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Tuesday, December 10, 2019

Merck, Sanofi Push To Add Cancer Drugs

Two of the world’s biggest drugmakers struck multibillion-dollar deals on Monday aimed at bolstering their lineups in the fiercely competitive cancer-drugs market.
Merck & Co. said it would acquire ArQule Inc. for about $2.7 billion, paying a 107% premium in a bid to diversify its cancer treatments beyond top-selling drug Keytruda. Meanwhile, Sanofi SA said it would spend $2.5 billion, a 172% premium, to acquire Synthorx Inc. in the French drugmaker’s own effort to catch up with oncology rivals.
Both deals reflect the industry’s intense pursuit of new products to sell in one of the world’s biggest and fastest-growing prescription-drug segments. The $123 billion world-wide cancer-drugs market is expected to almost double by 2024, according to a market-research firm, EvaluatePharma.
Bristol-Myers Squibb Co. recently closed on its $74 billion acquisition of rival Celgene Corp. to create a cancer-drugs powerhouse. Pfizer Inc., which has positioned itself to focus on cancer, bought Array BioPharma for $10.6 billion this summer. And Eli Lilly & Co. acquired Loxo Oncology for about $8 billion earlier this year.
The promise of new sales in a lucrative market appeals to pharmaceutical companies, which are counting on cancer treatments to provide new revenues as older products lose patent protection.
Making the segment even more attractive is the U.S. Food and Drug Administration’s willingness to approve new cancer drugs with smaller, faster and less-expensive clinical trials. And companies have found that health plans will pay for cancer drugs, even at prices that often top $100,000 for a year’s treatment.
Scientific breakthroughs, including the ability to target specific mutations and combine medicines, are also helping drive the industry’s interest, said Roy Baynes, Merck’s senior vice president of global clinical development and chief medical officer.
“The science is evolving very rapidly,” Dr. Baynes said in an interview. “The good news is that we are now focused on drugs which really do have big effect.”
But the interest in finding the next big new product has driven up the prices that big drugmakers have had to pay. Companies have paid mean premiums of 114% this year for small- to midsize deals such as Sanofi’s and Merck’s, up from 67% during the previous five years, according to analysts at Evercore ISI. The data are for drugs of all stripes, not just cancer treatments.
And the commercial market for cancer treatments has become hard-fought, forcing companies to race to be the first or second to market to secure a position before rivals.
Merck agreed to pay $20 a share in cash for ArQule, of Burlington, Mass. The deal is expected to close early in the first quarter of 2020.
It would increase Merck’s offerings of therapies that treat blood-related cancers. ArQule’s lead experimental treatment, called ARQ 531, is being tested in patients with blood cancers who carry a specific genetic mutation that prevented them from responding to previous treatments.
“It’s early, but it looks like it has a lot of potential,” Dr. Baynes said of the therapy.
Dr. Baynes acknowledged that other companies are developing therapies similar to ArQule’s, but such contests drive innovation.
Merck has been looking for deals to expand its portfolio of cancer treatments beyond Keytruda, as some investors and analysts have worried that Merck has become too dependent on the product. Keytruda’s global sales totaled nearly $7.2 billion last year.
Earlier this year, Merck, of Kenilworth, N.J., bought Tilos Therapeutics Inc. and Peloton Therapeutics Inc., both of which are developing cancer therapies.
Citigroup analysts said Merck’s expansion in hematology makes sense because it hasn’t been very active in that field, and expects the deal “to be the beginning rather than the end of similar moves.”
Many of the therapies that big drugmakers are acquiring are immunotherapies such as Keytruda or complement the drugs, a relatively new class of treatment that unleashes a patient’s own immune system in the fight against cancer.
Keytruda was once an afterthought buried in Merck’s research-and-development pipeline, but it has become a commercial juggernaut for the company during the past few years. It is now approved to treat a wide range of different types of tumors, including two types of blood cancers.
Companies adding cancer therapies to their pipelines are also doing so because those with multiple drugs for the same types of cancer can bundle the treatments in their contracts with pharmacy-benefit managers, insurers and hospitals. That has become crucial as health insurers look to what is known as outcome-based contracting, where costs are tied to whether patients respond to drugs.
For Sanofi, acquiring Synthorx, of La Jolla, Calif., is an attempt by the French pharmaceutical company to erase the gap with rivals that already sell the drugs. Synthorx’s lead agent is in the early phase of patient testing in a range of cancers, both on its own and in combination with existing cancer immunotherapies.
The deal is the first big move by Sanofi Chief Executive Paul Hudson, who began leading the company in September, and suggests that cancer treatment will be one of the company’s new priorities.
Sanofi said it would pay $68 a share in cash for Synthorx.
“This acquisition fits perfectly with our strategy to build a portfolio of high-quality assets and to lead with innovation,” Mr. Hudson said.
Sanofi is one of the most diversified companies in the industry, spanning branded prescription drugs, vaccines and over-the-counter treatments. Within branded drugs, it produces medicines ranging from insulin for diabetes to specialty medicines for rare diseases.

Sanofi shares rally on new margin goals, narrow drug focus

Shares in Sanofi rose on Tuesday after the French drugmaker said it would focus on vaccines and treatments like its promising eczema medicine Dupixent to grow sales, in a business revamp seen as potentially leading to spin-offs.

Like pharmaceutical rivals from Britain’s GlaxoSmithKline to Switzerland’s Novartis, the company, which also announced cost savings targets and a goal to boost margins, is trying to zoom in on potential blockbuster drugs.
Long a leader in the diabetes market with its prescription medication Lantus, Sanofi has struggled in recent years to keep up the pace in this field with new treatments, and revenues faltered as patents expired.
It now wants to reverse this course under new Chief Executive Paul Hudson, poached from Novartis in September, ending research in diabetes and cardiovascular diseases.
Sanofi is investing in its more buoyant businesses like rare diseases and making a further push in the cancer market, snapping up U.S. biotechnology firm Synthorx in a cash deal worth about $2.5 billion.
Sanofi shares were up 4.7% in morning trading, at 85.73 euros each. The company is due to set out more details of its strategic plans later on Tuesday in Cambridge, Massachusetts.
Year-to-date, shares are up 18% compared to a 25% rise for the European healthcare sector..
It highlighted the potential for some new launches like Dupixent, an eczema treatment approved in other therapeutic areas such as asthma, which it said could reach over 10 billion euros ($11.02 billion) in sales from under 1 billion euros in 2018.
“We are encouraged that Sanofi is prioritizing Dupixent,” analysts at Credit Suisse said in a note.
Sanofi also announced a target to reach a core operating margin of 30% by 2022, up from 25.8% last year, and ahead of some analysts’ targets, including those at Jefferies.
The group said it would carve out its consumer health business, home to over-the-counter products such as influenza treatment Tamiflu, as a standalone unit with its own operational dynamic, on top of three other main divisions.
Hudson did not comment on what this meant for the unit further out, although Sanofi has been considering a joint venture or an outright sale among options for the consumer health business, sources have previously said.
“The market is likely to take (that) as confirmation that the business will leave the group at some point in the future,” analysts at JPMorgan said.

Editas updates in vivo proof-of-concept data for EDIT-301

Editas Medicine (NASDAQ:EDITannounces in vivo proof-of-concept data supporting the development of EDIT-301 as a durable medicine to treat sickle cell disease and beta-thalassemia.
In this study, when EDIT-301 was infused into NBSGW mice, HbF levels in human red blood cells were increased by approx. 50% points above background at 16 weeks post-engraftment with pancellular distribution and no lineage skewing.
These elevated HbF levels were observed after editing with Cas12a which created an editing profile that enriched genomic changes that favored high and persistent HbF levels.
EDIT-301 is the first experimental medicine in development using Cas12a (formerly known as Cpf1).
Shares are up 3% premarket.

Healthpeak in lease amendment, extension with Amgen

Healthpeak Properties (NYSE:PEAK) executes a lease amendment and extension with Amgen (NASDAQ:AMGN) at Healthpeak’s Britannia Oyster Point campus in South San Francisco, which consists of 10 buildings and 900K square feet of space.
Amgen currently leases space across seven of the buildings at the campus, some of which is subleased by Amgen to third parties.
The amendment provides Amgen the ability to continue its occupancy at three of its currently leased buildings through 2029, while providing Amgen flexibility to terminate its occupancy in these buildings at earlier dates subject to advance notice requirements.
Leases for two buildings are set to expire in December 2021, the same as in the prior lease; two other buildings’ leases are set to expire in December 2023.

Monday, December 9, 2019

J&J CEO spurns U.S. congressional hearing on carcinogens in talc products

Johnson & Johnson Chief Executive Officer Alex Gorsky has declined to appear at a U.S. congressional hearing set for Tuesday on the safety of the company’s Baby Powder and other talc-based cosmetics.

In an announcement, the House of Representatives Subcommittee on Economic and Consumer Policy said that its efforts to persuade Gorsky to testify included “repeated attempts to accommodate the company” over nearly a month.
Democrat Raja Krishnamoorthi, chairman of the House panel investigating concerns about cancer-causing asbestos in cosmetic talc and powders, said he was disappointed Gorsky turned down the invitation.
“Mr. Gorsky refuses to speak to the Subcommittee under oath, yet he has not refrained from making multiple public comments on the topic,” Krishnamoorthi said in a statement.
J&J spokesman Ernie Knewitz said that the subcommittee had rejected the company’s offers to send a talc testing expert or a J&J executive in charge of consumer products.
Gorsky “is not, as we have repeatedly told the Subcommittee, an expert in the stated subject of the hearing,” Knewitz said. “We have respectfully declined the invitation for our CEO to testify.”
Knewitz said that the composition of the hearing, which includes two experts who have testified for plaintiffs against J&J, also factored into the company’s decision.
Gorsky has played a lead role in J&J’s efforts to reassure consumers and investors that its talc powders are safe and asbestos free. Last year, he issued a statement vouching for the safety of the products after a jury issued a $4.69 billion verdict in favour of 22 women who sued over allegations their ovarian cancers were caused by J&J powders.
Gorsky appeared on CNBC’s “Mad Money with Jim Cramer” and in a video posted on J&J’s website to rebut a December 2018 Reuters report that the company knew for decades about the presence of small amounts of asbestos in its talc and powders.
“Since tests for asbestos in talc were first developed, J&J’s Baby Powder has never contained asbestos,” Gorsky said in the video.
In October, Gorsky testified in a deposition in a lawsuit filed by an Indiana man, saying, “We unequivocally believe that our talc and our baby powder does not contain asbestos.” J&J faces more than 16,000 similar lawsuits.
Concerns over asbestos in talc cosmetics have grown in recent months as the U.S. Food and Drug Administration announced that the carcinogen had been found in several products, including a bottle of Baby Powder.
J&J said it recalled 33,000 bottles of Baby Powder “out of an abundance of caution.” Later, J&J said labs it hired found no asbestos – other than some contamination it blamed on an air conditioner – in samples from the same Baby Powder bottle and its production lot.
The FDA has said it stands by its finding.
Chief executives of companies embroiled in controversies routinely comply with lawmakers’ invitations to testify.
In recent months, the CEOs of Boeing and Facebook have appeared before congressional committees to answer questions about how their companies were safeguarding consumers.
Charles M. Elson, director of the John L. Weinberg Center for Corporate Governance at the University of Delaware, said CEOs have a responsibility to go to Washington when Congress calls, just like other citizens.
But Elson said Gorsky’s pass was understandable. He said the CEO and his advisers probably figured that the downside was greater to testifying than not.
“It’s being invited in for a punch in the nose,” Elson said. For Gorsky, “nothing good will come out of it.”

Giving common antibiotic before radiation may help body fight cancer

The antibiotic vancomycin alters the gut microbiome in a way that can help prime the immune system to more effectively attack tumor cells after radiation therapy. A new study in mice from researchers at the Abramson Cancer Center of the University of Pennsylvania found giving a dose of the common antibiotic not only helped immune cells kill tumors that were directly treated with radiation, but also kill cancer cells that were further away in the body, paving the way for researchers to test the approach in a human clinical trial. The Journal of Clinical Investigation published the findings today.
More than half of all patients with solid tumors undergo radiation therapy at some point during their treatment. In recent years, multiple studies have shown that giving patients higher doses of radiation over the course of fewer treatments – called hypo-fractionated radiotherapy – can induce a stronger immune response in patients. In addition, hypo-fractionated doses have the ability to impact other tumors cells in the body that weren’t directly treated with radiation. This is known as the abscopal effect.
“Our study shows that vancomycin seems to boost the effect of the hypo-fractionated radiation itself on the targeted tumor site while also aiding the abscopal effect, helping the immune system fight tumors away from the treatment site,” said the study’s senior author Andrea Facciabene, PhD, an associate professor of Radiation Oncology in Penn’s Perelman School of Medicine.
Facciabene and his team chose vancomycin for a few specific reasons. First, it mostly targets gram-positive bacteria, making it disruptive to the gut microbiome. Second, it’s a large molecule, which means it stays in the gut and does not circulate to the rest of the body the way other antibiotics do. The fact that it is not systemic limits the impact it has on the rest of the body’s microbiome.
In this study, researchers found vancomycin specifically improved the function of dendritic cells, which are the messenger cells that T cells rely on to know what to attack. While researchers used melanoma, lung, and cervical cancer models for this work, they note the approach could have implications for a wide variety of cancer types. This study also builds off the team’s previous research, which showed a similar effect in T cell therapies, meaning it adds to a growing body of evidence.
Still, the researchers note this study only scratches the surface when it comes to understanding the connection between the makeup of the gut microbiome and its impact on radiotherapy-induced immune responses to cancer. They say further research is needed to understand the implications of specific strains or clusters of bacteria.
“However, what’s clear is that antibiotics play a role and can potentially impact treatments and outcomes for cancer patients,” Facciabene said. The researchers are planning a phase 1 study to translate this approach into the clinic.
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Other Penn authors on the study include co-lead authors Mireia Uribe-Herranz, Stavros Rafail, Silvia Beghi, and Luis Gil-de-Gómez, as well as co-authors Ioannis Verginadis, Sergey Pustylnikov, Stefano Pierini, Renzo Perales-Linares, Ian A. Blair, Clementina A. Mesaros, Frederic Bushman, and Constantinos Koumenis.
The study was supported by the National Institutes of Health (R01CA219871-01A1)

Celyad Updates on Leukemia Program at ASH

  • Future development of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) program to be underpinned by proprietary OptimAb manufacturing process
  • Enrollment of DEPLETHINK trial evaluating CYAD-01 following preconditioning chemotherapy continues, while THINK trial progresses to expansion segment with plans to evaluate monotherapy CYAD-01 produced with OptimAb manufacturing process
  • CYCLE-1 trial evaluating next-generation, NKG2D-based CAR-T therapy CYAD-02 following preconditioning chemotherapy on track to begin enrollment in early 2020
  • Preliminary results from the r/r AML and MDS program using the OptimAb manufacturing process are expected by the end of first half 2020