U.S. antitrust official says worries over limiting vertical deals ‘misplaced’

A top antitrust official at the U.S. Justice Department attempted to reassure investors on Thursday that worries that regulators would crack down on proposed combinations of two companies on a supply chain — known as vertical mergers — were overblown.

Makan Delrahim, the assistant attorney general for antitrust, said that most proposed transactions were either good for consumers or neutral.

But the department’s decision in November to sue to stop AT&T Inc, which owns DirecTV, from buying Time Warner Inc made investors question whether other vertical deals might also meet with scepticism from antitrust enforcers.

Delrahim said that was overblown.

“I understand that some journalists and observers have recently expressed concern that the antitrust division no longer believes that vertical mergers can be efficient and beneficial to competition and consumers,” he said.

Delrahim said that some of these point at the decision to sue to try to stop AT&T from buying Time Warner “as a supposed bellwether,” he said. “Rest assured these concerns are misplaced.”

Two other vertical deals under review are Cigna Co plan to buy Express Scripts Holding Co for $52 billion (£38.7 billion) and CVS Health Corp’s planned merger with Aetna Incfor $69 billion.

https://bit.ly/2LyiqEn

4D Pharma Plans Cancer-Treatment Trial With Merck Unit

4D Pharma said it entered into a collaboration agreement with a subsidiary of Merck & Co. Inc. (MRK) to conduct a clinical trial evaluating its anti-cancer drug MRx0518 for use in tandem with a Merck therapy.

The pharmaceutical company said the phase 1 clinical trial will evaluate the effectiveness of MRx0518 in combination with cancer drug Keytruda in patients with renal, bladder and non-small cell lung cancer, as well as melanoma. The study will evaluate the safety, tolerability and preliminary clinical benefits of the drug combination, 4D pharma said.

https://bit.ly/2JtOdp2

Tonsil, adenoid removal ups long-term respiratory, allergic, infectious risks

Tonsil and adenoid removal associated with long-term risks of respiratory, allergic and infectious diseases Removing tonsils and adenoids in childhood increases the long-term risk of respiratory, allergic and infectious diseases, according to researchers who have examined – for the first time – the long-term effects of the operations.

The researchers suggest renewed evaluation of alternatives to these common pediatric surgeries that include removal of tonsils (tonsillectomy) to treat chronic tonsillitis or adenoids (adenoidectomy) to treat recurrent middle ear infections.

The adenoids and tonsils are strategically positioned in the nose and throat respectively to act as a first line of defense, helping to recognize airborne pathogens like bacteria and viruses, and begin the immune response to clear them from the body.

The collaborative study initiated by the Copenhagen Evolutionary Medicine program looked at the long-term effects of removing the tonsils and adenoids in childhood, compared with children who had not undergone the surgeries.

University of Melbourne researcher Dr Sean Byars and Professor Jacobus Boomsma from the University of Copenhagen led the research, with Professor Stephen Stearns from Yale University. The research is published in the Journal of the American Medical Association Otolaryngology Head and Neck Surgery.

The team analyzed a dataset from Denmark of 1,189,061 children born between 1979 and 1999, covering at least the first 10 years and up to 30 years of their life. Of the almost 1.2 million children, 17,460 had adenoidectomies, 11,830 tonsillectomy and 31, 377 had adenotonsillectomies, where both tonsils and adenoids removed. The children were otherwise healthy.

“We calculated disease risks depending on whether adenoids, tonsils or both were removed in the first 9 years of life because this is when these tissues are most active in the developing immune system,” Dr Byars said.

The analysis showed:

• Tonsillectomy was associated with an almost tripled relative risk – the risk for those who had the operation compared with those who didn’t – for diseases of the upper respiratory tract. These included asthma, influenza, pneumonia and chronic obstructive pulmonary disorder or COPD, the umbrella term for diseases such as chronic bronchitis and emphysema.
• The absolute risk (which takes into account how common these diseases are in the community) was also substantially increased at 18.61 percent.
• Adenoidectomy was found to be linked with a more than doubled relative risk of COPD and a nearly doubled relative risk of upper respiratory tract diseases and conjunctivitis. The absolute risk was also almost doubled for upper respiratory diseases but corresponded to a small increase for COPD, as this is a rarer condition in the community generally.

“The association of tonsillectomy with respiratory disease later in life may therefore be considerable for those who have had the operation,” Prof Boomsma said.

The team delved deeper into the statistics to reveal how many operations needed to be performed for a disease to occur at a greater rate than normal, known as the number needed to treat or NNT.

“For tonsillectomy, we found that only five people needed to have the operation to cause an extra upper respiratory disease to appear in one of those people,” added Prof Boomsma.

The team also analyzed conditions that these surgeries directly aimed to treat, and found mixed results:

• Adenoidectomy was associated with a significantly reduced risk for sleep disorders and all surgeries were associated with significantly reduced risk for tonsillitis and chronic tonsillitis, as these organs were now removed.
• However, there was no change in abnormal breathing up to the age of 30 for any surgery and no change in sinusitis after tonsillectomy or adenoidectomy.
• Following adenotonsillectomy the relative risk for those who had the operation was found to increase four or five-fold for otitis media (inflammation of the middle ear) and sinusitis also showed a significant increase.

The study suggests that shorter-term benefits of these surgeries may not continue up to the age of 30 apart from the reduced risk for tonsillitis (for all surgeries) and sleep disorders (for adenoidectomy).

Instead, the longer-term risks for abnormal breathing, sinusitis and otitis media were either significantly higher after surgery or not significantly different.

The researchers note that there will always be a need to remove tonsils and adenoids when those conditions are severe.

“But our observed results that show increased risks for long-term diseases after surgery support delaying tonsil and adenoid removal if possible, which could aid normal immune system development in childhood and reduce these possible later-life disease risks, Dr Byars said.

“As we uncover more about the function of immune tissues and the lifelong consequences of their removal, especially during sensitive ages when the body is developing, this will hopefully help guide treatment decisions for parents and doctors.”

Source:

https://www.unimelb.edu.au/

https://bit.ly/2JiwNQy

Evolent new deals partly de-risk 2019: Piper

Evolent Health new Medicaid deals partially de-risk 2019, says Piper Jaffray. Piper Jaffray analyst Sean Wieland notes that Evolent Health announced two additional partnerships in Florida with providers who will take on Medicaid risk. This expands the company’s eligible Medicaid membership reach in Florida to 1.1M and should drive $35M-$45M in revenue next year, he contends. The analyst believes these wins de-risk next year, while also driving operating leverage. Additionally, Wieland argues that there is more upside than downside on the risk/reward profile of the new partnerships. The analyst reiterates an Overweight rating and $30 price target on the shares

https://bit.ly/2JjHiTE

Clinical trial disruptor Science 37 in talks with SoftBank on a $150M investment

Just a few months after pharma giant Novartis partnered up with Science 37 on its virtual approach to clinical trial work, Recode reports that the would-be CRO disruptor is in talks with SoftBank execs on a $150 million investment.

SoftBank, which provided Roivant chief Vivek Ramaswamy with more than a billion dollars to invest in biotech, evidently has been drawn to Science 37’s promise that it can efficiently and effectively recruit patients for clinical trials without forcing them into a trial site. Using new telemedicine tech, they say they can accumulate clean datasets to show whether or not new drugs are working — hoping to disrupt the big players who now dominate the CRO world.

Quoting sources, Recode notes that Science 37 is planning to value itself at $300 million for this deal, up about $100 million since Lux Capital and Google’s GV helped back the company a little more than a year ago.

SoftBank’s big, $98 billion Vision Fund has made repeated forays into the world of drug development and technology. Aside from Roivant, the group participated in the massive $500 million round to back George Scangos’ Vir, which is working on an infectious disease drug pipeline.

The CRO business has undergone a decade of shaking out as private equity groups moved in to buy up the outsourcing companies and meld them into a set of large and aggressive global players, often with big staffs. Shaking them up with a new tech approach won’t come easily in an R&D world where safe and dependable are key watchwords in the high-risk world of drug development.

But Science 37 continues to build up a head of steam to give it a try.

https://bit.ly/2sFQ7ws

Tilting at vaccines giants, SutroVax fuels up on a $170M-plus quest

A little biotech tilting against giants in the global vaccines business has just lined up an $85 million round to back their clinical quest aimed at conquering the pneumococcal conjugate vaccine business. And they’ve added crossover investors — as well as a world-famous vaccines honcho — in the round as they continue to plot out a risky path forward into a mega-blockbuster market.

GlaxoSmithKline’s ex-vaccines chief Moncef Slaoui is coming on board as chairman of SutroVax as the Foster City, CA-based biotech pushes past the $170 million mark on fundraising. All that money, plus everything to come, is riding on the belief that the Sutro spinout has reliable tech that can whip up a first-in-class product that conjugates a big cluster of antigens to site-specific locations on a protein carrier without hobbling T-cell helpers, building a better vaccine the giants can’t touch.

CEO Grant Pickering tells me much of the new money will be used to line up the manufacturing work that will be needed as they begin to test their vaccine for pneumococcal pneumonia in humans.

Right now, that market is dominated by Pfizer’s $6 billion a year product Prevnar 13, which upped the ante on pneumococcus strains that can be guarded against. Prevnar 13 is the world’s best-selling vaccine. Merck just started a late-stage program for V114 that hopes to shove Pfizer aside with a new product that takes that to 15. And SutroVax says it can go past the 20 mark using tech for a conjugate vaccine that no other company can rival.

“Having just a few more strains really is a significant competitive advantage,” says Pickering, who is hoping to vault the giants with a product that can carve away billions — and keep it.

That’s not going to come cheap — and certainly won’t be easy. Pickering allows that the syndicate was brought together with an eye to keeping their options open on an IPO at some point. The CEO also isn’t ready to lay out his development timelines, exact number of strains they’re planning on or even when the first human will be tested.

Why flag your entire plan in a competitive field like this?

New investor TPG Growth, Medicxi and Foresite Capital all came on board with this round. That adds Medicxi’s Francesco de Rubertis to the group, while all of SutroVax’s existing institutional investors, including Abingworth, Longitude Capital, Frazier Health Care Partners, Pivotal bioVenture Partners, Roche Venture Fund, and CTI Life Sciences Fund came back.

Medicxi in turn is backed by a trio of giants — J&J, GSK and Novartis — and offers a “nice lens” into their thinking on this program, which dominates the biotech’s time. Slaoui, who offered a thumbs up for the company’s “huge potential,” will help with the global perspective as well.

https://bit.ly/2sPioQr

Potential ‘One-Two’ Punch for Treating MS

A potential one-two punch to treat multiple sclerosis (MS) comes in the form of an estrogen receptor β (ERβ) ligand that could both reduce the inflammation that limits current treatment efficacy and provide a more favorable environment for promoting myelin repair, new research suggests.

Treatment with several ERβ ligands in a mouse model of MS was associated with an increase in a neutrophil chemoreactant called CXCL1. Elevated levels of CXCL1 in the brain and periphery, in turn, correlated with increased axon remyelination.

“Existing therapies for MS are immunomodulatory and slow disease disability, but fail to reverse or prevent disease progression or restore and repair myelin,” study author Seema K. Tiwari-Woodruff, PhD, associate professor of biomedical sciences at the University of California (UC), Riverside, School of Medicine, told Medscape Medical News.

Identifying the mechanism behind therapeutic benefits of ERβ ligands is critical for developing new therapies that promote remyelination, she added. The study revealed the promise of one of these ligands in particular: indazole chloride.

“Although we weren’t surprised at the effectiveness of ERβ ligands, we were surprised by the finding that indazole chloride can curb ‘bad’ inflammation and enhance the ‘good’ inflammation,” Tiwari-Woodruff said.

Inflammation in the setting of autoimmune diseases like MS is harmful but inflammation in other settings, such as fighting infection and wound healing, is beneficial, she noted. The researchers found that indazole chloride reduces harmful inflammation and promotes beneficial inflammation by strengthening production of CXCL1, making new oligodendrocytes more resistant to harmful inflammatory signals while they remyelinate.

In addition to upregulation of CXCL1, compared with vehicle only, ERβ ligands improved axon myelination, decreased pro-inflammatory cytokines, and had no effect on leukocyte infiltration into the central nervous system.

“The finding is unique and encouraging as treating a complex disease such as MS requires modulating the immune system,” Tiwari-Woodruff said. “Indazole chloride has the potential to do just that.”

The results were published online May 29 in Proceedings of the National Academy of Sciences of the United States of America.

Building on Earlier Findings

Previous research by the UC Riverside team demonstrated that a modestly selective ERβ ligand, diarylpropionitrile, provided neuroprotection in a mouse model of MS but did little to limit inflammation caused by the disease (Neurobiol Dis. 2013;56:131-144).

“Recently, we, along with our collaborator Dr John Katzenellenbogen of the University of Illinois at Urbana-Champaign, found that the more selective ERβ ligand indazole chloride improves clinical disease and motor function in the same mouse model,” said Tiwari-Woodruff.

The current research also reflects initial estrogen studies. They showed that nonselective endogenous estrogens present during pregnancy reduced MS relapse frequency and severity through ER-α–mediated suppression of inflammation.

“Unfortunately, estrogenic signalling through ERα is also feminizing in males and associated with proliferative effects that increase cancer risk, limiting the usefulness of endogenous estrogens,” write the investigators. “In contrast, selective ERβ ligands offer many of estrogen’s benefits without these deleterious side effects.”

“Fast Moving and Exciting” Research

The current study is part of a research movement, noted Bruce Bebo, PhD, executive vice president of research at the National MS Society, when asked to comment.

“It’s a well-done, thorough paper that gets a little bit more at the mechanism for how estrogen receptor β ligands might be promoting repair,” he told Medscape Medical News

“One of the things that stood out for me was the observation that they could induce repair even in the context of extensive immune cell accumulation in the nervous system. That’s been one of the challenges in myelin repair — we pharmacologically promote repair in an area with a lot of active inflammation,” said Bebo.

“The area of myelin repair has received a lot of attention in the last 5 years. It’s a fast moving and exciting area of MS research,” he added.

“A lot of exciting approaches are being studied” in both basic research and clinical trials underway evaluating repair agents, Bebo noted. “In my opinion, it’s only a matter of time before we understand how we can promote repair in MS and…before we have a repair therapy in the clinics.”

Encouraged to Search Further

Because indazole chloride works differently than many currently available pharmaceutical agents, “we are hopeful that the effects we see in mice will translate into the clinic,” Tiwari-Woodruff said. “However, many encouraging preclinical studies in animals have ended in failure when brought to clinical trials, so more research is needed to say with certainty,” she added.

In fact, other ERβ ligands may feature a more potent beneficial effect, she said. For this reason, she is collaborating further with Katzenellenbogen to test new and potentially better analogues of indazole chloride.

“We have screened and submitted a patent application for over 15 indazole chloride analogues and are in the process of publishing a report of their efficacy in comparison to indazole chloride coming out soon,” Tiwari-Woodruff  said.

Finding an even more powerful ERβ ligand that inhibits critical elements of the immune attack and at the same time promote repair “would be a real potent combination,” Bebo commented.

The Bigger Picture

The interplay between central nervous system–derived and immune-derived signals is central to the induction and regulation of neuroinflammatory diseases such as MS, Tiwari-Woodruff said. “Our study opens up new possibilities that ERβ ligands like indazole chloride modulate inflammation to potentially promote myelin repair and remyelination.”

And the big picture potential could go beyond MS, she added. “We believe that indazole chloride-like compounds could be a potential targeted therapy for MS and other diseases with inflammatory demyelination.”

Tiwari-Woodruff and Bebo have disclosed no relevant financial relationships.

Proc Natl Acad Sci U S A. Published online May 29, 2018. Article

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