pharma

Some stocks are up on news of big biotech mergers, but others are down on hearing of the latest difficulties of gene therapy. One thing’s for sure—blood diseases are where it’s at.

Speaking of the latest difficulties, we start our January review by going back to that paper out of Stanford about a new obstacle to using CRISPR as a new drug platform. It’s called the human immune system. Major roadblock or small warning light?

“Smart people have been thinking about the wrinkles in CRISPR and Cas9 for a long time. This is one of them, and it’s not going to stop the technology from being used well in people in the long run,” says Nathan.

Neither of our commenters are happy with Luxturna’s pricing of $425,000 per eye. But who is happy with drug pricing these days? How are drug companies supposed to recoup their investment on roughly 2,000 patients?

“We’re gonna have to price these drugs based on the whole platform, but also we’ll have to look at creative things like . . . how successful it is,” says Laura.

Last, but not least, we finish up with the new paper out in Nature showing the sequencing of a reference genome using the MinION handheld nanopore sequencer. Laura says it’s a snooze, but then she comes around.

Fifteen years ago, folks in the industry were buzzing about RNAi the way they talk about CRISPR today. Then things went quiet for the technology, at least in the news. Until last year.

In September of 2017, Alnylam Pharmaceuticals, the leader in the RNAi space, announced such positive phase III study results that most experts in the business expect an FDA approval soon. It will be the first for an RNAi drug.

So what took the technology so long, and what was the key to the great results? These are questions we ask today of Chris Anzalone, the CEO of Arrowhead Pharmaceuticals, another runner in the RNAi race. Arrowhead scooped up various RNAi programs from some of the big pharma giants, including Roche and Novartis, during the "quiet" years. Coupling these assets with some of their own technology, they are going after not just some of the esoteric diseases we've come to expect from a new platform first proving itself, but are also targeting the very recognizable Hepatitis B.

How does Arrowhead plan to further differentiate themselves from Alnylam?

“One of our great contributions to the field and, frankly, to world health, is our ability to bring this outside the liver,” says Chris.

So far, the major programs from RNAi companies like Alnylam are all limited to liver diseases. Arrowhead is the first to have drug candidates which go after non-liver diseases. It's a major step forward for this RNAi technology.

How we will know when RNAi has matured, we ask Chris at the end.

A major chapter in the history of medicine has been written by UC San Francisco. They are writing the next for precision medicine.

Keith Yamamoto is in both chapters. Since the 1970s, he has been a researcher of cellular and molecular biology at UCSF and now serves as Vice Chancellor of Science Policy and Strategy as well. His career has always had these two parallel tracks of scientist and policy administrator. He has sat on various review boards at the NIH and chaired the Board of Life Sciences at the National Academy of Sciences where he worked with a group that would stimulate President Obama to launch his Precision Medicine Initiative (PMI) back in 2015. Today he shares with us what that was like for him.

Though the political wind blows a different direction at the national level these days, the momentum continues for the PMI at NIH, funded, as Keith points out, by congress with the Faster Cures bill for ten years.

And at UCSF? They are just getting started in precision medicine. With an illustrious history in medicine, an enviable location at the tech hub of the world, and resourced to the gills—the university can boast its sixth year in a row of being the top recipient of NIH funds, and rides around the top of the list for private contributions--UCSF is also one of the hosting universities for California’s own Precision Medicine Initiative, which just a few days ago received a huge boost from Governor Brown's new budget.

What is the university doing with all this gold? Keith says UCSF is building a machine, a precision medicine platform, that brings together data from all the disparate places we’ve talked about here on the program—the omics data, wearables information, electronic health records, etc—into an information commons similar to Google Maps, creating a "knowledge network." It’s a story we’re all familiar with, and if anyone can do it, certainly this is the place.

In addition, Keith describes one of the many collaborations UCSF is involved in called ATOM, or Accelerating Therapeutics for Opportunities in Medicine, a public-private consortium that brings the idea of big data sharing to drug discovery at the pre competitive level.

“What we’re moving is the starting line, rather than the finish line", says Keith.

The NIH has spearheaded similar efforts before. Perhaps with UCSF’s star computer science power this effort will go new places.

For those in our audience attending next week’s Precision Medicine World Conference in Silicon Valley, you can hear Keith talk on Accelerating Cancer Therapies and Exploiting Longitudinal Patient Data: Partnering to Achieve Precision Medicine.

Our first show of the year is an outlook on genomics for 2018. To do this we’re joined by our regular commentators, Nathan Pearson and Laura Hercher, and also by a special guest to mix things up a bit, Misha Angrist, Associate Professor at Duke University and Editor in Chief of Genome Magazine.

Misha wrote a seminal book on the rise of next gen sequencing and personal genomics (Here is Human Being: At the Dawn of Personal Genomics). After working at Knome, Ingenuity, and the New York Genome Center, Nathan recently founded his own company, Root, which works closely with tissue donor registries to give back DNA information to consumers for free. Laura is recognized as a leader in the field of genetic counseling, being a counselor herself and training many of today's working counselors.

Join us as we ask, where are we in genomics today?

Our topic today: biotech leadership. What makes a good biotech CEO? Are there unique issues to biotech and diagnostics that shape and demand a different kind of leadership?

But first an introduction to our guest. Each January after we put down the champagne glass, after we’ve danced in the new year, all of us in the field of biotech, pharma, diagnostics, and digital medicine feel the pull of another annual dance: the JP Morgan Healthcare Conference in San Francisco. And each year this second dance fills ever more ball rooms and spills out into ever more hallways, streets, cabs, pubs, restaurants and bars. There are “survival kits” for this dance.

But while it’s called the JP Morgan conference, in fact, much (most?) of the excitement takes place at the sister conference, the Biotech Showcase which explodes with the energy of the up and coming.

Sara Demy is the founder of the Biotech Showcase, reaching next month it’s 10th anniversary. Formerly at BIO (Biotechnology Industry Organization), she has worked directly with CEOs for many years and has gathered some ideas on biotech leadership. And in what turns out to be more of a tribute than a tutorial, she starts out by saying that the biotech CEO is “cut from a different cloth.”

"They lead a company that has no products, that's built on science, that may or may not bear fruit in the future. They have to raise a lot of money. They're not making money. They're not selling a product. But they have an end game in mind. That end game is what I think carries the successful CEOs through. And that end game is treating patients."

We end with a question about how the industry is doing on the topics of gender equality and sexual harassment. The annual JP Morgan has been known for parties unkind to women, and Sara says offending companies have turned their attitude around and are making amends.

The Biotech Showcase runs again January 8th, 9th and 10th, 2018.

To honor Laura's pentametric thirst,

We write the summary today in verse.

Was it a quake that had no epicenter,

That silly paper out by J. Craig Venter?

And after years of silencing the market

Has RNAi at last knocked out its target?

Then Nathan gives to yuppies devil's choice.

Which one libs: gluten dough or GMOs?

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.

Let’s say you’re a biomedical researcher looking for a place to make your mark. You find out that there is still a major disease that affects more than 2 million people in the US, and we still know virtually nothing about this disease at the molecular level. Wouldn't that stand out?

It certainly has to today's guest, Ron Davis, who is also a father searching for answers for his son. Ron has been the Director of the Stanford Genome Technology Center for decades. He collaborated on the first DNA microarray and made a major contribution to the Human Genome Project. For five years now, Ron has directed his comprehensive skill set in bioengineering--and his vast connections--to work on a cure for ME/CFS, or Chronic Fatigue Syndrome, a disease which has ravished his son, Whitney Dafoe.

With no funding from the NIH so far (he says they're not good at starting things), Ron is working to characterize the disease at the molecular level. A new device developed at his center that he calls a "nano needle" could enable the first definitive diagnostic test for patients with CFS.

The history of this disease is of patients desperate with hope but always facing a major stigma. Many medical professionals are still not on board with diagnosing a patient with CFS. Ron says this stigma and lack of interest by the research community has created a big chance.

“This is a tremendous opportunity. Here’s a major disease which at the molecular level you don’t know anything about. This has got to be the last disease like this."

Find an extensive recent written interview with Ron here.

The largest cut to NIH budget ever, rolling back genetic non-discriminatory law—the bad news continues to roll from Washington. But there was great news this month as well.

Both Nathan and Laura are fuming about HR 1313, or a Republican bill to roll back GINA protections. Laura points out that the proposed law builds on an exemption in GINA for wellness programs—a category difficult to define. And Nathan reminds us that families and children could be hurt by the new bill. Theral asks since when did privacy become partisan? GINA passed in ’08 with a vote of 95-0 in the Senate, 414-1 in the House (Ron Paul playing the weirdo there), and it was signed by George Bush.

Then on to some “game changing” drugs for multiple sclerosis and eczema and a successful gene therapy trial for severe sickle cell anemia. Not only are there new therapies, drug manufacturers seem to be getting the message on pricing.

Mike Murray and the crew over at Geisinger are making the implementation of genomic medicine look down right easy.

In today’s interview, Mike explains GenomeFIRST Medicine, a program at the Geisinger Health System in Pennsylvania to offer care “that is based on an individual’s DNA sequence.” The healthcare provider boasts its own biobank and has partnered up with Regeneron’s Genome Center to offer exome screening to self selected patients. As of DNA Day last year, April 25th 2016, 100,000 recruits had signed up.

What has made Geisinger, who was selected to join the nation Precision Medicine Initiative, so successful with genomics? Mike points to the leadership.

“We have incredible support from the highest levels of the organization. As we’ve rolled out genomics, they are supportive and interested. As long as we’re there to explain what we’re doing and why we’re doing it, we have them on our side,” he says.

Has there been any pushback from doctors or patients?

Mike says one of the challenges they hadn’t really considered has been a “naming issue.” Sometimes one of the variants a patient tests positive for “puts their clinical story together.” But other patients may test positive for something like lynch syndrome, for example, who haven’t really had any problems.

“They really don’t have lynch syndrome, “ he says, "they have a genetic variant that goes with it. Until they have problems associated with it, they just have risk for lynch syndrome. So the problem is how do you keep something like that high enough on the radar that people and their providers know what to look for, but not so high that insurers or other entities might say, we’re going to treat them like our standard approach to lynch syndrome?”

In fact, Mike and his team have thought quite far through this challenge of how to report genomic findings back to patients. He explains what they’ve come up with in this beautifully clear interview about one of America’s most genomically experienced and progressive health systems.