Evotec, Indivumed to Collaborate On Precision Medicine For Colorectal Cancer

The collaboration leverages Indivumed’s true multi-omics cancer database “IndivuType” and Evotec’s drug discovery platforms to identify new therapeutics for colorectal cancer

Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and Indivumed GmbHannounced today that they have entered into a research collaboration to discover and develop first-in-class therapeutics for the treatment of colorectal cancer (“CRC”). The collaboration, which runs for an initial term of two years, will combine Evotec’s proprietary bioinformatics analysis platform “PanHunter” as well as its small molecule and antibody discovery platforms with the CRC cohort of Indivumed’s true multi-omics cancer database “IndivuType”. The goal of this precision medicine collaboration is to deliver highly effective and durable treatments with clear strategies for CRC patient stratification.

https://www.marketscreener.com/EVOTEC-AG-436047/news/Evotec-And-Indivumed-Announce-Strategic-Drug-Discovery-Collaboration-On-Precision-Medicine-For-Col-28387687/

Bayer shareholder Deka joins chorus of complaints over Monsanto

One of Bayer’s largest shareholders tore into the company’s management on Wednesday for underestimating the legal risks of its takeover of Monsanto, setting the stage for a fiery annual general meeting after a 30 percent plunge in the shares.

Bayer has seen about 30 billion euros ($34 billion) wiped off its market value since August, when a U.S. jury found Bayer liable because Monsanto had not warned of weedkiller Roundup’s alleged cancer risks. It suffered a similar courtroom defeat last month.

“It’s quite drastic when a takeover triggers such value destruction and reputational damage so quickly. There can be no talk of a successful takeover any more,” Ingo Speich, the head of sustainability and corporate governance at Deka Investment, told Reuters. He will be among the shareholders to speak at the April 26 annual general meeting (AGM).

“What’s startling is that things have effectively moved beyond management’s control because we’re now at a point where the decisions over future development are made in court rooms,” he said, adding Bayer had clearly underestimated the risks.

With a holding of about 1 percent, Deka says it is Bayer’s 10th-largest shareholder overall, and the second-largest German one after DWS.

Major shareholder advisory firms Institutional Shareholder Services (ISS) and Glass Lewis last week recommended investors not to give the executive board their seal of approval at the AGM. Glass Lewis also advised against a vote of approval for the non-executive supervisory board.

A shareholder vote to ratify boards’ actions features prominently at every German AGM. Though largely symbolic, as it has no bearing on management liability, it is seen as a key gauge of shareholder sentiment.

Among shareholders that have vowed to deny top Bayer executives their vote of confidence is the former head of DWS, Christian Strenger.

Deka’s Speich declined to disclose how Deka would vote.

Company filings showed this week that Bayer’s supervisory board sought law firm Linklaters’ expert opinion for reassurance that the management board had complied with its duties when acquiring Monsanto for $63 billion last year.

The supervisory board in Germany’s two-tier corporate board system has to sign off on larger transactions. Bayer’s non-executive Chairman Werner Wenning was a driving force of the Monsanto deal, according to sources familiar with the matter.

Bayer is appealing, or has vowed to appeal, the two jury verdicts, but more than 11,000 plaintiffs are seeking damages.

The U.S. Environmental Protection Agency, the European Chemicals Agency and other regulators across the globe have found that glyphosate, the active ingredient in Roundup, is not likely carcinogenic to humans.

However, the World Health Organization’s cancer arm in 2015 reached a different conclusion, classifying glyphosate as “probably carcinogenic to humans.”

Speich said Bayer could now be vulnerable to attacks from activist shareholders who might seek to break it up, although the “bitter pill” of litigation risks might deter them for now.

Such risks could also distract management, he added, when it “should be fully absorbed by the integration of Monsanto,” Speich said.

https://www.marketscreener.com/BAYER-AG-436063/news/Bayer-shareholder-Deka-joins-chorus-of-complaints-over-Monsanto-28384490/

Bank Of America Upgrades Guardant Health On Huge Growth Potential

Guardant Health Inc GH 11.85% is off to a red-hot start to 2019, but one analyst says the rally may be just getting started.

The Analyst

Bank of America analyst Derik de Bruin upgraded Guardant from Neutral to Buy and raised his price target from $81 to $84.

The Thesis

While se Bruin says Guardant shares are admittedly expensive after its recent rally, the company’s massive growth potential has skewed the risk decidedly to the upside.

In the six months since Guardant’s IPO, shares have climbed from $19 to above $106 and then back to under $70. De Bruin has been hesitant to get behind such a volatile stock with a steep valuation, but several factors have improved the stock’s outlook in recent weeks.

First, Guardant’s LUNAR-1 data at the American Association of Cancer Research meeting was positive. Second, volatility associated with the IPO lock-up expiration has now passed. Third, there is now greater commercial coverage of G360 following publication of a lung cancer study in “JAMA Oncology.” Finally, de Bruin is now bullish on the liquid biopsy-based (LB) cancer market.

Bank of America projects a $20 billion addressable market for Guardant and is calling for compound annual revenue growth of 41 percent over the next five years. Guardant also entered the Japan market in 2018, which has roughly 3 million patients eligible for LUNAR-1, de Bruin said.

“We see upside potential from higher test volumes, higher commercial pricing, and if the LUNAR programs are successful,” de Bruin wrote in the note.

https://www.benzinga.com/analyst-ratings/analyst-color/19/04/13515869/bank-of-america-upgrades-guardant-health-on-huge-growth-potential

Non-antibiotic strategy for the treatment of bacterial meningitis

With the increasing threat of antibiotic resistance, there is a growing need for new treatment strategies against life threatening bacterial infections. Researchers at Lund University in Sweden and the University of Copenhagen may have identified such an alternative treatment for bacterial meningitis, a serious infection that can lead to sepsis. The study is published in Nature Communications.

Our immune system has several important defenders to call on when an infection affects the central nervous system. The researchers have mapped what happens when one of them, the white blood cells called neutrophils, intervene in bacterial meningitis.

If there is an infection, the neutrophils deploy to the infected area in order to capture and neutralise the bacteria. It is a tough battle and the neutrophils usually die, but if the bacteria are difficult to eliminate, the neutrophils resort to other tactics.

“It is as though in pure frustration they turn themselves inside out in a desperate attempt to capture the bacteria they have not been able to overcome. Using this approach, they capture a number of bacteria at once in net-like structures, or neutrophil extracellular traps (NETs). This works very well in many places in the body where the NETs containing the captured bacteria can be transported in the blood and then neutralised in the liver or spleen, for example. However, in the case of bacterial meningitis these NETs get caught in the cerebrospinal space, and the cleaning station there is not very effective,” explains Adam Linder, associate professor at Lund University and specialist in Infectious Diseases at Skåne University Hospital.

Researchers observed, by using advanced microscopy; that the cerebrospinal fluid of patients with bacterial meningitis was cloudy and full of lumps, which proved to be NETs. However, among patients with viral meningitis, the cerebrospinal fluid was free from NETs. When captured bacteria get caught in the cerebrospinal fluid, this adversely affects the immune system’s work of clearing away bacteria and also impedes standard antibiotics from getting at the bacteria, says Adam Linder.

Would it be possible to cut up the nets so that the bacteria are exposed to the body’s immune system, as well as to antibiotics, making it easier to combat the infection? As the NETs consist mainly of DNA, the researchers investigated what would happen if you brought in drugs used for cutting up DNA, so-called DNase.

“We gave DNase to rats infected with pneumococcus bacteria, which caused bacterial meningitis, and could show that the NETs dissolved and the bacteria disappeared. It seems that when we cut up the NETs, the bacteria are exposed to the immune system, which finds it easier to combat the bacteria single-handed. We were able to facilitate a significant reduction in the number of bacteria without antibiotic intervention, says Tirthankar Mohanty, one of the researchers behind the study.

Before antibiotics, the mortality rate for bacterial meningitis was around 80 per cent. With the advent of antibiotics, the mortality rate quickly fell to around 30 per cent.

In the 1950s, Professor Tillett at the Rockefeller University in the USA, found lumps in the cerebrospinal fluid of patients with bacterial meningitis. Professor Tillett discovered that these lumps could be dissolved using DNase. This was effective in combination with antibiotics and reduced the mortality rate for meningitis from around 30 per cent to about 20 per cent. However, this treatment had side effects, as the DNase was extracted from animals and could therefore trigger allergic side effects.

“At that time, everyone was so happy about the antibiotics, they reduced mortality for the infections and it was thought that we had won the war against bacteria. I believe we need to go back and take up a part of the research that took place around the time of the breakthrough for antibiotics. We can perhaps learn from some of the discoveries that were then flushed down the drain,” says Adam Linder.

“The development of resistance in bacteria is accelerating and we need alternatives to antibiotics. The drug we use in the studies is a therapeutic biological product derived from humans and has already been approved for human use. They are not expensive and have also been tested against many different bacteria and infections. Bacterial meningitis is a major challenge in many parts of the world. In India, for example, it is a major cause of death among children, so there would be significant benefits there from using such a treatment strategy,” says Tirthankar Mohanty.

The researchers want to go on to set up a major international clinical study and use DNase in the treatment of patients with bacterial meningitis.

---

Story Source:

Materials provided by Lund University. Note: Content may be edited for style and length.

---

Journal Reference:

1. Tirthankar Mohanty, Jane Fisher, Anahita Bakochi, Ariane Neumann, José Francisco Pereira Cardoso, Christofer A. Q. Karlsson, Chiara Pavan, Iben Lundgaard, Bo Nilson, Peter Reinstrup, Johan Bonnevier, David Cederberg, Johan Malmström, Peter Bentzer, Adam Linder. Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-09040-0

https://www.sciencedaily.com/releases/2019/04/190410083106.htm

Factors ID’d for healthy memory at any age

University of Alberta neuroscientists have identified different factors for maintaining healthy memory and for avoiding memory decline in those over age 55, according to a new study. The results have implications for the prevention of Alzheimer’s disease through targeted early intervention efforts.

Memory decline is one of the first signs of cognitive and neurodegenerative diseases, such as Alzheimer’s disease. Understanding and designing interventions for memory decline is critical for efforts toward preventing or delaying these illnesses.

“We found different risk factors for stable memory and for rapidly declining memory,” said Peggy McFall, lead author and research associate in the Department of Psychology. “It may be possible to use these factors to improve outcomes for older adults.”

McFall, who conducted the study in collaboration with Professor Roger Dixon, used machine learning to analyze data from a longitudinal study based in Edmonton, Alberta.

The study found that adults with healthy memory were more likely to be female, educated, and engage in more social activities, such as hosting a dinner party, and novel cognitive activities, such as using a computer or learning a second language. For adults age 55 to 75, healthy memory was associated with lower heart rate, higher body mass index, more self-maintenance activities, and living companions. Adults over 75 had faster gait and fewer depressive symptoms.

Those with declining memory tended to engage in fewer new cognitive activities. Younger adults, age 55 to 75, younger, had higher heart rates, and engaged in fewer self-maintenance activities, while adults over age 75 had slower gait and engaged in fewer social activities.

“These modifiable risk and protective factors may be converted to potential intervention targets for the dual purpose of promoting healthy memory aging or preventing or delaying accelerated decline, impairment, and perhaps dementia,” said McFall. For instance, clinicians might target specific groups with an intervention to increase new cognitive activities among men or improve mobility for those over age 75.

---

Story Source:

Materials provided by University of Alberta. Note: Content may be edited for style and length.

---

Journal Reference:

1. G. Peggy McFall, Kirstie L. McDermott, Roger A. Dixon. Modifiable Risk Factors Discriminate Memory Trajectories in Non-Demented Aging: Precision Factors and Targets for Promoting Healthier Brain Aging and Preventing Dementia? Journal of Alzheimer’s Disease, 2019; 1 DOI: 10.3233/JAD-180571

https://www.sciencedaily.com/releases/2019/04/190410090333.htm

Living transplant donors need long-term monitoring, too

While organ transplant recipients receive continual care as the end-stage treatment to their condition, attention also should be given to living donors, who can suffer from hypertension, diabetes and other disorders after donation, according to a study by researchers at UC San Francisco.

As reported online April 12, 2019, in JAMA Network Open, by aggregating data from publicly available clinical studies, the researchers found that nearly one in seven kidney donorsexperienced a potentially adverse event that may be related to their donation.

“Our findings are significant for the transplant community,” said co-senior author Minnie Sarwal, MD, Ph.D., professor of surgery, medicine and pediatrics at UCSF. “We want to encourage donation, yet making the process more transparent for outcomes and safer by improved monitoring for donors, which does not exist long term, also appears to be of critical importance.”

Solid organ transplant is the preferred treatment for most end-stage organ diseases, and about 6,000 adults in the United States and 30,000 worldwide are living donors annually. However, some living kidney donors develop postoperative kidney failure and enter the organ donation system as potential recipients on the transplant waiting list, and this group also is at increased long-term risk for cardiovascular and end-stage renal disease, as well as all-cause mortality, compared to matched nondonors eligible to donate.

In the new paper, Sarwal and her colleagues analyzed 20 clinical transplant studies compiled between 1963 and 2016 and housed in ImmPort, a clinical and molecular data repository hosted by the National Institute of Allergy and Infectious Diseases, to review 9,558 donors, referring to their final data set as “ImmTransplant.” To validate the study’s accuracy, they used data collected from 1987 to 2016 and stored in the U.S. national transplant registry maintained by the Organ Procurement and Transplantation Network administered by the United Network for Organ Sharing.

While no recorded events occurred in 85.3 percent of donors, the most common adverse events were hypertension (806 cases, 8.4 percent), diabetes (190, 2 percent), proteinuria (171, 1.8 percent) and lack of bowel movements post-surgery (147, 1.5 percent). Relatively few events (269) occurred in the first two years after donation, and of the 1,746 events occurring from two to 40 years after, 1,575 cases (90.2 percent) were nonsurgical.

U.S. transplant programs are required to follow up with donors for only two years after transplant.

Further, the researchers found that living kidney donors can experience renal or cardiovascular issues that increase their likelihood of renal failure without first experiencing intermediate events. Complications or conditions soon after donation also may not be predictive of long-term renal function or vice versa. As such, long-term systematic renal monitoring and routine regular checkups for living kidney donors is recommended.

Sarwal said this study supplements ongoing research while a nationwide registry is being established to improve the recruitment, awareness, education and long-term health management of potential living donors, per an initiative launched after a June 2016 White House organ donation and transplant summit.

Demographic characteristics from the study also can provide insights into donation patterns and potential strategies to better inform living donors, said Sarwal, treasurer of The Transplantation Society, an organization whose goal is to provide global leadership in transplantation.

For example, a spike was found in living kidney donations among U.S. women whose age was in the childbearing range (age 25). As kidney donation increases the risk of hypertension and preeclampsia in pregnancies, living donors in this age range should be better informed and counseled.

“We hope these findings supplement well-informed discourse for living organ donation among potential donors, recipients, clinicians, researchers and the public,” said lead author Jieming Chen, Ph.D., a former postdoctoral researcher at UCSF now with Genentech. “We’ve curated the transplant datasets in ImmPort as an initial proof of concept of its utility and applications so that the collection, curation and secondary analyses of other publicly available transplant data can be built on.”

https://medicalxpress.com/news/2019-04-transplant-donors-long-term.html

CVS Health initiated at BMO Capital

CVS Health initiated with a Market Perform at BMO Capital. BMO Capital analyst Matt Borsch initiated CVS Health with a Market Perform rating and a $58 price target. The analyst said that he is aware of the low valuation of the stock, but is “wary of further deterioration in the outlook given headwinds on CVS legacy businesses that have recently intensified,” and is not confident “the pressures will diminish next year.”

https://thefly.com/landingPageNews.php?id=2891079