Angion Biomedica Nears End of Clinical Trials for Organ-Repairing Molecule

Repairing a damaged organ in order to allow an individual to have a healthier life, as well as a greater quality of life, could soon be a reality as New York-based Angion Biomedica Corp.moves toward completing clinical trials of its lead asset.

The company is developing ANG-3777, a small molecule harnessing the effects of Hepatocyte growth factor (HGF). HGF is an organ repair protein best known for providing the liver with a unique ability to regenerate itself. Angion research has noted that HGF also triggers extensive self-repair pathways within the kidneys, liver, heart, brain and lungs. Angion researchers discovered a small molecule that allows the body to drive a healing response.

Angion Chief Executive Officer Jay Venkatesan, who joined the company last year, said in a typical case when a patient has an injured organ, the body will attempt to repair itself. Angion’s lead candidate operates along the HGF pathway and “drives some self-repair along the natural pathways,” he told BioSpace in an exclusive interview. Currently, Venkatesan said there is no therapeutic on the market that delivers the same effect. Angion has begun its research with ANG-3777 in the kidney, and if it continues to demonstrate efficacy and safety in the late-stage trial, Venkatesan said the company will likely explore its uses in other organs.

“Right now it seems to be a ubiquitous path,” Venkatesan said. That means that the Angion candidate could drive a healing response in almost any organ in the body. “It’s interesting to see what the limits are.”

AGN-377 is in two studies, a Phase II and a Phase III. The late-stage study concerns patients who have undergone a kidney transplant. The trial will continue a Phase II study of kidney transplant patients who had low or no urine output post-transplant. In the Phase II trial, patients were provided three doses of ANG-3777 within three days of the transplant. Over an assessed period of 28 days, the patients demonstrated increased urine output, lowered serum creatinine and improved renal function. Additionally, the results showed that the dosing reduced the need for dialysis. The Phase II observations, which Venkatesan said was meant to be a proof-of-concept study, will be confirmed in the Phase III GIFT (Graft Improvement Following Transplantation) study. In the late-stage trial, patients will be provided three doses of ANG-3777 or placebo within 30 hours of transplant. The trial will include about 300 people. Data from this trial is expected in the first quarter of 2020.

The data was compelling enough for Vivek Ramaswamy’s Sinovant to license AGN-3777 for potential commercialization in the People’s Republic of China, Hong Kong, Macau and Taiwan. Sinovant will conduct clinical trials of the asset, which it dubbed BB3, in China.

Angion is also conducting a mid-stage trial in cardiac patients. Data from this trial is expected in the second quarter next year. Angion plans to initiate a heart attack study as well in order to improve measure of heart function following catheterization.

ANG-377 isn’t the only exciting asset in Angion’s pipeline. Last week the company secured a $4.76 million Department of Defense follow-on grant for ANG-3070, the company’s precision drug candidate for the treatment of fibrotic diseases. Specifically, ANG-3070 is in development for primary focal segmental glomerulosclerosis (FSGS), a form of chronic kidney disease.

The DoD grant supports a previous $2.2 million grant that was used to establish preclinical proof-of-concept for ANG-3070 as an anti-fibrotic agent with the potential to delay or halt the progression of FSGS. Angion partnered with Nephrotic Syndrome Study Network to advance the study of ANG-3070. The study data is expected to support the completion of an Investigational New Drug Application and launch human studies of ANG-3070 for FGS and other fibrotic conditions. Venkatesan anticipates the potential start of Phase I trials in the third quarter of this year and the beginning of efficacy studies in 2020.

As Angion pushes forward with the development of its candidates, the company is also pushing forward in growth. Venkatesan said the company will likely double in headcount by the end of the year.

“I’ve been happy with the progress we’re making with 3777 and pushing 3070 into the clinic. Once that gets into the clinic, there’s a lot of places we can go with that,” Venkatesan said.

https://www.biospace.com/article/angion-biomedica-focuses-on-organ-repair-and-fibrotic-treatments/

Gilead Presents New NASH Data at the International Liver Congress

– New Proof-of-Concept Data for Combination of Investigational FXR Agonist Cilofexor and ACC Inhibitor Firsocostat in NASH —

Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data from the company’s clinical research program in nonalcoholic steatohepatitis (NASH) being presented at The International Liver Congress™ 2019 in Vienna. The data support Gilead’s efforts to develop combination therapies to target different aspects of NASH, evaluate the utility of noninvasive tests for the identification of patients living with the disease and advance overall understanding of the complexities and burden of NASH.

“NASH is a complex disease with multiple biological pathways that influence its progression. Combination therapeutic approaches which target these pathways, are likely to be needed to effectively treat patients living with NASH, particularly those with advanced fibrosis who have the greatest unmet need,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead Sciences. “We are encouraged by the results of our proof-of-concept study being presented this week and look forward to sharing further combination data from the Phase 2 ATLAS trial later this year.”

Combination Therapy Treatment for NASH

A proof-of-concept study demonstrated that the combination of the investigational, selective, non-steroidal farnesoid X receptor (FXR) agonist cilofexor (GS-9674) and the acetyl-CoA carboxylase (ACC) inhibitor firsocostat (GS-0976) resulted in improvements in hepatic steatosis, liver stiffness, liver biochemistry and serum fibrosis markers. In the study, 20 patients with NASH received cilofexor 30 mg and firsocostat 20 mg orally once daily for 12 weeks. A significant decline of at least 30 percent in hepatic fat measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline to 12 weeks was observed in 74 percent of patients. Improvements in liver biochemistry tests including serum ALT (median relative reduction, -37%; p<0.001) and GGT (-32%; p<0.001), along with markers of reduced bile acid synthesis, were observed at 12 weeks. Treatment was well tolerated and pruritus was not reported in any patients. Asymptomatic, Grade 3 hypertriglyceridemia was observed in two patients. No patients withdrew from the study due to adverse events.

https://www.marketscreener.com/GILEAD-SCIENCES-4876/news/Gilead-Sciences-Presents-New-Data-in-Nonalcoholic-Steatohepatitis-NASH-at-the-International-Live-28387562/

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.

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Story Source:

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

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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.

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Story Source:

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

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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