immuno oncology


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.

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.

August 2017 Review with Nathan and Laura: CAR-T Cashes In, Embryos Edited in US, and the Invitae Incident

Back from summer vacation, Nathan and Laura are smoking hot as they look back over some exciting headlines.

The summer boiled over with plenty to talk about, but it was just this week that delivered most of the news for our discussion today. Novartis’ gene therapy based on CAR-T technology was approved Wednesday, making it the first gene therapy to be approved ever in the US. Analysts will be trying to figure out how high high is when it comes to the price tag, but Nathan and Laura explain why this therapy is a big deal for patients.

As for the first gene editing of embryos in the US that happened earlier in August? Nathan says, yes, it’s a first, but the big story is how "strikingly reliable the CRISPR edit is in germline vs the rest of the body."

Finally, we heard a few days ago that genetic testing provider, Invitae (recently featured here on the program) had sent out a large batch of false negative tests. Laura, a genetic counselor, says that in the absence of FDA regulation the system is operating on trust.

“And I want to say,” she adds, “ I trust Invitae. They’re a good lab, and I think they’re handling this well.”

 

The First In-Human Gene Editing Trial in the U.S. - And It’s Not with CRISPR

The challenge for the first ever in-human gene editing trial, according to today’s guest, is with the delivery to the body.

“At the moment, the easiest place to deliver your gene or genome editing is to the liver, using AAV which are viruses that seek out and go to the liver cells," says Sandy Macrae, the CEO of Sangamo Therapeutics.

Sangamo is known for two things: They have pioneered the commercialization of an older gene editing technology called Zinc Fingers. And they have done a lot of work in the area of HIV.

Today, Sangamo is enrolling patients in a new trial which they say will be the first "in-vivo" trial using their Zinc Fingers for patients with hemophilia B, Hunter syndrome, and Hurler syndrome. The former gene editing work with the T cells of HIV patients, Sandy says, was done “ex-vivo”, or outside the body.

So why is Sangamo still using Zinc Fingers in the age of CRISPR? Sandy says that the older technology is much better developed for medical applications and is safer. The company has been able to get their off target effects to below the level of detection.

“When I was doing my postdoc, I would have used CRISPR. It’s better if you’re just wanting an easy experiment that isn’t about making a medicine but just getting a quick answer,” he says.

Because Sangamo has been the sole commercial developer of Zinc Fingers with not a lot of intellectual property dispute, the technology didn’t make the big PR splash that CRISPR has—nor, at the same time, did it generate all the fear.

We finish the interview with a question about what was the result of all Sangamo's work in HIV over the years.

When an Exome Test Is Part of the Therapy and Not a Diagnostic: John West on Personalis and Personalized Cancer Vaccines

About six years ago there was a wave of genome interpretation startups getting their first rounds of funding. One of them was Personalis, a company founded by a well known group of Stanford geneticists and bioinformaticians.

John West is the CEO of Personalis, and he joins us today to talk about how the company is participating in the dramatic shift in drug development toward immuno oncology drugs. Our listeners might remember John from his days at Solexa where he served as CEO and presided over the sale of the company to Illumina.

At the same time Personalis came on the scene, the first drug that would harness the immune system to fight cancer was being approved by the FDA, Yervoy by Bristol-Myers Squibb. This was the first of four drugs known as checkpoint inhibitor drugs. These four drugs have had spectacular success and together generate revenue of over 6 billion per year, a level which has doubled in the past year.

John and Personalis are working with biotech companies on a new generation of immuno therapies known as personalized cancer vaccines. These new drugs are actually custom synthesized for each patient after an “immunogram” or genetic workup of the tumor has been done. We know today that tumor growth is driven mostly by neoantigens, or new antigens which arise from mutations that happen after the cancer first appears, says John. So an immunogram done by Personalis must look at all the genes (over 20,000) and not just the original driver mutations. An immunogram could only be done in the last few years with the latest developments in next gen sequencing and algorithm creation.

How far along are these new personalized cancer vaccines? And what is the commercialization challenge for Personalis?

“We are essentially an integral part of the therapy,” says John. "So we don’t think of it as a diagnostic test. We think about it as the initial part of the manufacturing of the therapy."



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