Neurodegenerative Disease, Cancer Stocks Among Top Biotech Gainers In 2021

 Nasdaq Biotechnology ETF 

IBB 0.22% advancing about 8% year-to-date compared to the roughly 14% gain for the S&P 500 Index.

In comparison, the IBB was up 13.6% in the first half of 2020. The strength in the space in the last year was primarily due to risk aversion as the pandemic drove investors into defensive plays such as biotechs. Additionally, companies that kickstarted COVID-19 vaccine programs ran up sharply in 2020.

The relatively muted performance so far this year may have to do with the return of risk appetite leading to rotation out of the sector. The rally in vaccine stocks also moderated following emergency use authorizations being accorded for three COVID-19 shots.

Here are a few stocks that stood out with solid gains amid the muted overall sector performance:

Cassava Sciences Inc 

SAVA 1.44%: Shares of Cassava, a neurodegenerative disease company, spiked in early February on the back of positive results from the interim analysis of data from an open-label study of simufilam, its lead drug candidate for the treatment of Alzheimer's disease.

It hit an intraday high of $117.54 on Feb. 4. After pulling back and consolidating, the stock picked up pace in June. By virtue of the strong advance in the year-to-date period, the stock has tacked on about 1,150%.

Annovis Bio Inc ANVS 8.13%: This biopharma that focuses on therapies for neurodegenerative diseases has seen its shares surge by over 1, 060% so far this year.

The company's lead drug ANVS401 is being evaluated for multiple indications, including Alzheimer's disease and Parkinson's disease. It works by improving axonal transport by inhibiting the neurotoxic proteins that kill nerve cells. A positive Phase 2 readout for the asset in Alzheimer's disease sent the stock soaring in late April.

Atossa Therapeutics Inc ATOS 16.09%: The Seattle-based biopharma focusing on treatments for breast cancer and COVID-19 has surged up about 770% year-to-date.

From under $1 at the start of year, the stock rallied to a high of $4.90 in early February on the back of positive Phase 2 data for Endoxifen administered between diagnosis and surgery in breast cancer patients. The upward momentum faltered subsequently and the stock pulled back to a low of $1.48 on April 19.

Atossa recovered from there and the rally picked up steam in June amid the release of positive final Phase 2 data for Endoxifen and inclusion in the Russell 2000 and 3000 indexes.

Entera Bio Ltd. ENTX 1.43%: The biopharma, which develops orally delivered large molecule therapeutics for use in areas with significant unmet medical need, has seen its shares surge higher by over 460% so far this year.

The company's pipeline consists of EB613, which is being evaluated for osteoporosis, and EB612 for hypoparathyroidism.

Entera Bio shares jumped in early April when it reported positive topline biomarker data for EB613. The stock received a shot in the arm from the positive six-month bone mineral density results from the Phase 2 clinical trial of EB613, which the company reported last week.

PDS Biotechnology Corp PDSB 3.8%: PDS has gained about 450% year-to-date. The company has oncology and infectious disease programs.

The gains for the year-to-date period reflected the presentation of data from the Phase 2 combination study with PDS0101 in HPV-associated tumors at the ASCO conference, and also its COVID-19 program.

Anavex Life Sciences Corp. NASDAQAVXL shares have gained about 430% year-to-date. The company is developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders.

The company's lead product candidate blarcamesine (ANAVEX2-73) is being evaluated for multiple indications. The predictive biomarker of response established with SIGMAR1 mRNA expression correlates significantly with responses in primary and secondary clinical efficacy endpoints from the proof-of-concept Phase 2 trial in Parkinson's disease, the company announced. 

Brooklyn ImmunoTherapeutics Inc NYSEBTX: This New York-based gene and cell therapy company has clocked gains of about 375% year-to-date. 

The company is focused on exploring the role cytokine-based therapy can have in treating patients with cancer. The company is also exploring opportunities to advance oncology, blood disorder and monogenic disease therapies using highly innovative gene editing/cell therapy technology.

Brooklyn initiated a mid-stage study of IRX-2 in combination with Merck & Co., Inc.'s MRK 0.83% Keytruda and chemotherapy in triple-negative breast cancer.

In March, the company completed its reverse merger with NTN Buzztime.

Howard Federoff took over as CEO in early April. Later that month, the company acquired an exclusive license for mRNA gene editing and cell therapies technology of Factor Bioscience and Novellus Therapeutics, pursuant to an exercise of a previously announced option.

The company has also been added to the Russell 3000 Index.

Brooklyn's most advanced program is the study of the lead asset IRX-2, a human cell-derived biologic with multiple active cytokine components in patients with head and neck cancer. With commercialization years away — and ultimately contingent on IRX-2 clearing clinical and regulatory hurdles — the valuation of Brooklyn looks a little stretched.

https://www.benzinga.com/general/biotech/21/07/21773695/neurodegenerative-disease-cancer-stocks-among-top-biotech-gainers-in-2021

Milder COVID-19 symptoms tied to prior run-ins with other coronaviruses

 A study by Stanford University School of Medicine investigators hints that people with COVID-19 may experience milder symptoms if certain cells of their immune systems "remember" previous encounters with seasonal coronaviruses -- the ones that cause about a quarter of the common colds kids get.

These immune cells are better equipped to mobilize quickly against SARS-CoV-2, the coronavirus responsible for COVID-19, if they've already met its gentler cousins, the scientists concluded.

The findings may help explain why some people, particularly children, seem much more resilient than others to infection by SARS-CoV-2, the coronavirus that causes COVID-19. They also might make it possible to predict which people are likely to develop the most severe symptoms of COVID-19.

The immune cells in question, called killer T cells, roam through the blood and lymph, park in tissues and carry out stop-and-frisk operations on resident cells. The study, published online July 1 in Science Immunology, showed that killer T cells taken from the sickest COVID-19 patients exhibit fewer signs of having had previous run-ins with common-cold-causing coronaviruses.

Discussions about immunity to COVID-19 often center on antibodies -- proteins that can latch onto a virus before it's able to infect a vulnerable cell. But antibodies are easily fooled, said Mark Davis, PhD, a professor of microbiology and immunology; director of Stanford's Institute for Immunity, Transplantation and Infection; and a Howard Hughes Medical Institute investigator. Davis is the study's senior author.

"Pathogens evolve quickly and 'learn' to hide their critical features from our antibodies," said Davis, who is also the Burt and Marion Avery Family Professor. But T cells recognize pathogens in a different way, and they're tough to fool.

Our cells all issue real-time reports on their inner state of affairs by routinely sawing up some samples of each protein they've made lately into tiny pieces called peptides and displaying those peptides on their surfaces for inspection by T cells.

When a killer T-cell's receptor notices a peptide on a cell's surface that doesn't belong there -- for example, it's from a protein produced by an invading microorganism -- the T cell declares war. It multiplies furiously, and its numerous offspring -- whose receptors all target the same peptide sequence -- fire up to destroy any cell carrying these telltale-peptide indications of that cell's invasion by a pathogenic microbe.

Some of the original killer T cell's myriad daughter cells enter a more placid state, remaining above the fray. These "memory T cells" exhibit heightened sensitivity and exceptional longevity. They persist in the blood and lymph often for decades, ready to spring into action should they ever cross paths with the peptide that generated the wave of T-cell expansion that begat them. That readiness can save valuable time in stifling a previously encountered virus or a close cousin.

As the pandemic progressed, Davis mused: "A lot of people get very sick or die from COVID-19, while others are walking around not knowing they have it. Why?"

To find out, the study's first author, postdoctoral fellow Vamsee Mallajosyula, PhD, first confirmed that some portions of SARS-CoV-2's sequence are effectively identical to analogous portions of one or more of the four widespread common-cold-causing coronavirus strains. Then he assembled a panel of 24 different peptide sequences that were either unique to proteins made by SARS-CoV-2 or also found on similar proteins made by one or more (or even all) of the seasonal strains.

The researchers analyzed blood samples taken from healthy donors before the COVID-19 pandemic began, meaning they'd never encountered SARS-CoV-2 -- although many presumably had been exposed to common-cold-causing coronavirus strains. The scientists determined the numbers of T cells targeting each peptide represented in the panel.

They found that unexposed individuals' killer T cells targeting SARS-CoV-2 peptides that were shared with other coronaviruses were more likely to have proliferated than killer T cells targeting peptides found only on SARS-CoV-2. The T cells targeting those shared peptide sequences had probably previously encountered one or another gentler coronavirus strain -- and had proliferated in response, Davis said.

Many of these killer T cells were in "memory" mode, he added.

"Memory cells are by far the most active in infectious-disease defense," Davis said. "They're what you want to have in order to fight off a recurring pathogen. They're what vaccines are meant to generate."

Killer T cells whose receptors target peptide sequences unique to SARS-CoV-2 must proliferate over several days to get up to speed after exposure to the virus, Davis said. "That lost time can spell the difference between never even noticing you have a disease and dying from it," he said.

To test this hypothesis, Davis and his colleagues turned to blood samples from COVID-19 patients. They found that, sure enough, COVID-19 patients with milder symptoms tended to have lots of killer-T memory cells directed at peptides SARS-CoV-2 shared with other coronavirus strains. Sicker patients' expanded killer T-cell counts were mainly among those T cells typically targeting peptides unique to SARS-CoV-2 and, thus, probably had started from scratch in their response to the virus.

"It may be that patients with severe COVID-19 hadn't been infected, at least not recently, by gentler coronavirus strains, so they didn't retain effective memory killer T cells," Davis said.

Davis noted that cold-causing seasonal coronavirus strains are rampant among children, who rarely develop severe COVID-19 even though they're just as likely to get infected as adults are.

"Sniffles and sneezes typify the daycare setting," he said, "and coronavirus-caused common colds are a big part of the reason. As many as 80% of kids in the United States get exposed within the first couple of years of life."

Davis and Mallajosyula have filed, through Stanford's Office of Technology Licensing, for patents on the technology used in this study.

Davis is a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Stanford Maternal and Child Health Research Institute, the Stanford Cancer Institute and the Stanford Wu Tsai Neurosciences Institute.

Other Stanford study co-authors are former undergraduate student Conner Ganjavi; postdoctoral scholar Saborni Chakraborty, PhD; former life science research professionals Alana McSween and Allison Nau; graduate student Ana Jimena Pavlovitch-Bedzyk; life science research professional Julie Wilhelmy; Monali Manohar, PhD, laboratory director and research scientist at the Sean N. Parker Center for Asthma and Allergy Research; and Kari Nadeau, MD, PhD, professor of pediatrics and director of the Sean N. Parker Center.

The work was funded by the National Institutes of Health (grants AI057229 and U01 AI140498); Stanford's Institute for Immunity, Transplantation and Infection; the Howard Hughes Medical Institute; the Bill and Melinda Gates Foundation; the Sean N. Parker Center and the Sunshine Foundation.

Stanford's Department of Microbiology and Immunology also supported the work.

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Story Source:

Materials provided by Stanford Medicine. Original written by Bruce Goldman. Note: Content may be edited for style and length.

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Journal Reference:

1. Vamsee Mallajosyula, Conner Ganjavi, Saborni Chakraborty, Alana M. McSween, Ana Jimena Pavlovitch-Bedzyk, Julie Wilhelmy, Allison Nau, Monali Manohar, Kari C. Nadeau, Mark M. Davis. CD8+ T cells specific for conserved coronavirus epitopes correlate with milder disease in COVID-19 patients. Science Immunology, July 1, 2021; DOI: 10.1126/sciimmunol.abg5669

https://www.sciencedaily.com/releases/2021/07/210701140959.htm

Pioneering noninvasive technique for neurological conditions

 Indiana University School of Medicine researchers are developing a new, noninvasive brain stimulation technique to treat neurological disorders, including pain, traumatic brain injury (TBI), epilepsy, Parkinson's disease, Alzheimer's disease and more.

"Given the increasing use of brain stimulation in human brain study and treatment of neurological diseases, this research can make a big impact on physicians and their patients," said Xiaoming Jin, PhD, associate professor of anatomy, cell biology and physiology.

When someone experiences a brain injury, nerve injury, or neurodegeneration, such as in epilepsy and TBI, there is damage to the brain which can lead to loss and damage of nerve or neurons and development of hyperexcitability that underlies some neurological disorders such as neuropathic pain and epilepsy.

"The conventional treatment is mainly to try to directly inhibit such hyperexcitability," Jin said, "but we found the initial damage of the brain or nerve system was caused by a loss of brain tissue, which causes the nervous system to compensate for loss of function by working harder, so we need to stimulate activity instead of inhibit it."

The technique, described in a newly published paper in Neurotherapeutics, uses a new type of magnetoelectric nanoparticles that can be delivered to a specific part of the brain using a magnetic field. After, a magnetic wave can be emitted to stimulate neural activity in that particular part of the brain. The method is noninvasive, good for stimulating deep brain function and is more efficient than traditional methods of brain stimulation, without the need for genetic manipulation.

"This is the only new type of nanoparticle that allows us to effectively stimulate the brain without doing any invasive procedures," Jin said. "We can inject the nanoparticle as a solution into the vein and then bring it to any part of the body. When you apply a magnet on the head, you can localize and deliver the nanoparticle to the targeted brain region."

The team has been working on the technique for five years in collaboration with the University of Miami and hopes to begin studying the method in humans in the next couple of years. The study has received funding from the Defense Advanced Research Projects Agency (DARPA) of the United States Department of Defense, National Science Foundation, as well as the Indiana Clinical and Translational Sciences Institute (CTSI), which helped provide funding for a medical neuroscience graduate student, Tyler Nguyen, to participate in the research. Read the full published paper in Neurotherapeutics.

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Story Source:

Materials provided by Indiana University School of Medicine. Original written by Christina Griffiths. Note: Content may be edited for style and length.

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Journal Reference:

1. Tyler Nguyen, Jianhua Gao, Ping Wang, Abhignyan Nagesetti, Peter Andrews, Sehban Masood, Zoe Vriesman, Ping Liang, Sakhrat Khizroev, Xiaoming Jin. In Vivo Wireless Brain Stimulation via Non-invasive and Targeted Delivery of Magnetoelectric Nanoparticles. Neurotherapeutics, 2021; DOI: 10.1007/s13311-021-01071-0

https://www.sciencedaily.com/releases/2021/07/210702114657.htm

Cancer: Immunotherapies without side effects?

 In recent years, immunotherapy has revolutionised the field of cancer treatment. However, inflammatory reactions in healthy tissues frequently trigger side effects that can be serious and lead to the permanent discontinuation of treatment. This toxicity is still poorly understood and is a major obstacle to the use of immunotherapy. Scientists from the University of Geneva (UNIGE), Switzerland, and Harvard Medical School, United States, have succeeded in establishing the differences between deleterious immune reactions and those targeting tumour cells that are sought after. It appears that while the immune mechanisms are similar, the cell populations involved are different. This work, published in the journal Science Immunology, makes it possible to envisage better targeted, more effective, and less dangerous treatments for cancer patients.

Based on massive stimulation of the patient's immune system, immunotherapies have saved many lives. Unfortunately, they are not without consequences. "When the immune system is activated so intensively, the resulting inflammatory reaction can have harmful effects and sometimes cause significant damage to healthy tissue," says Mikaël Pittet, holder of the ISREC Foundation Chair in Onco-Immunology at UNIGE Faculty of Medicine Department of Pathology and Immunology and Centre for Translational Research in Onco-Haematology, and a member of the Swiss Cancer Centre Leman. "Therefore, we wanted to know if there are differences between a desired immune response, which aims to eliminate cancer, and an unwanted response, which can affect healthy tissue. The identification of distinctive elements between these two immune reactions would indeed allow the development of new, more effective and less toxic therapeutic approaches."

Using liver biopsy samples from patients treated at the CHUV and the HUG who had suffered such toxic reactions, the scientists studied the cellular and molecular mechanisms at work to reveal similarities and dissimilarities.

A similar response, but with different cells

In an immunotherapy-related toxic response, two types of immune cells -- macrophage and neutrophil populations -- appear to be responsible for attacking healthy tissue, but are not involved in killing cancer cells. In contrast, another cell type -- a population of dendritic cells -- is not involved in attacking healthy tissue but is essential for eliminating cancer cells. "Immunotherapies can trigger the production of specialised proteins that alert the immune system and trigger an inflammatory response, explains Mikaël Pittet. In a tumour, these proteins are welcome because they allow the immune system to destroy cancerous cells. In healthy tissue, however, the presence of these same proteins can lead to the destruction of healthy cells. The fact that these inflammatory proteins are produced by such different cells in tumours and healthy tissue is therefore an interesting finding."

Dendritic cells are very rare, whereas macrophages and neutrophils are much more common. Some macrophages are present in most of our organs from embryonic development stages and remain there throughout our lives. Contrary to what was previously thought, these macrophages do not necessarily inhibit inflammation but, stimulated by immunotherapies, can trigger a harmful inflammatory response in the healthy tissue where they reside, thus explaining why toxicity can affect different organs.

Neutralising neutrophils for a double benefit

When macrophages are activated by drugs, they produce inflammatory proteins. These in turn activate neutrophils, which execute the toxic reaction. "This opens the possibility of limiting immunotherapy's side effects by manipulating neutrophils," says Mikaël Pittet.

The research team confirmed their discovery by studying the immune reactions of mice whose cell activity was modulated with genetic tools. They were able to identify a loophole that could be exploited to eliminate these side effects. Indeed, neutrophils produce some factors that are important for the development of toxicity, including TNF-α, which could be a therapeutic target. TNF-α inhibitors are already used to modulate the immune response in people with arthritis and could perhaps be useful in the cancer setting to inhibit the toxic effects of neutrophils during immunotherapy. "Furthermore, inhibiting neutrophils could be a more effective way to fight cancer: in addition to triggering a toxic response, some of these cells also promote tumour growth. Thus, by managing to control them, we could have a double beneficial effect: overcome the toxicity in healthy tissues, and limit the growth of cancerous cells," concludes Mikaël Pittet.

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Story Source:

Materials provided by Université de Genève. Note: Content may be edited for style and length.

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Journal Reference:

1. Marie Siwicki, Nicolas A. Gort-Freitas, Marius Messemaker, Ruben Bill, Jeremy Gungabeesoon, Camilla Engblom, Rapolas Zilionis, Christopher Garris, Genevieve M. Gerhard, Anna Kohl, Yunkang Lin, Angela E. Zou, Chiara Cianciaruso, Evangelia Bolli, Christina Pfirschke, Yi-Jang Lin, Cecile Piot, John E. Mindur, Nilesh Talele, Rainer H. Kohler, Yoshiko Iwamoto, Mari Mino-Kenudson, Sara I. Pai, Claudio deVito, Thibaud Koessler, Doron Merkler, Alexander Coukos, Alexandre Wicky, Montserrat Fraga, Christine Sempoux, Rakesh K. Jain, Pierre-Yves Dietrich, Olivier Michielin, Ralph Weissleder, Allon M. Klein, Mikael J. Pittet. Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy. Science Immunology, 2021; 6 (61): eabi7083 DOI: 10.1126/sciimmunol.abi7083

https://www.sciencedaily.com/releases/2021/07/210703120509.htm

Our Narrow Understanding of Myocarditis After COVID Vaccines

 As the wave of vaccination to protect against COVID-19 spreads across the world, surveillance for possible vaccine-related adverse events remains active. So far, no data have emerged to definitively link the mRNA vaccines manufactured by Pfizer/BioNTech and Moderna with serious adverse events other than rare episodes of anaphylaxis, and the vaccines are performing well in their intended goal of reducing COVID-19 morbidity and mortality in vaccinated populations. Overall, the vaccines have been an unparalleled scientific success -- a source of light in the relentless storm of the COVID-19 pandemic.

Currently, there is a focus on the possible link between the mRNA vaccines and myocarditis. This attention has grown out of a small number of reported potential cases, predominantly in the U.S., Europe, and Israel. In both children and adults, cases of myocarditis have been identified shortly after administration of these vaccines -- typically 2 to 4 days after receiving the second dose -- and appear to follow a relatively benign course. Thanks to the detailed reports published in the literature, there is now an initial collection of data on these patients and their relevant clinical and diagnostic findings. Patients have typically had symptoms of chest pain, and were subsequently found to have elevated levels of troponin, abnormal electrocardiograms, and cardiac MRI patterns consistent with myocarditis. Thankfully, feared serious complications of myocarditis such as circulatory failure or dangerous arrhythmias appear to be exceptionally uncommon. Ideally, these reports will serve as foundational knowledge as our study of these relationships continues.

However, this research is still in its infancy and there remain several challenges in understanding the potential relationship between these vaccines and myocarditis.

Gaps in Our Knowledge

First, myocarditis remains a heterogenous disease with highly variable presentations and causes. As such, it is challenging to establish a comparison between historical cases of myocarditis and those seen in the current case reports. Second, the retrospective nature of the current case reports leaves them open to bias and limits the ability to offer an appropriate matched control group. The widespread press coverage of the topic could certainly result in availability bias on behalf of providers, and the lack of a protocolized diagnostic approach to these cases leaves open the possibility of missed alternative diagnoses (particularly infection with non-SARS-CoV-2 viruses, which have been previously implicated in myocarditis). Third, even if a causal relationship is established between COVID-19 vaccinations and myocarditis, the quantification and communication of risk is a complex task. Again, the question remains, As compared to what? Should we compare the risk of myocarditis associated with vaccination to the rate of myocarditis in those affected with COVID-19? To the risk of myocarditis in age-matched controls? To the risk of myocarditis in those receiving other vaccines?

Moving Toward a Better Understanding

As always, history holds valuable lessons: Other vaccinations have been previously linked to myocarditis. For example, surveillance and prospective data in patients receiving smallpox vaccination have identified higher than expected rates of myocarditis. These studies offer useful insights into our review of the current literature on COVID-19 vaccine recipients. Many cases of myocarditis after smallpox vaccines would have never been uncovered without a prospective trial, as many patients would not have sought medical care for the mild symptoms they experienced. Many vaccine recipients were likely to attribute symptoms of chest discomfort to the typical myalgias expected to occur after vaccination, and many of the symptoms may have responded to over the counter anti-inflammatories. As such, retrospective surveillance studies likely underreport the incidence of myocarditis after smallpox vaccination. Though the same may be true of COVID-19 vaccine recipients, we cannot draw these conclusions without prospective data. Therefore, the studies on smallpox vaccination and myocarditis should serve as an important guide for future investigations into the relationship between COVID-19 vaccination and myocarditis.

The growing number of reported cases of myocarditis after COVID-19 vaccination are an important contribution to the scientific literature. However, these should be seen as preliminary, and should serve to foster robust clinical, epidemiologic, molecular, and behavioral investigations in the future. Medical providers should be aware of the potential link between myocarditis and COVID-19 vaccination, but must continue to use best clinical judgement in evaluating patients and discussing risk. The COVID-19 vaccinations are a critical component in the global battle against a devastating pandemic, and the individual and public health benefit of these vaccines remains robust. Those who are eligible to receive the COVID-19 vaccines should continue to do so.

Kathryn F. Larson, MD, is a cardiology fellow at the Mayo Clinic in Rochester, Minnesota.

https://www.medpagetoday.com/opinion/second-opinions/93414

Arrowhead ENaC News 'Not Thesis Changing', RBC Says; PT Lowered to $83

 RBC Capital analyst Luca Issi lowered the price target on Arrowhead Pharma (NASDAQ: ARWR) to $83.00 (from $90.00) while maintaining a Outperform rating following news the company is voluntarily pausing the Phase I/II trial for ENaC due to local lung inflammation seen in rats. Issi said while unfortunate, the news is not "thesis changing."

The analyst commented, "While this is unfortunate, we have always been cautious on ENaC (we had it at 15% PoS) given IONS's recent discontinuation and the many prior failures. We are buyers into weakness as setbacks like this are part of drug development, and continue to like a rich pipeline that balances fairly de-risked liver targets (A1AT, APOC3, ANG3, HSD, LpA, HBV) with higher risk/reward extra-hepatic targets (HIF, DUX4, EnAC, Lung2). PT lowered by $7 to $83 as we remove EnAC and lower platform PoS."

https://www.streetinsider.com/Analyst+Comments/Arrowhead+Pharma+%28ARWR%29+ENaC+News+Not+Thesis+Changing%2C+RBC+Says%3B+PT+Lowered+to+%2483/18638479.html

Zymeworks (ZYME) Explores Potential Sale Following Takeover Approach

 Biopharmaceutical company Zymeworks Inc. (NYSE: ZYME) has received a takeover approach and is working with an investment bank

https://www.streetinsider.com/Hot+M+and+A/Zymeworks+%28ZYME%29+Explores+Potential+Sale+Following+Takeover+Approach+-+Source/18633227.html