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Monday, May 28, 2018

Regeneron’s Blue Sky R&D: Q&A


When attending the 2018 Annual J.P. Morgan Healthcare Conference (JPM) in San Francisco this past January, Regeneron Pharmaceuticals held one of my favorite breakout sessions. When Len Schleifer, M.D., Ph.D., Regeneron’s founder and CEO, walked into the Georgian room at the Westin St. Francis, he looked at me and said, “This is crazy,” giving me a fist bump as he made it to the stage to field questions for the Regeneron breakout session. He and his colleagues had just presented in the Colonial room across the hall and had to wade through a sea of people in line to attend the luncheon keynote address by Microsoft founder Bill Gates taking place down the hall. The breakout discussion was interesting, though it got even more so when the last question was asked regarding the “blue sky scenario” of the Regeneron Genetics Center (RGC). The question included the word “vision,” for Schleifer wore a knowing smile when stating, “Let’s hear from the visionary himself.” And with that he leaned back in his chair, punting the question over to his colleague George Yancopoulos, M.D., Ph.D., Regeneron’s president and chief scientific officer.
Yancopoulos provided an impassioned response rarely witnessed during JPM. His retort not only served as the inspiration for this blog, but drove my desire to interview the chief scientist for an upcoming feature in Life Science Leader magazine, which we were fortunate to get scheduled. During our conversation, I asked Yancopoulos what Schleifer’s smile was all about. And while there wasn’t enough room to share his response in our print edition, it seemed like a good addition for our exclusive and free-to-access Beyond The Printed Page online section of the magazine. But to read all that the chief scientist had to say, you’ll need a subscription. Please enjoy this latest Beyond The Printed Page Installment.
Why do you think when Len Schleifer was smiling when fielding the “blue-sky scenario” RGC question at JPM? Was it a bit of a brotherly jab at you for being the “visionary?”
There are lots of visionaries at Regeneron, including Len, though nobody’s more visionary than Roy Vagelos [Regeneron Pharmaceutical’s chairman of the board]. But here’s why I believe Len was smiling. For a long time, 30 years basically, Regeneron has been routinely criticized for doing blue-sky research. In fact, people questioning what we were doing actually used the term “blue sky” when disparaging us as a research boutique. “This is what happens when you put a bunch of scientists in charge of a company,” doubters would say. “They do all this interesting science and develop all this interesting technology, but where’s the beef? Where are the medicines coming out?” We, on the other hand, kept saying, “This is where drugs come from (i.e., fundamental science and fundamental technology), and if we do our jobs right by investing the time and money to build all these capabilities, then we will have an evergreen pipeline of drugs flowing out the back end.” With a solid foundation Regeneron won’t have to worry about buying or in-licensing something from the outside, as we are the company on the bleeding edge of science. We believe the technologies and science we are doing today will pay off in the next 10 to 20 years. Len was smiling because we’ve been around long enough and have seen what “blue sky” can lead to, and it’s been some of the most important medicines of our generation. No other company has been able to do what we have done since the most productive days of Genentech or Merck. You can’t find other companies that have repeatedly, in their own labs, gone from ideas and technologies to important medicines like Regeneron. We are working on a whole stream of things in our pipeline around muscle atrophy, new bispecifics for ways of attacking cancer cells, new ways of using immunotherapy, and new medicines for metabolic disorders and liver disease. All are coming from our own capabilities, our own labs, and our own technologies that people disparagingly referred to as blue-sky efforts so many years ago. But we have demonstrated that if done properly, blue-sky research does pay off.
How do you prevent Regeneron from going the way of other once-productive R&D innovation engines that today are much less relevant?
That is something I worry about; that size and success will do us in. I have four children, and I often tell them that they have a handicap when compared to me. I came from a poor immigrant family, and I knew that in order to survive and make it, I had to work 10 times harder than anybody next to me. My children are the beneficiaries of success, and they are going to have to figure out how to deal with that. I tell them, “The biggest enemy of future success is current success.” I think the secret, both for my children and Regeneron, is to not to get away from one’s roots, and that which made you successful. For me it was a drive and a thirst to use science to make a difference. That was my dream, and why I immediately became attracted to Len Schleifer. Because I believed that’s what he really wanted too. The people we attracted to join Regeneron were also like that, and we built an environment to make it a reality. We have to stay true to the notion of using science to make a difference. We have to continue to attract the best and the brightest people who are driven by the power of science. We have to continue to create a synergistic environment where people can do this together. We have to constantly challenge ourselves and stay passionate. This is why I think the metrics are consistent with the fact that we are still on track. Thirty years ago, we were doing “crazy mouse genetics” while people questioned the rationale. But we knew it was the bleeding edge of science. Today we are the world leader in human genetics, and people continue to question the rationale behind efforts like the Regeneron Genetics Center. But RGC is like a biopharma within a biopharma, and the young team that is running it is taking advantage of anything that we can teach and give them to do. They have the same hunger that made Regeneron successful, and we are helping to create a similar enabling environment. I really feel Regeneron is just coming into its prime. Those other companies that were once game changers but are now less relevant? That’s because when they entered their prime, many of the key people who helped build the place on fundamental science and technology were long gone. I believe Regeneron is a unique company in the history of the biopharma business, as it has an almost magical environment that none of us wants to leave. I think we are poised to do bigger, better, and more amazing things. We’re getting the resources and the technologies, we’re delivering, and we’re engaging a whole new set of partners to do it.

EU makes it easier for companies to produce generic medicines for export


The European Commission on Monday proposed to change intellectual property rules to let pharmaceutical companies produce generic drugs for export to countries and regions where they are not under extended patent protection.

Supplementary protection certificates (SPCs) were introduced to expand patents on certain pharmaceuticals to compensate for the long time it takes such products to come to the market.
While these rules were introduced to aid research investments, it appeared that companies were also shifting production of generics for export out of Europe as a result, the Commission said.
While such drugs would still be protected inside the European Union under the new proposal, companies could make generic versions inside Europe for export to countries where no additional patent protection existed.
“Our initiative will help us open a market of 95 billion euros worldwide,” EU Industry Commissioner Elzbieta Bienkowska told a news conference.
“The same kind of tool worked very well in Canada and helped the pharmaceutical industry to grow and to employ people. That was our reference,” she added.
The Commission said the proposal, which still needs to be approved by the European Parliament and member states, could generate some 1 billion euros ($1.2 billion) of net additional sales per year.

3 decades on dialysis: NC kidney patient beats the odds to reach rare milestone


Despite his age, Lloyd Cameron could be a poster child.
Cameron, 57, celebrated his 30th year being on dialysis Tuesday in Wilson.
The lifelong farm worker from Elm City was surrounded by nurses, doctors and friends as the rare anniversary was recognized at DaVita of Wilson.
“I love them all,” Cameron said of his supporters. “They have been so nice and kind to me. I guess that’s why I do so good. They keep me straight in line.”
Cameron has come in to the facility for dialysis three times a week since he was 27.
“I’m happy for being here for 30 years. It’s a big blessing …” Cameron said. “I hope to be here for 30 more.”
Lisa Lewis, a regional coordinator for DaVita, said Cameron’s milestone was unusual.
“Normally, they last maybe five to seven years,” Lewis said. “That is the average lifespan of a dialysis patient, so I would say 30 years is five times that. It’s pretty important. It;s a pretty big thing.”
Wanda Hinnant of Goldsboro, who worked at DaVita for 38 years, remembers treating Cameron when he first came in three decades ago.
“I think he’s a wonderful person,” Hinnant said. “He has taken care of himself, followed the rules, and that’s why he’s still here.”
Dana Barberio, registered nurse and facility administrator, explained what dialysis does.
“Basically, it’s when their kidneys stop working and they have to come in here to dialysis. We basically filter their blood and remove the fluid and toxins in their blood and return clean blood to them, and we basically do what their kidneys would normally do.”
The cleansing sessions take from two to four and a half hours.
The patients get very familiar with the nurses and doctors.
“They are really our family,” Barberio said. “They really do become part of our family, and we care deeply about every one of our patients.”
Barberio said Cameron’s accomplishment is “absolutely amazing.”
“It is a miracle. We very rarely get to celebrate this type of milestone. This is a very rare occasion,” Barberio said. “It is just wonderful to know that a patient has taken care of himself and is able this good and is still able to be with us and dialyze with us after 30 years. It’s wonderful.”
Dr. Anwar Al-Haidary, attending nephrologist and the director for the dialysis unit, said in the past, dialysis got a bad reputation.
“Medicine has advanced and dialysis has advanced to the stage now that people can live a normal life, and they can live up to 30 or 40 years,” Al-Haidary said.
Sometimes people think dialysis is a bad idea, but that shouldn’t be the case anymore, Al Haidary said.
“As you can see, this is a good example,” he said. “People who take their medicines regularly, who follow up with dialysis, can live a normal, long life.”

Bristol-Myers to webcast ASCO highlights June 4


Bristol-Myers Squibb Company (NYSE:BMY) will hold an investor event on Monday, June 4, 2018 at 8:30 p.m. EDT (7:30 p.m. CDT) to discuss data presented at the American Society of Clinical Oncology (ASCO) in Chicago.
Company executives will provide an overview of data presented from the company’s oncology portfolio, and address questions from investors and analysts.
Investors and the general public are invited to listen to a live webcast of the event at investor.bms.com. Materials related to the event will be available at the same website prior to the event. A replay of the event will be available and can be accessed at investor.bms.com.

China rare disease list could promote R&D, regulatory filings


Five Chinese government agencies, including the State Drug Administration and the National Health Commission, published a national list of 121 qualified rare diseases to support diagnosis and treatment of such conditions in a move that could spur R&D and regulatory submissions for rare disease therapies.
This is the first time China has recognized rare diseases on a national level, James Xuetold BioCentury. Xue is founder, chairman and CEO of Canbridge Life Sciences Ltd.(Beijing, China) and previously served as first China general manager of rare diseases pioneer Genzyme Corp., which is now part of Sanofi (Euronext:SAN; NYSE:SNY).
He said a publicly available list will help promote R&D, improve review and approval times, and could make it easier for companies to gain reimbursement for their drugs in China.
While China has historically shown a lack of focus on rare diseases, the list is one signal that the area is increasingly becoming a priority for the country.
However, China still has a way to go towards encouraging development of rare disease treatments. For instance, Xue said there is no definition or criteria for what constitutes a rare disease in the country and no national reimbursement policy for Orphan drugs.
Xue said current policies are geared more towards rare disease drugs already approved in western markets. There is “no policy on newly developed drugs in China that encourages companies to take risks and includes exclusivities like pricing reimbursement, or IP,” he said.
Of the 121 diseases on the list, which was released on May 22, 110 already have a drug approved by U.S.FDA, Xue said. The list may encourage sponsors of those drugs to pursue approval in China. It also could facilitate a shorter review timeline and allow them to reference the list to signal an unmet medical need in China while seeking reimbursement, according to Xue.
Additionally, Xue said any company that wants to submit an IND to study a rare disease treatment in China is likely to have receptive discussions with regulators, if the targeted disease is on the list.
Furthermore, he believes the list will be a useful guidance for initiating price reimbursement discussions. He expects guidance will be released to set terms for coverage for rare disease therapies “relative to what other countries price drugs.”
Over the past year, the State Drug Administration (formerly China FDA) has published a series of regulations intended to bring many of the agency’s policies closer in line with western standards.
Draft regulations released in May 2017 set 10 years of exclusivity for innovative drugs for rare or pediatric diseases. In December, SDA issued draft guidelines on a conditional approval pathway for life-threatening rare diseases and guidance to implement a priority review pathway that includes rare diseases. Guidance to encourage development of generics also includes drugs for rare diseases (see BioCentury Extra, Dec. 29, 2017).
Joining SDA and the National Health Commission in compiling the list were the Ministry of Science and Technology (MOST), the Ministry of Industry and Information Technology(MIIT) and the State Administration of Traditional Chinese Medicine of China.

Kite Eyes More Worldwide Facilities, Links To National Cancer Institute

Kite, a Gilead Company (Nasdaq: GILD), today announced it has leased a new facility in the Netherlands to engineer cell therapies in Europe. The 117,000 square-foot site in Hoofddorp (SEGRO Park Amsterdam Airport) will enable Kite to efficiently manufacture and deliver its cell therapies to people living with cancer in Europe and will provide more than 300 new jobs when fully operational in 2020.
The facility will engineer and produce innovative cell therapies, including axicabtagene ciloleucel, a Chimeric Antigen Receptor T cell (CAR T) therapy that is currently under review by the European Medicines Agency and which is approved in the United States as Yescarta®.
“We are pleased to be leading a new frontier of cancer innovation that is bringing hope for people living with cancer,” commented John F. Milligan, PhD, Gilead’s President and Chief Executive Officer. “This new European manufacturing facility will enable personalized cell therapies to be manufactured in closer geographic proximity to the patients who will receive them, potentially shortening the turnaround time for people who urgently need care.”
In addition to the Netherlands facility, Kite has recently purchased a new building in Santa Monica from Astellas Pharma Inc. that will be used for cell therapy research, development and the expansion of clinical manufacturing capabilities, and has leased a 26,000 square-foot facility in Gaithersburg, Maryland. The Maryland site will support the work of a new Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) to develop adoptive cell therapies targeting patient-specific tumor neoantigens. Neoantigens are mutations found on the surface of cancer cells that are unique to each person and tumor, offering the potential for more targeted antitumor activity.
“We are proud to be at the forefront of advancing cell therapy, which we believe has the potential to transform cancer treatment,” said Alessandro Riva, MD, Gilead’s Executive Vice President, Oncology Therapeutics & Head, Cell Therapy. “The addition of these three new facilities and the expanded CRADA with our research collaborators at the NCI will help us bring cell therapies to more people with cancer around the world.”

Rural NC Has Growing Pains as Novo Nordisk Builds Manufacturing Plant

In late March, Novo Nordisk broke ground on a new manufacturing facility in rural Clayton, North Carolina. It’s not unusual for small communities to both welcome the jobs and business, while expressing concern over the changes to the community, and Clayton is no different.
The manufacturing plant will make active pharmaceutical ingredients (API) for several of Novo Nordisk’s current and future GLP-1 and insulin medicines for diabetes patients. The plan is expected to be fully operational in 2020.
The facility will have 833,000 square feet with a footprint of 417,639 square feet. It is expected to create almost 700 new jobs, bringing the total to 1,700, which is exceptional when you consider that in the 2010 census, Clayton had a population of 16,116, currently around 20,000.
The jobs will have an average salary of $68,000, which is $22,000 more than the current average salary and $15,000 more than the median household income in Johnston County. The company also projects an employment effect during the construction period of up to 2,500 people.
The new site is adjacent to Novo Nordisks’ 457,000 square feet Clayton facility, which has expanded several times since 1996. Novo Nordisk is investing $2 billion into production facilities in Clayton; Malov, Denmark; and Kalundborg, Denmark, with most of it, $1.8 billion, going into the Clayton site.
Still, it’s a bit of a change for the community. The town’s mayor, Jody McLeod, told STAT,“We’ve gone from the farm to the pharm. I used to work in the tobacco fields during the summers. Then those tobacco fields became subdivisions. Then the industry came in.”
It’s not as if the area is unfamiliar with biopharma. It’s basically a suburb of Raleigh, and not far from Durham and Research Triangle Park. This is an area rife with biopharma companies, including Argos Therapeutics, BioAgilytix LabsbioMerieux,FUJIFILM Diosynth Biotechnologiesand others.
Roger Hill, a minister at the Powhatan Original Free Will, the 130-year-old Baptist Church in the area, tells STAT,“They’ve been good neighbors. I wonder in the back of my mind, with Novo continuing to expand, how long will it be until they’ll consider buying the property our church is on?”
Local officials pledged more than $100 million in corporate subsidies to Novo Nordisk.
The U.S. diabetes market has been tough, with insurers pushing back on pricing for drugs. It’s also a hotly contested market, with Eli Lilly’s Trulicity, an injectable GLP-1, Novo Nordisk’s Victoza, also an injectable GLP-1 battling for market share. Sanofi is also a major player in the diabetes market. In February 2018, Novo Nordisk announced results of its Phase III clinical trial of GLP-1 oral semaglutide. The drug met its primary statistical endpoint, showing significant and superior improvements in HbA1c for all three doses compared to placebo. The 14 mg dose also showed significant and superior weight loss compared to placebo.
The company has nine additional ongoing PIONEER trials of the drug this year and expects to make regulatory submissions in 2019.
The North Carolina plant is in part of what has been dubbed the “diabetes belt,” which ranges from Louisiana up to West Virginia and over to North Carolina. This is where there is a higher rate of diabetes in the U.S.
Before the plants were set in Clayton, Novo Nordisk’s APIs were manufactured in Denmark. The ones in the U.S., such as in Clayton or other areas outside of Denmark, manufactured medical devices or assemble packaging. At this point, although details of what will be manufactured at the Clayton site are vague, it looks like it will make insulin injectables and GLP-1, the hormone first derived from Gila monster venom, that stimulates insulin production. A Novo Nordisk spokesperson said it would “ensure diabetes production capacity in the U.S. for the decade ahead.”
For the most part, local officials are happy about Novo Nordisk’s growth and continuing presence. But it’s not without its downside. It hired a full-time city inspector to deal solely with Novo Nordisk permits. I will also need to manage a $32 million wastewater facility that Novo Nordisk has agreed to build at its own expense.
But it’s a lot of money and jobs coming into the community, and that tends to win over most skeptics. And one of the town’s small business owners, David Townsend, who runs Nancy Joe’s Homemade, a bakery, said sales have grown 300 percent since the company broke ground–a lot of dough.