cancer genomics


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.

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.

Charting the Dark Matter of Cancer Genomes with Jim Broach

We’ve heard a lot this year about the search for new structural variants and the hope that scientists will find new causal linkages for diseases such as cancer. But will the genome still yield dramatic genetic signatures such as KRAS, BRAF and EGFR that have been so helpful in cancer treatment?

Today’s guest says, yes, and he’s on the trail.

Jim Broach is the Director of Penn State’s Center for Personalized Medicine. He and his team have come up with the highest resolution genomic data to date on certain cancer cell lines using sequencing and mapping tools. In some cell lines his research has revealed 150-200 more structural variants than had previously been discovered.

“There are a whole set of structural variants which haven’t been taken into consideration to date,” he says in today’s interview. "For the next couple of years, this is the dark matter of the cancer genome. We’ve got to sort out which of these structural variants are going to be relevant in understanding how best to treat the patients. Once we generate that information, I think these structural variants will be just as relevant as the point mutations or as large scale translocations."

Jim mentions paired end reads and PacBio’s new long read technology, but the main tool he talks about is Bionano’s optical mapping technology. Previously the field used karyotyping to look for variants of this size, but he says Bionano has got their technology to the quality and price point where it will now replace the older technology.

How will Jim’s research impact treatment in the clinic? He is doing de novo sequences of cancer cell lines. Does he envision the need for de novo sequencing of a patient’s cells as part of a commercial assay?

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.

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.

Move Over PDL1: New Test Combo Adds RNAseq to Better Track Immune Escape

Reports from ASCO, the nation’s biggest cancer conference, this year again were full of stunning stories about the success of older and new immuno therapies. The race has never been hotter for biomarkers to target patient groups. Most of this new class of drugs--which harnesses the immune system to go after the cancer--inhibit an immune checkpoint called programmed cell death protein 1 or PDL1. So frontline cancer treatment these days typically includes a test for the PDL1 biomarker. But there are a breadth of potential targets in the immune system that promise to make this class of cancer drug even more effective.

Today we talk with Mark Gardner, CEO of OmniSeq, who has just received approval from New York State (the company is in Buffalo) to launch their new Immune Report Card.

“The biology is complicated. Even for folks that are PDL1 high, in the majority of cases those patients are not going to respond to these drugs. The average number of responders is 20-30%. So we know something else is going on. It turns out we’ve known some of the mechanisms for how the tumors are achieving "immune escape.” What we’ve not had the ability to do is to simultaneously measure across the range of hypotheses for how that tumor is escaping."

Omniseq's Immune Report Card includes mutational burden and MSI testing, which is common practice today. The two additional “legs” of the report are copy number variation for PDL1 as well as RNAseq.

Grail Merger, Genomic Autopsies, Overtreatment Alarm, and Controversy at Ancestry.com: May 2017 Review with Nathan and Laura

Is Grail already merging? Genomic autopsies? Does the House's new healthcare bill turn mere genetic risk into pre-conditions? Nathan and Laura are back to find meaning in the rush of May's headlines.

Laura cites a disturbing survey of over 2,000 women diagnosed with breast cancer that found half of them had unnecessary double mastectomies after genetic testing. She says unabashedly, “In big letters, it’s an ADVERTSIMENT FOR GENETIC COUNSELING.”

Speaking of alarms, Nathan says attorney Joel Winston’s blog against Ancestry.com’s terms and conditions was fear mongering.

We end with comments on the passing of one of the creators of the orphan drug industry, Henri Termeer.

Green Light for DTC, Blood Mammograms, and Ancient DNA: April 2017 with Nathan and Laura

For genomics nerds, April 2017 will be remembered as the date when the FDA adopted a more open policy towards 23andMe and direct-to-consumer (DTC) genetic testing. What does this decision mean, and just where is the FDA drawing the line? A genetic counselor herself, Laura found the decision “head turning.”

“There’s lots of reasons why some genetic counselors are not going to be thrilled to deal with everyone’s 23andMe results,” she says.

For the “cool new studies” section of today’s show, Laura is excited about a research project announced by Grail, a spinoff from Illumina working on a pan cancer screening test. And Nathan points out that the trend for researchers to look back at ancient DNA sharpened this month with two new studies that not only open up the possibilities for historians and archeologists but also have relevance to human health longterm.

“We’re getting much better at doing it,” he says. “So look for more of this ancient meta genomics where we can find little fragments of DNA outside of cells but intact in sites like soil. They’re very diverse, but we're starting to figure out really what was going on at a place some time in the past."

We finish with a couple stories that are giving pause to researchers working on gene therapy and immunotherapy.

It’s commentators Nathan Pearson and Laura Hercher joining Theral to talk genomics for April.

How to Improve Lab Tests in the Absence of FDA Regulation?

Rubbing shoulders at molecular medicine conferences these days one senses a sigh of relief when you talk about laboratory developed tests (LDTs). With the FDA’s decision to put regulation on hold coupled with the expected confirmation of Scott Gottlieb as FDA commissioner, those in the lab testing business seem to be confidently settling back to the status quo. And those who were arguing that all we need is a “beefed up” CLIA to hold labs to better testing standards don’t appear to be motivated to do so anymore.

Several questions arise when it comes to LDTs. First of all, if regulation was truly important for enabling this revolution we call precision medicine, then why couldn’t the Obama administration get it issued? In other words, is the status quo so bad? Secondly, without the FDA even threatening to regulate, will we see the “beefed up” CLIA that many labs argued is the best way forward? Without the stick of the FDA, is the carrot gone too?

Russell Garlick is the CSO of SeraCare, a private company that has worked to improve clinical laboratory standards for over thirty years. The company recently added a new business unit for precision medicine diagnostics, and Russell was brave enough to come on today and address these questions.

As for the status quo being good enough, Russell isn't happy.

“Many of the organizations undertaking clinical trials to recruit oncology patients have lost confidence because LDTs in one geography of the United States don’t perform the same as in other parts of the United States,” he says.

Russell has worked many years with labs on IVDs--the already regulated group of diagnostic tests. He sounds disappointed that the FDA has dropped their focus on LDTs, but is hopeful that existing organizations, such as the College of American Pathologists, or even private companies such as SeraCare might step in and seize an opportunity to improve things.

“There’s a lot of status quo. And frankly it’s a little bit disappointing,” he says, “because the laboratories can benefit from [improved standards]. It’s that inertia to do something new and different."



New to Mendelspod?

We advance life science research, connecting people and ideas.
Register here to receive our newsletter.

or skip signup