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Bruce Linton Talks Psychedelics Investments, Microdosing And LSD: ‘The Therapeutic Potential Of Psychedelics Is Greater Than Cannabinoids’ – Benzinga

Posted on December 23, 2019 by Danzig

Earlier this year, Canopy Growth (NYSE: CGC) co-founder and former CEO Bruce Linton invested in a neuropharmaceutical company, Mind Medicine Inc.

MindMed is a psychedelicresearch company thats developing non-hallucinogenic medicine from psychedelic sources. The company has also welcomed Linton to its board of directors.

The 53-year-old entrepreneur told Benzinga heplans to spend 2020 searching for new business ideas andwill start a new business in 2021.

Linton has long found the psychedelics sector to be compelling, Linton said.

Prohibition or poor regulatory frameworks globallydon't mean that the underlying regulated substances are in fact terrible. The therapeutic potential of psychedelics is greater than cannabinoids, for sure.

Supporting a company developing psychedelic substances for medicinal purposes is the best way to rediscover the therapeutic potential of certain plants and mushrooms that have long been banned by the FDA, he said.

"The whole point of this exercise is to build a large platform company that welcomes many, many research projects ... and turns them into finished outcomes that create therapeutic benefit," Linton said in reference to his involvement with Mind Medicine.

Once the therapeutic properties of psychedelics in treating conditions like ADHD, opioid addiction and severe depression are acknowledged, their histories of prohibition will be irrelevant, the cannabis exec said.

In that sense, the process for legalizing these substances is similar tocannabis, he said: achange in public perception is the main tool in fighting prohibition.

"At the end of the day, we're having the same conversation, with the same cohort."

See Also: The Keys To Understanding Psilocybin's Medical Value, Market Potential

Mind Medicine is researching the psychiatric potential of LSD and 18-MC, a synthesized version of ibogaine that is showing promising results in the treatment of opioid addiction.

The company recently raised $6.2 million to conduct Phase 2 clinical trials of18-MC.

Kevin OLeary, co-host of ABCs "Shark Tank," is among the companys investors.

Benzinga spoke with Mind Medicine co-founder and director JR Rahn.

Rahn, who has a tech background, decided to focus his entrepreneurial efforts on psychedelics after seeing many of his Silicon Valley colleagues microdosing LSD and other psychedelic compounds to increase focus and performance.

After researching the environment, Rahn said he decided to focus on the 18-MC molecule because of its promisein treating opioid addiction.

In 2013, the National Institute on Drug Abuse awarded a $6.7-million research grant to a pharmaceutical research company, Savant, to subsidize preclinical development of 18-MC for the treatment of obesity and substance use disorders.

Mind Medicine sprouted from Savant, Rahn said.

I co-founded the company with the Savant CEO. Savant sold the 18-MC program to MindMed in a share deal. Savants entire team has joined MindMed and is 100% focused on MindMed now. We used that money to do all this preclinical work and conduct a Phase 1 trial in humans to demonstrate that it was safe.

Rahn said his company aims to go public on Canadas NEO exchange in the first quarter of 2020, although the details are definitive.

The Benzinga Cannabis Capital Conference is heading to Miami Feb. 24-25 for its sixth installment.Click hereto learn more.

In recent years, psilocybinthe psychedelic molecule derived from magic mushroomshas been shaping up to be thestar compound in the psychedelic revolution of psychiatric treatment.

Psilocybin research is paving the way to psychedelic treatment in general and the development of psychedelics as an industry, Rahn said.

Yet hes placing his trust in the possibilities offered by 18-MC as a non-hallucinogenic psychedelic taken in microdoses.

Linton also commented on psilocybins commercial value.

The path to commercialization for the compound is financially unclear and difficult, he said. In Linton's view, commercial success relies on the possibility of modifying the original compounds.

"It's a very difficult molecule to alter. But there are a variety of other psychedelics that can be amended structurally to reduce their hallucinogenic effect, or they can actually have dose metering technologies that allow for well-structured delivery," he said.

"That to me gets to be very interesting commercially."

The definition of microdosing has yet to be standardized.

One approach would be to consider a "micro" dose of psychedelics to be one that's so low a hallucinogenic effect cannot be perceived, yet a therapuetic effect is achieved.

Yet as multiple scholars stated in a review paper on the subject, "there is no agreed scientific consensus on what microdosing is."

Linton is well aware of this fact.

"Whats micro?" he asks rhetorically. "How are you actually managing the dose? What's the frequency on micro? What are the primary indications that you're using it against? And what's the baseline of efficacy compared to other medicines? All that work is undone."

For Linton, the lack of knowledge on the subjectis more of an opportunity than a drawback.

"That means this is a bad idea currently because we have to do the work to show thats a great idea. If it was already a great idea, that means everybody did all the work. Im a big fan of investing in bad ideas."

Microdosing psychedelics offers vast potential not only in substance addiction, but also in the treatment of anxietyand adult ADHD.

The theory that this type of treatment can be dangerous to the heart especially using substances like LSD and 18-MC is unproven, Rahntold Benzinga.

"One of the things that well be doing is rigorous science and a Phase 2 clinical trial to demonstrate if there are issues relating to the heart or not. Because there aretheories that it might but there's been very little rigorous science on the microdosing subject."

See Also: Bruce Linton On His Next Steps, Says 'I'm Cheering For Entrepreneurs'

The pharmaceutical industry will be especially interested in psychedelics, Linton said.

Pharmaceutical companies need a pipeline of drugs that address mental health conditions and addiction, he said.

Rahn said there's a lack of investment in addiction medicine.

"On the opioid market, theres Suboxone. There are studies that demonstrate that it has a 90% failure rate. That's not good. We're not going to solve the opioid crisis that way."

For Linton, the debate around whether psychedelics have an effective impact on humans is no longer relevant.

"Humans have been using [psychedelics] for 3,000 or 4,000 years. Listen, if you don't think it does have an effect, then please go have an acid trip and tell me how it didn't affect you, he said. What I want to know is what amount, in what way, to get what outcome?"

Featured photo by Robina Weermeijer viaUnsplash.

Bruce Linton Talks Psychedelics Investments, Microdosing And LSD: 'The Therapeutic Potential Of Psychedelics Is Greater Than Cannabinoids' - Benzinga

Why Doctors Are Turning to Psychedelics to Treat Depression & Addiction – Men’s Journal

Posted on December 23, 2019 by Danzig

FOR DECADES, mental health experts have amassed anecdotal evidence that psychedelics could help people with intractable diseases like addiction, depression, and PTSD. Scientists at the Johns Hopkins Center for Psychedelic and Consciousness Research in Baltimore, which opened in the fall, plan to test these drugs rigorously so that one day they could be prescribed. We talked with two of the centers founding members, Alan Davis and Albert Garcia-Romeu, who are seeking out mental health and addiction treatments, to find out more about their research and how they plan to change our lives.

DAVIS: There are a couple of ways we believe it works. First is the experience itself. People who take psilocybin report having a deeply positive, mystical experience that seems to help them alter their perspective on their situation. More specifically, people with depression tend to feel isolated and disconnected from their daily lives. The experience of taking psilocybin makes them feel an intense interconnection that stays with them after the experience is over. People also report gaining insight on their depression, like they suddenly have an awareness of what they want to change in their life to help them move forward. That awareness, coupled with this mystical-like experience, serves as the catalyst for change.

ALBERT GARCIA-ROMEU: It helps people change their perspective, which is really useful for someone who is depressed or dealing with addiction. On the physical side, psilocybin disrupts patterns in the brainpatterns of negative thinking that become entrenched over time.

GARCIA-ROMEU: In a nutshell, psilocybin and other psychedelics like LSD bind to serotonin 2A receptors, creating mood-altering effects and changes in brain function. We know psilocybin decreases amygdala blood flow in people with depression, which is associated with better antidepressant effects. This is important because depressive symptoms seem to be associated with over-reactivity in the amygdala. Keep in mind that the data for psilocybin brain mechanisms in depression is very limited, from fewer than 20 people total. We are only starting to scratch the surface of how this works.

GARCIA-ROMEU: Honestly, its closer to a dorm room than a science lab. Our study setting looks like a therapists office: sofa, chairs, soft lighting. The most clinical item is a blood pressure monitor, which we use to keep track of physiological measures at 30- to 60-minute intervals throughout the sessions. One of the strongest predictors of a challenging experience or bad trip can be an overly cold and clinical setting, so we do our best to make it a place that feels warm and safe. Volunteers usually spend around eight hours here before any drug is administered, with the two people who monitor them after theyve taken the drug.

One misconception around this work: This is not a take-two-and-call-me-in-the-morning type of treatment.

DAVIS: The psilocybin is made for us by an academic chemist and put into a capsule thats taken orally. This isnt microdosing. A dose is moderate to highmore than recreational doses in a festival environment, for example.

DAVIS: We just wrapped up the main portion of the depression study, and now were doing follow-ups and preparing the data for publication. We had 24 participantsall studies here are done on people, not animals. Preliminary findings show approximately half of the participants had complete remission of depression at one month after the intervention of psilocybin plus psychotherapy, which is very promising.

DAVIS: We expect the full study to be published this coming year. After that, it can take several years before the treatments are approved by the FDA and made available to the public.

DAVIS: Funding. The government hasnt been backing this kind of work. So to get $17 million in private money [donors include entrepreneur Tim Ferriss, WordPress co-founder Matt Mullenweg, and the Steven & Alexandra Cohen Foundation]that goes a long way to getting the quality of studies we need to move the therapeutic research forward.

DAVIS: A couple of days after use, the person experiences a halo effect. Their mood improves, and they may be more open to suggestion. We use that time to help them make lifestyle changes to alter their outlook. Its not like the person just takes psilocybin, and thats it. We still use a full therapy approach, and were optimistic this may lead to greatly improved outcomes in people who have not found success in traditional treatment in the past.

GARCIA-ROMEU: That is probably one of the greatest misconceptions around this work. This is not a take-two-and-call-me-in-the-morning type of treatment. Nor is this like cannabis dispensaries where patients pick up the medication and take it at home, unsupervised. Psychedelics have the potential for much more intense and unpredictable psychoactive effects, so its best to administer them under carefully controlled conditions, in conjunction with intensive psychological support. Probably the best parallel in current medical care would be getting general anesthesia before surgerythis only happens at a medical facility under the careful supervision of a specially trained doctor and support staff.

DAVIS: Absolutely. We see a future where we can actually heal these problems instead of simply trying to reduce symptoms. Our results point to a potential neurological and psychological basis from which we can understand this healing potential, and that could revolutionize our understanding of what treatment actually means. No longer would we be trying to help people get by, but they might actually heal and then thrive.

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Why Doctors Are Turning to Psychedelics to Treat Depression & Addiction - Men's Journal

Manufacturing: the next breakthrough in gene therapy – STAT

Posted on December 23, 2019 by Danzig

I never thought Id see the day when words like process, scale, and automation would make news in the biopharma industry. Yet as the race heats up to bring more first-of-their-kind gene therapies to market, breakthroughs in manufacturing are often the key or break down the barrier to delivering these therapies to patients.

In my career, which has largely focused on drug manufacturing, Ive been lucky to be directly involved in the approval of six new medicines. My current work, as head of technical operations at Spark Therapeutics, is offering the biggest challenge: bringing Luxturna, the first gene therapy for a genetic disease, to patients and families in the U.S. Getting here has been no small task.

With no precedent to guide us, we had to forge new clinical, regulatory, and manufacturing pathways. Working through the unknown meant developing a robust set of assays to test various aspects of the gene therapy product just so we could better understand it. We also built, from scratch, the only in-house manufacturing facility for a licensed gene therapy that is approved by both the U.S. Food and Drug Administration and the European Medicines Agency. This facility is located on the 13th floor of a high-rise in West Philadelphia.

Gene therapy, as others in this space know, is not a one-size-fits-all approach. That means there isnt a gene therapy manufacturing playbook yet to guide the development of gene therapies, as there is for well-established therapeutic categories. And at least for now, every gene therapy is different. Each relies on a different delivery mechanism (vector) to transport functional copies of a gene into the patient.

Even if one day we have a platform that is flexible enough to accommodate multiple vector types, well still need to consider the fact that individual therapies require different dosing and modes of administration, both dependent on the patients cells and disease. While we certainly seek to standardize processes through enhanced analytics, automation, and even artificial intelligence, manufacturing each therapy will still require custom processes.

And time is of the essence, because patients and their families are waiting for these therapies. Given that many of these diseases have limited or no treatment options, regulatory authorities are rightly granting expedited approval pathways for investigational gene therapies. The tight timelines in these pathways narrow the window for manufacturing teams to plan and implement strategies to create gene therapies at scale for commercial use.

Here are three aspects I see as unique to the gene therapy manufacturing process:

Get comfortable with the uncomfortable. Given the shortened clinical development timelines and limited precedent to guide them, gene therapy manufacturers must make decisions about investing in Phase 3 manufacturing processes far in advance of knowing the clinical outcome of their therapy. Its important to trust your expertise and invest in well informed good risk. We saw the success of this at Spark with the first gene therapy, which is helping create a clearer road map for future ones.

Develop capability for capacity. Manufacturing a gene therapy is only half the battle. The other half is making enough of it, doing that as efficiently as possible, and getting it to the patients who need it. These challenges become even more urgent to tackle as the industry shifts to the next chapter in gene therapy development, from treatments made in small batches for small patient populations to bigger volumes for larger rare-disease populations and commercial scale.

Spark, for example, is optimizing the way it produces viral vectors, shifting from adherent cell lines, which attach cells to the sides of roller bottles, to a suspension process that is more efficient and scalable. In this process, bioreactors grow cells unattached, in a liquid or suspended environment. This alternate way of manufacturing uses well-established unit operations commonly employed in the biotechnology industry, making efficiency at scale more easily achievable. Less manual manipulation provides for more process consistency and higher success rates. Each of these elements aids in our ability to scale more easily.

Dont let perfection be the enemy of progress. Versions of this phrase have been attributed to Voltaire, Shakespeare, and Winston Churchill, among others, but the point here is that when it comes to manufacturing, the process is never perfect and can always be better. Our gene therapy manufacturing processes are constantly evolving based on what we learn from them and from new best practices. What matters most today is that we can manufacture gene therapies safely and effectively. The speed will continue to improve.

Manufacturers are accustomed to setting up highly repeatable processes for making and delivering medicines. But when it comes to gene therapies, we understand that the ingenuity for manufacturing needs to be as unique and cutting-edge as the therapies themselves.

While its exciting to see gene therapy manufacturing in the limelight today, I hope that the progress we are making will soon make these challenges old news.

Diane Blumenthal is the head of technical operations at Spark Therapeutics, where her responsibilities include manufacturing, quality control, and more.

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Manufacturing: the next breakthrough in gene therapy - STAT

Ring Therapeutics Launches to Expand Gene Therapy Viral Vector Options – Xconomy

Posted on December 23, 2019 by Danzig

XconomyBoston

Ring Therapeutics, a Flagship Pioneering spinout, launched Thursday with ambitious plans to expand the universe of vectors available for gene therapy delivery.

Gene therapy, treatments intended to treat disease by inserting a gene instead of using drugs or surgery, has had a banner year, with the second ever such therapy approved this year in the US.

Ring want to use itsresearch into viruses that exist in the human body without apparent negative effects to provide more and better options to fuel the rise of gene therapy treatments.

For the past two years, Flagship Pioneering partner and Rings founding CEO Avak Kahvejian says the company has been exploring the human commensal viromebasically, a group of viruses that exist within humans without negative effectsfor its potential to address limitations of the vectors currently used.

The sector relies heavily on adeno-associated viruses (AAVs), which naturally infect humans but arent known to cause disease, to deliver the DNA. Previous exposure, however, can spark an immune response.

A lot of the workhouses in gene therapy have either been pathogenic viruses or viruses that have been taken from other species or viruses that are highly immunogenic, or all of the above, Kahvejian tells Xconomy. That leads to a certain number of limitations, despite the successes and advances weve made to date.

A number of issues stymie widespread use of AAVs, Kahvejian says, including the fact that 10 percent to 20 percent of people have at one time or another been infected with such a virus, thereby building up an immune response to it. Another concern is where such gene therapies end up, because viruses tend to gravitate toward certain types of tissues, and to go elsewhere, require special tweaking.

The Cambridge, MA-based startup believes the viruses it has found are unlikely to cause an immune response or prove pathogenic, given their ubiquity in the body.

Like extrachromosomal DNAa new discovery at least one company is exploring for its potential as a target in cancer treatmentsthe viral sequencing Ring is studying are circular pieces of DNA that exist outside the 23 chromosomes of the human genome.

Ring says it has found thousands of these viruses that coexist with our immune system. It aims to use those to develop vectors that can facilitate gene replacement throughout the bodymultiple times, if necessary. While gene therapy is thought of as a one-time fix, cell turnover means whatever the fix engendered by the inserted gene could falter over time, necessitating a re-up.

Kahvejian wouldnt share a timeline for Rings plan to develop re-dosable, tissue-targeted treatments.

Were looking at the unique features and activities of these viruses in different tissues to establish the various vectors were going to pursue, he said.

Flagship, which pursues scientific questions in-house and builds and funds companies around the answershas put $50 million toward Ring, which has about 30 employees.

Rings president is Rahul Singhvi, an operating partner at Flagship. Most recently he was chief operating officer of Takedas global vaccine business unit. Its head of R&D is Roger Hajjar, who has led gene therapy trials in patients with heart failure.

Ring is the second startup Flagship has spun out this month. Cellarity launched last week.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

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Ring Therapeutics Launches to Expand Gene Therapy Viral Vector Options - Xconomy

Novartis in talks with patients upset about lottery-like gene therapy giveaway – Reuters

Posted on December 23, 2019 by Danzig

NEW YORK (Reuters) - Novartis is in discussion with patient groups over its lottery-style free drug program for its multi-million-dollar gene therapy for spinal muscular atrophy (SMA) after criticism that the process could be unfair to some babies with the deadly disease.

FILE PHOTO: The company's logo is seen at the new cell and gene therapy factory of Swiss drugmaker Novartis in Stein, Switzerland, November 28, 2019. REUTERS/Arnd Wiegmann

The company said on Friday that it will be open to refining the process in the future, but it is not making any changes at this time. The program is for patients in countries where the medicine, called Zolgensma, is not yet approved for the rare genetic disorder, which can lead to death and profound physical disabilities.

At $2.1 million per patient, Zolgensma is the worlds costliest single-dose treatment.

Novartis said the program will open for submission on Jan. 2 and the first allocation of drugs would begin in February. Novartiss AveXis unit, which developed the drug, will give out 50 doses of the treatment through June for babies under 2 years old, it said on Thursday, with up to 100 total doses to be distributed through 2020.

Patient advocacy group SMA Europe had a conference call with the company on Friday, according to Kacper Rucinski, a board member of the patient and research group who was on the call.

There are a lot of ethical questions, a lot of design questions that need to be addresses. We will be trying to address them in January, Rucinski said. He said the program has no method of prioritizing who needs the treatment most, calling it a Russian roulette.

The company said it developed the plan with the help of bioethicists with an eye toward fairness.

This may feel like youre blindly passing it out, but it may be the best we can do, said Alan Regenberg, who is on the faculty at Johns Hopkins Berman Institute of Bioethics and was not among the bioethicists Novartis consulted with on the decision. It may be impossible to separate people on the basis of prognosis out of the pool of kids under 2, he said.

According to Rucinski, the parties will continue their discussion in January to see what can be improved in the design of the program.

Novartis said on Thursday that because of manufacturing constraints it is focused on providing treatment to countries where the medicine is approved or pending approval. It has one licensed U.S. facility, with two plants due to come on line in 2020.

Zolgensma, hit by turmoil including data manipulation allegations and suspension of a trial over safety concerns, is the second SMA treatment, after Biogens Spinraza.

Not all of the SMA community are opposed to Novartis program.

Rajdeep Patgiri moved from the United Kingdom to the United States in April so his daughter could receive Zolgensma. She has responded well to the treatment, and Patgiri worries that negative attention to the program could keep patients from receiving the drug.

The best outcome for all patients would be if everybody could get the treatment. Given all the constraints, a lottery is probably the fairest way to determine who receives the treatment, he said.

Reporting by Michael Erman; Additional reporting by John Miller in Zurich; Editing by Leslie Adler

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Novartis in talks with patients upset about lottery-like gene therapy giveaway - Reuters

Gene Therapy for Sickle-Cell Anemia Looks Promisingbut It’s Riddled With Controversy – Singularity Hub

Posted on December 23, 2019 by Danzig

Gene therapy is fighting to enter mainstream medicine. With sickle cell disease, the fight is heating up.

Roughly two years ago, the FDA made the historic decision to approve the first gene therapy in the US, finally realizing the therapeutic potential of hacking our biological base code after decades of cycles of hope and despair. Other approvals soon followed, including Luxturna to target inherited blindness and Zolgensma, a single injection that could save children with a degenerative disease from their muscles wasting away and dying before the age of two.

Yet despite their transformative potential, gene therapy has only targeted relatively rareand often fataldisorders. Thats about to change.

This year, a handful of companies deployed gene therapy against sickle-cell anemia, a condition that affects over 20 million people worldwide and 100,000 Americans. With over a dozen therapies in the run, sickle-cell disease could be the indication that allows gene therapy to enter the mainstream. Yet because of its unique nature, sickle-cell could also be the indication that shines an unflinching spotlight on challenges to the nascent breakthrough, both ethically and technologically.

You see, sickle-cell anemia, while being one of the worlds best-known genetic diseases, and one of the best understood, also predominantly affects third-world countries and marginalized people of color in the US. So far, gene therapy has come with a hefty bill exceeding millions; few people afflicted by the condition can carry that amount. The potential treatments are enormously complex, further upping costs to include lengthy hospital stays, and increasing potential side effects. To muddy the waters even more, the disorder, though causing tremendous pain and risk of stroke, already has approved pharmaceutical treatments and isnt necessarily considered life-threatening.

How we handle gene therapies for sickle-cell could inform many other similar therapies to come. With nearly 400 clinical trials in the making and two dozen nearing approval, theres no doubt that hacking our genes will become one of the most transformative medical wonders of the new decade. The question is: will it ever be available for everyone in need?

Even those uninterested in biology have likely heard of the disorder. Sickle-cell anemia holds the crown as the first genetic disorder to be traced to its molecular roots nearly a hundred years ago.

The root of the disorder is a single genetic mutation that drastically changes the structure of the oxygen-carrying protein, beta-globin, in red blood cells. The result is that the cells, rather than forming their usual slick disc-shape, turn into jagged, sickle-shaped daggers that damage blood vessels or block them altogether. The symptoms arent always uniform; rather, they come in crisis episodes during which the pain becomes nearly intolerable.

Kids with sickle-cell disorder usually die before the age of five; those who survive suffer a lifetime of debilitating pain and increased risk of stroke and infection. The symptoms can be managed to a degree with a cocktail of drugsantibiotics, painkillers, and a drug that reduces crisis episodes but ups infection risksand frequent blood transfusions or bone marrow transplants. More recently, the FDA approved a drug that helps prevent sickled-shaped cells from forming clumps in the vessels to further combat the disorder.

To Dr. David Williams at Boston Childrens Hospital in Massachusetts, the availability of these treatmentshowever inadequatesuggests that gene therapy remains too risky for sickle-cell disease. Its not an immediately lethal diseaseit wouldnt be ethical to treat those patients with a highly risky experimental approach, he said to Nature.

Others disagree. Freeing patients from a lifetime of risks and pain seems worthy, regardless of the price tag. Inspired by recent FDA approvals, companies have jumped onto three different treatments in a bitter fight to be the first to win approval.

The complexity of sickle-cell disease also opens the door to competing ideas about how to best treat it.

The most direct approach, backed by Bluebird Bio in Cambridge, Massachusetts, uses a virus to insert a functional copy of the broken beta-globin gene into blood cells. This approach seems to be on track for winning the first FDA approval for the disorder.

The second idea is to add a beneficial oxygen-carrying protein, rather than fixing the broken one. Here, viruses carry gamma-globin, which is a variant mostly present in fetal blood cells, but shuts off production soon after birth. Gamma-globin acts as a repellent that prevents clotting, a main trigger for strokes and other dangerous vascular diseases.

Yet another idea also focuses on gamma-globin, the good guy oxygen-carrier. Here, rather than inserting genes to produce the protein, the key is to remove the breaks that halt its production after birth. Both Bluebird Bio and Sangamo Therapeutics, based in Richmond, California, are pursing this approach. The rise of CRISPR-oriented companies is especially giving the idea new promise, in which CRISPR can theoretically shut off the break without too many side effects.

But there are complications. All three approaches also tap into cell therapy: blood-producing cells are removed from the body through chemotherapy, genetically edited, and re-infused into the bone marrow to reconstruct the entire blood system.

Its a risky, costly, and lengthy solution. Nevertheless, there have already been signs of success in the US. One person in a Bluebird Bio trial remained symptom-free for a year; another, using a CRISPR-based approach, hasnt experienced a crisis in four months since leaving the hospital. For about a year, Bluebird Bio has monitored a dozen treated patients. So far, according to the company, none has reported episodes of severe pain.

Despite these early successes, advocates worry about the actual impact of a genetic approach to sickle-cell disease.

Similar to other gene therapies, the treatment is considered a last-line, hail Mary solution for the most difficult cases of sickle cell disease because of its inherent risks and costly nature. Yet end-of-the-line patients often suffer from kidney, liver, and heart damages that make chemotherapy far too dangerous.

Then theres the problem of global access. Some developing countries, where sickle-cell disease is more prevalent, dont even have consistent access to safe blood transfusions, not to mention the laboratory equipment needed for altering blood-producing stem cells. Recent efforts in education, early screening, and prevention have also allowed people to live longer and reduce the stigma of the disorder.

Is a $1 million price tag ever attainable? To combat exhorbitant costs, Bluebird Bio is offering an installment payment plan for five years, which can be terminated anytime the treatment stops working. Yet for patients in South Africa, India, or Cambodia, the costs far exceed the $3 per month price tag for standard treatment. Even hydroxyurea, the newly-approved FDA drug to reduce crisis pain episodes, is just a fraction of the price tag that comes with gene therapy.

As gene therapy technologies are further refined and their base cost reduced, its possible that overall costs will drop. Yet whether these treatments will be affordable in the long run remains questionable. Even as scientists focus on efficacy rather than price tag, NIH director Dr. Francis Collins believes not thinking about global access is almost unethical. There are historical examples for optimism: vaccines, once rather fringe, now touch almost every corner of our world with the help of scientific knowledge, advocacy groups, andfundamentallyproven efficacy.

With the rise of gene therapy, were now in an age of personalized medicine beyond imagination. Its true that perhaps sickle-cell disease genetic therapies arent quite there yet in terms of safety and efficacy; but without tackling access issues, the therapy will be stymied in its impact for global good. As genetic editing tools become more powerful, gene therapy has the potential to save even more livesif its made accessible to those who need it most.

Image Credit: Image by Narupon Promvichai from Pixabay

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Gene Therapy for Sickle-Cell Anemia Looks Promisingbut It's Riddled With Controversy - Singularity Hub

Dyno Therapeutics Launches to Improve Viral Vectors for Gene Therapy – BioSpace

Posted on December 23, 2019 by Danzig

Gene therapy is a way of delivering healthy genes or genetic material to cells in order to treat genetic disorders. The most common way to do this is using adeno-associated viruses (AAVs). The outer part of the virus, called the capsid, is generally retained, but the viral genes are replaced with the therapeutic genes. Attempts have been made to improve the capsid or shell of the virus, but usually fail. George Church and his team at Harvard Medical School with the original researchers at the Karolinska Institute and Lund University in Sweden, have developed a technique to modify the capsid. They have also launched a company, Dyno Therapeutics, to develop the approach.

The groups research, by senior author Tomas Bjrklund, with Lund, was published in PNAS, the Proceedings of the National Academy of Sciences of the United States of America.

The technique allows the researchers to engineer the virus shell to deliver the gene package to the exact cell type in the body they intend to treat. The process leverages computer simulations and modeling with gene and sequencing technology.

Thanks to this technology, we can study millions of new virus variants in cell culture and animal models simultaneously, Bjorklund said. From this, we can subsequently create a computer simulation that constructs the most suitable virus shell for the chosen applicationin this case, the dopamine-producing nerve cells for the treatment of Parkinsons disease.

The technique also dramatically decreases the need for laboratory animals. The millions of variations on the same therapy can be studied in the same individual.

The authors wrote, A challenge with the available synthetic viruses used for the treatment of genetic disorders is that they originate from wild-type viruses. These viruses benefit form infecting as many cells as possible in the body, while therapies should most often target a particular cell type, for example, dopamine neurons in the brain.

Current approaches to finding the most advantageous viruses for gene therapy use random screening, enrichment and, the authors say, serendipity. Their technique is dubbed BRAVE (barcoded rational AAV vector evolution). In BRAVE, each virus displays a peptide derived from a protein. That peptide as a known function on the AAV shell surface and what they call a unique molecular barcode in the packaged genome.

By sequencing the RNA-expressed barcodes, they can map the binding sequences from hundreds of proteins simultaneously. They liken the technique to accelerating evolution from millions of years to just weeks.

Bjorklund said The reason we can do this is that we study each generation of the virus in parallel with all the others in the same nerve cells. Unlike evolution, where only the best suited live on to the next generation, we can also learn what makes the virus work less well through this process. This is crucial when building computer models that interpret all the information.

The study showed the potential for using machine learning for AAV design, although the research fell short of actually designing an improved AAV that could be used in clinical testing. Thats where Dyno Therapeutics comes in, working to improve and develop the technique.

Luk Vandenberghe, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear, told C&EN, Chemical & Engineering News, What theyve done here is truly a remarkable tour de force.

Making advanced therapies takes industrializing personalization – STAT

Posted on December 23, 2019 by Danzig

Whats the best way to measure the real rate of progress in personalized cell therapies, gene therapies, and other advanced therapies?

Ive been tracking the ever-growing flow of reports about these therapies in scientific journals and press releases for 15 years, ever since I co-led the passage of Californias $3 billion Stem Cell Research and Cures Act in 2004.

But to truly gauge who will benefit from todays innovations, Ive learned I also need to study the stream of business and technology announcements that runs in parallel. That might seem more mundane but to veterans of advanced therapies, making the science work actually signals success for these gene-, tissue-, and cell-based advanced therapies.

The reason is simple. My experience working with advanced therapies has taught me, time and again, that true next-generation medicine requires the industrialization of personalization. That sounds like an oxymoron, but it isnt. To create individualized therapeutics in a sustainable way, we need to deliver even if it seems counterintuitive mass customization.

Breakthroughs such as CAR-T cell therapies are inspiring. They are also unsustainably expensive, difficult to manufacture, and complicated to deliver. We can change this by creating a more focused cross-collaborative production and delivery ecosystem.

The Food and Drug Administration anticipates that it will approve 10 to 20 advanced therapies a year beginning in 2025. It also expects to receive up to 200 clinical trial applications for cell and gene therapies per year, starting now. The more than 1,000 advanced therapy clinical trials now underway worldwide could enroll almost 60,000 patients, according to the Alliance for Regenerative Medicine. That pace wont be possible without new systems and networks that reduce cost, simplify manufacturing, and streamline delivery.

I can see some of these on the horizon when I read the biotech and pharma partnerships reported in BioSpace and BioCentury. Of the 100 most recent, almost 10% were dedicated to cell- and gene-therapy companies and organizations. These partnership announcements are typically viewed as opportunities to highlight new business deals or contract wins. But they are also daily snapshots of the infrastructure of an evolving next-generation health care system forming from within. Here are just a few examples from 2019:

Its encouraging to see biopharma manufacturing, logistics, transport, and other partners in the cell- and gene-therapy ecosystem coming together in new ways to ensure the successful and reliable delivery of advanced therapies for individual patients. But much more evolution is needed to provide sustainable patient access to advanced therapies.

We need even more industry collaboration to overhaul and connect existing health care systems, so production and delivery of cell- and gene-based therapies can be more automated and affordable. According to estimates from credible industry colleagues and leaders, end-to-end automation can shave costs by at least 20% to 30%, and at the same time greatly improve predictability and patient safety.

We must also make this new world simpler for health care providers. Doctors and nurses must not only understand how advanced therapies work medically, but be able to order and deliver them safely with a minimum of delay or hassle. As noted in the New Yorker, CAR-T requires bringing a manufacturing lens to medicine. Supporting health care providers means creating true collaboration between digital technology providers, hospitals, logistics providers, biotech and pharma companies, and manufacturing, like the Boston initiative I described earlier.

Standardization is often decried as cookie-cutter medicine. In this space, however, it is the wave of the future.

While patient biology is unique, and each patients cells may produce a one-of-a-kind manufacturing batch, essential parts of the production and delivery process should be as predictable and easy as possible. One key place to start is in-process drug labeling. When patients cells become the raw material for advanced therapies, these labels become more complex and more necessary: When a patient is about to receive a cell therapy infusion, its essential that the name on the bag of genetically re-engineered cells is his or hers. The Standards Coordinating Body, an FDA-funded but independent nonprofit, is now leading an industry-wide labeling initiative for cell and gene therapies.

There are other clear signs that the advanced therapies field gets it when it comes to infrastructure needs, such as the inclusion of digital health and handling of patient data as categories of focus in the federal Cures 2.0 initiative currently circulating in Washington. But much remains to be done.

In centers caring for individuals with cancer and rare diseases, thousands of patients are today receiving advanced therapies that are transforming their lives. We need to make that possible for many, many more by working together to industrialize and personalize in parallel.

Amy DuRoss is the CEO and co-founder of Vineti, a digital technology company that provides next-generation software platforms for advanced therapies. Before that she was managing director for new business creation for GE Ventures, chief business officer at Navigenics, the co-founder and executive director of Proposition 71, Californias $3 billion stem cell research initiative that passed in 2004, and chief of staff at the resulting California Institute for Regenerative Medicine.

New Gene Therapy Method May Open BRAVE New World in Parkinson’s – Parkinson’s News Today

Posted on December 23, 2019 by Danzig

A new method allows researchers to develop adeno-associated virus (AVV) commonly used as the vehicle for gene therapies that accurately target and deliver genes to specific cells in the body.

This new technology may be suitable to target dopaminergic neurons that are damaged in Parkinsons disease.

We believe that the new synthetic [lab-made] virus we succeeded in creating would be very well suited for gene therapy for Parkinsons disease, for example, and we have high hopes that these virus vectors will be able to be put into clinical use, Tomas Bjrklund, PhD,Lund University, Sweden, said in a press release.

Bjrklund is lead author of the studyA systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism, which was published in the journal Proceedings of the National Academy of Sciences.

The adeno-associated virus (AAV)is a common, naturally-occurring virus, which has been shown to work as an effective gene therapy delivery vehicle for genetic diseases, such asspinal muscular atrophy. In gene therapy, scientists deliver a working version of a faulty gene using a harmless AAV that was modified and inactivated in the lab. This way the virus functions only as a delivery vehicle and does not have the capacity to damage tissues and cause disease.

While AAVs have a natural ability to penetrate any cell of the body and infect as many cells as possible, their usefulness as a potential therapy requires the capacity to specifically deliver a working gene to a particular cell type, such as dopamine producing-nerve cells. Those are the ones hose responsible for releasing the neurotransmitter dopamine and that are gradually lost during Parkinsons disease.

A team of Swedish researchers have developed a new method called barcoded rational AAV vector evolution, or BRAVE that combines powerful computational analysis with the latest gene and sequencing technology to produce AAVs that can specifically target neurons.

To make AAVs neuron specific, the team selected 131 proteins known to specifically interact with synapses (the junctions between two nerve cells that allow them to communicate).

They then divided the proteins into small sequences, called peptides, and created a large library where each peptide could be identified by a specific pool of genetic barcodes (a short sequence of DNA that is unique and easily identified).

The peptide is then displayed on the surface of the AAV capsid, allowing researchers to test the simultaneous delivery of many cell-specific AAVs in a single experiment.

The team then injected these AAVs into the forebrain of adult rats and observed that around 13% of the peptides successfully homed to the brain. Moreover, 4% of the peptides were transported effectively through axons (long neuronal projections that conduct electrical impulses) toward the nerve cells body.

Researchers then selected 23 of these unique AAV capsids and injected them into rats striatum, a brain region involved in voluntary movement control and affected in Parkinsons disease. Twenty-one of the new AAV capsids had an improved transport capacity within nerve cells than in standard AAVs.

One particular capsid, called MNM008, showed a high affinity for rat dopaminergic neurons. Researchers then tested whether this viral vector also could target human dopaminergic neurons.

The team transplanted neurons generated from human embryonic stem cells into rats striatum. Six months later, they injected either MNM008 or a control AAV capsid and found that MNM008 was able to target these specific cells and be transported into dopaminergic neuronal cell bodies through axons.

Thanks to this technology, we can study millions of new virus variants in cell culture and animal models simultaneously. From this, we can subsequently create a computer simulation that constructs the most suitable virus shell for the chosen application in this case, the dopamine-producing nerve cells for the treatment of Parkinsons disease, Bjrklund said.

Overall, researchers believe the BRAVE method opens up the design and development of synthetic AAV vectors expressing capsid structures with unique properties and broad potential for clinical applications and brain connectivity studies.

The team has established a collaboration with a biotech company, Dyno Therapeutics, to use the BRAVE method in the design of new AAVs.

Together with researchers at Harvard University, we have established a new biotechnology company in Boston, Dyno Therapeutics, to further develop the virus engineering technology, using artificial intelligence, for future treatments, Bjrklund said.

Patricia holds a Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She has also served as a PhD student research assistant at the Department of Microbiology & Immunology, Columbia University, New York.

Total Posts: 208

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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New Gene Therapy Method May Open BRAVE New World in Parkinson's - Parkinson's News Today

Pharma’s gene and cell therapy ambitions will kick into high gear in 2020despite some major hurdles – FiercePharma

Posted on December 23, 2019 by Danzig

In January 2019, then-FDA commissioner Scott Gottlieb ushered in the new year with a bold prediction: The agency, he said, would be approving between 10 and 20 gene and cell therapies per year by 2025. At the time, there were a whopping 800 such therapies in the biopharma pipeline and the FDA was aiming to hire 50 new clinical reviewers to handle the development of the products.

That momentum will no doubt start to pick up in 2020, as several companies in late-stage development of their gene and cell therapies achieve key milestones or FDA approval. Among the companies expected to make major strides in gene and cell therapies next year are Biomarin, with valoctocogene roxaparvovec to treat hemophilia A, Sarepta and its gene therapy for Duchenne muscular dystrophy, plus multiple players developing CAR-T treatments for cancer, including Bristol-Myers Squibb and Gilead.

But with such explosive growth comes challenges. Gene and cell therapies require enormous up-front investing in complex manufacturing processes, as well asinnovative approaches to securing insurance coverage for products that come with eye-popping price tagssuch as Novartis $2 million gene therapy Zolgensma to treat spinal muscular atrophy. Those are just a few of the obstacles that will be front-and-center in 2020 as more gene and cell therapies make their way towardthe finish line.

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Pharma companies will face challenges figuring out how to incorporate gene and cell therapies into their overall business, said Michael Choy, partner and managing director at Boston Consulting Group, in an interview with FiercePharma. They dont fit well into the normal paradigms of budgeting and decision-making. They require a different pace of evolution and specialized expertise. For now, companies are shoe-horning gene therapies into their current model, but over the long-term there will have to be changes.

That will become increasingly clear in 2020 as both Big Pharma and small up-and-comers move towardthe clinic with their gene and cell therapies. John Zaia, M.D., director of the Center for Gene Therapy at City of Hope, predicts there will be at least three gene and cell therapy FDA approvals in 2020. He also expects to see momentum among companies seeking to improve on the technology to address unmet needs in medicine.

For example, Zaia believes off-the-shelf CAR-T cancer treatments will show promise in early studiesand will be met with enthusiasm in the cancer community, he told FiercePharma in an email. The first generation of FDA-approved CAR-T treatments, Novartis Kymriah and Gileads Yescarta, take several weeks to make because they require removing T cells from patients and engineering them to recognize and attack the patients'cancers. Several companies are advancing off-the-shelf CAR-T treatments, including Precision BioSciences, which has been building out a manufacturing plant equipped to make 10,000 doses per year.

RELATED: Biotech building facility to make genome-edited, off-the-shelf CAR-T therapies

Gene therapies for inherited diseases will make strides in 2020, too, Zaia predicts. City of Hope is one of the participants in a phase 1 study of CSL Behrings gene therapy to treat adults with sickle cell disease. CSL will be racing against several companies working on the disease, including Bluebird Bio, which is testing its beta thalassemia gene therapy Zynteglo in sickle cell. There is a big push from many research centers to cure sickle cell diseaseand early results with the use of gene therapy look very promising, Zaia said. Years of research is finally coming to realization.

With such robust R&D underway in gene and cell therapies, its no surprise several players are stepping up their investments in manufacturing. In October, Sanofi said it would retrofit a vaccine plant in France so it couldbe used for gene therapy manufacturing. Pfizer shelled out $19 million for a North Carolina facility that will serve as its manufacturing hub for gene therapies. Even Harvard University is getting into the game, working with a consortium of contract manufacturers to build a $50 million facility dedicated to making cell therapies and viral vectors for gene therapies.

But how will the healthcare system pay for all of these complex therapies? Its a question that will continue to dog the industry, BCGs Choy said. Theres a lot of interest in outcomes-based payments and payments over time, but the issue is theyre very difficult to implementbecause the infrastructure to track outcomes over time doesnt really exist, he said.

Still, payers and pharma companies are hinting at their willingness to put that infrastructure in place. Pfizer, which is developing DMD and hemophilia gene therapies, said recently its brainstorming with payers on innovative strategies for reimbursement. Novartis and Spark have already pioneered payment strategies that deviate from the standard pay-everything-up-front system. Novartis has some pay-for-performance contracts in place for the $475,000 Kymriah. And in September, Cigna agreed to cover Novartis Zolgensma and Sparks Luxturna on a per-month, per-member schedule.

RELATED: Novartis, Spark gene therapies win a boost with soup-to-nuts Cigna coverage

Despite the many challenges in cell and gene therapy, some players are showing theres likely to be a robust market for these innovative treatments. In its first quarter on the market, Zolgensma brought in $160 million in salesfar surpassing analysts expectations.

The promise of huge returns on gene and cell therapies will likely drive acquisitions in 2020, Choy predicted. These treatments are so transformative for patients, and as the clinical proof of effectiveness continues to grow, youre going to see a lot more deal-making in this area, he said.

Buyers will likely show a willingness to invest in early-stage gene and cell therapies, especially if they come with technology platforms that allow for the development of many follow-up products, Choy added. For these types of therapies, the lifecycles will be much shorter than they are for traditional pharmaceuticals, particularly for rare diseases, he said. If you administer a one-time therapy, that revenue peaks quite quickly and then drops off. So to have a sustainable revenue from a gene therapy business, you need to replace that, which requires managing a pipeline.

Judging from recent events in the burgeoning gene and cell therapy industry, the news flow in 2020 will be generated not just by the industrys largest players, but also by its upstarts. In December, Ferring Pharmaceuticals spinout FerGene turned heads with data showing that its gene therapy to treat non-muscle invasive bladder cancer eliminated tumors in more than half of participants in a phase 3 trial. And Gileads Kite Pharma just applied for FDA approval for its mantle cell lymphoma CAR-T, KTE-X19, based on a 93% overall response rate in a phase 2 trial.

There were 75 gene therapy clinical trials initiated in 2018, nearly doubling the trial starts of 2016momentum thats likely to continue next year, BCG said in a recent report. The scientific foundation is in place, BCG analysts concluded, but there is still much to do to deliver the full benefit of gene therapy to patients."

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Pharma's gene and cell therapy ambitions will kick into high gear in 2020despite some major hurdles - FiercePharma

Viewpoint: EU should take a lead in enforcing the corporate social responsibility of gene therapy manufacturers – Science Business

Posted on December 23, 2019 by Danzig

Gene therapy is providing unprecedented hope for growing numbers of patients and families. This game changer in medicine restores vision in babies born with congenital blindness, reconstitutes defences against infection in inherited immunodeficiencies and offers the perspective of curing the devastating neuromuscular disease, spinal muscular atrophy.

Gene therapy is also removing the need for repeat blood transfusions in adolescents with the inherited blood disorder, beta-thalassemia. Meanwhile, in oncology, CAR-T therapies, involving genetic modifications of a patients own immune cells, are proving life-saving for children or adults with certain types of blood cancers.

All these revolutionary treatments are now approved by regulatory agencies in Europe or the US. Unfortunately, they carry astronomical price tags which prevent their effective delivery to patients. As one case in point, Bluebird Bios Zynteglo for treating beta-thalassemia, has a list price of 1.57 million.

Can high prices be justified?

Gene therapy manufacturers defend their prices by pointing to high development and manufacturing costs, small markets, and unique therapeutic effectiveness as compared to the current standard of care. However, R&D costs are kept secret, and higher numbers of patients eligible for a given therapy do not translate into lower prices.

Indeed, several arguments the manufacturers put forward are dubious or even far-fetched. As of today, claims that a single administration of a gene therapy product will ensure a lifelong cure are simply not supported by the scientific evidence.

Likewise, value-based pricing is often misconceived. As stated by the US Institute for Clinical and Economic Review in its 2017 white paper on gene therapy, the established value of a treatment reflects the maximum price society might be prepared to pay for it - but should not dictate the price that is actually paid. In an ideal world, actual prices should provide market-consistent returns for shareholders and sufficient incentive to innovate.

The EU, a pioneer in gene therapy

European scientists, institutions and charities have been central to the development of gene therapy. The world's first successful clinical trial was reported in 2000 by Alain Fischer and his team at Necker Hospital in Paris, while the first authorisation of a gene therapy product in a regulated market was granted by the European Medicines Agency in 2012.

According to the Cordis database of EU-supported research, 86 gene therapy projects for rare diseases had funding from the European Commission during the FP7 (2007-2013) and Horizon 2020 (2014-2020) research programmes. One can estimate that overall more than 1 billion has been invested in this area by the EU Commission, member states and not-for-profit organisations.

To ensure European patients benefit from these achievements and investments, it is essential to ensure reasonable pricing of gene therapies. Laudable efforts are currently being made by the World Health Organization to increase transparency, and by some member states to join forces in negotiating prices, but such initiatives are unlikely to solve the current crisis as they do not address its root, namely that the sole objective of most gene therapy companies is to maximise the return on investment and shareholder value.

A way forward: enforcing the corporate social responsibility of gene therapy manufacturers

As I recently argued with Alain Fischer and the economist Mathias Dewatripont in the journal Nature Medicine (November 25, 2019), now is the time to reflect on how to enforce the corporate social responsibility of gene therapy companies.

Among the measures we would like to see considered are the insertion of clauses into technology transfer agreements made between academic organisations receiving grants from the European Commission and for-profit companies to make reasonable pricing compulsory.

We also propose to make reimbursement of gene therapies by EU healthcare payers conditional on the companies which are commercialising these products being certified for their corporate social responsibility. This is in line with several commitments made recently by pharma companies. For example, in August 2019, the CEOs of US-based pharma companies signed the Business Roundtable Statement, affirming their commitment to generate value for all their stakeholders not just their shareholders.

Also in August, Novartis announced it had joined the Value Balancing Alliance, a body whose goal is to increase transparency around business decisions, work with external bodies to develop accounting frameworks, and shift priority from profit maximisation to optimising value creation.

Earlier this year, the pharmaceutical company Chiesi was certified as a Benefit Corporation, meaning its legally defined goals include positive social impact in addition to profit.

Of course, the effective implementation of such commitments and their translation into reasonable pricing policies will require both incentives and regulatory controls. The starting point should be a renewed multi-stakeholder conversation with industry, investors, regulators, payers and, of course, patients.

Professor Michel Goldman is Co-director of the I3h Institute at the Universit Libre de Bruxelles and former Executive Director of the EU Innovative Medicines Initiative.

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Viewpoint: EU should take a lead in enforcing the corporate social responsibility of gene therapy manufacturers - Science Business

Takeda Presents Data for Hemophilia A and B Gene Therapy Optimization – Hemophilia News Today

Posted on December 23, 2019 by Danzig

Takedahas presented early data on the prevalence of and a possible solution for one of gene therapys main hurdles: the development of an immune reaction against the viral-based delivery vectors used in such therapies.

The findings, presented at the 61stAmerican Society of Hematology (ASH) Annual Meeting Dec. 710 in Orlando, Florida, may inform the development of investigational gene therapies forhemophilia A and B.

Takedas gene therapy pipeline for hemophilia includes TAK-754 for hemophilia A, which is currently in a Phase 1 clinical study, and TAK-748 for hemophilia B, still in pre-clinical development.

Gene therapy involves the use of a modified viral vector, which does not cause an infection, to deliver a copy of the gene that provides instructions for making the clotting factor missing in hemophilia patients. The goal is to allow patients to produce their own clotting factor at normal levels, and in a durable manner, to limit the need for regular infusions of factor concentrates.

Most gene therapies being developed for hemophilia use protein shells, or capsids, based on adeno-associated virus (AAV), particularly AAV5 and AAV8, for packing and delivering a working copy of the clotting factor gene. Takedas gene therapy candidates for hemophilia A and B both use recombinant (lab-made) versions of AAV8.

The vector delivers the gene into a patients liver cells, where most clotting factors are produced naturally.

One of the major challenges with this approach is the fact that some patients have been exposed in the past to naturally-occurring AAVs and have become immune to these vectors.

While natural exposure to AAVs does not result in any known disease, people develop antibodies (called neutralizing antibodies, or NAbs) and cell-mediated immune responses that recognize and attack AAV capsids. That blocks gene therapy delivery and compromises its safety and effectiveness. These antibodies are known as anti-AAV.

The presence of neutralizing antibodies against AAVs is one of the major limitations for the successful use of gene therapies, and one of the reasons why patients are excluded from gene therapy trials.

At the ASH meeting, one of the posters presented by Takeda, titled Co-Prevalence of Pre-Existing Immunity to Different Serotypes of Adeno-Associated Virus (AAV) in Adults with Hemophilia, reported a study of the prevalence of pre-existing natural immunity against AAVs in adults with hemophilia A and B.

The study enrolled 194 patients with hemophilia A and 48 with hemophilia B, in the U.S. and Europe (NCT03185897). Results showed that approximately 50% of them have neutralizing antibodies to AAV2 (the most common in natural infections), to AAV5 or to AAV8. (Notably, 40% of patients carried antibodies against all three vector types.)

Such patients probably will not respond to AAV-based gene therapies and will be excluded from trials. These data will add to our appreciation of preexisting AAV immunity that prevent patient participation in gene therapy trials, the abstract concluded.

Another study conducted by Takeda focused on a potential strategy to overcome this problem.

The data were presented in a poster titled AAV8-Specific Immune Adsorption Column: A Treatment Option for Patients with Pre-Existing Anti-AAV8 Neutralizing Antibodies.

Researchers developed an immune adsorption column (IAC) specifially designed to remove anti-AAV8 antibodies from patients plasma using apheresis. In this process, blood is drawn from the patient and separated in plasma and its other components, outside the patients body. The plasma is then run through a platform which could be the IAC column to remove anti-AAV8 antibodies. After this process, the plasma is given back to the patient.

The column under development has a coat of AAV8 capsids that serve as bait to specifically fish out AAV8-targeted antibodies.

Early laboratory tests showed that the column effectively eliminated anti-AAV8 antibodies from human plasma samples, a result further supported by animal studies.

IAC is an enabler for treatment of patients with pre-existing immunity against AAV8 and would also facilitate re-administration. IAC is intended to be applied in combination with Takedas AAV8 based hemophilia programs, researchers wrote.

As we continue to advance our hemophilia A and hemophilia B investigational gene therapy programs, Takeda is also investigating approaches to overcome the challenges of current AAV gene therapies that could potentially be applied to hemophilia and other rare monogenic [a single gene] diseases, Dan Curran, MD, head of Rare Diseases Therapeutic Area Unit at Takeda, said in a press release.

Developing new gene therapy approaches including those capable of treating pre-existing immunity to AAV, enabling re-dosing, lowering doses, enhancing biodistribution and developing alternative gene delivery vehicles are critical to one day providing functional cures to patients, Curran said.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Total Posts: 121

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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Takeda Presents Data for Hemophilia A and B Gene Therapy Optimization - Hemophilia News Today

GenScript Biotech to Host Global Forum on Cell and Gene Therapy and the Booming China Market During JPM Week – PRNewswire

Posted on December 23, 2019 by Danzig

NANJING, China, Dec. 16, 2019 /PRNewswire/ -- GenScript Biotech Corp., one of the leadingbiotechnology companies inChina, today announcedits inaugural GenScript Biotech Global Forum on Jan. 14 in San Francisco, coinciding with the JP Morgan Healthcare Conference week. The Forum, exploring the theme "Cell and Gene Therapy and the Booming China Market," will feature gene and cell therapy leaders in industry, academia and the investment community and is expected to draw several hundred attendees.

"Advancements in cell and gene therapy have attracted global attention in recent years, as the promise of bringing life-changing treatments to cancer patients and others comes closer to reality," said Frank Zhang, PhD., founder and CEO of GenScript. "GenScript's Global Forum aims to foster closer collaborations among scientists, regulators, and industry, not just in the booming China market but around the globe. We hope that by working together we can advance the industry and accelerate drug development."

GenScript's Global Forum, will take place from 1:30 p.m. to 5:30 p.m. at the Grand Hyatt San Francisco. Highlights of the agenda include:

For more information about the Forum and to register for the event please visit hereor https://www.genscript.com/biotech-global-forum-2020.html.

About GenScript Biotechnology

GenScript Biotech Corporation (Stock Code: 1548.HK) is a global biotechnology group. GenScript's businesses encompass four major categories based on its leading gene synthesis technology, including operation as a Life Science CRO, enzyme and synthetic biology products, biologics development and manufacturing, as well as cell therapy.

Founded in 2002 and listed on the Hong Kong Stock Exchange in 2015, GenScript has an established global presence across Greater China, North America, the EU, and Asia Pacific. Today, over 300,000 customers from over 160 countries and regions around the world have used GenScript's premier, convenient, and reliable products and services.

GenScript currently has more than 2900 employees globally, 34% of whom hold master's and/or Ph.D. degrees. In addition, GenScript has a number of leading commercial technologies, including more than 100 patents and over 270 patent applications. As of June 2019, GenScript's products and services have been cited by 40,300 scientific papers worldwide.

GenScript is committed to striving towards its vision of being the most reliable biotech company in the world to make humans and nature healthier through biotechnology.

For more information, please visit https://www.genscript.com/

Contact:

Corporate:Fiona CheCorporate Communication Manager, GenScript+86 -025-58897288-6321Fiona.che@genscript.com

Media Susan ThomasPrincipal, Endpoint Communications(619) 540-9195susan@endpointcommunications.net

SOURCE GenScript Biotech Corp.

https://www.genscript.com

GenScript Biotech to Host Global Forum on Cell and Gene Therapy and the Booming China Market During JPM Week - PRNewswire

The gene therapy research that could save a family of four – News – The University of Sydney

Posted on December 23, 2019 by Danzig

Neveah Taouk, 4

At last, when Mary was seven and Neveah three, new developments in whole-genome sequencing enabled specialists to identify the disorder. The diagnosis gave the Taouks information but not hope. They knew what the problem was, but there was no treatment and no cure.

Desperate, Charlie contacted specialists around the world. I must have spoken to at least fifty people scientists, doctors, professors, he says. Most of them had never heard of the condition.

His search eventually led to Dr Wendy Gold, a specialist in rare genetic disorders in children, based at the University of Sydney and the Childrens Hospital at Westmead. We arranged to talk, says Charlie. To be honest, I wasnt expecting much. But then she said, Have you heard of gene therapy?

Gene therapy is a new and rapidly evolving field of research. One of the therapys forms involves adding new genes to a patients cells to replace missing or malfunctioning genes. The new genes are typically delivered to the appropriate cells in the body using a benign virus as a carrier. Gene therapy is already being used to treat diseases including spinal muscular atrophy. It could also be a promising treatment for Parkinsons disease. Dr Gold believed there was a chance it could help the Taouk girls.

Waning treatment is a warning for all ‘one-and-done’ therapies – STAT

Posted on December 23, 2019 by Danzig

As a new mother, she didnt know to look for blue-tinged lips. She could just tell her babys color was off. On a chest X-ray, the clean, white-against-dark curves of his ribs were obscured, clouded by fluid. Pneumonia. That tipped Ray Ballards physicians off: He had a form of severe combined immunodeficiency SCID, for short a genetic mutation that hampered the growth of crucial immune cells, leaving him utterly vulnerable to infection.

The best fix was a transplant of his mothers bone marrow. The attitude was that in three to six months, you should be able to go back to normal life, recalled his mom, Barb Ballard.

That was true at least sort of. He got two more booster transplants before he hit 10. An antibiotic left him with hearing loss, and a virus with digestive tract damage. His lack of B cells meant he needed regular injections of other peoples antibodies, and his T cell counts were never ideal. But he was healthy enough to go to public school, to move through the hallways high-fiving half the guys, to slowly inhale and take aim during rifle team practice.

His T cells had to be working well enough that he wasnt coming down with everything that walked into the classroom, Ballard said.

Then, when Ray was around 18, his immunity began to wane. For him, it came in the form of a norovirus he couldnt shake. For others with the same rare disease, it appears as pneumonia or gastrointestinal trouble or an unexpected T cell decline. Over the last 10 years, the trend has become increasingly clear: The bone marrow transplants that kept certain babies with SCID alive sometimes stop working after years or decades of providing fairly reliable immune defenses.

Now, to patient advocates, this has become an urgent lesson in the language people use to talk about treatment and not just for SCID. They see their communitys experience as a cautionary tale for anyone developing or receiving a therapy thats marketed as potentially curative.

Theres an expectation and a hope: When they hear about bone marrow transplants, it sounds like a lifetime deal, a forever fix, said John Boyle, president and CEO of the Immune Deficiency Foundation. Weve discovered, as a result of this issue, that bone marrow transplant ended up not being the forever fix we thought it was.

Experts have known for years that some of these transplants wouldnt provide full immune protection over the course of a SCID patients entire life. They say clinicians should have avoided the word cure. But even scientific papers that hinted at such complications called the treatment curative. Just this year, an Immune Deficiency Foundation employee was given the unenviable task of sifting through the organizations thousands of pages of online material, scrubbing out every cure that popped up. It was only there a handful of times sometimes in quotes from clinicians, Boyle said but it was there and it needed to be removed.

The language patients hear can sometimes even change their outcomes. Weve heard of cases where, years later, they realized their immune system isnt as healthy as they thought, but nobody was tracking that because they hadnt maintained a relationship with the physician, or the physician didnt maintain a relationship with them, explained Ballard. The word cure, it gives them a false sense of security.

At a time when seemingly every biotech is promoting the idea of one-and-done therapies and setting prices accordingly these advocates hope companies, too, will be more wary. One of the things Im trying to make them very aware of is the need for lifelong follow-up, said Heather Smith, who runs the SCID Angels for Life foundation. For her, its personal: This summer, her son took part in a clinical trial for a gene therapy in the hope that it would provide the immune protection that his decades-old bone marrow transplant no longer could. My son will be followed for 15 years, she said. But what about after that?

Part of the issue with bone marrow transplants from one person to another is the natural genetic variation between us, particularly in the proteins that help our bodies distinguish its own cells from foreign ones. Receiving cells from someone whose proteins dont match yours could cause a civil war within you. Thats why bone marrow transplants began back in the 1950s with identical twins: Sharing those genes meant increasing the likelihood of harmony between the body and the graft.

But the vast majority of people dont have a protein-matched sibling, let alone an identical twin. So researchers set about figuring out how to transplant bone marrow from a parent to a child in spite of only sharing half of their genes and from a matched unrelated donor to a stranger. Like cooks intent on refining recipes to their taste, the doctors who adapted the technique for SCID often did so slightly differently from one another. Over the past 35 years, those idiosyncrasies have hardened into habits. Right now, everybody transplants their patients their way, said Dr. Sung-Yun Pai, an immune deficiency researcher and co-director of the gene therapy program at Boston Childrens Hospital.

Perhaps the most vociferous controversy has been about whether to use chemotherapy to wipe out the existing stem cells within a recipients bone marrow to make room for the donors. The doctors who do use chemo before a transplant might prescribe different doses; others forego it entirely.

The arguments were sound on both sides. On the one hand, the toxic drugs could clean out the niches within our bone and increase the chances that the donors cells take root. On the other, these chemicals could hamper growth, brain development, and fertility, could make an infant who was already sick even sicker, and could increase the likelihood of certain cancers later in life. Its like being exposed to a bunch of X-rays and sunlight, or other DNA-damaging agents, Pai explained.

Because SCID is so rare the most common subtype is thought to occur in 1 out of every 50,000 to 100,000 newborns and because every hospital was doing transplants slightly differently, it was hard for physicians to systematically study what was working best. But even early on, they could tell that some of the infants whod gotten no chemo were developing incomplete immune systems. They didnt produce their own B cells, for instance, and so needed regular injections of antibodies collected from other peoples blood.

In healthy infants, stem cells migrate from the crevices of the skeleton to an organ in the chest called the thymus, where theyre trained to become T cells. In these infants, the T cell counts grew after transplant but it wasnt necessarily because the sludge was securely taking hold in the niches of their bones. Rather, immunologists say, the donors progenitor cells were only transient. Some were able to head toward the thymus for schooling. Some graduated and started fighting off infections. But as those populations were depleted with age, there werent robust reserves of stem cells in the bone marrow that could arrive to produce more. To Pai, its like trying to fill a kindergarten class in a neighborhood where no ones having babies.

You and I continue to have a slow trickle of new T cells coming out, said Dr. Harry Malech, a senior investigator at the National Institutes of Health, who sits on the board of a gene therapy company, Orchard Therapeutics (ORTX), but does not receive any financial compensation. Instead of a torrent becoming slower, in these patients it goes from a trickle to practically nothing.

Thats why immunity starts to wane in kids like Ray Ballard. To many immunologists, it isnt a surprise, though they still arent sure why chemo-less transplants last longer for some of these kids than others. They can also understand how some families and clinicians might have viewed this treatment as a lifetime fix.

As Malech put it, If I said to you, Your child, instead of dying in infancy, will likely get to adulthood, go to school, have a normal life, you might think the word cure in your mind.

Even for parents who knew the protection might not last forever, the failure of a long-ago bone marrow transplant puts them in a bind. If they do nothing, their child will once again be vulnerable to any passing infection, which could prove fatal. They can try another round of the same procedure, though booster transplants sometimes come with added complications. Or they can try getting their child into a research trial for gene therapy, which comes with the risks of any experimental treatment.

Some feel an irrational guilt when the bone marrow they donated to their child stops functioning. Its your cells, and if it doesnt work, you failed them, said Ballard, who lives in Clifton, Va., about a 40-minute drive from Washington, D.C. Her son Ray had already had three transplants as a child. When his immune system started to fail again in early adulthood, gene therapy at the NIH seemed like the only reasonable choice.

That would involve researchers removing cells from his bone marrow, using an engineered virus as a kind of molecular syringe to slip in a healthy copy of the gene in which he had a defect, and then threading these corrected cells back into his veins a bone marrow transplant to himself. But preparing a virus can be tricky, and there were delays.

Meanwhile, Rays condition was getting worse. His norovirus was preventing him from absorbing much nutrition, and as Ballard put it, his bone structure was just crumbling at that point. His doctors told her he had the skeleton of an 85-year-old.

He died this past February, at 25 years old. One friend got his birth and death dates tattooed onto her shoulder. Another painted a portrait of him for Ballard, in which his arms are crossed, his lips pressed together in a wry smile.

At Boston Childrens, Pai is now helping to lead a randomized trial to better understand what dose of chemo works best for SCID patients receiving transplants. Over the last decade or so, she, Malech, and many other clinicians have also teamed up to track the long-term results of immune deficient patients whove received someone elses bone marrow.

Pai is hopeful that knowing about the phenomenon of waning immunity will give gene therapies a better shot at becoming a durable fix. They probably have a better chance of achieving a one-time, lifelong cure, but its never wrong to be humble, she said. Only after decades more and hundreds or thousands of patients will we know for sure.

Patient advocates point out that even then, these patients will still have the capacity of passing on their SCID-causing gene to future generations, and so the word cure is overly optimistic. Thats why I like the word remission, said Smith. That still gives you the hope. If you were given a cancer diagnosis, you wouldnt go through treatment and then just forget about it for the rest of your life.

As Boyle put it, Weve seen the promise and then weve seen the reality. Everyone who is looking at a transformational therapy should be optimistic, but also realistic, and not assume that this is truly one and done. (Boyles foundation has received financial support from Orchard Therapeutics, which is developing a gene therapy for a form of SCID.)

To Amy Saada, of South Windsor, Conn., that isnt theoretical. Her son Adam is now 12, and the immunity from the bone marrow transplant he got as a baby is wearing off. He isnt yet sick, but his parents know they need to decide between gene therapy or another transplant soon. She has a very clear memory of how long and uncertain the recovery from treatment felt. In some ways, she wishes she didnt know quite as much as she does; that way, she would feel less trepidation about what lies ahead.

Your heart kind of sinks, she said. Youve already been through it once, and it was hell. Its harder the second time.

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Waning treatment is a warning for all 'one-and-done' therapies - STAT

Ben Shipp edges Garett Reband in South Beach International Amateur playoff – Golfweek

Posted on December 23, 2019 by Danzig

In the end, Ben Shipp put himself exactly where he needed to be coming down the stretch at the South Beach International Amateur.

Despite entering the final round at Miami Beach Golf Club four shots off the pace, Shipp, a senior at North Carolina State, inched his way into contention and when the leaders stumbled down the stretch, found himself in a playoff for the title.

After two extra holes with Oklahoma senior Garett Reband, who had the lead or a share of it all week, Shipp earned his first title since the Puerto Rico Classic at the beginning of last springs college golf season.

South Beach International Amateur:Leaderboard

Shipp was only within reach of the leaders because of a third-round 67 at Miami Beach Golf Club. He played the front nine on Sunday in 2 over before turning and reeling off birdie, bogey, then eagle at Nos. 10-12. By the time Shipp made his next birdie, at No. 15, he had a share of the lead at 2 under. Reband made double at No. 15.

Both Reband and Shipp made birdie at No. 16 a drivable par 4 while Karl Vilips, the Australian teen who also was in contention, lost his share of the lead with a bogey.

Reband ultimately left the door open for Shipp with a bogey on No. 18. Shipp prevailed after two extra holes.

Shipp hails from Duluth, Georgia, and was runner-up in his last start of the fall college season, the Bank of Tennessee Collegiate. He advanced through the first two rounds of match play at this summers North & South Amateur, played at Pinehurst Nos. 2.

Reband ultimately finished second in Miami with Vilips in solo third at 1 under.

A pair of Englishmen finished fourth and fifth: Jake Bolton was even par and Benjamin Jones posted one of the best rounds of the day, 4-under 67, to finish at 1 over.

Patrick Welch, a sophomore teammate of Rebands at Oklahoma, also had a closing 67 that put him in a share of sixth at 3 over along with German Jannik De Bruyn.

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Ben Shipp edges Garett Reband in South Beach International Amateur playoff - Golfweek

The Story of Beach Sand Is Way More Interesting Than You Thought – TheInertia.com

Posted on December 23, 2019 by Danzig

This started as a mountain range. Photo: Bas Meelker/Shutterstock.com

Theres more to beach sand than meets the eye. It has stories to tell about the land and an epic journey to the sea. Thats because mountains end their lives as sand on beaches.

Over time, mountains erode. The mud, sand, gravel, cobbles, and boulders they shed are washed into streams, which come together to form rivers. As they flow down to the sea, all this sediment is ground up and worn down in natures version of a rock tumbler.

Big rocks break down into smaller pieces, so most of what reaches the sea is mud. These silt and clay particles are too small to perceive with the naked eye. But you can see individual grains of sand, which are just bigger bits of rock.

Next time youre at the beach, pick up a handful of sand and look closely at it. Are all the grains the same color, or a rainbow assortment? Are they jagged and angular, or smooth and round?

Some beaches in Hawaii have black sand because the islands were formed by erupting volcanoes. Many volcanic minerals are dark colored. Photo: dronepicr/Wikipedia, CC BY

Different colors of sand come from different minerals, like khaki feldspar, smoky white quartz, green olivine or black basalt. The mix of colors in beach sand tells you what kinds of rocks produced it.

The shape of sand grains also provides clues about where they come from. Angular grains of the same type of sand have not traveled as far as smooth round grains, which have been more worn down. And weak rocks break down to mud faster than hard rocks, so sand tends to be made of the harder types that break down slowly.

About a tenth of the supply of sediment that reaches the sea is sand. These particles are between about half a millimeter and 2 millimeters in size roughly as thick as a penny. These particles are large enough that they dont flow right out to the deep sea.

But the beach is just a temporary stop for sand. Big waves pull it offshore, and smaller waves push it along the coast. So keeping a beach nourished with sand is essential for keeping it sandy.

Yet today many beaches are starving. Many dams trap the sand that flows down rivers, piling it up in reservoirs. All in all, human activity has cut off about half the sand that would otherwise end up on the worlds beaches.

But humans havent turned the waves off, so as beach sand washes away and isnt replenished, the shoreline erodes. That means that many beaches around the world are shrinking, slowly but surely. So next time you dig your toes into beach sand think about the epic journey it took to arrive beneath your feet. Take a moment to think about where the sand came from and where its going.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The Story of Beach Sand Is Way More Interesting Than You Thought - TheInertia.com

Wave goodbye: Long Beach breakwater won’t be removed – Los Angeles Times

Posted on December 23, 2019 by Danzig

When Kelli Koller decided to open her Long Beach surf shop with a friend in late 2012, she knew it was a bit improbable in a city where the waves never rose more than a foot.

But her store reflected a sincere hope that rolling waves would finally return to the citys 5-mile shoreline.

At the time, Long Beach was swept up in a push to remove part of the 2.2-mile breakwater that hems in East San Pedro Bay, blocking any significant wave action. Break the Breakwater bumper stickers spread. Surfers talked about riding waves for the first time in five decades, restoring Long Beachs moniker as the Waikiki of Southern California. Other advocates hoped more free-flowing surf would reduce poor water quality plaguing some local beaches.

Yet, over the years, efforts stalled amid studies and questions. Two years ago, Koller closed her Seventh Wave Surf Shop.

An image from 1938, before the breakwater was constructed, shows a surfer riding a wave in Long Beach.

(Historical Society of Long Beach)

And now, the U.S. Army Corps of Engineers has concluded that any changes to the breakwater would be too costly and could hamper Navy operations there, as well as at the ports in Long Beach and Los Angeles, the oil islands and Long Beachs Carnival Cruise terminal.

The agency used wave models to simulate how changes to the breakwater could affect existing infrastructure. The data showed that the oil islands which were created to conceal offshore drilling operations along with the Shoreline Marina and the port would all need additional armoring if the waves returned, officials with the corps said in an interview this week.

Weve been working on the analysis for some time, said Raina Fulton, who oversees the corps project considerations. We didnt have complete answers based on data until recently, but weve had concerns all along.

The agency instead proposed an initiative, dubbed the Reef Restoration Plan, to cultivate 201 acres of aquatic habitat with kelp beds, rocky reefs and eelgrass to improve water quality and support habitat biodiversity in East San Pedro Bay.

John Kerwin, left, and John Domminis practice in Long Beach for the national surfing championships on Nov. 14, 1939. The construction of the Long Beach Breakwater ended surfing in the area.

(Art Rogers / Los Angeles Times)

If agreed to by the Long Beach City Council and approved by Congress, the initiative would be the corps first open-ocean ecosystem restoration project in the nation, officials said.

The plan could be a model worldwide, experts say. The project provides habitat for key life stages of a diverse population of fish and other aquatic species, primarily by providing foraging, sheltering and critical nursery functions that support population health and growth, the study says.

The restoration plan is projected to cost nearly $141 million. The federal governments share would be about $91.5 million, while Long Beach would be responsible for $49.3 million. Before anything is finalized, the corps is seeking feedback from the public on results of the study.

It has to be a project that both entities can support to move forward, City Manager Tom Modica said. The city could select a plan that includes changes to the breakwater, but that would not be one the corps would support.

The report included six options to improve the ecosystem along the coast: one that proposed no changes to the area, three that focused solely on restoration and two that included restoration efforts and removing parts of the breakwater to allow wave action.

One proposal with modifications to the breakwater included a process called notching, which removes two 1,000-foot sections in the middle of the barrier. Another option called for removing one-third of the eastern end of the breakwater. Those plans would cost $993 million or $670 million, respectively, according to the corps analysis.

Ultimately, the results of the study showed that modifying the breakwater constructed in the 1940s in part to shelter the fleet of Navy ships that dock in Long Beach would hurt naval operations, including activities in support of national security and other missions. The Navy operates an explosives anchorage used to transfer ammunition between vessels inside the breakwater. Those ships need calm water to conduct operations safely, according to the report.

Because of its purpose as a strategic contingency asset, the anchorage must be available for use on short notice at any given time, the report says.

City leaders and some residents had high hopes that waves in Long Beach could be an economic stimulus for the area, bringing increased tourism and recreational activities that could put more funds in city coffers for improvements and other projects. A previous city-funded study said the uptick in tourism could draw up to $52 million a year in local spending and $7 million annually in taxes and parking fees.

Army Corps officials contend the impact on the ports would probably outweigh any local economic benefit achieved by removing the breakwater.

Long Beach Mayor Robert Garcia, who has long championed the effort to modify the breakwater, said in a statement that he was disappointed with the results of the study and had been hopeful that breakwater modification was possible while protecting coastal homes and our port complex.

Fabi Sandoval and Erick Gasca try to fly their kite on a windless evening on the waveless shoreline of Long Beach.

(Mark Boster / For The Times)

He added that the city should be guided, however, by the data included in the reports that showed wave action could also contribute to coastal erosion and flooding in some areas a longtime concern for residents with oceanfront property.

U.S. Rep. Alan Lowenthal (D-Long Beach) also expressed disappointment.

Im aware that the U.S. Navy had some concerns, but I do not believe that they rose to the level that would forgo any reconfiguration options, he said.

Long Beach was once something of a surfing mecca, known for its roaring swells that attracted surfers from across the region. In 1938, the city hosted whats been billed as the first surfing contest on the United States mainland, according to local historians.

The event was memorialized in a black-and-white photograph that more than 80 years later continues to circulate as a rallying cry among a community of surfers hoping to bring back the waves. In the photograph, the surfers are lined up shoulder to shoulder along the Long Beach shore with massive wooden surfboards behind them in preparation to launch into the water.

Three years after that contest, work began on the Long Beach breakwater. After it was completed in 1949, the waves vanished and surf-loving crowds migrated to nearby spots like Huntington Beach or Manhattan Beach.

In 1996, the Long Beach chapter of the Surfrider Foundation formed and began publicly calling for removal of the breakwater. The chapters chair, Seamus Innes, said the organization was concerned with the Army Corps approach to the study and was reviewing its options.

Were disappointed that the Navy has put a nix on any sort of activity with the breakwater, he said. Weve been working on this for more than 20 years, and this may put the kibosh on us going forward.

Advocates for the removal of the breakwater have long contended that the structure traps urban runoff and stormwater from the Los Angeles River, diminishing water quality at local beaches. Tests in the last several years show the water in Long Beach is safe for swimming, except during the rainy winter season.

A beach report card released in June by the nonprofit group Heal the Bay gave two beaches in the city an A grade during the dry summer months. The stretch of beach at the Belmont Pier earned a B, and three other locations earned C grades during the same period.

One beach, though Long Beach City Beach at Coronado Avenue received an F grade, earning it a spot on the groups Beach Bummer list. The report indicated that water quality at that beach was degraded by dry weather runoff, which flows into the ocean through a storm drain on the beach.

Although water quality rankings show its safe to dive in, the lack of waves and a muddy tint to the ocean along certain stretches of beach are enough to turn some people away, even during the sweltering summer months, Koller said.

It can be hot as hell and theres almost no one in the water, she said. Ive done it because weve done paddle-outs for Surfrider, but we all paddle on our knees. Ive never wanted to get all the way in.

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Wave goodbye: Long Beach breakwater won't be removed - Los Angeles Times

The top 10 stories of 2019 in Long Beach – Long Beach Post

Posted on December 23, 2019 by Danzig

10. CSULB picks a new mascot

The Beach. The Dirtbags. And, the Sharks. After receiving backlash over its former mascot Prospector Pete, the university picked a new mascot, the Sharks, after a months-long process that included a student vote. The term 49er will still also be used, but only as a nickname referring to the year the university was foundednot the Gold Rush of 1849. And the Dirtbags moniker is only used for the baseball team. Following? Though one chapter has closed, its likely the universitys identity crisis hasnt ended yet.

After years of study and calls from environmental groups to tear down the breakwater that took waves away from Long Beach, the U.S. Army Corps of Engineers in late November determined removing parts of the 2.2-mile barrier was not feasible. City officials said the results of the study, more than a decade in the making, put to rest the citys long-time question of whether tearing down the breakwater, which was built by the U.S. Navy in the 1940s, was possible. The Army Corps instead proposed a reef restoration plan that is estimated to cost $141 million.

Metro completed a major renovation of its busiest and oldest rail line, formerly known as the Blue Line. The southern portion of the now-named A Line from Long Beach to Compton was shuttered on Jan. 26 and reopened in late May; the northern part from Compton to Los Angeles reopened in early November. The New Blue project, which cost $1.2 billion, included safety and other modernization improvements.

Not often do stories about things that didnt happen make this list, but a series of terrorist threatsone at Bixby Park, one at a hotel in East Long Beach, and another at Cal State Long Beachshook the citys nerves. In April, the FBI arrested Mark Domingo, a 26-year-old Army veteran from Reseda, on suspicion of trying to bomb a weekend rally that turned into a counter-protest of a white-nationalist demonstration that never materialized. In August, police arrested Rodolfo Montoya, 37, of Huntington Beach, after authorities said he made threats to attack his workplace at the Long Beach Marriott. And in October, CSULB police arrested Prateek Devulpally, 18, who they say confessed to sending a shooting threat from another students email account.

The Post broke the news in February that the Los Angeles Angels were in talks to bring the Major League Baseball team to Long Beach and build a stadium on a 13-acre waterfront lot next to the Long Beach Arena. The City Council held a closed session in March, but the closest the two sides came to a deal was a two-page term sheet outlining a broad vision for any ballpark. In early December, the Angels announced they had reached a deal to stay in Anaheim. In response to that news, Long Beach Mayor Robert Garcia said the negotiations alone had raised the profile of Long Beach, and the city looked forward to future plans for the so-called Elephant Lot in Downtown.

Councilwoman Jeannine Pearce, who represents the Downtown and Alamitos Beach areas, announced in November she would not seek a second term in March after a series of stories in the Post detailing her potential conflicts of interest. In May Pearce told the Post she received payments for consulting work from one of the principals at Urban Commons, the company that operates the Queen Mary, for work in the cannabis industry. A consultant hired by the city to investigate the report found that she indeed likely had conflicts and should recuse herself from votes dealing with the ship, cannabis and other related areas. The Fair Political Practices Commission is also investigating.

The icon of Long Beach, the Queen Mary, is in trouble. This year brought revelations that its operator, Urban Commons, was in danger of defaulting on its lease for failing to make critical repairs; an inspector described the ships condition as possibly unsalvageable; and an audit of the companys finances showed the ship lost roughly $6 million in 2018, and may be unable to sustain operations. Meanwhile, a company affiliated with Urban Commons launched a public offering on the Singapore Stock Exchange in hopes of raising $566 million; the offering lost significant value following reports about the ships condition.

On Oct. 29, a gunman started shooting into the backyard of a Rose Park home where 25 to 30 people had gathered for a Halloween-themed birthday party. Three people were killed and nine were injured. A day after the carnage, police chief Robert Luna described the shooting as one of the worst hes seen in his 34 years at the department: I cant remember an incident where we had this many victims, he said. The dead included Maurice Poe, 25, of Long Beach; Melvin Williams II, 35, of Gardena; and Ricardo Torres, 28, of Inglewood. The shooter or shooters remain at large.

The city of Long Beach collectively grieved when a family of three was killed by a suspected drunk driver in Bixby Knolls on Halloween night. Joseph Awaida, 30, died at the hospital shortly after the crash; his son Omar, 3, died the following night, and the boys mother, Raihan Dakhil, 32, was taken off life support on Nov. 3. An outpouring of vigils, memorials and fundraisers ensued in the following days; more than 7,000 donors gave to a pair of online fundraisers in the familys name that raised over $400,000. The 20-year-old driver of the SUV, Carlo Navarro, stopped at the scene and cooperated, authorities said. He has pleaded not guilty to three counts of murder and gross vehicular manslaughter.

Whether it be a renaissance or gentrificationwhichever description fits your perspectivethe massive changes brought on by development in Long Beach cannot be disputed. This year saw the completion of two significant projects: A new Civic Center and library, a $1 billion transformation of the Downtown core; and the long-delayed 2nd + PCH commercial complex, which replaced the storied SeaPort Marina Hotel. Another significant project for the Downtown area was the completion of a major expansion of the Aquarium of the Pacific. The city has some $3.5 billion worth of development projects in the pipeline; if the building continues, Long Beach will be a much different city at the close of the next decade.

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The top 10 stories of 2019 in Long Beach - Long Beach Post

Photos: Beach-cities drive pits Manhattan and Hermosa Beach in friendly competition to collect the most toys for needy – The Daily Breeze

Posted on December 23, 2019 by Danzig

A South Bay holiday staple, the 27th Annual Beach Cities Toy Drive gift wrapping party welcomed dozens of volunteers who spent their weekend helping wrap gifts that have been donated for the holiday season at the Hermosa Beach Community Centers gymnasium Saturday, Dec. 21.

Beginning in 1992 as a friendly competition between Manhattan and Hermosa Beach to see which city could collect the most toys, the event has grown into a massive undertaking. Arriving at 11 a.m. with scissors and wrapping paper, volunteers began wrapping hundreds of gifts, stopping only to enjoy their donated lunches.

Hundreds of volunteers gathered in the Hermosa Beach Community Center gym with wrapping paper and tape to help wrap thousands of gifts donated for the 27th Annual Beach Cities Toy Drive & Wrapping Party Saturday, Dec. 21. The wrapped gifts were distributed to local charity organizations. (Hunter Lee, Press-Telegram/SCNG)

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The wrapping party rotates each year between cities, with last years event held at the Josyln Center in Manhattan Beach.

When the last present was wrapped, volunteers went home to their families to enjoy the holiday weekend. The toys will be distributed among South Bay charity organizations.

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Photos: Beach-cities drive pits Manhattan and Hermosa Beach in friendly competition to collect the most toys for needy - The Daily Breeze

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