing testing for the same patient, or what’s becoming known as “real time oncology?”

Olivier addresses the great reimbursement irony in the field of drugs and diagnostics. Without the biomarker tests, the drugs may not work for the right patients. Yet the diagnostics companies receive pennies while the drug makers are getting away with— well, we all know that issue. Olivier says one drug maker recently preempted this problem by offering to just pay for the diagnostic up front in geographies where the diagnostic reimbursement was being questioned, which is good for everyone, including the patients, and shows some vision. This problem of undervaluing diagnostics has bedeviled our industry for a long time and becomes especially crucial with immuno therapies that rely on patient stratification and ongoing profiling.

In our final question about what we’ll see in the year ahead, it’s cautioned that though patients are seeing more and new therapy options, the complexity of treatment is becoming ever more demanding on some people who are already pretty sick.

Huh? 30 Million Americans Have a Rare Disease? Howard Jacob on the State of Clinical Sequencing

Here’s a title for you. Chief Genomics Officer. Today’s guest is also the VP of Genomic Medicine and a faculty investigator at the HudsonAlpha Institute for Biotechnology.

He launched the world’s first genomic medicine program becoming the first person in history to use genome sequencing to diagnose, treat, and cure a patient. Few people exude the sheer force and vision for the future of genomic medicine that comes from Howard Jacob. We’re very pleased to have him on Mendelspod for the first time to talk about progress with rare disease, sequencing technology, and how he would teach genomic medicine to young people today . . . And of course, that genomic age old question: the exome or the whole genome?

With their Own Manufacturing Facility, Seattle Children’s Goes Big into CAR-T, Rare Disease

The past few months have seen the first approvals at the FDA for CAR-T cancer therapies. But trials have been going on for years. And not just by big pharma.

Today’s guest, Dr. Michael Jensen, is a researcher at Seattle Children’s Hospital and started his first CAR-T cell trial back in 2002.

“It’s been a long road to get to the point where we understand enough about the science and physiology of this technology to make it work int he clinic," he tells us in today's interview.

Seattle Children’s has set out a tremendously bold vision: think hybrid academic center and biotech company. They are currently building a $350 million, half a million square foot research tower along with a 30,000 square foot GMP manufacturing facility--all under the non-profit umbrella. This is an upgrade on the current GMP facility and will be one of the biggest such facilities of its kind in academia.

Michael says that the center is out ahead of big pharma with CAR-T therapies because they are not going for big drug approvals, but rather focused on early proof of concept work.

“Our role is to innovate in early phase studies with the hope that positive data will result in a Novartis or Gilead or Juno or Bluebird coming in and taking it across the finish line.”

What the non-profit center is able to do that big pharma never will be able to, therefore, is to go after all cancers and pediatric diseases, no matter how rare.

We begin the interview with a rundown on the ongoing CAR-T trials at Seattle Children's and their plans to translate success in blood cancers to solid tumor cancers.

With Immuno Oncology Comes a New Focus on Rare Cells

Modena, Italy is the town where one of the world's rarest cars were first developed and built: the Ferrari sports car. It’s also home to one of the world’s oldest universities where today’s guest spends his time studying rare human cells.

Andrea Cossarizza is Professor of Pathology at the University of Modena and Reggio Emilia School of Medicine and the President Elect of ISAC, or the International Society for the Advancement of Cytometry. He joins us today to talk about the role that improved cytometry technologies are playing in detecting rare cells and how this is being translated into better treatments for patients with cancer and other diseases such as immune disorders.

With the advent of immuno therapy has come a renewed interest in rare cells, or cells that occur with less frequency than 1 in 1000. Rare cells include the antigen specific T cells that we hear so much about with immuno oncology. But rare cells are also studied in many immune and inflammatory diseases such as HIV.

“This is a very new and interesting field which will have enormous importance in the future,” says Andrea, who wrote the chapter on rare cells in a new book on single cell analysis.

Andrea says that though new immuno therapies have shown such enormous promise, they only work on about half the patients. Being able to detect rare immune cells in advance of treatment will help clinicians to know which patients will respond.

What are the challenges that are emerging in this new field? When should the patient be tested? How does rare cell detection technology need to develop?

Join us as we lift the hood on the future of rare cell detection.

Why Childhood Cancers Need Their Own Gene Panel: Tim Triche

When we first talked with Tim Triche of LA Children's Hospital, we found out he was a bit of an outlier among cancer researchers. He was an advocate for poking around in the non-coding RNA.

Today we welcome Tim back to the show to talk about a new gene panel that he has designed specifically for childhood cancers. It’s a first of its kind and was modeled quite closely on the gene panel for the NCI’s MATCH trial. The new panel has both a DNA and an RNA component, and the RNA side is by far the biggest.

"There are 1,400 different amplicons on this panel looking for RNA fusions. Thermo Fisher tells me it’s the most ambitious RNA panel that they’ve ever undertaken," Tim says in today's interview.

"When 100 cancer patients walk in your office, then 100 cancer patients walk in your office," says Tim, quoting a common line in the field that points to the uniqueness of every cancer.

Yet even though every cancer is different, certain biological commonalities combined with better sequencing tools is enabling the design of new gene panels to guide in diagnosis and treatment. More and more a cancer is looked at based on the drug that might treat it rather than the organ in which it grows. The new panel can guide this treatment.

Some of the most important targets on the panel are RNA fusion transcripts. What are they, and why are they so important for helping kids?

Childhood cancers come from inherited mutations, whereas most adult cancers have to do with the skin or the linings of the organs due to mutations caused by environmental impacts. Fusion transcripts are very common in the youth cancers and have been a big part of routine diagnostics.

If a mutation is there early in life, is it likely to turn into cancer sooner rather than later? Yes, says Tim.

“If you look at the incidence of childhood tumors, there’s a big bump in the first months or year or two of life, and then they disappear thereafter."

Additional benefits from these new next gen sequencing panels are that they can work with very small “real world” samples of tumor tissue, and they can also be used as discovery tools. Tim says the panel, called OncoKids, is ready to go for frontline therapy, and is hoping to get the word out to oncologists everywhere.

Exploring the Exome and the Future of Genomics with Jay Shendure

Back in 2009, University of Washington professor, Jay Shendure, wrote a definitive paper offering up a roadmap for exome sequencing. Since then, the cost of sequencing has come down so far that many have debated whether or not to do whole genome sequencing vs. just the exome.  

As it turns out, the exome, as a unit, has been very fruitful for both clinicians and scientists, particularly in the area of rare disease discovery and diagnosis. Most genetic testing companies these days have the exome on their product lists.

In today's program, Jay says that we are still in the heyday of the exome; there is still much low hanging fruit.   However, some eight years after his landmark paper, he warns we will soon come to the end of that cycle.

“There clearly is a lot that we haven’t explained. But doing the same thing over and over again isn’t going to get us there. We’ve got to take a step back and systematically investigate the various explanations for the keys that aren’t clearly labeled and not under the lamppost.”

What are some examples of new hypotheses for decoding the genome? Jay points to searching in non-coding regions, epigenetic mechanisms, somatic mosaisicm, and di-genic mutations.

As we go ever deeper into the genome, what are Jay's thoughts on the need for going wider with lots of genomes? And is he on the same page with his UW colleague, Evan Eichler, when it comes to long reads?

Jay is a scientist's scientist. Coming out of George Church's lab at Harvard, he's worked over the years on new methods for genomicists. One of his latest projects dives into developmental biology. He says we've spent a lot of time looking at the "what" of genomics. Now it's time to look at the “how” and “why."

Thermo, Pfizer, and Novartis Pull Off a First for NGS in Lung Cancer

Today we get to bring you a feel good story, one of the major achievements so far in precision oncology. Three large companies—Thermo Fisher, Pfizer, and Novartis—put aside their differences to come together for patients.

The patients are those who suffer from non-small cell lung cancer. In June, the FDA approved for the first time an NGS panel with multiple genes for multiple drugs that treat this kind of cancer.

“It’s groundbreaking for patients, because instead of having to wait for a hierarchal testing approach to their cancer, this one test could be able to give the answer for the patient."

By hierarchical, Annie Martin, the VP Global Head of Precision Medicine at Novartis, means the usual stepwise approach to testing for patients with this cancer. Typically patients are tested for first EGFR, followed by ALK, followed by ROS1, followed by BRAF. Now, thanks to a new NGS panel out by Thermo, all of these tests will be done at once and has been approved for various therapies.

In addition to Annie, we’re also joined by Thermo’s Joydeep Goswami, President of Clinical Next Generation Sequencing and Oncology at Thermo Fisher and by Hakan Sakul, VP of Diagnostics at Pfizer to talk about their collaboration.

How did Thermo decide on this panel, and what possible future uses to do they see? And how did the three large corporations—one diagnostics and two pharmas--come together to pull this off?

Join us with three of the industry’s leaders as we uncover the work behind a major milestone for precision oncology.

Making Genetic Testing Mainstream Medicine with Sean George, Invitae

Invitae appointed their co-founder Sean George as CEO earlier this year. He joins us to share his bold vision for the field of genetic testing.

Sean mentions the word “scale” several times in today’s interview. Invitae was by no means the first on the scene, beginning in late 2013 (just after the Myriad Supreme Court decision), but with plenty of funding and talent they have sought to push the needle forward in a big way when it comes to genetic tests. The company has always exuded the message that there is all this valuable genetic information available now, and it’s just not getting to people who could benefit.

Sean says that this urgency is what drives him in a quest to “prevent unnecessary suffering that exists today by tearing down the barriers that are keeping this powerful and fundamental information from benefiting people’s lives.”

What are the barriers? Sean says cost is number one. That there are many out there who would buy genetic tests but can’t because of the price. In an age of astronomical drug prices, is it really that crucial to squeeze off a few dollars from a genetic test? And how does Sean and Invitae make the decision when to offer a test?

While Invitae has not gone the direct-to-consumer (DTC) route, Sean says they have a bit of a hybrid model where they market directly to consumers, but sell only into the clinic.

Sean agrees that the industry has had some “whiplash”, moving forward with excitement only to have big set backs. He says that in his company presentations, he likes to show two New York Times headlines:

The first goes, “10 Years after the Human Genome Project, What Does It Matter?” And the second headline taken from 1991: “Personal Computers: So Who Needs Them Anyway?”

Need Better Standards for Your Clinical Assays? NIST Can Help

The life science tools space is flourishing. Biomedical research output is at an all time high. Today’s guest says there are over 40,000 papers published each year on cancer biomarkers.

But very few of those become commercialized tests. Why?

Many had hoped the FDA would step in and save the diagnostics industry from itself, from a race to the bottom when it came to being able to reproduce clinically relevant tests. But that’s obviously on hold. In the meantime, others are stepping in. And there is one government agency which has no regulatory authority but some power to help out.

Kenneth Cole is the group leader for developing bioassay methods and standards at the National Institute of Standards and Technology. His group has just created a new set of standards and methods for HER2 testing which is available to the clinical lab community to help improve their own assays. It’s been said on the program that this very common test for use in cancer therapy has a false positive rate of 20 percent. That's too many patients getting told the wrong thing.

Ken’s group is now going to work on EGFR and other common tests, and they can help the testing community in several ways. First of all, Ken says, they have a “the luxury of being able to focus in on the measurement techniques and on examining all the sources of variability in an assay." They also work on characterizing cell lines, which have become “an essential part of modern biology.” Ken says a big part of the work at NIST is the education of the community and of the new crop of scientists.

Do you have an assay you’d like help with? Ken is easy to reach, and NIST welcomes your requests. They have set up many partnerships from loose collaborations to projects with IP protection.

Often the best place to find solutions is in going back to the basics.



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